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IntroductionOxidative stress and inflammatory responses are critical factors in ulcerative colitis disease pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) modulates oxidative stress and suppresses inflammatory responses, and the protective benefits of Nrf2 activation have been associated with the therapy of ulcerative colitis. MicroRNA-200a (miR-200a) could target Kelch-like ECH-associated protein 1 (Keap1) and activate the Nrf2-regulated antioxidant pathway. Nevertheless, whether miR-200a modulates the Keap1/Nrf2 pathway in dextran sulfate sodium (DSS)-induced colonic damage is unknown. Here, our research intends to examine the impact of miR-200a in the model of DSS-induced colitis.MethodsPrior to DSS intervention, we overexpressed miR-200a in mice for four weeks using an adeno-associated viral (AAV) vector to address this problem. ELISA detected the concentration of inflammation-related cytokines. The genes involved in inflammatory reactions and oxidative stress were identified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence. Moreover, we applied siRNAs to weakened Nrf2 expression to confirm the hypothesis that miR-200a provided protection via Nrf2.ResultsThe present study discovered miR-200a down-regulation, excessive inflammatory activation, enterocyte apoptosis, colonic dysfunction, and Keap1/Nrf2 antioxidant pathway inactivation in mouse colitis and NCM460 cells under DSS induction. However, our data demonstrated that miR-200a overexpression represses Keap1 and activates the Nrf2 antioxidant pathway, thereby alleviating these adverse alterations in animal and cellular models. Significantly, following Nrf2 deficiency, we failed to observe the protective benefits of miR-200a against colonic damage.DiscussionTaken together, through activating the Keap1/Nrf2 signaling pathway, miR-200a protected against DSS-induced colonic damage. These studies offer an innovative therapeutic approach for ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, the incidence of which has been on the rise in recent years. Nuclear factor erythroid 2-related factor 2 (Nrf2), known for its key function as a transcription factor, is pivotal in inducing antioxidant stress and regulating inflammatory responses. Numerous investigations have demonstrated the involvement of the Nrf2 pathway in maintaining the development and normal function of the intestine, the development of UC, and UC-related intestinal fibrosis and carcinogenesis; meanwhile, therapeutic agents targeting the Nrf2 pathway have been widely investigated. This paper reviews the research progress of the Nrf2 signaling pathway in UC.

Interleukin-1 receptor-associated kinase 1/4 (IRAK1/4) is the main kinase of the Toll-like receptor (TLR)-mediated pathway, considered a new target for treating inflammatory diseases. Studies showed a significant correlation between TLRs and inflammatory responses in ulcerative colitis (UC). Therefore, in this study, after inducing experimental colitis in mice with 3% dextran sulfate sodium (DSS), different concentrations of IRAK1/4 inhibitors were administered intraperitoneally. Then, the disease activity index was assessed, including the degree of pathological damage, by HE staining. Subsequently, while western blotting detected the TLR4/NF-κB pathway and intestinal barrier protein expression (Zonula-1, Occludin, Claudin-1, JAM-A), real-time polymerase chain reaction (RT-PCR) detected the mRNA expression levels of IRAK1/4 and mucin1/2. Furthermore, the expression levels of Zonula-1 and occludin were detected by immunofluorescence, including the plasma FITC-dextran 4000 concentration, to evaluate intestinal barrier permeability. However, ELISA measured the expression of inflammatory factors to reflect intestinal inflammation in mice. Investigations showed that the IRAK 1/4 inhibitor significantly reduced clinical symptoms and pathological DSS-induced colitis damage in mice and then inhibited the cytoplasmic and nuclear translocation of NF-κB p65, including the phosphorylation of IκBα and reduction in downstream inflammatory factor production. Therefore, we established that the IRAK1/4 inhibitor effectively improves colitis induced by DSS, partly by inhibiting the TLR4/NF-κB pathway, reducing inflammation, and maintaining the integrity of the colonic barrier.

Summary: Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p

Social organizations, which exist outside of governmental and market systems, are vital actors in social governance. Investigating the pathways through which social organizations participate in vaccination and immunization efforts can significantly contribute to the advancement of immunization programs. This paper elaborates on the practical need, theoretical basis, and policy support for social organizations′ involvement in vaccination and immunization activities. It identifies various challenges faced by these organizations, including incomplete collaborative mechanisms, limited societal recognition, and intrinsic organizational shortcomings. Furthermore, the paper explores strategies for enhancing social organizations′ participation in vaccination and immunization work, such as strengthening public education, providing consultation and advice, supporting grassroots immunization efforts, offering psychological assistance, linking social resources, and aiding in quality assurance. Recommendations are proposed with the aim of providing a reference for the efficient involvement of social organizations in vaccination and immunization activities.

The genus Thymallus, belonging to the Salmoniformes, Salmonidae and Thymallinae, is distributed in three main areas in China, namely, the Irtysh River Basin, the Heilongjiang River Basin and the Yalu River Basin. Research has shown that the diversity of extant Thymallus in China is much higher than that in the vast European and North American regions, but the taxonomic results of some species are still controversial. Among them, those whose taxonomic status has been clarified and whose nomenclature is not controversial are T. arcticus, T. grubii and T. tugarinae, and the one that is still controversial is T. yaluensis. Named by Mori in 1928, T. yaluensis is mainly distributed in the Yalu River Basin and is geographically isolated from the T. arcticus, T. grubii and T. tugarinae. In 2007, a study on the comparison of countable traits of Thymallus found that the countable traits of the T. yaluensis were in the middle between the T. grubii and T. tugarinae, and the validity of the taxonomic status of T. yaluensis has been formally questioned ever since; in 2008, a study using mitochondrial DNA control region sequences to study the evolutionary relationships of fishes in the genus Thymallus pointed out that the T. yaluensis is synonymous with the T. grubii. In 2016, researchers used mitochondrial genome data to confirm once again that there was no difference between the T. yaluensis and the T. grubii. However, this conclusion does not seem to be accepted by the academic community, and in recent years, there are still some scholars who regard the T. yaluensis as an independent species. Morphological methods are the most commonly used methods in species identification, which can be categorized into traditional morphological method and framework measurement method. The traditional morphological method mainly analyzes the horizontal and vertical traits of the fish body, and it is mostly limited to the head and tail traits, which can't measure the whole surface of the fish body comprehensively. The framework measurement method, however, is based on a certain number of anatomical coordinate points and measures the entire fish body in multiple directions, which can provide a more comprehensive response to the morphological differences of the fish body. So far, the studies on the interspecific differences of Thymallus in China have mostly focused on the molecular biology level, while the morphological differences have been less studied, only in T. grubii and T. tugarinae. The rapid development of molecular marking technology provides an important auxiliary means for species classification, but the apparent morphological differences are still recognized as the most intuitive basis for species classification. In order to clarify the morphological differences of Thymallus in China, this study comprehensively used traditional morphological methods and framework measurement method, and took the T. grubii, T. arcticus, T. yaluensis and T. tugarinae as the research objects, Statistical analysis was conducted on their 10 segmentation characteristics and 32 standardized metric features. The results showed that: (1) there was no significant difference (P > 0.05) between all the subsection characteristics of T. yaluensis and T. grubii, and there were significant differences (P < 0.05) in more than five segmentation characteristics between T. grubii, T. arcticus and T. tugarinae. (2) The coefficient of variation analysis showed that except for caudal peduncle length/body length, the differences in morphological characters between T. yaluensis and T. grubii were at the level of differences between geographic populations within species. (3) The principal component analysis screened out eight principal components with eigenvalues greater than 1, and the cumulative contribution rate reached 81.170%, among which the first and second principal components with the highest contribution rate mainly explained the differences in trunk and head between Thymallus, respectively. The construction of scatter plots of the first and second principal components revealed that the individual crossover between T. yaluensis and T. grubii had a high degree and could not be distinguished individually, while T. tugarinae and T. grubii show a lower level of overlap and partial distinction. Only T. arcticus can be distinctly separated. (3) Discriminative analysis was used to screen out 14 standardized measurement features to establish the Fisher linear discriminant function, and the discriminative rate of individuals being correctly assigned to their respective groups was as high as 97.30%. (4) Cluster analysis showed that compared with T. grubii, T. yaluensis had the highest degree of similarity with it, followed by T. tugarinae, and T. arcticus had the lowest degree of similarity with T. grubii. The comprehensive analysis showed that: (1) T. yaluensis should not be designated as a valid species and its scientific name should be revised to T. grubii. (2) Morphological differences among T. grubii, T. arcticus and T. tugarinae are mainly reflected in their segmentation characteristics and the measurement characteristics of trunk and head. The results of this study will provide a reference for the study of species classification and evolutionary relationships of the genus Thymallus.

In a genome-wide association study, we identified a rice UDP-glycosyltransferase gene, OsUGT706D2, whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid (ABA). OsUGT706D2 positively regulated the biosynthesis of tricin-4′-O-(syringyl alcohol) ether-7-O-glucoside at both the transcriptional and metabolic levels. OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid (ABA) signaling pathway. Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance. ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance. These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.

Thymallus sp. is a native fish species distributed in the Irtysh River Basin in China. Unfortunately, environmental damage and overfishing have led to a significant decline in Arctic grayling resources, pushing them towards endangerment. However, there is a lack of comprehensive genetic information regarding the wild populations of Thymallus sp., which poses challenges for the development of effective conservation strategies for their genetic resources. In response, this study collected 180 samples from six major tributaries within the Irtysh River Basin. It conducted a thorough investigation of Thymallus sp.'s morphological and genetic variations using morphometric measurements and microsatellite markers. The results showed that the morphological differences among the six populations were relatively minor, and none of the morphological traits reached the subspecies level or higher. Genetic analysis showed that all six populations of Thymallus sp. possessed high genetic diversity, with genetic variations among populations accounting for only 6.30 % of the total variation, suggesting that the current status of the germplasm resources was relatively good. However, due to overfishing, which had led to a decline in the number of effective breeding groups, some inbreeding has occurred within populations. Moreover, the construction of dams has hindered gene exchange, leading to a certain tendency towards genetic differentiation within the populations. This was evidenced by the clustering of Burqin and Haba into one genetic group, while Kuirt, Kayit, Kalaerzis, and Crane were classified into another genetic group. This study offers an important reference for the management and conservation of Thymallus sp. populations in the Irtysh River Basin.

Background: The research trends regarding standardised patients(SPs) in the education of health professions students have not been systematically studied. Methods: All published literature on SPs from January 1994 to January 2024 in Web of Science was screened by two reviewers. Bibliometric analysis and knowledge mapping visualisation analysis were performed using Cite Space software. The country, institution, journal, keyword co-occurrence, and keyword emergence were visualised. Result: A total of 3259 records were analysed. The amount of relevant literature in the past 30 years showed an upward trend involving 109 disciplinary categories, with the United States dominating. The five central research teams were from the United States and Canada. Nursing education is increasingly using SPs, especially in advanced nursing practice. As for the hotspot and trend analysis, the results indicate that there is still continuous attention to the impact of applying standardised patients on improving the communication ability, competence and performance of medical students. Additionally, there is a growing interest in exploring the application of visual simulation or artificial intelligence in standardised patient-related research. Conclusions: Research on SPs' has received continued attention. To cater to the diverse requirements of education and clinical context, there is a need for further exploration of SPs utilisation. AI-relevant SPs might be a new alternative for various scenarios in the future.

Abstract SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages’ role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

The photovoltaic/thermal (PV/T) system is a promising option for countering energy shortages. To improve the performance of PV/T systems, compound parabolic concentrators (CPCs) and phase-change materials (PCMs) were jointly applied to construct a concentrating photovoltaic/thermal system integrated with phase-change materials (PV/T-CPCM). An open-air environment is used to analyze the effects of different parameters and the intermittent operation strategy on the system performance. The results indicate that the short-circuit current and open-circuit voltage are positively correlated with the solar irradiance, but the open-circuit voltage is negatively correlated with the temperature of the PV modules. When the solar irradiance is 500 W⋅m−2 and the temperature of the PV modules is 27.5 ºC, the short-circuit current and open-circuit voltage are 1.0 A and 44.5 V, respectively. Higher solar irradiance results in higher thermal power, whereas the thermal efficiency is under lower solar irradiance (136.2–167.1 W⋅m−2 is twice under higher solar irradiance (272.3–455.7 W⋅m−2). In addition, a higher mass flow rate corresponds to a better cooling effect and greater pump energy consumption. When the mass flow rate increases from 0.01 to 0.02 kg⋅s–1, the temperature difference between the inlet and outlet decreases by 1.8 ºC, and the primary energy-saving efficiency decreases by 0.53%. The intermittent operation of a water pump can reduce the energy consumption of the system, and the combination of liquid cooling with PCMs provides better thermal regulation and energy-saving effects under various conditions.

Abstract Background Diabetes has become a prominent global public health problem, which is an important cause of death, disease burden, and medical and health economic burden. Previous studies have reported that majority of persons diagnosed with diabetes later presented with psychological and mental health diseases. The study aimed to explore the mediation role of anxiety on social support and depression among diabetic patents in elderly caring social organizations (SOs). Methods A multi-stage stratified cluster random sampling method was used in this cross-sectional study, and a questionnaire consisting of demographic questionnaire, MSPSS, GAD-7, and CES-D-10 was utilized to gather data. SPSS 22.0 and MPLUS 7.4 were used for statistical analysis. Spearman correlation analysis was employed to investigate correlations of key variables. A generalized linear model was used to exam factors associated with depression. Finally, the mediation effect among study variables was investigated by structural equation modeling (SEM). Results The average scores of social support, anxiety, and depression were 58.41 ± 14.67, 2.95 ± 3.95, and 7.24 ± 5.53, respectively. The factors of gender, social support, and anxiety were identified as significantly influential factors related to depression among diabetic patients in elderly caring SOs. The effect of social support on depression was significantly mediated by anxiety (β = -0.467, 95%CI: -0.813 to -0.251). Furthermore, anxiety partially mediated the relationship between family support and depression (β = -0.112, 95%CI: -0.229 to -0.012), and anxiety functioned as a complete mediator in the effect of significant others' support and depression (β = -0.135, 95%CI: -0.282 to -0.024). Conclusions The indirect effect of social support on depression through anxiety among diabetic patients in elderly caring SOs was elucidated. Social support played a key role in maintaining and regulating their mental health, particularly from family and significant others. Social support provided by both family and significant others exerted an important influence on maintaining and regulating their mental health. In light of this pathway, the elderly caring SOs should enhance the magnitude of social support from these two sources, thereby diminishing the likelihood of experiencing anxiety and depression.

Plant height (PH) is a critical agronomic trait in Brassica napus, significantly impacting yield. Consequently, identifying genes associated with plant height is a pivotal objective in oilseed rape breeding. This study employed a combination of bulk segregant analysis sequencing (BSA-seq) and RNA sequencing (RNA-seq) for analysis. A novel quantitative trait locus (QTL), qPH_C02, was identified between 63,989,634 and 64,945,122 bp on chromosome C02, from which eight candidate genes were screened. The Gene Ontology (GO) analysis revealed enrichment in peroxisomes, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated enrichment in the oxidative phosphorylation (OP) pathway. It is hypothesized that the observed differences in plant height and silique length may be attributed to the regulation of peroxidase activity in the OP pathway, which in turn alters plant energy metabolism and controls nutrient uptake. Subsequently, we will further test this hypothesis. The results of this study will contribute to our understanding of the genetic basis for differences in plant height and provide a foundation for the selection and breeding of Brassica napus varieties with desired plant shapes.

Endophytes, symbiotically with their host plants, are frequently found in the roots of Panax ginseng. To explore ginsenosides biotransformation by endophytic fungi, 26 such fungi were isolated from ginseng roots sourced from four distinct planting regions, and their glycosyl hydrolysis activities were measured. Of these endophytic, 20 isolates exhibited glycosidase enzymes capable of cleaving glycosidic bonds of glucose, arabinofuranose and arabinopyranose. Notably, the glycosidase BglNh gene was isolated and cloned from Nectria haematococca, one of the endophytic fungi. Enzymatic assessments unveiled that BglNh specifically catalyzes the hydrolysis of glucose residues located external to the C-3 position of protopanaxadiol ginsenosides under optimal reaction conditions (pH 6.0 and temperature 35 °C). Our findings demonstrate the efficient conversion of major ginsenosides Rb1, Rb2 and Rc to minor ginsenosides Gyp17, CO and CMc1, highlighting the potential of these fungi for ginsenoside biotransformation and bioactive compound production.

Abstract Despite the fact that the response of tropical hydroclimate to North Atlantic cooling events during the Heinrich Stadial 1 (HS1) has been extensively studied in African, South American and Indonesia, the nature of such responses remains debated. Here we investigate the tropical hydroclimate pattern over the Indo-Asian-Australian monsoon region during the HS1 by integrating hydroclimatic records, and examining a δ18Oseawater record from Globigerinoides ruber (white) in the tropical Indian Ocean. Our findings indicate that tropical hydrological conditions were synchronously arid in both hemispheres during the early HS1 (~18.3-16.3 ka) in the Indo-Asian-Australian monsoon region, except for a narrow, wet hydrological belt in northern low latitudes, suggesting the existence of a contracted tropical precipitation belt at that time. This study reveals that the meltwater discharge and resulting changes in global temperatures and El Niño exerted a profound influence on the tropical hydroclimate in the Indo-Asian-Australian monsoon region during the early HS1.

Abstract Background Modular tissue engineering (MTE) is a novel “bottom-up” approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. Results Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. Conclusions The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Abstract Background With the deepening of China’s aging population, higher demands have been placed on the supply of elderly care services. As one of the main sources of providing elderly care services, the quality of service provided by elderly caring social organizations (SOs) directly affects the quality of life of the elderly. In recent years, mental health issues among the elderly have become increasingly prominent, especially with the onset of the COVID-19 pandemic. Necessitating the need to pay much more attention to the social support and mental health of this population. This study, therefore, explores the mediating role of institutional satisfaction between the social support and anxiety levels of elderly people in Chongqing’s elderly caring SOs. Method This study employed a multi-stage stratified random sampling method to survey 1004 service recipients in elderly caring social organizations from July to August 2022. The self-made sociodemographic questionnaire, institutional satisfaction questionnaire, MSPSS, and GAD-7 were used to collect data on sociodemographic characteristics, institutional satisfaction, social support, and anxiety levels of older adults. Exploratory Factor Analysis and Cronbach’s alpha were used to test construct validity and scale reliability, respectively. Data features were described with One-Way Analysis of Variance, while Multiple Linear Regression and Structural Equation Modeling were used to evaluate relationships between social support, institutional satisfaction, and anxiety levels. Results The average institutional satisfaction score for elderly people in elderly caring SOs was 48.14 ± 6.75. Specifically, the satisfaction score for environmental quality and the satisfaction score for service quality were 16.63 ± 2.56 and 31.52 ± 4.76, respectively. In terms of socio-demographic variables, the presence of visits from relatives, personal annual average income, and self-rated health status all have significant effects on anxiety. Elders who receive visits from relatives have lower levels of anxiety compared to those who do not. Personal annual average income and self-rated health status are negatively correlated with anxiety levels. Social support had significant positive effect on institutional satisfaction, while institutional satisfaction had significant negative effect on anxiety. Institutional satisfaction partially mediated the relationship between social support and anxiety. Conclusions Our research demonstrates that improving the quality of organizational services in elderly caring SOs and increasing institutional satisfaction among the elders has significant potential for reducing anxiety levels among the elderly. Additionally, the social support by visits from family members cannot be overlooked. We encourage increasing the frequency of family visits through various means to enhance the support provided to elderly individuals.

ObjectivesTo examine the gut microbiota characteristics in children with immunoglobulin A vasculitis and their interrelationships with the host, while evaluate the vertical inheritance of microbiota in the development and progression of IgA vasculitis.MethodsThis study investigated the gut microbiome of 127 IgA vasculitis mother-child pairs and 62 matched healthy mother-child pairs, and compared the gut microbial composition of different groups. The pathway enrichment analysis evaluated potential gut microbiome-mediated pathways involved in the pathophysiology of IgA vasculitis. The Spearman correlation analysis illustrated the relationships between clinical variables and bacterial biomarkers.ResultsThis study identified distinct intestinal microbiome in IgA vasculitis children compared to healthy children, and further pointed out the association in gut microbiota between IgA vasculitis children's and their mother's. The relative abundance of Megamonas and Lactobacillus in IgAV children was positively correlated with that in their mothers. The pathway enrichment analysis found microbial biosynthesis of vitamins and essential amino acids was upregulated in children with IgA vasculitis. Correlation analysis showed bacterial biomarkers were correlated with indicators of blood coagulation.ConclusionChildren with IgA vasculitis have unique bacterial biomarkers and may affect coagulation function, and their gut microbiome was closely associated with that of their mothers. The observed association in gut microbiota between IgA vasculitis children and their mothers suggested a potential intergenerational influence of the maternal microbiota on the development or progression of IgA vasculitis in children.

ABSTRACTAntimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

Study region: Three subbasins with different karstification degrees in Southwest China. Study focus: To investigate the mechanism of karst influence on drought propagation, this paper used a daily-scale threshold level method to identify drought events and comparatively analyzed the differences in drought propagation characteristics among three subbasins. New hydrological insights for the region: (i) The karstification degree is appreciably correlated with the drought propagation from meteorological to hydrological droughts, and the stronger the karstification, the closer the relationship. (ii) Daily-scale drought events performed better in identifying drought characteristics; of all drought events, 55% were meteorological and 24% were hydrological and lasted

ObjectiveObservational studies have shown an association between systemic autoimmune disease (AD) and multiple malignancies. However, due to the difficulty indetermining the temporal nature of the order, their causal relationship remains elusive. Based on pooled data from a large population-wide genome-wide association study (GWAS), this study explores the genetic causality between systemic autoimmune disease and renal malignancy.MethodsWe took a series of quality control steps from a large-scale genome-wide association study to select single nucleotide polymorphisms (SNPs) associated with systemic autoimmune disease as instrumental variables(IVs) to analyze genetic causality with renal malignancies. Inverse variance weighting (IVW), MR- Egger, weighted median, simple model and weighted model were used for analysis. The results were mainly based on IVW (Random Effects), followed by sensitivity analysis. Inverse-Variance Weighted(IVW) and MR-Egger were used to test for heterogeneity. MR- Egger is also used for pleiotropic testing. A single SNP analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate causality, and sensitivity analysis was performed to evaluate pleiotropy and instrumental validity.ResultsAcute and subacute iridocylitis (P = 0.006, OR = 1.077), Ankylosing spondylitis (P = 0.002, OR = 1.051), and spondyloarthritis (P = 0.009, OR = 1.073) were positively associated with an increased risk of renal malignancy. Coxarthrosis (P = 0.008, OR = 0.483), Juvenile rheumatism (P = 0.011, OR = 0.897), and Systemic lupus erythematosus (P = 0.014, OR = 0.869) were negatively associated with an increased risk of renal malignancy. The results of sensitivity analysis were consistent without heterogeneity or pleiotropy.ConclusionOur study suggests a causal relationship between different systemic autoimmune diseases and renal malignancies. These findings prompt health care providers to take seriously the potential risk of systemic autoimmune disease and provide new insights into the genetics of kidney malignancies.

With the great advantages and continuous innovations, prolific research efforts have been devoted to the Stirling engine (SE) domain driven by the sustainability development. In this study, a bibliometric analysis is conducted to explore the research tend and hotspots of SE. The country co-authorship, institute co-authorship and keyword networks are engendered from the visual map using VOSviewer, showing China ranks the first with the total number of published articles and the majority publications are presented by Chinese Academy of Sciences. Owing to the highest node centrality, the research findings in USA can be considered the most influential and greatly worthy being referred, particularly represented by the early contribution for thermo-acoustic SE. The total 7 keyword clusters are classified through the top terms in Citespace and 4 of them are related to its energy supply system, demonstrating the typical application of SE-based combined heat and power (CHP) and integrated multi-energy complementary system have gained much attention. Based on this, a detailed review of SE-based energy supply systems is further conducted through the system forms, 4E performance evaluation and soft model combing optimization solutions. Several relevant issues hindering the improvement of these terms are summarized, providing the potential guides to help develop the SE-based energy supply system.

BackgroundThere is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SARS-CoV-2 infection.MethodUsing single-cell meta-analysis in combination with bulk-RNA analysis, we identified three drug targets and potential receptors for SARS-CoV-2 infection in lung tissues from patients with diabetes, hypertension, and hypertension-diabetes, referred to as “co-morbid” patients. Using single-cell meta-analysis analysis in combination with bulk-RNA, we identified drug targets and potential receptors for SARS-CoV-2 infection in the three co-morbidities.ResultsThe single-cell meta-analysis of lung samples from SARS-CoV-2-infected individuals with diabetes, hypertension, and hypertension-diabetes comorbidity revealed an upregulation of fibroblast subpopulations in these disease conditions associated with a predictive decrease in lung function. To further investigate the response of fibroblasts to therapeutic targets in hypertension and diabetes, we analyzed 35 upregulated targets in both diabetes and hypertension. Interestingly, among these targets, five specific genes were upregulated in fibroblasts, suggesting their potential association with enhanced activation of endothelial cells. Furthermore, our investigation into the underlying mechanisms driving fibroblast upregulation indicated that KREMEN1, rather than ACE2, could be the receptor responsible for fibroblast activation. This finding adds novel insights into the molecular processes involved in fibroblast modulation in the context of SARS-CoV-2 infection within these comorbid conditions. Lastly, we compared the efficacy of Pirfenidone and Nintedanib as therapeutic interventions targeting fibroblasts prone to pulmonary fibrosis. Our findings suggest that Nintedanib may be a more suitable treatment option for COVID-19 patients with diabetes and hypertension who exhibit fibrotic lung lesions.ConclusionIn the context of SARS-CoV-2 infections, diabetes, hypertension, and their coexistence predominantly lead to myofibroblast proliferation. This phenomenon could be attributed to the upregulation of activated endothelial cells. Moreover, it is noteworthy that therapeutic interventions targeting hypertension-diabetes demonstrate superior efficacy. Regarding treating fibrotic lung conditions, Nintedanib is a more compelling therapeutic option.

Abstract Studies show that birds cognize human disturbance as a potential predation risk. However, the responses of breeding birds to long‐term continuous disturbance by research activities and whether researcher disturbance affects the fitness of target species remain poorly understood. In this study, we used field observation data collected over 6 years to assess the potential impacts of research activities on nest‐site selection and nest success of the Emei Shan Liocichla (Liocichla omeiensis), a vulnerable babbler species endemic to Southwest China. Our results showed that Emei Shan Liocichlas tended to nest in taller nesting plants or the higher parts of nesting plants to increase nest‐site height following researcher disturbance. The average height of Emei Shan Liocichla nests increased by 52.2% over the 6‐year study period, from 129.8 ± 9.2 cm in 2009 (n = 11) to 197.5 ± 12.1 cm in 2015 (n = 18). While some pairs adopted a different strategy, placing their nests in Rosaceae plants with thorns instead of the bamboo Chimonobambusa szechuanensis (the favored nesting plant of the Emei Shan Liocichla) under high interference pressure, which made it more difficult for researchers to approach their nests. There were no significant differences both in clutch size and nest success between the low‐ and high‐disturbance groups. The study revealed the behavioral response pattern of breeding Emei Shan Liocichlas to researcher disturbance, which will contribute to conservation of this threatened songbird and the knowledge of reproductive strategies of birds. Developing specific guidelines for fieldwork and strengthening visitor management within its core habitat of Emei Shan Liocichla during breeding period should be considered.

According to its function as increasing disposable income, pension is believed to reduce absolute poverty of recipients. However, nowadays, researchers haven't reached the consensus on whether pensions reduce the relative poverty or not. Given the data from the China Health and Retirement Longitudinal Study (CHARLS) 2018, this study investigates on if pension has positive effect on the reduction of relative poverty by performing the heteroskedastic probit model with 2SLS and IV estimators.The result shows that: (1) Pension has a noticeable ani-poverty effects. Three relative poverty line charts indicate a decrease by 4.8 %, 4.28 % and 4.39 % in the probability of beneficiaries falling into relative poverty for each 1 % increase in pensions. (2) Pension contributes greatly to relative poverty reduction at the regional level, this contribution appears to have an urban-rural heterogeneity, with features of central > western > eastern and rural > town. (3) Pension increases the effect to improve the relative poverty through the mediating effect of intergenerational support from children. (4) To improve relative poverty situation, individual health status shows a positive moderating effect on pensions. For recipients with good health status, their probability of falling into relative poverty are less likely than the others.

The CCT gene family is present in plants and is involved in biological processes such as flowering, circadian rhythm regulation, plant growth and development, and stress resistance. We identified 87, 62, 46, and 40 CCTs at the whole-genome level in B. napus, B. rapa, B. oleracea, and A. thaliana, respectively. The CCTs can be classified into five groups based on evolutionary relationships, and each of these groups can be further subdivided into three subfamilies (COL, CMF, and PRR) based on function. Our analysis of chromosome localization, gene structure, collinearity, cis-acting elements, and expression patterns in B. napus revealed that the distribution of the 87 BnaCCTs on the chromosomes of B. napus was uneven. Analysis of gene structure and conserved motifs revealed that, with the exception of a few genes that may have lost structural domains, the majority of genes within the same group exhibited similar structures and conserved domains. The gene collinearity analysis identified 72 orthologous genes, indicating gene duplication and expansion during the evolution of BnaCCTs. Analysis of cis-acting elements identified several elements related to abiotic and biotic stress, plant hormone response, and plant growth and development in the promoter regions of BnaCCTs. Expression pattern and protein interaction network analysis showed that BnaCCTs are differentially expressed in various tissues and under stress conditions. The PRR subfamily genes have the highest number of interacting proteins, indicating their significant role in the growth, development, and response to abiotic stress of B. napus.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that poses a significant challenge to medical professionals due to its increasing incidence and prevalence coupled with the limited understanding of its underlying molecular mechanisms. In this study, we employed a novel approach by integrating five expression datasets from bulk tissue with single-cell datasets; they underwent pseudotime trajectory analysis, switch gene selection, and cell communication analysis. Utilizing the prognostic information derived from the GSE47460 dataset, we identified 22 differentially expressed switch genes that were correlated with clinical indicators as important genes. Among these genes, we found that the midkine (MDK) gene has the potential to serve as a marker of Idiopathic pulmonary fibrosis because its cellular communicating genes are differentially expressed in the epithelial cells. We then utilized midkine and its cellular communication-related genes to calculate the midkine score. Machine learning models were further constructed through midkine and related genes to predict Idiopathic pulmonary fibrosis disease through the bulk gene expression datasets. The midkine score demonstrated a correlation with clinical indexes, and the machine learning model achieved an AUC of 0.94 and 0.86 in the Idiopathic pulmonary fibrosis classification task based on lung tissue samples and peripheral blood mononuclear cell samples, respectively. Our findings offer valuable insights into the pathogenesis of Idiopathic pulmonary fibrosis, providing new therapeutic directions and target genes for further investigation.

Pulmonary fibrosis is a progressive and ultimately fatal lung disease, exhibiting the excessive production of extracellular matrix and aberrant activation of fibroblast. While Pirfenidone and Nintedanib are FDA-approved drugs that can slow down the progression of pulmonary fibrosis, they are unable to reverse the disease. Therefore, there is an urgent demand to develop more efficient therapeutic approaches for pulmonary fibrosis. The intracellular DNA sensor called cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) plays a crucial role in detecting DNA and generating cGAMP, a second messenger. Subsequently, cGAMP triggers the activation of stimulator of interferon genes (STING), initiating a signaling cascade that leads to the stimulation of type I interferons and other signaling molecules involved in immune responses. Recent studies have highlighted the involvement of aberrant activation of cGAS-STING contributes to fibrotic lung diseases. This review aims to provide a comprehensive summary of the current knowledge regarding the role of cGAS-STING pathway in pulmonary fibrosis. Moreover, we discuss the potential therapeutic implications of targeting the cGAS-STING pathway, including the utilization of inhibitors of cGAS and STING.

Hexadecylamine (HDA) was in situ encapsulated into SiO2 nanoshells, to obtain the HDA@SiO2 nanocapsule with excellent thermal reliability during the process of energy release/storage. Closed-pore structured HDA@SiO2 nanocapsule was successfully synthesized. The latent heats of crystallization and melting for HDA@SiO2 nanocapsule are 189.3 and 193.8 Jg−1, with the 91.2 wt% encapsulated HDA in the nanocapsule. The crystallization and melting temperatures (TCand TM) are 33.34 °C and 49.53 °C for HDA@SiO2 nanocapsule, respectively. After undergoing 200 thermal cycles, the latent heats of HDA@SiO2 nanocapsule decreased by 0.16% and 0.46% with the unchanged phase transition temperature, indicating HDA@SiO2 nanocapsule has superior operational reliability. Moreover, the thermal conductivity of HDA@SiO2 is 0.13 Wm−1K−1, an approximately 20% improvement over that of pure HDA. The temperature of degradation and evaporation of HDA@SiO2 nanocapsule was increased by more than 10 °C compared with that of bulk HDA. The HDA@SiO2 nanocapsule exploited in this work exhibits excellent operational reliability and high latent heat during the process of energy release/storage, which makes it more suitable and competitive in the recycling and utilization of thermal and solar energy.

Abstract Background Integrative analysis approaches of metagenomics and metabolomics have been widely developed to understand the association between disease and the gut microbiome. However, the different profiling patterns of different metabolic samples in the association analysis make it a matter of concern which type of sample is the most closely associated with gut microbes and disease. To address this lack of knowledge, we investigated the association between the gut microbiome and metabolomic profiles of stool, urine, and plasma samples from ischemic stroke patients and healthy subjects. Methods We performed metagenomic sequencing (feces) and untargeted metabolomics analysis (feces, plasma, and urine) from ischemic stroke patients and healthy volunteers. Differential analyses were conducted to find key differential microbiota and metabolites for ischemic stroke. Meanwhile, Spearman’s rank correlation and linear regression analyses were used to study the association between microbiota and metabolites of different metabolic mixtures. Results Untargeted metabolomics analysis shows that feces had the most abundant features and identified metabolites, followed by urine and plasma. Feces had the highest number of differential metabolites between ischemic stroke patients and the healthy group. Based on the association analysis between metagenomics and metabolomics of fecal, urine, and plasma, fecal metabolome showed the strongest association with the gut microbiome. There are 1073, 191, and 81 statistically significant pairs (P

Abstract Current non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.

ABSTRACT The induction of aberrant DNA methylation is the major pathway by which Helicobacter pylori infection induces stomach adenocarcinoma (STAD). The involvement of the non-H. pylori gastric microbiota in this mechanism remains to be examined. RNA sequencing data, clinical information, and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA) STAD project. The Kraken 2 pipeline was employed to explore the microbiome profiles. The microbiome was associated with occurrence, distal metastasis, and prognosis, and differential methylation changes related to distal metastasis and prognosis were analyzed. Bi-directional mediation effects of the intratumoral microbiome and host DNA methylation changes on the metastasis and prognosis of STAD were identified by mediation analysis. The expression of the ZNF215 gene was verified by real-time quantitative PCR (RT-qPCR). A cell counting kit 8 (CCK8) cell proliferation experiment and a cell clone formation experiment were used to evaluate the proliferation and invasion abilities of gastric cells. Our analysis revealed that H. pylori and other cancer-related microorganisms were related to the occurrence, progression, or prognosis of STAD. The related methylated genes were particularly enriched in related cancer pathways. Kytococcus sedentarius and Actinomyces oris, which interacted strongly with methylation changes in immune genes, were associated with prognosis. Cell experiments verified that Staphylococcus saccharolyticus could promote the proliferation and cloning of gastric cells by regulating the gene expression level of the ZNF215 gene. Our study suggested that the bi-directional mediation effect between intratumoral microorganisms and host epigenetics was key to the distal metastasis of cancer cells and survival deterioration in the tumor microenvironment of stomach tissues of patients with STAD. IMPORTANCE The burgeoning field of oncobiome research declared that members of the intratumoral microbiome besides Helicobacter pylori existed in tumor tissues and participated in the occurrence and development of gastric cancer, and the methylation of host DNA may be a potential target of microbes and their metabolites. Current research focuses mostly on species composition, but the functional genes of the members of the microbiota are also key to their interaction with the host. Therefore, we focused on characterizing the species composition and functional gene composition of microbes in gastric cancer, and we suggest that microbes may further participate in the occurrence and development of cancer by influencing abnormal epigenetic changes in the host. Some key bioinformatics analysis results were verified by in vitro experiments. Thus, we consider that the tumor microbiota-host epigenetic axis of gastric cancer microorganisms and the host explains the mechanism of the microbiota participating in cancer occurrence and development, and we make some verifiable experimental predictions.

In the original publication [...]

Abstract Background High-cost, time-consuming and complex processes of several current approaches limit the use of noninvasive prenatal diagnosis (NIPD) for monogenic disorders in clinical application. Thus, a more cost-effective and easily implementable approach is required. Methods We established a low-cost and convenient test to noninvasively deduce fetal genotypes of the mutation and single nucleotide polymorphisms (SNPs) loci by means of targeted amplification combined with deep sequencing of maternal genomic and plasma DNA. The sequential probability ratio test was performed to detect the allelic imbalance in maternal plasma. This method can be employed to directly examine familial pathogenic mutations in the fetal genome, as well as infer the inheritance of parental haplotypes through a group of selected SNPs linked to the pathogenic mutation. Results The fetal mutations in 17 families with different types of monogenic disorders including hemophilia A, von Willebrand disease type 3, Duchenne muscular dystrophy, hyper-IgM type 1, glutaric acidemia type I, Nagashima-type palmoplantar keratosis, and familial exudative vitreoretinopathy were identified in the study. The mutations included various forms: point mutations, gene inversion, deletions/insertions and duplication. The results of 12 families were verified by sequencing of amniotic fluid samples, the accuracy of the approach in fetal genotyping at the mutation and SNPs loci was 98.85% (172/174 loci), and the no-call rate was 28.98% (71/245 loci). The overall accuracy was 12/12 (100%). Moreover, the approach was successfully applied in plasma samples with a fetal fraction as low as 2.3%. Conclusions We have shown in this study that the approach is a cost-effective, less time consuming and accurate method for NIPD of monogenic disorders.

Bovine parvovirus (BPV) is a pathogen responsible for respiratory and digestive tract symptoms in calves and abortion and stillbirth in pregnant cows. In this study, we developed a colloidal gold immunochromatographic (GICG) strip with an enhanced signal for detecting BPV according to the double-antibody sandwich principle and an enzyme-based signal amplification system to amplify the signal. This system utilizes horseradish peroxidase reacting with a substrate solution containing 3,3′,5,5′-tetramethylbenzidine and dextran sulfate to obtain insoluble blue products on the test and control lines. We optimized different reaction conditions, including the amount of monoclonal antibodies (mAbs), pH of the colloidal gold solution, coating solution, blocking solution, sample pad treatment solution, antibody concentration in the control line, and antibody concentration in the detection line. The sensitivity of the signal-enhanced GICG strip showed that the minimum amount for detecting BPV was 102 TCID50, 10 times higher than that of the traditional GICG strip. The results of the specificity test showed that the signal-enhanced GICG strip had no cross-reactivity with BRV, BVDV, or BRSV. The results of the repeatability test showed that the coefficient of variation between and within batches was less than 5%, showing good repeatability. Moreover, for validation, PCR and the signal-enhanced GICG strip were used to detect 280 clinical bovine fecal samples. The concordance rate compared with PCR was 99.29%. Hence, the developed strip exhibited high sensitivity and specificity for the detection of BPV. Therefore, this strip could be a rapid, convenient, and effective method for the diagnosis of BPV infection in the field.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition with a high global morbidity and mortality rate that affects the whole body. Their primary consequences are mostly caused by the macrovascular and microvascular bed degradation brought on by metabolic, hemodynamic, and inflammatory variables. However, research in recent years has expanded the target organ in T2DM to include the lung. Inflammatory lung diseases also impose a severe financial burden on global healthcare. T2DM has long been recognized as a significant comorbidity that influences the course of various respiratory disorders and their disease progress. The pathogenesis of the glycemic metabolic problem and endothelial microangiopathy of the respiratory disorders have garnered more attention lately, indicating that the two ailments have a shared history. This review aims to outline the connection between T2DM related endothelial cell dysfunction and concomitant respiratory diseases, including Coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).

Lactobacillus johnsonii has been used as a probiotic for decades to treat a wide range of illnesses, and has been found to have specific advantages in the treatment of a number of ailments. We reviewed the potential therapeutic effects and mechanisms of L. johnsonii in various diseases based on PubMed and the Web of Science databases. We obtained the information of 149 L. johnsonii from NCBI (as of 14 February 2023), and reviewed their comprehensive metadata, including information about the plasmids they contain. This review provides a basic characterization of different L. johnsonii and some of their potential therapeutic properties for various ailments. Although the mechanisms are not fully understood yet, it is hoped that they may provide some evidence for future studies. Furthermore, the antibiotic resistance of the various strains of L. johnsonii is not clear, and more complete and in-depth studies are needed. In summary, L. johnsonii presents significant research potential for the treatment or prevention of disease; however, more proof is required to justify its therapeutic application. An additional study on the antibiotic resistance genes it contains is also needed to reduce the antimicrobial resistance dissemination.

Polyphenol oxidase (PPO) is the key enzyme in the melanogenesis pathway of enzymatic browning that converts phenolic substrates to quinones and eventually polymerizes to form melanin. In this study, the genome-wide characterization of the Abppo gene family was performed, and six Abppo genes were identified. These genes were divided into three groups based on sequence alignment and phylogenetic analysis, with members of the same group possessing similar motif structures. Expression analysis showed that the Abppo genes demonstrate diverse expression patterns at different growth stages and postharvest storage. In addition, the expression of Abppo genes could be significantly induced by abscisic acid, salicylic acid, methyl jasmonate, and gibberellic acid 3, indicating their potential roles in response to abiotic stresses. These results provide insights into the potential functions of the Abppo gene family, offering a theoretical reference in the future for mushroom breeders.

IntroductionClimate change and anthropogenic activities are the greatest threats to floodplain ecosystems. A growing body of literature shows that floodplain ecosystems have experienced increased chemical fertilizer and pesticide loads, which will disturb the above and belowground ecosystems. However, we lack knowledge regarding the effects of such human activities on the vegetation and soil microbiomes in these ecosystems.MethodsIn the present study, plant functional traits and Illumina Mi-Seq sequencing were to assess the impact of nitrogen fertilizer and glyphosate addition on the structure and function of the vegetation and soil microbiomes (bacteria, fungi, and protists) in a floodplain ecosystem, and to assess the influence of seasonal variation.ResultsWe identified distinct response mechanisms of plant and microbial communities to the addition of nitrogen fertilizer and glyphosate, and seasonal variation. Nitrogen fertilizer and glyphosate significantly affected plant diversity, aboveground and underground biomass, and C and N content and significantly changed the leaf area and plant stature of dominant plants. However, the addition of nitrogen fertilizer and glyphosate did not significantly affect the diversity and structure of bacterial, fungal, and protist communities. The application of nitrogen fertilizer could improve the negative effects of glyphosate on the functional traits of plant communities. The seasonal variation of floodplain has significantly changed the soil’s physical, chemical, and biological properties. Our results showed that compared with that in summer, the soil ecosystem multifunctionality of the floodplain ecosystem in autumn was significantly lower. Seasonal variation had a significant effect on plant diversity and functional traits. Moreover, seasonal variation significantly affected the community compositions, diversity, and structure of bacteria, fungi, and protists. Seasonal variation had a stronger impact on fungal community assembly than on that of bacteria and protists. In summer, the assembly of the fungal community was dominated by a deterministic process, while in autumn, it is dominated by a stochastic process. In addition, the negative association among bacteria, fungi, and protists has been strengthened in autumn and formed a more robust network to cope with external changes.DiscussionThese results extended our understanding of the ecological patterns of soil microbiomes in floodplain ecosystems and provided support for enhancing the ecological barrier function and the service potential of floodplain ecosystems.

Purpose: In this study, we intended to compare and rank the efficacy and acceptability of antiseizure medications (ASMs) for adjunctive treatment of children with drug-resistant focal-onset seizures.Method: We conducted a computerized search of PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar to identify eligible randomized controlled trials (RCTs) published before 31 May 2022. We included studies evaluating the efficacy and tolerability of antiseizure medications for children with drug-resistant focal-onset seizures. The efficacy and safety were reported in terms of responder and dropout rate along with serious adverse events, the outcomes were ranked with the surface under the cumulative ranking curve (SUCRA).Results: A total of 14 studies (16 trials) with 2,464 patients were included, involving 10 active antiseizure medications. For the primary endpoint of at least 50% reduction in focal-onset seizures, the surface under the cumulative ranking curve ranking suggested that lamotrigine and levetiracetam were more effective as compared with other antiseizure medications; moreover, levetiracetam had the highest probability of rank first for achieving seizure freedom. Concerning tolerability, oxcarbazepine and eslicarbazepine acetate were associated with higher dropout rates relative to other antiseizure medications and placebo, and topiramate was associated with higher occurrence of side effects. No significant differences were found between active antiseizure medications concerning dropout for side effects.Conclusion: According to the surface under the cumulative ranking curve ranking, lamotrigine, levetiracetam, and oxcarbazepine were more efficacious than other active antiseizure medications in terms of responder rate. Concerning tolerability, oxcarbazepine was more likely to lead to dropout and topiramate was associated with higher occurrence of side effects.

Few methods exist to add a carbon and nitrogen atom across an unfunctionalized alkene. Here the authors show a method to regio- and diastereoselectively add aryl and amino groups to terminal and internal alkenes, via nickel catalysis and a removable directing group.

Abstract Background Examinations based on lung tissue specimen can play a significant role in the diagnosis for critically ill and intubated patients with lung infiltration. However, severe complications including tension pneumothorax and intrabronchial hemorrhage limit the application of needle biopsy. Methods A refined needle biopsy technique, named bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB), was performed on four intubated patients between August 2020 and April 2021. BUS-PTNB was done at bedside, following an EPUBNOW (evaluation, preparation, ultrasound location, bronchus blocking, needle biopsy, observation, and withdrawal of blocker) workflow. Parameters including procedure feasibility, sample acquisition, perioperative conditions, and complications were observed. Tissue specimens were sent to pathological examinations and microbial tests. Results Adequate specimens were successfully obtained from four patients. Diagnosis and treatment were correspondingly refined based on pathological and microbial tests. Intrabronchial hemorrhage occurred in patient 1 but was stopped by endobronchial blocker. Mild pneumothorax happened in patient 4 due to little air leakage, and closed thoracic drainage was placed. During the procedure, peripheral capillary hemoglobin oxygen saturation (SPO2), blood pressure, and heart rate of patient 4 fluctuated but recovered quickly. Vital signs were stable for patient 1–3. Conclusions BUS-PTNB provides a promising, practical and feasible method in acquiring tissue specimen for critically ill patients under intratracheal intubation. It may facilitate the pathological diagnosis or other tissue-based tests for intubated patients and improve clinical outcomes.

Biomaterial implantation for bone defect repair is a complex cascade reaction process, which mainly includes early inflammatory response and subsequent osteogenic repair. In this work, quercetin / nano-hydroxyapatite / poly (glycolide-co-epsilon-caprolactone) (Que/n-HA/PGCL) nanocomposite microspheres were successfully prepared by airflow shearing method, possessing interconnected porous structure with unique “eyeball-like” surface morphology. The encapsulation efficiency of microspheres reaches as high as 80 % and Que release was stable and continuous, only released 7.5 % at 120 h in the 4 wt% group. Moreover, Que-loaded microspheres triggered positive immunomodulation via upregulation of M2 macrophage polarization evidenced by decreased expression of pro-inflammatory cytokines TNF-α, iNOS and the increased expression of anti-inflammatory cytokines Arg1, IL-10 in RAW264.7 cells, which was beneficial to BMSCs osteogenic differentiation in the co-culture system. Meanwhile, the capability to directly promote osteo-differentiation was manifested by upregulation of Runx2, ALP, OPN, OCN gene expression and the increase of differentiation markers. Furthermore, the assessment of Que/n-HA/PGCL microspheres in vivo confirmed desirable bone repair contributed to efficient immunomodulation and excellent osteo-differentiation. Thus, the Que/n-HA/PGCL microspheres could serve as potential functional filling materials for bone repair, which could be applied to efficient drug delivery platform in the future clinical applications.

COVID-19 prognoses suggests that a proportion of patients develop fibrosis, but there is no evidence to indicate whether patients have progression of mesenchymal transition (MT) in the lungs. The role of MT during the COVID-19 pandemic remains poorly understood. Using single-cell RNA sequencing, we profiled the transcriptomes of cells from the lungs of healthy individuals (n = 45), COVID-19 patients (n = 58), and idiopathic pulmonary fibrosis (IPF) patients (n = 64) human lungs to map the entire MT change. This analysis enabled us to map all high-resolution matrix-producing cells and identify distinct subpopulations of endothelial cells (ECs) and epithelial cells as the primary cellular sources of MT clusters during COVID-19. For the first time, we have identied early and late subgroups of endothelial mesenchymal transition (EndMT) and epithelial-mesenchymal transition (EMT) using analysis of public databases for single-cell sequencing. We assessed epithelial subgroups by age, smoking status, and gender, and the data suggest that the proportional changes in EMT in COVID-19 are statistically significant. Further enumeration of early and late EMT suggests a correlation between invasive genes and COVID-19. Finally, EndMT is upregulated in COVID-19 patients and enriched for more inflammatory cytokines. Further, by classifying EndMT as early or late stages, we found that early EndMT was positively correlated with entry factors but this was not true for late EndMT. Exploring the MT state of may help to mitigate the fibrosis impact of SARS-CoV-2 infection.

Integrin α6 (ITGα6) is involved in a variety of cellular physiological responses and plays an important role in the immune response. Currently, common carp is severely affected by the virus of Cyprinid herpesvirus 3 (CyHV-3) in aquaculture. Studies have shown that ITGα6 is associated with herpesvirus infection. However, the role of ITGα6 in the response to CyHV-3 virus infection is still unclear. In this paper, we cloned the ITGα6 from common carp (CcITGα6) and studied its expression profile after infection with CyHV-3. Two transcripts of CcITGα6 were cloned, named CcITGα6a and CcITGα6b. The full-length cDNA of the CcITGα6a transcript was 3867 bp, the ORF was 3273 bp, and 1090 amino acids were encoded. The full-length cDNA of the CcITGα6b transcript was 3368 bp, the ORF was 3189 bp, and 1062 amino acids were encoded. Two transcripts of CcITGα6 consist of four parts: the signal peptide, extracellular region, transmembrane region, and cytoplasmic region. The difference between the two CcITGα6 transcripts lies in the cytoplasmic region and no homologous sequence. Similarly, the secondary structure, glycosylation sites, and phosphorylation sites were different in the cytoplasmic region. Phylogenetic analysis showed that CcITGα6 was highly conserved and clustered with zebrafish ITGα6b. The two CcITGα6 transcripts were constitutively expressed in ten sample tissues but displayed distinct expression patterns. The highest relative expression levels of the two transcripts of CcITGα6 were observed in the head kidney, whereas the lowest was observed in the heart. The relative expression levels of the CcITGα6b transcript in the five tissues were significantly higher than the relative expression levels of the CcITGα6a transcript (p