Galectins are a family of beta-galactoside-binding proteins that are characterised by their carbohydrate recognition domain (CRD) and include galectin-1 and galectin-3. These galectins have been implicated in numerous diseases due to their pleiotropic nature, including cancer and fibrosis, with therapeutic inhibitors being clinically developed to block the CRD. One of the early methods developed to characterise these galectins was hemagglutination of red blood cells. Although insightful this approach has been hampered by a lack of sensitivity and accurate quantification of the agglutination observed. In this study we aimed to validate a more precise and quantitative method to enable further investigation of differences between galectins in respect to agglutination induction in different blood groups as well as characterisation of small molecule inhibitors. Quantification of hemagglutination was shown to be optimal using U-bottom plates imaged and analysed with FIJI ImageJ rather than flat bottom plates read for absorbance on an optical density plate reader. Galectin-3-induced red blood cell agglutination efficacy increased significantly from blood group O to A to B. However, for both the galectin-1 monomer and concatemer a more comparable effect was observed between blood group B and O but with more potent effects than in blood group A. Inhibition assays for both galectin-3 and galectin-1 induced-hemagglutination were able to demonstrate clear concentration-responses and expected selectivity profiles for a set of small molecule glycomimetics, confirming historical profiles obtained in biochemical binding and functional cellular assays.

Core chlorophytes possess glycerol-3-phosphate dehydrogenases (GPDs) with an unusual bidomain structure, consisting of a glycerol-3-phosphate phosphatase (GPP) domain fused to canonical GPD domains. These plastid-localized enzymes have been implicated in stress responses, being required for the synthesis of glycerol under high salinity and triacylglycerols under nutrient deprivation. However, their regulation under varying environmental conditions is poorly understood. C. reinhardtii transgenic strains expressing constitutively bidomain GPD2 did not accumulate glycerol or triacylglycerols in the absence of any environmental stress. Although, the glycerol contents of both wild type and transgenic strains increased significantly upon exposure to high salinity. Cycloheximide, an inhibitor of cytoplasmic protein synthesis, abolished this response in the wild type. In contrast, GPD2 transgenic strains were still capable of glycerol accumulation when cultured in medium containing cycloheximide and NaCl. Thus, pre-existing GPD2 protein appears to become activated for glycerol synthesis upon salt stress. Interestingly, staurosporine, a non-specific inhibitor of protein kinases, prevented this post-translational GPD2 protein activation. Structural modeling analyses suggested that substantial conformational rearrangements, possibly triggered by high salinity, may characterize an active GPD2 GPP domain. Understanding this mechanism(s) may provide insights into the rapid acclimation responses of microalgae to osmotic/salinity stress.

This work reports the isolation, purification, and anti-inflammatory evaluation of compounds from the plant species Ageratina pichinchesis. Using open-column chromatography, 11 known compounds were purified, whose chemical structures were elucidated by nuclear magnetic resonance techniques (1D and 2D). All compounds were evaluated in the in vitro model of RAW 264.7 mouse macrophage cells measuring nitric oxide inhibition as a determination of the anti-inflammatory effect. Outstandingly, the compound betuletol 3-O-β-glucoside (11) exhibited inhibition of nitric oxide with an IC50 of 75.08 ± 3.07% at 75 µM, additionally, it inhibited the secretion of interleukin 6 (IL-6) and activation of nuclear factor (NF-kβ). These results show that compound 11 could be considered as a potential anti-inflammatory agent in suppressing the expression of NF-kβ target genes such as the proinflammatory pathway and inducible nitric oxide synthase (iNOS). Consequently, the medicinal use attributed in traditional medicine to the A. pichinchensis species is due to the diversity of compounds that the plant biosynthesizes, demonstrating that its effect relates to anti-inflammatory effects associated with compound 11.

With the development of modern industry, the issue of water pollution has garnered increasing attention. Photocatalysis, as a novel green environmental technology that is resource-efficient, environmentally friendly, and highly promising, has found extensive applications in the field of organic pollutant treatment. However, common semiconductor materials exhibit relatively low photocatalytic efficiency in the visible light range or inefficient separation of photogenerated charges, resulting in their limited ability to harness solar energy effectively. Consequently, the development of new photocatalysts has become a pivotal focus in current photocatalysis research to enhance solar energy utilization. This revision provides a brief explanation of the photocatalytic mechanism of the AgIO3/CTF heterojunction photocatalyst. Due to the Localized surface plasmon resonance (LSPR) effect, Ag nanoparticles demonstrate significant absorption in the visible light region, playing a crucial role in the highly efficient photocatalytic reduction of organic pollutants.

Biomimetic materials are substances that replicate natural structures. There are several methods for producing such materials with highly developed surfaces from a wide range of polymers, but electrospinning is of particular interest due to its simplicity of implementation and the ability to modify the produced fibrous materials resembling structures found in living organisms. This study explores new biomimetic materials based on polyhydroxyalkanoates, specifically poly-3-hydroxybutyrate, modified with chlorophyll derivatives. The research investigates the impact of chlorophyll derivatives on the morphology, supramolecular structure, and key properties of nonwoven materials. The obtained results are of interest for the development of new biomimetic environmentally friendly materials for biomedicine with special properties.

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Norovirus (NoV) is recognised as a major cause of epidemic and sporadic acute gastroenteritis (AGE) in all age groups. Information on the genetic diversity of the NoVs circulating in the 1980s and 1990s, before the development and adoption of dedicated molecular assays, is limited compared to the last decades. In the period 1986-2020, uninterrupted viral surveillance was conducted in symptomatic children hospitalized for AGE in Palermo, Italy, providing a unique time capsule for exploring the epidemiological and evolutionary dynamics of enteric viruses. In this 35-year long time span NoVs of genogroup II (GII) were detected in 15.6% of AGE requiring hospitalization, whilst GI NoVs in 1.4%. Overall, the predominant NoV capsid (Cap) genotype was GII.4 (60.8%), with temporal replacement of the GII.4 Cap variants and associated polymerase (Pol) types. The chronology of emergence and circulation of the different GII.4 variants were consistent with the data available in literature. Also, for GII.3 and GII.2 NoVs the circulation of different lineages/strains, differing in either the Cap or Pol genes or in both, was observed. This long-term study revealed the ability of NoVs to modify continuously and rapidly their genomic makeup and highlights the importance of surveillance activities for vaccine design.

Edge computing has emerged as a significant computing trend alongside the rapid expansion of the Internet of Things (IoT). Computing operations at the network’s edge offer a solution to the high latency and service overload challenges often associated with cloud computing. Additionally, the Secure Hash Algorithm-3 (SHA-3) plays a crucial role in ensuring data integrity and is implemented for numerous applications in the IoT field. Therefore, integrating the SHA-3 accelerator into edge computing is essential. Moreover, recent studies about SHA-3 have primarily focused on achieving high performance and optimizing resource utilization for SHA-3. However, these studies have overlooked the crucial aspect of data transfer between the external memory and the hash function block, as transfer time plays a significant role. This paper proposes an efficient SHA-3 architecture designed for System-on-Chip (SoC) Field Programmable Gate Array (FPGA) to address the aforementioned challenges and be suitable for real edge computing. The architecture contains three key techniques. First, the harmony of padding and Direct Memory Access (DMA) for managing the data transfer process and enhancing performance efficiency based on Serial Input to Parallel Output (SIPO) and a barrel shifter. Secondly, implementing internal pipelining within the Round Function (RF) to reduce critical path delays and optimize resource utilization. Finally, designing four modes (SHA3-224, SHA3-256, SHA3-384, and SHA3-512) to cater to various applications. Our architecture is implemented and tested on the DE10-Standard Development Kit (Cyclone V SX SoC-5CSXFC6D6F31C6N), which is integrated into the FPGA and is controlled by a Dual-Core ARM Cortex-A9 processor. The result is up to 38.34 Gbps in throughput and 5.61 Mbps/ALM in efficiency for the RF computation, 28.02 Gbps in throughput, and 3.63 Mbps/ALM for the full proposed architecture.

Cervical cancer is the most common female reproductive tract tumor and is currently the only cancer that can be prevented by vaccination. Early detection and treatment of cervical cancer can be achieved through regular screening for human papillomavirus (HPV). Therefore, in this paper, an electrochemical sensor was designed to detect HPV 16 using a dual signal amplification technique. APTES modified glassy carbon electrode to improve stability. Combining gold nanoparticles and chain amplification reactions for signal amplification purposes. The limit of detection (LOD) was 1.731×10-16 mol/L, and the detection range of this electrochemical sensor was increased in comparison to previous research, with a linear response range from 1.0×10-13 mol/L to 1.0×10-5 mol/L (R2 = 0.99232) for the target detector.In addition, the sensor showed equally good recovery in sophisticated human serum samples. It shows that it has good interference resistance and the designed biosensor can be a powerful and reliable tool for clinical disease diagnosis.

Isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was obtained 95% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction at room temperature for 190 minutes in dichloromethane. The structure of isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) was established by NMR, FTIR, and the high resolution of mass spectroscopies. In vitro sun protection factor evaluation exhibited value of 37.10 ± 0.03 which indicates that isoamyl (E)-3-(3,4-dimethoxyphenyl)acrylate (1) as a sunscreen agent with high protection.

Background The main aim of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. Methods Chronic inflammatory anaemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. In RS, it is important to maintain good tissue oxyporesis, avoiding blood hyperviscosity. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Haemoglobin (Hb) levels, Corpuscular Indexes, Transferring saturation (TSAT) ferritin concentrations and creatinine clearance have been measured the first day after surgery (T0), after the first week (T1) and after five weeks (T2). At T0 all patients showed low hemoglobin levels (average 7.4 g/dl, STD 0,71range 6,2-7,4 g dL-1), with an MCV of 72, MCH 28, MCHC 33, RDW 16, Sideremy 35, Ferritin 28, Ret% 1,36, TRF 277 and Creatinine Clearance 119. . We assessed all patients for clinical status, medical history and comorbidities before starting therapy. Results. In collaboration between the two departments, we started a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, on the second day after surgery. Thirteen patients received ESAs and FCM (500-1000 mg per session), three patients received ESAs and iron gluconate (1 vial every other day). No patients received blood transfusions. No side effects were observed and, most importantly, no limb or flap rejection. Conclusions Preliminary data from our protocol show an optimal therapeutic response in a surgical setting with limited data in the scientific literature. The enrolment of further patients will allow us to validate this therapeutic protocol with statistically significant data.

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English, Japanese, Korean, and Chinese sources while combining bibliometrics and network analyses for data visualisation. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median=3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. Cancer patients reported reduced side effects from chemoradiotherapy and improved quality of life in human studies, indicating RBAC’s impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

Binge drinking is a pattern of alcohol abuse. Its prevalence and associated risk factors are not well documented. Heavy drinking, on the other hand, has a well-studied association with bereavement . This report uses a cross-sectional, population-based survey to estimate prevalence of bingeing and its association with new bereavement. Bingeing is defined as 4 or more drinks (women) or 5 or more drinks (men) in a 2-to-4-hour setting. For the first time, the Georgia Behavioral Risk Factor Surveillance Survey (BRFSS) included a bereavement item, ‘Have you experienced the death of a family member or close friend in the years 2018 or 2019?’. Methods: Georgia BRFSS is a complex sampling survey administered annually. It is designed to represent the 8.1 million persons in the U.S. state of Georgia aged 18 years and older. Alcohol consumption patterns are routinely measured in the common core. In the 2019 field survey, the state added a new item probing for bereavement in the prior 24 months predating the pandemic of COVID-19. Imputation and weighting techniques were applied to yield population prevalence rates of new bereavement, bingeing, and their co-occurrence with other high-risk health states. Models, adjusted for age, gender, and race were used to estimate the risk for other unhealthy behaviors posed by the co-occurrence of bereavement and bingeing. Results: In Georgia, bereavement is common (45.8 %), and alcohol consumption is common (48.8 %). Bereavement and alcohol use co-occurred among 1,796,817 persons (45 % of all drinkers). The subset of co-occurring bereavement and binging totaled 608,282 persons. Within this group, the highest rates of bereavement were associated with death of a friend / neighbor (30.7%) or 3 plus deaths (31.8%). Conclusions: While bingeing is a known risk to public health, its co-occurrence with recent bereavement is a new observation. Public health surveillance systems need to monitor this co-occurrence to protect both individual and societal health. In a time of global bereavement, documenting its influence on binge drinking can support the work towards Sustainable Goal #3 – Good health and Well-Being. Keywords: BRFSS, Binge Drinking, Population Survey, Bereavement, SDG#3. Mental Health

Plants are constantly exposed to a variety of different environmental stresses, including drought, salinity, and elevated temperatures. These stress cues are assumed to aggravate in the future driven by the global climate change scenario which we are currently experiencing. These stressors have largely detrimental effects on plant growth and development and, therefore, put global food security in jeopardy. For this reason, it is necessary to expand our understanding of the underlying mechanisms by which plants respond to abiotic stresses. Especially boosting our insight into the ways by which plants balance their growth and their defense programs appears to be of paramount importance, as this may lead to novel perspectives that can pave the way to increase agricultural productivity in a sustainable manner. In this review, our aim was to present a detailed overview of different factettes of the crosstalk between the antagonistic plant hormones abscisic acid (ABA) and auxin, two phytohormones that are the main drivers of plant stress responses, on the one hand, and plant growth, on the other.

Today's major challenge for smart Microgrids is to ensure the security of communications in a large number of changing data sets that are vulnerable to attacks by denial of services in constant evolution. The Internet Protocol Traceback defines a set of methods that help identify the source of an attack with minimal requirements for memory and processing. However, the concept of Traceback is not yet being used in smart Microgrids. As a result, the main challenge of this article is to incorporate a new Traceback approach into the cybernetic system of a smart mesh Microgrid, which can be tested using a network simulator (NS-3) based on delay, debit, and packet loss rate parameters. In fact, the simulation results show the efficacy of this approach compared to others existing in the literature. Furthermore, using the proposed Traceback technique and the mesh nodes, we were able to create a smart meshed Microgrid. Moreover, using the Traceback approach given for merging Intel Galileo Gen.1 nodes with the Compex WLE200NX.11a/b/g/n to establish a secure test bench, which is deployed as a prototype at the Sfax Digital Research Center in Tunisia, we were able to create an intelligent Microgrid. In fact, by identifying all attack vectors and revealing their origins, we could boost the efficiency of our operation by 100%.

Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.

With the introduction of HTTP/3, whose transport is no longer the traditional TCP protocol but the novel QUIC protocol, research for solutions to the unfairness of Adaptive Streaming over HTTP (HAS) has become more challenging. That is, because of different transport layers, the HTTP/3 may not be available for some networks and the clients have to use HTTP/2 for their HAS applications instead. Therefore, the scenario that HAS over HTTP/3 (HAS/3) compete against HTTP/2 (HAS/2) must be considered seriously. However, there have been a shortage of investigations on the performance and the origin of the unfairness in such a cross-protocol scenario in order to produce proper solutions. Therefore, this paper provides a performance evaluation and root-cause analysis of the cross-protocol unfairness between HAS/3 and HAS/2. It is concluded that, due to differences in the congestion control mechanisms of QUIC and TCP, HAS/3 clients obtain larger congestion windows, thus requesting higher video bitrates than HAS/2. As the problem lies in the transport layer, existing client-side ABR-based solutions for the unfairness from the application layer may perform suboptimally for the cross-protocol case.

Adrenergic receptor β3 (ADRβ3) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of the ligand to ADRβ3 activates adenylate cyclase and increases cAMP in the cells. ADRβ3 is highly expressed in white and brown adipocytes and controls key regulatory pathways of lipid metabolism. Trp64Arg (W64R) polymorphism in the ADRβ3 has been associated with the early development of type 2 diabetes mellitus, lower resting metabolic rate, abdominal obesity, and insulin resistance. It is unclear how the substitution of W64R affects the functioning of ADRβ3. This study was initiated to functionally characterize this obesity-linked variant of ADRβ3. We evaluated in detail the expression, subcellular distribution, and post-activation behavior of the WT and W64R ADRβ3 using a single cell quantitative fluorescence microscopy. When expressed in HEK 293 cells, ADRβ3 shows a typical distribution displayed by other GPCRs with a predominant localization at the cell surface. Unlike Adrenergic receptor β2 (ADRβ2), agonist induced desensitization of ADRβ3 does not involve loss of cell surface expression. WT and W64R variant of ADRβ3 displayed comparable biochemical properties and there was no significant impact of the substitution of Tryptophan with Arginine on the expression, cellular distribution, signaling, and post-activation behavior of ADRβ3. The obesity-linked W64R variant of ADRβ3 is indistinguishable from the WT ADRβ3 in terms of expression, cellular distribution, signaling, and post-activation behavior.

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson’s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

Toward the standardization of O. biennis sprout extract (OBS-E), we aimed to obtain indicator compounds, using a validated method. HPLC-UVD allowed simultaneous quantification of indicator compounds quercetin 3-glucuronide and ellagic acid. The method was validated in terms of specificity, linearity, precision, accuracy, and limit of detection/limit of quantification (LOD/LOQ). High specificity and linearity was demonstrated, with correlation coefficients of 1.0000 for quercetin 3-glucuronide and 0.9998 for ellagic acid. The LOD/LOQ values were 0.486/1.472 μg/mL for quercetin 3-glucuronide and 1.003/3.039 μg/mL for ellagic acid. Intra-day and inter-day variability tests produced relative standard deviation for each compound of &lt;2%, a generally accepted precision criterion. High recovery rate were also obtained, indicating accuracy validation. The OBS-E prepared using various concentrations of ethanol were then analyzed. The 50% ethanol extract had highest content of quercetin 3-glucuronide, whereas the 70% ethanol extract possessed the lowest. However, the ellagic acid content was highest in the 70% ethanol extract and lowest in the 90% ethanol extract. Thus, quercetin 3-glucuronide and ellagic acid can be used industrially as indicator compounds for O. biennis sprout products, and our validated method can be used to establish indicator compounds for other natural products.

We present a cost- and time-efficient method for the controlled preparation of single phase La(IO3)3 nanoparticles via a simple soft-chemical route which takes a matter of hours, thereby providing an alternative to the common hydrothermal method which takes days. Nanoparticles of pure α-La(IO3)3 and pure δ-La(IO3)3 were synthesised via the new method depending on the source of iodate ions, thereby demonstrating the versatility of the synthesis route. The crystal structure, nanoparticle size-dispersal and chemical composition were characterised via angle- and energy-dispersive powder X-ray diffraction, scanning electron microscopy and Fourier-transform infrared spectroscopy.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

Fish oil rich in docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), vitamin D₃ and natural astaxanthin sustainably extracted from anchovy fillet leftovers using biobased limonene only, can be conveniently stabilized by adsorption on periodic mesoporous silicas. The simplicity of the process, the high load of entrapped fish oil, and the biocompatible nature of silica support numerous forthcoming applications of this new class of “Omeg@Silica” materials.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

Background: Although a cholesterol-lowering diet and the addition of plant sterols and stanols are suggested for the lipid management of children and adults with familial hypercholesterolemia, there is limited evidence evaluating such interventions in this population. Objectives: To investigate the impact of cholesterol-lowering diet and other dietary interventions on the incidence or mortality of cardiovascular disease and lipid profile of patients with familial hypercholesterolemia. Search methods: Relevant trials were identified by searching US National Library of Medicine National Institutes of Health Metabolism Trials Register and clinicaltrials.gov.gr using the following terms: diet, dietary, plant sterols, stanols, omega-3 fatty acids, fiber and familial hypercholesterolemia. Selection criteria: Randomized controlled trials evaluating the effect of cholesterol-lowering diet or other dietary interventions in children and adults with familial hypercholesterolemia were included. Data collection and analysis: Two authors independently assessed the trial eligibility and bias risk and one extracted the data, with independent verification of data extraction by a colleague. Results: A total of 17 trials were finally included, with a total of 376 participants across 8 comparison groups. The included trials had either a low or unclear bias risk for most of the parameters used for risk assessment. Cardiovascular incidence or mortality were not evaluated in any of the included trials. Among the planned comparisons regarding patients’ lipidemic profile, a significant difference was noticed for the following comparisons and outcomes: omega-3 fatty acids reduced triglycerides (mean difference [MD]: -0.27 mmol/L, 95% confidence interval [CI]: -0.47 to -0.07, p<0.01) when compared with placebo. A non-significant trend towards a reduction in subjects’ total cholesterol (MD: -0.34, 95% CI: -0.68 to 0, mmol/L, p=0.05) and low-density lipoprotein cholesterol (MD: -0.31, 95% CI: -0.61 to 0, mmol/L, p=0.05) was noticed. In comparison with cholesterol-lowering diet, the additional consumption of plant stanols decreased total cholesterol (MD: -0.62 mmol/l, 95% CI: -1.13 to -0.11, p=0.02) and low-density lipoprotein cholesterol (MD: -0.58 mmol/l, 95% CI: -1.08 to -0.09, p=0.02). The same was by plant sterols (MD: -0.46 mmol/l, 95% CI: -0.76 to -0.17, p<0.01 for cholesterol, and MD: -0.45 mmol/l, 95% CI: -0.74 to -0.16, p<0.01 for low-density lipoprotein cholesterol). No heterogeneity was noticed among the studies included in these analyses. Conclusions: Available trials confirm that the addition of plant sterols or stanols has a cholesterol-lowering effect on such individuals. On the other hand, supplementation with omega-3 fatty acids effectively reduces triglycerides and might have a role in lowering the cholesterol of patients with familial hypercholesterolemia. Additional studies are needed to investigate the effectiveness of a cholesterol-lowering diet or the addition of soya protein and dietary fibers to a cholesterol-lowering diet in familial hypercholesterolemia.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

Galectin-3 is considered a cancer biomarker and bioindicator of fibrosis and cardiac remodeling, and, therefore, it is desirable to develop convenient methods for its detection. Herein, an approach based on the development of multivalent electrochemical probes with high galectin-3 sensing abilities is reported. The probes consist of multivalent presentations of lactose–ferrocene conjugates scaffolded on poly(amido amine) (PAMAM) dendrimers and gold nanoparticles. Such multivalent lactose–ferrocene conjugates are synthesized by coupling of azidomethylferrocene-lactose building blocks on alkyne-functionalized PAMAM, for the case of the glycodendrimers, and to disulfide‐functionalized linkers that are then used for the surface modification of citrate-stabilized gold nanoparticles. The binding and sensing abilities towards galectin 3 of both ferrocene-containing lactose dendrimers and gold nanoparticles have been evaluated by means of isothermal titration calorimetry, UV-vis spectroscopy, and differential pulse voltammetry. The highest sensitivity by electrochemical methods to galectin-3 was shown by lactosylferrocenylated gold nanoparticles, which are able to detect the lectin in nanomolar concentrations.

Gold clusters protected by 3-MBA ligands (MBA = mercaptobenzoic acid, -SPhCO2H) have attracted recent interest for their unusual structures and advantageous ligand-exchange and bioconjugation properties. Azubel et al. first determined the core structure of an Au68-complex, which was estimated to have 32 ligands (3-MBA groups). To explain the exceptional structure-composition and reaction properties of this complex, and its larger homologs, Tero et al. proposed a “dynamic stabilization” via carboxyl O-H--Au interactions. Herein, we report the first results of an integrated LC/MS analysis of unfractionated samples of gold / 3-MBA clusters, spanning the narrow size range 13.4 to 18.1 kDa. Using high-throughput procedures adapted from bio-macromolecule analyses, we show that integrated capillary HPLC-ESI-MS, based upon aqueous-methanol mobile phases and ion-pairing reverse-phase chromatography, can separate several major components from the nanoclusters mixture that may be difficult to resolve by standard native gel electrophoresis due to their similar size and charge. For each component, one obtains a well-resolved mass spectrum, nearly free of adducts or signs of fragmentation. A consistent set of molecular mass determinations is calculated from detected charge-states tunable from 3- (or lower), to 2+ (or higher). One thus arrives at a series of new compositions (n, p) specific to the Au/3-MBA system. The smallest major component is assigned to the previously unknown (48, 26); the largest one is evidently (67, 30), vs. the anticipated (68, 32). Various explanations for this discrepancy are considered. A prospective is given for the several members of this novel series, along with a summary of the advantages and present limitations of the micro-scale integrated LC/MS approach to characterize such metallic-core macro-molecules, and their derivatives.

Based on a modified dice-and-fill technique, a PIN-PMN-PT single crystal 1-3 composite with the kerf of 12 μm and pitch of 50 μm was prepared. The as-made piezoelectric composite material behaved with high piezoelectric constant (d33 = 1500 pC/N), high electromechanical coefficient (kt = 0.81), and low acoustic impedance (16.2 Mrayls). Using lithography and flexible circuit method, a 48-element phased array was successfully fabricated from such a piezoelectric composite. The array element was measured to have a central frequency of 20 MHz and a fractional bandwidth of approximately 77% at −6 dB. Of particular significance was that this PIN-PMN-PT single crystal 1-3 composite-based phased array exhibits a superior insertion loss compared with PMN-PT single crystal and PZT-5H-based 20 MHz phased arrays. The focusing and steering capabilities of the obtained phased array were demonstrated theoretically and experimentally. These promising results indicate that the PIN-PMN-PT single crystal 1-3 composite-based high frequency phased array is a good candidate for ultrasound imaging applications.

In this present study, 3-pentadecyl-phenol was selected as a modifier to prepare a foamable phenolic resin with excellent performance, which was successfully prepared by in-situ modification. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (¹H NMR, ¹³C-NMR) were used to test and characterize the molecular structure of the modified resin. The results showed that 3-pentadecyl-phenol successfully modified the molecular structure of phenolic resin with a reduction in resin gel time. The effect of changing the added amount of 3-pentadecyl-phenol on the mechanical properties, microstructure and flame retardancy of the modified foam was investigated. The results showed that when the amount of added 3-pentadecyl-phenol was 15% of the total amount of phenol, this resulted in the best toughness of the modified foam, which could be increased to 300% compared to the bending deflection of the unmodified phenolic foam. The cell structure showed that the modified phenolic foam formed a more regular and dense network structure and the closed cell ratio was high. Furthermore, the compressive strength, bending strength, and limited oxygen index were improved, while the water absorption rate was lowered. However, the foam density could be kept below 40 mg/cm³, which does not affect the load.

Streptococcus mutans (S. mutans) is the main etiological bacteria present in the oral cavity that leads to dental caries. All of the S. mutans in the oral cavity form biofilms that adheres to the surfaces of teeth. Dental caries are infections facilitated by the development of biofilm. An esterified derivative of epigallocatechin-3-gallate (EGCG), epigallocatechin-3-gallate-sterate (EGCG-S) was used in this study to assess its ability to inhibit the growth and biofilm formation of S. mutans. The effect of EGCG-S on bacterial growth was evaluated with colony forming units (CFU) and log reduction; biofilm formation was qualitatively determined by Congo red assay, and quantitatively determined by crystal violet assay, fluorescence-based LIVE/DEAD assays to study the cell viability, and scanning electron microscopy (SEM) was used to evaluate the morphological changes. The results indicated that EGCG-S was able to completely inhibit growth and biofilm formation at concentrations of 250 µg/ml. Its effectiveness was also compared with a commonly prescribed mouthwash in the United States, chlorhexidine gluconate. EGCG-S was shown to be equally effective in reducing S. mutans growth as chlorhexidine gluconate. In conclusion, EGCG-S is potentially a natural anticariogenic agent by reducing bacterial presence in the oral cavity.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of &lt;100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

This study investigates the preparation of KNN-ZnO composites through optimized sintering conditions under both inert and oxygen atmospheres. Initial experiments employing inert hot pressing were hindered by the necessity for annealing, which resulted in cracks due to the differing thermal expansion coefficients of KNN and ZnO, rendering this method unsuitable for composite fabrication. Consequently, sintering under an oxygen atmosphere was adopted, yielding a uniform distribution of ZnO particles within the KNN matrix. The resultant microstructure demonstrated significant densification, enhanced homogeneity, and minimal porosity. Electrical performance evaluations revealed that while the incorporation of ZnO led to a slight reduction in the ferroelectric properties (d₃₃ and polarization) of the KNN matrix, it concurrently improved the electromechanical quality factor (Q_m) by 40%. However, the overall enhancements were less pronounced when compared to analogous BNT-BT systems, underscoring the necessity for further optimization of processing conditions to boost electromechanical efficiency and piezoelectric response in KNN-based ceramics.

Looking for effective synthetic methods for 1H-pyrazolo[3,4-b]quinolines preparation, we came across a procedure where in a three component reaction catalyzed by L-proline, 4-aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines are formed. These compounds can be easily oxidized to a fully aromatic system, which gave hope for a synthetic method that could replace e.g. Friedländer condensation, often used for this purpose, although severely limited by the availability of suitable substrates. However, after careful repetition of the procedures described in the publication, it turned out that the compounds described therein do not form at all. The actual compounds turned out to be 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles). 4-Aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines were prepared by another method and used as standards to compare the products formed in the original procedure.

Thermal sterilization is generally avoided for 3-D printed components because of the relatively low deformation temperatures for common thermoplastics used for material extrusion-based additive manufacturing. 3-D printing materials required for high-temperature heat sterilizable components for COVID-19 and other applications demands 3-D printers with heated beds, hot ends that can reach higher temperatures than polytetrafluoroethylene (PTFE) hot ends and heated chambers to avoid part warping and delamination. There are several high temperature printers on the market, but their high costs make them inaccessible for full home-based distributed manufacturing required during pandemic lockdowns. To allow for all these requirements to be met for under $1,000, the Cerberus – an open source three-headed self-replicating rapid prototyper (RepRap) was designed and tested with the following capabilities: i) 200^oC-capable heated bed, ii) 500^oC-capabel hot end, iii) isolated heated chamber with 1kW space heater core and iv) mains voltage chamber and bed heating for rapid start. The Cereberus successfully prints polyetherketoneketone (PEKK) and polyetherimide (PEI, ULTEM) with tensile strengths of 77.5 and 80.5 MPa, respectively. As a case study, open source face masks were 3-D printed in PEKK and shown not to warp upon widely home-accessible oven-based sterilization.

This study presents an optimized design for a Segmented Sinusoidal Parameter Winding with Magnetic Wedge Variable Reluctance Resolver (SSPWMW-VRR), addressing challenges like winding asymmetry and harmonic distortion in conventional designs. By integrating Particle Swarm Optimization (PSO) for winding design, Magnetic Equivalent Circuit (MEC) analysis for leakage flux, and machine learning techniques (XGBoost and Multi-Layer Perceptron), the stator slot shape was fine-tuned for improved accuracy. XGBoost outperformed MLP in prediction accuracy with a Mean Absolute Error (MAE) of 0.1172. Finite Element Analysis (FEA) simulations and experimental validation demonstrated a reduction in position errors from ±30’ in conventional VRRs to ±5’ in the optimized design, along with significant harmonic reduction.

The dietary supplement industry is a growing market with a variety of suppliers, producers, and distributors in terms of size and quality. Because of the little amount of regulation placed on the dietary supplement industry compared to the pharmaceutical industry in the United States, there is less pressure on supplement companies ensure that their labels accurately reflect the actual product’s content. There are few studies on the quality of fish oil sold in the U.S., particularly about quantitation of ω-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The aim of this study was to compare the amount of ω-3 fatty acids found in fish oil capsules and liquids bought from local stores to their label claim. Of the 16 fish oil products tested, 6 were ± 20% outside of the label claim for EPA and 10 of 15 were ± 20% outside of the label claim for DHA. One product did not have a label claim for DHA. The large variance in the amount of omega-3s from the product label could mislead consumers to ingesting significantly more or less than expected.

In previous papers we have derived equations of motion with radiation terms and proved the existence-uniqueness of periodic solution of the 3-body problem of classical electrodynamics. The number of equations of motion – 12 is more than the number of unknown functions – 9. It turns out that 9 equations are independent and the rest 3 ones are consequences of them. These three equations have a solution and they give the expressions for the energy of the moving particles. The main goal of the present paper is to estimate the energy of rounding about the nuclei particles and compare it with the values given by quantum mechanics.

Obesity is associated with chronic low-grade inflammation. Polyunsaturated fatty ac-ids such as omega-3 (n-3), are essential in the pro-resolution of inflammation. An 8-week double-blind randomized clinical trial was conducted with a n-6:n-3, 5:1 ratio, along with daily 1.8 g of n-3 supplementation vs. placebo. A total of 40 subjects were included, 21 in omega 3 group and 19 in placebo group. The n-3 supplementation had a superior effect compared to placebo increasing levels of Resolvin D1 [129.3 (-90.1 - 193.5) vs. -16.8 (-237.8 - 92.5) pg/mL, p=0.041], IL-10 [1.4 (-0.7 - 4.6) vs. -2.0 (-5 - 0.05) pg/mL, p=0.001], and decreasing IL-6 [-0.67 (2.72 - -0.59) vs. 0.03 (-0.59 - 1.84) pg/mL p=0.015], and MCP-1 [-29.6 (-94.9 - 5.50) vs. 18.3 (-97.3 - 66.35) pg/mL, p=0.040]. In con-clusion, n-3 supplementation promoted resolution of inflammation by increasing sys-temic levels of Resolvin D1, IL-10, and decreasing IL-6 and MCP-1.

This paper, from the perspective of Mode 3 of knowledge production, takes the important carrier of knowledge, scientific research papers, as the research object. The mainstream databases (SCIE and SSCI) are chosen as the data sources. Firstly, bibliometric methods are applied to analyze the cooperation status among the main bodies of paper production, including authors and their affiliated institutions, countries, and disciplines; secondly, the Analytic Hierarchy Process (AHP) is used to construct a comprehensive evaluation model for the state of research cooperation in carbon neutrality. Based on the evaluation model, the cooperation characteristics of different disciplinary fields and the relationship between paper cooperation status and high-impact research papers are comparatively analyzed. At the same time, an analysis is conducted on the support from the government, the sponsorship from enterprises, and the participation of the public in the process of paper production. Finally, some suggestions are put forward on how to build an innovative ecosystem for carbon neutrality research from the perspective of Mode 3 of knowledge production.

International law faces numerous challenges in the 21st century, ranging from the traditional issues of sovereignty to emerging threats like cyber warfare and climate change. This article explores the evolving landscape of international law, discussing both the challenges it faces and the prospects for its future. By examining the role of international organizations, the impact of technological advancements, and the growing influence of non-state actors, this article provides a comprehensive overview of the current state of international law and offers insights into how it can adapt to meet the demands of an increasingly interconnected world.

Businesses now formally enter the phase of "think power differentiation and gap" in response to the new economic climate. While AI, big data, empowerment via the internet, and other aspects of the digital economy help to improve technical capabilities and save operating costs, they also push businesses to innovate their strategies at a faster rate. Enterprises are strategically choosing to de-enterprise, moving from focusing on a single business functioning benefit to building an ecosystem of platform services that will give them a competitive edge. Additionally, the organization's structure is evolving continually from a vertical model to a curved working style, in order to achieve this, businesses must recognize the importance of data analysis in day-to-day management and operations, encourage the development of an organizational atmosphere that is driven by data, fully utilize digital technology, modularize areas or production links that perform related tasks, and encourage the reform of organizational structures. By streamlining the output of the product or service to the external community while also enhancing the company's financial performance model, switching from process-to result-oriented evaluation, and putting in place a customized authority and accountability framework. Replace outcome-focused evaluation with process-focused evaluation, and create a customized incentive scheme that balances power, accountability, and rewards.

Abstract: Effectiveness of a Single Fixed Dose 3 mg Rasburicase for Prevention and Management of Hyperuricemia of Tumor Lysis Syndrome in adult Cancer Patients Background: Tumor lysis syndrome (TLS) is a potentially life-threatening complication associated with certain types of cancer. Rasburicase is an essential medicine required to prevent and treat the hyperuricemia associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed dose strategy of 3 mg rasburicase had been used in many adult cancer patients in our center. Objective: The objective of this study was to assess the effectiveness of a 3 mg fixed dose of rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. Methods: We conducted a retrospective, observational cohort study between March 2020 and November 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum UA levels of

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Lysophosphatidic acid (LPA) type 3 (LPA3) receptor mutants were generated in which the sites detected phosphorylated were substituted by non-phosphorylatable amino acids. Substitutions were made in the intracellular loop 3 (IL3 mutant), the carboxyl terminus (Ctail), and both domains (IL3/Ctail). The wild-type (WT) receptor and the mutants were expressed in T-REx HEK293 cells, and the consequences of the substitutions were analyzed employing different functional parameters. Agonist- and LPA-mediated receptor phosphorylation was diminished in the IL3 and Ctail mutants and essentially abolished in the IL3/Ctail mutant, indicating that the main sites were substituted and distributed in both domains. The WT and mutant receptors increased intracellular calcium and ERK 1/2 phosphorylation in response to LPA and PMA. An increase in baseline ERK phosphorylation was detected in the IL3/Ctail mutant. LPA and PMA-induced receptor interaction with β-arrestin 2 and LPA3 internalization were severely diminished in the mutants. Mutant-expressing cells also exhibit increased baseline proliferation and response to different stimuli, which were inhibited by the antagonist Ki16425, suggesting a role of LPA receptors in this process. Migration in response to different attractants was markedly increased in the Ctail mutant, which the Ki16425 antagonist also attenuated.

The main purpose of this article is to consider the smoothness control of a weak solution after some moment if there is known solution regularity until this moment. The necessary tools can be varied. It is possible to control kinetic energy dissipation to fix moment or changing of velocity square or summability of acceleration square to fix at point time.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

A new approach is presented for dynamic modeling of chemical and isotopic evolution of C1-3 during the hydrocarbon generation process. Based on systematic data obtained from published papers for pyrolysis of various hydrocarbon sources(type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, asphalt, etc), the empirical evolution framework of chemical and isotopic composition of C1-3 during the hydrocarbon generation process was built. Although the empirical framework was built only by fitting large amount of pyrolysis data, the chemical and isotopic composition of C1-3 derived from the pyrolysis experiments all follow the evolution laws, convincing us that it is applicable to the thermal evolution process of various hydrocarbon sources. Based on the simplified formula of the isotopic composition of mixed natural gas at different maturities (δ13Cmixed) δ13Cmixed=(X〖*n〗_iA 〖*δ〗^13 C_iA+Y〖*n〗_iB 〖*δ〗^13 C_iB)/(X〖*n〗_iA+Y〖*n〗_iB ), it can be derived that the cumulative isotopic composition of alkane generated in certain maturity interval can be expressed by the integral of the product of instantaneous isotopic composition and instantaneous yield at certain maturity point, and then divided by the cumulative yield of alkane generated in corresponding maturity interval. Thus, the cumulative isotopic composition(A(X)), cumulative yield(B(X)), instantaneous isotope(C(X)),and instantaneous yield(D(x)) in the dynamic model comply with the following formula during the maturity interval of (X0-X) A(X)=(∫_(X_0)^X▒〖C(X)*D(X)dx〗)/(B(X)), where A(X) and B(X) can be obtained by fitting of pyrolysis data, and D(x) can also be obtained from the derivation of B(X). The dynamic model was applied on the pyrolysis data of Pingliang Shale to illustrate the quantitative evolution of cumulative yield ,instantaneous yield, cumulative isotope and instantaneous isotope of C1-3 with increasing maturity.The dynamic model can quantify the yield of methane, ethane and propane as well as δ13C1, δ13C2 and δ13C3 respectively during the hydrocarbon generation process, which is of great significance to evaluate the natural gas resources of hydrocarbon source rock with different maturity and to identify the origin and evolutionary process of hydrocarbons by chemical and isotopic data. Moreover, this model provides an approach to study the dynamic evolution of isotope series of C1-3 (including reversed isotopic series), which is hopeful to reveal the mechanism responsible for isotopic reversal when combined with post-generation studies.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

In the context of evaluating physical function in individuals with stroke, the 3-meter backward walk test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test-retest reliability and construct validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) three times by different physiotherapists. Results indicated the 3MBWT displayed high reliability (r=0.97-0.98) and showed significant construct validity with other established walking tests like the 6MWT (r=-0.78) and 10MWT (r=0.71), with a moderate correlation to the FGA (r=-0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and validates well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

Powdery mildew disease, caused by Sphaerotheca fusca, is a major disease affecting cucumbers cultivated in greenhouses. This study was conducted to find defense genes induced by DL-3-amino-butyric acid (BABA) and powdery mildew in cucumber. The 2000 and 5000 mg/L BABA treated cucumber exhibited disease severity of 25% and 5%, respectively, whereas the water treated cucumber leaves were severely infected, with a disease severity of 90%. BABA did not effect spore germination of the powdery mildew pathogen,. showing BABA is not antifungal agent against the pathogen. In quantitative real-time PCR analysis, BABA treated cucumber upregulated transcriptional level of the defense genes CsPAL, CsPR3,CsPR1, CsLOX1, CsLOX23, Cs LecRK6.1, CsWRKY20, and Cupi4 in cucumber to maximum levels at 48 h, whereas CsLecRK6.1 reached maximum expression after 24 h and futher salicylic acid (SA) levels were significantly increased in BABA-treated cucumber plants. In addition, the infected cucumber with powdery mildew enhanced the expression levels from1.6 to 47.3 fold of the defense genes PAL, PR3, PR1, Lox1, Lox 23, LecRK6.1, WRKY20, and Cupi4 compared to heathy cucumber. The results suggests the BABA induced defense response is associated with SA signal pathway-dependent systemic acquired resistance (SAR) in cucumber, which is involved in plant resistance mechanisms.

In urban Vehicular Ad Hoc Network (VANET) environments, buildings play a crucial role as they can act as obstacles that attenuate the transmission signal between vehicles. Quantifying the impact of buildings on the transmission quality is essential, especially in critical scenarios involving emergency vehicles, where reliable communication is of utmost importance. In this research, we propose a supervised learning approach based on artificial neural networks (ANNs) to develop a predictive model capable of estimating the level of signal degradation, represented by the bit error rate (BER), based on the obstacles perceived by moving emergency vehicles. By establishing a relationship between the level of signal degradation and the encountered obstacles, our proposed mechanism enables efficient routing decisions to be made prior to the transmission process. Consequently, data packets are routed through paths that exhibit the lowest BER. To gather the necessary training data, we employed SUMO and NS-3 simulations. The simulation results demonstrate that our developed model successfully learns and accurately estimates the BER for new data instances. Overall, our research contributes to enhancing the performance and reliability of communication in urban VANET environments, especially in critical scenarios involving emergency vehicles, by leveraging supervised learning and artificial neural networks to predict signal degradation levels and optimize routing decisions accordingly.

Indole-3-acetic acid (IAA) is a key vegetative hormone that plays crucial roles in plant growth and development. In this study, the effect of the exogenous application of IAA as a biostimulant in the cultivation of onions (Allium cepa) was investigated. Different IAA concentrations were evaluated to determine their effects on onion growth and chemical parameters. Various physical and chemical parameters such as total fresh weight, plant height, chlorophyll content, nitrates, total phenols, and antioxidant capacity (DPPH) were analyzed. The results revealed that exogenous application of IAA had a significant impact on onion growth and quality. Specifically, it was found that certain concentrations of IAA fostered a greater fresh weight of the bulb, an increase in the levels of phenolic compounds and a greater DPPH. However, the onion response to IAA was dependent on the concentration. In conclusion, the present study provides evidence that the exogenous application of IAA as a biostimulant can improve onion growth and quality. These results are relevant for the development of sustainable agricultural practices and could be oriented towards crop improvement.

The altimeter-derived ocean currents have been sparsely evaluated against in situ measurements in the Arctic, particularly for extended time periods. This study uses the extensive mooring array situated in the Fram Strait, representing one of the longest ocean current records, to investigate the relationship between in situ and satellite-derived currents in the region. The primary objective of this research is to analyze the vertical structure of the West Spitsbergen Current (WSC), its spatio-temporal coherence, and its association with surface geostrophic currents during the period of 1997-2012. To assess the vertical structure of the WSC, we utilized the Empirical Orthogonal Functions (EOF) and cross-correlation analysis between neighboring moorings. Remarkably, both velocity components exhibited robust vertical coherence, particularly within the waters of the North Atlantic Inflow, at depths exceeding 800 m. These findings underscore the potential for surface measurements to effectively complement data gaps and facilitate the reconstruction of deeper currents with a monthly temporal resolution. Notably, the surface measurements explain approximately 67% of the variance in the top 800 m of the water column.This comprehensive investigation advances our understanding of the West Spitsbergen Current and its vertical characteristics in the Arctic. Moreover, our findings highlight the valuable synergy between in situ and satellite-derived data, providing critical insights for future ocean current studies in this ecologically sensitive region.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

Crataegus Oxyacantha is used in the treatment of cardiovascular diseases. In related to your biosafety, only in vitro and in vivo genotoxicity of the fruit and the leaf is described, however, the teratogenic potential is unknown. The aim this study was evaluating the transplacental genotoxicity effect of aqueous and hydroalcoholic extract of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in liver. Three different doses of the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), sampling in rats were every 24 h during the last 6 days of gestation and only one sample was taken in neonates at birth. A sample of the mother's and neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the aqueous and hydroalcoholic extract generated cytotoxic and genotoxic damage in the short term. On the other hand, only the aqueous extract showed a teratogenic effect. Based on these results, the aqueous and hydroalcoholic extracts of the C. oxyacantha leaf should not be administered during pregnancy.

In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

G‐quadruplexes (G4) are structures formed at the ends of the telomere, these are rich in guanines and were stabilized by molecules that bind to specific sites. TMPyP4 and Thymoquinone (TQ) are small molecules that bind to the G4, they have drawn attention because of their role as telomerase inhibitors. The aim of this study was to evaluate the effects of telomerase inhibitors on cellular proliferation, senescence, and death. Two cell lines LC‐HK2 (NSCLC) and RPE‐1 were treated with TMPyP4 (5μM) and TQ (10μM). Both inhibitors were effective in decreasing telomerase activity. TMPyP4 increased the percentage of cells with membrane damage associated with cell death and decreased the frequency of cells in the S‐phase. TMPyP4 changed the cell adhesion ability and modified the pattern of focal adhesion. TQ acted in a dose‐dependent manner, increasing the frequency of senescent cells, and inducing cell cycle arrest in the G1. In conclusion, the effects of both drugs on LC-HK2 and RPE-1 cell lines were different although both are telomerase inhibitors, because TMPyP4 decreased proteins of cell adhesion and TQ induces a decrease in cell viability.

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs) involved in the regulation of 60% of human gene activity remains poorly explored. Similar to what we have previously done with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 hours post-infection, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h while at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. By RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17 and FURIN), in renin–angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1β, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.

The KRAS mutant population has been undruggable for 40 years. G12C inhibitors and immunotherapy are the beginning of success. It is necessary to summarize the successful experience of the existing treatment model and explore the direction of the next treatment. In this review, we discuss the latest developments in targeted therapy and immunotherapy for KRAS-mutation NSCLC, aiming to provide direction or enlightenment for future treatment strategies.

Carthamin potassium salt isolated from Carthamus tinctorius L. was purified by an improved traditional Japanese method, without using column chromatography. The 1H and 13C nuclear magnetic resonance (NMR) signals of the pure product were fully assigned using one- and two-dimensional NMR spectroscopy, while the high purity of the potassium salt and deprotonation at the 3’ position of carthamin were confirmed by atomic adsorption spectroscopy and nano-electrospray ionization mass spectrometry.

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

The theories of quantum mechanics and relativity dramatically altered our understanding of the universe ushering in the era of modern physics. Quantum theory deals with objects probabilistically at small scales, whereas relativity deals classically with motion in space and time. We show here that the mathematical structures of quantum theory and of relativity follow together from pure thought, defined and uniquely constrained by the same elementary ``combining and sequencing'' symmetries that underlie standard arithmetic and probability. The key is uncertainty, which inevitably accompanies observation of quantity and imposes the use of pairs of numbers. The symmetries then lead directly to the use of complex \sqrt{-1} arithmetic, the standard calculus of quantum mechanics, and the Lorentz transformations of relativistic spacetime. One dimension of time and three dimensions of space are thus derived as the profound and inevitable framework of physics.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

The main goal of our work is the revealing of problematic issues related to estimates of the absorption coefficient of colored organic matter in the northern seas from data of the Ocean and Land Color Instrument (OLCI) on the Sentinel-3 satellites. In particular, a comparison of the OLCI standard error estimates ADG443_NN_err., relating to the measurement and retrieval of the geophysical products, with the uncertainties in the real situation of the northern seas, where the natural conditions are extremely unfavorable (first of all, frequent cloudiness, low Sun heights). We conducted a comprehensive multi-sensor study of the uncertainties using various approaches, first at all, directly comparing the data from satellite (OLCI Sentinel-3 and four other ocean color sensors) and field measurements in five sea expeditions 2016-2019, by using the different processing algorithms. Our analysis has shown that the real uncertainties of the final product are significantly higher than the calculated errors of the ADG443_NN_err., which is 100% and ~10%. The main reason for that is the unsatisfactory atmospheric correction. We present the results of the analysis of the different effecting factors (satellite sensors, processing algorithms, use of the other parameters), and formulate the tasks of future work.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Detailed kinetics for a 3-wavelength photopolymerization confinement (PC) system is presented for both numerical solutions and analytic formulas. The dynamic profiles are simulated for oxygen, free radical, and conversion for various situations of: blue-light only, 2-light (red and UV), and 3-light (red, blue, UV). An effective PC requires two conditions: (i) a strong N-inhibition for uncured regime with a low conversion (triggered by the UV-light); and (ii) a weak S-inhibition (oxygen-induced) for high conversion under the blue-light or blue and red-light initiation. Good PC candidates are governed by collective factors of: (i) the double ratio of light-intensity and initiator-concentration, (ii) monomers rate-constant; and (iii) effective absorption constants at specific wavelength and initiators. A new reverse feature for the role of N-inhibition on the blue-conversion is found. Higher oxygen concentration leads to a lower conversion, which could be enhanced by reducing the S-inhibition via a red or blue-light pre-irradiation, having a pre-irradiation time TP=200 s for red-light only, and reduced to 150 s, when both red and blue-light. System under UV-only leads a conversion lower than that of blue-only. However, conversion could be improved by the dual-light (blue and UV), and further enhanced by the pre-irradiation of red-light. The two competing factors, N-inhibition and S-inhibition, could be independently and selectively tailored to achieve: (a) high conversion of blue-light (without UV-light), enhanced by red-light pre-irradiation for minimal S-inhibition; and (b) efficient PC initiated by UV-light produced N-inhibition for reduced confinement thickness and for high print speed.

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. In this study, the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in liver were investigated. Rats were fed the diets with (0.54 %) or without EGCG supplementation for four weeks and were then intraperitoneally injected with acetaminophen (1g/kg). Results showed EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by increasing the Bax/Bcl2 ratio in liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen-glutathione and acetaminophen-protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in liver after acetaminophen treatment. Our results indicate that EGCG may lower oxidative stress and reduce the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in liver and thus lower hepatotoxicity

A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of antinflammatory mediators, cell membrane fluidity, intracellular signalling and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represent a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.

Genetic activation of the class I PI3K pathway is very common in cancer. This mostly results from oncogenic mutations in PIK3CA, the gene encoding the ubiquitously expressed PI3Kα catalytic subunit, or from inactivation of the PTEN tumour suppressor, a lipid phosphatase which opposes class I PI3K signalling. The clinical impact of PI3K inhibitors in solid tumours, aimed at dampening cancer-cell-intrinsic PI3K activity, has thus far been limited. Challenges include poor drug tolerance, incomplete pathway inhibition and pre-existing or inhibitor-induced resistance. The principle of pharmacologically targeting cancer-cell-intrinsic PI3K activity also assumes that all cancer-promoting effects of PI3K activation are reversible, which might not be the case. Emerging evidence suggests that genetic PI3K pathway activation can induce and/or allow cells to tolerate chromosomal instability, which – even if occurring in a low fraction of the cell population – might help to facilitate and/or drive tumour evolution. While it is clear that such genomic events cannot be reverted pharmacologically, a role for PI3K in the regulation of chromosomal instability could be exploited by using PI3K pathway inhibitors to prevent those genomic events from happening and/or reduce the pace at which they are occurring, thereby dampening cancer development or progression. Such an impact might be most effective in tumours with clonal PI3K activation and achievable at lower drug doses than the maximum-tolerated doses of PI3K inhibitors currently used in the clinic.

Environmental isolates, genetically manipulated organisms, plants, animals and their products and economical methods are being expertly explored to biosynthesize poly-3-hydroxybutyrate plastics of comparable properties to petroplastics. This study assessed a hypothesized feasibility of utilizing a proliferative pleustophytic greenery, water hyacinth (Eichhornia crassipes (Mart.) Solms-Laubach) in Lake Victoria, Uganda as a potential carbon source for poly-3-hydroxybutyrate biosynthesis. The poly-3-hydroxybutyrate biosynthesizing bacteria (Bacillus megaterium) was isolated from municipal sewage sludge and harnessed for batch fermentation of acid-catalysed water hyacinth biomass. Poly-3-hydroxybutyrate formed in the cytoplasm of the bacterial cells was extracted by chloroform extraction method, and thereof confirmed and quantified by UV spectroscopy. Batch fermentation was carried out in 100ml of the culture media in a 250ml fermenter for different times (48, 96, 144 and 192 hours) to determine the best incubation time for maximum yield. An all-out net yield of 61.3% was realized after 96 hours of fermentation. Utilization of this ecological plague for poly-3-hydroxybutyrate biosynthesis is a promising strategy for regulating the weed population along the length of Nile River and the Victorian basin.

The co-circulation of duck hepatitis A virus subtypes 1 (DHAV-1) and 3 (DHAV-3) in ducklings has resulted in significant economic losses. Because ducklings infected with DHAV-1 or DHAV-3 show similar clinical signs and gross lesions, it is important to discriminate these subtypes as early as possible for better clinical management. On the basis of multiple alignments of the 5′-noncoding region sequences of strains DHAV-1 and DHAV-3, universal and type-specific primers were designed and synthesized. Using the primers in a one-tube reverse transcription-PCR (RT-PCR) assay, reference strains of DHAV-1 and DHAV-3 (isolated over a span of 60 years and covering many different countries) were successfully amplified, indicating that the primer sequences were completely conserved. The amplicon sequences results and the sizes of amplicons from reference DHAV-1 and DHAV-3 isolates correlated completely with their genotypes. Moreover, with this one-tube RT-PCR system, the amplicon sizes of liver samples of reference DHAV-1- or DHAV-3-infected birds matched perfectly with their respective genotypes, as determined by virus isolation and neutralization tests. No other RNA viruses of duck origin were detected with the synthesized primers. The sensitivity of viral RNA detection was 10 pg. With this system, 20% genotype 1, 45% genotype 3, and 9% co-infection of the two genotypes were detected in 55 clinical samples. This novel approach could be used for the rapid genotyping DHAV-1 and/or DHAV-3 infection in routine clinical surveillance or epidemiologic screening.

A series of penta-1,4-dien-3-one containing a H-phosphonate scaffold were designed and synthesized. The structures of all title compounds were determined by 1H-NMR, 13C-NMR, 31P-NMR, and HRMS. Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compounds 3c and 3o exhibited substantial antibacterial activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). In addition, compounds 3c, 3f, and 3r showed remarkable curative activities against tobacco mosaic virus (TMV), with 50% effective concentration (EC50) values of 290.0, 234.0, and 373.6 μg/mL, respectively. These were superior to that of ningnanmycin (386.2 μg/mL). Compound 3r exhibited comparative protective activity against TMV, with an EC50 value of 291.1 μg/mL, which was better than that of ningnanmycin (297.1 μg/mL). Notably, the solubility of all title compounds improved relative to the lead compound curcumin. These results suggest that penta-1,4-dien-3-one containing a H-phosphonate scaffold may be considered as an activator for antibacterial and antiviral agents.

Caspase-3, onto which there is a convergence of the intrinsic and extrinsic apoptotic pathways, is the main executioner of apoptosis. We here review the current literature on the intervention of the protease in the execution of naturally occurring neuronal death (NOND) during cerebellar development. We will consider data on the most common altricial species (rat, mouse and rabbit), as well as humans. Among the different types of neurons and glia in cerebellum, there is ample evidence for an intervention of caspase-3 in the regulation of NOND of the post-mitotic cerebellar granule cells (CGCs) and Purkinje neurons as a consequence of failure to establish proper synaptic contacts with target (secondary cell death). It seems possible that also the GABAergic interneurons undergo a similar type of secondary cell death, but the intervention of caspase-3 in this case still remains to be clarified in full. Remarkably, CGCs also undergo primary cell death at the precursor/pre-migratory stage of differentiation, in this case without the intervention of caspase-3. Glial cells as well undergo a process of regulated cell death, but it seems possible that expression of caspase-3, at least in the Bergmann glia, is related to differentiation rather than death.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

Ziyuan-3 (ZY-3) satellite is the first civilian stereo mapping satellite in China and was designed to achieve the 1: 50000 scale mapping for land and ocean. Rigorous sensor model (RSM) is required to build the relationship between the three-dimensional (3D) object space and two-dimensional (2D) image space of ZY-3 satellite imagery. However, each satellite sensor has its own imaging system with different physical sensor models, which increase the difficulty of geometric integration of multi-source images with different sensor models. Therefore, it is critical to generate generic model， especially rational polynomial coefficients (RPCs) of optical imagery. Recently, relatively a few researches have been conducted on RPCs generation to ZY-3 satellite. This paper proposes an approach to evaluate the performance of RPCs generation from RSM of ZY-3 imagery. Three scenarios experiments with different terrain features (such as ocean, city and grassland) are designed and conducted to comprehensively evaluate the replacement accuracies of this approach and analyze the RPCs fitting error. All the experimental results demonstrate that the proposed method achieved the encouraging accuracy of better than 1.946E-04 pixel in both x-axis direction and y-axis direction, and it indicates that the RPCs is suitable for ZY-3 imagery and can be used as a replacement for the RSM of ZY-3 imagery.

The paper presents an innovative hexapod walking robot built with 3-UPU parallel mechanism. In the robot, the parallel mechanism is used as both an actuator to generate walking and also a connecting body to connect two groups of three legs, thus enables the robot to walk with simple gait by very few motors. In the paper, the forward and inverse kinematics solutions are obtained. The workspace of the parallel mechanism is analyzed using limit boundary search method. The walking stability of the robot is analyzed, which yields the robot’s maximum step length. The gait planning of the hexapod walking robot is studied for walking on both flat and uneven terrains. The new robot, combining the advantages of parallel robot and walking robot, has a large carrying capacity, strong passing ability, flexible turning ability, and simple gait control for its deployment for uneven terrain.

An efficient, eco-compatible and very cheap method for the construction of triazoles via eliminative azide–olefin cycloaddition (EAOC) reaction has been developed by a catalytic system IL/FeCl3, offering an highly regioselective approach to structurally diverse 1,5-disubstituted 1,2,3-triazoles in up to 95% yield. This strategy features the reuse of catalytic system through simple operations. Mechanistic studies indicated that an asynchronous concerted dipolar cycloaddition-elimination process might be involved.

Corona loss generated from conductors is one of the important design factors on ac transmission lines. Based on helical charge simulation method, the 3-D corona loss calculation model considering the conductors’ outer strands in the corona cage is established. With regard to 2-D corona-loss calculation method, the calculation model proposed in this paper can take the electric field strength’s nonuniformity along the axial direction of stranded conductor into consideration, furthermore, it can also calculate the corona loss when the conductor has sag. The calculation results of the LGJ-300/40 and LGJ-400/35 in the small corona cage well coincide with the measurement results, which indicates that the corona-loss calculation model is appropriate. In addition, the corona loss of the bundle conductors 4 × LGJ720 with sag in UHV corona cage is also analyzed.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

Distribution systems can form islands when faults occur. Each island represents a subsection with variable boundaries subject to the location of a fault(s) in the system. A subsection with variable boundaries is referred to as island in this paper. For operation in autonomous mode, it is imperative to detect the island configurations and stabilize these subsections. This paper presents a novel scheme for the detection of islanding boundaries and stabilizing the system during autonomous operation. In the first stage, a boundary detection method is proposed to detect the configuration of the island. In the second stage a dynamic voltage sensitivity factor (DVSF) is proposed to assess the dynamic performance of the system. In the third stage, a wide area load shedding program is adopted based on DVSF to shed the load in weak busbars and stabilize the system. The proposed scheme is validated and tested on a generic 18-bus system using a combination of EMTDC/PSCAD and MATLAB softwares.

We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

Bean is a remarkable crop widely used as food worldwide, underscoring the significance of scientific research conducted on this plant. Developing a strong root system in the early stages of growth, which can spread wider and deeper, along with the consequent development of the shoot system crucial for photosynthesis, enhances the plant's productivity and resistance to diseases and pests. In the current study, the reactions of cultivars Önceler-98 and Topçu beans to different concentrations of IBA (indole-3-butyric acid) during the seedling stage were investigated. Three different concentrations, namely 0 (Control), 50, 100, and 150 µM IBA, were applied, and their effects on root length (RL), root fresh weight (RFW), root dry weight (RDW), number of nodules on roots (RNN), shoot length (SL), shoot fresh weight (SFW), and shoot dry weight (SDW) parameters were measured. The pattern of the experiment was a randomized complete block factorial design with four replications and, statistically significant (p≤0.05) and highly significant (p≤0.01) differences were observed among the means of root and shoot traits. As a result, it was found that the cultivar Önceler-98 generally exhibited better responses to IBA solutions, and the optimal concentration range for both varieties was between 50-100 µM, decreasing at 150 µM and higher concentrations, yet still yielding superior means compared to the control.

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Carotid intima-media thickness (C-IMT) is a non-invasive marker of atherosclerosis. Low omega-3 polyunsaturated fatty acids (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the link of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and C-IMT in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24-hour recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFAs profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p=0.007), C-IMT (p=0.002), serum CRP (p=0.044), iPTH (p=0.01) and 25(OH)D3 (p=0.006). ALA intake of more than 0.23 g/daily was associated with lower SBP (p=0.001), serum 25(OH)D3 (p=0.004), and C-IMT (p=0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status considering CVD health in CKD patients.

Solution-based inorganic-organic halide perovskites are of great interest to researchers because of their unique optoelectronic properties and easy processing. However, polycrystalline perovskite films often show inhomogeneity due to residual strain induced during the film’s post-processing phase. In turn, these strains can impact both their stability and performances. An exhaustive study of residual strains can provide a better understanding and control of how they affect the performance and stability of perovskite films. In this work, we explore this complex interrelationship between residual strains and electrical properties for methylammonium \chemform{CH_3NH_3PbI_{3-x}Cl_x} films using grazing incident X-ray diffraction (GIXRD). We correlate with their resistiviy and carrier mobility using Hall effect. The sin^2($\psi$) technique is used to optimize the annealing parameters for the perovskite films. We also establish that temperature-induced relaxation can yield significant enhancement of the charge carrier transports in perovskite films. Finally, we also use Raman micro-spectroscopy to assess the degradation of perovskite films as a function of their residual strains.

Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as ASD necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, and communication, restricted, repetitive behavioral patterns with association to several additional impairments such as somatosensory, motor and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD like-behavior from the etiologic, pathogenetic and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), Lipopolysaccharide (LPS) and propionic acid or other well-documented immunogens or pathogens, like mycobacterium tuberculosis. Another approach is the use of chemicals like valproic acid, Polychlorinated biphenyls (PCBs), organophosphate pesticides - chlorpyrifos (CPF) and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during the early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic like behavior (i.e. fragile X, Rett syndrome, SHANK gene mutation Neuroligin genes and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans.

In this research, the primary goal was to investigate the relationship between strategic planning and organizational performance in Iraq's manufacturing context. The study's primary data sources were 360 manager respondents. The structured questionnaire was used to collect primary data from manufacturing firms located throughout Iraq. To analyze the result, the researcher used descriptive statistics, correlation, and multiple regression analysis. SPSS version 16 software was used to conduct data analysis. The result reveals that the process of strategic planning has a beneficial effect on financial performance. Environmental scanning has a statistically significant positive effect on a company's non-financial performance. Management participation and planning formality positively and statistically significantly affect a business's non-financial performance at the 10 percent level. The domain of strategy and technique has not impacted the company's non-financial performance.

Today, various dietary supplements are taken to improve endurance performance during physical activity. These supplements have proven to be very successful in controlling and balancing various hormone levels and have contributed to the prevention and healing of metabolic disorders and physical injuries. In this study, we sought to investigate the effects of the ACTN3 gene and nutrient supplementation, including beta-alanine, ashwagandha, L-carnitine, and iron, on athletic performance. The ACTN3 gene has been identified as a potential genetic determinant of athletic performance, particularly in activities that require high levels of power and strength. This study investigated the interaction between the ACTN3 gene and supplementation and highlighted the potential for personalized approaches to improve athletic performance. 24 subjects per group, were randomized in a parallel-group design to examine the effects of supplementation on the ACTN3 gene and athletic performance over a 21-day intervention period. Participants in the intervention were divided into four groups of six members each. The same subjects who did not take supplements formed the control group. In addition, the subjects were divided into 4 groups (G1, G2, G3, and G4), each consisting of subgroups of control and a treated. All treated groups (TG1, TG2, TG3, and TG4) received 4 supplements for 21 days, namely S1 (ashwagandha), S2 (iron), S3 (beta-alanine) and S4 (L-carnitine), together with the 4 control groups, i.e. CG1, CG2, CG3 and CG4, who received no supplements during the same period. In particular, this study determines the effect of these 4 supplements on actn3 gene expression, testosterone, cholesterol and BUN levels of the participants. The P-values determined for all parameters showed statistically significant values and the final result showed that all supplements had positive effects on the tested parameters. The result showed a highly significant difference between the intake of supplements before and after the intake of 24 athletes per group on the ACTN3 gene expression level and biochemical indicators.

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

This report provides a comprehensive overview of occupational asthma and respiratory hypersensitivity, focusing on some chemicals used in the workplace Includes numerous case studies and research papers related to occupational exposure methacrylates, such as HEMA-HPMA, and respiratory hypersensitivity are discussed And the relationship is explored The book also examines asthma pathophysiology, emerging drug delivery systems used to treat asthma, and the potential of nanoparticles , dendrimers and micellar systems have to improve pulmonary drug delivery in detail The worldwide prevalence of asthma is highlighted, with higher rates in high-GDP countries. The book highlights the need to improve asthma diagnosis, treatment and biomarkers, particularly in rural and low-income countries where the disease is often underdiagnosed and inadequately treated, and discusses the role of inflammation in asthma, in particular secondary inflammation characterized by specific cytokines and inflammation cells In addition, the paper explores various drug delivery methods, such as parenteral and parenteral drugs, pressurized inhalers (pMDIs), dry powder inhalers ( DPIs), nebulizers, nanoparticles, liposomes, micellar systems, microparticles , dendrimers, and gene therapy . These systems aim to increase pulmonary delivery of drugs and improve clinical outcomes. The potential of dendrimer bilirubin-based nanoparticles and micellar systems in the treatment of asthma and lung inflammatory diseases, including asthma, has been discussed in summary, this paper provides an overview of occupational asthma and respiratory hypersensitivity, and this discussion highlights the association between methacrylate exposure and respiratory hypersensitivity.

To accurately and non-destructively monitor the growth of spring wheat in the Hetao Irrigation Area, UAV remote sensing was employed during various fertility stages. Digital image indices from diverse fertilization treatments were calculated and compared with physiological indices to identify the most sensitive digital image indices corresponding to these indices. The study underscored the critical importance of the flowering stage in the growth of spring wheat, thus highlighting the necessity of focusing on this stage. This finding reiterated that the flowering stage was pivotal for spring wheat development in the Hetao Irrigation Area. Several digital image indices, such as GLA, R, G, INT, g, GRVI, MGRVI, RGBVI, EXG, and GRRI, exhibited a high frequency of significant correlations with physiological indices during the four primary reproductive stages of wheat. Consequently, these sensitive digital image indices during the flowering stage can more effectively characterize the physiological indices of spring wheat.