The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

SIRT6 is a NAD+ dependent enzyme and stress response protein that has sparked the curiosity of a plethora of researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in several different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses and so on. Only in recent times however did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles and structure [1]. Even until very recently, SIRT6 was known more for chromatin signaling but being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases namely, diabetes, cancer, neurodegenerative diseases and heart disease has been demonstrated. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies, involving SIRT6, that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest understanding of SIRT6 and how it can alter the course of several life-threatening diseases that cripple today’s society such as processes related to aging, cancer, neurodegenerative diseases, heart disease and diabetes. In addition, SIRT6 has shown to be involved in liver disease, inflammation and bone related issues but more emphasis is given to the former. Lastly, any recent promising pharmacological investigations and study of potential therapeutic targets are also delineated in this review.

The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g. sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms and protochordates. These organisms illustrate a kaleidoscope of MISC-types that participate in the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and scarce ties were established with biomedical industries in attempts to harness MISCs for human welfare. Thus, it is important to: i) consolidate the fragmented European community working on MISCs; ii) promote and coordinate European research on MISC biology; iii) stimulate young researchers to embark on research in MISC-biology; iv) develop, validate, and network novel MISC tools and methodologies; v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognised gaps, the EC-COST Action 16203 “MARISTEM”, has recently been launched. At its initial stage the consortium unites 26 scientists from EC countries, Cooperating countries and Near Neighbor Countries.

Background: Codonopsis pilosula (CP) is one of the most popular Qi-invigorating herbal medicines and has been extensively used to promote health and vitality in China for a long time. C. pilosula polysaccharide (CPP) is the principal active components of CP, which is considered as the reason for CP widespread application. However, there are not revealed that CPP exert a Qi-invigoration effect by protecting mitochondria and/or improving mitochondrial function in the existing traditional Chinese medicine theories. Methods: Herein, we extracted CPP from C. pilosula and investigated the effects of CPP on energy metabolism and mitochondrial protection. Based on the mice chronic hypoxia model for imitating the “Qi” deficiency state of the human body in traditional Chinese medicine, which was administered with CPP by oral gavage daily for 10 days, mitochondrial permeability transition (MPT), lipid peroxidation product malondialdehyde (MDA) in brain, mitochondrial respiratory function, the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in liver cells were assayed. Adenylate energy charge (AEC), total adenylate pool (TAP), ATP/ADP, and ATP/AMP ratios were calculated. Results: CPP could inhibit the formation of MDA in mice brains, decrease oxygen consuming rate and respiratory control ratio (RCR) of liver mitochondria, increase levels of ATP, TAP and AEC in liver cells under chronic hypoxia condition. Conclusion: Overall, CPP can invigorate “Qi” by improving mitochondrial energy metabolism and bioenergetic levels.

The alarming rise of antibiotic resistance has made it imperative to find novel antimicrobial medications. This study reports the design and synthesis of new molecules based on benzofu-ran-pyrazole scaffolds hybridized with various N/O heterocycles using the molecular hybridiza-tion process. The newly synthesized candidates were confirmed using micro-analytical and spectral analyses, and their antimicrobial characteristics were assessed against different bacterial and fungal isolates in comparison with novobiocin and clotrimazole as antibacterial and anti-fungal standards, respectively. In addition, the new compounds were further evaluated as in vitro antioxidants and anti-inflammatory congeners. The most promising broad spectrum antimicrobial compounds 9, 10 with values ranging from 2.50-20.60 μg/mL were further examined as E. coli DNA gyrase B enzyme suppressors using novobiocin as a reference drug. In silico computational and ADMET studies were carried out for the most active compounds.

The high thrust linear motor used for electromagnetic launch is switched with the anti-shunt thyristor as the switch. During the switching process, different current path states will appear, which will lead to changes in motor parameters and current fluctuation. Aiming at the air-core synchronous linear motor with parallel and series power supply, this paper analyzes the change of current path caused by the change of trigger signal of anti-parallel thyristor in the process of sectionalized stator switching. The motor circuit model of the switching process is derived. A new sectionalized stator switching method is proposed to realize the smooth switching of the sectionalized stator powered linear motor. Finally, the correctness of the analysis and modeling is verified by simulation, and the effectiveness of the sectionalized stator switching method is tested by using the test prototype.

Background/Objectives: The Perilla frutescens plant has historically been used to protect against inflammation and redox stress. This has been attributed in part to the high content of various polyphenols. Despite this, the complement of polyphenolic components in Perilla extract is not yet fully defined. The aim of this study was to characterise the polyphenolic composition in Perilla extract, and its effect on the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), which during inflammation and oxidative stress binds to the antioxidant response element (ARE) found on the promoter of phase II antioxidant enzymes. Methods: Following extraction using four solvents of different properties, the total phenolic, flavonoid and ortho-diphenolic content of Perilla extract were determined. Individual phenolic compounds were identified and quantified by RP-HPLC. Dual Luciferase assay using a reporter plasmid containing a human NQO1 ARE-luciferase fusion was employed to determine the potential protective effect of the Perilla fractions against redox stress. Results: HPLC analysis revealed that the highest phenolic content was present in the polar extracts. A total of 35 distinct polyphenolic compounds were identified, with rosmarinic acid being the major constituent. On cells in vitro, the methanol Perilla fraction showed protection against redox stress, with the luciferase assay displaying up to 1.5 fold increase in the induction of the human NQO1 ARE-luciferase reporter. Conclusions: While Perilla extract seems to be mainly protecting against inflammation and redox stress through the action of rosmarinic acid, further work is required on the synergystic effects between different polyphenols.

The increasing prevalence of multidrug-resistant pathogens (MDR), persistent biofilms, oxidative stress, and cancerous cell proliferation pose significant challenges in healthcare and environmental settings, highlighting the urgent need for innovative and sustainable therapeutic solutions. The exploration of nanotechnology, particularly the use of green-synthesized nanoparticles, offers a promising avenue to address these complex biological challenges due to their multifunctional properties and biocompatibility. Utilizing a green synthesis approach, Mauritia flexuosa Mf-AgONPs were synthesized and characterized exhibiting potent antibacterial effects against both non-resistant and MDR bacterial strains, with minimum inhibitory concentrations (MICs) ranging from 11.25 to 45 µg/mL. Mf-AgONPs also demonstrated significant antifungal efficacy, particularly against Candida glabrata, with a MIC of 5.63 µg/mL. Moreover, the nanoparticles showed strong biofilm inhibition capabilities and substantial antioxidant properties, underscoring their potential to combat oxidative stress. Additionally, Mf-AgONPs exhibited pronounced anti-tumor properties against various cancer cell lines, displaying low IC50 values across various cancer cell lines while maintaining minimal hemolytic activity at therapeutic concentrations. These findings suggest that Mf-AgONPs synthesized via an eco-friendly approach offer a promising alternative for biomedical applications, including antimicrobial, antifungal, antioxidant, and anticancer therapies, warranting further in vivo studies to fully exploit their therapeutic potential.

Bacterial infection poses a serious threat to human life due to its rapidly growing resistance to antibacterial drugs, which is a significant public health issue. This study was focused on the design and synthesis of a new series of 25 analogues bearing 5-cyano-6-oxo-4-substituted phenyl-1,6-dihydropyrimidine scaffold hybridized with different substituted benzene-sulfonamides through thioacetamide linker M1-25 via the treatment of the key intermediates 2-mercapto-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitriles 1a-c with different 2-chloro-N-substituted benzene-sulfonamide derivatives 4a-e overnight at room temperature. The spectroscopic data of all the new compounds (IR, 1H-NMR, 13C-NMR, and Mass) was studied in detail to confirm their molecular structures. The antimicrobial activity of the new molecules was studied against various Gram-positive, Gram-negative, and fungal strains. All the tested compounds showed promising broad spectrum antimicrobial efficacy, especially against K. pneumoniae and P. aeruginosa, with ZOI values ranging from 15 to 30 mm. Furthermore, the most promising compounds M6, M19,M 20, and M25 were subjected to minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. In addition, the anti-virulence activity of the compounds was also examined using multiple biofilm assays. The new compounds revealed promising suppressing activity of microbial biofilm formation in the examined K. pneumoniae and P. aeruginosa microbial isolates. Additional in silico ADMET studies were conducted to represent their oral bioavailability, drug-likeness characteristics, and human toxicity risks. The obtained data suggest the newly prepared pyrimidine-benzene-sulfonamide derivatives may serve as model compounds amenable for further optimization and development of new antimicrobial and antisepsis candidates.

This study aims to examine the safety profile of antiepileptic drugs (AEDs) using real-world data, with a focus on neurological, skin, and sexual/reproductive disorders. Data were collected from AED-caused reports in the Korea Adverse Event Reporting System Database (KAERS-DB) from 2012 to 2022. Totally, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). However, for non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). In contrast, non-SCBs induced dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Among the most commonly reported ADRs, rash, pruritus, and urticaria occurred on average two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher’s exact test, p<0.0001). Based on real-world data, we identified the safety profiles of AEDs. AED-induced ADRs exhibited different patterns depending on the mechanism. Therefore, it is important to establish different pharmacovigilance strategies to ensure proper monitoring.

This paper presents an approach to improve the robustness of tip-tilt controllers for fast-steering mirror (FSM)-based laser beam steering (LBS) systems in the presence of dynamic disturbances such as external shocks. To this end, we propose the addition of a disturbance observer (DOB)-based anti-shock controller in parallel to the original linear servo control loop to improve its control performance in the presence of external shocks. To increase the tip-tilt control performance against external shocks, the DOB-based control method, which is an improved control method for eliminating nonperiodic disturbances, is implemented in the original tip-tilt control system. Results indicate that the control error of the DOB-based anti-shock controller decreased, resulting in an efficient improvement in its disturbance-rejection performance.

Elastic yarns are the key component of high-performance compression garments. However, it remains a challenge to fabricate anti-fatigue yarns with high mechanical force and long elongation for generating compression garments with prolonged wear. In this paper, we report the development of anti-fatigue double-wrapped yarns with excellent mechanical properties by wrapping high-denier Spandex with nylon filaments in opposite twists. In particular, 560D high-denier Spandex as the core was untwisted which can maximumly reduce the interaction between the core and wrapping filaments, enabling high elongation of the double-wrapped yarns. In addition, we chose 70D nylon filaments with a tensile force of 387.40 ± 8.82 cN as the wrapping materials to provide sufficient force for double-wrapped yarns. Notably, opposite twists were induced for the inner and outer wrapping filaments to achieve a balanced stable yarn structure. By systematically optimizing manufacturing parameters including inner wrapping density, outer wrapping density, taking-up ratio, and drafting ratio, we obtained double-wrapped yarn with excellent tensile force (952.00 ± 24.03 cN) and elongation (357.28% ± 9.10%). Notably, the stress decay rate of optimized yarns was only 12.0% ± 2.2%. In addition, the optimized yarn was used as the weft-lining yarn for generating weft-lined fabrics, the elastic recovery rate of the obtained fabric was only 2.6% after cyclic stretching, much lower than the control fabric. Our design of anti-fatigue double-wrapped yarns could be widely used for fabricating high-performance compression garments.

Today, there are commercially available high-performance electric wheelchairs, capa-ble of responding to strong limitations. However, despite these advancements, there is a significant portion of the population with severe disabilities who cannot access this mobility solution due to safety reasons. Indeed, either due to motor issues preventing reliable control of the wheelchair's commands, or associated visual or cognitive pathologies, the use of an electric wheelchair by these individuals would put them at risk and could also constitute a danger to those around them. This is why our research team is working on the development of augmented wheelchairs that allow a greater autonomy. We are mainly developing a system compatible with all electric wheel-chairs on the market, capable of making them anti-collision and anti-fall on uneven ground (sidewalks, stairs, etc.). In this article, we present our solution regarding the anti-collision function, in particular the sensors used to do this, as well as the strategy. We will focus on the shortcomings and weaknesses of various types of sensors and demonstrate how, by combining them in a certain way, we can develop a collision avoidance device capable of managing the diversity of everyday life situations. The two types of sensors that will be combined here are an in-house developed special near infrared sensor from the laboratory and a commercially available ultrasonic sensor. We will present the internal operation of the sensors, their limitations, experimental tests involving integration with the wheelchair, and the structure of the complete device.

A three-arm, randomized, placebo controlled clinical study has been performed to evaluate the effects of a lyophilized pineapple extract titrated in bromelain (Brome-Inf®), and purified bro-melain on pain, swelling, trismus and quality of life (QoL) after the surgical removal of the lower third molars. Moreover, the need for non-steroidal anti-inflammatory drugs (NSAIDs) has also been evaluated and compared with a placebo group. The study included 42 people that required the extraction of a single mandibular third molar under local anesthesia. The patients were ran-domized and distributed to receive Brome-Inf®, purified bromelain or placebo and started the treatment the day of surgery and continued it for the next 7 days. The primary outcome was the requirement of NSAIDs in the three groups. The outcome variables were pain, swelling and trismus, which were measured postoperatively at 1, 3, and 7 days. The differences in the efficacy of the freeze-dried pineapple extract and single-component bromelain were also evaluated. At the end of the study, the assumption of ibuprofen (from days 1-7) was statistically higher in the placebo group (p

Aging, a natural process occurring in both normal and degenerative conditions, is closely associated with collagen degradation, impacting various bodily systems such as the skin. The continuous aging of the skin, influenced by both intrinsic and extrinsic factors, underscores the importance of collagen in dermatological and cosmetic contexts. Notably, collagen supplements enriched with essential amino acids like proline and glycine along with marine fish collagen have become popular for their safety and effectiveness in mitigating the aging process. To compile relevant literature on the anti-aging applications of marine collagen, a systematic search and analysis of peer-reviewed papers was conducted using reputable databases including PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1956 to 2023. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging and promoting overall skin health. Many bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the peptide production of hyaluronic acid is discussed as a mechanism to fortify collagen and enhance skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in addressing skin and bone damage. Insights from this review illuminate the diverse biomedical applications of marine collagen alongside keystone molecular editing tools such as CRISPR, positioning it as a versatile resource in anti-aging interventions. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

The gold(I) N-heterocyclic carbene (NHC) complexes, containing a combination of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (iPr) and the corresponding 7-azaindole derivative (HL1-4), were prepared and structurally characterized. The complexes of the composition of [Au(iPr)(HLn)], where n = 1–4 for 5-fluoro-7-azaindole (1), 5-bromo-7-azaindole (2), 3-chloro-7-azaindole (3) and 3-iodo-7-azaindole (4), were further evaluated for their in vitro anti-cancer and anti-inflammatory activities. The results showed that complexes (1–4) behave as considerably cytotoxic against human ovarian cancer cell line A2780 (with IC50 = 4–9 mircoM) and cisplatin-resistant cell line A2780R (with IC50 = 5–8 microM, except for 2 with IC50 > 25 microM), providing significantly higher cytotoxicity than anticancer drug cisplatin. Moreover, they also revealed a relatively good selectivity over normal cells (MRC-5), with the values of selectivity index, SI > 2.5. The complex 4 was further studied for its cellular effects in A2780 cells by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential. The ability of complexes (1–4) to influence the activity of pro-inflammatory transcription factor NF-κB and secretion of TNF-α were evaluated, showing that complex 4 reveals comparable effects as the inflammatory drug Auranofin.

Amphibians are widely known as a prolific source of bioactive metabolites. In this work we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad Rhinella alata collected in Panama. Bio-guided isolation and structural elucidation was carried out using chromatographic and spectroscopic techniques. The organic crude extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against Trypanosoma cruzi trypomastigotes. Seven steroids (1-7) of the bufadienolide family were isolated and their structures determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin (3) is reported as a new natural product. Compounds 1, 3-7, resulted with a good anti-trypanosomal activity profile, among these 16β-hydroxyl-hellebrigenin (1) and bufalin (7) showed significant selectivity for T. cruzi. Furthermore, molecular docking analysis showed compounds 1, 3 and 7 interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain, at the catalytic site. Given the lack of therapeutic options to currently treat the American trypanosomiasis, this work can serve as the basis for further studies that aim the development of bufadienolides or their derivatives as drugs against Chagas disease.

High-performance properties of interpenetration polymer network (IPN) hydrogels, based on physically crosslinked chitosan (CS) and chemically crosslinked poly(N-isopropylacrylamide) (PNiPAM), have been successfully developed. The IPN of CS/PNiPAM is proposed to overcome the limited mechanical properties of the single CS network. In this study, the viscoelastic behaviors of prepared materials in both solution and gel states have been extensively examined, considering the UV exposure time and crosslinker concentration as key factors. The effect of these factors on gel formation, hydrogel structures, thermal stabilities of networks, and HeLa cell adhesion were studied sequentially. The sol-gel transition was effectively demonstrated through the scaling law, which agrees well with Winter and Chambon's theory. By subjecting the CS hydrogel to the process operation in an ethanol solution, its properties can be significantly enhanced with increased crosslinker concentration, including the shear modulus, crosslinking degree, gel strength, and thermal stability in its swollen state. The IPN samples exhibit a smooth and dense surface with irregular pores, allowing for much water absorption. The HeLa cells were adhered to and killed using the CS surface cationic derivative, then released through hydrolysis by utilizing the hydrophilic/hydrophobic switchable property or thermo-reversible gelation of the PNiPAM network. The results demonstrated that IPN is a highly attractive candidate for anti-fouling materials.

The goal of the current study was to discover a novel potential probiotic strain of Lactobacillus spp. with anti-Escherichia coli activity from locally produced yogurt in Tongi, Gazipur, Bangladesh, compare its antagonistic activity with a commercial probiotic mixture of several strains, and approve a novel method for confirming the viability and relative abundance of the microbial community in a probiotic mixer. We carried out 16S sequencing, 16S metagenomics, Transmission Electron Microscopy (TEM) analysis, and other in vitro laboratory experiments to reach this objective. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus (16S sequence accession number OQ652026). It was gram-positive, anaerobic, lactose fermenting, and round-ended rod that typically measured 0.7 to 1.3 µm by 2.2 to 9 µm. In addition to having seven probiotic characteristics, it also showed an antagonistic impact on six different pathogens, but what's more noteworthy is that E. coli was the pathogen it inhibited most strongly (inhibition zone diameter was 18.88±0.18 mm). The most important and ground-breaking finding of this work was determining the probiotic features of a new probiotic strain, TY-11, whose antibacterial activity was virtually as effective as that of the probiotic combination with three different strains. Furthermore, the results of 16S high throughput sequencing and the conventional plate count method demonstrated a strong correlation (0.999) at the genus level, indicating that the use of both of these approaches in combination may be a practical way to assess the relative abundance of the microbial community and their viability in commercially available probiotic blends.

Anti-DNA antibodies are hallmark autoantibodies produced in systemic lupus erythematosus (SLE), but their pathogenetic roll is not fully understood. Accumulating evidence suggests that some anti-DNA antibodies enter different types of live cells and affect the pathophysiology of SLE by stimulating or impairing these cells. Circulating neutrophils in SLE are activated by type I interferon or other stimuli and primed to release neutrophil extracellular traps (NETs) on additional stimulation. Anti-DNA antibodies are also involved in this process and may induce NET release. Thereafter, they bind and protect extracellular DNA in the NETs from digestion by nucleases, resulting in increased NET immunogenicity. This review discusses the pathogenetic role of anti-DNA antibodies in SLE, mainly focusing on recent progress in the two research fields concerning antibody penetration into live cells and NETosis.

Algal-bacterial granular sludge, a new biological technology, has been widely recognized due to its highly effective pollutant treatment and energy efficiency. This study investigated the effects of environmental concentrations of Cr(VI) (0.5-2.5 mg/L) on the performance of algal-bacterial gran-ular sludge and self-defensive responses after 90 days of cultivation. The results showed that Cr(VI) affected chemical oxygen demand (COD), ammonia-N and phosphate removal with different trends being apparent. A linear decline in COD removal was observed, whereas an initial de-creasing and then increasing ammonia-N and phosphate removal took place. Algal-bacterial granular sludge effectively removed Cr(VI) from wastewater through biological adsorption and reduction, showing the potential to treat Cr(VI)-contaminated wastewater. Cr(VI) affected the community abundance of the algal-bacterial granular sludge, in which Chlorophyceae and cya-nobacteria were vulnerable under Cr(VI)-induced stress. To reduce the toxicity of Cr(VI), over-produced EPS-PN and antioxidant enzymes (MDA, SOD and CAT) acted as self-defensive responses to resist oxidative damage. This study showed that algal-bacterial granular sludge can remove 00.5 mg/L of Cr(VI) without performance loss. It is hoped that this study can provide useful information for improved engineering feasibility of algal-bacterial granular sludge.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

: (1) Background: Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However atypical HBV serologies occur and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. (2) Methods: Plasma samples from an HIV-1 cohort in Botswana (2013-2018) were used. Samples were screened for HBsAg and anti-HBc. Next generation sequencing was done using the GridION platform. Wilcoxon rank-sum test and Chi-squared tests were used for comparison of continuous and categorical variables respectively. (3) Results: HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1 – 18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p&lt;0.001), female (p=0.02), ART naïve (p=0.04) and had detectable HIV viral load (p=0.02). There were no mutational differences in sequences isolated from participants with HBsAg+/anti-HBc- versus those with HBsAg+/anti-HBc+ serology. (4) Conclusions: We report a high HBsAg+/anti-HBc– atypical serology profile prevalence among PWH in Botswana. We caution against HBV testing algorithms that consider only anti-HBc+ samples for HBsAg testing as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.

Lipoxygenases are non-heme iron-containing enzymes that catalyze the oxidation of polyunsaturated fatty acids, resulting in the production of lipid hydroperoxides, which are precursors of inflammatory lipid mediators. The enzymes are widely distributed in humans, other eukaryotes, and cyanobacteria. Lipoxygenases hold promise as therapeutic targets for several human diseases, including cancer and inflammation-related disorders. Inhibitors of lipoxygenase have potential applications in pharmaceuticals, cosmetics, and food. Bioactive peptides are short amino acid sequences embedded within parent proteins, which can be released by enzymatic hydrolysis, microbial fermentation, and gastrointestinal digestion. A wide variety of bioactivities have been documented for protein hydrolysates and peptides derived from different biological sources. Recent findings indicate that protein hydrolysates and peptides derived from both edible and non-edible bioresources can act as lipoxygenase inhibitors. In this review, we explore current knowledge on the production of anti-lipoxygenase protein hydrolysates and peptides from millet grains, chia seeds, insects, milk proteins, fish feed, velvet antler blood, fish scales, and feather keratins. We delve into the anti-lipoxygenase activities and modes of action of these protein hydrolysates and peptides, while also highlighting the strengths and shortcomings of previous research. Additionally, we propose potential research directions and areas of improvement that can propel the discovery of anti-lipoxygenase peptides in the near future.

This paper presents designing an attitude motion control strategy for a half-car model using an anti-jerk predictive controller. Anti-jerk predictive controller based on active aerodynamics surfaces is employed to deal with the anticipated future road maneuvers and improve vehicle ride performance by canceling out external jerks acting on the vehicle body. The body jerks are produced during vehicle traversing on a double lane-change maneuver, acceleration, or braking. The control strategy helps the vehicle to achieve a realistic operation of the active aerodynamic surface to improve the vehicle’s ride performance, i.e., ride comfort and road holding during cornering, acceleration, or braking. The anti-jerk predictive controller is developed based on the predictive control strategy, which predicts future road inputs and uses them to compensate for the vehicle’s attitude motion. The simulation results show that the proposed control strategy effectively reduces the effects of vehicle body jerks transmitted to the passengers, improving ride comfort without degrading vehicle handling. The anti-jerk predictive controller successfully tracks the desired attitude position by canceling the external body jerks.

Metformin (MeT) is an FDA-approved drug with a myriad of health benefits. Besides being used as an anti-diabetic drug, MeT is also effective against various cancers, liver-, cardiovascular-, and renal diseases. It has also been proven to demonstrate anti-ageing and neuroprotective effects. This study was undertaken to examine its unique potential as an anti-virulence drug against an opportunistic bacterial pathogen, Pseudomonas aeruginosa. Due to the menace of multidrug resistance in pathogenic microorganisms, many novel or repurposed drugs with anti-virulence prospects are emerging as next-generation therapies with the aim to overshadow the application of existing antimicrobial regimens. The quorum sensing (QS) mechanisms of P. aeruginosa are an attractive drug target for attenuating bacterial virulence. In this context, the anti-QS potential of MeT was scrutinized using biosensor assays. MeT was comprehensively evaluated for its effects on different motility phenotypes, virulence factor production (phenotypic and genotypic expression) along with biofilm development in P. aeruginosa in vitro. At sub-lethal concentrations, MeT displayed prolific quorum quenching (QQ) ability and remarkably inhibited AHL biosynthesis in P. aeruginosa. Moreover, MeT (1/8 MIC) effectively downregulated the expression levels of various QS- and virulence genes in P. aeruginosa, which coincided with a notable reduction in the levels of alginate, hemolysin, pyocyanin, pyochelin, elastase, and protease production. In silico analysis through molecular docking also predicted strong associations between the QS receptors of P. aeruginosa and MeT. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, the QQ, anti-virulence, and anti-fouling potential of MeT was elucidated for the first time against P. aeruginosa.

According to the eminent scholar, philosopher, and physician Avicenna, "the doctor has three tools: the word, the plant, the knife." The plant kingdom is recognized as humanity's earliest and most ancient healing source, employed for the management and prevention of illnesses. Tracing back through history, the most ancient documented proof of plants' utilization in medicine dates back to a Sumerian clay slab discovered in Nagpur roughly 5000 years ago. This artifact included a compilation of twelve medicinal recipes that involved over 250 diverse plant species. Sumerian healers extracted powders and infusions from plant roots and stems, while also crediting healing properties to pears and figs. Additionally, they utilized dried and ground young shoots of willow and plum trees, pine and fir needles as a component in compresses and poultices. Often, powders from animal and mineral sources were blended with those extracted from dried and crushed plants. Notably, in addition to water, wine and beer served as solvents. Thus, at least 80 centuries ago, people utilized the most uncomplicated medicinal plant-based preparations for treatment [1]. The "Pen T'Sao," an ancient Chinese text on roots and herbs, authored by Emperor Shen Nung approximately 2500 BC, contains descriptions of 900 medicaments (comprising dried components of medicinal plants). Several of these substances are still in use today, including Rhei rhisoma, camphor, Theae folium, Podophyllum, great yellow gentian, ginseng, datura, cinnamon bark, and ephedra [2]. Regarding Kazakh folk medicine, an area that has yet to be fully explicated and substantiated, it can be stated that the traditional medicinal knowledge of the Kazakh people transcends the mere treatment of ailments and rests on robust theoretical underpinnings. Oteiboydak Tleukabyluly (1388-1478), an astute healer and prominent figure in Kazakh folk medicine during the 15th century, comprehensively explicated the secrets of the healing art in his medical and ethnographic work "Medical Narrative," which he composed between 1466 and 1473 at the behest of az-Zhanibek Khan, who held him in high esteem as a great healer. This medical encyclopedia delineates the functions of various organs of the human body and provides a catalogue of the primary diseases associated with them. Furthermore, it includes a meticulous description of the methods used in traditional medicine at present, such as setting bones, listening to the pulse, and incantations. Through practical experimentation and experimentation conducted in the steppe laboratory, the healer formulated a total of 1,108 different medicinal compounds, of which 858 were derived from medicinal plants, 318 were extracted from animal organs, and roughly 60 were sourced from metals. The moniker "Teacher without a teacher" was bestowed on Oteiboydak Tleukabylov, who discovered methods for treating 1,050 different diseases [3]. At present, the employment of phytotherapy has gained widespread acceptance on a global scale. According to the World Health Organization's (WHO) global review of national policies concerning traditional, complementary, and alternative medicine, as well as the regulation of herbal medicines, there is an evident growth in the European and Asian market for herbal medicines [4]. Kazakhstan boasts a natural flora of over 6,000 plant species [5]. The exact number of medicinal plant species present in Kazakhstan remains uncertain, as the list continues to expand annually. More than 150 plant species have been employed in both official and folk medicine for various ailments. This review focuses on a selection of medicinal plants growing within the territory of the Republic of Kazakhstan that have traditionally been used to alleviate skin diseases. In conducting this study (2010-2023), emphasis was placed on the plants' phytochemical composition, with a particular focus on the principal components responsible for their therapeutic effects against inflammatory skin conditions such as dermatitis, atopic dermatitis, and eczema.

We report the isolation of two novel degrading bacterial strains active against the potential environmental pollutant acetamino-phen/paracetamol. Streptomyces Chrestomyceticus (RS2) and Streptomyces Flavofuscus (M33) collected from El-Natrun Valley, Egypt, water, sediment, and sand samples were taxonomically characterized via conidiophores morphologic characterization under Trans-mission Electron Microscope (TEM). Genotypic identification, done based on their 16S rRNA gene sequence analysis followed by BLAST alignment and deposited on the NCBI as 2 novel strains. The phylogenetic tree was constructed using an appropriate software. Acetaminophen degradation-products chemical structure was identified by GC/LC MS. The biological antimicrobial activity of some selected acetaminophen degradation-products extracts and derived compounds was examined against panel of test micro-organisms and found to be have high anti-microbial effect. In addition, in silico cheminformatics Swiss ADMET evaluation of these selected deg-radation extract for gastric absorption, distribution, hepatic metabolism, renal excretion as well as distribution to CNS and finally not mutagenic/teratogenic or genotoxic virtually. In vitro cytotoxic activity of these selected bio-degradation products was performed against HepG2 and MCF7 cancer cell lines, revealing that M33 and RS2 extract effect on acetaminophen/paracetamol bio-degradation products are potentially safe with higher IC50 on HepG2 and MCF7, in comparison to acetaminophen/paracetamol with IC50 of 108.5 μg/ml. Moreover, the in vivo acute oral single dose toxicity experiment was conducted, being compared with acetamino-phen/paracetamol to confirm that the bio-degradation products have lower toxicity than acetaminophen in vivo and in silico.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to eradication failure in many cases, but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. Targeting the three EPSs secreted by P. aeruginosa (alginate, Psl and Pel) is currently under investigation as a way of disrupting the biofilm extracellular matrix to potentiate the action of antibiotics. In this review, we look at each EPS as a potential therapeutic target for combatting pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

Torenia Concolor Lindley var. formosama Yamazaki ethanolic extract (TCEE) is reported to have anti-inflammatory and anti-obesity properties. However, the effects of TCEE and its underlying mechanisms in the activation of endothelial nitric oxide synthase (eNOS) have not yet been investigated. Increasing the endothelium-derived nitric oxide (NO) production has been known to be beneficial against the development of cardiovascular diseases. In this study, we investigated the effect of TCEE on eNOS activation and NO-related endothelial function and inflammation by using in vitro system. In endothelial cells (ECs), TCEE increased NO production in a concentration-dependent a manner without affecting the expression of eNOS. In addition, TCEE increased the phosphorylation of eNOS at serine 635 residue (Ser635) and Ser1179, Akt at Ser473, calmodulin kinase II (CaMKII) at threonine residue 286 (Thr286) and AMP-activated protein kinase (AMPK) at Thr172. Moreover, TCEE-induced NO production, and EC proliferation, migration and tube formation were diminished by pretreatment with LY294002 (an Akt inhibitor), KN62 (a CaMKII inhibitor) and compound C (an AMPK inhibitor). Additionally, TCEE attenuated the tumor necrosis factor-α-induced inflammatory response as evidenced by the expression of adhesion molecules in ECs and monocyte adhesion onto ECs. These inflammatory effects of TCEE were abolished by L-NG-nitroarginine methyl ester (a NOS inhibitor). Collectively, our findings suggest that TCEE confers protection from endothelial dysfunction by activating the Akt/CaMKII/AMPK/eNOS/NO signaling pathway.

The proposed research methodology aims to design a generally implementable framework for providing a house owner/member with the immediate notification of an on-going theft (unauthorized access to their premises). For this purpose, a rigorous analysis of existing systems was undertaken to identify research gaps. The problems found with existing systems were that they can only identify the intruder after the theft, or cannot distinguish between human and non-human objects. Wireless Sensors Networks (WSNs) combined with the use of Internet of Things (IoT), Cognitive Internet of Things, Internet of Medical Things, and Cloud Computing are expanding smart home concepts and solutions, and their applications. The primary objective of the present research work was to design and develop IoT and cloud computing based smart home solutions. In addition, we also propose a novel smart home anti-theft system that can detect an intruder, even if they have partially/fully hidden their face using clothing, leather, fiber, or plastic materials. The proposed system can also detect an intruder in the dark using a CCTV camera without night vision facility. The fundamental idea was to design a cost-effective and efficient system for an individual to be able to detect any kind of theft in real-time and provide instant notification of the theft to the house owner. The system also promises to implement home security with large video data handling in real-time.

This study comprehensively investigates the stress distribution and aging effects in Ethylene Propylene Diene Monomer (EPDM) and Liquid Silicone Rubber (LSR) gasket materials through a novel integration of hyperelastic modeling and advanced machine learning techniques. By employing the Mooney-Rivlin, Ogden, and Yeoh hyperelastic models, we evaluate the mechanical behavior of EPDM and LSR under conditions of no aging, heat aging, and combined heat and sulfuric acid exposure. Each model reveals distinct sensitivities to stress distribution and material deformation, providing unique insights into material degradation processes. Additionally, we utilize machine learning for predictive analysis, enhancing our understanding of stress responses and identifying critical aging effects. The findings offer practical implications for selecting suitable gasket materials and developing predictive maintenance strategies in industrial applications, such as fuel cells, where material integrity under stress and aging is paramount. This dual approach highlights the mechanical resilience and vulnerabilities of EPDM and LSR and opens avenues for real-time predictive analytics and material performance optimization.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

The present study sought to determine the effect of incorporating a Chitosan-TiO2 nano-composite on the color stability of pigmented Room Temperature Vulcanization (RTV) maxillofacial silicone subjected to a variety of accelerated aging conditions. The experimental setup consisted of one hundred groups of five disk-shaped specimens (22mm diameter, 2mm thick) each, created using RTV silicon elastomer type A-2186, with the total sample distributed into four groups based on the pigments combined with the silicon—specifically, brilliant red, blue, and yellow dry intrinsic pigments (at 0.2% concentration by weight) and a fourth group that remained non-pigmented. Each of these primary groups was further subdivided into five categories corresponding to the silicon variants treated with different nanoparticles—2% TiO2, 3% Chitosan, a hybrid nano-combination of 1% TiO2/Chitosan, 1% synthesized Chitosan-TiO2 Nanocomposite, and a control group devoid of nanoparticle additions. The synthesized Chitosan-TiO2 Nanocomposite was effectively prepared using the core-shell method. The color stability of each silicon category, irrespective of whether pigmented or non-pigmented was evaluated by calculating the color difference (ΔE) pre- and post-subjection to five distinct accelerated aging conditions: 30 hours in an antibacterial cleaning solution, six months in sebum, six months in sweat, UV-accelerated aging for 720 hours, and outdoor weathering for six months. Color measurements were taken using a Colorimeter within the CIELAB color system. Statistical analyses, including one-way ANOVA at a significance level of p < 0.05, were employed to discern significant differences among the various accelerated aging conditions across the five silicon categories. Further comparisons were made using Dennett's T3 multiple comparison test, Tukey HSD multiple comparisons, and a t-test, with SPSS for Windows version 27.0 as the software platform. Results indicated that all silicon types, whether pigmented or not, exhibited varying degrees of color change under different aging conditions. Red-colored samples, across all silicon categories, demonstrated significant color alterations after 720 hours of UV-accelerated aging, with the most pronounced change in the 3% Chitosan samples and the least in the 2% TiO2 samples. Six months of outdoor weathering led to a marked increase in ΔE values across all categories. The blue-pigmented silicon samples treated with 2% TiO2 showed the highest color modification, while the yellow-pigmented silicon and non-pigmented silicon also underwent significant color shifts, particularly in the control and Chitosan-TiO2 categories, respectively. The study underscores the pervasive influence of outdoor weathering on color stability across all silicon categories. It also demonstrates that while nanoparticle incorporation offers some resilience against accelerated aging, it fails to provide adequate protection against the specific effects of UV radiation encountered during outdoor weathering.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

The average age of in-service bridges has increased in recent years in the United States. To address this issue, structural health monitoring and damage identification approaches can be employed to prioritize maintenance/replacement of aging bridges. Among the damage identification and operational health monitoring approaches, finite element (FE) model updating methods can offer a solution to evaluate the mechanics-based characteristics of bridges. However, in a real-world setting, unidentifiability and mutual dependency between model parameters, modeling errors, especially due to boundary conditions, as well as ill-conditioning of updating algorithms can pose challenges to the application of FE model updating methods. To address these challenges, this study presents a two-step FE model updating approach. In the first step, modal-based model updating is used to estimate linear model parameters mainly related to the stiffness of boundary conditions and material properties. In the second step, in order to refine parameter estimation accounting for nonlinear response behavior of the bridge, a time-domain model updating is carried out. In this step, boundary conditions are fixed at their final estimates using modal-based model updating. To prevent the convergence of updating algorithm to local solutions, the initial estimates for nonlinear material properties are selected based on their corresponding final estimates in the modal-based model updating. To validate the applicability of the two-step FE model updating approach, a series of forced-vibration experiments are designed and carried out on a pair of decommissioned and deteriorated prestressed bridge I-girders. After carrying out the two-step FE model updating, the final estimates of concrete compressive strength are shown to provide reasonable assessment of the damage extent in the girders.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

Optical characterization and thermal aging tests are performed on a sputter-deposited coating, consisting of SiO₂/Cr₂O₃/Cr/Cr₂O₃ layers, designed and developed as a selective solar absorber to be used for unconcentrated solar thermal applications. Both measurements are performed by using a home-made apparatus, which mimics a flat plate collector under high vacuum. A Performance Criterion (PC_η(T)), based on absorber efficiency is proposed, and a forecast of service lifetime is obtained. As a result of the thermal aging tests, the selective solar absorber under study appears to be highly efficient at mid temperatures (up to 573 K) and thermally stable at temperatures (up to 690 K).

The noradrenergic theory of Cognitive Reserve (Robertson, 2013-2014) postulates that the upregulation of the Locus Coeruleus - Noradrenergic System (LC-NA) originating in the Brainstem might facilitate cortical networks involved in attention, and protracted activation of this system throughout the lifespan may enhance cognitive stimulation contributing to Reserve. To test the above-mentioned theory, a study was conducted on a sample of 686 participants (395 controls, 156 Mild Cognitive Impairment, 135 Alzheimer’s Disease) investigating the relationship between LC volume, attentional performance and a biological index of brain maintenance (BrainPAD – an objective measure which compares an individual’s structural brain health, reflected by their voxel-wise grey matter density, to the state typically expected at that individual’s age). Further analyses were carried out on Reserve indices including education and occupational attainment. Volumetric variation across groups was also explored along with gender differences. Control analyses on the Serotoninergic (5-HT), Dopaminergic (DA) and Cholinergic (Ach) systems were contrasted with the Noradrenergic (NA) hypothesis. The antithetic relationships were also tested across the neuromodulatory subcortical systems.Results supported by bayesian modelling showed that LC volume disproportionately predicted higher attentional performance as well as biological brain maintenance across the three groups. These findings lend support to the role of the noradrenergic system as a key mediator underpinning the neuropsychology of Reserve, and they suggest that early prevention strategies focused on the noradrenergic system (e.g. cognitive-attentive training, physical exercise, pharmacological and dietary interventions) may yield important clinical benefits to mitigate cognitive impairment with age and disease.

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked with age-related epigenetic changes in fathers sperm. Understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here we characterize changes in sperm sncRNA between young pubertal and mature rats. We also analyze modification of these changes by exposure to environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). SncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. Distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (2-fold change, FDR p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, piRNA were enriched for LTR targets. BDE-47 accelerated age dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposures.

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. It is associated with aging and hair cell death due to oxidative stress-induced mitochondrial dysfunction. Although transgenic mice and long-term cultures for induction of aging have been used to study ARHL, there are presently no ARHL animal models stimulated by intermittent environmental change for aging. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined based on the expression of the hearing loss-induced phenotype and aging related factors in the short term. The incidence of hearing loss was significantly different among the groups subjected to intermittent hypoxic environment, high-fat diet (HFD), and injection with D-galactose. Continuous oxidative stress and HFD were factors that accelerated cellular aging. Increase in UCP2 affected oxidative stress and mitochondrial dysfunction. CDH23, SLC26A4, KCNQ4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in cells of the hearing organ. We found that intermittent hypoxic, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects intermittent environmental changes, will benefit future research on ARHL.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

Lung cancer is one of the deadliest cancers, leading to about 125,070 deaths in the U.S. each year. Survival rates depend on the type and spread of cancer, with localized non-small cell lung cancer (NSCLC) having a 5-year survival rate of 64%. High mortality is primarily due to late detection and the older age of patients, making surgery too risky. As a result, preventative measures like vaccines are crucial. This paper reviews the literature on CIMAvax-EGF, an EGF-based vaccine for lung cancer, evaluating its preventive potential, impact on survival in advanced NSCLC, and effect on lung cancer mortality in combination with other therapies. CIMAvax-EGF is a promising vaccine targeting the Epidermal Growth Factor (EGF), which promotes cancer cell growth. The vaccine prevents EGF from binding to its receptor by inducing anti-EGF antibodies, potentially halting cancer progression. It shows significant potential for treating advanced NSCLC, with vaccinated patients having a median overall survival of 12.43 months compared to 9.43 months in unvaccinated individuals. A Phase III trial showed that 78.8% of patients had a good antibody response (GAR), leading to longer survival. CIMAvax-EGF is well-tolerated, with mild to moderate side effects, and its efficacy is enhanced when combined with other therapies, such as immune checkpoint inhibitors. Given its ability to target cancer's underlying mechanisms and boost other treatments, CIMAvax-EGF represents a significant advancement in the fight against lung cancer. Administering this vaccine preventively and during treatment could be a major step in reducing lung cancer mortality.

Flavonoids are secondary plant metabolites involved in biological activity that are present in plentiful proportions in many plant origin foods and beverages. Owing to their chemical difference and qualities that make them beneficial for human health, they have received a lot of focus in research. This review therefore presents an account on the chemical structure of flavonoids, food sources and their metabolism with emphasis on bioavailability. And they also examine their antioxidant, anti-inflammatory, anticancer, cardiovascular protective, neuroprotective, and antimicrobial properties and reveal related molecular processes. In addition, it overviews the clinical data concerning their possible use in the prevention and treatment of chronic diseases. Some of the problems that attend current flavonoid research are also dealt with; such issues as variation in the bioactivity of flavonoids and scarcity of clinical studies. This review is designed to present current state of knowledge and to provoke further research concerning the further potential of flavonoids in enhancing human health.

Rising obesity and associated multi-systemic complications amplify the health burden. Euphorbia kansui (EK) extract is clinically recognized for managing obesity. In human study, 240 obese individuals were categorized into two cohorts: those receiving solely herbal medicine (HM group), and those administered EK concomitantly with herbal medicine (EK group). An in vivo examination using C57BL/6-Lepob/Lepob mice elucidated mechanisms involving macrophages and gut microbiota, with associated metabolic advantages. The clinical study revealed a significant 7.22% body weight reduction during 91.55 average treatment days, and examined 16.71% weight loss at 300 days after treatment. In the whole subjects, 60.4%, 21.3% and 6.3% achieved weight reductions exceeding 5%, 10% and 15%, respectively. Impressively, the EK group exhibited superior weight loss compared to the HM group (EK: -7.73% vs. HM: -6.27%, p=0.012). The anti-obesity effect was positively associated with EK therapy frequency and herbal medicine duration. In vivo, EK significantly improved insulin sensitivity and mitigated infiltration of adipose tissue macrophages (ATMs) by modulating the CD11c+ and CD206+ subtypes. EK also correlated with increased Bacteroidetes and Firmicutes populations and reduced Proteobacteria and Verrucomicrobia. Consequently, EK is an effective adjunctive anti-obesity therapy offering metabolic benefits by modulating ATMs and gut microbiota profiles.

Background. Coronary artery disease (CAD) with extensive stenosis presents significant clinical challenges. This case report details the management and outcomes of a 61-year-old male with a notable history of CAD, initially treated with coronary artery bypass grafting (CABG), followed by an innovative intravenous hydrogen and oxygen nanobubble therapy due to recurrent symptoms.Case Presentation. Mr. BH was diagnosed with significant stenosis in the left anterior descending (LAD) artery and left circumflex (LCx) artery, initially managed by CABG. Recurring symptoms led to the adoption of a novel treatment involving hydrogen and oxygen nanobubbles. Following treatment initiation, Mr. BH experienced substantial improvements in physical capacity and symptomatic relief, with an ability to climb 22 flights of stairs and resolution of previous symptoms such as dyspnea and cough. Despite these improvements, subsequent imaging revealed in-stent restenosis and progression of graft disease.Discussion. The application of hydrogen and oxygen nanobubbles as a therapy in CAD is explored, highlighting potential mechanisms such as reduction of oxidative stress and improvement in endothelial function. This case contrasts the effects of conventional surgical and pharmaceutical interventions with the novel nanobubble therapy, illustrating both the benefits and complexities of managing advanced CAD with innovative treatments.Conclusion. While Mr. BH showed clinical improvement with nanobubble therapy, the development of new severe stenosis and restenosis underscores the need for further research to understand the long-term efficacy and mechanisms of nanobubble therapy in complex CAD cases. This case suggests that while innovative therapies may provide symptomatic relief and functional improvement, they do not obviate the need for ongoing surveillance and possibly further intervention.

The aim of this article is to present the course of the COVID-19 pandemic in Poland in 2020-2022, the formation of ad hoc health and anti-crisis policies, an assessment of crisis management and the perceived impact of the pandemic and anti-crisis measures.The paper draws on literature, official reports on the pandemic, data from Eurostat and other information from state institutions and public organisations.Particular attention was paid to the analysis and evaluation of the objectives, instruments and effects of the policies pursued by the state in a coordinated manner, i.e. the anti-pandemic policy and the anti-crisis policy. The anti-pandemic policy in Poland has failed to protect the country from significant personal losses and negative impacts on the health of the population and demographic processes.The anti-crisis policy of the state carried out with the mobilisation of businesses and disciplined society, in the form of anti-crisis shields supplemented and adjusted on an ongoing basis, allowed Poland to avoid a deep crisis and economic recession. Attention was drawn to the need to coordinate the management of health and economic crises nationally and internationally, and to the need to have a medium-term anti-crisis state strategy and a system for the early detection of crisis symptoms.

Both soybean variety and processing affect product characteristics. This study’s objective was to characterize the effect of four extraction methods (variations of soaking and grinding) combined with cooking on the content and composition of phenolic substances, antioxidant and anti-DU145 prostate cancer cell proliferative properties of soymilk prepared from a yellow soybean of the ProSoy variety, which is a high protein variety. Results showed soymilk processing yield was the greatest by Method 4, but Method 2 gave the highest solids and protein yields by about 14 and 12%, respectively. Method 4, a two-step grinding also increased yields (8 and 7%, for solids and protein, respectively), and in all but one instance produced higher total phenolic content (TPC), total flavonoid content (TFC), condensed tannin content (CTC) and total isoflavone content in both raw and cooked soymilk as compared to Method 1. Cooking soymilk reduced 14-17% of total phenolic substances. Cooking reduced anticancer capacity of Method-4-prepared soymilk phenolic extract by increasing IC50 value from about 4.9 mg/mL to 6.8 mg/mL. The increases in phenolic compounds and antioxidants produced in Prosoy soymilk by Methods 2 and 4 with simultaneous increases in product solids yield are significant to benefit the soymilk industry and consumer health. Keywords: ProSoy yellow soybean, soymilk processing, phenolics, isoflavones, antioxidant capacity, anti-DU145 prostate cancer proliferation

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

The increasing demand by consumers for popular healthy fruits, such as the watermelon (Citrullus lanatus), generate substantial bio-wastes, making it imperative to harness the value of these by-products. Watermelon has low-calorie content and several other nutritional benefits that make it suitable for weight management and heart-healthy diets. Within this article, the nutritional composition and bioactives of watermelon which are strongly linked to the prevention of cardiovascular disorders (CVD), cancer, and age-related conditions, will be thoroughly reviewed. In addition, the therapeutic potential effects of watermelon consumption, such as anti-inflammatory, cardio-protective and anti-cancer properties, are also examined, with emphasis to the importance of incorporating watermelon into regular diets for overall health improvement. Additionally, the study explores various applications of watermelon by-products in functional foods, contributing to meeting recommended daily nutrient allowances, as well as in other functional products like cosmetics, with health promoting properties. In conclusion, this comprehensive review underscores the role of watermelon and its by-products for the development of products that can contribute to the prevention of chronic diseases and promote overall well-being

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

Bioactive surface coatings have retained the attention of researchers and physicians due to their versatility and range of applications in orthopedics, particularly in infection prevention. Antibacterial metal nanoparticles (mNPs) are a promising therapeutic, with vast application opportunities on orthopedic implants. The current research aimed to construct a polyelectrolyte multilayer on a highly porous titanium implant using alternating thin film coatings of chitosan and alginate via the layer-by-layer (LbL) self-assembly technique, along with the incorporation of silver nanoparticles (AgNPs) or titanium dioxide nanoparticles (TiO2NPs), for antibacterial and osteoconductive activity. These mNPs were characterized for their physicochemical properties using quartz crystal microgravimetry with dissipation system, nanoparticle tracking analysis, scanning electron microscopy, and atomic force microscopy. Their cytotoxicity and osteogenic differentiation capabilities were assessed by AlamarBlue and alkaline phosphatase (ALP) activity assays, respectively. The antibiofilm efficacy of the mNPs tested against Staphylococcus aureus. The LbL polyelectrolyte coating was successfully applied to the porous titanium substrate. A dose-dependent relationship between nanoparticle concentration and ALP as well as antibacterial effects was observed. TiO2NP samples were also less cytotoxic than AgNP counterparts, although similarly antimicrobial. Together, these data serve as a proof-of-concept for a novel coating approach for orthopedic implants with antimicrobial and osteoconductive properties.

Macrophages play a pivotal role in the process of healing burns. One of the major risks in the course of burns healing, in the absence of regenerating epidermis, is infections which greatly contribute to morbidity and mortality in such patients. Therefore, it is widely agreed that accelerating recruitment of macrophages into burns may contribute to faster regeneration of the epidermis and thus, decreasing the risk of infections. This review describes a unique method for rapid recruitment of macrophages into burns and activation of these macrophages to mediate accelerated regrowth of the epidermis and healing of burns. The method is based on application of bio-degradable “alpha-gal” nanoparticles to burns. These nanoparticles present multiple alpha-gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc-R) which bind the abundant natural anti-Gal antibody that constitutes ~1% of immunoglobulins in humans. Anti-Gal/alpha-gal nanoparticles interaction activates the complement system, resulting in localized production of the complement cleavage-peptides C5a and C3a that are highly effective chemotactic factors for monocytes derived macrophages. The macrophages recruited into the alpha-gal nanoparticles treated burns are activated following interaction between the Fc portion of anti-Gal coating the nanoparticles and the multiple Fc receptors on macrophages cell membranes. The activated macrophages secrete a variety of cytokines/growth factors that accelerate the regrowth of the epidermis and regeneration of the injured skin, thereby cutting the healing time by half. Studies on healing of thermal injuries in the skin of anti-Gal producing mice, demonstrated a much faster recruitment of macrophages into burns treated with alpha-gal nanoparticles than in control burns treated with saline and healing of the burns within 6 days, whereas healing of control burns takes ~12 days. alpha-Gal nanoparticles are non-toxic, and do not cause chronic granulomas or keloids. These findings suggest that alpha-gal nanoparticles treatment may harness anti-Gal for inducing similar accelerated burn healing effects also in humans.

We here investigate the dynamical behavior of a fractional-order predator-prey system with anti-predator behavior and Holling IV type functional response. First we study the non-negativity, existence, uniqueness, and boundedness of solutions to the system from a mathematical analysis perspective. Then, we analyze the stability of its equilibrium points and the possibility of bifurcations using stability analysis methods and bifurcation theory, and prove the existence of a supercritical Hopf bifurcation in the system. After providing numerical simulations to illustrate the conclusions theoretically derived, by summarizing those various analytical results obtained, we finally present three interesting conclusions that can contribute to better understanding and preservation of ecological systems.

Laser direct writing allows for the fabrication of complex structures, which is particularly advantageous in micro-optic applications. However, the increasing demand for optics quality requires the lowest optical power loss, which can occur from unwanted reflections. This research demonstrates the possibility of forming an anti-reflective coating on hybrid-polymer micro-lenses fabricated by employing laser direct writing (LDW), without changing their geometry. Such coating deposited by atomic layer deposition (ALD) decreased the reflection from 3.3 % to 0.1 % at the wavelength of 633 nm for one surface of SZ2080™.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens means requirement of harsh treatment methods such as medicinal drugs or antibiotics. However, such treatments impact the gut microbiome, and create dysbiosis, often leading to opportunistic pathogens, anti-microbial resistance, or functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). Recent studies have shown that these impacts do not remain confined to gut, and are reflected across the gut-brain, gut-liver, and gut-lung axes, among others. Therefore, apart from the medicinal treatment, nutritional supplementation is also a key aspect of providing the recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, the nutritional supplementation also helps to build a resilience against the opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterises the fundamental host-pathogen interaction biochemical pathways, at various infection and recovery stages. This same mechanism also allows to track the impact of abovementioned treatment methods of gut microbiome remediation. This manuscript is organised in sections delving into system biology approaches and upcoming developments to understand (1) Infection mechanism and current global status; (2) Cross-organ impacts of dysbiosis, particularly within gut-liver and gut-lung axes; (3) Nutritional interventions. It highlights the impact of antimicrobial resistance (AMR) and Multi-drug resistance (MDR) from a perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena.

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

Understanding the complex interactions between metabolism and the immune system (“meta-flammation”) is crucial for the identification of key immunomodulatory factors as potential therapeutic targets in obesity and in cardiovascular diseases. Cathelicidin antimicrobial peptide (CAMP) is an important factor of innate immunity and is expressed in adipocytes. CAMP therefore might play a role as an adipokine in metaflammation and adipose inflammation. Toll-like receptor (TLR) 9 is another component of the innate immune system that is expressed and functionally active in adipocytes. The aim of the present study was to investigate the impact of TLR9 signaling on CAMP expression in adipocytes and in adipose tissue. CAMP gene expression in murine 3T3-L1 and human SGBS adipocytes and in murine and human adipose tissues was quantified by real-time PCR. TLR9 knockdown was applied in murine 3T3-L1 adipocytes via siRNA transfection. Adipocyte inflammation was induced in vitro by TNFα stimulation. Serum CAMP concentrations in TLR9 knockout (KO) and in wildtype mice were quantified by ELISA. CAMP gene expression was considerably increased in 3T3-L1 adipocytes during differentiation. TNFα significantly induced CAMP gene expression in mature adipocytes, which was antagonized by inhibitors of NF-κB and PI3K signaling. Cell-free nucleic acids (cfDNA) as endogenous TLR9 ligand significantly impaired CAMP gene expression, whereas synthetic agonistic and antagonistic TLR9 ligands had no effect. Cellular TLR9 knockdown reduced adipocyte CAMP gene expression in vitro and male TLR9 knockout mice exhibited lower systemic CAMP concentrations than wildtype mice. CAMP and TLR9 gene expression were correlated positively in murine and human subcutaneous but not in intraabdominal/visceral adipose tissues. These findings suggest a regulatory role of TRL9 in adipocytic CAMP expression as a novel putative molecular mechanism in adipose tissue innate immunity.

In the history of civil aircraft transportation, ice formation has been identifies as a key factor in the safety of flight. Anti-icing and deicing system have emerged through the years with the aim to prevent or to eliminate ice formation on wing airfoil, control surface and probes. Modern flying machine demand more efficiency in order to reduce the carbon footprint and increase the sustainability of flight transport. In order to achieve this goal the need to have efficient aircraft with efficient and low power consuming system is fundamental. This paper proposes a new model for ice accretion using computational fluid dynamics (CFD). This model permits to simulate the shape of the ice formed over a profile varying boundary conditions (i.e.- speed, liquid water content and so on). The proposed model takes into account also the amount of heat transferred between water and the surrounding environment and includes the effects of air turbulence on the ice formation process. The CFD simulations have been validated with NASA experimental outcome and show good agreement. The proposed model can be also used to investigate the effects of various parameters such as air speed, Liquid Water Content and air temperature on the ice formation process. The results evidences that the proposed model can accurately predict ice formation process and is suitable to optimize the design of anti-icing or deicing system for aircraft and helicopters. This approach is not limited to aerospace but can also be exported to other applications such as transportation, wind turbine, energy management and infrastructure.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.

The COVID-19 pandemic affects all parameters, especially health care professionals, drugs and medical supplies. The KERRA is a mixed medicinal plant capsule that is used for the treatment of patients with high fever with food and drug administration approved by FDA Thailand. Recently, KERRA showed quicker recovery for COVID-19 patients. Therefore, it is possible that some ingredients in KERRA could inhibit SARS-CoV-2. In this study, two important replication-related enzymes in SARS-CoV-2, a main protease and an RNA-dependent RNA polymerase (RdRp), were used to study the effect of KERRA. The results showed that KERRA inhibited the SARS-CoV-2 main protease and SARS-CoV-2 RdRp with IC50 values of 49.91 ± 1.75 ng/mL and 36.23 ± 5.23 µg/mL, respectively. KERRA displayed no cytotoxic activity on macrophage cells at concentrations lower than 1 mg/mL and exhibited anti-inflammatory activity. Additionally, KERRA was against a feline coronavirus (feline infectious peritonitis [FIP]) infection with an EC50 value of 134.3 g/mL. This study supports the potential use of KERRA as a candidate drug for COVID-19.

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

Porifera, commonly referred to as marine sponges, have stood out as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention along years. They are widespread in all continents, and several structurally unique compounds have been identified from species of this genus. Terpenes, mainly sesterterpenoids, represent the great majority of secondary metabolites isolated from Phorbas species, even though several alkaloids and steroids have also been reported. Many of these compounds have shown a variety of biological activities. Particularly, Phorbas sponges have been demonstrated to be a source of cytotoxic metabolites. In addition, MNPs exhibiting cytostatic, antimicrobial and anti-inflammatory activities, have been isolated and structurally characterized. This work brings an overview of Phorbas secondary metabolites reported since the first study published in 1993 until 2020, and their biological activities.

Oxidative stress initiates and facilitates the disruption of the structural integrity of hepatic mitochondria, which leads to steatosis, steatohepatitis, fibrosis, and cirrhosis. It is now evident that mitochondrial dysfunction could be responsible for alcoholic liver disease (ALD). The challenge in treating ALD has been the limited availability of hepatoprotective agents and the lack of highly efficient delivery systems. Recent studies have shown that mitochondria-targeted therapies could address mitochondrial dysfunction (MD), which may greatly improve hepatoprotection and ALD treatment. This mini-review discusses the potential role of mitochondria-targeted antioxidants (MTAs) in the maintenance of hepatocellular integrity. This report also considers the mechanism of liver injury induced by alcohol and the progression of ALD from a mitochondrial oxidative damage perspective as well as the possible mechanistic actions of hepatoprotective antioxidants. Preliminary studies suggest the prospect of MTAs as anti-ALD and hepatoprotective agents.

Immune checkpoint inhibitors (ICIs) – anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events have been linked to these agents. However, tuberculosis (TB) reactivation during their use is increasingly reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 Immune histochemistry (IHC) strongly positive in 95% of tumor cells. The patient presented with high-grade fever and a history of productive cough for a 1-week duration. A few days later, she was diagnosed with pulmonary tuberculosis following the 6th cycle of Pembrolizumab, an anti-PD-1 monoclonal antibody. AFB smear and TB PCR from BAL were positive (rifampin resistance not detected), and she was accordingly started on Anti-TB medications. Immunotherapy was held. Of note, the patient had a history of sick contact with a patient with active TB infection ten years ago, but there was no documentation of latent TB or previous TB infection. Her HIV status is negative. Her sputum AFB smear continued to be positive after four weeks of anti-TB medications. Later, the patient was discharged after her sputum was cleared from AFB (negative x 2 sets). We assumed that our patient developed reactivation of pulmonary tuberculosis secondary to an immune checkpoint inhibitor (Pembrolizumab). She was not re-challenged with Pembrolizumab following TB diagnosis. To our knowledge, this is the first reported case from the Arab and the Middle East; it reinforces the previous observations of the association between ICIs administration and the development of MTB. Nevertheless, further studies in the clinical setting are necessary to establish the exact mechanism involved in this association. Oncologists' awareness & prompt recognition of this potential hazardous consequence are essential. Since there is no clear evidence whether LTBT prior PD-1/PD targeted immunotherapy is required, targeted LTBT before starting ICIs immunotherapy with TB chemoprophylaxis; yet to be explored, particularly in the regions where the MTB prevalence is high.

Solid tumors display complex biology and most therapies including chemotherapy cannot prevent therapy resistance and relapse. Most therapeutics target cancer cells, but recent data suggest the presence of cancer stem cells as cells with self-renewal and tumorigenic abilities. Cancer stem cell markers have been suggested to have prognostic value and can be targeted during cancer treatment and in resistant disease. CSCs have been postulated to play significant contextual roles in tumor initiation, progression, therapy resistance and metastasis. CSCs have thus been targeted by new generation cancer drugs. The transcriptional expression of several CSC markers in different cancers was evaluated by searching publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We report here new findings on expression and prognostic significance of CSC markers in several cancers by examining the expression of CSCs markers in tumor tissues versus the adjacent normal tissues. We found that CSC markers were mostly highly expressed various tumors such as colon, lung, pancreatic and esophageal cancers. No CSC marker is expressed in the same pattern in all cancers and individual CSC marker expression was not linked to patient survival. This analysis calls for continued research on CSCs and clinical evaluation of the CSC markers in relation to prognosis of cancers in large population samples. Novel cancer drugs ought to target CSCs, cancer cells and tumor microenvironment variations.

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

The aim of the study was to determine the possibility of suppression of the prostaglandin synthesis by new derivatives of N-phenylanthranilic acids; they inhibit the activity of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme using the method of a flexible molecular docking. For the docking studies the crystallographic structural models with high resolution from Protein Data Bank were used: mPGES-1 in the complex with glutathione (pdb code 4AL0). A flexible molecular docking was carried out using the Molecular Operating Environment (MOE) software package. According to the results of the docking studies four scoring functions were calculated (Affinity dG Scoring, Alpha HB Scoring, London dG Scoring, GBVI/WSA dG Scoring). The values of the scoring functions calculated indicate the thermodynamic probability and energy favorability of forming complexes between molecules of the substances under research and the specified receptor, in which arrangement of ligands in the active site of the receptor and residues of amino acids of side chains are of similar geometry and types of binding of the known inhibitors of mPGES-1 determined on the basis of the crystallographic studies.

From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated, among them, four icetexanes, and one abietane (1–5), which are first reported. Their structures were established by spectroscopic means, mainly ¹H and ¹³C NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the isolated diterpenoids were tested for their antiproliferative, anti-inflammatory, and radical scavenging activities using the sulforhodamine B assay on six cancer cell lines, the TPA induced ear edema test in mice, and the reduction of the DPPH assay, respectively. Some diterpenoids showed anti-proliferative activity, these being icetexanes 6 and 3, which were the most active with IC₅₀ (µM) = 0.27 ± 0.08 and 1.40 ± 0.03, respectively, for U251 (human glioblastoma) and IC₅₀ (µM) = 0.0.46 ± 0.05, and 0.82 ± 0.06 for SKLU-1 (human lung adenocarcinoma), when compared with adriamycin (IC₅₀ (µM) = 0.08 ± 0.003, and 0.05 ± 0.003, as the positive control, respectively. Compounds 3 and 10 showed significant reduction of the induced ear edema of 37.4 ± 2.8 and 25.4 ± 3.0% (at 1.0 µmol/ear), respectively. Compound 4 was the sole active diterpenoid in the antioxidant assay (IC₅₀ = 98. 4 ± 3.3), using α-tocopherol as positive control, IC₅₀ (µM) = 31.7 ± 1.04. The diterpenoid profile found is of chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora with other members of the section Tomentellae.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

We summarize structural instabilities exhibited by the one dimensional (1D) (arene)2X family of organic conductors in relation with their electronic and magnetic properties. With a charge transfer of one electron to each anion X these salts exhibit a quarter-filled (hole) conduction band located on the donor stacks. Compounds built with donors such as fluorenthene and perylene derivatives and anions X such PF6 or AsF6 exhibit a high temperature (TP~170K) conventional Peierls transition which is announced by a sizeable regime of 1D 2kF charge density wave fluctuations (kF is the Fermi wave vector of the 1D electron gas located on Per stacks). Surprisingly, and probably because of the presence of a multi-sheet warped Fermi surface, the Peierls transition is considerably reduced in the perylene series α-(Per)2[M(mnt)2] where X is the dithiolate molecule with M=Au, Cu, Co and Fe. A special attention is devoted in this paper to physical properties of α-(Per)2[M(mnt)2] salts which with M=Pt, Pd and Ni incorporate segregated S=1/2 1D antiferromagnetic (AF) dithiolate stacks with 1D metallic Per stacks. We analyse conjointly the structural and magnetic properties of these salts in relation with the 1D spin-Peierls (SP) instability located on the dithiolate stacks. We show that the SP instability of the Pd and Ni derivatives occurs in the classical (adiabatic limit) while the SP instability of the Pt derivative occurs in the quantum (anti-adiabatic limit). Furthermore we show that in the Pd and Ni derivatives frustrated 1st neighbour direct and 2nd neighbour indirect (through a fine tuning with the mediated 2kF RKKY coupling interaction on Per stacks) AF interactions add their contribution to the SP instability to open a singlet-triplet gap. Our analysis of the data show unambiguously that magnetic α-(Per)2[M(mnt)2] salts are a typical realization of the physics predicted for two chain 1D Kondo lattices.

It is often said in human society that it all starts from the mind, and this is true. The answer to the question “Why is it that pets require much fewer years to fully develop than humans?” could be headed to the Theory of Relativity and the perceived time according to the levels of instinct and rationality. It is perhaps no wonder that the French language translates the word “mind” as “l’esprit”, which also means “spirit” in the English language. Given that the Theory of Relativity applies to all physical matter, the theory applies to chemistry, biology and psychology as well. The level of instinct is proportional with the perceived speed of time and implicitly, to the speed of time itself for the whole organism, given that the nervous system coordinates all bodily functions. A pet may experience a few years as humans experience over a decade, making their perceived lifetime to be approximately equal to the human’s. The same applies to the perception of space and its components. This aspect would emphasise upon the fact that all life on Earth shows the same degree of value with regards to uniqueness. Nevertheless, the values represented by the hierarchy of competences among living organisms at the same time differs based on species. Honour of uniqueness and hierarchy of competences represent two scientific concepts that never overcross. As a result, there is no evidence to suggest that scientific facts as such constitute a form of contradiction to philosophical and religious ideas, given that religion refers to animals as companions of humans. With regards to the clock of the living organism; there are three kinds of clocks in a living organism: the emotional clock, the cognitive clock and the molecular clock. These three categories actually constitute the temporal layers of our dimension, so they are in a relationship of interdependence. When one has a feeling that time is slower or quicker, they are not fully experiencing that change in the time speed, but only partially. And one can profoundly experience the change of perceived time speed when they experience profound feelings, which sweep them away from reality. Complete, deep mental focus can bring about this profound change in perception, which will make the individual feel as if they are in a different form of reality. When one is more instinctive, the person in cause perceives time as slower and sees more opportunities within the same frame of time and space. When one experiences the “Fight or flight” mode, the person in the cause finds themselves to be in danger and has two options; to try to prevail over the danger or to flee it. Whilst experiencing such a mode, people are much more alert and therefore, time passes more slowly and the physical space dilates. When people are relaxed, however, time and space become smaller, and when they are in a deep state of resting, they become very small. And where there is a smaller dimension, there is a greater speed, just as the circulating air gains speed when it crosses narrow passages.

1960s Europe saw a large number of residential neighborhoods built to house those migrating from the countryside. Today, more than 50 years later, these neighborhoods suffer high levels of functional, social, and technical obsolescence. In response to this, University of Seville developed the Aura Strategy as an intervention methodology to find global solutions to issues in outdated neighborhoods. To provide visibility to this aspect of the Aura strategy, the retrofit proposal presented in this article provides a solution to improve the roofing of buildings in a case study neighborhood (Polígono de San Pablo, Seville) and an analysis of the results in terms of energy and financial savings for local residents. The results show that for a population of roughly 18,000 (in 2018), net savings, including energy and retrofitting costs, ranging from nearly 6.5 to over 8.6 million can be made over the 20-year life cycle span. Likewise, the results obtained on the reduction of thermal loads indicate a 72% decrease in energy consumption, equivalent to a saving of close to 4,500 tons of greenhouse gas emissions for the district and the entire life cycle time period, with the consequent benefits on the impact on air quality and and the fight against climate change. climate change.

Falls, highly common in the constantly increasing global aging population, can have a variety of negative effects on their health, well-being, and quality of life, including restricting their capabilities to conduct Activities of Daily Living (ADLs), which are crucial for one’s sustenance. Timely assistance during falls is highly necessary, which involves tracking the indoor location of the elderly during their diverse navigational patterns associated with ADLs to detect the precise location of a fall. With the decreasing caregiver population on a global scale, it is important that the future of intelligent living environments can detect falls during ADL.s while being able to track the indoor location of the elderly in the real world. Prior works in these fields have several limitations, such as – the lack of functionalities to detect both falls and indoor locations, high cost of implementation, complicated design, the requirement of multiple hardware components for deployment, and the necessity to develop new hardware for implementation, which make the wide-scale deployment of such technologies challenging. To address these challenges, this work proposes a cost-effective and simplistic design paradigm for an Ambient Assisted Living system that can capture multimodal components of user behaviors during ADLs that are necessary for performing fall detection and indoor localization in a simultaneous manner in the real world. Proof of concept results from real-world experiments are presented to uphold the effective working of the system. The findings from two comparison studies with prior works in this field are also presented to uphold the novelty of this work. The first comparison study shows how the proposed system outperforms prior works in the areas of indoor localization and fall detection in terms of the effectiveness of its software design and hardware design. The second comparison study shows that the cost for the development of this system is the least as compared to prior works in these fields, which involved real-world development of the underlining systems, thereby upholding its cost-effective nature.

Neuronal lesion or injury is a traditional approach to investigate neural circuit. Is any new neural pathway or new neurodegeneration related central nerve system injury? Spinal disc herniation can cause the spinal cord injury. However, the histological examination is still lack. It happened that a case of spinal disc herniation of a 10-year old dog was examined with NADPH diaphorase (N-d) histology. We did not find the N-d neurodegenerative aberrant in the tissue of the mid-rostral lumber segment besides the metamorphoses by the compression of the disc herniation. However, the severe neuropathological changes majorly occurred in the lumbosacral spinal cord. We found more diverse neurodegenerative alterations: the aging-related N-d body (ANB), megaloneurite and N-d homogeneous formazan globule in the lumbosacral spinal cord. We also found that a new circuit pathway (intermedial collateral pathway) showed by a megaloneurite between the lateral collateral pathway and the medial collateral pathway. The enormous notch caused by spinal disc herniation located at the mid-rostral lumber segments. The aging-related neurodegeneration occurred the specific lumbosacral segments. The homogeneous formazan globule was round or oval homogeneous N-d positivity which distributed in the gray matter and dorsal column. In the medulla oblongata, ANBs were revealed in the gracile nucleus, nucleus reticularis lateralis (ventrolateral spinal trigeminal nucleus) and middle of the spinal trigeminal nucleus.

Purpose: To evaluate the impact of intravitreal bevacizumab (IVB) therapy on anatomical and visual outcomes in patients with macular neovascularization (MNV) secondary to chronic cen-tral serous chorioretinopathy (cCSC). Methods: This retrospective observational study reviewed the medical records of treatment-naïve patients diagnosed with cCSC complicated by MNV, treated with IVB injections over a 5-year period. The presence of MNV was confirmed using op-tical coherence tomography angiography (OCTA). Best-corrected visual acuity (BCVA), subfoveal choroidal thickness (SFCT), and subretinal fluid (SRF) were recorded pre- and post-IVB treat-ment. Results: Twenty-two eyes of 22 patients (mean age, 68 ± 11 years) were included. After a mean follow-up of 21.0 ± 14.6 months, SRF significantly decreased from baseline (176.86 ± 115.62 µm) to the final follow-up (80.95 ± 87.32 µm, P = 0.003). Greater SRF reduction was associated with more injections (>7) (P = 0.047). However, no significant changes were observed in BCVA (P > 0.05) or SFCT (P > 0.05), irrespective of follow-up duration or injection frequency. Complete res-olution of SRF was achieved in 9 patients (40.9%), and a significantly greater reduction in SFCT was observed in complete responders compared to non-responders (P = 0.03). Conclusion: IVB therapy significantly reduced SRF in cCSC patients with secondary MNV, though it did not lead to visual improvement or significant changes in SFCT. However, greater choroidal thinning in patients with complete fluid resorption may suggest distinct underlying mechanisms or alterna-tive sources of subretinal fluid beyond the MNV itself.

As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ^◦C were reduced by three orders of magnitude (from 10^-9 M to 10^-6 M) compared to the K d at 37 ^◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

Conjugative transposons in Gram-negative bacteria have a significant role in the dissemination of antibiotic-resistance-conferring genes between bacteria. This study aims to genomically characterize plasmids and conjugative transposons carrying integrons in clinical isolates of Klebsiella pneumoniae. Genetic composition of conjugative transposons and phenotypic assessment of 50 multidrug-resistant K. pneumoniae isolates from Tertiary-care Hospital (SQUH), Muscat, Oman was investigated. Horizontal transferability was investigated by filter- mating conjugation experiments. Whole genome sequencing (WGS) was performed to determine the sequence type (ST), acquired resistome and plasmidome of integron-carrying strains. Class 1 integron was detected in 96% of isolates and among integron-positive isolates, 18 stains contained variable regions. Horizontal transferability by conjugation confirmed the successful transfer of integrons between cells and WGS confirmed their presence in conjugative plasmids. Dihydrofolate reductase (dfrA14) was the most prevalent (34.8%) gene cassettes in class 1 integrons. MLST analysis detected predominantly ST-231 and ST-395. BlaOXA-232 and blaCTX-M-15 were the most frequently detected carbapenems and beta-lactamases in sequenced isolates. This study highlighted the high transmissibility of MDR-conferring conjugative plasmids in clinical isolates of K. pneumoniae. Therefore, the wise use of antibiotics and the adherence to effective infection control measures are necessary to limit further dissemination of multidrug-resistant organisms.

Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e. GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have lower expression of GRb, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease modifying therapies to better treat these two sight threatening forms of glaucoma.

Methicillin-resistant Staphylococcus aureus (MRSA) exerts a considerable concern in healthcare and the community. Globally MRSA strains cause numerous infections with high morbidity and mortality rates. The success of MRSA is a result of the extensive production of virulence factors. With the limited treatment options for the MRSA infection and growing resistance problem, an urgent call is needed to search for an alternative to antibiotics. One of the promising strategies is targeting the quorum sensing (QS) system, of the MRSA, by using a dendrimer loaded with kinase inhibitor peptide. This study formulates a poly-amidoamine dendrimers (PAMAM) G4 dendrimers loaded with Quorum Quencher (QQ), QQ3 peptide which is a Histidine Kinase inhibitor. The physicochemical properties of the formula were characterized using different in-vitro analysis method such as Zetasizer and transmission electron microscope (TEM). The antibacterial activity and anti-virulence effect of the formula was tested against MRSA and different mutant stains using growth assay, haemolysis assay and biofilm assay. Overall, QQ3-G4 complex showed antibacterial and anti-virulence activity and it can be a potential alternative treatment to overcome antimicrobial resistance and treat MRSA infection.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

The purpose of the study was to determine the “retinal thickness deviation” (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations be-tween RTD and best-corrected visual acuity (BCVA). We conducted a retrospective study, in-cluding consecutive DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline, 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) μm at baseline, 97.0 (99.7) μm at 12 months and 89.9 (75.3) μm at 24 months of follow-up (P < .001). RTD showed a moderate association with BCVA at baseline (R2=0.134, p<0.001) and 12 months (R2=0.197, p<0.001), and a substantial association at 24 months (R2=0.272, p<0.001). The CST showed a moderate association with BCVA at baseline (R2=0.132, p<0.001) and 12 months (R2=0.136, p<0.001), while the association was weak at 24 months (R2=0.065, p=0.009). In conclusion, RTD showed a good association with visual outcome in DME eyes undergoing intravitreal treatment.

The pandemic associated with SARS-CoV-2 is a worldwide public health challenge. The WHO has proposed to achieve 70% COVID-19 vaccination coverage in all countries by mid-2022. Nevertheless, the prevention strategy based on COVID-19 vaccination and other applied prevention measures have not been sufficient to prevent SARS-CoV-2 epidemic waves. The study assessed the vaccination coverage that would be required to establish herd immunity against SARS-CoV-2 by taking into account virus transmissibility (Ro values from 1.1 to 10) and Covid-19 vaccination effectiveness. The study found that Covid-19 vaccination programs could establish herd immunity against SARS-CoV-2 with Ro &lt; 3 with levels of Covid-19 vaccination effectiveness of 10−100% and against viruses with Ro values ranging from 3 to 10 with levels of Covid-19 vaccination effectiveness of 70−100%. Factors reducing Covid-19 vaccination effectiveness (emergent variants, reinfections, high risk individuals) and factors increasing SARS-CoV-2 transmissibility (close settings) increased percentages of vaccination coverage that would be required to establish herd immunity. The vaccination coverage objective of 70% could be adequate against SARS-CoV-2 with Ro values of 1.1−2.5, while percentages of vaccination coverage of 80% and 90% could be more adequate against viruses with Ro values of 2.5−3.5 and &gt;3.5, respectively. On February 2022, the vaccination coverage for complete vaccination was lower than 70% in 73.2% of the countries of the world. Percentages of Covid-19 vaccination coverage must be increased in most countries of the world to increase individual and herd immunity levels in the population.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Triple negative breast cancer (TNBC) has a higher mRNA expression of programmed cell death ligand 1 (PD-L1) which is a ligand to programmed cell death protein 1 (PD-1). The binding of the ligand leads to suppressed activity of T-cell-mediated immune response against cancer cells. The approval of anti-PD-L1 drugs including pembrolizumab and atezolizumab in subgroups of TNBC offer potential improvement to the current treatment regimens available for TNBC. We conducted a meta-analysis to review the efficacy of pembrolizumab and atezolizumab for the treatment of TNBC in both adjuvant and neo-adjuvant settings. A systematic strategy was used as per the PRISMA 2020 statement. All statistical analyses were conducted using Review Manager 5.4. Outcome measures included objective response rate, progression free survival, overall survival in adjuvant therapy groups, and pathological complete response rates in neoadjuvant groups. Six clinical trials were included. For adjuvant therapies, the ORR (OR=1.26, P = 0.04) of Atezolizumab/Pembrolizumab plus chemotherapy was higher in intention to treat (ITT) arms than the placebo groups in TNBC. A positive effect size was found for PFS in the ITT arms (Cohen’s d = 1.55, P<0.001). The Atezolizumab plus chemotherapy group had a positive effect size for OS compared to the control groups (Cohen’s d = 0.52, P<0.001). In the neo-adjuvant setting, patients in ITT arms had higher pCR rates as compared to the control groups (OR= 1.61, P = 0.001). Our findings collate evidence of pembrolizumab and atezolizumab as a viable treatment option among patients with TNBC with PDL1+ subgroups deriving benefits.

Mutual survival among different species of living organisms is quite common in our living world. That mutual survival can produce symbiotic or parasitic relationship among different living organisms. But at the same time, some relationships are harmful to the living organisms creating pathogenic relationships. Why some mutual survivals are beneficial, whereas some relationships are harmful creating different diseases in the living world? That harmful or pathological relationship producing different diseases in both the animal and plant kingdom has been extensively studied by the scientific community several times under the heading of ‘Host-pathogen interaction’ and ‘Disease pathogenesis’. But it is still not clear why some mutual survivals are beneficial or non-harmful, whereas some co-survivals are harmful producing different disease conditions in the living world mainly due to different immune mediated reactions or direct toxic effect of substances produced by an organism. To find the answer to this question, we have to search retrospectively to the evolutionary pattern of our diverse living world. If it is assumed that we have originated from Last Universal Common Ancestor (LUCA) by different cumulative mutations, horizontal gene transfer, mobile genetic elements (MGE), transposition and natural selection, then it would be quite pragmatic to consider that two things were moving side by side in our ancient living world. On one hand it’s purpose was to create the diversification of both unicellular and multi-cellular living world and on the other hand it’s another purpose was to maintain the specific identity of the living organisms. It is the second purpose or the maintenance of specific identity that ultimately led to the development of Immune system.

One in eight women will be diagnosed with breast cancer (BC) in their lifetime, resulting in over 2 million cases annually. BC is the most common cancer among women. Unfortunately, the etiology of majority of cases remains unknown. Recently, evidence has shown that the human microbiota plays an important role in health and disease. Intriguingly, studies have revealed the presence of microorganisms in human breast tissue, which was previously presumed to be sterile. Next-generation sequencing technologies have paved way for the investigation of breast microbiota, uncovering bacterial signatures that are associated with BC. Some of the bacterial species were found to possess pro-carcinogenic and/or anti-carcinogenic properties, suggesting that the breast microbiota has potentially crucial roles in maintenance of breast health. In this review, we summarize the recent findings on breast tissue microbiota and its interplay with BC. Bacterial signatures identified via next-generation sequencing as well as their impact on breast carcinogenesis and cancer therapies are reviewed. Correlation of breast tissue microbiota and other factors, such as geographical and racial differences, in BC is discussed. Additionally, we discuss the future directions of research on breast microbiota as well as its potential role in prevention, diagnosis and treatment of BC.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

The current state-of-the-art does not provide a universal and rapid method of determining the state of health (SOH) of a battery or a supercapacitor without carefully examining the degradation of hundreds of full charge/discharge cycles. Lithium-ion batteries, sodium-ion batteries and supercapacitors of different cell chemistries were studied by impedance spectroscopy during lifetime tests. Faradaic and capacitive charge storage are distinguished by the relationships between stored electric charge and capacitance. For batteries, impedance spectroscopy is best applicable in the flat region of the voltage-charge curve. An approximately linear correlation between pseudocapacitance and Ah capacity is observed as long as overcharge and deep discharge are avoided. The correct calculation of quantities related to complex impedance and differential capacitance is outlined – which may also be useful as an introductory text and tutorial for newcomers to the field. Novel diagram types are proposed for the purpose of instant performance and failure diagnosis of batteries and supercapacitors.

Thin twin-roll cast strips from a model Al-Cu-Mg-Li-Zr alloy with a small addition of Sc were prepared. A combination of a fast solidification rate and a favorable effect of Sc microalloying impacts the size and distribution of primary phase particles and the dimension of eutectic cells. Small interdendritic spacing in the range of 10-15 um enables substitution of the initial long-term homogenization annealing by a two-step annealing at 300 and 450 °C and a short solution treatment at 530 °C before quenching and the final age-hardening procedure. A dense dispersion of small Al3(Sc,Zr) precipitates intensively inhibiting recrystallization forms during this treatment. Further refining and fragmentation of the structure were performed using constrained groove pressing before the solution treatment. Small pre-straining of quenched specimens and subsequent age-hardening simulating T8 temper were used to promote the formation of a homogeneous distribution of strengthening particles and to suppress preferential heterogeneous precipitation on subgrain and grain boundaries. Microstructural features and microhardness evolution during annealing were critically examined and confronted with microstructural characteristics observed on reference mold cast alloy or alloys without Sc alloying. The proposed treatment represents a model near net shape procedure for manufacturing thicker sheets for the aerospace industry.

In this paper, we identify several relative ordering properties of the modified proportional hazard rate and modified proportional reversed hazard rate models. For this purpose, we use two well-known relative orderings, namely the relative hazard rate ordering and the relative reversed hazard rate ordering. The investigation is to see how a relative ordering between two possible base distributions for the response distributions in these models is preserved when the parameters of the underlying models are changed. We will give some examples to illustrate the results and the conditions under which they are obtained.

Background: The link between nocturia and aging male symptoms (AMS) has not been scientifically established. This study aimed to measure the degree of severity of AMS that impact on the health-related quality-of-life (HRQoL) in adult males living with nocturia, and to determine the predictive values of nocturnal factors on AMS. Methods: It is an extended analysis of new data collected by using the Hong Kong Traditional AMS (HK-AMS) scale and Cantonese version of the Pittsburgh Sleep Quality Index (PSQI) in a recently published cross-sectional population-based survey. Results: Of the 781 respondents that have completed the set of questionnaires, 68% and 61% of men living with nocturia reported clinically significant (at moderate-to-severe levels) somato-vegetative and sexual AMS, whereas the prevalence and severity were increased with advancing nighttime voiding frequency. The nocturia-specific QoL (NQoL) score and nocturnal frequency were found to be significant predictive factors for composite, somato-vegetative and sexual AMS, in addition to age, global OSQI score, and certain metabolic diseases. Conclusions: Current findings suggested the inclusion of nocturia when measuring the male-specific HRQoL related to aging.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.