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Abstract Background Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear. Methods Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber. Results We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor. Conclusion Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment. Graphical abstract

Abstract Noble metal-free nickel manganese oxysulfide (NiMnOS) catalysts were successfully prepared via a facile and eco-friendly approach at a low synthesis temperature of 90 °C in a water bath. The catalysts were synthesized by varying Ni: Mn molar ratios such as 25:75, 50:50, 75:25 and abbreviated as NiMnOS-25, NiMnOS-50, and NiMnOS-75, respectively. The bare NiOS and MnOS were also prepared for comparison purposes. The characterizations of the prepared samples were conducted with different techniques, and the catalytic activity was investigated through the reduction of methylene blue (MB) dye in the presence of NaBH4 in an aqueous solution. Among the prepared catalysts, NiMnOS-25 exhibited excellent performance and reduced 98.46% of MB within 5 min. However, NiOS, NiMnOS-50, NiMnOS-75, and MnOS were reduced 9.6%, 98.41%, 97.04%, and 6.40% of MB dye, respectively, within 7 min. The catalytic reduction activity could be mainly attributed to the synergistic effects of the metals (Ni and Mn), more exposed active sites. Therefore, the bimetal NiMnOS catalyst could be a promising candidate for the reduction of organic dyes in wastewater treatment technologies.

P32 protein serves as a crucial structural component of Goat pox virus (GTPV), which causes a highly virulent infectious disease in sheep and goats. Despite the fact that P32 has been widely expressed in the previous studies, it is difficult to obtain recombinant P32 efficiently. This study aimed to achieve soluble expression of P32 recombinant protein and to develop its specific monoclonal antibody. The gene fragment of P32Δ (GP32Δ) was synthesized by optimizing the coding sequence of amino acids 1-246 of the known goatpox P32 protein. Subsequently, GP32Δ was cloned into a prokaryotic expression vector for expression and purification, resulting in the successful production of soluble recombinant protein rP32Δ. Utilizing rP32Δ, an indirect ELISA method was established by immunizing 6-week-old BALB/c mice with inactivated GTPV as the antigen. Through hybridoma technology, three monoclonal antibody hybridoma cell lines secreting anti-goat pox virus rP32Δ were screened, designated as 2F3, 3E8, and 4H5, respectively. These monoclonal antibodies, classified as IgG1, IgG2a, and IgG2b, respectively, with κappa light chains, were characterized following ascites preparation and purification. Indirect ELISA results demonstrated that the ELISA potency of the three monoclonal antibodies exceeded 1:12800. Furthermore, Western blot analysis revealed specific reactivity of both 3E8 and 4H5 with rP32Δ, while immunofluorescence assays confirmed 3E8's ability to specifically recognize GTPV in cells. The preceding findings demonstrate the successful acquisition of the soluble expressed recombinant P32 protein and its specific monoclonal antibody 3E8 in this study, thereby laying a foundational material basis for the establishment of a GTPV detection method.

Abstract Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, hypoxic conditions repress antiviral-responsive genes independently of HIF signaling. EGLN1 is identified as a key mediator of the oxygen enhancement of antiviral innate immune responses. Under sufficient oxygen conditions, EGLN1 retains its prolyl hydroxylase activity to catalyze the hydroxylation of IRF3 at proline 10. This modification enhances IRF3 phosphorylation, dimerization and nuclear translocation, leading to subsequent IRF3 activation. Furthermore, mice and zebrafish with Egln1 deletion, treatment with the EGLN inhibitor FG4592, or mice carrying an Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct link between oxygen and antiviral responses, but also provide insight into the mechanisms by which oxygen regulates innate immunity.

Abstract Nutrient enrichment is a major global change component that often disrupts the relationship between aboveground biodiversity and ecosystem functions by promoting species dominance, altering trophic interactions, and reducing ecosystem stability. Emerging evidence indicates that nutrient enrichment also reduces soil biodiversity and weakens the relationship between belowground biodiversity and ecosystem functions, but the underlying mechanisms remain largely unclear. Here, we explore the effects of nutrient enrichment on soil properties, soil biodiversity, and multiple ecosystem functions through a 13-year field experiment. We show that soil acidification induced by nutrient enrichment, rather than changes in mineral nutrient and carbon (C) availability, is the primary factor negatively affecting the relationship between soil diversity and ecosystem multifunctionality. Nitrogen and phosphorus additions significantly reduce soil pH, diversity of bacteria, fungi and nematodes, as well as an array of ecosystem functions related to C and nutrient cycling. Effects of nutrient enrichment on microbial diversity also have negative consequences at higher trophic levels on the diversity of microbivorous nematodes. These results indicate that nutrient-induced acidification can cascade up its impacts along the soil food webs and influence ecosystem functioning, providing novel insight into the mechanisms through which nutrient enrichment influences soil community and ecosystem properties.

Abstract The application of network formulaology and network pharmacology has significantly advanced the scientific understanding of traditional Chinese medicine (TCM) treatment mechanisms in disease. The field of herbal biology is experiencing a surge in data generation. However, researchers are encountering challenges due to the fragmented nature of the data and the reliance on programming tools for data analysis. We have developed TCMNPAS, a comprehensive analysis platform that integrates network formularology and network pharmacology. This platform is designed to investigate in-depth the compatibility characteristics of TCM formulas and their potential molecular mechanisms. TCMNPAS incorporates multiple resources and offers a range of functions designed for automated analysis implementation, including prescription mining, molecular docking, network pharmacology analysis, and visualization. These functions enable researchers to analyze and obtain core herbs and core formulas from herbal prescription data through prescription mining. Additionally, TCMNPAS facilitates virtual screening of active compounds in TCM and its formulas through batch molecular docking, allowing for the rapid construction and analysis of networks associated with “herb-compound-target-pathway” and disease targets. Built upon the integrated analysis concept of network formulaology and network pharmacology, TCMNPAS enables quick point-and-click completion of network-based association analysis, spanning from core formula mining from clinical data to the exploration of therapeutic targets for disease treatment. TCMNPAS serves as a powerful platform for uncovering the combinatorial rules and mechanism of TCM formulas holistically. We distribute TCMNPAS within an open-source R package at GitHub ( https://github.com/yangpluszhu/tcmnpas ), and the project is freely available at http://54.223.75.62:3838/ .

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH.MethodsSingle-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining.ResultsThe results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression.ConclusionCD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

Purpose Metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive cancer with generally poor outcomes. Effective methods for predicting survival in patients with metastatic LCNEC are needed. This study aimed to identify independent survival predictors and develop nomograms for predicting survival in patients with metastatic LCNEC. Patients and Methods We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, identifying patients with metastatic LCNEC diagnosed between 2010 and 2017. To find independent predictors of cancer-specific survival (CSS), we performed Cox regression analysis. A nomogram was developed to predict the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC. The concordance index (C-index), area under the receiver operating characteristic (ROC) curves (AUC), and calibration curves were adopted with the aim of assessing whether the model can be discriminative and reliable. Decision curve analyses (DCAs) were used to assess the model’s utility and benefits from a clinical perspective. Results This study enrolled a total of 616 patients, of whom 432 were allocated to the training cohort and 184 to the validation cohort. Age, T staging, N staging, metastatic sites, radiotherapy, and chemotherapy were identified as independent prognostic factors for patients with metastatic LCNEC based on multivariable Cox regression analysis results. The nomogram showed strong performance with C-index values of 0.733 and 0.728 for the training and validation cohorts, respectively. ROC curves indicated good predictive performance of the model, with AUC values of 0.796, 0.735, and 0.736 for predicting the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC in the training cohort, and 0.795, 0.801, and 0.780 in the validation cohort, respectively. Calibration curves and DCAs confirmed the nomogram’s reliability and clinical utility. Conclusion The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.

Abstract The global concern over water pollution caused by organic pollutants such as methylene blue (MB) and other dyes has reached a critical level. Herein, the Allium cepa L. peel extract was utilized to fabricate copper oxide (CuO) nanoparticles. The CuO was combined with MgAl-layered double hydroxides (MgAl-LDHs) via a co-precipitation method with varying weight ratios of the CuO/LDHs. The composite catalysts were characterized and tested for the degradation of MB dye. The CuO/MgAl-LDH (1:2) showed the highest photocatalytic performance and achieved 99.20% MB degradation. However, only 90.03, 85.30, 71.87, and 35.53% MB dye was degraded with CuO/MgAl-LDHs (1:1), CuO/MgAl-LDHs (2:1), CuO, and MgAl-LDHs catalysts, respectively. Furthermore, a pseudo-first-order rate constant of the CuO/MgAl-LDHs (1:2) was 0.03141 min−1 while the rate constants for CuO and MgAl-LDHs were 0.0156 and 0.0052 min−1, respectively. The results demonstrated that the composite catalysts exhibited an improved catalytic performance than the pristine CuO and MgAl-LDHs. The higher photocatalytic performances of composite catalysts may be due to the uniform distribution of CuO nanoparticles into the LDH matrix, the higher surface area, and the lower electron and hole recombination rates. Therefore, the CuO/MgAl-LDHs composite catalyst can be one of the candidates used in environmental remediation.

Abstract The causal relationship between gut microbiota and DNA methylation phenotypic age acceleration remains unclear. This study aims to examine the causal effect of gut microbiota on the acceleration of DNA methylation phenotypic age using Mendelian randomization. A total of 212 gut microbiota were included in this study, and their 16S rRNA sequencing data were obtained from the Genome-wide Association Study (GWAS) database. The GWAS data corresponding to DNA methylation phenotypic age acceleration were selected as the outcome variable. Two-sample Mendelian randomization (TSMR) was conducted using R software. During the analysis process, careful consideration was given to address potential biases arising from linkage disequilibrium and weak instrumental variables. The results from inverse-variance weighting (IVW) analysis revealed significant associations (P

Abstract Injury or stress can induce intracellular translocation and release of nuclear HMGB1, a DAMP molecule known to participate in inflammation and other pathological processes. Active release of HMGB1 from stimulated macrophages can be mediated by inflammasomes, which cleave Gasdermin D to form pores on cytoplasmic membranes. We previously had shown that active release of HMGB1 from autophagy deficient hepatocytes also depended on the inflammasome but how the inflammasome was activated was not known. Here we report that persistent activation of transcription factor NRF2 under the autophagy deficient condition led to transcriptional upregulation of Caspase-11 expression, which could then activate the CASPASE-1inflammasome. Using chromatin immunoprecipitation (CHIP) and luciferase-based reporter assays, we show that NRF2 directly binds to the Caspase-11 promoter and transcriptionally increase the expression of Caspase-11. Genetic deletion of Caspase-11 in autophagy-deficient livers represses the release of HMGB1 and its pathological consequence, ductular cell proliferation. Consistently, deletion of NLRP3, which can activate CASPASE-1 mediated inflammasomes under other types of signals, did not prevent HMGB1 release and ductular cell proliferation in autophagy deficient livers. Surprisingly, while cleavage of GASDEMIN D occurred in autophagy-deficient livers its deletion did not prevent the HMGB1 release, suggesting that CASPASE-11-mediated inflammasome activation may also engage in a different mechanism for HMGB1 release by the autophagy deficient hepatocytes. Collectively, this work reveals the novel role of NRF2 in transcriptional upregulation of Caspase-11 and in inflammasome activation to promote active release of HMGB via a non-Gasdermin D mediated avenue.

Objectives Studies have shown that good cognitive function can moderate the relationship between non-exercise physical activity (NEPA) and activities of daily living (ADLs) disability to some extent, and this study mainly explores the relationship between ADL and NEPA and cognitive function in Chinese older adults.Setting and participants Data came from a nationally representative sample of 2471 Chinese old adults (aged 65+) from the 2011, 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey.Primary and secondary outcome measures A cross-lagged panel model combined with mediation analysis was used to determine the relationship between ADL and NEPA and the mediating effect of cognitive function on the ascertained ADL–NEPA relationship.Results The more frequently people over the age of 65 in China participate in NEPA, the lower the risk of ADL disability. Cognitive function partially mediated this expected relationship, accounting for 9.09% of the total NEPA effect on ADL.Conclusion Participating in more NEPA could reduce the risk of ADL disability, and participating in NEPA may reduce the risk of ADL disability through cognitive function to some extent.

A bismuth-titanium bimetal oxysulfide BiTiOS catalyst was prepared via hydrolysis and characterized by different testing techniques. This BiTiOS catalyst, forming the Ti-doped Bi2(O,S)3 phase, can format the oxygen vacancy, increase its electrochemically active surface sites, enhance the electron lifetime, and facilitate fast electron transfer. The BiTiOS catalyst exhibits good electrochemical performance and long-term stability due to its excellent catalytic reduction activity for toxic organic of p-nitrophenol, organic dyes of methyl orange, methylene blue, and rhodamine, and the heavy metal ion of Cr(VI) in the presence of NaBH4 in the dark. The BiTiOS catalyst with the best reduction activity was prepared at a molar ratio of n(Bi): n(Ti): n(TAA) at 1: 2: 4. The 100 mL for each 20 ppm MO, MB, RhB, and 4-NP was reduced entirely in 4, 4, 2, and 8 min, respectively. In comparison, the reduction of 100 mL of 50 ppm Cr(VI) took 22 min. The BiTiOS-2 catalyst, showing fast reduction efficiency and excellent stability and durability, is expected to have great potential in wastewater treatment.

Previously, we reported that the mammalian lysine monomethylase SET7 impairs the transcriptional activity of hypoxia-inducible factor (HIF), and set7-deficient zebrafish exhibit enhanced tolerance to hypoxia stress. Megalobrama amblycephala, an extensively farmed endemic species in China, is highly sensitive to hypoxia stress, which has posed a serious threat to its intensive and large-scale culture. Therefore, it is meaningful to identify key candidate genes related to the hypoxia tolerance trait in Megalobrama amblycephala. In this study, we found that set7 is highly conserved across species. The luciferase reporter assay showed that Megalobrama amblycephala set7 inhibits the transcriptional activity of hif-1αa/b and hif-2αa/b. Furthermore, using the fluorescent glucose analog 2-NBDG, we observed that overexpression of Megalobrama amblycephala set7 inhibited glucose uptake in EPC cells under hypoxic conditions. Our findings may provide clues to understand the function of Megalobrama amblycephala set7 in the hypoxia signaling pathway, and provide a potential target for genetic breeding of hypoxia tolerant species.

Abstract Transgenic soybean is one of the most planted crops for human food and animal feed. The channel catfish (Ictalurus punctatus) is an important aquatic organism cultured worldwide. In this study, the effect of six different soybean diets containing: two transgenic soybeans expressing different types of cp4-epsps, Vip3Aa and pat genes (DBN9004 and DBN8002), their non-transgenic parent JACK, and three conventional soybean varieties (Dongsheng3, Dongsheng7, and Dongsheng9) was investigated in juvenile channel catfish for eight weeks, and a safety assessment was performed. During the experiment, no difference in survival rate was observed in six groups. The hepatosomatic index (HSI) and condition factor (CF) showed no significant difference. Moreover, comparable feed conversion (FC), feeding rate (FR), and feed conversion ratio (FCR) were found between transgenic soybean and JACK groups. Assessment of growth performance showed that the weight gain rate (WGR) and specific growth rate (SGR) of channel catfish were consistent. In addition, there were no changes in enzyme activity indexes (lactate dehydrogenase (LDH), total antioxidant capacity (T-AOC), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) in channel catfish among treatments. The research provided an experimental basis for the aquaculture feed industry to employ transgenic soybean DBN9004 and DBN8002 for commercial purposes.

Abstract Serine proteases (SPs) and their homologs (SPHs) are among the best-characterized gene families. They are involved in several physiological processes, including digestion, embryonic development and immunity. In the current study, a total of 177 SPs-related genes were characterized in the genome of Ostrinia furnacalis. The activation site of SPs/SPHs and enzyme specificity of SPs were identified, and the findings showed that most of the SPs analyzed possessed trypsin substrate specificity. Several SPs/SPHs with similar simple gene structures had tandem repeat-like distributions on the scaffold, indicated that gene expansion has occurred in this large family. Furthermore, we constructed 30 RNA sequencing libraries including four with developmental stage and four middle larval stage tissues to study the transcript levels of these genes. Differentially upregulated and downregulated genes were obtained via data analysis. More than one-quarter of the genes were specifically identified as highly expressed in the midgut in compared to the other three tissues evaluated. In the current study, the domain structure, gene location and phylogenetic relationship of genes in O. furnacalis were explored. Orthologous comparisons of SPs/SPHs between model insects and O. furnacalis indicated their possible functions. This information provides a basis for understanding the functional roles of this large family.

RNA is an important information and functional molecule. It can respond to the regulation of life processes and is also a key molecule in gene expression and regulation. Therefore, RNA detection technology has been widely used in many fields, especially in disease diagnosis, medical research, genetic engineering and other fields. However, the current RT-qPCR for RNA detection is complex, costly and requires the support of professional technicians, resulting in it not having great potential for rapid application in the field. PCR-free techniques are the most attractive alternative. They are a low-cost, simple operation method and do not require the support of large instruments, providing a new concept for the development of new RNA detection methods. This article reviews current PCR-free methods, overviews reported RNA biosensors based on electrochemistry, SPR, microfluidics, nanomaterials and CRISPR, and discusses their challenges and future research prospects in RNA detection.

Polymeric immunoglobulin (Ig) receptor-like (pIgRL) molecules have been identified in teleost fish. However, compared to functional studies of their related genes (e.g., mammalian CD300 family) in eliminating pathogen invasion while preserving homeostasis, the roles of pIgRL in teleost fish remain unclear. In this study, we demonstrated that a pair of pIgRL molecules in zebrafish, pIgRL3.5 and pIgRL4.2, were highly expressed in the intestine and immune cells. Moreover, we constructed an Edwardsiella piscicida infection model, which induced strong inflammatory responses in the zebrafish intestine. Interestingly, pIgRL3.5 and pIgRL4.2 exhibited opposite inducible expression patterns in response to bacterial infection, suggesting that they perform different roles. More importantly, by conducting overexpression and knockdown experiments, our findings demonstrated that zebrafish pIgRL3.5 played a protective role in host defense against E. piscicida infection by inhibiting excessive inflammatory responses. In contrast, pIgRL4.2 facilitated pathogen growth and dissemination in zebrafish intestine. Collectively, our findings are the first to demonstrate that a pair of pIgRL molecules in teleost fish play opposite roles in mucosal immune response to bacterial infection. Therefore, our results provide crucial insights into the conserved role of pIgRL molecules in immune regulatory functions throughout vertebrate evolution.

Oxygen (O2) profoundly influences the physiological processes of aerobic organisms through a range of mechanisms. Recently, increasing evidence has revealed the relationship between viral infection and oxygen levels. However, due to a lack of feasible methods and in vivo models, how oxygen directly affects antiviral capability remains largely unknown. In contrast to terrestrial animals, fish live in water for life, where oxygen levels change more frequently than on land in areas with similar altitude. Therefore, fish appear to be ideal organisms for elucidating the effect of oxygen levels on antiviral responses. In this study, we report that zebrafish under low oxygen conditions are more susceptible to SVCV infection. Further assays indicate that low oxygen tension not only suppresses SVCV-induced IFN activation but also promotes SVCV replication in both zebrafish cell lines and zebrafish. This study provides novel insights into the effect of oxygen on antiviral responses and virus replication.

Monoclinic argentite Ag2S-based AgCoOS oxysulfide catalyst with high catalytic reduction performance in the dark with NaBH4 was prepared via a facial method. The co-doping of transition metal cations and anions was employed to effectively adjust the electron transfer property of the catalyst, with O used to modify the energy band structure and Co to provide extra active sites for the electrophilic and nucleophile reactions. The hybridization of O and S orbitals promoted the stability of the Ag2S-based catalyst. The optimized doping amount of 2.40% led to the highest catalytic reduction performance, as demonstrated by AgCoOS-3 catalyst, which achieved a complete reduction of 4-NP, MB, MO, and RhB (100 ml, 50 ppm) within 10 min, 6 min, 8 min, and 6 min, respectively, while maintaining good stability during the cycling tests. The response surface and contour plots were adopted to provide insights into the interactions between variables and their impact on the catalytic reduction reaction performance. The results suggest that the high-performance Co, O co-doped Ag2S catalyst synthesized by the green procedures has excellent potential for industrial wastewater treatment applications.

Abstract Background As the studies regarding the brain metastasis (BM) of pulmonary large cell neuroendocrine carcinoma (LCNEC) are insufficient, the present research aims to describe the risk factors and prognostic factors that are related to cancer‐specific survival (CSS) for LCNEC patients with BM. Methods The data of LCNEC patients between January 2010 and October 2018 were obtained from the SEER database. Binary logistic regression analyses were utilized to screen the possible risk factors related to BM. Prognostic factors for LCNEC patients with BM were indentified by Cox regression analyses. Moreover, a nomogram was established to predict the 6‐, 12‐, and 18‐month CSS rates. The concordance index (C‐index), receiver operating characteristic (ROC) curves and calibration curves were utilized to assess the discrimination and reliability of the model. Clinical decision curves (DCAs) were used to evaluate the clinical benefits and utility of our model. Results Totally, 1875 patients were enrolled, with 294 (15.7%) of them having BM at diagnosis. Multivariate logistic regression analyses revealed that patients with age

Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia‐inducible factor 1α (HIF‐1α), and thus, we hypothesized that SIRT3 may influence hypoxia‐induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC‐2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia‐responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia‐inducible factor 1α (HIF‐1α) and activates its downstream target gene expression in GC‐2 cells. We also show that the SIRT3 inhibitor 3‐TYP suppresses HIF‐1α target gene expression and alleviates hypoxia‐induced apoptosis of GC‐2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia‐induced apoptosis of mouse type B spermatogonia GC‐2 cells.

Abstract A growing body of evidence has indicated an expanding functional network of B‐cell lymphoma 2 (BCL‐2) family proteins beyond regulation of cell death and survival. Here, we examined the role and mechanisms of BH3 interacting‐domain death agonist (BID), a pro‐death BCL‐2 family member, in the development of diet‐induced metabolic dysfunction. Mice deficient in bid (bid−/−) were resistant to high‐fat diet (HFD)–induced obesity, hepatic steatosis, and dyslipidemia with an increased insulin sensitivity. Indirect calorimetry analysis indicated that bid deficiency increased metabolic rate and decreased respiratory exchange ratio, suggesting a larger contribution of lipids to overall energy expenditure. While expression of several genes related to lipid accumulation was only increased in wild‐type livers, metabolomics analysis revealed a consistent reduction in fatty acids but an increase in certain sugars and Krebs cycle intermediates in bid−/− livers. Gut microbiota (GM) analysis indicated that HFD induced gut dysbiosis with differential patterns in wild‐type and in bid−/− mice. Notably, abrogation of GM by antibiotics during HFD feeding eliminated the beneficial effects against obesity and hepatic steatosis conferred by the bid deficiency. Conclusion: These results indicate that the protective role of bid‐deficiency against diet‐induced metabolic dysfunction interacts with the function of GM.

Abstract Background In view of the fact that there is no effective treatment for dementia, the number of years that dementia patients have to live with dementia will gradually increase for the rest of their lives, and the disability loss caused by dementia will increase. It is urgent to study the influence of risk factors on dementia by making use of the potential of prevention. The purpose of this study is to quantify the burden of dementia disability attributable to risk factors by assessing the population attributable fractions (PAFs) in Jiangxi Province, which is one of the regions of moderate aging process of China. Methods The prevalence data of nine risk factors were obtained through the Sixth National Health Service Survey in 2018, which covered 2713 older people. Levin’s formula was used to calculate the PAF for each risk factor for dementia. We adjusted the PAF for communality between risk factors, and used these values to calculate overall weighted PAFs and the years lived with disability (YLDs), which were attributable to nine risk factors. Results The number of dementia cases and their proportions that can theoretically be prevented by nine identified risk factors were 111636 (99595-120877) and 66.8% (59.6-72.3), respectively. The total YLDs of dementia were estimated to be 61136 (46463-78369) (males: 36434 [24100-49330], females: 23956 [14716-34589]). Physical inactivity (11639 [8845-14920]), low social contact (9324 [7086-11952]), and hearing loss (5668 [4307-7265] were the top three contributors to dementia. Conclusions The moderate aging areas represented by Jiangxi Province have great potential in the prevention of dementia. Targeted interventions and management of risk factors can effectively reduce the disability burden of dementia.

Abstract Background A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits. However, the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs. Results Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq, and identified 557,273 merged peaks, which greatly expanded the pig regulatory element repository. We revealed tissue-specific regulatory elements which were associated with tissue-relevant biological functions. We identified both positive and negative significant correlations between the regulatory elements and gene transcripts, which showed distinct distributions in terms of their strength and distances from corresponding genes. We investigated the presence of transposable elements (TEs) in open chromatin regions across all tissues, these included identifications of porcine endogenous retroviruses (PERVs) exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements. Furthermore, we prioritized a potential causal variant for polyunsaturated fatty acid in the muscle. Conclusions Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions, as well as regulatory variants of loci associated with complex traits in pigs.

Objective:. The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined. Methods:. PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models. Results:. Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], –0.126–0.609) and dropout rate of 2.1% (95% CrI, 0.007–0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017–0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76–0.96) for the achievement of progression-free survival and overall survival, respectively. Conclusion:. In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.

Microplastics (MPs) and the heavy metal cadmium (Cd) have attracted global attention for their toxicological interactions in aquatic organisms. The purpose of this investigation was evaluating the effect of MPs (1 mg L−1) and Cd (5 mg L−1) on the liver function, immune response of crucian carp (Carassius carassius) after 96 h exposure, and intestinal microbiota after 21 days, respectively. Co-exposure to MPs and Cd significantly enhanced MP accumulation in the liver of the crucian carp compared to the accumulation with exposure to MPs alone. Co-exposure to MPs and Cd triggered notable histopathological alterations accompanied by increased hepatic cell necrosis and inflammation, and was associated with higher aspartate aminotransferase and alanine aminotransferase levels, lower superoxide dismutase and catalase activity levels, but higher malondialdehyde content and total antioxidant capacity in the liver. Moreover, the combined treatment of MPs and Cd led to the up-regulated transcription of genes related to immune response, such as interleukin 8 (il-8), il-10, il-1β, tumor necrosis factor-α, and heat shock protein 70, both in the liver and spleen. Co-exposure to MPs and Cd reduced the variety and abundance of the intestinal microbiota in the crucian carp. Our research indicates that the combined exposure to MPs and Cd may exert synergistic toxic effects on crucian carp, which could impede the sustainable growth of the aquaculture industry and pose potential risks to food safety.

Abstract As a main regulator of cellular responses to hypoxia, the protein stability of hypoxia-inducible factor (HIF)-1α is strictly controlled by oxygen tension dependent of PHDs-catalyzed protein hydroxylation and pVHL complex-mediated proteasomal degradation. Whether HIF-1α protein stability as well as its activity can be further regulated under hypoxia is not well understood. In this study, we found that OTUB1 augments hypoxia signaling independent of PHDs/VHL and FIH. OTUB1 binds to HIF-1α and depletion of OTUB1 reduces endogenous HIF-1α protein under hypoxia. In addition, OTUB1 inhibits K48-linked polyubiquitination of HIF-1α via its non-canonical inhibition of ubiquitination activity. Furthermore, OTUB1 promotes hypoxia-induced glycolytic reprogramming for cellular metabolic adaptation. These findings define a novel regulation of HIF-1α under hypoxia and demonstrate that OTUB1-mediated HIF-1α stabilization positively regulates HIF-1α transcriptional activity and benefits cellular hypoxia adaptation.

Objectives The purpose of this study was to use easily obtained and directly observable clinical features to establish predictive models to identify patients at increased risk of stroke.Setting and participants A total of 46 240 valid records were obtained from 8 research centres and 14 communities in Jiangxi province, China, between February and September 2018.Primary and secondary outcome measures The area under the receiver operating characteristic curve (AUC), sensitivity, specificity and accuracy were calculated to test the performance of the five models (logistic regression (LR), random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost) and gradient boosting DT). The calibration curve was used to show calibration performance.Results The results indicated that XGBoost (AUC: 0.924, accuracy: 0.873, sensitivity: 0.776, specificity: 0.916) and RF (AUC: 0.924, accuracy: 0.872, sensitivity: 0.778, specificity: 0.913) demonstrated excellent performance in predicting stroke. Physical inactivity, hypertension, meat-based diet and high salt intake were important prediction features of stroke.Conclusion The five machine learning models all had good predictive and discriminatory performance for stroke. The performance of RF and XGBoost was slightly better than that of LR, which was easier to interpret and less prone to overfitting. This work provides a rapid and accurate tool for stroke risk assessment, which can help to improve the efficiency of stroke screening medical services and the management of high-risk groups.

BackgroundBibliometric analysis is a quantitative method which applies mathematical and statistical tools to evaluate the inter-relationships and impacts of publications, authors, institutions and countries in a specific research area. Systematic reviews and meta-analyses (SRMAs) are summaries of the best available evidence to address a specific research question via comprehensively literature search, in-depth analysis and synthesis of results. To date, there have been several studies summarizing the publication trends of SRMAs in research specialties, however, none has conducted specifically in ophthalmology. The purpose of this study is to establish the scientometric landscape of SRMAs published in the field of ophthalmology over time.MethodsWe retrieved relevant ophthalmological SRMAs and the corresponding bibliometric parameters during 2000 to 2020 from Web of Science Core Collection. Bibliometric analysis was performed using bibliometrix package. Pre-registration and guideline compliance of each article was independently assessed by two investigators.ResultsA total of 2,660 SRMAs were included, and the average annual growth rate was 21.26%. China and the United States were the most productive countries, while Singapore was the country with the highest average citations per document. Wong TY was not only the most productive, but also the most frequently cited author. The most productive affiliation was National University of Singapore (n = 236). Systematic reviews and meta-analyses output in most subspecialties had steadily increased with retina/vitreous (n = 986), glaucoma (n = 411) and cornea/external diseases (n = 303) constantly as the most dominant fields. Rates of pre-registration and guideline compliance had dramatically increased over time, with 20.0 and 63.5% of article being pre-registered and reported guideline in 2020, respectively. However, SRMAs published on ophthalmology journals tended to be less frequently pre-registered and guideline complied than those on non-ophthalmology journals (both p

Abstract Water pollution as a result of releasing organic and inorganic pollutants is the main concern and health risk factor for human beings. To minimize the effect of toxicity from pollutants, enormous method has been applied. In this report, the CuAl-layered double hydroxide/MgO2 composite catalysts were synthesized via in-situ growth of magnesium peroxide on the layered double hydroxide (LDH) sheet. The preparations of the catalysts were performed with varying the ratio of LDH: MgO2 which was abbreviated as CuAl-LDH/MgO2-35, CuAl-LDH/MgO2-50, and CuAl-LDH/MgO2-65 for 35:65, 50:50, and 65:35% weight ratios, respectively. The prepared catalysts were characterized and evaluated for methyl orange (MO) dye degradation at room temperature under dark conditions. Among the catalysts, CuAl-LDH/MgO2-50 showed an excellent Fenton-like reaction under neutral condition at which 97% of MO was degraded in the 100 min reaction. However, CuAl-LDH, MgO2, CuAl-LDH/MgO2-35, and CuAl-LDH/MgO2-65 catalysts degrade only 61, 8, 35, and 69% of MO dye. The highest degradation efficiency for CuAl-LDH/MgO2-50 could be due to the presence of optimum amount of copper along with the sufficient amount of generated hydrogen peroxide from MgO2 to run the Fenton-like reaction process. Moreover, the catalyst can also be able to use repeatedly with a minimum loss of activity. In general, the result suggests that CuAl-LDH/MgO2 composite is an option for the degradation of organic pollutants.

Effective regulation of gene-edited products and resolution of public concerns are the prerequisites for the industrialization of gene-edited crops and their derived foods. CRISPR-associated protein, the core element of the CRISPR system, requires to be regulated. Thus, there is an urgent need to establish qualitative and quantitative detection methods for the Cas gene. In the present study, the primers and probes were designed and screened for Cas12a (Cpf1), which is the most commonly used target site in gene editing; we performed PCR system optimization, determined the optimal primer concentration and annealing temperature, and established qualitative PCR and quantitative PCR (qPCR) assays for detecting Cpf1 in gene editing by specificity and sensitivity tests. In specificity testing, qualitative PCR and qPCR methods could 100% detect samples containing Cpf1 DNA, while the detection rate of other samples without Cpf1 was 0%. In the assay sensitivity test, the limit of detection of qualitative PCR was 0.1% (approximately 44 copies), and the limit of detection of the qPCR method was 14 copies. In the stability test, both the qualitative PCR and qPCR methods were repeated 60 times at their corresponding lowest detection limit concentrations, and the results were positive. Thus, the qualitative and quantitative assays for Cpf1 are specific, sensitive, and stable. The method provides technical support for the effective monitoring of gene-edited products and their derived foods in the future.

Tunicates are widely distributed worldwide and are recognized as abundant marine bioresources with many potential applications. In this review, state-of-the-art studies on chemical composition analyses of various tunicate species were summarized; these studies confirmed that tunicates contain nutrients similar to fish (such as abundant cellulose, protein, and ω-3 fatty acid (FA)-rich lipids), indicating their practical and feasible uses for food or animal feed exploration. However, the presence of certain toxic elements should be evaluated in terms of safety. Moreover, recent studies on bioactive substances extracted from tunicates (such as toxins, sphingomyelins, and tunichromes) were analyzed, and their biological properties were comprehensively reviewed, including antimicrobial, anticancer, antioxidant, antidiabetic, and anti-inflammatory activities. In addition, some insights and prospects for the future exploration of tunicates are provided which are expected to guide their further application in the food, animal feed, and pharmaceutical industries. This review is critical to providing a new pathway for converting the common pollution issues of hydroponic nutrients into valuable marine bioresources.

Insects employ multifaceted strategies to combat invading fungi, with immunity being a promising mechanism. Immune pathways function in signal transduction and amplification, ultimately leading to the activation of antimicrobial peptides (AMPs). Although several studies have shown that immune pathways are responsible for defending against fungi, the roles of parasitoid immune pathways involved in antifungal responses remain unknown. In this study, we evaluated the roles of the Toll and IMD pathways of a pupal parasitoid, Pteromalus puparum (Hymenoptera: Pteromalidae), in fighting against Beauveria bassiana (Hypocreales: Cordycipitaceae). Successful colonization of B. bassiana on P. puparum adults was confirmed by scanning electron microscopy (SEM). AMPs were induced upon B. bassiana infection. The knockdown of key genes, PpTollA and PpIMD, in Toll and IMD signaling pathways, respectively, significantly compromised insect defense against fungal infection. The knockdown of either PpTollA or PpIMD in P. puparum dramatically promoted the proliferation of B. bassiana, resulting in a decreased survival rate and downregulated expression levels of AMPs against B. bassiana compared to controls. These data indicated that PpTollA and PpIMD participate in Toll and IMD-mediated activation of antifungal responses, respectively. In summary, this study has greatly broadened our knowledge of the parasitoid antifungal immunity against fungi.

Wool-coiled MoSrOS bimetal oxysulfide catalysts were synthesized by a simple method. The catalysts were characterized by different instruments. The MoSrOS reduction activities were also investigated by the reduction of Cr(VI), Rhodamine-B (RhB), Methyl orange (MO), Methylene blue (MB) and 4-nitrophenol (4-NP). The results showed that 100 mL (20 ppm) of 4-NP was completely reduced into 4-aminophenol (4-AP) in 20 min. Moreover, 100 mL (20 ppm) of MB, 100 mL (50 ppm) of RhB, 100 mL (50 ppm) of MO and 100 mL (50 ppm) of Cr(VI) were completely reduced within 6, 20, 40, and 30 min, respectively, by MoSrOS-2 bimetal oxysulfide catalyst. Hence, the wool-coiled MoSrOS bimetal oxysulfide catalysts could be used in the detoxification of toxic organic and inorganic pollutants.

BackgroundAsthma is a major global health challenge. The global strategic management and prevention of asthma report has been published, but health system planning for asthma requires a careful assessment of asthma epidemiology. This study described the incidence and mortality of global asthma from 1990 to 2019.MethodsBased on data from the global burden of disease study (GBD) 2019, we present spatial and temporal trends in asthma incidence and mortality for the world and its 204 countries and territories from 1990 to 2019. Meanwhile, age-period-cohort analysis was used to explore factors influencing asthma incidence and mortality.ResultsFrom 1990 to 2019, the incidence of asthma decreased from 601.20 per 1,00,000 to 477.92 per 1,00,000, and the mortality of asthma decreased from 8.60 per 1,00,000 to 5.96 per 1,00,000. High sociodemographic index (SDI) areas have higher age-standardised asthma incidence and low sociodemographic index areas have higher age-standardised asthma mortality. The age-period-cohort analysis results showed that the relative risk (RR) of incidence was high in children and the RR of mortality was high in elderly individuals. The RR of both asthma incidence and mortality showed a decreasing trend over time. The RR of asthma incidence in the recent birth cohort was higher than that in the previous birth cohort. The RR of asthma mortality continued to decline with the change in the birth cohort.ConclusionsGlobal asthma incidence and mortality decreased from 1990 to 2019. The decline in asthma incidence was mainly attributed to age effects and period effects, and the decline in asthma mortality was mainly attributed to period effects and cohort effects. Focusing on the risk of incidence in children and the risk of mortality in the elderly, promoting healthy lifestyles and controlling environmental risk factors can help to better control asthma.

Contagious ecthyma is a highly contagious viral disease with zoonotic significance caused by orf virus (ORFV) that affects domestic, ruminants and humans. Live attenuated virus and attenuated tissue culture vaccines are widely used in the fight against ORFV, however, the conventional attenuated vaccine strains have many drawbacks. The aim of this project was to construct a promising contagious ecthyma vaccine strain with safety, high protection efficacy and accessibility by genetic manipulation to against the disease. Using a natural ORFV-GS14 strain as the parental virus, recombinant virus, rGS14-ΔCBP-ΔGIF, with double deletions in the genes encoding the chemokine binding protein (CBP) and granulocyte/macrophage colony-stimulating factor inhibitory factor (GIF) was generated and characterized in vitro and in vivo. Results showed that the growth kinetics curve of rGS14-ΔCBP-ΔGIF and parental virus was consistent, both reaching plateau phase at 48 h post infection, which indicated that the double deletion of cbp and gif genes had little impact on the replication properties of the recombinant virus in primary goat testis (PGT) cell cultures compared with the parental virus. The safety of the double gene-deleted virus was evaluated in lambs. The lambs were monitored for 21 days post infection of the recombinant virus and no ORFV associated symptoms were observed in 21 days post-infection except for slight fever and anorexia in 5 days post-infection, and all lambs inoculated with either recombinant virus or PBS exhibited no clinical signs. To assess the protection efficacy of the rGS14-ΔCBP-ΔGIF, groups of four lambs each were inoculated with rGS14-ΔCBP-ΔGIF, rGS14-ΔCBP, rGS14-ΔGIF or PBS and challenged by a wild type virulent ORFV strain that was isolated from proliferative scabby lesions tissues of infected goat at 21-day post-inoculation. During 14 days post-challenging, lambs inoculated with rGS14-ΔCBP-ΔGIF all remained healthy with unimmunized group all infected, while the single gene-deleted viruses only protected 40% to 50% animals. These results indicated that the double gene-deleted recombinant virus could provide complete protection against virulent ORFV challenging. In conclusion, the double gene-deleted recombinant virus strain, rGS14-ΔCBP-ΔGIF, would be a promising candidate vaccine strains with safety, high protection efficacy and availability.

Glyphosate is one of the most widely used non-selective herbicides, and the creation of glyphosate-resistant cultivars solves the problem of limited spraying area. Therefore, it is of great significance to quickly identify resistant cultivars without destruction during the development of superior cultivars. This work took maize seedlings as the experimental object, and the spectral indices of leaves were calculated to construct a model with good robustness that could be used in different experiments. Compared with no transfer strategies, transferability of support vector machine learning model was improved by randomly selecting 14% of source domain from target domain to train and applying transfer component analysis algorithm, the accuracy on target domain reached 83% (increased by 71%), recall increased from 10 to 100%, and F1-score increased from 0.17 to 0.86. The overall results showed that both transfer component analysis algorithm and updating source domain could improve the transferability of model among experiments, and these two transfer strategies could complement each other’s advantages to achieve the best classification performance. Therefore, this work is beneficial to timely understanding of the physiological status of plants, identifying glyphosate resistant cultivars, and ultimately provides theoretical basis and technical support for new cultivar creation and high-throughput selection.

AimsTo reveal the impact of eleven risk factors on stroke and provide estimates of the prevention potential.MethodsWe completed a multicenter case-control study in Jiangxi, China, a middle-income area. Neuroimaging examination was performed in all cases. Controls were stroke-free adults recruited from the community in the case concentration area. Conditional logistic regression and unconditional logistic regression were used for subgroup analysis of stroke type, and other groups (sex, age and urban-rural area), respectively. Odds ratios (ORs) and their population attributable risks (PARs) were calculated, with 95% confidence intervals.ResultsA total of 43,615 participants (11,735 cases and 31,880 controls) were recruited from February to September 2018, of whom we enrolled 11,729 case-control pairs. Physical inactivity [PAR 69.5% (66.9–71.9%)] and hypertension [53.4% (49.8–56.8%)] were two major risk factors for stroke, followed by high salt intake [23.9% (20.5–27.3%)], dyslipidemia [20.5% (17.1–24.0%)], meat-based diet [17.5% (14.9–20.4%)], diabetes [7.7% (5.9–9.7%)], cardiac causes [5.3% (4.0–6.7%)], alcohol intake [4.7% (0.2–10.0%)], and high homocysteine [4.3% (1.4–7.4%)]. Nine of these factors were associated with ischemic stroke, and five were associated with intracerebral hemorrhage. Collectively, eleven risk factors accounted for 59.9% of the PAR for all stroke (ischemic stroke: 61.0%; intracerebral hemorrhage: 46.5%), and were consistent across sex (men: 65.5%; women: 62.3%), age (≤55: 65.2%; >55: 63.5%), and urban-rural areas (city: 62.2%; county: 65.7%).ConclusionThe 11 risk factors associated with stroke identified will provide an important reference for evidence-based planning for stroke prevention in middle-income areas. There is an urgent need to improve awareness, management and control of behavioral and metabolic risk factors, particularly to promote physical activity and reduce blood pressure.

Contagious ecthyma is a zoonotic disease caused by the orf virus (ORFV). Since there is no specific therapeutic drug available, vaccine immunization is the main tool to prevent and control the disease. Previously, we have reported the construction of a double-gene deletion mutant of ORFV (rGS14ΔCBPΔGIF) and evaluated it as a vaccine candidate. Building on this previous work, the current study reports the construction of a new vaccine candidate, generated by deleting a third gene (gene 121) to generate ORFV rGS14ΔCBPΔGIFΔ121. The in vitro growth characteristics, as well as the in vivo safety, immunogenicity, and protective efficacy, were evaluated. RESULTS: There was a minor difference in viral replication and proliferation between ORFV rGS14ΔCBPΔGIFΔ121 and the other two strains. ORFV rGS14ΔCBPΔGIFΔ121 induced continuous differentiation of PBMC to CD4+T cells, CD8+T cells and CD80+CD86+ cells and caused mainly Th1-like cell-mediated immunity. By comparing the triple-gene deletion mutant with the parental strain and the double-gene deletion mutant, we found that the safety of both the triple-gene deletion mutant and the double-gene deletion mutant could reach 100% in goats, while the safety of parental virus was only 50% after continually observing immunized animals for 14 days. A virulent field strain of ORFV from an ORF scab was used in the challenge experiment by inoculating the virus to the hairless area of the inner thigh of immunized animals. The result showed that the immune protection rate of triple-gene deletion mutant, double-gene mutant, and the parental virus was 100%, 66.7%, and 28.6%, respectively. In conclusion, the safety, immunogenicity, and immune-protectivity of the triple-gene deletion mutant were greatly improved to 100%, making it an excellent vaccine candidate.

Background & Aims: The functions of the liver and the intestine are closely tied in both physiological and pathologic conditions. The gut microbiota (GM) often cause deleterious effects during hepatic pathogenesis. Autophagy is essential for liver homeostasis, but the impact of hepatic autophagy function on liver-gut interaction remains unknown. Here we investigated the effect of hepatic autophagy deficiency (Atg5Δhep) on GM and in turn the effect of GM on the liver pathology. Methods: Fecal microbiota were analyzed by 16S sequencing. Antibiotics were used to modulate GM. Cholestyramine was used to reduce the enterohepatic bile acid (BA) level. The functional role of fibroblast growth factor 15 (FGF15) and ileal farnesoid X receptor (FXR) was examined in mice overexpressing FGF15 gene or in mice given a fibroblast growth factor receptor-4 (FGFR4) inhibitor. Results: Atg5Δhep causes liver injury and alterations of intestinal BA composition, with a lower proportion of tauro-conjugated BAs and a higher proportion of unconjugated BAs. The composition of GM is significantly changed with an increase in BA-metabolizing bacteria, leading to an increased expression of ileal FGF15 driven by FXR that has a higher affinity to unconjugated BAs. Notably, antibiotics or cholestyramine treatment decreased FGF15 expression and exacerbated liver injury. Consistently, inhibition of FGF15 signaling in the liver enhances liver injury. Conclusions: Deficiency of autophagy function in the liver can affect intestinal environment, leading to gut dysbiosis. Surprisingly, such changes provide an adaptive protection against the liver injury through the FGF15-FGFR4 signaling. Antibiotics use in the condition of liver injury may thus have unexpected adverse consequences via the gut-liver axis.

BackgroundCrigler-Najjar syndrome type 2 (CNS-II) is a rare genetic disease that is associated with a lack of uridine diphosphate-glucuronosyltransferase. Esophageal carcinoma is the sixth most common cause of cancer-related death worldwide, for which surgery is the most effective treatment. Reports on patients with both conditions requiring surgery are limited and The impact of hyperbilirubinemia caused by CNS-II on the perioperative period is unknown. Previous studies have found that patients with Crigler-Najjar syndrome have an increased risk of gallstones and related complications, which also poses corresponding challenges to the treatment. Herein, we present a patient with CNS-II who underwent successful thoracoscopic surgery for esophageal carcinoma.Case summaryA 65-year-old male presented to our hospital with a choking sensation after eating. A physical examination showed yellowing of the sclera and skin. The patient manifested persistent jaundice since birth and had visited many hospitals, but the cause remained undiagnosed. We performed genetic testing, which confirmed CNS-II. Gastroscopy indicated esophageal carcinoma. A multidisciplinary team discussion was carried out to determine the appropriate treatment and perioperative management for this patient. The results show that surgical resection was the most appropriate approach. Finally, the patient underwent thoracoscopic surgery for esophageal carcinoma without complications.ConclusionEsophageal carcinoma in patients with Crigler-Najjar syndrome is a rare case, and perioperative management is key in the treatment process. It is necessary to pay close attention to the changes of the disease to prevent complications.

Abstract Background The soil mycobiome is composed of a complex and diverse fungal community, which includes functionally diverse species ranging from plant pathogens to mutualists. Among the latter are arbuscular mycorrhizal fungi (AMF) that provide phosphorous (P) to plants. While plant hosts and abiotic parameters are known to structure AMF communities, it remains largely unknown how higher trophic level organisms, including protists and nematodes, affect AMF abundance and community composition. Results Here, we explored the connections between AMF, fungivorous protists and nematodes that could partly reflect trophic interactions, and linked those to rhizosphere P dynamics and plant performance in a long-term manure application setting. Our results revealed that manure addition increased AMF biomass and the density of fungivorous nematodes, and tailored the community structures of AMF, fungivorous protists, and nematodes. We detected a higher abundance of AMF digested by the dominant fungivorous nematodes Aphelenchoides and Aphelenchus in high manure treatments compared to no manure and low manure treatments. Structural equation modeling combined with network analysis suggested that predation by fungivorous protists and nematodes stimulated AMF biomass and modified the AMF community composition. The mycorrhizal-fungivore interactions catalyzed AMF colonization and expression levels of the P transporter gene ZMPht1;6 in maize roots, which resulted in enhanced plant productivity. Conclusions Our study highlights the importance of predation as a key element in shaping the composition and enhancing the biomass of AMF, leading to increased plant performance. As such, we clarify novel biological mechanism of the complex interactions between AMF, fungivorous protists, and nematodes in driving P absorption and plant performance. Video Abstract

Abstract Both contemporary and historical factors are documented to be crucial in regulating species diversity and distribution. Soil fauna contribute substantially to global biodiversity and ecosystem functioning, while it is unclear whether and to what extent historical factors shape their diversity patterns. Here, we used soil nematodes as a model organism to test historical effects on soil fauna and to investigate the relative importance of climatic, soil, and historical factors. Based on nematode distribution data in 16 natural sites at a large scale (ranging from 22 to 40°N) in mainland China, we conducted elastic net regression model to test the effects of climatic (e.g., mean and seasonality of temperature/precipitation), soil (e.g., soil carbon, nitrogen, and pH), and historical (e.g., temperature/precipitation anomaly and the velocity of the change since the Last Glacial Maximum) variables on nematode genus richness and Shannon's diversity. Additionally, variation partitioning was used to determine the contribution of the three predictor sets to the explanation of both Jaccard and Bray–Curtis community dissimilarity. We found that climate generally explained more variations in both diversity and composition than soil and historical predictors in our samples. We also showed that although historical factors (e.g., temperature change velocity) were correlated with nematode diversity and composition, the pure effects of these historical factors were negligible. In other words, the historical effects were commonly represented by their interactions with current climatic and soil factors within our selected sites. Our results indicated that contemporary factors, especially climate, may outperform historical factors in regulating soil nematode diversity patterns at large scales.

Taking the cylindrical float of the floating fence of a floating litter collection device as the research object, based on the shallow immersion characteristics of the cylindrical float, the Morison equation is modified, and the interaction between regular waves and the partially immersed horizontal cylindrical float is discussed in combination with scale model test. The results show that the modified Morison equation can accurately predict the wave force of the horizontal cylindrical float and reveal the influence of amplitude, immersion depth and period on the wave force of the cylindrical float. For partially immersed cylindrical floats, the wave force increases with the increase in wave height and decays with the increase in period. The positive value distribution of the wave force is larger than that of the negative direction, and the difference between the positive and negative directions is mainly affected by the immersion depth.

High penetration of distributed photovoltaics (PVs) has caused severe voltage violation problem in distribution networks. In view of the actual situations, this paper proposes a coordinated optimization method for distributed PVs clusters considering inadequate measurement data. Based on pivotal measurement data, each cluster firstly uses network simplification method to obtain a simplified network with complete measurement information. And then each cluster implements coordinated optimization with adjacent clusters to minimize its network losses, PVs generation losses and voltage violation amount of downstream cluster. The coordinated optimization includes two stages, i.e. evaluating voltage regulation capability of intra-cluster reactive power resources and implementing cluster autonomous optimization control. These two stages can use the reactive power resources of upstream clusters to solve the voltage violation of downstream clusters, which avoids unnecessary generation losses of distributed PVs. The effectiveness and accuracy of the proposed method are demonstrated via simulation tests on a real 10kV feeder in China and modified IEEE 123-bus system. Compared with distributed optimization method, the proposed coordinated optimization requires much less calculation time and communication data between clusters.

Mycoplasma capricolum subsp. capripneumoniae (Mccp) is the cause of contagious caprine pleuropneumonia (CCPP), which is a highly significant respiratory disease in goats leading to significant economic losses in Africa and Asia. Currently available procedures for the diagnosis of CCPP have some limitations in sensitivity, specificity, operation time, requirement of sophisticated equipment or skilled personnel, and cost. In this study, we developed a rapid, sensitive, and specific colloidal gold-based immunochromatographic assay (GICA) strip for the efficient on-site detection of antibodies against Mccp in the serum within 10 min. For the preparation of this colloidal GICA strip, recombinant P20 protein, the membrane protein of Mccp, was expressed by Escherichia coli prokaryotic expression system after purification was used as the binding antigen in the test. The rabbit anti-goat immunoglobulin G labeled with the colloidal gold was used as the detection probe, whereas the goat anti-rabbit immunoglobulin G was coated on the nitrocellulose membrane as the control line. The concentration of the coating antibody was optimized, and the effectiveness of this colloidal GICA strip was evaluated. Our results proved that the detection limit of the test strip was up to 1:64 dilutions for the Mccp antibody-positive serum samples with no cross-reactivity with other pathogens commonly infecting small ruminants,including goat pox virus, peste des petits ruminants virus, foot-and-mouth disease virus type A, or other mycoplasmas. Moreover, the colloidal GICA strip was more sensitive and specific than the indirect hemagglutination assay for the detection of Mccp antibodies. The 106 clinical serum samples were detected by the colloidal GICA strip compared with the complement fixation test, demonstrating an 87.74% concordance with the complement fixation test. This novel colloidal GICA strip would be an effective tool for the cost-effective and rapid diagnosis of CCPP in the field.

The Cu-doped ZnO photocatalysts were prepared with a green and coprecipitation approach by using water hyacinth (Eichhornia crassipes) aquatic plant extract. In the preparation process, different amount of copper precursors such as 1, 2, 3, 4, and 5% of molar ratio were added to zinc nitrate precursors and abbreviated as Cu-ZnO (1%), Cu-ZnO (2%), Cu-ZnO (3%), Cu-ZnO (4%), and Cu-ZnO (5%), respectively. The characterization of the obtained samples was carried out, and the removal of the methylene blue (MB) dye was examined. Out of all catalysts, Cu-ZnO (3%) had the best photocatalytic performance and 89% of the MB dye was degraded. However, the degradation performances of blank (without catalysts), ZnO, Cu-ZnO (1%), Cu-ZnO (2%), Cu-ZnO (4%), and Cu-ZnO (5%) catalysts were 6, 54, 69, 83, 80, and 73%, respectively. Therefore, the use of water hyacinth plant extract with the optimum amount of Cu added to ZnO during the preparation of the catalyst could have a promising application in the degradation of organic pollutants.

Background: Age-related macular degeneration (AMD) has been the leading cause of irreversible blindness in industrialized countries. Emerging data suggest that serum vitamin D levels may be associated with AMD but show mixed results. National-level population data on the relationship between vitamin D and AMD severities are still lacking. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. Retinal photographs were taken and graded for AMD stage. The odds ratio (OR) of AMD and its subtype was calculated after adjusting for confounding factors. Restricted cubic spline (RCS) analyses were used to explore potential non-linear relations. Results: A total of 5041 participants with a mean age of 59.6 years were included. After adjusting for covariates, participants with higher level of serum 25-hydroxyvitamin D [25(OH)D] had significantly greater odds of early AMD (OR, 1.65; 95% CI, 1.08–2.51) and decreased risk of late AMD (OR, 0.29; 95% CI, 0.09–0.88). When stratified by age, a positive association between the level of serum 25(OH)D and early AMD was present in the