Immunology and microbiology research in the West Indies has witnessed remarkable growth and innovation, playing a pivotal role in advancing our understanding of immune mechanisms, disease pathogenesis, and therapeutic interventions. This manuscript presents a comprehensive exploration of key areas in West Indian immunology research, spanning from the utilization of bacterial proteins as antibody reagents to the intricate realms of clinical immunology and disease management. The utilization of bacterial immunoglobulin-binding proteins (IBPs), including protein A (SpA), protein G (SpG), and protein L (SpL), has revolutionised serological diagnostics in the region. promise in early disease detection and precision medicine. Microbiological studies in the Caribbean region have shed light on antimicrobial resistance patterns, particularly the emergence of extended-spectrum beta-lactamases (ESBLs), guiding antimicrobial stewardship programs and informing therapeutic strategies. Clinical immunology research has elucidated the molecular pathways underlying immune-mediated disorders, leading to tailored management strategies for conditions such as severe combined immunodeficiency (SCID), neuropsychiatric lupus erythematosus (NPLE), and others. In summary, West Indian immunology and microbiology research has made significant contributions to global healthcare, fostering collaboration, innovation, and improved patient outcomes.

The acute phase protein serum amyloid A (SAA) is associated with endothelial dysfunction and early-stage atherogenesis. Stimulation of vascular cells with SAA increases gene expression of pro-inflammation cytokines and tissue factor (TF). Activation of the transcription factor, nuclear factor kappa-B (NFkB), may be central to SAA-mediated endothelial cell inflammation, dysfunction and pro-thrombotic responses, while targeting NFkB with a pharmacologic inhibitor, BAY11-7082, may mitigate SAA activity. Human carotid artery endothelial cells (HCtAEC) were pre-incubated (1.5 h) with 10 µM BAY11-7082 or vehicle (control) followed by SAA (10 μg/mL; 4.5 h). Under these conditions gene expression for TF and TNF increased in SAA-treated HCtAEC and pre-treatment with BAY11-7082 significantly (TNF) and marginally (TF) reduced mRNA expression. Intracellular TNF and IL-6 protein also increased in HCtAEC supplemented with SAA and this expression was inhibited by BAY11-7082. Supplemented BAY11-7082 also significantly decreased SAA-mediated leukocyte adhesion to apolipoprotein E-deficient mouse aorta in ex vivo vascular flow studies. In vascular function studies, isolated aortic rings pre-treated with BAY11-7082 prior to incubation with SAA showed improved endothelium-dependent vasorelaxation and increased vascular cGMP content. Together these data suggest that inhibition of NFkB activation may protect endothelial function by inhibiting the pro-inflammatory and pro-thrombotic activities of SAA.

To demonstrate if botulinum toxin type A (BoNT-A) improves mandibular range of motion and muscle sensibility to palpation in refractory myofascial pain (MFP) patients. METHODS: Eighty consecutive female subjects with refractory MFP, were randomly divided into four equal groups (n=20): BoNT-A low (BoNTA-L/10 U in each temporalis and 30 U in each masseter), BoNT-A medium (BoNTA-M/20 U in each temporalis and 50 U in each masseter), BoNT-A high (BoNTA-H/25 U in each temporalis and 75 U in each masseter) and saline solution 0.9% (SS, placebo control group/0.4 mL in each temporalis and 0.6 mL in each masseter). Clinical measurements of the mandibular movements included: pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements. Palpation tests were performed bilaterally in masseter and temporalis muscle. Results were expressed as median, minimum, maximum, and means ± standard deviation (SD). Chi-Square Test was used to compare differences among groups. A 5% probability level was considered significant in all tests RESULTS: Regardless of dose, all parameters of mandibular range of motion significantly improve after 180 days in BoNT- A groups, when compared to the control group. Pain to palpation on muscles, significantly reduced in all BoNT- A groups regardless of dose, when compared to the control group, after 28 and 180 days of treatment. CONCLUSIONS: Independent of doses, BoNT-A improved mandibular range of motion and muscle sensibility to palpation in refractory MFP patients when compared to SS injections.

Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates, however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age. The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the 1^st trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order and age at SDQ completed. The median concentrations of BPA, MnBP, MiBP, MEHP and MECPP were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. BPA level was associated with increased hyperactivity/inattention risk among girls (OR=1.66, 95% CI: 0.95-2.90) and∑DBP_m (MnBP + MiBP) level was associated with decreased total difficulties risk overall and among girls (OR=0.48, 95% CI: 0.20-1.13, OR=0.24, 95% CI: 0.06-1.03, respectively) without significance. MECPP level was associated with increase conduct problems risk (OR=2.78, 95% CI: 1.36-5.68). Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age, however, suggested possible association between MECPP levels and increased risk of conduct problems.

The development of novel porous composite materials for organic dye degradation and removal has received increasing attention due to water contamination problem. In this paper, hydrothermal synthesized nano zeolite A have been encapsulated with porous periodic mesoporous organosilica (PMO) through a simple modified StÖber method an organosilane-directed growth-induced etching strategy, the obtained yolk-shell structured sample was further functionalized by the impregnation of copper, realizing the composite material with hierarchical porous and catalytic properties. The morphology, porosity and metal content of the zeolite Cu/A and Cu/A@Et-PMO were fully characterized. As compared to the parent material, the composite Cu/A@Et-PMO have an efficient adsorption and catalytic degradation performance on methylene blue (MB), the removal efficiency reached as high as 95% of 60 mg/L MB with 10min. These novel structured porous composites may have great potential for adsorption and degradation application including waste effluents.

Separation and interpretation of rebellious Circulating Tumor Cells (CTCs) originating from the primary tumor or cancer tissue plays a significant role in diagnostics, cancer progression analyses, suitable medicine exploration, and treatment proficiency examination. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, leading to new tumors in that area. Although a dramatic rate of deaths begins from spreading CTCs around the body, valuable measures have been made to control their development. However, the first step is separating these harmful cells from the bloodstream and investigating their features. Having examined the characteristics of CTCs as cancer’s main strength, researchers can introduce complementary treatments that can affect cancerous cells without damaging the healthy cells. Therefore, according to their unique characteristics, numerous techniques have been established for continuous and fast separation and sorting of CTCs. Nevertheless, few separators enjoy the efficient performance and appropriate accuracy and can be produced in mass numbers due to the available fabrication equipment. Microfabrication advancements enable separators to combine the advantages of active and passive methods in a small-scale platform for probing individual cells and separation purposes. Reduction in reagents, sample volume, analysis time, and less harmfulness to patients are some of the motivations that encourage researchers to employ microfluidic instruments for CTCs separation from other blood cells over the last two decades. However, microfabrication limitations mean effective separators, and the diagnostic option they provide, are not readily available. Addressing these limitations requires optimizing the design and fabrication of separators such that they are reduced in their size and fabrication cost, while also maintaining high-throughput separating capability. The emergence of the Lab-On-a-Chip (LOC) and then Lab-On-a-CD (LOCD) technologies, having more inherent benefits than conventional microfluidic devices, has created new opportunities and become increasingly widespread in recent years. Evidence suggests that employing single methodologies or integrating approaches without sufficient understanding of potential outcomes is unlikely to result in successful diagnostic results. This paper contributes an extensive review of several separation systems, including fundamental theories and experimental details, and describes detailed operating principles and device performance.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

Abstract: The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ and Hippo signaling is also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicated increased nuclear localization of Yes associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in absence or presence of by exogenously added TGFβ2. To confirm the molecular mechanisms of verteporfin induced inhibition of TGFβ2-dependent extra-cellular matrix (ECM) reorganization we performed gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirmed that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell be-havior and ECM remodeling is mediated by YAP1. Thus, TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Mitochondrial dysfunctions remained a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria which is also known as the power-generating set of the cell, have a dominant role in several processes associated with the genomic integrity and cellular equilibrium maintenance. They are involved in maintaining optimal cells functioning and guidance from possible DNA damage which could lead to mutations and onset of diseases. Conversely, system perturbations which could be due to environmental factors or senescence induce changes in the physiological balance and result in the mitochondrial functions impairment. The focal point of this review focuses on mitochondrial dysfunction as a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria which are common amongst the most recurring neurodegenerative diseases including Alzheimers and Parkinsons disease. Do mitochondrial dysfunctions represent an early event in causing a shift towards neuropathological processes?

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.

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.

In humans, finely tuned gamma synchronization (60-90 Hz) rapidly appears at movement onset in a motor control network involving primary motor cortex, the basals ganglia and motor thalamus. Yet the functional consequences of brief movement-related synchronization are still unclear. Distinct synchronization phenomena have also been linked to different forms of motor inhibition, including relaxing antagonist muscles, rapid movement interruption and stabilizing network dynamics for sustained contractions. Here I will introduce detailed hypotheses about how intra- and inter-site synchronization could interact with firing rate changes in different parts of the network to enable flexible action control. The here proposed cause-and-effect relationships shine a spotlight on potential key mechanisms of cortico-basal ganglia-thalamo-cortical communication. Confirming or revising these hypotheses will be critical in understanding the neuronal basis of flexible movement initiation, invigoration and inhibition. Ultimately, the study of more complex cognitive phenomena will also become more tractable once we understand the neuronal mechanisms underlying behavioural readouts.

Accruing evidence on the influence of β-carotene regarding the prevention of several chronic diseases - in addition to its well-acknowledged role in vision has been a strong driver for developing alternative delivery systems. Though oral delivery is accepted as the most fitting, mild and safe path for delivering bioactive agents, β-carotene delivery via food items poses challenges due to its lipophilic nature, poor water-solubility, high chemical/photochemical instability and poor oral bioavailability. Nanotechnology has opened new windows for delivering bioactive agents. Their physiochemical characteristics, i.e. small size, high surface area, unique composition, biocompatibility and biodegradability make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in target tissues, but also lessens its sensitivity against environmental factors during processing. Regardless of these benefits, nanocarriers inherit some limitations, such as variations in sensory quality, modification of the food matrix, increasing costs, as well as limited consumer acceptance and regulatory challenges. This research area has been rapidly evolved, with a plethora of innovative nano-engineered materials, including micelles, nano/microemulsion, liposomes, niosomes, solid-lipid nanoparticles and nanostructured lipid carriers. These nano-delivery systems make conventional delivery systems appear archaic and promise better solubilization, protection during processing, improved shelf-life, higher bioavailability as well as controlled and targeted release. This review provides information on the state of knowledge on β-carotene nano-delivery systems adopted for developing functional foods: depicting their classification, composition, preparation methods, challenges, release-and absorption of β-carotene in the GIT and possible risks and future prospects.

The astacin protease Meprin β represents an emerging target for drug development due to its potential involvement in disorders such as acute and chronic kidney injury and fibrosis. Here, we elaborate on the structural basis of inhibition by a specific Meprin β inhibitor. Our analysis of the crystal structure suggests different binding modes of the inhibitor to the active site. This flexibility is caused, at least in part, by movement of the C-terminal region of the protease domain (CTD). The CTD movement narrows the active site cleft upon inhibitor binding. Compared with other astacin proteases, among those the highly homologous isoenzyme Meprin α, differences in the subsites account for the unique selectivity of the inhibitor. Although the inhibitor shows substantial flexibility in the orientation within the active site, the structural data as well as binding analyses including molecular dynamics simulations support a contribution of electrostatic interactions, presumably by arginine residues, to binding and specificity. Collectively, the results presented here and previously support an induced fit and substantial movement of the CTD upon ligand binding and, possibly, during catalysis. To the best of our knowledge, we here present the first structure of a Meprin β holoenzyme containing a zinc ion and a specific inhibitor bound to the active site. The structural data will guide rational drug design and the discovery of highly potent Meprin inhibitors.

Given the high prevalence of cutaneous genus beta human papillomavirus (β-HPV) infections, it is important to understand how they are manipulating their host cells. This is particularly true for cellular responses to UV damage, since our skin is continually exposed to UV. The E6 protein from β-HPV (β-HPV E6) decreases the abundance of two essential UV-repair kinases (ATM and ATR). Since β-HPV E6 reduces their availability, the impact on downstream signaling events has been uncertain. We demonstrate that β-HPV E6 decreases ATM and ATR activation. This inhibition extended to XPA, an ATR target necessary for UV repair, lowering both its phosphorylation and accumulation. β-HPV E6 hinders POLη phosphorylation and foci formation, critical steps in translesion synthesis. ATM’s phosphorylation of BRCA1 is also attenuated by β-HPV E6. However, β-HPV E6’s hindrance of ATM/ATR signaling during UV-associated cell cycle arrest was incomplete. While there was less phosphorylation of immediate downstream targets (CHK1), events further down the cascade were not decreased. These observations are consistent with β-HPV infections making UV radiation more deleterious and support the proposed role of β-HPV in early stages of non-melanoma skin cancer development.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

This study is aimed to point out the possible application of the Enzyme-Linked ImmunoSorbent Assay (ELISA) test on table olives. Because olives, like many other foods, are not free from mycotoxin contamination, the main focus of this work was assessing the presence or absence of aflatoxins and ochratoxin A. The work was carried out in two phases. In the first phase, tests were carried out on commercial olives to assess the efficacy of the method and the kit (Veratox® 'Neogen' and AgraQuant® 'Romer Labs') by comparing them with the Liquid Chromatography coupled to a mass-mass spectrometer (LC-MS/MS); in order to understand if there were any interferences in antigen-antibody recognition; subsequently, mycotoxins were inoculated on the same samples with a known quantity, in order to assess the concentrations obtained and compare them to the expected ones. The second step involved modifying the method, so to improve the recovery of inoculated mycotoxins in the samples under study. Afterwards we evaluated the presence of mycotoxins in table olives supplied in the project. The results showed the effectiveness of the ELISA test, especially in the mycotoxin recovery phase. Indeed, after the modification of the mycotoxin extraction method, recoveries increased from 55% to over 70% for aflatoxins, and from 40% to over 55% for ochratoxin A. When analysing the samples provided by the above-mentioned company, the results showed some false positives, in particular in relation to ochratoxin A ’s analysis, mainly related to the first sample submission. Taking this into account, the ELISA test can be considered as an initial screening method applicable as a control programme for the evaluation of mycotoxins in olives which helps by saving time and costs. It should always be kept in mind that, if positive values should emerge, the LC-MS/MS analysis should be carried out.

Fungal spores are universal atmospheric components associated to allergic reactions. Alternaria (Ascomycota) is considered the most allergenic spore taxa. Alt a 1 is the major allergen of Alternaria and is present also in other Pleosporales. In this study, standard Hirst-based sampling and analyzing methods for measuring spore daily concentrations of Alternaria, Curvularia, Drechslera-Helminthosporium, Epicoccum, Leptosphaeria, Pithomyces, Pleospora and Stemphyllium (all included in the taxon Pleosporales) have been used besides two high-volume samplers, Burkard Cyclone (2017) and MCV CAV-A/mb (2019-2020), and ELISA Kits for measuring the allergen. The detection and quantification of Alt a 1 was only possible in the samples from the MCV sampler. Although Alt a 1 was better correlated with Alternaria spores than with Pleosporales spores, the three of them showed high correlations. It is shown, for the first time, a high and significant correlation of Alt a 1 with temperature, a negative one with relative humidity and no correlation with precipitation. The aerobiological monitoring of these three elements ensures the best information for understanding the affectation to allergy sufferers but, if not possible, as a minimum public health service aiming at the detection, treatment and prevention of allergy, the study of the airborne Alternaria spores should be ensured.

To drive safely, the driver must be aware of the surroundings, pay attention to the road traffic, and be ready to adapt to new circumstances. Most studies on driving safety focus on detecting anomalies in driver behavior and monitoring the cognitive capabilities of drivers. In our study, we proposed a classifier for basic activities in driving a car, based on a similar approach that could be applied to the recognition of basic activities in daily life, that is, using electrooculographic (EOG) signals and a one-dimensional convolutional neural network (1D CNN). Our classifier achieved an accuracy of 80% for the 16 primary and secondary activities. The accuracy related to primary activities in driving, including crossroad, parking, roundabout was 97.9%, 96.8%, 97.4%, and 99.5%, respectively. The F1 score for secondary driving actions (0.99) was higher than for primary driving activities (0.93–0.94). Furthermore, using the same algorithm, it was possible to distinguish four secondary activities related to activities of daily life and secondary when driving a car.

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in human. The calcium ion has been shown to be involved in many cellular signal transduction pathways as well as in the regulation of cell adhesion, which is necessary for the embryo implantation process. Exposure to endocrine-disrupting chemicals (EDs) during early gestation results in disruption of intrauterine implantation and uterine reception, leading to implantation failure. In this study, ovarian estrogen (E2), bisphenol A (BPA), or 4-tert-octylphenol (OP), with or without ICI 182,780 (ICI) were injected subcutaneously from gestation day 1 to gestation day 3 post-coitus. The expression levels of the calcium transport genes were assessed in maternal uteri and implantation sites. The number of implantation sites was significantly low in the OP group, and implantation sites were absent in the E2 and EDs+ICI groups. There were different calcium transient transport channel expression levels in uterus and implantation site samples. The levels of TRPV5 and TRPV6 gene expression were significantly increased by EDs with/without ICI treatment in uterus. Whereas, TRPV5 and TRPV6 gene expression were significantly lower in implantation sites samples. NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Compared to vehicle treatment in uterus, both the MUC1 mRNA and protein levels were markedly high in all but the BPA group. Taken together, these results suggest that both BPA and OP can impair embryo implantation through alteration of calcium transport gene expressions and by affecting uterine receptivity.

The rates of obesity and obesity-related diseases continue to increase worldwide, classifying obesity as a global epidemic. Endogenous opioids have been implicated in influencing feeding behavior; however, the role of each opioid peptide is still only partially characterized. Therefore, we assessed the role of the proopiomelanocortin (POMC)-derived peptide beta-endorphin (β-END) in long-term high-fat diet (HFD) feeding and glucose homeostasis and assessed if sex-related differences exist in these processes. Male and female mice lacking the ability to produce β-END and their respective controls were subjected to a 12-week HFD consumption to determine the role of the opioid peptide in food intake and glucose homeostasis. Body weight and food intake were measured weekly for twelve weeks. At weeks 6 and 12, plasma glucose levels were measured using an oral glucose tolerance test. Here, we report that male β-END deficient mice gained more weight and consumed more calories than their wildtype controls; however, this difference was not observed in the female mice. Regardless of genotype, female mice consumed more calories per body weight when compared to male mice despite their smaller body weights. Moreover, our findings suggest differences in glucose homeostasis between the wildtype and knockout mice and that these were only observed at week six but not at week 12. Overall, our study suggests that endogenous β-END may play a role in controlling body weight, feeding behavior, and glucose homeostasis and that sex-related differences may exist in this regard.

The aim of this work is to broaden the theory of computation by making use of fuzzy sets and multisets, which are generalization of ordinary sets. We study fuzzy multiset finite automata (FMFA), which are characterized by the incorporation of vagueness when it comes to the choice of the next state and multiple occurrences of the same input symbol. The resulting automaton is a genaralization of both classical automata and fuzzy automata. We discuss the algebraic characteristics of FMFA sub-automata—separatedness, strongly connectedness, cyclic, directable, and triangular FMFA in terms of equivalence classes induced by an equivalence relation defined on state set of FMFA. Intrestingly, for a given FMFA, a new FMFA can be constructed that is a homomorphic image of the original FMFA. We define different posets structures that can be associated with a given FMFA and show that some of them are upper semilattices and discuss the inter-relationship of a given poset, a finite upper semilattice (FUSL), a FMFA and a posets/FUSL associated with a given FMFA. Finally, we introduce the concept of decomposition of a FMFA in two different ways and characterize the strongly connected, triangular and directable FMFA.

Insect behavior is coordinated mainly by smell, through the diverse odor-binding proteins (OBP) that allow them to identify and recognize their environment. Sensory information collected through smell is then analyzed and interpreted in the brain, allowing for correct insect functioning. The behavior of honey bees (Apis mellifera L.) can be affected by different pathogens, such as deformed wing virus (DWV). In particular, DWV variant A (DWV-A) is capable of altering olfactory sensitivity, reducing the gene expression of different OBPs, including those associated with nursing behavior. DWV is also capable of replicating itself in the sensory lobes of the brain, further compromising the processing of sensory information. This study evaluated the behavioral response of nurse honey bees exposed to a pheromone compound and the alterations in the gene expression of pre- and post-synaptic neuronal genes neuroxins-1 and neurogilin-1 in the bee heads and OBP proteins in antennae of nurse bees inoculated with DWV-A. The behavioral response of nurse bees exposed to the larval pheromone compounds benzyl alcohol was analyzed using a Y-tube olfactometer. The viral load, gene expression of OBP5 and OBP11 in antennae and the neuroxins-1 and neurogilin-1 in the bee heads were analyzed by qPCR. High viral loads significantly reduced the ability of 10- and 15-day-old nurse honey bees to choose the correct pheromone compound. Also, the gene expression of OBP5, OBP11, neuroxin-1 and neurogilin-1 in nurse honey bees decreased when they were highly infected with DWV-A. These results suggest that a DWV-A infection can disturb information processing and cause nurse honey bees to reduce their activity inside the hive, altering internal cohesion.

Herein, we developed a highly sensitive and specific bimolecular fluorescence complementation (BiFC)-based influenza A virus (IAV) sensing system created by combining a galactose/glucose-binding protein (GGBP) with an N-terminal large domain (YN1-172) and a C-terminal small domain (YC173-239) of enhanced yellow fluorescence protein (eYFP). The GGBP-based BiFC reporter exhibits the fluorescence reconstitution as a result of conformational changes in GGBP when lactose, derived from 6’-silalyllactose used as a substrate for neuraminidase (NA), binds to GGBP in the presence of IAV. The system showed a linear dynamic range from 1 x 100 TCID50/mL to 1 x 107 TCID50/mL, with a detection limit of 4 x 101 TCID50/mL for IAV (H1N1), demonstrating ultra-high sensitivity. Our system exhibited fluorescence intensity enhancements in the presence of IAV, while displaying weak fluorescence signals when exposed to NA-deficient viruses such as RSV A, RSV B, adenovirus and rhinovirus, thereby indicating selective responses for IAV detection. Taken together, our system provides a simple, highly sensitive and specific IAV detection platform based on BiFC capable of detecting the ligand-induced protein conformational changes, obviating the need for virus culture or RNA extraction processes.

Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on antinociceptive activity and itch-associated scratching behavior (LLS) in mice, and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose, and inhibited IL-31-induced LLS. These results suggested that repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. IL-31 and morphine combination increased analgesic action which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p < 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p < 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Abstract: Breast cancer is one of the leading causes of death in the female population due to the re-sistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubil-ity and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxy curcumin magnesium complex with cyclodex-trin (DiMeOC-Mg-BCD, 5) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media (PBS) was improved by a factor of 6x over the free metal complex (DiMeOC-Mg). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the MMP-2 and MMP-9, IL-6, and STAT3 expression levels on MDA MB 231 cell lines. Results of an antitumor assay in an in-ovo model showed up to 30% inhi-bition of tumour growth for breast cancer (MDA-MB-231) when using 5 (0.650 mg/Kg dose), and 17.29 % inhibition with the free homoleptic metal complex (1.5 mg/Kg dose, DiMeOC-Mg). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new DiMeOC-Mg-BCD exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

This research focuses on deriving the equation of motion for fermions on a ring. The paper proposes an alternative equation for fermions on the ring, incorporating a self-rotation angle denoted as $\Delta$, and explores its relationship with the original equation.

Introduction: Indonesia consists of a plural society with different ethnic, religious, racial, skin color, and other cultures. The difference must be understood by everyone, especially the younger generation in the digital age. If the younger generation does not have a sufficient understanding of multicultural education values, it will impact the moral crisis of the Indonesian nation. This research emphasizes the importance of multicultural education to the younger generation to understand the differences (pluralism) in society and respect them. Method: The method uses a qualitative method with the literature review method by collecting data on ten journals published in 2019, 2020, 2021. Results: The rise of socio-cultural conflicts in Indonesia is why applying multicultural values to the younger generation. Multiculturalism is needed to establish morals and sensitivity for a young person in the face of various social problems and symptoms at a growing age. Conclusion: Multicultural education is vital to the younger generation considering Indonesia has diverse nations and cultures. The efforts that can make to improve the morale of the nation's children, namely by learning citizenship education and religious education and utilizing information technology to spread things related to the values of multicultural education to the broader community

MIPs inspired by antigen-antibody interactions have received substantial interest as a biomimetic artificial receptor system in environmental applications. Herein, we present a molecularly imprinted surface plasmon resonance (SPR) sensor integrated with Au nanoparticles for the identification of bisphenol A (BPA), an endocrine-disrupting chemical. The synthetic wastewater samples were analyzed to ensure the method's reliability and feasibility. Under ideal conditions, the suggested approach performed well in terms of analytical performance to BPA, with a wide linear range of 0.1 to 10 ppb and LOD of 10 ng/L. The sensor results and the Langmuir adsorption model have good agreement. It has also been shown that repeated use of the biosensor can be achieved. According to selectivity studies, BPA adsorbed within the imprinted cavities favorably compared to 4-nitrophenol and phenol. The produced BPA-imprinted SPR sensor provides improved sensitivity based on the signal amplification strategy, unconjugated sensing without the need for labeling, real-time sensing, low sample consumption rates, quantifiable assessment, and very good kinetic rate constant calculation in actual samples. Also, because the produced sensor is reusable with relative standard deviations (RSD)<1.25, indicating the sensor's accuracy, the SPR-based biomimetic BPA sensor is simple to practice and may be an economical option.

Influenza is a highly contagious, acute respiratory illness, which represents one of the main health issues worldwide. Even though some antivirals are available, the alarming increase of virus strains resistant to them highlights the need to find new drugs. Previously, Superti et al. have deeper investigated the mechanism of the anti-Influenza virus effect of bovine Lactoferrin (bLf) and the role of its tryptic fragments (the N and C-lobes) in the antiviral activity. Recently, through a truncation library, we identified the tetrapeptides, SKHS (1) and SLDC (2), derived from bLf C-lobe fragment 418-429, which were able to bind hemagglutinin (HA) and inhibit cell infection in a concentration range of femto- to picomolar. Starting from these results, in this work, we initiated a systematic SAR study on the peptides mentioned above, through an Alanine scanning approach. We carried out binding affinity measurements by microscale thermophoresis (MST) and Surface Plasmon Resonance (SPR), and hemagglutination inhibition (HI) and virus neutralization (NT) assays on synthesized peptides. Computational studies were performed to identify possible lig-and-HA interactions. Results obtained led to the identification of an interesting peptide endowed with broad anti-Influenza activity and able to inhibit viral infection to a greater extent of reference peptide.

The conformational state of the activation loop (A-loop) is pivotal for the activation of most protein kinases. Hence, the characterization of the conformational dynamics of the A-loop is important to increase our understanding of the molecular processes related to diseases and to support the discovery of small molecule kinase inhibitors. Here, we carry out a combination of Molecular Dynamics (MD) and Essential Dynamics (ED) analyses to fully map the effects of phosphorylation, ADP, and conformation disrupting (CD) inhibitors (i.e., CD532 and MLN8054) on the dynamics of the A-loop of Aurora-A. MD revealed that the stability of the A-loop in an open conformation is enhanced by single phospho-Thr-288, while paradoxically, the presence of second phosphorylation at Thr-287 decreases such stability and renders the A-loop more fluctuant in time and space. Moreover, we found that such post-translational modification has a significant effect on the direction of A-loop motions. ED analysis suggests that the presence of the phosphate moiety induces the dynamics of Aurora-A to sample two distinct energy minima, instead of a single large minimum, as in unphosphorylated Aurora-A states. This suggests that the conformational distributions of Aurora-A with both single and double phospho-threonine modifications are remarkably different from the unphosphorylated state. In the closed states, binding of CD532 and MLN8054 inhibitors has the effect of increasing the distance of the N- and C-lobes of the kinase domain of Aurora-A, and the angle analysis between those two lobes during MD simulations showed that the N- and C-lobes are kept more open in presence of CD532, compared to MLN8054. As the A-loop is a common feature of Aurora protein kinases, our studies provide a general description of the conformational dynamics of this structure upon phosphorylation and different ligands binding.

Cyanobacteria are ubiquitous phototrophic bacteria that inhabit diverse environments across the planet. They dominate many eutrophic lakes impacted by excess nitrogen (N) and phosphorus (P) forming dense accumulations of biomass known as cyanobacterial harmful algal blooms or cyanoHABs. Their dominance in eutrophic lakes is attributed to a variety of unique adaptations including N and P concentrating mechanisms, N fixation, colony formation that inhibits predation, vertical movement via gas vesicles, and the production of toxic or otherwise bioactive molecules. While some of these molecules have been explored for their medicinal benefits, others are potent toxins harmful to humans, animals, and other wildlife known as cyanotoxins. In humans these cyanotoxins affect various tissues, including the liver, central and peripheral nervous system, kidneys, and reproductive organs among others. They induce acute effects at low doses in the parts-per-billion range and some are tumor promoters linked to chronic diseases such as liver and colorectal cancer. The occurrence of cyanoHABs and cyanotoxins in lakes presents challenges for maintaining safe recreational aquatic environments and the production of potable drinking water. CyanoHABs are a growing problem in the North American (Laurentian) Great Lakes basin. This review summarizes information on the occurrence of cyanoHABs in the Great Lakes, toxicological effects of cyanotoxins, and appropriate numerical limits on cyanotoxins in finished drinking water.

Medicinal plants possess a surplus of novel and biologically active secondary metabolites that are responsible for counteracting diseases. Traditionally, Gomphandra tetrandra (Wall.) Sleumer is used to treat mental disorders. The present research was designed to explore phytochemicals from the ethanol leaf extract of Gomphandra tetrandra (Wall.) Sleumer to identify the potential pharmacophore(s) in the treatment of neurological disorders. The chemical compounds of the experimental plant were identified through GC-MS analysis. Besides, in-vitro antioxidant activity was assessed using different methods. Furthermore, in-vivo neurological activity was assessed in Swiss-albino mice. Computer aided analysis was appraised to determine the best-fit phytoconstituent of a total of fifteen identified compounds in the experimental plant extract against beta-amyloid precursor protein. The experimental extract revealed fifteen compounds in GC-MS analysis and the highest content was 9, 12, 15-octadecatrienoic acid (Z, Z, Z). Also, the extract showed potent anti-oxidant activity in in-vitro assays. Furthermore, in in-vivo neurological assays, the extract disclosed significant (p<0.05) neurological activity. The most favorable phytochemicals as neurological agents were selected via ADMET profiling and molecular docking was studied with beta-amyloid precursor protein. Moreover, in the computer aided study, 1, 5-Diphenyl-2H-1, 2, 4-triazoline-3-thione (Pub Chem CID: 2802516) was more active than other identified compounds with strong binding affinity to beta-amyloid precursor protein. The present in vivo and in silico studies revealed neuropharmacological features of G. tetrandra leaves extract as a natural agent against neurological disorders, especially Alzheimer’s disease.

Study of gross alpha (GA) and gross beta (GB) activity in road and surface deposited sediments were performed in various geographical areas in three Russian cities. To perform radiation measurements, new methods were applied which allow dealing with low mass and low volume dust size (2-100μm) samples obtained after the size fractionation procedure. The 2-10 μm fraction size has the highest gross beta activity concentration (GB)– 1.32Bq/g in Nizhny Novgorod (NN) and Rostov-On-Don (RND) while the 50-100 μm fraction size in Ekaterinburg. This is maybe associated with the subsistence of radionuclides that conveyed through natural processes and anthropogenic applications. The highest gross alpha activity concentration (GA) in fraction sizes was found in Rostov-on-Don city within the 50-100 μm– 0.22Bq/g. The fraction size 50-100 μmhas a higher gross alpha activity concentration than 2-10 and 10-50 μmfraction sizes due to natural partitioning of the main minerals constituting the urban surface deposited sediment (USDS). The geochemical processes that occur during the formation and transportation of USDS are reflected in the observed dependencies.Developed experimental methods of radiation measurements allowed to the extent the methodological base of urban geochemical studies.

The Lluta River is the northernmost coastal wetland in Chile, representing a unique ecosystem and an important source of water in the extremely arid Atacama Desert. During peak season, the wetland is home to more than 150 species of wild birds and is the first stopover point for many migratory species that arrive in the country along the Pacific migratory route, representing a priority site for avian influenza virus (AIV) surveillance in Chile. The aim of this study was to determine the prevalence of influenza A virus (IAV) in the Lluta River wetland, to identify subtype diversity and to evaluate ecological and environmental factors that drive the prevalence at the study site. The wetland was studied and sampled from September 2015 to October 2020. In each visit, fresh fecal environmental samples (n = 178) of wild birds were collected for IAV detection by real-time RT-PCR. Furthermore, a count of wild birds present at the site was performed and environmental variables, such as temperature, rainfall, vegetation coverage (Normalized Difference Vegetation Index - NDVI) and water body size were determined. A generalized linear mixed model (GLMM) was built to assess the association between AIV prevalence and explanatory variables. Influenza positive samples were sequenced, and the host species was determined by barcoding. Of the 4,349 samples screened during the study period, overall prevalence in the wetland was 2.07% (95% CI: 1.68 to 2.55) and monthly prevalence of AIV ranged widely from 0% to 8.6%. A great diversity of hemagglutinin (HA) and neuraminidase (NA) subtypes were identified, and 10 viruses were isolated and sequenced, including low pathogenic H5, H7 and H9 strains. In addition, several reservoir species were recognized (both migratory and resident birds), including the newly identified host Chilean flamingo (Phoenicopterus chilensis). Regarding environmental variables, prevalence of AIV was positively associated with NDVI (OR=3.65, p<0.05) and with the abundance of migratory birds (OR=3.57, p<0.05). These results emphasize the importance of the Lluta wetland as a gateway to Chile for viruses that come from the Northern Hemisphere and contribute to the understanding of AIV ecological drivers.

Rotavirus is a major cause of diarrhea globally in animals and young children under 5 years. Here, molecular detection and genetic characterization of porcine rotavirus in smallholder and commercial pig farms in the Lusaka Province of Zambia were con-ducted. Screening of 148 stool samples by RT-PCR targeting the VP6 gene revealed a prevalence of 22.9 % (34/148). Further testing of VP6-positive samples with VP7-specific primers produced 12 positives, which were then Sanger-sequenced. BLASTn of the VP7 positives showed sequence similarity to porcine and human rota-virus strains with identities ranging from 87.5% to 97.1%. By next-generation se-quencing, the full-length genetic constellation of the representative strains RVA/pig-wt/ZMB/LSK0137 and RVA/pig-wt/ZMB/LSK0147 were determined. Geno-typing of these strains revealed a known Wa-like genetic backbone and their genetic constellations were G4-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1, respectively. Phylogenetic analysis revealed that these two viruses might have their ancestral origin from pigs, though some of their gene segments were related to human strains. The study shows evidence of reas-sortment and possible interspecies transmission between pigs and humans in Zambia. Therefore, the “One Health” surveillance approach for rotavirus A in animals and humans is recommended to inform the design of effective control measures.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

Background: It is known that Preeclampsia affects the lactogenesis. However, data on effects of this pathology on the human milk neurobiomarkers composition are not available. The aim of this study is to investigate the effects of this gestational pathology on Activin A levels, a neurobi-omarker known to play an important role in the development and protection of the central nerv-ous system. Methods: The women recruited were divided in two different study groups: preeclamptic or normotensive women. All the human milk samples were collected using the same procedure. Activin A was quantified using an ELISA test. To investigate the effect of Preeclampsia on the Activin A concentration in the 3 lactation phases, mixed linear model with unistructural covariance structure, mother as random effect, and fixed effects were performed. Results: Activin A was detected in all samples. There were no significant differences between Preeclamptic and Normotensive women. The only significant effect is related to the lactation phase: it is significant the difference between colostrum and mature milk (p<0.01). In conclusion these results allow us to affirm that breast milk beneficial properties are maintained even if preeclampsia occurs.

This study aims to develop and implement a methodology for retrieving bio-optical parameters in a lagoon located in the Biobío region, in south-central Chile by analyzing time series of Landsat-8 satellite images, specifically using the multispectral OLI sensor. The bio-optical parameters, i.e., chlorophyll-a (mg·m^-3) and turbidity (NTU) were also measured in-situ synchronized with the satellite passes to minimize the impact of atmospheric distortions. To calibrate the satellite images, various atmospheric correction methods (including ACOLITE, C2RCC, iCOR, and LaSRC) were evaluated during the image preprocessing phase. Spectral signatures obtained from the scenes for each atmospheric correction method were then compared with spectral signatures acquired in-situ on the water surface. In short, the ACOLITE model emerged as the best fit for the calibration process. Subsequently, we harnessed the reflectance data derived from the ACOLITE model to establish correlations between various spectral indices and the in-situ data. The empirical retrieval models (based on band combinations) that showed superior performance, as indicated by higher R² values, were subjected to rigorous statistical validation and optimization by applying a bootstrapping approach. Our analysis covered a spectrum of dates, seasons, and years, which allowed us to search deeper into the evolution of the trophic state associated with the lake. We identified a striking eight-year period (2014-2022) characterized by a decline in chlorophyll-a concentration in the lake possibly attributable to governmental measures in the region for the protection and conservation of the lake. The results of this initial study serve as the basis for the creation of a modern monitoring system that enhances traditional point-based methods, offering a holistic view of the ongoing processes within the lake.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

Terminalia arjuna possesses significant cardio protective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid “Terminalone A (1)” and two known flavonoids i.e. 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH was used as a scavenger) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Background: Acute appendicitis (AA) is the most common cause of emergency surgery. Perforation is more common than adults. Early diagnosis and new markers are needed. The aim of this study was to investigate the effects of plasma Fetuin-A (FA) levels in patients with the acute abdomen (AB). Material and Method: This prospective study included 107 patients younger than 16 years of age who were admitted to the emergency department for abdominal pain between January 2018 and December 2018. The patients who presented to abdominal pain were divided into two groups as AA and other causes (OC) of AB. T Patients with acute appendicitis; intraperitoneal, retrocolic / retrocecal and appendicitis were divided into three groups. Also, the AA group was divided into two groups as perforated appendicitis and non-perforated appendicitis. Serum FA levels of the patients were evaluated in the emergency department. Results: In the AA group, C-reactive protein (CRP) and white blood cell (WBC) levels were higher, and FA levels were significantly lower than in the AB group. Intraperitoneal localization was 95.2% and perforation was frequent. When significant values in the univariate regression analysis for acute abdomen and perforation were compared in the multivariate regression analysis, CRP, WBC, and FA levels were found to be prognostic. Also, decreased FA levels were associated with AA while too much decreased FA levels were associated with the risk of perforation. Conclusion: While trying to diagnose AA in children, the FA level, CRP and WBC may be predictive values to identify risk factors.

Particles in classical physics are distinguishable objects, which can be picked out individually on the basis of their unique physical properties. By contrast, in quantum mechanics the standard view is that particles of the same kind (``identical particles'') are completely indistinguishable from each other. This standard view is problematic: Particle indistinguishability is irreconcilable not only with the very meaning of ``particle'' in ordinary language and in classical physical theory, but also with how this term is used in the practice of present-day physics. Moreover, the indistinguishability doctrine prevents a smooth transition from quantum particles to what we normally understand by ``particles'' in the classical limit of quantum mechanics. Elaborating on earlier work, we here discuss an alternative to the standard view that avoids these and similar problems. As it turns out, this alternative approach connects to recent discussions in quantum information theory concerning the question of when identical particles can be considered to be entangled.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

This research work uses a simplified approach to combine location information from beacons propagation signal interaction with a mobile device with local building information to give real-time location and guidance to a user inside a building. This is an interactive process with visualisation information that can help user’s orientation inside unknown buildings and the data stored from different users can provide useful information about users movements inside a public building. Beacons installed on the building at specific pre-defined position emit signals that give a geographic position with an associated imprecision, related with Bluetooth’s range. This uncertainty is handled by building layout and users’ movement in a developed system that maps users’ position, gives guidance and store user movements. This system is based on an App (Find Me!) for Android OS (Operating System) which captures the Bluetooth Low Energy (BLE) signal coming from the beacon(s) and shows, through a map, the location of the user ‘s smartphone and guide him to the desired destination. Also, the beacons can deliver relevant context information. The application was tested by a panel of new and habitual campus users against traditional wayfinding alternatives yielding navigation times about 30% smaller, respectively.

The Vaal Dam catchment, which is the source of potable water for Gauteng province, holds various human activities including mining, urbanization, agricultural and industrial activities coupled with high fluxes of nutrients from different areas within the catchment. This situation led to an enhancement of Harmful Algal Blooms (HABs) in the dam reservoir. Phosphorus and Nitrogen are the limiting nutrients for HABs in many eutrophic aquatic systems when their concentrations are raised in such waters. In this study, multi-time-series plot types and scutter plots were analysed to reveal the relationship between HABs proxy chlorophyll-a (Chl-a) and the potential nutrients. Also (Chl-a) data extracted from landsat-8 satellite images were visualised to show the spatial distribution of HABs in the reservoir. The results showed that the Vaal Dam HABs productivity is a function of the total phosphorus (TP) and the organic nitrogen (KJEL_N) levels, which were positively correlated with chlorophyll-a (Chl-a) concentration. The long-term analysis of Chl-a in-situ data (1986 – 2022) measured at one point within the reservoir showed an average of 11.25μg/l but at some stochastic dates, the Chl-a concentration jumped to very high values reaching the maximum value of 452.8μg/l. Such high values are associated with high records of TP and KJEL_N concentrations at the same dates which clearly reveals their effect on the productivity levels. The decadal time series and its trend analysis showed that the average productivity level of Chl-a increased during the studded period from 4.75μg/l in the first decade (1990 – 2000) to 10.51μg/l in the second decade (2000 – 2010) reaching 16.7 during the last decade (2010 – 2020). The increasing averages of the decadal values are associated with the increasing decadal average of its driving factors, TP from 0.1043 to 0.1096 to 0.1119mg/l for the three decades, respectively and KJEL_N from 0.80mg/l in the first decade to 1.14mg/l in the last decade. The decadal average of temperature showed no significant increase, 17.9 °C in the first decade and 18 °C in the last decade which suggests that temperature is not the only enhancing factor of the HABs productivity in the Vaal Dam. The satellite data analysis during the last decade revealed that the HABs spatial dynamics is a function of the dam geometry and the levels of the discharges from its two feeding rivers. Higher concentrations were observed where the reservoir is meandering and within the areas of restricted water circulation.

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration which are based on the use of TCR alpha/beta depletion, CD45 RA depletion, T regulatory cells enrichment, NK cell-based immunotherapies and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.

Three-dimensional matrices are a new strategy used to tackle type I diabetes; a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), component that has been used to support cell growth. However, pure collagen possesses some difficulties including low stiffness and strength, and high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta-pancreatic cells. We analyzed the physicochemical characteristic of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced viability, proliferation, respiratory capacity and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Arthrospira platensis is a class of microalgae with high economic value. Its high adaptability, high photosynthetic efficiency, and fast growth rate make it one of the few microalgae that can be cultivated on a large scale. Therefore, using the selenium enrichment property of Arthrospira platensis to cultivate selenium-enriched Arthrospira platensis will not only enhance the physiological efficacy of Arthrospira platensis but also increase its economic value significantly. In this study, we investigated the effects of sodium selenite on the growth and photosynthetic performance of Arthrospira platensis selenium by setting different amounts and methods of sodium selenite addition, and we explored the optimal culture conditions. The results showed that the experimental group treated with sodium selenite at 120 mg/L had the fastest growth, and the contents of soluble protein, phycocyanin, and Chlorophyll a increased by approximately 67.9%, 1.44 times, and 38.8%, respectively, compared to the control group. Superoxide dismutase (SOD) and catalase (CAT) activity increased by 1.88-fold and 65%, respectively, and malondialdehyde (MDA) levels were reduced by 62% compared to the control group. The results of the OJIP assay showed that the J and I points were significantly higher at the batch addition and treatment concentration of 120 mg/L, with the rate of QA being reduced and the proportion of the slowly reduced PQ pool being increased. The values of the maximum light energy conversion efficiency (Fv/Fm) per unit of reaction center were higher in both sodium selenite treatment groups than in the control group, indicating that the light energy conversion efficiency of Arthrospira was promoted under all concentration treatment conditions. The batch addition of sodium selenite at concentrations less than 120 mg/L resulted in significantly higher ABS/RC values than the control, and they were far superior to the one-time addition method. The reason for this may have been that the batch addition of sodium selenite at low concentrations increased the light absorption capacity of the unit reaction center of the Arthrospira PSII, resulting in a rise in captured light energy, a rise in the energy captured by the reaction center for electron transfer (ETo/RC), a decrease in the energy dissipated in the absorption of light energy by the reaction center (DIo/RC), and an increase in the photosynthetic performance index (PI abs).

Objective: We previously provided evidence to confirm that soluble Fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio, are useful tools to direct the management of preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR near delivery. In this study we examine the potential additive value of Inhibin-A, a hormone marker of the transforming growth factor family. Methods: We used a cohort of 125 pregnant women enrolled near delivery at clinics of the University Medical Center of Ljubljana, Slovenia. There were 31 cases of PE, 16 of FGR, 42 of PE+FGR, 15 iatrogenic preterm delivery (PTD), and 21 unaffected controls with delivery of a healthy baby at term. Cases delivered before 34 weeks’ gestation included 13 of PE, 12 of FGR, 22 of PE+FGR, and 6 of PTD. We recorded demographic characteristics and medical history and the levels of PlGF, sFlt-1 and Inhibin-A. The predictive accuracy of each biomarker, their ratios, and combinations was estimated from areas under the curve (AUC) of Receiver Operating Characteristics (ROC) curves. We estimated accuracy by the continuous marker model and a cut-off model. Results: Combining Inhibin-A with PlGF or with the sFlt-1 / PlGF ratio showed a 10-20% increase in AUCs and 5-15% increase in the detection rate, at 10% false positive rate, of PE, and a lower, but significant, increase for PE+FGR but not for FGR alone. The use of a cut-off model was adequate, although a bit higher accuracy was obtained from the continuous model. Highest correlation was found for PlGF with all three complications. Conclusion: Inhibin-A improves the accuracy of predicting PE and PE+FGR provided by the angiogenic markers alone, bringing the results to a diagnostic level, thus assisting in directing clinical management. Inhibin-A had no added value for the accuracy of predicting FGR alone.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

Due to the fact that abrasive media can deform flexibly in abrasive flow machining (AFM) making this method easily to polish the complex holes and the curved surface of the hard machining shapes. Although abrasive media dominate the polishing behavior in AFM process, the mechanism of the abrasive media are not easy to understand because of the high viscous gels, therefore, many finishing works need lots of time to design AFM process. Power laws of the abrasive gels is studied here to evaluate the non-Newtonian flow of abrasive gels in complex holes polishing firstly, at the mean time different abrasive gels are utilized to finish the complex holes to follow the results by non-Newtonian flow calculation. Moreover, traditional AFM has difficulty to achieve a uniform roughness of radial distribution in the complex holes polishing because of the non-uniform abrasive forces. So a helical passageway is proposed to create a multiple motion of abrasive medium and to obtain the even surface of the complex holes in AFM process.

In this paper, we define a (p,v)-extension of Hurwitz-Lerch Zeta function by considering an extension of beta function defined by Parmar et al. [J. Classical Anal. 11 (2017) 81–106]. We obtain its basic properties which include integral representations, Mellin transformation, derivative formulas and certain generating relations. Also, we establish the special cases of the main results.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction, and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in a BP-induced mutagenesis in mice. The tested products significantly (p<0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16±9.09 μg/mL, 5.96±1.55 μg/mL and 3.05±0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1±63.40 μg/mL and 203.10±17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p<0.05) benzo[a]pyrene (BP)-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p<0.05) the BP-induced micronuclei and oxidative damage, together with an increase of glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for adjuvant therapy of cancer.

Benzo[a]pyrene (B[a]P), is a family member of polycyclic aromatic hydrocarbons and a widespread environmental pollutant and neurotoxicant that contribute to the development of cancer. Microtubules are polymers of tubulin that form part of the cytoskeleton and target for anticancer drugs. Furthermore, NPY significantly increased the percentage of cells in S and G2/M phases. However, little is known about the specific role of NPY in proliferation and the underlying protective mechanism remains unclear. Hence, the aim of this work was to investigate the effect of B[a]P on SH-SY5Y neuroblastoma cells and to explore the potential mechanism for alteration of tubulin-microtubule equilibrium causing mitotic arrest and NPY expression. The present findings showed B[a]P treatment significantly increase number of SH-SY5Y cells in S and G2/M phase as compared to G1 phase and provokes cell cycle arrest that correlated with significant decrease in G0/G1 cells. Immunofluorescence study showed significantly distorted tubulin arrangement from metaphasic plate in formation of bipolar mitotic spindle apparatus. Further, higher doses of B[a]P treatment lead to chromosomal abnormalities accompanied by DNA damage due ROS causing oxidative stress showing significant decrease in tubulin protein around spindle. The results of present study demonstrated that NPY exerts a proliferative and protective effect on B[a]P-induced oxidative stress in a dose-dependent manner in vitro and importantly, these effects may be mediated via mitotic arrest and involved in spindle arrangement during cell division. Our findings addresses a novel pathological outcomes of B[a]P-induced NPY expression by oxidative stress through spindle abnormalities leading to microtubule disruption.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

In this study, we evaluated the effects of Cyclosporine A (CsA) on Lipopolysaccharide (LPS)-induced cytokine production in the genital tract of female rabbits. Twelve sexually mature and healthy female rabbits were randomly divided into four groups (n = 3 each). The rabbits in the LPS group were given an intrauterine infusion of Escherichia coli LPS (4 mg/kg body weight (BW)). Rabbits in the CsA group were given CsA (20 mg/kg BW). Rabbits in the LPS + CsA group were given LPS (4 mg/kg BW) and CsA (20 mg/kg BW). The control group received only LPS and CsA carrier. The gene expression and protein levels of pro- and anti-inflammatory cytokines were observed using qRT-PCR and immuno-histochemical (IHC) assay, respectively. Our study showed that IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-4, IL-10, IL-13, and TGF-β were expressed in female genital organs. The LPS challenge increased the mRNA expression of IL-6 and TNF-α in the uterine body and IL-1β in the uterotubal junction compared to the control group. CsA increased the basal mRNA expression of anti-inflammatory cytokines (i.e., IL-4 in the uterine body, uterotubal junction, and oviductal ampulla; IL-10 in the cervix, oviductal isthmus, and ampulla; and TGF-β in the uterotubal junction and oviductal ampulla) and pro-inflammatory cytokines (i.e., IL-6 and IL-8 in the cervix; IL-1β in the oviductal isthmus; TNF-α in the oviductal ampulla; and IFN-γ in the uterine body compared to the control group). In addition, CsA inhibited the mRNA expression of pro-inflammatory cytokines, such as IL-6 in the uterine body, uterotubal junction, and oviductal isthmus; TNF-α in the uterine body; and IFN-γ in the uterotubal junction and oviductal isthmus induced by the LPS challenge. The IHC assay showed the LPS-induced increase in protein production of IL-6 in the uterine body and oviductal isthmus. CsA increased the protein production of IL-10 in the cervix, uterine body, oviductal ampulla, and isthmus. Moreover, CsA decreased the protein production of IL-6 in the uterine body and oviductal isthmus induced by LPS.

Mathematical algorithms relate satellite data of ocean color with the surface Chlorophyll–a con-centration (Chl-a), a proxy of phytoplankton biomass. These mathematical tools work best when they are adapted to the unique bio-optical properties of a particular oceanic province. Ocean color algorithms should also consider that there are significant differences between datasets derived from different sensors. Common solutions are to provide different parameters for each sensor or use merged satellite data. In this paper we use satellite data from the Copernicus merged product suite and in situ data from the southernmost part of the California Current System to test two widely used global algorithms, OCx and CI, and a regional algorithm, CalCOFI2. The OCx al-gorithm gave the best result, therefore, it was regionalized and, again, tested. The database was then separated according to (a) dynamic boundaries in the area, (b) bio-optical properties and (c) climatic condition (El Niño/La Niña). Regional algorithms were obtained and tested for each partition. The Chl-a retrievals for each model were tested and compared. The best fit for the data was for the regional algorithms that considered the climatic conditions (El Niño/La Niña). These results will allow the construction of consistent regionally adapted time-series and, therefore, demonstrates the importance of El Niño/La Niña events on the bio-optical properties of the area.

The objective of this study was to evaluate the occurrence of Clostridium perfringens in stool samples and swabs collected from wild mammals in the Amazon biome. Sixty-five faecal and swab samples were collected in situ and ex situ from 16 species and three genera of wild mammals, some of which were in good health and some of which had diarrhoea. After pre-enrichment, the samples were plated on selective agar for C. perfringens. Characteristic colonies were subjected to multiplex PCR for the detection of genes encoding the main C. perfringens toxins (alpha, beta, epsilon, and iota toxin and enterotoxin). Among the 65 samples, 40 (61.5%) were positive for the gene encoding the alpha toxin and were classified as type A. Faecal samples were more than four times more likely to be positive for C. perfringens than were swab samples. No other toxinotypes were found. The findings of this study suggest that C. perfringens type A is commonly found as a commensal in mammal species of the Amazon biome. This seems to be the first study to identify C. perfringens type A in species such as B. variegatus (common ground sloth), C. didactylus (two-toed sloth), P. flavus (Jupará), T. tetradactyla (anteater), S. collinsi (squirrel monkey), S. niger (black marmoset), and S. apella (Guyana capuchin) and in the genus Didelphis sp. (opossum).

IgA nephropathy (IgAN) is a kidney disease that is characterized by the deposition of IgA (immunoglobulin A) in the kidney tissue, leading to inflammation and damage. This disease is a common chronic glomerulopathy that affects people worldwide (1). Therefore, it is crucial to identify factors that worsen the disease, monitor its activity, and predict appropriate treatments. Complement component 4d (C4d) is a protein that is involved in the activation of the complement system, which is a part of the immune system.

Neuroendocrine tumors (NETs) of duodenal origin are an unusual subset among all NETs, comprising only about 3% of this neoplasm class. In general, NETs are characterized by overexpression of somatostatin receptors and carry an excellent prognosis with early diagnosis and intervention. Chromogranin A (CgA), a protein originating in secretory vesicles of neurons and endocrine cells, has gained wide usage in NET diagnosis and surveillance. Lanreotide is a synthetic octapeptide somatostatin analog with potent anti-proliferative action which has been approved by the FDA (U.S.) and EMA (E.U.) for NET treatment. It is known for its inhibitory effects on growth hormone, serotonin, CgA, and other markers. Here we describe a 56yr-old female with functional NET of duodenal origin, where serum CgA was successfully reduced from 3636 to <100 ng/mL after multidose lanreotide within five months. Of note, no metastatic spread was identified on positron emission tomography/computed tomography with 64Cu-labeled somatostatin analog tracer. Surgical resection of distal antrum, pylorus, and proximal duodenum followed without complication. Histology revealed several foci of well-differentiated tumor cells with characteristic neuroendocrine features and clear surgical margins; low proliferation index (2%) was noted on Ki-67 staining. While select laboratory and imaging modalities are available for diagnosis and monitoring of duodenal NET, this is the first reported therapeutic use of lanreotide in this NET setting. The observed serum CgA attenuation, even before surgery, supports its effectiveness in management of primary nonmetastatic duodenal NET.

In this paper, MnO2 nanowire (MnO2-NW) modified carbon paper (CP) electrode was developed as a novel electrochemical sensor for sensitive determination of tetrabromobisphenol A (TBBPA). MnO2 nanowire was prepared by a hydrothermal synthesis method, and the morphology and structure of MnO2 were characterized using scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical performance of TBBPA on MnO2-NW/CP was investigated by cyclic voltammetry, and the result confirmed that MnO2-NW/CP exhibited excellent sensitive for the determination of TBBPA due to the high specific surface area and good electrical conductivity of the nanowire-like MnO2. Moreover, the important electrochemical factors such as pH value, incubation time and modified material proportion were systematically studied to improve the determination sensitivity. The interferences from similar structure compounds on TBBPA have also been investigated. Under the optimal conditions, MnO2-NW/CP displayed the linear range of 70 500 nM for TBBPA with the detection limit of 3.1 nM, which was superior to some electrochemical methods in references. The work presents a novel and simple method for the determination of TBBPA.

This study aimed to assess the variations in the nutritional attributes of thirteen Moringa oleifera cultivars. Leaves from six-month-old plants were harvested and tested for various nutritional attributes. There were significant (p ≤ 0.05) differences in the carbohydrates, energy, some of the sugars and fibre amongst the cultivars. The levels of moisture in the cultivars ranged from 7.10% to 8.20%. Additionally, there were significant (p ≤ 0.05) differences across the cultivars in microelements studied except for zinc (Zn). These data revealed that plants from different geographical provenances differed in their adapting to varied environments. In general, under the same cultivation, management and environmental conditions, the main reasons for these differences occurred in cultivars could be associated with the genetic background of each M. oleifera germplasm. However, the study cautions on the differences of nutritional properties, as some of the cultivars have been reported not to be pharmacological potent.

A sensitive electrochemical sensor based on AuPtPd trimetallic nanoparticles functionalized multi-walled carbon nanotubes coupled with chitosan modified glassy carbon electrode (GCE/CS/MWCNTs-AuPtPd) for the rapid detection of bisphenol A (BPA) was proposed. AuPtPd trimetallic nanoparticles were first assembled on MWCNTs to obtain MWCNTs-AuPtPd nanocomposite. Then the MWCNTs-AuPtPd was further dispersed on the surface of chitosan modified electrode surface to fabricate the GCE/CS/MWCNTs-AuPtPd sensor. Due to the superior catalytic properties of MWCNTs-AuPtPd and the good film formation of chitosan, the constructed sensor displayed good performances for BPA detection. The structural morphology of CS/MWCNTs-AuPtPd was characterized by many methods, such as SEM, UV-vis and TEM. Under the optimal conditions, the designed sensor showed a linear range from 0.05 to 100 µM for BPA detecting with a low detection limit of 1.4 nM. The designed sensor was further used to realize the determination of BPA in real samples and the recoveries ranged from 94.4% to 103.6%. The results demonstrated that the electrochemical sensor designed by CS/MWCNTs-AuPtPd nanocomposites was reliable and could be a useful tool for the monitoring of food safety.

Due to increased energy intensive human activities resulting accelerated demand for electric power coupled with occurrence of natural disasters with increased frequency, intensity, and duration, it becomes essential to explore and advance renewable energy technology for sustainability of the society. Addressing the stated problem and providing a radical solution has been attempted in this study. To harvest the renewable energy, among variety of solar cells reported, a composite a-Si/CZTS photovoltaic devices has not yet been investigated. The calculated parameters for solar cell based on the new array of layers consisting of a-Si/CZTS are reported in this study. The variation of i) solar cell efficiency as a function of CZTS layer thickness, temperature, acceptor, and donor defect concentration; ii) variation of the open circuit current density as a function of temperature, open circuit voltage; iii) variation of open circuit voltage as a function of the thickness of the CZTS layer has been determined. There has been no reported study on a-Si/CZTS configuration-based solar cell, analysis of the parameters, and study to address the challenges imped efficiency of the photovoltaic device and the same has been discussed in this work. The value of the SnO2/a-Si/CZTS solar cells obtained from the simulation is 23.9 %.

Streptococcus pneumoniae causes invasive infections such as otitis media, pneumonia and meningitis. It produces pneumolysin (Ply) toxin, which forms a pore to host cell membrane and has multiple functions in S. pneumoniae pathogenesis. The Ply C-terminal domain 4 mediates binding to membrane cholesterol and induces the formation of pores composed of up to 40 Ply monomers. Ply has a key role in the establishment of nasal colonization, pneumococcal transmission from host to host and pathogenicity. Altogether, 27 hydrolyzable tannins were tested for Ply inhibition in hemolysis assay and tannin-protein precipitation assay. Pentagalloylglucose (PGG) and gemin A showed nanomolar inhibitory activity. Ply oligomerization on the erythrocyte surface was inhibited with PGG. PGG also inhibited Ply cytotoxicity to A549 human lung epithelial cells. Molecular modelling of Ply interaction with PGG suggested that it binds to the pocket formed by domains 2, 3 and 4. In this study, we reveal the structural features of hydrolyzable tannins that are required for interaction with Ply. Monomeric hydrolysable tannins containing a sufficient number of polyvalent and flexible galloyl groups have highest inhibitory power to Ply cytotoxicity, and are followed by oligomers. Of the oligomers, macrocyclic and C-glycosidic structures were weaker in their inhibition than the glucopyranose-based oligomers. Accordingly, PGG-type monomers and certain oligomers might have therapeutic value in the targeting of S. pneumoniae infections.

Preeclampsia (PE) is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction and the impairment of placenta vascular endothelial integrity. This study aimed to investigate the effect of serum copper (Cu) level on some angiogenesis-related factors including vascular endothelial growth factor-A (VEGF-A), soluble Fms-like tyrosine kinase-1 (sVEGF-R1), soluble endoglin (sEng) and cerruloplasmin (Cp) in Iraqi women with preeclampsia (PE) and control pregnant women. Therefore, 60 women with PE in addition to 30 healthy pregnant women were enrolled in the study. Serum concentration of sEng, VEGF-A, sVEGF-R1, and Cu in PE group significantly increased (p<0.05) in the PE group compared with that in the control group. Increased production of antiangiogenic factors, soluble VEGF-A and sEng contribute to the pathophysiology of PE, indicating the involvement of these parameters in the angiogenic balance in patients with PE. Tests for between-subject effects showed that the circulating angiogenesis factors and Cu were significantly associated with the presence of PE. Serum Cu level was significantly correlated with VEGF- A and VEGF-R1 levels but not with sEng. Multiple regression analysis revealed that only Cp and BP can significantly predict the complications in women with PE. In conclusion, serum Cu has a role in the angiogenesis in women with PE and may be a new drug target in the prevention or treatment of PE.

Dewetting transition - a concept borrowed from fluid mechanics - is a physiological process which takes place inside the hydrophobic pores of ion channels. This transient phenomenon causes a metastable state which forbids water molecules to cross the microscopic receptors’ cavities. This leads to a decrease of conductance, a closure of the hole and, subsequently, severe impairment of cellular performance. We suggest that artificially-provoked dewetting transition in ion channels’ hydrophobic pores could stand for a molecular candidate to erase detrimental organisms, such as viruses, bacteria and cancer cells. We describe a novel type of high-affinity monoclonal antibody, which: a) targets specific trans-membrane receptor structures of harmful or redundant cells; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flows inside ion channels. Therefore, we achieve an artificial dewetting transition inside receptors’ cavities which causes transmembrane ionic flows discontinuity, channel blockage and subsequent damage of morbid cells. As an example, we describe dewetting monoclonal antibodies targeting the M2 channel of the Influenza A virus: they might prevent water to enter the pores, thus leading to virion impairment.

A novel virus with distinct genome features was discovered by high throughput sequencing in a symptomatic blackcurrant plant. The virus tentatively named as blackcurrant virus A (BCVA) has distinct genome organization and molecular features bridging genera in the order Tymovirales. The genome consists of 7106 nucleotides excluding the poly(A) tail. Five open reading frames were identified with the first encoding a putative viral replicase with methyl transferase (MTR), AlkB, helicase and RNA dependent RNA polymerase (RdRp) domains. The other four putative proteins exhibit no significant homology to other virus proteins. The genome organization downstream of the replicase resembles that of members of the order Tymovirales with an unconventional triple gene block (TGB) movement protein arrangement. Phylogenetic analysis using replicase conserved motifs loosely placed BCVA within the Betaflexiviridae whereas it was evolutionarily distant to existing members of the family when using the putative TGBp 1-like and coat protein sequences. Our analysis strongly suggests that BCVA is a novel virus that should be classified as a species in a new genus in the Betaflexiviridae or a new family in the order Tymovirales.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

Methionine 77 in calmodulin can be stereospecifically oxidized to methionine sulfoxide by mammalian methionine sulfoxide reductase A. Whether this has in vivo significance is unknown. We therefore created a mutant mouse in which wild-type calmodulin-1 was replaced by a calmodulin containing a mimic of methionine sulfoxide at residue 77. Total calmodulin levels were unchanged in the homozygous M77Q mutant, which is viable and fertile. No differences were observed on learning tests, including the Morris water maze and associative learning. Cardiac stress test results were also the same for mutant and wild type mice. .However, young male and female mice were 20% smaller than wild type mice, although food intake was normal for their weight. Young M77Q mice were notably more active and exploratory than wild type mice. This behavior difference was objectively documented on the treadmill and open field tests. The mutant mice ran 20% longer on the treadmill than controls, and in the open field test, the mutant mice explored more than controls and exhibited reduced anxiety These phenotypic differences bore a similarity to those observed in mice lacking calcium/calmodulin kinase Iiα (CaMKIIα). We then showed that M77Q calmodulin was less effective in activating CaMKIIα than wild type calmodulin. Thus, characterization of the phenotype of a mouse expressing a constitutively active mimic of calmodulin led to the identification of the first calmodulin target that can be differentially regulated by the oxidation state of Met77. We conclude that reversible oxidation of methionine 77 in calmodulin by MSRA can regulate cellular function.

Most astrophysicists today believe that the present universe was produced in a big bang. This article explores the big cycle of matter and energy in the universe, with the big bang as an important part of the cycle.The authors approve of the idea that the universe is gravitationally closed. That is, its average density is higher than the critical value. All the matter and radiation cannot fly out the closed universe.The 3k background radiation is a vast heat ocean in the closed universe, stable and eternal. It is not the afterglow of the thermal radiation of the decoupled fire ball, 380,000 years after the big bang, as many people believed so far. The big bang and the following big expansion drove the matter of more than 2×10¹² galaxies to the remote space. Their potential energies become higher and higher, while their huge kinetic energies that they derived from the big bang become smaller and smaller until drop down to zero. The galaxies will then return back one after another, passing the central region of the universe with tremendously great kinetic energies. They of course cannot all return back directly to their start point of the big bang and restore to the state of the original cosmic core. They will rush to pass the central region and fly to the other sides of the universe, and shuttle around the central part ceaselessly. From the big bang to the following expansion, to the numerous galaxies, to the more than 2×10²³ stars, and to the stars releasing huge nuclear energy due to their internal nuclear fusion each for about 10¹⁰ years, all these enormous processes are irreversible, resulting in enormous increase in entropy. These processes produce large amount of light and other radiations and pour them into the extremely vast heat ocean. These light and other radiations will also be shuttling ceaselessly in the vast heat ocean until, by their interaction with the rare dusts in the galaxies, they mingle into the 3K thermal radiation of the heat ocean. In all the galaxies, there are various black holes. Every black hole, since its birth, ceaselessly extracts the matter and radiation that approach it, and gets larger. In the above mentioned shuttling of all the galaxies, numerous stars and black holes in these galaxies have many chances to approach even meet each other. A black hole can annex other celestial bodies that it meets, including annex other black holes. All these processes carry on and on ceaselessly, resulting in the matter of these celestial bodies to concentrate again and again. The number of all the celestial bodies including the black holes reduces ceaselessly, and the mass of the survived black holes become larger, and their shuttling amplitudes become shorter. The larger black holes and the shorter amplitudes result in the rate of concentration of mass to be faster. Eventually, all the matter in the universe will be concentrated to form a tremendously large central black hole. The central black hole has an astonishingly large Schwarzschild sphere, absorbing the thermal radiation from the vast heat ocean very rapidly and ceaselessly until some threshold value of its internal energy is exceeded, and a new big bang breaks out. The black holes provide a way in the Universe to re-concentrate matter and energy again. Black holes are Maxwell’s demons in the Nature.

Lyme disease (LD) is a tick-transmitted infection caused by Borrelia burgdorferi sensu lato species which includes B. burgdorferi, B. afzelii, and B. garinii. The majority of patients with early LD can be cured by standard treatment, yet some still suffer from post-treatment Lyme disease syndrome (PTLDS). The presence of Borrelia persisters has been proposed as a contributing factor, which cannnot be completely killed by the currently used antibiotics for Lyme disease. Finding new pharmaceuticals targeting Borrelia persisters is crucial in developing more effective treatment. Here, we first confirmed the existence of persisters in cultures of B. garinii and B. afzelii and then conducted high-throughput screening of a custom drug library against persister-rich stationary-phase cultures of B. garinii and B. afzelii. Among 2427 compounds screened, hypocrellin A (HA), anthracycline class of drugs, and topical antibiotics along with some other natural compounds were identified to have strong potential in killing persisters of B. garinii and B. afzelii. HA was the most active anti-Borrelia compound, capable of eradicating stationary-phase Borrelia persisters, in particular when combined with doxycycline and/or ceftriaxone. Liposoluble antioxidant vitamin E was found to antagonize the activity of HA, indicating HA’s target is the cell membrane where HA-triggered reactive oxygen species (ROS) generation took place in the presence of light. HA was found to have distinct bactericidal activity against Borrelia species but had poor or no activity against Gram-positive and Gram-negative bacteria. Identification of the above-mentioned drug candidates may help to develop more effective therapies for LD.

Artificial membrane systems can serve as models to investigate molecular mechanisms of different cellular processes, including transport, pore formation, and viral fusion. However, the current simulacrums such as SUVs, GUVs, and the supported lipid bilayers suffer from issues, namely high curvature, heterogeneity, and surface artefacts, respectively. Freestanding membranes provide a facile solution to these issues, but current systems developed by various groups use silicon or aluminium oxide wafers for fabrication that involves access to a dedicated nanolithography facility and high cost while conferring poor membrane stability. Here, we report the development, characterization and applications of an easy-to-fabricate suspended lipid bilayer (SULB) membrane platform leveraging commercial track-etched porous filters (PCTE) with defined microwell size. Our SULB system offers a platform to study the lipid composition-dependent structural and functional properties of membranes with exceptional stability in a high throughput fashion. With dye entrapped in PCTE microwells by SULB, we show that sphingomyelin significantly augments the activity of pore-forming toxin, Cytolysin A (ClyA) and the pore formation induces lipid exchange between the bilayer leaflets. Further, we demonstrate high efficiency and rapid kinetics of membrane fusion by dengue virus in our SULB platform. Our suspended bilayer membrane mimetic offers a novel platform to investigate a large class of biomembrane interactions and processes.

BPA is a commonly used compound in many industries and has versatile applications in polycarbonate plastics and epoxy resins production. BPA is classified as endocrine-disrupting chemical which can hamper fetal development during pregnancy and may have long term negative health outcomes in humans. Dietary sources, main route of BPA exposure, can be contaminated by the migration of BPA into food during processing. The global regulatory framework for using this compound in food contact materials is currently not harmonized. This review aims to outline, survey, and critically evaluate BPA contamination in meat products, including level of BPA and/or metabolites present, exposure route, and recent advancements in the analytical procedures of these compounds from meat and meat products. The contribution of meat and meat products to the total dietary exposure of BPA ranges between 10 and 50% depending on the country and exposure scenario considered. From can lining materials of meat products, BPA migrates towards the solid phase resulting higher BPA concentration in solid phase than the liquid phase of the same can. The analytical procedure is comprised of meat sample pre-treatment, followed by cleaning with SPE, and chromatographic analysis. Considering several potential sources of BPA in industrial and home culinary practices, BPA can also accumulate in non-canned or raw meat products. Very few scientific studies have been conducted to identify the amount in raw meat products. Similarly, analysis of metabolites and identification of the origin of BPA contamination in meat products is still a challenge to overcome.

Starting from acid chlorides, alkynes, tryptamines, and acroyl chloride, 21 densely substituted tetrahydro-beta-carbolines are prepared in a four-component one-pot reaction. In this study, the aza-Michael addition step to generate intermediate enaminones is optimized in the presence of ytterbium triflate. Moreover, apart from acroyl chloride, all reactants can be deployed in almost equimolar ratios, which increases the atom economy of the sequence. For mechanistic rationali-zation, the concluding aza-anellation was investigated by DFT calculations on potential inter-mediates and corresponding activation energies, revealing that the aza-anellation rather pro-ceeds via ene-reaction than via electrocyclization.

In the study of rough sets, there are many covering approximation spaces, how to classify covering approximation spaces has become a hot issue. In this paper, we propose concepts covering approximation $T_{1}$-space, $F-$symmtry, covering rough continuous mapping, covering rough homeomorphism mapping to solve this question. We also propose a new method for constructing topology in Theorem 5.1, and get the following properties: (1) For each $x\in U$, $\{X_{i}:i\in I\}\subseteq \mathcal{P}(U)$ is all the subsets of $U$ which contains $x$ and $*$ is a reflexive relation on $U$. If $V\in \tau$ is a subset of $U$ and $x\in V$, then $\underline{*}(\bigcap \limits_{i\in I}X_{i})$ is the smallest subset of $U$ and $x \in \underline{*}(\bigcap \limits_{i\in I}X_{i})\subseteq V$. Denoted by $C(x)=\bigcap \{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$. (2)If $V\in \tau$ is a subset of $U$, then $V =$ $\bigcup \limits_{x\in V} C(x)$. (3) Let $\{\underline{*}(X_{i}):x\notin \underline{*}(X_{i}), i\in I\}$, then $\overline{\{x\}}$ $=$ $U \setminus \bigcup \limits_{x\notin \underline{*}(X_{i}), i\in I}\underline{*}(X_{i})$; (4) Let $*$ be a reflexive relation on $U$. For every $X\subseteq U$, we have $int(\underline{*}(X))=\underline{*}(X)$. Where $int(\underline{*}(X))$ represents the interior of $\underline{*}(X)$. (5) Let $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ be a family subsets of $U$, then $\{\underline{*}(X_{i}):x\in \underline{*}(X_{i}),i\in I\}$ is a base for $(U,\tau)$ at the point $x$. \\

Among bryophytes, the Plagiochila genus represents a large group of leafy liverworts, with over 500 species. Plagiochilins A-to-X are sesquiterpenoids isolated from Plagiochila species. The lead compound plagiochilin A (Plg-A), endowed with anticancer and anti-parasitic properties, has been characterized as a potent mitosis inhibitor, acting selectively at the late stage of cytokinesis termed abscission. The compound perturbs the dynamic of microtubules, blocking cell cycle progression and triggering the death of malignant cells. Based on the compound mechanism of action and the analogy with other natural products bearing a dihydro-pyrone moiety, we postulated that Plg-A could bind to the pironetin site of α-tubulin. A molecular docking analysis has been performed to compare binding of all 24 plagiochilins to α-tubulin and to establish structure-binding relationships. The identification of Plg-E and Plg-G as the best binders in the series pointed out to the importance of the C13-OH or C=O group for α-tubulin recognition. This observation led to the testing of the natural product ester plagiochilin A-15-yl n-octanoate and the corresponding alcohol (Plg-OH), both identified as robust α-tubulin binders. The study provides a rational to explain potentially the mechanism of action of Plg-A and to guide the design of new derivatives.

$\beta$-decay is one of the key factors to understand the $r$-process and evolution of massive stars. The Gamow-Teller (GT) transitions drive the $\beta$-decay process. We employ the proton-neutron quasiparticle random phase approximation (pn-QRPA) model to calculate terrestrial and stellar $\beta$-decay rates for 50 top-ranked nuclei possessing astrophysical significance according to a recent survey \cite{Nab21}. The model parameters of the pn-QRPA model effect the predicated results of $\beta$-decay. The current study investigates the effect of nucleon-nucleon pairing gaps on charge-changing transitions and the associated $\beta$ decay rates. Three different values of pairing gaps, namely TF, 3TF and 5TF, were used in our investigation. It was concluded that both GT strength distributions and half-lives are sensitive to pairing gap values. The 3TF pairing gap scheme, in our chosen nuclear model, resulted in best prediction with around 80$\%$ of the calculated half-lives within a factor 10 of the measured ones. The 3TF pairing scheme also led to calculation of biggest $\beta$-decay rates in stellar matter.

The available magnetic field strength for high resolution NMR in persistent superconducting magnets has recently improved from 23.5 to 28 Tesla, increasing the proton resonance frequency from 1 to 1.2 GHz. For magic-angle spinning (MAS) NMR, this is expected to improve resolution, provided the sample preparation results in homogeneous broadening. We compare two-dimensional (2D) proton detected MAS NMR spectra of four membrane proteins at 950 and 1.2 GHz. We find a consistent improvement in resolution that scales superlinearly with the increase in magnetic field for three of the four examples. In 3D and 4D spectra, which are now routinely acquired, this improvement indicates the ability to resolve at least 2 and 2.5 times as many signals, respectively.

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

Probabilistic and parsimony-based arguments regarding available genetics data are used to propose that Hardy and Higgin’s amyloid cascade hypothesis is valid but is commonly interpreted too narrowly to support, incorrectly, the primacy of the amyloid beta peptide (Aβ) in driving Alzheimer’s disease pathogenesis. Instead, increased activity of the βCTF (C99) fragment of APP is likely the critical pathogenic determinant altered by mutations in the APP gene. This model is consistent with the regulation of APP mRNA translation via its 5’ iron responsive element (IRE). Similar arguments support that the pathological effects of familial Alzheimer’s disease mutations in the genes PSEN1 and PSEN2 are not exerted directly via changes in APP cleavage to produce different ratios of Aβ length. Rather, these mutations likely affect the stability of presenilin holoprotein and/or γ-secretase multimers with consequences for γ-secretase activity and other important cellular functions. All fAD mutations in APP, PSEN1, and PSEN2 likely find unity of pathological mechanism in their actions on endolysosomal acidification and mitochondrial function, with detrimental effects on iron homeostasis and promotion of “pseudo-hypoxia” being of central importance. Aβ production is enhanced and distorted by oxidative stress and accumulates due to decreased lysosomal function. It may act as a disease-associated molecular pattern (DAMP) enhancing oxidative stress-driven neuroinflammation during the cognitive phase of the disease. We also discuss fascinating, but largely ignored, data on presenilin biology that may be important in understanding presenilins’ central role in familial Alzheimer’s disease.

The mutton quality of Chinese Tan lambs (Ovis aries) has declined as feeding patterns have shifted from pasturing to pen rationing. Mutton quality is affected by fatty acids, and rumen microorganisms play a role in the synthesis of short-chain fatty acids, long-chain fatty acids, and conjugated linoleic acids. We used 16S rDNA sequencing to analyze the effects of two feeding patterns on the rumen bacteria of Tan lambs. In a randomized block design with 24 newborn Tan lambs, 12 lambs were fed by ewes in pasture and 12 were fed by pen-fed ewes. At 2 months, the biceps femoris and the longissimus dorsi were analyzed by gas chromatography for intramuscular fat content and fatty acid composition, and DNA in the rumen contents was extracted and used to analyze the structure of the bacterial community. Different feeding patterns had no significant effect on the intramuscular fat content of the biceps femoris and longissimus dorsi of the lambs, but there was a significant effect on fatty acid composition. Rumen bacteria were significantly more diverse in the pasture group than in the pen-ration group (P < 0.01). Twenty-one phyla were identified in the pasture group, and 14 phyla were identified in the pen-ration group. The dominant phyla in the pasture group were Bacteroidetes and Fibrobacteres; the dominant phyla in the pen-ration group were Proteobacteria and Bacteroidetes. The relative abundance of Proteobacteria was significantly higher in the pen-ration group than in the pasture group (P < 0.01). Diversity at the genus level was also higher in the pasture group, with 176 genera in the pasture group and 113 genera in the pen-ration group. The dominant genera in the pasture group were Prevotella_1, Rikenellaceae_RC9_gut_group, and Bacteroidales_BS11_gut_group_Na; the dominant genera in the pen-ration group were Prevotella_1, Prevotella_7, Succinivibrionaceae_UCG-001, and Succinivibrionaceae_NA.

Searching for neutrinoless double beta decay is a top priority in particle and astroparticle physics, being the most sensitive test of lepton number violation and the only suitable process to probe the Majorana nature of neutrinos. In order to increase the experimental sensitivity for this particular search, ton-scale detectors operated at nearly zero-background conditions with a few keV energy resolution are required. In this scenario, cryogenic detectors have proven effective in addressing many of these issues simultaneously. After long technical developments, the CUORE experiment established the possibility to operate large scale detectors based on this technology. Parallel studies pointed out that scintillating cryogenic detectors represent a suitable upgrade for the CUORE design, directed towards higher sensitivities. In this work, we review the recent development of cryogenic detectors, starting from the status of the art and outlying the path toward next-generation experiments.

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c &/or irregular blood glucose levels. Diabetic patient’s mortality rates with COVID-19 are higher than cardiovascular or cancer patients. Recently Bacillus Calmette–Guérin (BCG) has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to Beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from TB and leprosy and has been repositioned for treatment of bladder cancer, diabetes & multiple sclerosis. Recently, the COVID-19 epidemiological study confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 & diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide & PCPRI laboratory findings after BCG vaccination for a 9 years’ patient. The patient was re-vaccinated based on a negative tuberculin test & no scar at the site of injection of the 1st BCG vaccination at birth. Furthermore, the authors in the present article described a prospective BCG multi-dose clinical study in full details that they will apply in case of acceptance of their submitted grant & the ethical committee approval. The aim of the clinical study is to check if double dose BCG (4 weeks apart) will show a significant difference in the protection of health care professionals in Egypt. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions & exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

Hypertension is a common and growing medical problem that leads to enormous cardiovascular and kidney disease worldwide. While many drugs exist to treat hypertension, there is large individual variation in how a given individual responds to different agents, which contributes to dismal rates of hypertension control. While demographic factors predict which drugs may work better in certain individuals, a great degree of this variation has a genetic basis. In recent years, genome wide association studies have begun to identify specific gene variants that predict drug response to particular agents. This review identifies the major genetic variants influencing antihypertensive response that have emerged from this growing body of work. For novel genetic variants without a previously known biologic basis in blood pressure, it is crucial to validate initial findings in subsequent studies. This information may eventually lead to a more personalized approach to hypertension management that will improve blood pressure control and patient outcomes. The integration of this large amount of data and its real world application will be highly challenging, but strategies to accomplish this are discussed.

Purification of biologically-derived therapeutics is a major cost contributor to the production of this rapidly growing class of pharmaceuticals. Monoclonal antibodies comprise a large percentage of these products therefore new antibody purification tools are needed. Small peptides, as opposed to traditional antibody affinity ligands such as Protein A, may have advantages in stability and production costs. Multiple heptapeptides that demonstrate Fc binding behavior that have been identified from a combinatorial peptide library using M13 Phage Display are presented herein. Seven unique peptide sequences of diverse hydrophobicity and charge were identified. All seven peptides showed strong binding to the four major human IgG isotypes, human IgM, as well as binding to canine, rat, and mouse IgG. These seven peptides were also shown to bind human IgG4 from DMEM cell culture media with 5% FCS and 5 g/L ovalbumin present. These peptides may be useful as surface ligands for antibody detection and purification purposes. Molecular docking and classical molecular dynamics (MD) simulations were conducted to elucidate the mechanisms and energetics for the binding of these peptides to the Fc region. The binding site was found to be located between the two glycan chains inside the Fc fragment. Both hydrogen bonding and hydrophobic interactions were found to be crucial for the binding interactions. Excellent agreement for the binding strength was obtained between experimental results and simulations.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Obesity and overweight are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia, which are closely related to a sedentary lifestyle and lack of exercise. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and decreases the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel®) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders. In the current study, 17 obese subjects (average BMI 30.0±1.1 kg/m2, eight male and nine female) were recruited to participate in a program combining exercise and policosanol (20 mg) consumption for 12 weeks. After completion, their BMI, waist circumference, total fat mass, systolic blood pressure (SBP), and diastolic blood pressure (DBP) decreased by approximately 15% (p=0.022), 12.7% (p=0.008), 33% (p=0.006), 11% (p<0.046), and 13% (p=0.007), respectively. In the serum lipid profile, at week 12, they showed a remarkable decrease in the total cholesterol (TC) and triglyceride (TG) levels, up to 17% (p<0.019) and 54% (p<0.002) from the baseline, respectively. Although the serum HDL-C was increased by approximately +12% from the baseline, the percentage of HDL-C in TC, HDL-C/TC (%), was increased by up to +32% (p=0.007) at week 12. The serum coenzyme Q10 (CoQ10) level was increased 1.2-fold in all participants at week 12 from the baseline. In particular, the male participants showed a 1.4-fold increase (p=0.027) from the baseline. The larger increase in serum CoQ10 was correlated with the larger increase in the serum HDL-C during 12 weeks. The hepatic function parameters were improved; the serum -glutamyl transferase decreased at week 12 by up to 55% (p<0.007), while the aspartate aminotransferase and alanine transaminase levels decreased within the normal range. In the lipoprotein level, the extent of oxidation and glycation were reduced significantly in VLDL and LDL, with a remarkable decrease in the TG content in particles. The antioxidant abilities of HDL2 and HDL3, such as paraoxonase (PON) and ferric ion reduction ability (FRA), were enhanced significantly by up to 1.8-fold (p<0.001) and 1.6-fold (p<0.001) at week 12. The particle size and number of HDL2 were increased up to +10% during the 12 weeks with a remarkable decrease in the TG content, glycation extent, oxidation up to 32% (p=0.032), 18% (p=0.043), and 11% (p=0.023), respectively. The particle number and diameter of HDL3 were increased by up to +9% with a remarkable increase in the PON activity, FRA activity, and TC content of +82% (p<0.001), +56% (p<0.001), and +32% (p=0.009), respectively. Expression of apolipoproteinA-I in HDL2 and HDL3 were significantly elevated more in both gender around 30~48% with more distinct band intensity and less glycation at week 12. These improvements in HDL quality and functionality were linked to the higher survivability of adult zebrafish and their embryos. Under the co-presence of carboxymethyllysine (CML), a microinjection of HDL2 to zebrafish embryo from week 0 resulted in approximately 47% survivability with developmental defects and attenuated speed. On the other hand, the HDL2 microinjection from week 12 resulted in remarkably higher survivability (~ 70%). In conclusion, 12 weeks of Cuban policosanol (Raydel®, 20 mg) consumption with high-intensity exercise showed significant improvement in blood pressure, body fat mass, blood lipid profile without liver damage, CoQ10 metabolism, and renal impairment. At week 12, all participants showed a remarkable decrease in oxidation and glycation extent in the VLDL and LDL with a decrease in the TC and TG content. Significant enhancement of the qualities and functionalities in HDL2 and HDL3 by the policosanol consumption were also detected: increase in apoA-I content, TC content, particle size, and particle numbers along with antioxidant abilities, such as PON and FRA.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered a recent pandemic of respiratory disease and affected almost every country all over the world. A large amount of natural bioactive compounds is under clinical investigation for various diseas-es. Especially, marine natural compounds are gaining more attention in the new drug develop-ment process. The present study has aimed to identify potential marine-derived inhibitors against the target proteins of COVID-19 using a computational approach. Currently, 16 marine clinical-level compounds were selected for computational screening against the four SARS-CoV-2 main proteases. Computational screening resulted from the best drug candidates for each target based on the binding affinity scores and amino acid interactions. Among these, five marine-derived compounds namely Chrysophaentin A (-6.6 kcal/mol), Geodisterol sulfates (-6.6 kcal/mol), Hymenidin (-6.4 kcal/mol), Plinabulin (-6.4 kcal/mol) and Tetrodotoxin (-6.3 kcal/mol) expressed the minimized binding energy and molecular interactions such as covalent and hydrophobic interactions to the SARS CoV-2 Main Protease. Using Molecular dynamic stud-ies, the Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), Radius of Gyration (ROG), and Hydrogen bonds (H-Bonds) values were calculated for SARS-CoV-2 Main Protease with Hymenidin docked complex. Additionally, in silico Druglikeness and pharmaco-kinetic property assessments of the compounds demonstrated favorable druggability. These re-sults suggested that marine natural compounds are capable of fighting SARS-CoV-2. Further, in vitro and in vivo studies need to be carried out to confirm their inhibitory potential.

Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.

Viral hepatitis is currently acknowledged as a significant public health issue that necessitates a prompt and immediate response. Hepatitis is a significant worldwide health problem that causes the death of approximately 1.5 million individuals annually. The objective of this study was to ascertain the occurrence rate of hepatitis A, E, B, and C infections in the Hajjah governorate of Yemen from 2020 to 2023.A retrospective study was conducted in the Hajjah Governorate of Yemen for four years, 2020– 2023. About 41162 cases were collected from the clinical records of epidemiological surveillance in the Public Health Office of the Hajjah Governorate. All cases were diagnosed in different laboratories based on direct observation of viral hepatitis in the blood sample. The required data were obtained by using the designed questionnaire. The findings of the present investigation were summarized as follows: The current findings indicate that the prevalence rate of Hepatitis A and E was 761 (1.85%), while the prevalence rate of Hepatitis B and C was 971 (2.36%) among the participants of the study. The current findings indicate that the incidence of Hepatitis A and E was greater in 2022 (2.3%), while Hepatitis B and C had a higher rate in 2020 (2.9%). The study revealed a higher prevalence of hepatitis A and E among individuals originating from Al Miftah district 116, with a rate of 7.5%. Furthermore, the prevalence of hepatitis B and C in Hajjah city was significantly higher, reaching 579 cases (22.9%). The month with the highest incidence of hepatitis A and E viruses was September, with a rate of 85 cases (2.6%), while the lowest incidence was observed in April, with a rate of 1.3%. The prevalence of hepatitis B and C viruses was highest in October 1997, with a rate of 2.8%, followed by November 1997 with the same rate. The lowest observed incidence of 1.6% was recorded in April. In Autumn, a significant prevalence of hepatitis A and B viruses, as well as hepatitis B and C viruses, was identified at rates of 2.2% and 2.6%, respectively.The study findings indicate that the occurrence of HAV, HEV, HBV, and HCV in the study area is consistent with global trends. Although the study found a low prevalence of hepatitis viruses, these types of viruses will continue to pose a significant risk to public health. Based on this study, it is imperative for authorities to actively enhance public awareness in order to enable prompt planning and essential arrangements for an effective response to outbreaks or epidemics. This will ultimately lead to a reduction in illness, death, and economic burden.

Our understanding of the diversity of life on our planet and the possibility of finding or sustaining life elsewhere in the universe plays a central role in supporting human space settling and exploration. Astrobiology and its outcomes require a multidisciplinary and comprehensive approach, in which the microbial, geological, chemical, astronomical, and physical domains of research are interlinked. An example of the applications of astrobiology and space microbiology is the use of extremophiles for in-situ resource utilization through biomining and bioleaching. To better understand the multidisciplinary research landscape in this area, we have quantitatively reviewed the global scientific literature on astrobiology with a focus on biomining and bioleaching through bibliometric network analysis, investigating patterns and trends in its development over time. The network analysis of the keywords co-occurrence highlights different connecting and overlapping clusters, illustrating the multidisciplinary character of astrobiology. Temporal analyses show a recent focus on topics related to microbiology and geomicrobiology, emphasizing the role that these fields will play in future astrobiology research. In conclusion, astrobiology, biomining, and bioleaching research are timely responding to the identification of these techniques as tools for biotechnological applications, expected to play a crucial role in long-term human space exploration.