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The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the developing mouse brain. ILC2s expanded and produced IL-13 in the developing brain meninges. Loss of ILC2s or IL-13 signaling to interneurons decreased inhibitory, but not excitatory, cortical synapses. Conversely, ILC2s and IL-13 were sufficient to increase inhibitory synapses. Loss of this signaling pathway led to selective impairments in social interaction. These data define a type 2 neuroimmune circuit in early life that shapes inhibitory synapse development and behavior.

Importance: The prevalence estimates of physical activity, sedentary behavior, and sleep (collectively known as movement behaviors) in 3- and 4-year-old children worldwide remains uncertain., Objective: To report the proportion of 3- and 4-year-old children who met the World Health Organization guidelines for physical activity, sedentary behavior, and sleep across 33 countries., Design, Setting, and Participants: Pooled analysis of data from 14 cross-sectional studies (July 2008 to September 2022) identified through systematic reviews and personal networks. Thirty-three countries of varying income levels across 6 geographical regions. Each study site needed to have at least 40 children aged 3.0 to 4.9 years with valid accelerometry and parent-/caregiver-reported screen time and sleep duration data. Data were analyzed from October 2022 to February 2023., Exposures: Time spent in physical activity was assessed by reanalyzing accelerometry data using a harmonized data-processing protocol. Screen time and sleep duration were proxy reported by parents or caregivers., Main Outcomes and Measures: The proportion of children who met the World Health Organization guidelines for physical activity (≥180 min/d of total physical activity and ≥60 min/d of moderate- to vigorous-intensity physical activity), screen time (≤1 h/d), and sleep duration (10-13 h/d) was estimated across countries and by World Bank income group and geographical region using meta-analysis., Results: Of the 7017 children (mean [SD] age, 4.1 [0.5] years; 3585 [51.1%] boys and 3432 [48.9%] girls) in this pooled analysis, 14.3% (95% CI, 9.7-20.7) met the overall guidelines for physical activity, screen time, and sleep duration. There was no clear pattern according to income group: the proportion meeting the guidelines was 16.6% (95% CI, 10.4-25.3) in low- and lower-middle-income countries, 11.9% (95% CI, 5.9-22.5) in upper-middle-income countries, and 14.4% (95% CI, 9.6-21.1) in high-income countries. The region with the highest proportion meeting the guidelines was Africa (23.9%; 95% CI, 11.6-43.0), while the lowest proportion was in North and South America (7.7%; 95% CI, 3.6-15.8)., Conclusions and Relevance: Most 3- and 4-year-old children in this pooled analysis did not meet the current World Health Organization guidelines for physical activity, sedentary behavior, and sleep. Priority must be given to understanding factors that influence these behaviors in this age group and to implementing contextually appropriate programs and policies proven to be effective in promoting healthy levels of movement behaviors.

Liver regeneration (LR) is a unique biological process with the ability to restore up to 70% of the organ. This allows for the preservation of liver resections for various liver tumors and for living donor liver transplantation (LDLT). However, in some cases, LR is insufficient and interventions that can improve LR are urgently needed. Gut microbiota (GM) is one of the factors influencing LR, as the liver and intestine are intimately connected through the gut-liver axis. Thus, healthy GM facilitates normal LR, whereas dysbiosis leads to impaired LR due to imbalance of bile acids, inflammatory cytokines, microbial metabolites, signaling pathways, etc. Therefore, GM can be considered as a new possible therapeutic target to improve LR. In this review, we critically observe the current knowledge about the influence of gut microbiota (GM) on liver regeneration (LR) and the possibility to improve this process, which may reduce complication and mortality rates after liver surgery. Although much research has been done on this topic, more clinical trials and systemic reviews are urgently needed to move this type of intervention from the experimental phase to the clinical field., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The morphology of calcium oxalate monohydrate precipitates (COM, Ca(C 2 O 4 )·H 2 O, P2 1 /c, whewellite) occurring as crystals or intergrowths, as well as distribution of crystal-bearing idioblasts, have been studied for the first time in the bark of stone birch Betula ermanii from Sakhalin Island sampled in an area affected by mud volcanism and an unaffected typical forest environment taken for reference. The study addresses several issues (i) number and size of phytoliths and their distribution in different cell types; (ii) density of calcification in specific cells; (iii) habits of single crystals, twins, and complex intergrowths, as well as frequency of different morphologies and their relations. The trends of time-dependent morphological changes in separately analyzed crystals and intergrowths record the evolution of COM morphology from nuclei to mature grains. Of special interest are the nucleation sites and features of organic and inorganic seeds and nuclei for COM phytoliths. The precipitation process and crystal habits are mainly controlled by supersaturation, and it is thus important to constrain the Ca distribution patterns in different bark tissues. The B. ermanii samples were analyzed by several methods: scanning electron microscopy (SEM) for the distribution patterns and micromorphology of COM precipitates and bulk Ca content in bark; electron probe microanalysis (EPMA) for the mineral chemistry of COM precipitates; inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS) for trace elements in bulk bark and wood. RESEARCH HIGHLIGHTS: The distribution and morphology of whewellite precipitates in the analyzed B. ermanii bark samples indicate that the aqueous solution was most strongly supersaturated with respect to the Ca(C 2 O 4 )·H 2 O solid phase at the parenchyma-sclerenchyma boundary, where most of the COM spherulites are localized and often coexist with large single crystals and contact COM twins., (© 2024 Wiley Periodicals LLC.)

Background and Aims: It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms., Approach and Results: Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD ( p = 1.1 × 10 -4 ). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 ( p = 8.05 × 10 -10 ) and FNBP1 ( p = 4.74 × 10 -9 ); suggestive, DUSP6 ( p = 1.51 × 10 -7 ) and ANKUB1 ( p = 4.69 × 10 -7 )] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [ CXCR1 ( p = 1.01 × 10 -6 ) , AAMP ( p = 1.07 × 10 -6 ), and TRBV24 ( p = 1.23 × 10 -5 )] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies., Conclusion: These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Purpose: The Social Responsiveness Scale (SRS) is frequently used in research settings to measure characteristics associated with autism spectrum disorders (ASD). A short version has been developed but not yet tested for certain properties of the full SRS, such as familiality. The purpose of this study was to determine if prior familiality findings for the full SRS can be replicated using the short form by measuring the associations of the parental Social Responsiveness Scale-Short Form (SRS-SF) scores with child ASD diagnoses and child SRS-SF scores., Methods: We used a nested case-control study within a longitudinal cohort study design. Participants were selected from the Nurses' Health Study II (NHS II). Cases were children of study participants who had been diagnosed with ASD, while controls had not been diagnosed with ASD and were frequency matched by year of birth to cases. 2144 out of 3161 eligible participants returned SRS forms for a child and at least one parent. Participants in NHS II completed SRS forms for their spouses and spouses completed SRS forms for NHS II participants. Parental SRS-SF scores were based on a subset of 16 questions from the SRS. ASD diagnosis among children was reported by the mothers and validated in a subset using the Autism Diagnostic Interview-Revised, as well as child SRS-SF scores., Results: Children whose parents both had elevated SRS-SF scores (those in the top 20% of the study distribution) had a higher odds of ASD diagnosis than those who did not have elevated parental scores (OR 2.25; 95% CI 1.41, 3.58). Additionally, children whose fathers had elevated SRS-SF scores had a higher odds of ASD diagnosis (OR 2.18; 95% CI 1.60, 2.97) than those whose fathers scores were not elevated. In sex-stratified analyses, male children with elevated parental SRS-SF scores had a higher odds of ASD diagnosis than those who did not have elevated parental scores. These associations were not as evident among female children. Parental SRS-SF scores also predicted child SRS-SF scores among controls., Conclusion: These findings are similar to prior findings for the full SRS and support the ability of the SRS-SF to capture familiality of ASD-related traits., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With increasing clinical applications and interest in targeted alpha therapy, there is growing interest in developing alternative chelating agents for [ 212 Pb]Pb 2+ and [ 212/213 Bi]Bi 3+ that exhibit rapid radiolabeling kinetics and kinetic inertness. Herein we report the synthesis and detailed investigation of diacetate and dipicolinate 18- and 21-membered macrocyclic chelators BADA-18, BADA-21, BADPA-18, and BADPA-21 for the complexation of Pb 2+ and Bi 3+ ions with potential use in the preparation of radiopharmaceuticals. The formation of mononuclear complexes was established by using ESI-mass spectrometry, and their stability constants were determined by potentiometric titration. A thorough study of the structure of the metal complexes was carried out by using X-ray diffraction and NMR spectroscopy. It was shown how the stability of the complex is influenced by an increase in the size of the macrocycle, the replacement of acetate arms with picolinate ones, the rigidity of the ligand, as well as the type of conformation ( syn - or anti -) of the metal complex. The new ligands were radiolabeled with [ 210 Pb]Pb 2+ and [ 207 Bi]Bi 3+ , and the in vitro stability of the resulting complexes in a competitive environment of serum and biologically significant metal ions was assessed. Rapid complex formation in 1-2 min at room temperature, as well as the high kinetic inertness of the complexes Pb(BADPA-18) and Bi(BADPA-18) in biological media, demonstrate its potential for use in targeted radionuclide therapy.

Molecular studies identifying alterations associated with PTSD have predominantly focused on candidate genes or conducted genome-wide analyses, often encountering issues with replicability. This review aims to identify robust bi-directional epigenetic and microRNA (miRNA) regulators focusing on their functional impacts on post-traumatic stress disorder (PTSD) and their utility in clinical diagnosis, whilst examining knowledge gaps in the existing research. A systematic search was conducted across multiple databases, including Web of Science, Scopus, Global Health (CABI), and PubMed, augmented by grey literature, yielding 3465 potential articles. Ultimately, 92 studies met the inclusion criteria and were analysed to pinpoint significant epigenetic changes with clinically relevant potential in PTSD. The selected studies explored histone modifications, CpG sites, single nucleotide polymorphisms (SNPs), and miRNA biomarkers. Specifically, nine studies examined epigenetic markers, detailing the influence of methylation on chromatin accessibility at histone positions H3K4, H3K9, and H3K36 within a PTSD context. Seventy-three studies investigated DNA methylation, identifying 20 hypermethylated and five hypomethylated CpG islands consistently observed in PTSD participants. Nineteen studies linked 88 SNPs to PTSD, with only one SNP replicated within these studies. Furthermore, sixteen studies focused on miRNAs, with findings indicating 194 downregulated and 24 upregulated miRNAs were associated with PTSD. Although there are epigenetic mechanisms that are significantly affected by PTSD, a granular deconstruction of these mechanisms elucidates the need to incorporate more nuanced approaches to identifying the factors that contribute to PTSD. Technological advances in diagnostic tools are driving the need to integrate detailed participant characteristics, trauma type, genetic susceptibilities, and best practices for robust reporting. This comprehensive approach will be crucial for enhancing the translational potential of PTSD research for clinical application.

Objective: Cannabis is increasingly the first substance used by young people and research indicates that cannabis use may precede the onset of tobacco use. Little is known, however, about the role of cannabis use in stages of electronic nicotine delivery systems (ENDS) uptake and progression across young adulthood. This study examined the associations between past 30-day (P30D) cannabis use frequency and transitions in ENDS use among young adults., Methods: 5,018 18-29-year-olds (64.2% female) were recruited from 24 Texas colleges to participate in a multi-wave study across a 4.5-year period from 2014 to 2019. A continuous time, multi-state Markov model was used to assess associations between P30D cannabis use frequency and three ENDS use transitions, spanning at least six months 1) never to P30D use (initiation); 2) P30D to non-P30D use (desistance); and 3) non-P30D to P30D use (re-uptake). The model also included socio-demographic and time-varying intrapersonal (other tobacco use, alcohol use, sensation seeking, depressive symptoms) and interpersonal (peer ENDS use) confounding factors., Results: Past 30-day cannabis use frequency was associated with an increased probability of ENDS initiation and decreased probability of desistance in the model adjusted for socio-demographic and confounding factors. Past 30-day cannabis use frequency was not associated with an increased probability of ENDS re-uptake in the adjusted model., Conclusions: Cannabis use is associated with the uptake and continuation of ENDS use. Findings are concerning given that the most popular ENDS devices used by young adults contain high concentrations of nicotine that increase the risk for nicotine dependence and lifelong use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Branched-chain amino acids (BCAAs) play an important role in the functioning of mammalian cells and the central nervous system. However, available genetically encoded indicators for BCAAs are based on Förster resonance energy transfer and have a limited dynamic range. We developed a single fluorescent protein-based sensor for BCAAs, called NeIle, which is composed of circularly permutated mNeonGreen protein inserted into the leucine-isoleucine-valine binding protein (LIVBP) from Escherichia coli bacteria. In solution, the NeIle indicator displayed a positive fluorescence response to adding isoleucine, leucine, and valin amino acids with high Δ F / F dynamic ranges of 27-, 19-, and 11-fold and the corresponding affinity values of 5.0, 2.9, and 75 mM, respectively. The spectral and biochemical properties of the NeIle indicator were characterized in solution. We characterized the brightness of the NeIle indicator in living mammalian cells, including cultured neurons. Using the NeIle indicator, we successfully visualized the dynamics of isoleucine transients in different organelles of mammalian cells. We obtained and analyzed the X-ray crystal structure of the NeIle indicator in an isoleucine-bound state. Structure-guided directed mutagenesis of the NeIle indicator revealed the basis of its fluorescence response and selectivity to isoleucine.

Introduction: The mechanisms of the SARS-CoV-2-triggered complex alterations in immune cell activation and production of cytokines in lung tissue remain poorly understood, in part because of the limited use of adequate tissue models that simulate the structure and cell composition of the lung in vivo . We developed a novel ex vivo model of SARS-CoV-2 infection of lung explants, that maintains the intact tissue composition and the viral load for up to 7-10 days. Using this model, we studied cytokine production during SARS-CoV-2 infection., Materials and Methods: Lung tissue was monitored for viability and cell composition using flow cytometry and histological analysis. SARS-CoV-2 infection was verified immunohistochemically, viral loads in tissue and culture medium were monitored by qPCR. A panel of 41 cytokines was measured in culture medium using xMAP technology., Results: The explant lung tissue was viable and maintained viral infection that influenced the cytokine production. Elevated concentrations of G-CSF, GM-CSF, GRO-a, IFN-g, IL-6, IL-8, IP-10, MCP-3, MIP-1a, PDGF-AA, and VEGF, and decreased IL-1RA concentration were observed in infected tissue compared to non-infected tissue., Discussion: Our results generally reflect the data obtained in COVID-19 patients. GRO-a, IFN-g, IL-6, IL-8, MCP-1, MCP-3, and RANTES correlated with the viral load, forming a distinct pro-inflammatory cluster. Thus, our lung ex vivo model faithfully reproduces some aspects of cytokine alterations in COVID-19 patients at an early disease stage, making the investigation of SARS-CoV-2 infection mechanisms more accessible and providing a potential platform for antiviral drug testing., Competing Interests: Authors AP and FR were employed by HyTest Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vorobyeva, Potashnikova, Maryukhnich, Rusakovich, Tvorogova, Kalinskaya, Pinegina, Kovyrshina, Dolzhikova, Postnikov, Rozov, Sotnikova, Kanner, Logunov, Gintsburg, Vasilieva and Margolis.)

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased., Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT)., Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage., Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain., Competing Interests: A.A.I., I.V.K., M.E.F., A.V.K., and A.V.V. have author’s rights to the patents RU2749193 and RU2795160 (registered by Betuvax). E.A.R.-R. and M.A.S. had received payment from the company Betuvax for providing the experiment. A.A.I., I.V.K., M.E.F., A.V.K., A.V.V., and T.V.I. are shareholders of Betuvax. A.V.V., T.V.I., M.M.S., and K.S.K. are employees of Betuvax. A.A.I., as the founder of Artgen Biotech, provided the funding, participated in the design of this study, and in the decision to publish the results. The funders participated in the design of this study, the writing of the manuscript, and the decision to publish the results.

Annulated azecines, mostly partially saturated benzo[d]azecine and dibenzo[c,g]azecine fusion isomers, constitute a unique class of alkaloids and nature-inspired azaheterocyclic compounds with interesting reactivity, physicochemical and biological properties. Due to difficulties associated with the synthesis of the benzazecine (or bioisosteric) scaffold they are not the focus of organic and medicinal chemists' consideration, whereas it is worth noting the range of their pharmacological activities and their potential application in medicinal chemistry. Herein, we reviewed the synthetic methodologies of arene-fused azecine derivatives known up to date and reported about the progress in disclosing their potential in drug discovery. Indeed, their conformational restriction or liberation drives their selectivity towards diverse biological targets, making them versatile scaffolds for developing drugs, including antipsychotic and anticancer drugs, but also small molecules with potential for anti-neurodegenerative treatments, as the recent literature shows., Competing Interests: Declaration of competing interest On behalf of all the co-authors, I declare that the authors of the manuscript entitled “Advances in synthesis of novel benzazecines and their unique pharmacological properties” have no competing interests to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

In the presence of temporally organized stimuli, there is a tendency to entrain to the beat, even at the neurological level. Previous research has shown that when adults listen to rhythmic stimuli and are asked to imagine the beat, their neural responses are the same as when the beat is physically accented. The current study explores the neural processing of simple beat structures where the beat is physically accented or inferred from a previously presented physically accented beat structure in a passive listening context. We further explore the associations of these neural correlates with behavioral and self-reported measures of musicality. Fifty-seven participants completed a passive listening EEG paradigm, a behavioral rhythm discrimination task, and a self-reported musicality questionnaire. Our findings suggest that when the beat is physically accented, individuals demonstrate distinct neural responses to the beat in the beta (13-23 Hz) and gamma (24-50 Hz) frequency bands. We further find that the neural marker in the beta band is associated with individuals' self-reported musical perceptual abilities. Overall, this study provides insights into the neural correlates of spontaneous beat processing and its connections with musicality., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Scartozzi et al.)

Cloudberry ( Rubus chamaemorus L .) is a plant rich in various biologically active compounds. In this work, the composition and concentrations of pentacyclic triterpenoids (PCTs) and phytosterols in various parts of cloudberries were studied using high-performance liquid chromatography-tandem mass spectrometry by multiple reaction monitoring mode (MRM, targeted analysis) and precursor ion scan mode (non-targeted analysis and semi-quantitative determination). Moderately polar fractions of cloudberry leaves, sepals and berries extracts are rich in β-sitosterol glycoside and various triterpenoid acids, among which tormentic acid (∼190-1800 μg/g dw part of cloudberries) and its hydroxyl derivatives (∼3.1-470 μg/g dw part of cloudberries) predominate. Non-polar fractions are characterised by the presence of amyrins (0.76-110 μg/g dw part of cloudberries), β-sitosterol (62-750 µg/g dw part of cloudberries) and β-sitosterol glycoside (∼92-360 μg/g dw sepals).

Background: Many bacteria are capable of reducing selenium oxyanions, primarily selenite (SeO 3 2- ), in most cases forming selenium(0) nanostructures. The mechanisms of these transformations may vary for different bacterial species and have so far not yet been clarified in detail. Bacteria of the genus Azospirillum , including ubiquitous phytostimulating rhizobacteria, are widely studied and have potential for agricultural biotechnology and bioremediation of excessively seleniferous soils, as they are able to reduce selenite ions., Methods: Cultures of A.brasilense Sp7 and its derivatives (mutant strains) were grown on the modified liquid malate salt medium in the presence or absence of selenite. The following methods were used: spectrophotometric monitoring of bacterial growth; inhibition of glutathione (GSH) synthesis in bacteria by L-buthionine-sulfoximine (BSO); optical selenite and nitrite reduction assays; transmission electron microscopy of cells grown with and without BSO and/or selenite., Results: In a set of separate comparative studies of nitrite and selenite reduction by the wild-type strain A.brasilense Sp7 and its three specially selected derivatives (mutant strains) with different rates of nitrite reduction, a direct correlation was found between their nitrite and selenite reduction rates for all the strains used in the study. Moreover, for BSO it has been shown that its presence does not block selenite reduction in A.brasilense Sp7., Conclusions: Evidence has been presented for the first time for bacteria of the genus Azospirillum that the denitrification pathway known to be inherent in these bacteria, including nitrite reductase, is likely to be involved in selenite reduction. The results using BSO also imply that detoxification of selenite through the GSH redox system (which is commonly considered as the primary mechanism of selenite reduction in many bacteria) does not play a significant role in A.brasilense . The acquired knowledge on the mechanisms underlying biogenic transformations of inorganic selenium in A.brasilense is a step forward both in understanding the biogeochemical selenium cycle and to a variety of potential nano- and biotechnological applications., (© 2024 The Author(s). Published by IMR Press.)

Hydrogen peroxide (H 2 O 2 ) in plants is produced in relatively large amounts and plays a universal role in plant defense and physiological responses, including the regulation of growth and development. In the Rhizobium -legume symbiosis, hydrogen peroxide plays an important signaling role throughout the development of this interaction. In the functioning nodule, H 2 O 2 has been shown to be involved in bacterial differentiation into the symbiotic form and in nodule senescence. In this study, the pattern of H 2 O 2 accumulation in pea ( Pisum sativum L.) wild-type and mutant nodules blocked at different stages of the infection process was analyzed using a cytochemical reaction with cerium chloride. The observed dynamics of H 2 O 2 deposition in the infection thread walls indicated that the distribution of H 2 O 2 was apparently related to the stiffness of the infection thread wall. The dynamics of H 2 O 2 accumulation was traced, and its patterns in different nodule zones were determined in order to investigate the relationship of H 2 O 2 localization and distribution with the stages of symbiotic nodule development in P. sativum . The patterns of H 2 O 2 localization in different zones of the indeterminate nodule have been partially confirmed by comparative analysis on mutant genotypes.

Background: Ontologies are fundamental components of informatics infrastructure in domains such as biomedical, environmental, and food sciences, representing consensus knowledge in an accurate and computable form. However, their construction and maintenance demand substantial resources and necessitate substantial collaboration between domain experts, curators, and ontology experts. We present Dynamic Retrieval Augmented Generation of Ontologies using AI (DRAGON-AI), an ontology generation method employing Large Language Models (LLMs) and Retrieval Augmented Generation (RAG). DRAGON-AI can generate textual and logical ontology components, drawing from existing knowledge in multiple ontologies and unstructured text sources., Results: We assessed performance of DRAGON-AI on de novo term construction across ten diverse ontologies, making use of extensive manual evaluation of results. Our method has high precision for relationship generation, but has slightly lower precision than from logic-based reasoning. Our method is also able to generate definitions deemed acceptable by expert evaluators, but these scored worse than human-authored definitions. Notably, evaluators with the highest level of confidence in a domain were better able to discern flaws in AI-generated definitions. We also demonstrated the ability of DRAGON-AI to incorporate natural language instructions in the form of GitHub issues., Conclusions: These findings suggest DRAGON-AI's potential to substantially aid the manual ontology construction process. However, our results also underscore the importance of having expert curators and ontology editors drive the ontology generation process., (© 2024. The Author(s).)

Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives . We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions . It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families ( Pasteurellaceae, Barnesiellaceae, Eubacteriaceae ) was observed.

The division of a cellular compartment culminates with the scission of a highly constricted membrane neck. Scission requires lipid rearrangements, topology changes, and transient formation of nonbilayer intermediate structures driven by curvature stress. Often, a side effect of this stress is pore-formation, which may lead to content leakage and thus breaching of the membrane barrier function. In single-membrane systems, leakage is avoided through the formation of a hemifusion (HF) intermediate, whose structure is still a subject of debate. The consequences of curvature stress have not been explored in double-membrane systems, such as the mitochondrion. Here, we combine experimental and theoretical approaches to study neck constriction and scission driven by tension in biomimetic lipid systems, namely single- and double-membrane nanotubes (sNTs and dNTs), respectively. In sNTs, constriction by high tension gives rise to a metastable HF intermediate (seen as stalk or worm-like micelle), whereas poration is universally slower in a simple neck. In dNTs, high membrane tension causes sequential rupture of each membrane. In contrast, low tension leads to the HF of both membranes, which may lead to a leaky fusion pathway, or may progress to further fusion of the two membranes along a number of transformation pathways. These findings provide a new mechanistic basis for fundamental cellular processes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Here we present the biological properties of the arylbipyridine platinum (II) complex (arylbipy-Pt) and describe the potential mechanism of its antitumor action which differs from that of the well-known cisplatin. Leading to the oxidative stress and lipid peroxidation, the arylbipyridine platinum (II) complex showcases the significant cytotoxicity against the glioblastoma cells as shown by the MTT test. Using the 5-ethyl-2-deoxyuridine we study the proliferative activity of glioblastoma cells to affirm that arylbipyridine platinum (II) complex does not impede cell division or DNA replication. Staining by the MitoCLox dye and 2',7'-dichlorodihydrofluorescein diacetate demonstrates that the glioblastoma cells treated with arylbipy-Pt exhibit a strong increase of the lipid peroxidation and the stimulation of the reactive oxygen species formation. The hypothesis that arylbipy-Pt promotes oxidative death of tumor cells is confirmed by control experiments using N-acetyl-L-cysteine as an antioxidant. Further evidence for the oxidative mechanism of action is provided by real-time PCR, which shows high expression levels for genes associated with the heat shock proteins HSP27 and HSP70, which can be used as markers of tumor cell ferroptosis. To elucidate the chemical nature of the arylbipy-Pt complex activity, we perform 195 Pt NMR spectroscopy and cyclic voltammetry measurements under biologically relevant conditions. The results obtained clearly indicate the structural transformation of the arylbipy-Pt complex in the DMSO-saline mixture, which is crucial for its further antitumor activity via the oxidative pathway. The found correlation between the molecular structure of arylbipy-Pt and its effect on the tumor cell cycle paves the way for the rational design of Pt complexes possessing the alternative mechanism of antitumor activity as compared to DNA intercalation, providing possible solutions to the major problems such as toxicity and drug resistance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

A comparative study of the copolymerization of racemic propylene oxide (PO) with CO 2 catalyzed by racemic (salcy)CoX (salcy = N , N '-bis(3,5-di- tert -butylsalicylidene)-1,2-diaminocyclohexane; X = perfluorobenzoate (OBzF 5 ) or 2,4-dinitrophenoxy (DNP)) in the presence of a [PPN]Cl ([PPN] = bis(triphenylphosphine)iminium) cocatalyst is performed in bulk at 21 °C and a 2.5 MPa pressure of CO 2 . The increase in the nucleophilicity of an attacking anion results in the increase in the copolymerization rate. Racemic (salcy)CoX provides a high selectivity of the copolymerization, which can be higher than 99%, and the living polymerization mechanism. Poly(propylene carbonate) (PPC) with bimodal molecular weight distribution (MWD) is formed throughout copolymerization. Both modes are living and are characterized by low dispersity, while their contribution to MWD depends on the nature of the attacking anion. The racemic (salcy)CoDNP/[PPN]DNP system is found to be preferable for the production of PPC with a high yield and selectivity.

Introduction: This study at the University of South Carolina School of Medicine Greenville examines medical students' preferences and concerns regarding exam scheduling, focusing on the schedule's impact on student academic performance and well-being., Methods: A cross-sectional survey was administered to second, third, and fourth year medical students, receiving a 53% response rate. The survey, consisting of 11 multiple-choice questions and one open-ended question, assessed preferences for exam days, weeks, sequence of different types of exams, and the timing of schedule releases., Results: Evaluation using descriptive statistics and thematic analysis revealed a strong preference for scheduling Biomedical Science (BMS) exams on Fridays, avoiding weeks with holidays, and separating BMS exams from Integrated Practice of Medicine (IPM) assessments. Students reported that concurrent IPM content delivery during BMS exam weeks negatively impacted their academic performance. Additionally, there was a significant demand for early release of exam schedules to better manage work-life balance., Discussion: These findings highlight the critical role of exam scheduling in influencing medical students' academic success and overall well-being, suggesting the need for early communication of schedules and equitable assessment planning., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Funkhouser and Blenda.)

Objective: Multidrug-resistant, highly pathogenic Escherichia coli strains are the primary causative agents of intestinal and extraintestinal human diseases. The extensive utilization of antibiotics for farm animals has been identified as a contributing factor to the emergence and dissemination of E. coli strains that exhibit multidrug resistance and possess high pathogenic potential. Consequently, a significant research objective is to examine the genetic diversity of pathogenic E. coli strains and to identify those that may pose a threat to human health. Methods: In this study, we present the results of genome sequencing and analysis, as well as the physiological characterization of E. coli strain APEC 36, which was isolated from the liver of a broiler chicken with generalized colibacillosis. Results: We found that APEC 36 possess a number of mechanisms of antibiotic resistance, including antibiotic efflux, antibiotic inactivation, and antibiotic target alteration/replacement/protection. The most widely represented group among these mechanisms was that of antibiotic efflux. This finding is consistent with the strain's documented resistance to multiple antibiotics. APEC 36 has an extremely rare variant of the beta-lactamase CTX-M-169. Notwithstanding the multitude of systems for interfering with foreign DNA present in the strain, seven plasmids have been identified, three of which may possess novel replication origins. Additionally, qnrS1 , which confers resistance to fluoroquinolones, was found to be encoded in the genome rather than in the plasmid. This suggests that the determinants of antibiotic resistance may be captured in the genome and stably transmitted from generation to generation. Conclusions: The APEC 36 strain has genes for toxins, adhesins, protectins, and an iron uptake system. The obtained set of genetic and physiological characteristics allowed us to assume that this strain has a high pathogenic potential for humans.

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant., Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5., Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant., Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus.

Binary and ternary copolymers of acrylonitrile (AN), tert -butyl acrylate (TBA), and n -butyl acrylate (BA) are synthesized through conventional radical polymerization in DMSO in the presence of 2-mercaptoethanol. The thermal behavior of binary and ternary copolymers is studied under argon atmosphere and in air. It is demonstrated that the copolymers of AN contain 1-10 mol.% of TBA split isobutylene upon heating above 160 °C, resulting in the formation of the units of acrylic acid in the chain. The carboxylic groups formed in situ are responsible for the ionic mechanism of cyclization, which starts at lower temperatures compared with pure polyacrylonitrile (PAN) or AN copolymer with BA. The activation energy of cyclization through ionic and radical mechanisms depends on copolymer composition. For the ionic mechanism, the activation energy lies in the range ca. 100-130 kJ/mole, while for the radical mechanism, it lies in the range ca. 150-190 kJ/mole. The increase in the TBA molar part in the copolymer is followed by faster consumption of nitrile groups and the evolution of a ladder structure in both binary and ternary copolymers. Thus, the incorporation of a certain amount of TBA in PAN or its copolymer with BA allows tuning the temperature range of cyclization. This feature seems attractive for applications in the production of melt-spun PAN by choosing the appropriate copolymer composition and heating mode.

To identify modifier loci underlying variation in body mass index (BMI) in persons with cystic fibrosis (pwCF), we performed a genome-wide association study (GWAS). Utilizing longitudinal height and weight data, along with demographic information and covariates from 4,393 pwCF, we calculated AvgBMIz representing the average of per-quarter BMI Z scores. The GWAS incorporated 9.8M single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) > 0.005 extracted from whole-genome sequencing (WGS) of each study subject. We observed genome-wide significant association with a variant in FTO (FaT mass and Obesity-associated gene; rs28567725; p value = 1.21e-08; MAF = 0.41, β = 0.106; n = 4,393 individuals) and a variant within ADAMTS5 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 5; rs162500; p value = 2.11e-10; MAF = 0.005, β = -0.768; n = 4,085 pancreatic-insufficient individuals). Notably, BMI-associated variants in ADAMTS5 occur on a haplotype that is much more common in African (AFR, MAF = 0.183) than European (EUR, MAF = 0.006) populations (1000 Genomes project). A polygenic risk score (PRS) calculated using 924 SNPs (excluding 17 in FTO) showed significant association with AvgBMIz (p value = 2.2e-16; r 2  = 0.03). Association between variants in FTO and the PRS correlation reveals similarities in the genetic architecture of BMI in CF and the general population. Inclusion of Black individuals in whom the single-gene disorder CF is much less common but genomic diversity is greater facilitated detection of association with variants that are in LD with functional SNPs in ADAMTS5. Our results illustrate the importance of population diversity, particularly when attempting to identify variants that manifest only under certain physiologic conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor with very poor prognosis due to frequent recurrence and short overall survival (OS) time, which according to different sources, is not longer than 17 months after the diagnosis. Infiltrative growth pattern often leads to tumor propagation into functionally significant brain areas while surgery is cytoreductive and does not necessarily alter the prognosis. Many patients are in the working age, thus finding conservative approaches to the treatment of this type of neoplasms is of utmost importance. The aim of the work is to demonstrate the effectiveness of treatment of GBM using cytokine genetic therapy (CGT) and present an algorithm for patient management., Case Description: This paper describes the first case of successful intra-arterial (IA) bevacizumab therapy with following CGT of a 46-year-old patient with recurrent GBM after a combined treatment. Sixteen courses of 15 mg/kg IA bevacizumab with hyperosmolar opening of blood-brain barrier (BBB) resulted in stabilization of the neoplastic process. After that, 9 courses of CGT with recombinant interferon gamma (IFN-γ) and tumor necrosis factor (TNF)-thymosin α1 were performed. Both magnetic resonance imaging (MRI) with contrast and positron emission tomography (PET) confirmed a complete response to the combined treatment. OS time is currently more than 25 months from the diagnosis. The observation continues., Conclusions: This case study expands the range of treatment options for GBM, especially in the context of intolerance and high toxicity of cytostatic drugs, and may lead to improved recurrence-free survival (RFS).

Despite extensive Salmonella controls used at processing, 5.5% of salmonellosis cases are linked to turkey. This study had two objectives: (i) to summarize USDA-FSIS turkey Salmonella verification program data and (ii) to evaluate Salmonella through turkey production and processing of 22 flocks. In objective 1, USDA-FSIS data show the average Salmonella prevalence in ground turkey from 2016 to 2022 was 15.9%, and that the leading serovar changes frequently. For objective 2, bootsocks (n = 22) were collected on-farm right after load-out. At processing, prescald wingtips (n = 6 composites of 10/flock), prechill wingtips (n = 6 composites of 10/flock), mechanically separated turkey (MST; n = 6 bins/flock), and ground turkey (n = 6 bins/flock) were collected. Salmonella prevalence was determined by a commercial qPCR and culture confirmed. In 33.2% of PCR-positive samples, Salmonella was not confirmed by culture, highlighting a discrepancy between molecular and culture detection. On-farm, 8/22 flocks were Salmonella positive, compared to 21 flocks that were positive at one or more processing locations, including 18 flocks that were positive in at least one final product sample. A logistic regression showed higher Salmonella prevalence in prescald (53.8%) than in prechill (18.2%), MST (27.3%) or ground turkey (26.5%). CRISPR-SeroSeq analysis of 148 culture-positive samples detected 18 Salmonella serovars and showed 35.1% of samples contained multiple serovars. In 16 flocks, one or more serovars detected in final products were absent from any upstream samples. Two-thirds of final product samples containing serovar Typhimurium typed as a live-attenuated Typhimurium vaccine strain. Salmonella on-farm and at prescald did not reflect Salmonella observed in final product. These data underscore the complexity of serovar tracking in turkey production and highlight challenges to identify surveillance samples that accurately represent Salmonella in turkey products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: “Nikki W. Shariat reports financial support was provided by US Poultry and Egg Association. Anna V. Carlson reports a relationship with Cargill Inc that includes: employment. Angela L. Siemens reports a relationship with Cargill Inc that includes: employment. Nikki W. Shariat has patent pending to University of Georgia Research Foundation. University of Georgia Research Foundation has licensed CRISPR-SeroSeq to Ancera − N.W.S. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”, (Copyright © 2024. Published by Elsevier Inc.)

Intracardiac tumors, though uncommon, necessitate a swift and accurate diagnosis for personalized treatment and prognosis estimation. While multi-modality imaging often determines the etiology of these cardiac masses, histological confirmation remains essential for definitive diagnosis and its specific treatment. Since cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount. The least invasive strategy would be to achieve this by means of endomyocardial biopsy (EMB); however real-time additional imaging is essential to reduce the risk of perforation/tamponade and to minimize sampling error. Intracardiac echocardiography (ICE) emerges as an excellent tool to achieve this goal preventing procedural complications and reducing the likelihood of sampling errors obtaining a definitive histopathological diagnosis in all cases. This paper outlines our diagnostic algorithm for optimal patient selection, details three illustrative cases, and elucidates the steps to acquire histopathology via percutaneous transvenous biopsy with ICE guidance in patients with right-sided cardiac tumors. Given the rarity of intracardiac tumors, we advocate these patients be managed by a dedicated multidisciplinary cardio-oncology team including an interventional cardiologist., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Objective: Glutamic acid decarboxylase, an enzyme in GABA biosynthesis, is encoded by the GAD1 gene, the transcriptional activity of which is affected by the rs3749034 polymorphism. The aim was to investigate the effects of rs3749034 on cognitive event-related potentials (P300) in healthy subjects and schizophrenic patients., Methods: Determination of rs3749034 polymorphism was performed in 89 healthy volunteers and 109 schizophrenic patients (males). Two-stimulus oddball task performance and P300 auditory evoked potentials were analyzed and patient symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS)., Results: An increased frequency of C allele carriers was disclosed in patients. In controls, superior task performance was observed in cytosine-thymine carriers, while a greater P300 amplitude and shorter latency were found in C/C carriers. Analogous effects were found in patients with a disease onset before 25 years of age. Higher N5 and lower P3 and G5 PANSS scales were revealed in C/C homozygotes., Conclusions: The findings substantiate an involvement of GABA-ergic mechanisms in maintaining an optimal excitatory-inhibitory balance and an association of rs3749034 with early-onset disorder and negative symptoms of schizophrenia., Significance: These results are important for understanding underlying mechanisms and the development of evidence-based methods for assessing the risk of schizophrenia., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Post-transcriptional mechanisms are fundamental safeguards of progenitor cell identity and are often dysregulated in cancer. Here, we identified regulators of P-bodies as crucial vulnerabilities in acute myeloid leukaemia (AML) through genome-wide CRISPR screens in normal and malignant haematopoietic progenitors. We found that leukaemia cells harbour aberrantly elevated numbers of P-bodies and show that P-body assembly is crucial for initiation and maintenance of AML. Notably, P-body loss had little effect upon homoeostatic haematopoiesis but impacted regenerative haematopoiesis. Molecular characterization of P-bodies purified from human AML cells unveiled their critical role in sequestering messenger RNAs encoding potent tumour suppressors from the translational machinery. P-body dissolution promoted translation of these mRNAs, which in turn rewired gene expression and chromatin architecture in leukaemia cells. Collectively, our findings highlight the contrasting and unique roles of RNA sequestration in P-bodies during tissue homoeostasis and oncogenesis. These insights open potential avenues for understanding myeloid leukaemia and future therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Changes in the immune status and the content of blood transport components reflect adaptations in the human body in response to adverse factors, showcasing the organism's adaptive capabilities and functional state. In this study, we aimed to determine the features of the immune system and levels of transport components of the blood system in residents of the Arctic of the Russian Federation., Methods: The peripheral venous blood of 191 residents of the Arctic of the Russian Federation (Murmansk Oblast) aged 21-55 analyzed comprehensively. Blood was sampled from the ulnar vein on an empty stomach in the morning. The hemogram, phagocytic activity of neutrophils, lymphocyte content with CD3, CD4, CD8, CD10, CD19, CD16, CD71, CD25, HLA-DR and CD95 phenotypes, concentrations of cytokines: TNF-α, IFN-γ, IL-6, IL-10, extracellular receptor pool: sCD71, sCD62L, sApo-1/Fas, sFasL, circulating immune complexes (CIC) and blood transport components: haptoglobin (Hp), transferrin, IgM, IgG, IgA, IgE (immunoglobulins M, G, A and E) low-density lipoproteins (LDL), and high density lipoprotein (HDL) were evaluated. The results were analyzed using descriptive statistics and comparative, factorial, and regression analyses., Results: Residents of the Murmansk Oblast exhibit a high prevalence of erythrocytosis (62.3%), thrombocytosis (25.0%), leukocytosis (20.1%), and increased hemoglobin (Hb) concentrations (42.5%), coupled with a significantly decreased level of active phagocytes (47.6%). A significantly decreased level of lymphocytes with phenotypes CD3 (92.4%), CD4 (40.4%), CD71 (62.3%) was revealed, coupled with the activation of lymphocytes with phenotypes CD16 (50.1%), CD8 (37.5%), CD19 (15.9%) and increased concentrations of pro-inflammatory IFN-γ (47.9%), IL-6 (33.3%), and TNF-α (20.1%). Elevated levels of sCD71 (56.6%), sCD62L (32.1%), sApo-1/Fas (22.1%), sFasL (10.2%), and autoantibodies to double-stranded DNA (57.1%), RNA (10.4%), and oLDL (oxidized-modified LDL) (16.3%) were recorded in residents of the Murmansk Oblast. Arctic residents showed elevated concentrations of Hp (63.3%), IgM (63.9%), IgA (42.4%), IgE (18.8%), LDL (24.9%), and a decreased level of HDL (21.1%) owing to an ApoA-I ligand deficiency (58.1%). Elevated levels of Hp in the blood are associated with increased erythrocyte aggregation frequency, T-lymphocyte activation, and increased concentration of free receptors of the extracellular pool. Increased IgM and IgA levels in the blood are attributed to the need to bind components of the extracellular receptor pool sCD71, sCD62L, sApo-1/Fas, sFasL and are associated with decreased levels lymphocyte with CD8 and CD16 phenotypes. The humoral immune response in Arctic residents is triggered when the cellular component of immunity is under strain which compounded by ineffective clearance of metabolic byproducts owing to imbalanced LDL and HDL lipid transport complexes., Conclusions: The immune system of Arctic residents is characterized by excessive cytotoxic activity of lymphocytes and increased concentrations of pro-inflammatory cytokines, free forms of receptors of the extracellular pool, and autoantibodies. The change in the content of transport components of the blood system is directed at maintaining homeostasis by exhibiting antioxidant, anti-inflammatory, and immunoregulatory properties., (© 2024 Wiley Periodicals LLC.)

Platyhelminthes, also known as flatworms, is a phylum of bilaterian invertebrates infamous for their parasitic representatives. The classes Cestoda, Monogenea, and Trematoda comprise parasitic helminths inhabiting multiple hosts, including fishes, humans, and livestock, and are responsible for considerable economic damage and burden on human health. As in other animals, the genomes of flatworms have a wide variety of paralogs, genes related via duplication, whose origins could be mapped throughout the evolution of the phylum. Through in-silico analysis, we studied inparalogs, i.e., species-specific duplications, focusing on their biological functions, expression changes, and evolutionary rate. These genes are thought to be key players in the adaptation process of species to each particular niche. Our results showed that genes related with specific functional terms, such as response to stress, transferase activity, oxidoreductase activity, and peptidases, are overrepresented among inparalogs. This trend is conserved among species from different classes, including free-living species. Available expression data from Schistosoma mansoni, a parasite from the trematode class, demonstrated high conservation of expression patterns between inparalogs, but with notable exceptions, which also display evidence of rapid evolution. We discuss how natural selection may operate to maintain these genes and the particular duplication models that fit better to the observations. Our work supports the critical role of gene duplication in the evolution of flatworms, representing the first study of inparalogs evolution at the genome-wide level in this group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep ( n =  24) were subject to 2-hours tMCAo and randomized ( n =  6/group) to receive early NK1-R treatment (days 1-3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The NK1-R antagonist drug (EU-C-001) was kindly donated by PresSura Neuro, however, they had no input in the experimental design, conduct of the study, nor data analysis.

Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation at forces >8pN (slip bond). Molecular dynamics of PD-1-PD-L2 complex suggests force may cause relative rotation and translation between the two molecules yielding distinct atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced distinct interactions maintain the same binding affinity but suppressed/eliminated catch bond, lowered rupture force, and reduced inhibitory function. Our results uncover a mechanism for cells to probe the mechanical support of PD-1-PD-Ligand bonds using endogenous forces to regulate PD-1 signaling., (© 2024. The Author(s).)

The mechanisms responsible for the growth and development of vascular beds in intestinal villi during postnatal ontogenesis remain enigmatic. For instance, according to the current consensus, in the sprouting type of angiogenesis, there is no blood flow in the rising capillary sprout. However, it is known that biomechanical forces resulting from blood flow play a key role in these processes. Here, we present evidence for the existence of the intussusception type of angiogenesis during the postnatal development of micro-vessel patterns in the intestinal villi of rats. This process is based on the high-level flattening of blood capillaries on the flat surfaces of intestinal villi, contacts among the opposite apical plasma membrane of endothelial cells in the area of inter-endothelial contacts, or the formation of bridges composed of blood leucocytes or local microthrombi. We identified factors that, in our opinion, ensure the splitting of the capillary lumen and the formation of two parallel vessels. These phenomena are in agreement with previously described features of intussusception angiogenesis.

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of pulmonary fibrosis, characterized by scar formation in the lung interstitium. Transforming growth factor beta (TGF-β) is known as a key mediator in the fibrotic process, acting on fibroblasts and mediating their proliferation and differentiation into myofibroblasts. Although the immune system is not considered responsible for the initiation of IPF, markers of tolerogenic immunity define the pro-fibrotic microenvironment in the lungs. In homeostatic conditions, regulatory T cells (Tregs) constitute the main lymphoid population responsible for maintaining peripheral tolerance. Similar to Tregs, regulatory B cells (Bregs) represent a recently described subset of B lymphocytes with immunosuppressive functions. In the context of IPF, numerous studies have suggested a role for Tregs in enhancing fibrosis, mainly via the secretion of TGF-β. In humans, most studies show increased percentages of Tregs associated with the severity of IPF, although their exact role remains unclear. In mice, the most commonly used model involves triggering acute lung inflammation with bleomycin, leading to a subsequent fibrotic process. Consequently, data are still conflicting, as Tregs may play a protective role during the inflammatory phase and a deleterious role during the fibrotic phase. Bregs have been less studied in the context of IPF, but their role appears to be protective in experimental models of lung fibrosis. This review presents the latest updates on studies exploring the implication of regulatory lymphoid cells in IPF and compares the different approaches to better understand the origins of conflicting findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Curioni, Borie, Crestani and Helou.)

Hierarchically structured supraparticles can be produced by drying droplets of colloidal suspensions. Using binary suspensions provides degrees of structural and functional control beyond those possible for single components, while remaining tractable for fundamental mechanistic studies. Here, we implement evaporative co-assembly of two distinct particle types - 'large' polystyrene microparticles and 'small' inorganic oxide nanoparticles (silica, titania, zirconia, or ceria) - dried on superhydrophobic surfaces to produce bowl-shaped supraparticles. We extend this method to raspberry colloid templating, in which the binary suspension consists of titania nanoparticles together with gold-decorated polystyrene colloids. Following removal of the polymer particles, we demonstrate catalytic oxidative coupling of methanol to methyl formate using the resulting mesoporous supraparticles, showcasing their practical application.

Two complexes {[GdCu 5 (GlyHA) 5 (H 2 O) 7 Cr(C 2 O 4 ) 3 ]·11.02H 2 O} n (1) and {{[GdCu 5 (GlyHA) 5 (H 2 O) 6 ]μ 2 -[Cu(C 2 O 4 ) 2 (H 2 O)]} 2 μ 4 -[Cu(C 2 O 4 ) 2 ]·15.8H 2 O} n (2), were obtained as outcomes of the reactions between the cationic hexanuclear {GdCu 5 (GlyHA) 5 } 3+ 15-metallacrown-5 complex (where GlyHA 2- = glycinehydroxamate) and the anionic oxalate complexes K 3 [Cr(C 2 O 4 ) 3 ] or K 2 [Cu(C 2 O 4 ) 2 ]. Both 1 and 2 possess polymeric 1D-chain structures according to X-ray structural analysis. As a consequence of the geometric orientations of the donor atoms in the oxalates from [Cr(C 2 O 4 ) 3 ] 3- , the Cu 5 mean planes of neighboring 15-metallacrown-5 units {GdCu 5 (GlyHA) 5 } 3+ are angled at 75.5° to each other, which leads to formation of a zig-zag motif in the 1D-chains of complex 1. The centrosymmetric complex 2 contains two structurally different bis(oxalato)cuprate anions μ 2 -[Cu(C 2 O 4 ) 2 (H 2 O)] 2- , for one of which, coordination to two adjacent {GdCu 5 (GlyHA) 5 } 3+ units leads to formation of linear 1D-chains in 2, while the second type, μ 4 -[Cu(C 2 O 4 ) 2 ] 2- , is coordinated to four {GdCu 5 (GlyHA) 5 } 3+ units, causing the cross-linking of single 1D-chains into a double-chain 1D coordination polymer. Studies of χ M T vs. T data for 1 and 2 in a 2-300 K temperature range revealed the presence of both ferromagnetic and antiferromagnetic interactions amongst paramagnetic centres. The experimental χ M T vs. T data for 1 were fitted using a model which takes into account exchange interactions between adjacent copper(II) ions, the Gd-Cu exchange interactions within {GdCu 5 (GlyHA) 5 } 3+ units and additionally Gd-Cr exchange interactions. Fitting of the χ M T vs. T data for 2 was not possible, since coordination of μ 4 -[Cu(C 2 O 4 ) 2 ] 2- to {GdCu 5 (GlyHA) 5 } 3+ led to the non-equivalence of several Cu-Cu exchange interactions within the metallacrown units and hence a superfluity of fittable parameters. Complexes 1 and 2 are the first examples of 15-metallacrown-5 complexes demonstrating a magnetocaloric effect (-Δ S M at 13 T reaches 24.26 J K -1 kg -1 at 5 K and 19.14 J K -1 kg -1 at 4 K for 1 and 2, respectively).

99m Tc is a well-known radionuclide that is widely used and readily available for SPECT/CT (Single-Photon Emission Computed Tomography) diagnosis. However, commercial isotope carriers are not specific enough to tumours, rapidly clear from the bloodstream, and are not safe. To overcome these limitations, we suggest immunologically compatible recombinant proteins containing a combination of metal binding sites as 99m Tc chelators and several different tumour-specific ligands for early detection of tumours. E1b protein containing metal-binding centres and tumour-specific ligands targeting integrin α v β 3 and nucleolin, as well as a short Cys-rich sequence, was artificially constructed. It was produced in E. coli , purified by metal-chelate chromatography, and used to obtain a complex with 99m Tc. This was administered intravenously to healthy Balb/C mice at an activity dose of about 80 MBq per mouse, and the biodistribution was studied by SPECT/CT for 24 h. Free sodium 99m Tc-pertechnetate at the same dose was used as a reference. The selectivity of 99m Tc-E1b and the kinetics of isotope retention in tumours were then investigated in experiments in C57Bl/6 and Balb/C mice with subcutaneously transplanted lung carcinoma (LLC) or mammary adenocarcinoma (Ca755, EMT6, or 4T1). The radionuclide distribution ratio in tumour and adjacent normal tissue (T/N) steadily increased over 24 h, reaching 15.7 ± 4.2 for EMT6, 16.5 ± 3.8 for Ca755, 6.7 ± 4.2 for LLC, and 7.5 ± 3.1 for 4T1.

RNA methylation adjacent to the 5' cap plays a critical role in controlling mRNA stability and protein synthesis. In trypanosomes the 5'-terminus of mRNA is protected by hypermethylated cap 4. Trypanosomes encode a cytoplasmic recapping enzyme TbCe1 which possesses an RNA kinase and guanylyltransferase activities that can convert decapped 5'-monophosphate-terminated pRNA into GpppRNA. Here, we demonstrated that the RNA kinase activity is stimulated by two orders of magnitude on a hypermethylated pRNA derived from cap 4. The N6, N6-2'-O trimethyladenosine modification on the first nucleotide was primarily accountable for enhancing both the RNA kinase and the guanylyltransferase activity of TbCe1. In contrast, N6 methyladenosine severely inhibits the guanylyltransferase activity of the mammalian capping enzyme. Furthermore, we showed that TbCmt1 cap (guanine N7) methyltransferase was localized in the cytoplasm, and its activity was also stimulated by hypermethylation at 2'-O ribose, suggesting that TbCe1 and TbCmt1 act together as a recapping enzyme to regenerate translatable mRNA from decapped mRNA. Our result establishes the functional role of cap 4 hypermethylation in recruitment and activation of mRNA recapping pathway. Methylation status at the 5'-end of transcripts could serve as a chemical landmark to selectively regulate the level of functional mRNA by recapping enzymes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization., Competing Interests: 7.Conflict of Interest None declared.

Hernia repairs are among the most common surgical procedures performed by general surgeons annually in the United States, defined as the abnormal protrusion of tissue and/or organs through an anatomical defect in the surrounding wall at various locations in the human body. While some hernias can remain asymptomatic and seemingly harmless, some may lead to intestinal obstruction, ischemic bowel from strangulation of blood supply, or septic shock if not diagnosed and addressed within a short period of time. This case report is about an elderly woman who presented with a Richter's. A Richter's hernia is an atypical type of strangulation where only a portion of the bowel, the antimesenteric border, is trapped within the anatomical defect. Given the limited extent of entrapped bowel, numerous different presentations can be seen, including but not limited to signs of obstruction without signs of ischemia or, in some instances, lack of either sign of obstruction or ischemia. Within this report, we will discuss the need for high clinical suspicion for Richter's hernias when evaluating strangulated hernias without systemic signs of sepsis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yumen et al.)

Members of the Ascarididae family are common zoonotic pathogens in humans and play an economic role in domestic and livestock animal husbandry. This family includes the obligatorily parasitic nematodes of the genus Baylisascaris , with the raccoon roundworm Baylisascaris procyonis being the most well-known representative. B. procyonis uses the raccoon ( Procyon lotor ) as its primary host and can utilise a broad range of mammals as paratenic hosts. Sexual reproduction of the adult nematodes occurs in the small intestine. Eggs are excreted into the environment through feces, where they develop into the infectious stage under suitable conditions within a few days to weeks. Infection of primary and paratenic hosts occurs through the oral ingestion of these infectious eggs. Raccoons can also become infected by ingesting infected paratenic hosts. Humans serve as accidental hosts and can suffer significant damage to organ tissues, the visual system, and the central nervous system after ingesting infectious eggs. The aim of the study was to investigate the effects of ambient temperature on embryonic development and to document the morphological changes during embryogenesis. Live specimens were collected from the raccoon intestine and incubated. Single-celled eggs were collected during this process. The eggs were decorticated and then preserved. To test the effects of ambient temperature, the eggs were incubated at 5 °C, 10 °C, 15 °C, 20 °C, 25 °C, 30 °C, 35 °C, and 38 °C and monitored at 24-h intervals for their developmental stages. Detailed photographic documentation of the developmental stages was conducted. An increase in ambient temperature led to a reduction in development time. The temperature range within which embryogenesis proceeded to the L1 larval stage was between 10 °C and 30 °C. Incubation at 5 °C did not produce L1 larvae even after 11 months. Incubation at 35 °C and 38 °C resulted in the complete degeneration of the eggs before reaching the L1 larval stage., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Magnesium alloys are considered as promising materials for use as biodegradable implants due to their biocompatibility and similarity to human bone properties. However, their high corrosion rate in bodily fluids limits their use. To address this issue, amorphization can be used to inhibit microgalvanic corrosion and increase corrosion resistance. The Mg-Zn-Ga metallic glass system was investigated in this study, which shows potential for improving the corrosion resistance of magnesium alloys for biodegradable implants. According to clinical tests, it has been demonstrated that Ga ions are effective in the regeneration of bone tissue. The microstructure, phase composition, and phase transition temperatures of sixteen Mg-Zn-Ga alloys were analyzed. In addition, a liquidus projection of the Mg-Zn-Ga system was constructed and validated through the thermodynamic calculations based on the CALPHAD-type database. Furthermore, amorphous ribbons were prepared by rapid solidification of the melt for prospective alloys. XRD and DSC analysis indicate that the alloys with the most potential possess an amorphous structure. The ribbons exhibit an ultimate tensile strength of up to 524 MPa and a low corrosion rate of 0.1-0.3 mm/year in Hanks' solution. Therefore, it appears that Mg-Zn-Ga metallic glass alloys could be suitable for biodegradable applications.

The purpose of the study was to examine trajectories in hookah use behaviors across young adulthood and socio-demographic correlates of the trajectories. Data were drawn from Project M-PACT for the years 2014-2019. Participants were 5,220 college students aged 18 to 25 years at baseline. Growth curve models with an accelerated design were fit to examine four hookah use trajectories across ages 18 to 30, adjusted for covariates. Prevalence of current hookah use decreased between 2014 and 2019, from 17% to 7% and the frequency of use decreased by almost one day a month. Trajectories of hookah use alone and concurrent with cigarettes or with e-cigarettes also decreased as students increased in age. Current hookah users were likely to be young, male, racial/ethnic minority, and attending a four-year college. Observed disparities among hookah users have implications, in particular regarding the role of social context, race, and ethnicity, in tailoring smoking interventions.

Nonsymmetric diarylethenes with an additional "stiff" cyclohexenol ring undergo various types of tandem transformations launched by light-induced 6π-photocyclization. Among these, there are two novel reactions (formal [1,3]-H migration and complete aromatization to an anthracene derivative) as well as photorearrangement and formal methane elimination. This diverse reactivity demonstrates the great potential of semi - stiff -diarylethenes in synthetic photochemistry.

Deaminase-T7 RNA polymerase fusion (MutaT7) proteins are a growing class of synthetic biology tools used to diversify target genes during in vivo laboratory evolution. To date, MutaT7 chimeras comprise either a deoxyadenosine or deoxycytidine deaminase fused to a T7 RNA polymerase. Their expression drives targeted deoxyadenosine-to-deoxyguanosine or deoxycytidine-to-deoxythymidine mutagenesis, respectively. Here, we repurpose recently engineered substrate-promiscuous general deaminases (GDEs) to establish a substantially simplified system based on a single chimeric enzyme capable of targeting both deoxyadenosine and deoxycytidine. We assess on- and off-target mutagenesis, strand and context preference, and parity of deamination for four different MutaT7 GDE constructs. We identify a single chimera that installs all possible transition mutations more efficiently than preexisting, more cumbersome MutaT7 tools. The optimized MutaT7 GDE chimera reported herein is a next-generation hypermutator capable of mediating efficient and uniform target-gene diversification during in vivo directed evolution.

Introduction: Social media use and vaping nicotine are highly prevalent in the daily lives of young adults, especially among Mexican-American college students. The excessive and compulsive use of social media platforms, coupled with the urge to stay continuously connected, can lead to problematic social media use. To date, no studies have explored the impact of problematic social media use on the daily patterns of vaping among this vulnerable population., Methods: In Spring 2023, we employed Ecological Momentary Assessment over a period of 14 days to collect real-time daily data on participants' social media use and vaping behaviors via a mobile phone-based application. Participants were 51 Mexican-American college students aged 18-25 years, 72.5% female, who were current vapers. We used generalized linear regression models to examine differences in vaping behaviors among participants with and without problematic social media use. All regression models adjusted for age, sex, and SES., Results: Participants with problematic social media use vaped on an average of 5.9 days compared to 5.7 days reported by those without problematic social media use ( p  < .05). Problematic social media use is associated with more frequent daily vaping [b = 0.03; 95% CI: 0.02-0.05], increased number of days vaping [b = 0.14; 95% CI: 0.07-0.20], and vaping higher nicotine concentrations [b = 0.08; 95% CI: 0.03-0.14]., Conclusion: Results suggest that problematic social media use significantly increases the risk of daily vaping among Mexican-American college students. Findings highlight the need to strengthen digital resilience and social media literacy to help college students navigate and mitigate the risks of social media., Competing Interests: The author declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Harrell serves as a consultant in litigation involving the vaping industry., (© The Author(s) 2024.)