Iterative design of polymer fabric cathode for metal-ion batteries.

Organic electrode materials (OEMs) have attracted significant attention for use in aqueous zinc-ion batteries (AZIBs) because of their abundant resources and flexible designability. However, the development of high-performance OEMs is strongly hindered by their high solubility, poor conductivity, sluggish ion diffusion kinetics, and difficult coordination toward Zn2+. Herein, inspired by fabric crafts, we have designed a robust polymer fabric through the iterative evolution of the building blocks from point to line and plane. The evolution from point to line could not only improve the structural stability and electrical conductivity but also adjust the active site arrangement to enable the storage of Zn2+. In addition to further boosting the aforementioned properties, the evolution from line to plane could also facilitate the construction of noninterference channels for ion migration. Accordingly, the poly(1,4,5,8-naphthalenetetracarboxylic dianhydride/2,3,5,6-tetraaminocyclohexa-2,5-diene-1,4-dione) (PNT) polymer fabric has the most enhanced structural stability, optimized active site arrangement, improved electrical conductivity, and suitable ion channels, resulting in a record-high capacity retention of 96% at a high mass loading of 56.9mg cm-2 and a stable cycle life of more than 20,000 cycles at 150C (1C=200 mA g-1) in AZIBs. In addition, PNT exhibits universality for a wide range of ions in organic electrolyte systems, such as Li/Na/K-ion batteries. Our iterative design of polymer fabric cathode has laid the foundation for the development of advanced OEMs to promote the performance of metal-ion batteries.

Clinical Value of Narrow Band Imaging Endoscopy in the Early Diagnosis and Staging Assessment of Laryngeal and Hypopharyngeal Cancer.

OBJECTIVE: To explore the clinical value of narrow band imaging (NBI) endoscopy in the early diagnosis and staging assessment of laryngeal and hypopharyngeal cancer. METHODS: A total of 78 patients with lesions in the hypopharynx or larynx were examined using endoscopy, observed under both white light and NBI modes, and graded using NBI. Using Lugol's iodine solution, laryngeal and hypopharyngeal lesions were graded using iodine staining. Using histopathological examination or postoperative pathological results as the diagnostic criteria, the sensitivity, specificity, and accuracy of endoscopy and iodine staining in diagnosing early cancer and precancerous lesions were evaluated. RESULTS: Multiple lesions were identified by both methods, and pathological examination confirmed 86 lesions, including early squamous cell carcinoma and precancerous lesions, such as early esophageal cancer, high-grade esophageal intraepithelial neoplasia, and hypopharyngeal cancer. Endoscopy showed significantly higher accuracy, detection rate, sensitivity, and specificity in NBI mode than in white light mode (96.12%, 86.05%, 97.37%, 86.67% vs 86.05%, 76.74%, 86.84%, 80%, respectively; P < 0.05). NBI grading and iodine staining grading showed good consistency with pathological diagnosis, with a Kappa value of 0.684 and 0.622, respectively. CONCLUSIONS: NBI endoscopy allows for better observation of subtle structural changes on the surface of lesions compared to white light endoscopy. It provides high accuracy in detecting early laryngeal and hypopharyngeal cancer and precancerous lesions, determining biopsy sites, facilitating early diagnosis, and establishing safe surgical margins. NBI endoscopy offers a viable alternative for non-invasive screening and early diagnosis of laryngeal and hypopharyngeal cancer, showing great potential for clinical advancement.

Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

Research on CO Migration Patterns in Shallowly Buried Coal Seam Composite Goafs.

To address the issue of CO exceedance in the close-range composite goaf, this paper focuses on the composite goaf of the Shaping Mine as the research subject and investigated the migration dynamics of CO within shallowly buried composite goaf areas. Sulfur hexafluoride gas (SF6) tracer experiments were conducted at the 13103 working face in Shaping Mine to assess surface fissures and air leakage, yielding insights into the distribution patterns of air leakage channels and facilitating the identification of critical areas for channel sealing. Programmed heating and oxidation experiments were conducted on coal seams 8# and 13# to determine the CO generation patterns during coal oxidation. The results show that higher concentrations of O2 corresponded to elevated CO production at equivalent temperatures. Subsequent data analysis unveiled exponential relationships between the O2 consumption rate and CO production rate within the goaf area, offering a theoretical framework for understanding CO migration patterns. Through numerical simulations, the study analyzed the CO migration patterns in the composite goaf area, observing downward diffusion of CO emanating from coal oxidation in the overlying goaf areas followed by dispersion toward the working face and roadways. Driven by airflow dynamics, CO accrued in the return air corner of the working face. Building upon these insights, comprehensive CO management strategies were implemented, resulting in sustained reductions of temperatures and CO concentrations to safe levels within the original high-temperature, high-concentration CO zones. Notably, CO concentrations at the return air corner of the working face continued to decline over the management period, reaching below 24 ppm within 10 to 15 days, highlighting the effectiveness of the management measures in ensuring safe underground production.

Numerical Analysis of the Airflow Field and Experiments of Fiber Motion for Solution Blowing.

Solution blowing is a rapidly developing technology for the rapid and large-scale preparation of nanofibers, driven by its advantages, such as wide adaptability to raw materials, simple and safe operation, and ease of scalable production. Most of the research related to solution blowing mainly focuses on the fiber spinning and forming principle, fiber structure and properties, and the development of new materials. Limited studies have focused on the airflow field and fiber motion in solution blowing. In this paper, nine nozzles for solution blowing with varying geometrical parameters were designed by adjusting the outer nozzle diameter, inner nozzle outstretched distance, and inner nozzle diameter. The centerline airflow velocity, turbulence intensity, and velocity distribution of the solution blowing were analyzed using the numerical simulation method. The results showed that the outer nozzle diameter had the greatest influence on the air velocity and turbulence intensity. The airflow velocity increased and the turbulence intensity decreased with the increase of the outer nozzle diameter. The inner nozzle outstretched distance only affected the airflow convergence point and had less effect on the airflow velocity and turbulence intensity. The captured trajectory of the polymer jet initially shows a straight or slightly curved development that eventually diverges from the airflow field. With an increasing distance, dispersed fibers exhibit instability, including loop formation, bonding, and separation. The experimental observation of fiber morphology in the solution-blowing web further verified the instability during the fiber movement.

Plant-derived essential oil contributes to the reduction of multidrug resistance genes in the sludge composting process.

Multidrug-resistant bacteria and multi-resistance genes in sludge have become a serious issue for public health. It is imperative to develop feasible and environmentally friendly methods of sludge composting to alleviate multidrug resistance genes. Plant-derived essential oil is an effective natural and eco-friendly antibacterial, which has great utilization in inhibiting pathogens in the agricultural industry. Nevertheless, the application of plant-derived essential oil to control pathogenic bacteria and antibiotic resistance in composting has not been reported. This study conducted a composting system by adding plant-derived essential oil i.e., oregano essential oil (OEO), to sludge composting. The findings indicated that multidrug resistance genes and priority pathogens (critical, high, and medium categories) were reduced by (17.0 ± 2.2)% and (26.5 ± 3.0)% in the addition of OEO (OH treatment) compared to control. Besides, the OH treatment changed the bacterial community and enhanced the gene sequences related to carbohydrate metabolism in compost microorganisms. Mantel test and variation partitioning analysis revealed that the target virulence factors (VFs), target mobile genetic elements (MGEs), and priority pathogens were the most important factors affecting multidrug resistance in composting. The OH treatment could significantly inhibit the target VFs, target MGEs, and priority pathogens, which were helpful for the suppression and elimination of multidrug resistance genes. These findings provide new insights into the regulation of multidrug resistance genes during sludge composting and a novel way to diminish the environmental risk of antibiotic resistance.

Sustained high expression of NRF2 inhibits cell apoptosis in arsenite-transformed human keratinocytes.

Our previous study identified that nuclear factor-erythroid-2 p45-related factor 2 (NRF2) was activated in arsenite-induced tumorigenesis. However, the underlying mechanisms of NRF2 mediating apoptosis in arsenic-induced skin carcinogenesis remain unknown. This study explored the dynamic changes in apoptosis rate and the expression of apoptosis proteins in immortalized human keratinocytes (HaCaT) malignant transformation caused by 1.0 µM NaAsO2 at passages 0, 1, 7, 14, 21, 28, and 35. The result showed that the apoptosis rate decreased. The apoptosis-related proteins cleaved-caspase-3/caspase-3 ratio decreased in the later stages (passages 21, 28, and 35). Moreover, the expression of intrinsic ER stress pathway-related CHOP, ATF4, ATF6, and the intrinsic mitochondrial pathway-related Bax protein decreased in the later stages, while Bcl-2 and Mcl-1 increased, and NRF2 protein levels also increased. The apoptosis rate increased by silencing NRF2 expression in arsenite-transformed HaCaT (T-HaCaT) cells. Meanwhile, the expression of pro-apoptotic proteins (cleaved-caspase-3/caspase-3, CHOP, Bax) and ATF4, ATF6 increased. On the contrary, antiapoptotic protein levels (Bcl-2 and Mcl-1) decreased. The ability of colony formation and migration of T-HaCaT cells decreased. In conclusion, arsenite activated NRF2 in the later stages, decreasing apoptosis characterized by inhibiting endoplasmic reticulum stress-depended and mitochondria-depended apoptosis pathway, and further promoting NaAsO2-induced HaCaT cellular malignant transformation.

Evaluation of hydrochar-derived modifier and water-soluble fertilizer on saline soil improvement and pasture growth.

Soil salinization poses a serious threat to crop growth. The selection of appropriate soil modifiers and water-soluble fertilizers for saline soils represents a crucial method for enhancing crop yields. The modifiers and medium-element water-soluble fertilizers were prepared using hydrochar derived from rice straw. Two distinct experiments were designed to study the effect of modifiers and water-soluble fertilizers on saline soils. The first experiment, designated as the "Soil Cultivation Experiment" , sought to investigate the impact of various modifiers on soil quality. The second experiment, designated as the "Method of Field Micro-Area Experiment", aimed to assess the influence of water-soluble fertilizers on saline soils. The results showed that the application of modifiers and water-soluble fertilizers significantly enhanced comprehensive soil physical and chemical properties, crop growth, soil enzyme activity, and other key indicators in saline and alkaline soils. The optimal dosage of the modifier was 20 g/kg, which reduced the pH value from 8.62 to 8.21 and the decreased alkalinity by 8.26%. Furthermore, their application effectively boosted nutrient levels, including organic matter, and increased soil enzyme activity. The biomass of alfalfa showed enhancements of 63.01% and 20.87% and the biomass of leymus chinensis increased by 29.39% and 9.02% for the two batches, respectively. Notably, the application of water-soluble fertilizer yielded achieved superior results. This study also provided a theoretical basis for their future application in soda saline-alkali soil.

Scalable Preparation of Liquid Infused Coatings for Lubrication of 103 m2 Dry Ski Slopes.

To facilitate effective training for freestyle skiers on artificial dry ski slopes, it is crucial to reduce the friction coefficient of the slopes and closely match it with that of snow. Traditional lubrication methods, such as water or soapy water, come with multiple disadvantages, including water waste, which leads to environmental pollution, short-lived effectiveness, and high costs. In this study, we have successfully developed a method for the scalable preparation of a liquid-infused coating (LIC) by tandem spraying inexpensive and environmentally friendly SiO2 particles and silicone oil lubricants. Experimental results showed that the resulting LIC is capable of imparting slippery properties to various surfaces, regardless of the surface chemistry. Moreover, the presence of LIC could reduce the friction coefficient significantly. By carefully regulating the surface composition, we achieved a friction coefficient of 0.059 between a snowboard and the LIC-functionalized ski slope, closely matching that between the snowboard and snow in a typical skiing competition venue (∼0.06). We successfully applied LIC onto 103 m2 dry ski slopes, providing a training ground for professional freestyle skiers.

S-glutathionylation in hepatocytes is involved in arsenic-induced liver fibrosis through activation of the NLRP3 inflammasome, an effect alleviated by NAC.

Arsenic, a toxicant widely distributed in the environment, is considered as a risk factor for liver fibrosis. At present, the underlying mechanism still needs to be explored. In the present study, we found that, for mice, chronic exposure to arsenic induced liver fibrosis, activated the NLRP3 inflammasome, and increased the levels of reactive oxygen species (ROS). After hepatocytes were co-cultured with hepatic stellate cells (HSCs), we observed the arsenic-activated NLRP3 inflammasome in hepatocytes, and the co-cultured HSCs were activated. Further, we found that, in livers of mice, arsenic disturbed GSH metabolism and promoted protein S-glutathionylation. A 3D molecular docking simulation suggested that NLRP3 binds with GSH, which was confirmed by immunoprecipitation experiments. N-acetylcysteine (NAC) increased the levels of GSH in hepatocytes, which suppressed the S-glutathionylation of NLRP3 and blocked arsenic-induced activation of the NLRP3 inflammasome. Mechanistically, an imbalance of the redox state induced by arsenic promotes the S-glutathionylation of NLRP3, which regulates activation of the NLRP3 inflammasome, leading into the activation of HSCs. Moreover, NAC increases the levels of GSH to block arsenic-induced S-glutathionylation of NLRP3, thereby blocking arsenic-induced liver fibrosis. Thus, via activating HSCs, the S-glutathionylation of NLRP3 in hepatocytes is involved in arsenic-induced liver fibrosis, and, for hepatocytes, NAC alleviates these effects by increasing the levels of GSH. These results reveal a new mechanism and provide a possible therapeutic target for the liver fibrosis induced by environmental factors.

The attachment factors and attachment receptors of human noroviruses.

Human noroviruses (HuNoVs) are the leading etiological agent causing the worldwide outbreaks of acute epidemic non-bacterial gastroenteritis. Histo-blood group antigens (HBGAs) are commonly acknowledged as cellular receptors or co-receptors for HuNoVs. However, certain genotypes of HuNoVs cannot bind with any HBGAs, suggesting potential additional co-factors and attachment receptors have not been identified yet. In addition, food items, such as oysters and lettuce, play an important role in the transmission of HuNoVs. In the past decade, a couple of attachment factors other than HBGAs have been identified and analyzed from foods and microbiomes. Attachment factors exhibit potential as inhibitors of viral binding to receptors on host cells. Therefore, it is imperative to further characterize the attachment factors for HuNoVs present in foods to effectively control the spread of HuNoVs within the food chain. This review summarizes the potential attachment factors/receptors of HuNoVs in humans, foods, and microbiome.

Exploring the environmental influences and community assembly processes of bacterioplankton in a subtropical coastal system: Insights from the Beibu Gulf in China.

Due to rapid urbanization, the Beibu Gulf, a semi-closed gulf in the northwestern South China Sea, faces escalating ecological and environmental threats. Understanding the assembly mechanisms and driving factors of bacterioplankton in the Beibu Gulf is crucial for preserving its ecological functions and services. In the present study, we investigated the spatiotemporal dynamics of bacterioplankton communities and their assembly mechanisms in the Beibu Gulf based on the high-throughput sequencing of the bacterial 16 S rRNA gene. Results showed significantly higher bacterioplankton diversity during the wet season compared to the dry season. Additionally, distinct seasonal variations in bacterioplankton composition were observed, characterized by an increase in Cyanobacteria and Thermoplasmatota and a decrease in Proteobacteria and Bacteroidota during the wet season. Null model analysis revealed that stochastic processes governed bacterioplankton community assembly in the Beibu Gulf, with drift and homogenizing dispersal dominating during the dry and wet seasons, respectively. Enhanced deterministic assembly of bacterioplankton was also observed during the wet season. Redundancy and random forest model analyses identified the physical properties (e.g., temperature) and nutrient content (e.g., nitrate) of water as primary environmental drivers influencing bacterioplankton dynamics. Moreover, variation partitioning and distance-decay of similarity revealed that environmental filtering played a significant role in shaping bacterioplankton variations in this rapidly developed coastal ecosystem. These findings advance our understanding of bacterioplankton assembly in coastal ecosystems and establish a theoretical basis for effective ecological health management amidst ongoing global changes.

The activation of TLR4-MyD88 signaling promotes hepatic dysfunction and fibrotic changes in SD rats resulting from prolonged exposure to sodium arsenite.

Arsenic, a poisonous metalloid element, is linked to liver diseases, but the exactmechanisms for this process are not yet to be completely elucidated. Toll like receptor 4 (TLR4), acting as a pathogenic pattern recognition receptor, plays a pivotal role in various inflammatory diseases via the myeloid differentiation factor 88 (MyD88) pathway. This study aims to investigate the involvement of the TLR4-MyD88 signaling pathway in liver injury induced by prolonged exposure to sodium arsenite (NaAsO2) in Sprague-Dawley rats. Our research findings demonstratethe activation of TLR4-MyD88 signaling pathway in long-term NaAsO2-exposed rat liver tissues, leading to a significant release of inflammatory factors, which suggests its potential involvement in the pathogenesis of NaAsO2-induced liver injury. We further administered lipopolysaccharide (LPS), a natural ligand of TLR4, and TAK-242, a specific inhibitor of TLR4, to rats in order to validate the specific involvement of the TLR4-MyD88 signaling pathway in NaAsO2-induced liver injury. The results showed that, 1 mg/kg.bw LPS treatment significantly activated TLR4-MyD88 signalling pathway and its mediated pro-inflammatory factors, leading to up-regulation of activation indicators in hepatic stellate cells (HSCs) as well as increased secretion levels of extracellular matrix (ECM) in the liver, and ultimately induced liver fibrosis and dysfunction in rats. Relevantly, subsequent administration of 0.5 mg/kg.bw TAK-242 significantly attenuated the expression levels of TLR4 and its associated proteins, mitigated collagen deposition, and partially improved liver fibrosis and dysfunction caused by NaAsO2 in rats. Our study fully confirms the pivotal role of the TLR4-MyD88 signaling in promoting liver injury induced by NaAsO2, thereby providing a novel molecular target for preventing and treating patients with arsenic poisoning-related liver injury.

LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.

BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Resveratrol Alleviates Arsenic Exposure-Induced Liver Fibrosis in Rats by Inhibiting Hepatocyte Senescence.

Arsenic is an environmental pollutant that has garnered considerable attention from the World Health Organization. Liver fibrosis is an advanced pathological stage of liver injury that can be caused by chronic arsenic exposure and has the potential to be reversed to prevent cirrhosis and hepatic malignancies. However, effective treatment options are currently limited. Given the profibrogenic effect of hepatocyte senescence, we established a rat model of sub-chronic sodium arsenite exposure and investigated the ability of resveratrol (RSV), a potential anti-senescence agent, to ameliorate arsenic-induced liver fibrosis and elucidate the underlying mechanism from the perspective of hepatocyte senescence. The results demonstrated that RSV was capable of mitigating fibrosis phenotypes in rat livers, including the activation of hepatic stellate cell (HSC), the generation of extracellular matrix, and the deposition of collagen fibers in the liver vascular zone, which are all induced by arsenic exposure. Furthermore, as an activator of the longevity factor SIRT1, RSV antagonized the arsenic-induced inhibition of SIRT1 expression, thereby restoring the suppression of the senescence protein p16 by SIRT1. This prevented arsenic-induced hepatocyte senescence, manifesting as a decrease in telomere shortening and a reduction in the release of senescence-associated secretory phenotype (SASP)-related proteins. In conclusion, this study demonstrated that RSV counteracts arsenic-induced hepatocyte senescence and the release of SASP-related proteins by restoring the inhibitory effect of SIRT1 on p16, thereby suppressing the activation of fibrotic phenotypes and mitigating liver fibrosis. These findings provide new insights for understanding the mechanism of arsenic-induced liver fibrosis, and more importantly, they reveal novel potential interventional approaches.

Comparative physiological, biochemical and transcriptomic analyses to reveal potential regulatory mechanisms in response to starvation stress in Cipangopaludina chinensis.

Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.

Seasonal dynamics of antibiotic resistance genes and mobile genetic elements in a subtropical coastal ecosystem: Implications for environmental health risks.

Antibiotic resistance poses a considerable global public health concern, leading to heightened rates of illness and mortality. However, the impact of seasonal variations and environmental factors on the health risks associated with antibiotic resistance genes (ARGs) and their assembly mechanisms is not fully understood. Based on metagenomic sequencing, this study investigated the antibiotic resistome, mobile genetic elements (MGEs), and microbiomes in a subtropical coastal ecosystem of the Beibu Gulf, China, over autumn and winter, and explored the factors influencing seasonal changes in ARG and MGE abundance and diversity. Results indicated that ARG abundance and diversity were higher in winter than in autumn, with beta-lactam and multidrug resistance genes being the most diverse and abundant, respectively. Similarly, MGE abundance and diversity increased in winter and were strongly correlated with ARGs. In contrast, more pronounced associations between microbial communities, especially archaea, and the antibiotic resistome were observed in autumn than in winter. The co-occurrence network identified multiple interactions between MGEs and various multidrug efflux pumps in winter, suggesting a potential for ARG dissemination. Multivariate correlation analyses and path modeling indicated that environmental factors driving microbial community changes predominantly influenced antibiotic resistome assembly in autumn, while the relative importance of MGEs increased significantly in winter. These findings suggest an elevated health risk associated with antimicrobial resistance in the Beibu Gulf during winter, attributed to the dissemination of ARGs by horizontal gene transfer. The observed seasonal variations highlight the dynamic nature of antibiotic resistance dissemination in coastal ecosystems, emphasizing the need for comprehensive surveillance and management measures to address the growing threat of antimicrobial resistance in vulnerable environments.

Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D.

Introduction: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing ß cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear. Objectives: This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset. Methods: The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development. Results: B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag-/- mice transplanted with fecal samples from Tlr9 fl/fl Cd19-Cre+ mice showed delayed diabetes onset, indicating microbiota's impact. Conclusion: B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.

Association between mosaic loss of chromosome Y and pulmonary fibrosis susceptibility and severity.

Background Pulmonary fibrosis (PF) is a rare lung disease with diverse pathogenesis and multiple interconnected underlying biological mechanisms. Mosaic loss of chromosome Y (mLOY) is one of the most common forms of acquired chromosome abnormality in men, which has been reported to be associated with increased risk of various chronic progressive diseases including fibrotic diseases. However, the exact role of mLOY in the development of PF remains elusive and to be elucidated. Methods: We adopted three complementary approaches to explore the role of mLOY in the pathogenesis of PF. We used copy number on chromosome Y to estimate mLOY comparing patients in PROFILE and gnomAD cohorts and between cases and control patients from the GE100KGP cohort. Correlation of mLOY with demographic and clinical variables was tested using patients from PROFILE cohort. Lung single-cell transcriptomic data were analysed to assess the cell types implicated in mLOY. We performed Mendelian randomisation to examine the causal relationship between mLOY, IPF, and telomere length. Results: The genetic analysis suggests that mLOY is found in PF from both case cohorts but when compared with an age matched population the effect is minimal (P = 0.0032). mLOY is related to age (P = 0.00021) and shorter telomere length (P = 0.0081) rather than PF severity or progression. Single-cell analysis indicates that mLOY appears to be found primarily in immune cells and appears to be related to presence and severity of fibrosis. Mendelian randomisation demonstrates that mLOY is not on the causal pathway for IPF, but partial evidence supports that telomere shortening is on the causal pathway for mLOY. Conclusion: Our study confirms the existence of mLOY in PF patients and suggests that mLOY is not a major driver of IPF. The combined evidence suggests a triangulation model where telomere shortening leads to both IPF and mLOY.