Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic properties. The interaction of non-steroidal anti-inflammatory drugs with cell membranes can affect their physicochemical properties, which, in turn, can cause a number of side effects in the use of these drugs. Electron paramagnetic resonance (EPR) spectroscopy could be used to study the interaction of diclofenac with the membrane, if its spin-labeled analogs existed. This paper describes the synthesis of spin-labeled diclofenac (diclofenac-SL), which consists of a simple sequence of transformations such as iodination, esterification, Sonogashira cross-coupling, oxidation and saponification. EPR spectra showed that diclofenac-SL binds to in a lipid membrane composed of palmito-yl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). 2H electron spin echo spectroscopy (ESEEM) was used to determine the position of the diclofenac-SL relative to the membrane surface. It has been established that the average its depth of immersion corresponds to the 5th position of the carbon atom in the lipid chain.

The affordable production of valuable antioxidant extracts from plant resources depends on the availability of enabling technologies, such as hydrodynamic cavitation (HC), characterized by unrivalled effectiveness, efficiency, and scalability in the extraction of natural products. As sources of phytochemicals showing biological effects on human health, including anti-cancer properties, pomegranate (Punica granatum L.) fruits were processed using HC. Fractions collected during the process (M1-M5) were lyophilized (L), filtered (A), or used as such (C), for identifying their best conservation practice. Biochemical profile and in vitro antioxidant power were investi-gated by spectrophotometric and chromatographic assays. The antiproliferative effect of L-M3, resulting from just 15 minutes of extraction, was tested on human breast cancer line (AU565-PAR) and peripheral blood mononuclear (PBMCs) cells from healthy donors. M3-M4 fractions from L and C series revealed the highest antiradical activity and phenolic content. Cell growth, death, and redox state were assessed, showing that the pomegranate extract M3 significantly reduced tumor cell proliferation and intracellular oxygen reactive species. No effect on PBMCs was de-tected. Thus, the use of antioxidants isolated using HC as adjuvants in anticancer therapies might be advantageous and affordable; moreover, since oxidative stress contributes to cancer devel-opment, its reduction might be the leading mechanism.

The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antibiotic resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The aim of this study was to characterize TiO2-NP formulations and evaluate their antibacterial and wound healing abilities. The diameters and zeta potentials were determined using the Zetasizer in conjunction with dynamic light scattering. The agar-well diffusion method, time-kill kinetic assay and crystal violet assay were used to evaluate their antimicrobial activities. Wound healing assays were conducted both in-vitro and in-vivo. The study demonstrated that TiO2-NP formulations exhibit significant antimicrobial properties against various bacterial strains such as S. aureus and E. coli. No measurable E. coli growth was observed within a 15-mins period following exposure to TiO2-NP formulations. The TiO2-NP formation can improve wound healing by enhancing cell migration and collagen formation in both in-vitro and in-vivo conditions. In summary, our study suggests that TiO2-NP has the potential for use as an antimicrobial agent for animal wound treatment due to its ability to suppress bacterial growth and biofilm formation, as well as to enhance wound healing.

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive proper-ties, especially given the beneficial properties of its fruits in this regard. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. Extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary de-pending on the organ, with the highest amount of polyphenols found in the leaves extract. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.88 mgTE/g for leaves to 65.25 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.93 mg TE/g) and the highest level was found for the barberry leaves (140.49 mgTE/g). The oxygen radical absorption capacity test (ORAC) showed the lowest value for the stem (167.70 mgTE/g) and the highest level for the leaves (267.81 mgTE/g). The range of percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of flavonoids, TPC, TFC, and the content of selected flavonoids. For the first time, phenolic acids, flavonoid agly-cones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. For the first time, the following phenol-ic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris: 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, flavonoid glycosides: eleuthero-side E, rutin, isoquercitin, luteoloside, nar-cissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones: catechin, luteolin, and eriodictyol were determined qualitatively and quantitatively for the first time as well.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury, caused by several factors, including ischemia, toxins and inflammation, has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. Thus, this review aimed to describe the pharmacological properties of phytocompounds from Amazonian plant species and their effectiveness in the prevention and treatment of Acute Kidney Injury. (AKI). The classes of Amazonian plant compounds with significant biological activities most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although many of them with insufficiently explored potential, mainly in face of AKI, a clinical condition with high morbidity and mortality.

Tuberculosis (TB) is a leading infectious disease with serious antibiotic resistance. The benzothiazinone (BTZ) scaffold PBTZ169, an inhibitor of the decaprenylphosphoryl-β-D-ribose 2'-oxidase (DprE1) in Mycobacterium tuberculosis (Mtb), showed anti-TB potential in animal model and piloted clinical tests. Although highly potent, the BTZ type DprE1 inhibitors in general shows extremely low aqueous solubility, which adversely affect the drug like property. To improve the compounds physiochemical properties, we generated a series of BTZ analogues. Several optimized compounds had MIC values against Mtb in single digit nanomolar. The representative compound 37 displayed improved solubility and bioavailability compared to the lead compound. Additionally, compound 37 shows Mtb-killing ability in an acute infection mouse model.

Production of lumpfish (Cyclopterus lumpus) has become crucial in controlling sea lice levels in salmonid aquaculture. To improve their breeding, there is a need for early sex identification. The genomic region containing anti-Müllerian hormone (amh) gene was suggested as the candidate sex-determining gene in lumpfish. However, the genome of lumpfish contains three copies of amh with ambiguous sex specificity, designated amh1, amh2, and amh3. The study aims to analyse the male-specific region between these amh paralogues, for its application as a sex marker. In this study, we utilised polymerase chain reaction (PCR)-based assays to identify the male-specific amh markers in lumpfish and estimate the length of the male-specific region in the lumpfish genome. Our results suggest that a region of approximately 26 kilobase (kb) region containing amh1 and amh2 is male-specific, while both sexes share amh3. The developed PCR-based genetic sex identification assays targeting amh1 and amh2 exhibited more than 97% accuracy. Further experiments in other members of the Cyclopteridae: Aptocyclus ventricosus, Eumicrotremus taranetzi, and E. asperrimus revealed male-specific amh fragments only in A. ventricosus. Phylogenetic analyses using the available Cyclopteridae amh sequences suggest that male-specific amh arose early in the Cyclopteridae lineage. These findings and development of the PCR test will be of service to lumpfish aquaculture as well as to future studies attempting to further elucidate the sex-determination system and sex chromosome evolution in lumpfish.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

Mass cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in scientific literature and is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptides and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Immune checkpoint inhibitors (ICI) are currently use in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. Aim of our study was to find predictive biomarkers of ICI treatment. We analyzed by immunohistochemistry various cell subsets, including CD3+ cells, CD8+ cells, CD68+ cells, CD20+ cells, FoxP3+ cells, and molecules as LAG-3, IDO1, TGfβ. Comprehensive genomic profiles were analyzed. Correlation of various biomarkers with efficacy of ICI treatment in patients with advanced solid tumors was evaluated. We evaluated 56 patients treated with ICI monotherapy. Longer median progression-free survival (PFS) was found in tumors negative for nuclear FoxP3 (P = 0.002, HR 0.14) and in TMB-high tumors (P = 0.024, HR 0.38). Longer overall survival (OS) was found in patient with intraepithelial CD8 negativity (P = 0.045, HR 0.47). In malignant melanoma CD68 negativity, FoxP3 negativity and PDL TPS ≥ 1 was associated with longer PFS. In NSCLC FoxP3 was associated with longer PFS and OS. We found that absence of expression of several biomarkers such as CD68 and FoxP3 is associated with better survival. TMB-high and PD-L1 expression not universally but in certain disease could predict response.

Background: When homeostasis is disturbed it can occur a pathological event named inflammation. The main drugs used in the treatment consist of the non-steroidal and steroidal anti-inflammatory drugs. However, the side effects remain an obstacle during the treatments. In this work we aimed to evaluate three new regioisomers analogues of naphthyl-N-acylhydrazone derivatives. Methods: Acute models of inflammation in vivo (formalin-induced licking and carrageenan-induced inflammation) as well as in vitro were used to evaluate the effects of LASSBio-2039, LASSBio-2040, and LASSBio-2041. Results: All three substances (at 1, 10 or 30 µmol/kg) presented significant effect in the in vivo model reducing leukocyte migration, nitric oxide (NO) and interleukin-1β production. It was observed that only LASSBio-2039 significantly reduced cell migration in vitro. None of the LASSBios did affect inducible nitric oxide synthase activity nor presented NO scavenger effect. It was not observed any toxic effect neither in vivo nor in vitro. The new regioisomers analogues of naphthyl-N-acylhydrazone derivatives presented a significant anti-inflammatory activity suggesting LASSBio-2039 with a direct effect in leukocytes migratory capacity. Conclusions: Taken together the data indicate that these substances present promising effect for de development a prototype for new drugs.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

Epilepsy is a chronic neuronal disorder characterized by periodic, unpredictable, and recurrent seizures due to either a genetically determined or an acquired brain disorder. Although many anti-epileptics drugs (AEDs) are developed to control epilepsy, 30% of patients still need additional drugs or experience recurrent seizures and psychiatric and behavioral side effects. Thus, the need for medical care for patients with uncontrolled epilepsy remains unmet. The Genus Artemisia L. is one of the largest genera in the Asteraceae family with more than 500 species widely distributed in Europe, Asia, and North America. Many Artemisia species have been used in various treatments since ancient times as folk remedies. They demonstrated strong antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recent studies reveal that some species of Artemisia demonstrated a therapeutic benefit for epilepsy by its anti-oxidant, anti-inflammatory, neuroprotective, and anticonvulsant properties. In this review, we investigate the current state of the literature regarding the neuroprotective and antiepileptic potentials of the genus Artemisia and its possible underlying mechanisms.

Argulus is an ectoparasite that frequently infects goldfish, with severe effects and a high death rate. The use of plant extracts has been widely reported to have antiparasitic activities, including one of the solasodine compounds in sour eggplant extracts. This research evaluated the antiparasitic activities of Compositions A (Solanum ferox and Zingiber zerumbet extract at 400 and 200 ppm, respectively), B (SFE and Boesenbergia pandurata at 900 ppm), and C (single Solanum ferox at 400 ppm). The research stages comprised 1) isolation and analysis of solasodine content in sour eggplant extracts and its extract composition, 2) in vitro antiparasitic activities on Argulus sp. at doses of 50 and 100 ppm with a testing time of 60–240 minutes, and 3) in vivo antiparasitic activities on Argulus sp. on goldfish at a dose of 100 ppm and observation for 2–12 hours of medication. The results showed that sour eggplant extracts had a solasodine concentration of 7.151 mg/L, whereas the derivative compositions A, B, and C were 656, 485, and 295 ppm, respectively. The in vitro testing demonstrated that composition A was effective for killing approximately 80–100% of Argulus, whereas compositions B and C killed 80–90% and 60–70%, respectively. Viewed from the effectiveness for killing parasites, the result was excellent (above 50%). The in vivo medication test was continued using three extract compositions at a dose of 100 ppm. Compositions A, B, and C were found to be capable of releasing 81.33, 75.67, and 71.00 arguli, respectively, per fish. We concluded that the single SFE extract and a concoction with BPE and ZZE had reasonable antiparasitic activity, whereas the concoction of SFE and ZZE killed more Argulus parasites at a higher rate.

Neocarya macrophylla (Sabine) Prance (Nm, Chrysobalanaceae) is used traditionally as food, for medicinal spiritual and industrial purposes. It is also used as soap, dye, glue, fodder, termite repellent, firewood and for structural materials. Few studies on the physicochemical, nutritional contents, phytochemical and pharmacological activities have validated the benefits of Nm to humanity as food, in cosmetics and pharmaceutical products. The major bioactive constituents identified in the plant so far are steroids and flavonoids (such as stigmasterol, quercetin, catechin and its related glycosides). Extracts of the plant have shown good antivenom, antimicrobial, analgesic, anti-inflammatory, antimycobacterial, anthelmintic and antioxidant activities. Acute toxicity studies conducted have confirmed the plant to be toxic. More studies on the plant are required in order to exploit other biological activities as claimed by traditional healers and also to isolate more bioactive compounds. In addition, the safety and tolerability assessment of Nm should be undertaken due to its widespread usage.

Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.

In recent years, intelligent fault diagnosis algorithms using deep learning method have achieved much success. However, the signals collected by sensors contain a lot of noise, which will have a great impact on the accuracy of the diagnostic model. To address this problem, we propose a one-dimensional convolutional neural network with multi-scale kernels (MSK-1DCNN) and apply this method to bearing fault diagnosis. We use a multi-scale convolution structure to extract different fault features in the original signal, and use the ELU activation function instead of the ReLU function in the multi-scale convolution structure to improve the anti-noise ability of MSK-1DCNN; then we use the training set with pepper noise to train the network to suppress overfitting. We use the Western Reserve University bearing data to verify the effectiveness of the algorithm and compare it with other fault diagnosis algorithms. Experimental results show that the improvements we proposed have effectively improved the diagnosis performers of MSK-1DCNN under strong noise and the diagnosis accuracy is higher than other comparison algorithms.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Functional ZnO nanostructured surfaces are important in a wide range of applications. Here we report facile fabrication of ZnO surface structures at near room temperature with morphology resembling that of sea urchins, with densely packed, μm-long, tapered nanoneedles radiating from the urchin centre. The ZnO urchin structures were successfully formed on several different substrates with high surface density and coverage, including silicon (Si), glass, polydimethylsiloxane (PDMS), and copper (Cu) sheets, as well as Si seeded with ZnO nanocrystals. Time-resolved SEM revealed growth kinetics of the ZnO nanostructures on Si, capturing the emergence of “infant” urchins at the early growth stage and subsequent progressive increase in the urchin nanoneedle length and density, whilst the spiky nanoneedle morphology was retained throughout the growth. ε-Zn(OH)₂ orthorhombic crystals were also observed alongside the urchins. The crystal structures of the nanostructures at different growth time were confirmed by synchrotron X-ray diffraction measurements. On seeded Si substrates, a two-stage growth mechanism was identified, with a primary growth step of vertically aligned ZnO nanoneedle arrays preceding the secondary growth of the urchins atop the nanoneedle array. The antibacterial, anti-reflective, and wetting functionality of the ZnO urchins—with spiky nanoneedles and at high surface density—on Si substrates was demonstrated. First, bacteria colonisation was found to be suppressed on the surface after 24 h incubation in Gram-negative E. coli culture, in contrast to control substrates (bare Si and Si sputtered with 20 nm ZnO thin film). Secondly, the ZnO urchin surface, exhibiting superhydrophilic property with a water contact angle ~0°, could be rendered superhydrophobic with a simple silanization step, characterised by a water static contact angle θ of 159° ± 1.4° and contact angle hysteresis ∆θ < 7°. The dynamic superhydrophobicity of the surface was demonstrated by bouncing-off of a falling 10 μL water droplet, with a contact time of 15.3 milliseconds (ms), captured using a high-speed camera. Thirdly, it was shown that the presence of dense spiky ZnO nanoneedles and urchins on the seeded Si substrate exhibited a reflectance R < 1% over the wavelength range λ = 200–800 nm. The ZnO urchins with unique morphology via a facile fabrication route at room temperature, readily implementable on different substrates, may be further exploited for multifunctional surfaces and product formulations.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

White spot lesions (WSLs), a side effect of orthodontic treatment, can result in reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass (BAG) mixture(BAG@GO) was added to Low Viscosity Transbond XT(LV) in a ratio of 1, 3, 5%. The composite’s characterization and its physical and biological properties were verified with scanning electron microscopy(SEM) and X-ray diffraction(XRD); its microhardness, shear bond stress (SBS), cell viability, and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL was evaluated using antibacterial activity of S. mutans. Anti-demineralization was analyzed using a cycle of the acid-base solution. Adhesives with 3 or 5 wt.% of BAG@GO showed significant increase in microhardness compared with LV. The sample and LV groups showed no significant differences in SBS or ARI. The cell viability test confirmed that none of the sample groups showed higher toxicity compared to the LV group. Antibacterial activity was higher in the 48-hour group than in the 24-hour group; the 48-hour test showed that BAG@GO had a high antibacterial effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO concentration, the higher the anti-demineralization effect.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

Butanol extracts from leaves, twigs and fruits of Elaeagnus rhamnoides (L.) A. Nelson (sea buckthorn, SBT) were fractionated into phenolic and non-polar lipid components. Their chemical composition was analyzed using the Thermo Ultimate 3000RS chromatographic system, equipped with a diode array detector, a corona-charged aerosol detector, and coupled with a (Q-TOF) mass spectrometer. Assuming that an effect on natural microbiotaand host epithelial cells needs to be assessed, regardless of the purpose of using SBT formulations in vivo, the MIC/MBC/MFC of the fractions and reference phytocompounds were screened involving 17 species of Gram-positive and Gram-negative bacteria and Candida species. The impact of the fractions (subMIC) on the important in vivo persistence properties of S. aureus and C. albicans strains was evaluated. Tests for adhesion and biofilm formation on an abiotic surface and the surfaces conditioned with fibrinogen, collagen, plasma or artificial saliva showed the inhibitory activity of the fractions. The effects on FITC-labeled staphylococci adhesion to fibroblasts (HFF-1) and epithelial cells (Caco-2), and on fungal morphogenesis, indicated that SBT extracts have high anti-virulence potential. Cytotoxicity tests (MTT-reduction) on the standard fibroblast cell line showed variable biological safety of the fractions depending on their composition and concentration.

The tetracyclic pyrido[4,3-b]carbazole olivacine and four of its oxygenated derivatives have been synthesized by a late-stage palladium-catalyzed Heck-type cyclization of the pyrrole ring as key step. In a test for inhibition of the growth of Mycobacterium tuberculosis 9-methoxyolivacine showed the most significant anti-TB activity with an MIC₉₀ value of 1.5 μM.

Tea (Camellia sinenesis) is a health beneficial beverage and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of hetero-polysaccharides bounded with proteins. There were tests showing that TPS had various bioactivities, such as antioxidant, antitumors, antihyperglycemia, anti-inflammation and improving immunity. However, inconsistent results concerning chemical composition and bioactivity of TPS were published in recent years. The advances in chemical composition and bioactivities of TPS were reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS were also discussed.

When predicting the health impacts of PM2.5 from future air quality changes, it’s crucial to consider both air quality improvements and population aging. This study divided future emission scenarios into a Base and Control scenario to project air quality from 2015 to 2030 and assess health outcomes. The GUIDE model, an Integrated Assessment Model (IAM), was used to estimate future emissions, while the CMAQ (Chemical Transport Model) and BenMAP (Health Impact Model) evaluated health impacts resulting from changes in air quality in Korea. The study focused on the impact of population aging on future health outcomes. Both scenarios showed improved PM2.5 concentrations, with the Control scenario seeing more substantial improvements due to stronger policy measures. When applying current age patterns, health impacts decreased as PM2.5 concentrations. However, when considering future population aging, health impacts increased despite improved air quality. This finding suggests that, although PM2.5 concentrations are expected to decline, the increasing proportion of elderly individuals will exacerbate health risks. Therefore, accounting for aging population trends is essential when studying the health impacts of future air quality changes.

Aging is the important risk factor for tumorigenesis. Metabolic reprogramming is hallmark of both aging and tumor initiation. However, how the crosstalk between aging and metabolic reprogramming affects the tumor microenvironment (TME) to promote tumorigenesis was poorly explored. We utilized a computational approach proposed by our previous work, termed as MMP3C (Modeling Metabolic Plasticity by Pathway Pairwise Comparison), to depict age-related metabolic plasticity using pan-cancer bulk RNA-seq data. Through MMP3C analysis across 17 age-related cancer types, a high metabolic organized heterogeneity was found across those cancer types. Subsequent analysis revealed a higher degree of glycolysis and impaired oxidative phosphorylation in older patients. Similar phenomenon was also observed at the single cell resolution. Many energy generation pathways, i.e., TCA cycle, oxidative phosphorylation were weakened in activated T cells and macrophages, while it increased in exhausted T cells, immunosuppressive macrophages, and Tregs in older patients. It was suggested that aging-induced metabolic switches alter the utilization of glucose, thereby influencing immune function and resulting in the remodeling of the tumor microenvironment. This study provides new insights into the associations between tumor metabolism and TME mediated by aging, linking with novel strategies for cancer therapy.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2,256 documents, leading to the selection of 15 clinical trials for synthesis. Here we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

T-cell independent (TI) pathway activated by microbiota results in the generation of low-affinity homeostatic IgA with a critical role in intestinal homeostasis. Moderate aerobic exercise (MAE) provides a beneficial impact on intestinal immunity but the action of MAE on TI-IgA generation under senescence conditions is unknown. This study aimed to determine the effects of long-term MAE on TI-IgA production in young (3 months old) BALB/c mice exercised until adulthood (6 months) or aging (24 months). Lamina propria (LP) from the small intestine was obtained to determine B cells and plasma cells sub-populations by flow cytometry and molecular factors related to class switch recombination (TSLP/APRIL/BAFF/iNOS/RDH) and synthesis of IgA (α-chain/IL-6/IL-21/TGF-β); and epithelial cells to evaluate IgA-transitosis (pIgR/TNFα/IFN-/IL-4), by RT-qPCR technique. Results were compared with data obtained from sedentary age-matched mice. Statistical analysis was computed with ANDOVA and P&lt;0.05 was considered as statistically significant difference. Under senescence conditions MAE promoted the B cell and IgA+B cells and APRIL that may im-prove the intestinal response and ameliorated the inflammatory environment associated pre-sumably with the downmodulation of pIgR. Data suggested that MAE improved the IgA and downmodulate the cytokine pro-inflammatory expression favoring homeostatic conditions in aging.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

Smoking is a pervasive global health concern associated with a myriad of diseases, but its impact on cellular aging, particularly in relation to telomeres, is increasingly recognized. Telomeres, protective caps at the ends of chromosomes, play a crucial role in maintaining genomic integrity. This review critically examines the existing evidence on the association between smoking and telomere atrophy, exploring the molecular mechanisms involved and the implications for accelerated aging and heightened disease risk. The comprehensive analysis encompasses both cross-sectional and longitudinal studies, elucidating potential gender and age disparities. Insights into the molecular pathways linking smoking to telomere shortening are discussed, along with the broader implications for public health. The review concludes by outlining potential interventions and suggesting future research directions in this critical area.

Curcumin is a natural dietary polyphenol which that possesses potent anti-aging and neuroprotective properties through various mechanisms and signaling pathways. This study aimed to investigate the effect of curcumin on factors involved in neurogenesis and angiogenesis in the aged brain. Old female Wistar rats were divided into three equal groups (n=7): control, sham, and curcumin (received curcumin, i.p., 30 mg/kg and 5 days/week for 8 weeks) rats. Curcumin treatment caused a significant increase in the vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF) and anti-apoptotic protein BCl-2 in the brains of aging rats but no significant effect on anti-apoptotic Bax protein. Additionally, curcumin attenuated brain lipid peroxidation and decreased transforming growth factor β1 (TGF-β1). These results suggested that curcumin possesses neuroprotective effects against brain aging, which were mediated by improvment in neurogenesis and angiogenesis. Also, curcumin could alleviate brain aging which may be due to attenuating oxidative stress, inhibiting apoptosis and down-regulating TGF-β1, which in turn enhances VEGF and BDNF. Therefore, curcumin has potential therapeutic value in the treatment of neurological apoptosis, neurogenesis and angiogenesis changes caused by brain aging.

Burying and burrowing are promising rodent-typical behaviors to model neuropsychiatric symptoms (NPS). However, the original tests could be insufficient to conclude which NPS are modeled. Here, we propose methodological modifications such as the two-zone configuration and dual analysis in the Marble Burying Test (MB). Also, a new Brief Burrowing Test (BB), a 20 min brief version of the Deacon’s Burrowing Test (DB). We comprehensively studied these behaviors in 12-month-old male and female mice with normal and Alzheimer’s disease (AD)-pathological aging. The results: 1) confirm our precedent report of sexual dimorphism, with enhanced burying in male 3xTg-AD mice; 2) describe for the first time burrowing behavior in 3xTg-AD mice and its sex dependence; 3) regardless of the pattern, MB and BB reflected a goal-directed rather than an indiscriminate digging; 4) using the MB and BB to model anxiety-like behavior it’s not recommended; 5) burying and burrowing represent a repetitive rather than a stereotyped-like or perseverative behavior. In addition: 1) burying and burrowing behavioral patterns are alike, connected by several correlations; 2) the two-zones configuration is a useful tool to assess the intentionality of the burying and burrowing behaviors and to perform a more accurate screening of the NPS modeled by them.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

The high demand for liquefied natural gas (LNG) requires more LNG carriers (LNGCs) to be in operation. During transportation, there is a high risk due to the required extremely low temperatures and the explosive nature of LNG cargo. Moreover, when there is a lack of experience in operating old LNGCs, there is a serious concern regarding operational accidents. A systematic maintenance strategy, especially for LNG cargo containment systems, is crucial for maintaining safe LNG transportation at sea. The purpose of this study is to develop preventive LNG cargo containment system maintenance models by using LNGC dock specifications from LNGCs of various ages. The dock specifications from a conventional LNGC repairing dock were analyzed using natural language processing techniques in order to develop preventive maintenance models of the LNG cargo containment system. From these results, and by considering the ship’s age, it was found that for young LNGCs the priority for repair should focus on checking routine consumable spare parts by tank inspections, whereas for older LNGCs the focus should be on tank condition maintenance rather than on other facilities. These results are expected to be useful in the development of a maintenance strategy of preventive LNG cargo containment systems in maritime LNG transportation.

Although the signaling function of Na/K ATPase is been studied for decades, the chasm between the pumping function and the signaling function of Na/K – ATPase is still an open issue. This article explores the relationship between ion pumping and signaling with attention to the amplification of oxidants through this signaling function. Starting with some experimental observations published by our laboratories and others, we develop some predictions regarding cellular oxidant stress.

The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) position, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18-64 years old adults were calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP position were evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta=-0175; p<0.001), followed by urban residence (beta=-0.149; p<0.001), and the bigger list size (beta1601-2000=-0.054; p<0.001; beta2001-X=-0.096; p<0.001). The geographical localization influenced significantly also the risk. Although, GMP with a GP aged older than 65 years (beta=0; p=0.995) did not affected the risk, GP vacancy was associated with higher risk (beta=0.010; p=0.033), but the corresponding number of attributable cases was 23.54 for 9 years. The vacant GP position is associated with significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

Gut dysbiosis and an inflamed bowel are growing concerns in mammals, including dogs. Probiotic supplements have been used to restore the natural microbial community and improve gastrointestinal health. Biofilm formation, antimicrobial activities, and immunological responses of probiotics are crucial to improving gut health. Thus, we tested a commercial probiotic blend (LabMAX-3), a canine kibble additive comprising Lactobacillus acidophilus, Lacticasibacillus casei, and Enterococcus faecium for their ability to inactivate common enteric pathogens; their ability to form biofilms, epithelial cell adhesion and anti-inflammatory response on Madin-Darby Canine Kidney (MDCK) cell line. Probiotic LabMAX-3 blend, or individual isolates, showed a strong inhibitory effect against Salmonella enterica, Listeria monocytogenes, enterotoxigenic Escherichia coli, and Campylobacter jejuni. LabMAX-3 formed biofilms comparable to Staphylococcus aureus. LabMAX-3 adhesion to the MDCK cell line (with or without lipopolysaccharide, LPS) pretreatment showed comparable adhesion and biofilm formation (p < 0.05) to L. casei ATCC 334 used as a control. LabMAX-3 had no cytotoxic effects on the MDCK cell line during 1 h exposure. The IL-10 and TNFα ratio of LabMAX-3, compared to the L. casei control, showed a significant increase (p < 0.05), indicating a more pronounced anti-inflammatory response. The data show that LabMAX-3, a canine kibble supplement, can improve gastrointestinal health.

We provide representations for the generalized Drazin inverse of an anti-triangular matrix of the form $\left( \begin{array}{cc} a&b\\ 1&0 \end{array} \right)$ in a Banach algebra $\mathcal{A}$, under the condition that $ab=ba$. Specifically, we present the representation of Drazin inverse for these types of anti-triangular matrices in Banach algebras.

Abstract: Conventional antibiotic and multidrug treatments become less and less effective and a discovery of new effective and safe antibacterial agents got a global priority. The returning to the natural antibacterial product is relatively new current trend. Terrestrial biota is a rich source of biologically active substances whose antibacterial potential was not fully utilized. Aim of this review is to present the current state-of-the art of terrestrial biota-derived antibacterial agents and inspired by nature treatments. It is a summary of the most important sources and new identified or modified antibacterial agents and treatments during the last 5 years. It focuses on the significance of plants- animals- and bacteria-derived biologically active agents as powerful alternatives to antibiotics as well as on the advantages of utilizing natural antibacterial molecules alone or in combinations with antibiotics. The main conclusion is that the terrestrial biota derived antibacterial products and substances open variety of new ways to modern improved therapeutic strategies. New terrestrial sources of known antibacterial agents and new antibacterial agents from terrestrial biota were discovered during the last 5 years, which are under investigation together with some long ago known but now surviving their renaissance for the development of new medical treatments. Use of natural antibacterial peptides as well as combinational therapy by commercial antibiotics and natural products outlines as the most promising for treating of bacterial infections. In vivo testing and clinical trials are necessary to reach clinical application.

Glucocorticoids (GCs) are widely used in blood cancer treatment despite their multiple adverse effects. Biological response to GCs is mediated by glucocorticoid receptor (GR) by transactivation (TA), associated with side effects, and transrepression (TR), mediating anticancer effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could be better option for cancer treatment. One of well-characterized SEGRAs is 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), demonstrated anticancer activity in vitro and in vivo, however its translational potential is limited due to chemical instability. CpdA derivatives CpdA-01-08 were designed by two synthetic strategies. Derivative CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. Analysis of CpdA-03 ligand properties in lymphoma Granta and leukemia CEM cell lines revealed its SEGRA profile: it induced GR TR without triggering GR TA, as evidenced by changes in expression of GR target genes. Effects of CpdA-03 on cell viability, growth, and apoptosis were similar to reference GR ligand, dexamethasone (Dex), and the proto-type compound CpdA. In vivo testing of CpdA-03 anti-lymphoma activity in transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, this work introduces CpdA-03 as promising new SEGRA with potential for further development as anti-lymphoma drug with fewer side effects.

Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

This study examines the synergistic interaction between the immunomodulatory functions of lactic acid bacteria postbiotics and the anti-inflammatory properties of Smilax China L. extract through a combined fermentation process. Using atopic dermatitis (AD) as a model, characterized by an immune imbalance that leads to skin inflammation, we developed a fermented product, MB-2006, and compared its effects to those of heat-killed probiotics, Lactobacillus acidophilus (LAC) and Lac-tobacillus rhamnosus (LRH). Our experiments focused on elucidating the mechanism of action of MB-2006 in AD-like HaCaT keratinocyte cells, particularly its impact on the NF-kB pathway, a pivotal regulator of inflammation. MB-2006 proved more effective in reducing inflammation markers such as IL-4 and thymic stromal lymphopoietin (TSLP), and in inhibiting NF-kB activation, compared to LAC and LRH. Significantly, MB-2006 also reduced the expression of thymus- and activation-regulated chemokine (TARC), highlighting a synergistic effect that enhances its thera-peutic potential. These results suggest that the combined fermentation of Smilax china L. extract with lactic acid bacteria enhanced both the anti-inflammatory and immunomodulatory effects, pre-senting a promising integrative approach to treating conditions like AD. Further studies are needed to validate these results in clinical settings and fully explore the potential of this synergistic fer-mentation process.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, that is managed by using non-steroidal anti-inflammatory drugs (NSAIDSs). Information is limited about how NSAIDSs affect the therapeutic potential of stem cells. Therefore, we investigated the effects of ibuprofen and diclofenac in low and high therapeutic doses on the properties of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro. Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Our results suggest that concomitant use of the NSAIDSs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, which can affect the efficacy of stem cell therapy.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Antler is the fastest growing tissue. Because is based on proto-oncogenes, to avoid the risk of cancer, antlers evolved strong anticancer mechanisms, and thus its extract (DVA) is effective also against the few human tumours studied so far. We assessed whether DVA is a general anticancer compound testing direct effects in cells of different tumours: glioblastoma (GBM), colorectal and breast cancer, and leukaemia. DVA reduced viability of tumour but not healthy cells. Mobility decreased at least at the longest test (72 h). Intraperitoneal/oral 200 mg DVA/kg administration in GBM xenograft mice for 28 d reduced tumour weight 66.3% and 61.4% respectively, and also spleen weight. In addition, tumours treated with DVA showed symptoms of liquefactive necrosis. Serum cytokines showed DVA up-regulated factors related with tumour fighting and down-regulated those related with inducing immune tolerance to the tumour. DVA shows general anticancer effects in the lines tested and, in GBM mice, also strong indirect effects apparently mediated by the immune system.

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

In our study, we assessed the effects of verbenone, the most widely studied bark beetle aggregation inhibitor, on saproxylic beetles of a Mediterranean pine forest in Tuscany. Verbenone pouches were devised in the laboratory and then applied to Ips sexdentatus pheromone traps so that catches could be compared to those of traps with just the bait. The trial was carried out in spring-summer 2023, collecting insect catches every two weeks. A total of 9440 beetles were collected, belonging to 32 different families and 57 species. About 80% of captures were bark beetles, mainly Orthotomicus erosus. Beetle predators accounted for about 17% of the captures, with a total of 12 species. Some of these predator species had never been studied yet in relation to verbenone effects, like other saproxylic beetles recorded in this study. A significant reduction of captures was recorded for some beetles (e.g. I. sexdentatus and O. erosus), for other species no differences emerged, and in some cases captures increased significantly when verbenone was present in the traps (i.e.. Hylurgus ligniperda, Corticeus pini, Aulonium ruficorne). The diversity of caught saproxylic beetles increased significantly in verbenone traps, highlighting possible implications of the use of verbenone when managing bark beetle outbreaks.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Shigellosis is a pathological condition that affects the digestive system to possibly cause diarrhoea. Shigella species, which are responsible for this disease, are highly contagious and spread through contaminated food and water. The increasing development of resistance by Shigella species necessitate the urgent need to search for new therapies against shigellosis causing diarrhoea. The scientific validation of medicinal plants, such as Diospyros gilletii, which is used for the traditional treatment of diarrhoeal conditions is worthwhile. The present study aims to investigate the antibacterial activity of extracts from D. gilletii against selected Shigella species. Extracts from D. gilletii stem bark were prepared by maceration using various solvents. An-tibacterial activity of D. gilletii extracts was evaluated on Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei using a microdilution method, whereas cytotoxicity test was performed on Vero and Raw cells using resazurin-based colorimetric assay. Bacterial membrane permeability studies were evaluated using pro-pidium iodide (PI) and 1-N-phenylnaphthylamine (NPN) uptake assays, whereas inhibition and eradica-tion tests on bacterial biofilms were carried out by spectrophotometry. As a result, methanol, ethanol and hydroethanol extracts of D. gilletii inhibited the growth of S. boydii, S. flexneri and S. sonnei with MIC values ranging from 125 to 500 µg/mL, without toxicity to Vero and Raw cells. Time kill kinetics revealed bacteri-cidal orientation at 2MIC and 4MIC, and bacteriostatic outcome at 1/2MIC. The mechanistic basis of anti-bacterial action revealed that D. gilletii extracts inhibited and eradicated Shigella biofilms, and promoted the accumulation of NPN and PI within the inner and outer membrane of bacteria to increase membrane per-meability, thereby causing membrane damage. This novel contribution toward the antibacterial and mech-anisms of action of D. gilletii extracts against Shigella species substantiate the use of this plant in the tradi-tional treatment of infectious diarrhoea.

Streptococcus thermophilus is widely used as a starter culture in the dairy industry and has garnered attention as a beneficial bacterium owing to its health-promoting functionalities in humans. In this study, the probiotic potential of S. thermophilus MCC0200, isolated from a dairy product, was investigated through a combinatorial approach of in-vitro and in-silico studies. MCC0200 demonstrated the ability to survive harsh gastro-intestinal transit (GIT), adhere to intestinal mucosa and exert health-promoting traits in in-vitro studies. These findings were corroborated with in-silico evidence, wherein MCC0200 genome harboured genes associated with tolerance to GIT conditions, intestinal adhesion and colonization. Genome mapping also highlighted the ability of MCC0200 to produce compounds advantageous for host (folate, bacteriocins), to release enzymes that can reinforce the host ability (antioxidative enzymes), to metabolize food components that can be harmful to sensitive people (lactose). MCC0200 also demonstrated a positive effect on reducing cholesterol levels, proving to be a potential candidate for food and pharmaceutical applications. Absence of transmissible antibiotic resistance genes and virulence genes underscored the GRAS nature of MCC0200. This study explored the potential of Streptococcus thermophilus for its probable applications as a probiotic beyond the dairy industry.

Background: Retinal diseases such as neovascular age related macular degeneration (nAMD), diabetic macular edema (DME) or branch-/central retinal vein occlusion (B/CRVO) have significant implications for patients' social and psychological well-being. To gain a comprehensive understanding of patients' backgrounds and attitudes, we developed an exploratory questionnaire, the Basic Care and Patient Satisfaction Questionnaire (BPZ-9). Methods: The ALBATROS study aimed to assess the care situation of treatment-naïve patients diagnosed with either nAMD, DME or B/CRVO. The data collection took place at the beginning of treatment and after twelve months of anti-VEGF (vascular endothelial growth factor) therapy. The BPZ-9 instrument comprises nine questions to evaluate patients’ psychological and social situation and their satisfaction with treatment. Results: Data were collected from 1.478 nAMD (mean 78 years), 445 DME (67 years), 233 BRVO (70 years) and 144 CRVO (71 years) patients at 102 study centers throughout Germany. Approximately one third of the patients was living alone and six percent were in organized care. One in four patients had difficulties to walk and one in five needed accompany for treatment. Anxiety to lose vision was present in three out of four patients at the beginning and slightly decreased to two out of three over the 12-month treatment preriod. The distress of having a retinal disease was generally higher than the distress related to treatment. Most patients reported high treatment satisfaction (73%) and felt well informed (81%). Conclusion: Patients receiving anti-VEGF therapy commonly experience impaired mobility, dependency on others, distress and the fear of vision loss.

Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural ones is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and ef-fective strategy to include them in the diets of diabetic and obese people is through beverages. This review aimed to report the anti-diabetic potential of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase en-zymes, and to improve glucose uptake. In vivo, the beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable and fruit-based functional beverages to be a natural innovative therapy for the management of diabetes.

A twin-screw extruder was used to fabricate poly(butylene succinate) (PBS)/high density polyethylene (HDPE) blends (7:3 weight ratio) and blend-based nanocomposites. Carbon nanotubes (CNTs), graphene nanoplatelets (GNPs) and organoclays (15A and 30B) served as the nanofiller, while maleated HDPE (PEgMA) acted as an efficient compatibilizer for the blend. In the composites, individual nanofillers were mostly localized in HDPE domains, but some fillers were also observed at PBS-HDPE interfaces. The sea-island morphology of compatibilized blend evolved into a pseudo-co-continuous morphology in the composites. Differential scanning calorimetry results confirmed that PEgMA with HDPE evidently accelerated the crystallization of PBS in the blend. The possible nucleation effect of added fillers on PBS crystallization was obscured by the formation of quasi-connected HDPE domains, causing less PBS nucleation sites. The presence of nanofillers improved the thermal stability and burning anti-dripping behavior of the parent blend. The anti-dripping efficiency of added fillers followed the sequence: CNT>15A>30B>GNP. Rigidity of the blend was increased after formation of nanocomposites. In particular, adding GNP resulted in 31% increase in flexural modulus. Development of a pseudo-network structure in the composites was confirmed by measurement of rheological properties. Electrical resistivity of the blend was reduced by more than 6 orders of magnitude at 3 phr CNT loading, demonstrating the achievement of double percolation morphology.

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. In this study, we investigated the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Our results showed that TRF effectively suppressed the formation of reactive oxygen species, and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit the significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural active against BL-induced skin damages and hyperpigmentation via its antioxidative and anti-melanogenic properties.

We performed a retrospective, observational study for 51 eyes of 51 treatment-naive patients with polypoidal choroidal vasculopathy (PCV), whose lesion ranged within the 6x6mm scope of optical coherence tomography angiography (OCTA). Patients were divided into two groups based on the pattern of branching vascular network (BVN) on OCTA: ill-defined group and well-defined group. BVN morphology was not related to baseline best-corrected visual acuity (BCVA). But the BCVA in the ill-defined BVN group (-0.18 [interquartile range: -0.40 to 0.00]) was significantly improved after anti-vascular endothelial growth factor (VEGF) injections, compared with that (0.00 [interquartile range: -0.18 to 0.00]) in the well-defined group (z=2.143, p=0.032). Multiple logistic regression analysis showed that male sex, smaller number of injections, and presence of polypoidal lesions on OCTA images at baseline predicted a poor prognosis of polypoidal lesions on OCTA images after anti-VEGF therapy (all p&lt;0.05). Finally, BCVA at baseline and the number of injections were protective factors for BCVA after anti-VEGF therapy (all p&lt;0.05). In contrast, history of hypertension and macular edema at baseline were risk factors for BCVA after anti-VEGF injections (all p&lt;0.05). Our results revealed the visual and morphological prognosis of patients with active subfoveal circumscribed PCV after anti-VEGF therapy.

Anastatica hierochuntica L. (Brassicaceae) has been claimed to treat various conditions including complicated childbirth. The principal objective of this research was to provide scientific evidence on the contractile effect of the aqueous and hydroethanolic extracts of the whole plant from A. hierochuntica during labor. Qualitative and quantitative methods helped identify and quantify the phytoconstituents in both extracts. The antioxidant activity was studied using four standard methods. The inhibitory power of the extracts on pro-inflammatory enzymes such as 15-lipoxygenase and phospholipase A2 was determined. The contractile effects of the extracts were evaluated using isolated pregnant mice uteri. Steroids, triterpenoids, flavonoids, tannins, coumarins, and reduced compounds were identified in both extracts. The extracts demonstrated the ability to reduce oxidative stress. The hydroethanolic extract displayed the most significant anti-lipoxygenase activity with an IC50 value of 55.82 ± 1.15 µg/mL. The lethal dose (LD50) of extracts was estimated to be superior to 2000 mg/kg bw. The ability of the samples to produce one cm amplitude of contraction at 50% effective concentrations (EC50) was 1.51 ± 0.08 mg/mL for aqueous extract and 3.57 ± 0.61 mg/mL for hydroethanolic extract. These findings could provide evidence for using Anastatica hierochuntica to augment labor.

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p &lt; 0.05 ~ p &lt; 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Suffocation syndrome is the leading cause of hypoxia and mortality in the most common lung diseases, asthma and COVID-19. Inhaled corticosteroids (ICSs) have been shown to be the main-stay of critical care in these diseases. Meanwhile, mortality from strangulated hypoxia is highest in low-income countries because ICSs are not currently available to many patients. Warm alkaline hydrogen peroxide solutions (WAHPSs) have reportedly been invented in recent years to urgently turn thick sputum, mucus, pus, serous fluid, blood clots and many other biological masses con-taining the enzyme catalase into a fluffy oxygenated foam. It has been shown that the mechanism of action of WAHPSs consists in alkaline saponification of lipid and protein-lipid complexes of bi-ological masses and their transformation into oxygen foam, because hydrogen peroxide is urgently decomposed into water and oxygen gas under the action of the biological masses catalase enzyme At that excess oxygen is absorbed into blood through lungs and increases blood oxygen saturation. Based on the described mechanism of action of WAHPSs and the high availability of their ingre-dients, it is suggested that mortality from choking and hypoxia in asthma and COVID-19 can be reduced by combining ICSs with inhaled WAHPSs, especially in poor countries. The essence of the inventions underlying the formation of WAHPSs is given.

Secondary metabolites such as flavonoids are considered to be promising in the treatment of NAFLD, which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated with regard to their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from STZ-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose-dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver TG levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

Accumulation of extra fats in the body results in disturbance in homeostasis causing obesity. The pathophysiology of obesity has been associated with various genetic, epigenetic factors and the disturbed lifestyles of an individual. One of the outcomes is disturbance in the sleep cycle which leads to sleep disorders. The evolutionary significance of sleep lies in the fact that it saves energy and is crucial for adjustment of an individual to ecological and environmental factors, and thus maintains homeostasis. Sleep has an anabolic function and replenishes the wakefulness-associated loss of glycogen stores. However, the modern lifestyle is well known to disrupt sleep behavior and patterns affecting human health negatively. Alteration in homeostasis leads to several acute and chronic pathophysiological conditions like obesity and related metabolic morbidities being one amongst them. Shorter sleep duration and poor sleep quality are important risk factors associated with the development of obesity and have more adverse effects on energy homeostasis. Consequently, it is crucial to comprehend the obesity and sleep relationship and its therapeutic strategies, given that strong crosstalk exists between energy balance that favors obesity and sleep apnea. It is therefore highly recommended to the people with a high risk of obesity to maintain sleep discipline and good sleep hygiene in our daily life. Interventions are required to improve both sleep quality and quantity, and associated obesity. More focused research is needed for uncovering the pieces of evidence that determine whether such interventions can improve obesity-related health consequences. The present review discusses the important findings on the therapeutic and neuroendocrine mechanisms regulating sleep and obesity.

The bridge crane is often used in a complex environment, often subject to interference of all loads. Some uncertainties factors often have an inevitable impact on its swing. So the force situation of the bridge crane during a working cycle is analyzed, and a three-dimensional dynamic mathematical model of the bridge crane is built. Through the simulation analysis of the model under the action of driving force and wind load, the change law of the swing angle of the bridge crane is studied. Then, the fuzzy control theory is used to determine the control parameter in the anti sway control process. The position, swing angle deviation and deviation rate of the bridge crane are taken as the input, and the parameter correction is obtained after the fuzzification by using the center of gravity method, the anti sway fuzzy control system of the bridge crane is designed and simulated. The research results show that the fuzzy PID anti sway controller can not only improve the adaptability of the control system, but also overcome the large overshoot, quickly restrain the swing, and effectively realize the anti sway function of the bridge crane.

Four previously undescribed highly oxygenated diterpenoids (1–4), zeylleucapenoids A–D, characterized by halimane and labdane skeletons, were isolated from the aerial parts of Leucas zeylanica. Their structures were elucidated primarily by NMR experiments. The absolute configuration of 1 was established by theoretical ECD calculations and X-ray crystallographic analysis, whereas those for 2−4 were assigned by theoretical ORD calculations. Zeylleucapenoid D (4), with an IC₅₀ value of 38.45 μM in RAW264.7 macrophages and nontoxic activity for zebrafish embryo, and obviously inhibited pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. Compound 4 inhibited of the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, molecular docking analysis indicated the possible mechanism of action for 4 may be bind to targets by hydrogen- and hydrophobic- bond interactions.

Oxidative stress and inflammation are basic pathogenic factors involved in tissue injury, pain, as well as acute and chronic diseases. Since long-term uses of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) cause severe adverse effects, novel effective materials with minimal side effects are required. In this study, polyphenol content and antioxidative activity of rosebud extracts from 24 newly-crossbred Korean roses were analyzed. Among them, Pretty Velvet rosebud extract (PVRE) were found to contain high polyphenols and to show in vitro antioxidative and anti-inflammatory activities. In RAW 264.7 cells stimulated with lipopolysaccharide (LPS), PVRE down-regulated mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and thereby decreased nitric oxide (NO) and prostaglandin E2 (PGE2) production. In an air-pouch inflammation model, treatment with PVRE decreased λ-carrageenan-induced tissue exudation, infiltration of inflammatory cells including neutrophils, monocytes and lymphocytes, and tumor necrosis factor-α and interleukin-1β concentrations, as achieved with dexamethasone (a steroid). Notably, PVRE also inhibited PGE2, similar to dexamethasone and indomethacin (an NSAID). The anti-inflammatory effects of PVRE were confirmed by microscopic findings, attenuating tissue erythema, edema, and inflammatory cell infiltration. These results indicate that PVRE exhibits dual (steroid- and NSAID-like) anti-inflammatory activities by blocking both the iNOS ― NO and COX-2 ― PG pathways, and that PVRE could be a promising anti-inflammatory material for diverse issue injuries.

Curcuma longa is only a rich source of curcumin (1) and its major analogues demethoxycurcumin (2) and bisdemethoxycurcumin (3) among the Curcuma species. The content ratio of these three curcumins in turmeric is depended on the varieties and growing environment. Recently, curcumin (1) has been reported as potential inhibitor of hepatic and enzymatic protein tyrosine phosphatase 1B (PTP1B) and its related disorders such as hypertriglyceridemia, hyperlipidemia and liver steatosis. Thus, we further purified curcumins (1–3) from C. longa and investigated their inhibitory effects against PTP1B and α-glucosidase enzymes. As the result, curcumins (1–3) exhibited potential PTP1B inhibition with IC50 values of 37.8 ± 1.4, 45.3 ± 0.7, and 72.6 ± 1.1 μM, respectively, and α-glucosidase inhibition with similar manner (IC50 values of 78.2 ± 0.2, 82.4 ± 0.6, and 90.6 ± 1.0 μM, respectively). These results reveal a key role of methoxylation in the variation of PTP1B and α-glucosidase inhibitory activity for these curcumins. In addition, density functional theory (DFT) was used accompanying with molecular docking (MD) to analyze the ligand stability and the interaction of curcumins (1–3) with PTP1B and glucoside hydrolase proteins. Assay-based results and the MD data obtained are highly correlation suggesting that the deterioration of the enzyme activity caused by the distortion of structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in protein structure. This reported for the first time that inhibitory effects of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined in vitro and in silico as well.

Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.

Background: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes with many side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. Methods: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. Results: Substances significantly reduced cell migration induced by carrageenan. It was also observed an intense inhibition in protein extravasation and cytokines (IL-6, IL-1β, and TNF-α) production as well as nitric oxide reduction. INL-11 demonstrated to be the most potent since the reduction was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and iNOS activity. INL-11 was the most effective in reducing cell migration in vitro. Conclusions: our data suggest that these substances are suitable for further development to new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Multiple biological pathways manifest and latent, meant for human survival, become a liability in cancer cure. With an increasing understanding of innumerable complex paths, cancer progression and development of resistance is no surprise. For the three “vasculature-immune-phenotypic” fundamental changes, hypoxia is the maestro orchestrating the whole gamut of changes (through the master manipulator - HIF-1 α), simultaneously transactivating hundreds of pro-angiogenic genes. Such a complex molecular bio-network begs the question, “Is our cancer research caught in such a tangled web that we have lost sight of the Spider?”. Hypoxia is this Spider weaving compensatory webs with every intervention/ obstruction. Anti-angiogenic (AAG) research has been conducted mainly in silos – exploring independent paths. This review conceptualizes a convergence of a multitude of research worldwide to a single theme of normalizing vasculature as a primary baseline for overcoming resistance to AAGs or their combinations.

Citrus flavonoids are well-known for beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; also clinical trials are inconsistent. The limited bioavailability of them can be, at least in part, the reason of these discrepancies. Therefore many efforts were performed towards the improvement of their bioavailability. Hydrodynamic cavitation methods were successfully applied to the extraction of byproducts of the Citrus fruits industry, showing high process yields and affording stable phytocomplexes, known as IntegroPectin, endowed with great amounts of bioactive compounds and high water solubility. Cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. A further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of flavonoids, showed anti-ischemic cardioprotective activity, better than pure naringenin (the bioactive aglycone of naringin). On cardiac isolated mitochondria, this extract confirmed that naringenin/naringin were involved in the activation of mitochondrial potassium channels. The hydrodynamic cavitation-based extraction confirmed a valuable opportunity for the exploitation of Citrus fruits waste, with the end product presenting high levels of Citrus flavonoids and an improved bioaccessibility that enhances its nutraceutical and economic value.

Sesamum indicum is considered an underutilized oil-bearing seed in the semi-arid regions of Ghana. Nonetheless, it is a promising source of food with both nutritional and therapeutic benefits. The aim of the present study was to evaluate the antioxidant properties S. indicum seeds using different extraction solvents. The seeds were obtained from the local farmers and prepared for analysis. The bioactive compounds present in the seeds were extracted using hexane, ethyl acetate, ethanol and water and their yields quantified. Total phenolic content (TPC), Condensed tannin content (TTC) and Total antioxidant capacity (TAC) , and DPPH radical scaveging assay were analyzed using standard methods. Antinutrients such as saponins, alkaloids, phytates and oxalates were also analyzed from the powdered seeds. Two chemometric methods; hierarchical cluster analysis (HCA) and Pearson correlation were employed to evaluate the interdependence of the various parameters to result in their antioxidant properties. The re-sults revealed that the solvents utilized had a significant impact on the extraction yield, phyto-chemical component concentration, and antioxidant activities. Hexane extracts of S. indicum seeds significantly exhibited the highest antioxidant activity (p &lt; 0.05). It was marked with the highest TAC value of 232.6 ± 6.267 mg/g AAE and a strong DPPH scavenging activity with an IC50 of 52.81 ± 2.30 µg/mL. Correlations (p &lt; 0.05) was established between TPC,CTC, TAC and DPPH radical scavenging activity) of the extracts. Antinutrients such as; phytate, oxalate, saponins and alkaloids were found to be 7.691 ± 0.8576, 1.501 ± 0.1375, 21.33 ± 4.619 and 317.33 ± 30.29 mg/g respectively. Data obtained suggest that S. indicum possess rich bioactive compounds that can be used in neutraceuticals and food products.

Crown of thorns starfish (Acanthaster planci) are coral predators with advantages of having toxicity in their venom and tissue regeneration capabilities. With all these characteristics, only a handful of studies have highlighted the association of microorganisms with this organism. Crown of thorns starfish are common in Fiji and their analyses of microbial diversity for secondary metabolites could be of great interest to the scientific community. This study is an attempt to investigate Fijian-based A. planci for their venom and associated actinomycetes antibacterial activity and further identify the type of enzymes present in the crude venom extract. The CoTS venom extract (0.192 g) harbor enzymes such as gelatinase, caesinase, and amylase. An abundant and potent actinomycete strain, represented as FJA1 showed antibacterial activity against Enterococcus faecium with an inhibition zone of 10 mm. Moreover, all pathogenic test microorganisms were resistant against concentrations of 500 µg and 1 mg of A. planci venom extract.

Abstract: This work is part of the interest of solving the problems of water contamination with last generation pollutants, for which a novel and in an aqueous medium FeBTC material incorporated with magnetite nanoparticles was proposed. That material was synthesized by in situ solvothermal method, the Fe3O4 nanoparticles were added during the Fe-BTC MOF synthesis and used in the drug’s adsorption. The materials were characterized by XRD, FTIR and Raman spectroscopy, and N2-physisorption at 77 K. Fe3O4-FeBTC material showed a maximum adsorption capacity of 357.1 mg g−1 for diclofenac sodium, 70.9 mg g−1 for naproxen sodium, and 122.9 mg g−1 for Ibuprofen. A pseudo-second-order kinetic model can describe the adsorption process, and the thermodynamic study revealed that the adsorption of the three drugs was a feasible, spontaneous, and exothermic process. The incorporation of magnetite nanoparticles in the FeBTC considerably increased the adsorption capacity of pristine FeBTC. Also, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing its thermal and aqueous media stability. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played a vital role in drug adsorption. The competition of sites in the multicomponent mixture's adsorption showed selective adsorption at diclofenac sodium and naproxen sodium.

Pathological vessel growth harms vision and may finally lead to vision loss. Anti-angiogenic gene therapy with viral vectors for ocular neovascularization has shown great promise in pre-clinical studies. Most of the studies has conducted with different adeno-associate serotype vectors. In addition, Adeno and lentivirus vectors have been used. Therapy has targeted to block vascular endothelial growth factors or other pro-angiogenic factors. Clinical trials of intraocular gene therapy for neovascularization have shown the treatment to be safe without severe adverse events or systemic effects. Nevertheless, clinical studies have not proceeded phase 2 trials further.

Extracellular vesicles are considered a novel therapeutic tool, due to their ability to transfer their cargoes to target cells. Different strategies to directly load extracellular vesicles with RNA species have been proposed. Electroporation has been used for the loading of non-active vesicles, however the engineering of vesicles already carrying a therapeutically active cargo is still under investigation. We here set up a coincubation method to increase the anti-tumor effect of extracellular vesicles isolated from human liver stem cells (HLSC-EVs). Using the coincubation protocol, vesicles were loaded with the anti-tumor miRNA-145, and their effect was evaluated on renal cancer stem cell invasion. Loaded HLSC-EVs maintained their integrity and miR transfer ability, and miR-145 was protected by RNAse digestion possibly due to its binding to RNA-binding proteins on HLSC-EV surface, such as Annexin A2. Moreover, miR-145 coincubated HLSC-EVs were more effective in inhibiting the invasive properties of cancer stem cells, in comparison to naïve vesicles. The protocol reported here exploits a well-described property of extracellular vesicles to bind nucleic acids on their surface and protect them from degradation, in order to obtain an effective miRNA loading that results in the increase of the effect of naïve active extracellular vesicles.

IgA vasculitis is a hypersensitivity vasculitis, which is usually self-limiting. Renal involvement is the most damaging long-term complication of IgA vasculitis, happening in 20% - 100% of cases. Some factors have been reported to be associated with renal involvement in IgA vasculitis; however, no biomarker has been proved as a risk factor for renal involvement and its severity yet. We followed 48 patients with a confirmed diagnosis of IgA vasculitis for six months. We checked these patients for renal involvement by microscopic urine examination. We checked aPL antibodies in all patients on admission and 12 weeks later. Urinalysis showed renal involvement in 14 of 48 patients with IgA vasculitis (29.16%). Antiphospholipid antibodies were positive in 9 patients with IgA vasculitis and renal involvement (9 out of 14, 64.28%), while they were positive in only six patients with IgA vasculitis without renal involvement (6 out of 34, 17.64%), showing a moderate correlation between positive aLP and renal involvement in patients with IgA vasculitis, with a kappa index of 0.457. Serum aPL antibodies, as a tool to predict renal involvement in IgA vasculitis, show a sensitivity of 64.3%, a specificity of 82.4%, PPV of 60.0%, and NPV of 84.8%, demonstrating that a positive serum aPL antibody can be used to positively predict the renal involvement, while a negative result is not strong enough to rule out future renal involvement.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

Acetyleugenol is a phytochemical compound with broad effect against infectious diseases and tumors. Here, we extracted, characterized and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)―a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial pathogenic isolates with best activity against Proteus sp., Salmonella typhi, Staphylococcu aureus, and Streptococcus pneumonia, which showed similar or better zone of inhibition to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogs were subjected to molecular docking experiments against two potential tuberculosis drug targets―MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores comparing to the acetyleugenol. The indole analogs EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with –11.08 and –10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analog has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogs with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

Acute myeloid leukemia (AML) is an incurable hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells. Thus, the SP/NK-1R system is involved in AML and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is up-dated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (> 20 mg/kg/day) for a period of time according to the response to treatment is suggested).

A new compound containing a triene, a tetrahydropyran ring and glycine ester functionalities, restricticin B (1), together with four known compounds (2-5) were obtained from the EtOAc extract of the marine fungus Penicillium janthinellum. The planar structure of 1 was determined by detailed analyses of MS, 1D and 2D NMR data. The relative and absolute configurations of 1 were established via analyses of NOESY spectroscopy data, comparison of optical rotation values with those of restricticin derivatives reported and electronic circular dichroism (ECD). All the compounds were screened for their anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglia cells. Restricticin B (1) and N-acetyl restricticin (2) exhibited anti-neuroinflammatory effects by suppressing the production of pro-inflammatory mediators in activated microglial cells.

In our tactic to construct bio-active molecules, a series of novel pyrimido[2,1-c][1,2,4]triazine-3,4-diones based heterocycles, were synthesized and evaluated for their in vitro antimicrobial impacts. The exploratory bioassay results declared that, the majority of the evaluated compounds exhibited considerable anti-microbial activity comparable to the reference drugs. Conjugates 15j, 15f, 15i, 15h, 15g and 15a were found to be the most potent antibacterial, indicating that conjugates bearing electron-attracting substituents exhibited higher potency than these with electron-releasing substituents.

An improved anti-noise morphology vision navigation algorithm is proposed for intelligent tractor tillage in a complex agricultural field environment. At first the two key steps, Guided Filtering and improved anti-noise morphology navigation line extraction were addressed in detail. Then the experiments were carried out in order to verify the effectiveness and advancement of the presented algorithm. Finally, the optimal template and it’s application condition were studied for improving the image processing speed. The comparison experiment results show that the YCbCr color space has minimum time consumption of 0.094 s in comparison with HSV, HIS and 2R-G-B color spaces. The Guided Filtering method can effectively distinguish the boundary between the new and old soil than other competing vanilla methods such as Tarel, Multi-scale Retinex, Wavelet-based Retinex and Homomorphic Filtering inspite of having the fastest processing speed of 0.113 s. The extracted soil boundary line of the improved anti-noise morphology algorithm has best precision and speed compared with other operators such as Sobel, Roberts, Prewitt and Log. After comparing different size of image template, the optimal template with the size of 140×260 pixels can meet high precision vision navigation while the course deviation angle is not more than 7.5°. The maximum tractor speed of the optimal template and global template are 51.41 km/h and 27.47 km/h respectively which can meet real-time vision navigation requirement of the smart tractor tillage operation in the field. The experimental vision navigation results demonstrated the feasibility of the autonomous vision navigation for tractor tillage operation in the field using the new and old soil boundary line extracted by the proposed improved anti-noise morphology algorithm which has broad application prospect.

The Abnormal increase in the mass of adipose tissue during adipogenesis results in obesity. Obesity is a predominant disorder and its widespread has become a critical concern worldwide. This is due to the burden of its associated co-morbidities like cancer, cardiovascular diseases and diabetes. Over-nutrition and the sedentary lifestyle are considered as the most significant causes of abnormal adipose tissue development. Appropriate lifestyle and behavioural interventions are the corner stones of successful weight loss, but to maintain such a lifestyle is highly challenging. Accordingly, natural products from plants either as crude extracts or purified phytochemicals have shown to have anti-obesogenic properties and are generally non-toxic and cost-effective. In this review, we discuss the comparative analysis of molecular mechanisms involved in adipogenesis and the recently reported anti-obesogenic effects of various plant products. We will provide a common platform for understanding obesity and adipogenesis, and a possible mechanism of action for anti-obesogenic plant products through AMP-activated protein kinase (AMPK), which will support the scientific development of traditional herbal medicine.

An improved anti-noise morphology vision navigation algorithm is proposed for intelligent tractor tillage in a complex agricultural field environment. Firstly, the two key steps, Guided Filtering and improved anti-noise morphology navigation line extraction, were addressed in detail. Then the experiments were carried out in order to verify the effectiveness and advancement of the presented algorithm. Finally, the optimal template and its application condition were studied for improving the image processing speed. The comparison experiment results show that the YCbCr color space has minimum time consumption, 0.094 s, compared with HSV, HIS and 2R-G-B color spaces. The Guided Filtering method can enhance the new & old soil boundary effectively than any other methods such as Tarel, Multi-scale Retinex, Wavelet-based Retinex and Homomorphic Filtering, meanwhile, has the fastest processing speed of 0.113 s. The extracted soil boundary line of the improved anti-noise morphology algorithm has best precision and speed compared with other operators such as Sobel, Roberts, Prewitt and Log. After comparing different size of image template, the optimal template with the size of 140×260 pixels can meet high precision vision navigation while the course deviation angle is not more than 7.5°. The maximum tractor speed of the optimal template and global template are 51.41 km/h and 27.47 km/h respectively which can meet real-time vision navigation requirement of the smart tractor tillage operation in the field. The experimental vision navigation results demonstrated the feasibility of the autonomous vision navigation for tractor tillage operation in the field using the new & old soil boundary line extracted by the proposed improved anti-noise morphology algorithm which has broad application prospect.

The rapid development of multicopters has led to many security problems. In order to prevent multicopters from invading restricted areas or famous buildings, an Anti-UAV Defense System (AUDS) has been developed and become a research topic of interest. Topics under research in relation to this include electromagnetic interference guns for unmanned aerial vehicles (UAVs), high-energy laser guns, US military net warheads, and AUDSs with net guns. However, these AUDSs use either manual aiming or expensive radar to track UAVs. This paper proposes a dual-axis rotary platform with UAV automatic tracking. The tracking platform uses visual image processing technology to track and lock the dynamic displacement of a UAV. When a target UAV is locked, the system uses a nine-axis attitude meter and laser rangefinders to measure its flight altitude and calculates its longitude and latitude coordinates through sphere coordinates to provide UAV monitoring for further defense or attack missions. Tracking tests of UAV flights in the air were carried out using a DJI MAVIC UAV at a height of 30 meters to 100 meters. It was set up for UAV image capture and visual recognition for tracking under various weather conditions by a thermal imager and a full-color camera respectively. When there was no cloud during the daytime, the images captured by the thermal imager and full-color camera provide a high-quality image recognition result. However, under dark weather, black clouds will emit radiant energy and seriously affect the capture of images by a thermal imager. When there is no cloud at night, the thermal imager performs well in UAV image capture. When the UAV is tracked and locked, the system can effectively obtain the flight altitude and longitude and latitude coordinate values.

Silybum marianum L. is a well-known medicinal herb, primarily used in liver protection. Light strongly affects several physiological processes along with secondary metabolites biosynthesis in plants. Herein, S. marianum was exploited for in vitro potential under different light regimes in the presence of melatonin. The optimum callogenic response occurred in combination of 1.0 mg/L α-naphthalene acetic acid and 0.5 mg/L 6-Benzylaminopurine under photoperiod. Continuous light associated with melatonin treatment increased total flavonoid content (TFC), total phenolic content (TPC) and antioxidant potential, followed by photoperiod and dark treatments. The increased level of melatonin has a synergistic effect on biomass accumulation under continuous light and photoperiod, while adverse effect was observed under dark condition. More detailed phytochemical analysis showed maximum total silymarin content (11.92 mg/g DW) when placed under continuous light + 1.0 mg/L melatonin. Individually, the level of silybins (A and B), silydianin, isolsilychristin and silychristin was found highest under continuous light. Anti-inflammatory activities were also studied and highest percent inhibition was recorded against 15-LOX for cultures cultivated under continuous light (42.33%). The current study helps to better understand the influence of melatonin and different light regimes on silymarin production as well as antioxidant and anti-inflammatory activities in S. marianum callus extracts.

This paper investigates the cooperative anti-jamming distributed channel selection problem in UAV communication networks. Considering the existence of malicious jamming and co-channel interference, a location-aware cooperative anti-jamming scheme is designed for the purpose of maximizing the users' utilities. Users in the UAV group cooperate with each other via location information sharing. When the received interference energy is lower than mutual interference threshold, users conduct channel selection strategies independently. Otherwise, users take joint actions with a cooperative anti-jamming pattern under the impact of mutual interference. Aimed at the independent anti-jamming channel selection problem under no mutual interference, a Markov Decision Process framework is introduced, whereas for the cooperative anti-jamming channel selection case under the influence of co-channel mutual interference, a Markov game framework is employed. Furthermore, motivated by reinforcement learning with a ``Cooperation-Decision-Feedback-Adjustment" idea, we design a location-aware cooperative anti-jamming distributed channel selection algorithm (LCADCSA) to obtain the optimal anti-jamming channel strategies for the users with a distributed way. In addition, the channel switching cost and cooperation cost, which have great impact on the users' utilities, are introduced. Finally, simulation results show that the proposed algorithm converges to a stable solution with which the UAV group can avoid the malicious jamming as well as co-channel interference effectively.

Bee Pollen (BP) has many advantageous properties relying on its multitargeting potential, a new tendency in handling many challenging illnesses. In cancer and neurodegeneration, the antioxidant, anti-inflammatory, immunomodulatory, and antimutagenic effects of BP could be of unequaled importance and need further pharmacological and clinical investigation. Although being still limited, available data interestingly spotlights some floral sources with new and promising activities in-line with this investigation. In addition, we have identified many crucial bioactivities that are widely recognized to individual BP compounds but remain completely untapped in this valuable bee cocktail. A wide range of these compounds have been recently found to be endowed with great potential in modulating pivotal process in neurodegeneration and cancer pathophysiology, such as epigenetic regulation, microbiota composition and function, autophagy, cell death mechanisms, protein misfolding and aggregation and many other effects that we will detail in our current work. In addition, some widely present compounds in BP have only recently been isolated, while the number of studied BPs remain extremely limited compared to the endless pool of plant species that are distributed worldwide. Nevertheless, we have concomitantly elucidated that clinical profits from these promising perspectives are still impeded by some challenging hurdles such as limited bioavailability of the studied phytocompounds, diversity and lack of phytochemical standardization of BP, and the difficulty of selective targeting in some pathophysiological mechanisms. We finally present some interesting insights to guide future research and pave the way for urgent and simplified clinical investigations.

Frailty syndrome is a complex and multifaceted condition that significantly impacts the health and well-being of older adults. This article provides a comprehensive overview of frailty syndrome, including its definitions, evolution, and the rising role of biomarkers and electroencephalography (EEG) in its diagnosis. The discussion explores the reasons behind the rise of frailty syndrome, the difficulties in managing it, and the global research efforts aimed at understanding and addressing this condition. The economic costs associated with frailty syndrome are highlighted, along with the countries that are currently and will be more affected in the near future. Strategies to postpone or avoid frailty syndrome are discussed, with an emphasis on the importance of muscle strength exercises over aerobic exercises to combat sarcopenia. The article concludes by emphasizing the need for a multidisciplinary approach to frailty management and the importance of social support and engagement in preventing and managing frailty.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Development of load-bearing polymer composite constructions in civil engineering, such as industrial chimneys and gas ducts, requires filling some research gaps. These gaps are related to long-term behavior under mechanical and temperature loads, cyclic ones as well. Such conditions mean that viscoelasticity should be considered. First of all, viscoelastic parameters should be calculated, based on the used inner structure model. Then, due to the high working temperatures, thermal aging should be considered as well. This research is devoted to effects of thermal aging on viscoelastic behavior of polymers. Two sets of experiments were conducted: creep tensile tests and cyclic heating in constrained state. The Kelvin-Voigt viscoelasticity model was used to determine the rheological parameters of binder from experimental creep curves. Thermally-aged binder turned out to lose its viscous properties and became elastic. Cyclic heating was used to compare the behavior of normal and thermally-aged binder and to evaluate the possibility of temperature stress accumulation. Similar to creep tests, cyclic heating showed that aged binder lost viscosity and worked almost perfectly elastic. Non-aged binder was prone to stress accumulation much more. As a result, the rheological behavior of aged and non-aged binder was compared and showed a significant difference. In addition, the influence of temperature stress accumulation on stress—strain state was evaluated and turned out to be significant as well. The obtained results can be further used to predict the mechanical behavior of structures made of polymer composites operating for a long time at elevated temperatures, including those exceeding the glass transition temperature.

Conclusion: When applied to the air-abraded Filtek™ Bulk Fill Flowable Restorative composite surface, 10-MDP-containing adhesives perform better than 10-MDP-free adhesives. The binding strength was unaffected by the 10-MDP-containing adhesives' chemical makeup. The bond strength endurance of adhesives containing 10-MDP decreases with age. Keywords: keyword 1; keyword 2; keywords: low-viscosity bulk fill composite, universal adhesives, self-etch adhesive, 10-MDP, aging, bond strength.

When developing bone implants Young's modulus is one of the primary characteristics of the material that should be considered. The study focuses on the possibility of regulating the modulus of the alloy Ti-50.8 at % Ni by varying its initial structure as well as aging-induced microstructure in a wide range. Microstructure observations were performed using TEM and SEM observations. The calorimetric studies of martensitic transformations were carried out using "Mettler Toledo 822e". Tensile tests were performed in a test temperature range of ‒196≤T≤+100°C using an «IN-STRON 5966». The grain/subgrain size of B2-austenite strongly affects the modulus magnitude. This effect is ambiguous for a material with a grain size of 0.13–3 µm and depends on the test temperature. The effectiveness of aging on the modulus reduction depends on the initial structure: it is most pronounced in an alloy with a relatively coarse grain size of 9 µm and brings a decrease by 3.8 times at a temperature of 37°C. Bone-like elastic modulus (10–30 GPa) at a human body temperature of 37°C is realized in an aged fine-grained NiTi alloy. An ultrafine-grained sub-structure exhibits he same values of Young's modulus in the temperature range from -100°С to 25°С.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.