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● Matching nitrification inhibitors with soil properties and nitrifiers is vital to achieve a higher NUE. ● Enhancing BNF, DNRA and microbial N immobilization processes via soil amendments can greatly contribute to less chemical N fertilizer input. ● Plant-associated microbiomes are critical for plant nutrient uptake, growth and fitness. ● Coevolutionary trophic relationships among soil biota need to be considered for improving crop NUE. Soil microbiomes drive the biogeochemical cycling of nitrogen and regulate soil N supply and loss, thus, pivotal nitrogen use efficiency (NUE). Meanwhile, there is an increasing awareness that plant associated microbiomes and soil food web interactions is vital for modulating crop productivity and N uptake. The rapid advances in modern omics-based techniques and biotechnologies make it possible to manipulate soil-plant microbiomes for improving NUE and reducing N environmental impacts. This paper summarizes current progress in research on regulating soil microbial N cycle processes for NUE improvement, plant-microbe interactions benefiting plant N uptake, and the importance of soil microbiomes in promoting soil health and crop productivity. We also proposes a potential holistic (rhizosphere-root-phyllosphere) microbe-based approach to improve NUE and reduce dependence on mineral N fertilizer in agroecosystems, toward nature-based solution for nutrient management in intensive cropping systems.

Objective: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. Methods: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. Results: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. Conclusions: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP. [ABSTRACT FROM AUTHOR]

The similarity and correlation analysis of word concepts has a wide range of applications in natural language processing, and has important research significance in information retrieval, text classification, data mining, and other application fields. This paper analyzes and summarizes the information of sememes relationship through the definition of words in HowNet and proposes a method to distinguish the similarity and correlation of words. Firstly, using a combination of the part of speech and sememes to distinguish the similarity and correlation between words concept. Secondly, the similarity and correlation calculation results between vocabulary concepts are used to further optimize the judgment results. Finally, the similarity and correlation distinction and discrimination between vocabulary concepts are realized. The experimental results show that the method reduces the complexity of the algorithm and greatly improves the work efficiency. The semantic similarity and correlation judgment results are more in line with the human intuitive experience and improve the accuracy of computer understanding of natural language. which provides an important theoretical basis for the development of natural language.

Galli gigerii endothelium corneum (GGEC) is a traditional Chinese medicine commonly used in clinical practice to treat various conditions such as indigestion, vomiting, spermatorrhea, and enuresis. In this study, the volatile components of different concoctions of GGEC were examined by gas chromatography-ion mobility spectrometry (GC-IMS), and the changes of the components were compared by fingerprinting, combined with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to analyze the main volatile components and find out the different markers that can distinguish the different concoctions of GGEC. In the result, the GC-IMS fingerprints of GGEC and its different concoctions showed differences in their volatile components, of which 49 volatiles were clearly characterized, with some components including monomers and dimers. The characteristic volatile components of raw GGEC (SP) were n-nonanal, (E)-2-octenal, beta-ocimene, 2-ethyl-1-hexanol, etc. The characteristic volatile components of stir-fried GGEC (QC) are heptanal, 2-octanol, (E)-2-heptenal, etc. The characteristic volatile components of sand ironing GGEC (ST) are isoamyl acetate, decanal, cyclohexanone, 2-ethyl pyrazine, etc. The characteristic volatile components of stir-fried GGEC with vinegar (CZ) are thiazole, linalool, 2,3,5-trimethylpyrazine, etc. The characteristic volatile components of stir-fried GGEC with milk (FH) are 2-methylbutanoic acid, ethyl acetate, ethyl 2-hydroxypropanoate, butyl acetate, etc. By chemometric analysis, components such as n-nonanal, (E)-2-octenal, 2-pentyl-furan, butanal, 1,4-dioxane, and 2-methylpropanoic acid could be used as difference markers to distinguish different concoction products of GGEC. Furthermore, by analyzing different volatile compounds, we can examine the changes in volatile components during processing of GGEC, which can provide experimental data for the identification and establishment of quality standards. [ABSTRACT FROM AUTHOR]

The challenges of how to simultaneously ensure global food security, improve nitrogen use efficiency (NUE) and protect the environment have received increasing attention. However, the dominant agricultural paradigm still considers high yield and reducing environmental impacts to be in conflict with one another. Here we examine a Three-Step-Strategy of past 20 years to produce more with less in China, showing that tremendous progress has been made to reduce N fertilizer input without sacrificing crop yield. The first step is to use technology for in-season root-zone nutrient management to significantly increase NUE. The second is to use technology for integrated nutrient management to increase both yield and NUE by 15%—20%. The third step is to use technology for integrated soil-crop system management to increase yield and NUE by 30%—50% simultaneously. These advances can thus be considered an effective agricultural paradigm to ensure food security, while increasing NUE and improving environmental quality.

Promoting the development of China's digital economy and the level of urban disaster reduction and governance is of great significance for accelerating the improvement of China's urban resilience and promoting the coordinated development of regional cities. This paper analyzed the spatial and temporal distribution characteristics and driving paths of urban resilience in 31 Chinese provinces, autonomous regions, and municipalities directly under the central government and proposed relevant measures to promote urban resilience. First, the urban resilience evaluation system was constructed and the entropy value method was applied to calculate the urban resilience index of each region. Second, the spatial distribution of urban resilience was explored based on the urban resilience index of each region. Finally, a qualitative comparative analysis method was used to explore the driving paths of urban resilience enhancement. The study showed that there were large regional differences in the urban resilience index, with an overall spatial pattern of "good in the east, middle in the center, and low in the west" and an overall trend of gradual increase. There are five configuration paths to generate a high urban resilience index, which can be specifically digital industry-driven path, technology factor-driven path, government input- and talent pool-driven path under market factors, technology factor- and government factor-driven path, and government investment- and infrastructure-driven path under market factors, and it is found that the digital industry-driven path is a more common path of digital economy-driven urban resilience improvement in China. The finding of this study reveals the nature of complex interactions among drivers in the process of urban resilience enhancement in China, which breaks through the limitations of traditional statistical analysis methods and provides a new perspective for the study of urban resilience issues. [ABSTRACT FROM AUTHOR]

Objective: To detect the chemical constituents in Jianqu samples under different fermentated states by using UPLC-QTOF-MS/MS technology, to conduct preliminary analyses, and to establish an HPLC method for the simultaneous determination of hesperidin and naringenin in Jianqu, and the variation of the two components during fermentation were compared. Methods: Waters ACQUITYTM UPLC HSST3 column (2.1 mm × 100 mm, 1.8 μm) was used; the mobile phase was 0.1% formic acid aqueous solution (A)-0.1% formic acid acetonitrile (B); The flow rate was 0.4 mL·min−1 with gradient elution; the column temperature was 45 °C; injection volume was 5 μL. The mass spectra of the samples were collected by negative ion mode under the electrospray ion source, and the data were screened and matched by UNIFI software. Hypersil gold C18 column (100 mm × 2.1 mm, 1.9 μm) was used; the mobile phase was acetonitrile (A)-0.1% acetic acid (B);; the flow rate with gradient elution was 0.3 mL·min−1; the column temperature was 30 °C; the injection volume was 2 μL. The content changes of hesperetin and naringenin in Jianqu at different fermentation time were detected. Results: A total of 54 compounds were identified, including flavonoids, amino acids, organic acids, terpenoids, coumarins, lignans, and other compounds. Under the selected HPLC conditions, the linear relationship between hesperidin and naringenin was discovered (r2 = 0.9996). The content of hesperidin and naringenin changed significantly in the whole fermentation process. The highest concentration of content was observed at 36 h of fermentation and then decreased to varying degrees. Conclusion: This experiment can effectively identify various chemical components in Jianqu during different fermentation periods, and determine the content of the characteristic components, so as to provide a scientific basis for further study of Jianqu fermentation processing technology as well as a sound pharmacodynamic material basis. [ABSTRACT FROM AUTHOR]

Silicosis is a systemic disease characterized by chronic persistent inflammation and incurable pulmonary fibrosis with the underlying molecular mechanisms to be fully elucidated. In this study, we employed tandem mass tag (TMT) based on quantitative proteomics technology to detect differentially expressed proteins (DEPs) in lung tissues of silica-exposed rats. A total of 285 DEPs (145 upregulated and 140 downregulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathway and functional classification of the proteins. Results showed that these DEPs were mainly enriched in the phagosome, lysosome function, complement and the coagulation cascade, glutathione metabolism, focal adhesion and ECM-receptor interactions. To validate the proteomics data, we selected and analyzed the expression trends of six proteins including CD14, PSAP, GM2A, COL1A1, ITGA8 and CLDN5 using parallel reaction monitoring (PRM). The consistent result between PRM and TMT indicated the reliability of our proteomic data. These findings will help to reveal the pathogenesis of silicosis and provide potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD020625. [ABSTRACT FROM AUTHOR]

Abstract: Two marine heat wave events along Western Australia (WA) during the alternate austral summer periods of 2010/2011 and 2012/2013, both linked to La Niña conditions, severely impacted marine ecosystems over more than 12° of latitude, which included the unprecedented bleaching of many coral reefs. Although these two heat waves were forced by similar large‐scale climate drivers, the warming patterns differed substantially between events. The central coast of WA (south of 22°S) experienced greater warming in 2010/2011, whereas the northwestern coast of WA experienced greater warming in 2012/2013. To investigate how oceanic and atmospheric heat exchange processes drove these different spatial patterns, an analysis of the ocean heat budget was conducted by integrating remote sensing observations, in situ mooring data, and a high‐resolution (∼1 km) ocean circulation model (Regional Ocean Modeling System). The results revealed substantial spatial differences in the relative contributions made by heat advection and air‐sea heat exchange between the two heat wave events. During 2010/2011, anomalous warming driven by heat advection was present throughout the region but was much stronger south of 22°S where the poleward‐flowing Leeuwin Current strengthens. During 2012/2013, air‐sea heat exchange had a much more positive (warming) influence on sea surface temperatures (especially in the northwest), and when combined with a more positive contribution of heat advection in the north, this can explain the regional differences in warming between these two La Niña‐associated marine heat wave events. [ABSTRACT FROM AUTHOR]

Macrophages play an important role in causing silicosis eventually becoming an irreversible fibrotic disease, and there are no specific drugs for silicosis in the clinic so far. Pirfenidone has consistently been shown to have anti-inflammatory and anti-fibrotic effects, but the specific mechanism by which it ameliorates fibrosis in silicosis is unclear. A rat silicosis model was established in this study, and lung tissues and serum were collected by batch execution at 14, 28, and 56 days. Also, the effects of Pirfenidone on macrophage polarization and pulmonary fibrosis were evaluated in silicosis with early intervention and late treatment by histological examination, Enzyme-linked immunosorbent assay, Hydroxyproline assay, Western blot and Quantitative reverse transcription polymerase chain reaction. The results showed that Pirfenidone significantly reduced pulmonary fibrosis in rats with silicosis, and both early intervention and late treatment effectively inhibited the expression of α-SMA, Col-I, Vimentin, Hydroxyproline, IL-1β, IL-18, and the M2 macrophage marker CD206 and Arg-1, while only early intervention effectively inhibited E-cad, TGF-β1, TNF-α, and the M1 macrophage marker iNOS, CD86. Furthermore, Pirfenidone dramatically reduced the mRNA expression of the JAK2/STAT3. These findings imply that Pirfenidone may reduce pulmonary fibrosis in silicosis rats by inhibiting macrophage polarization via the JAK2/STAT3 signaling pathway. [Display omitted] • Pirfenidone inhibits macrophage polarization and pulmonary fibrosis in silicosis rats. • JAK2 and STAT3 are involved in silicosis fibrosis process and can be inhibited by pirfenidone. • Pirfenidone may improve silicosis fibrosis by inhibiting macrophage polarization through the JAK2/STAT3 pathway. • The early intervention effect of pirfenidone in rats with silicosis is better than the later treatment effect. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the effects of subchronic exposure to chlorpyrifos on reproductive toxicology of male rats. Forty healthy male rats were divided into four groups: three exposure groups and a control group. Chlorpyrifos was administered orally to male rats at 0, 2.7, 5.4, and 12.8mg/kg for 90 days to evaluate the toxic alterations in testicular histology, testicular marker enzyme activities and related genes expression levels, sperm dynamics, and testosterone levels. The body weight and the testis weight of animals did not show any significant changes. Chlorpyrifos brought about marked reduction in testicular sperm counts, sperm motility, and significant growth of sperm malformation rate in exposed males. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. The levels of testosterone (T) showed a decreasing tendency, and there was a statistical difference between the 5.4, 12.8 mg/kg groups, and the control group. The levels of follicle stimulating hormone (FSH) were significantly increased in 5.4 and 12.8 mg/kg groups, but there were no obvious effects on the levels of luteinizing hormone (LH) and estradiol (E2). A significant increase in the activities of LDH and LDH-x was observed in chlorpyrifos exposed rats in 5.4 and12.8 mg/kg groups, but the expression levels of related genes had no significant differences between chlorpyrifos exposure groups and the control group. These results suggest that chlorpyrifos has adverse effects on reproductive system of male rats. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1083-1088, 2014. [ABSTRACT FROM AUTHOR]

The structures and immunomodulatory activities of two polysaccharides (SDH-WA and SDH-0.2A) from Rehmanniae Radix Praeparata (RRP) were investigated. RRP crude polysaccharide was obtained by water extraction and purified. Ion chromatography, high-performance gel permeation chromatography, Fourier-transform infrared spectroscopy, methylation analysis, gas chromatography–mass spectrometry, and nuclear magnetic resonance were used to characterize the polysaccharides. The main chain of SDH-WA was →6)-α-D-Gal p -(1→6)-α-D-Gal p -(1→5)-α-L-Ara f -(1→3,5)-α-L-Ara f -(1→, terminal sugar residue α-L-Ara f -(1→ linked to residue →3,5)-α-L-Ara f -(1→ on the main chain by an O-3 bond. The other two terminal sugar residues α-D-Gal p -(1→ and →6)-β-D-Gal p were linked to the end of the main chain. The main chain of SDH-0.2A was →2,4)-α-L-Rha p -(1→4)-α-D-Gal p A-(1→. Three branched chains α-D-Gal p -(1→6)-α-D-Gal p -(1→5)-α-L-Ara f -(1→3,5)-α-L-Ara f -(1→, →3,6)-β-D-Gal p -(1→5)-α-L-Ara f -(1→, and →4)-β-D-Gal p -(1→5)-α-L-Ara f -(1→ were linked to the main chain residue →2,4)-α-L-Rha p -(1→ by an O-2 bond. Three terminal sugar residues α-D-Gal p -(1→, α-L-Ara f -(1→, and →6)-β-D-Gal p were linked to the end of the chain. Both polysaccharides showed no cytotoxic effects on and significantly promoted the phagocytic activity of RAW264.7 cells. They dose-dependently improved lysozyme activity and stimulated the production of TNF-α and IL-6 by RAW264.7 cells, but attenuated the secretion of lysozymes, TNF-α, IL-6, IL-1β, and nitric oxide by lipopolysaccharide-induced RAW264.7 cells. The present studies suggest that PRR polysaccharide is a valuable source with immunomodulating. • Two polysaccharides (SDH-WA, SDH-0.2A) were purified from Rehmanniae Radix Praeparata. • Structures of SDH-WA and SDH-0.2A were characterized. • Immunomodulating activities of SDH-WA and SDH-0.2A in RAW264.7 cells were studied. [ABSTRACT FROM AUTHOR]

• On day 28, lung fibrosis in silica-induced rats was confirmed. • Silica induces changes in 682 lncRNAs (300 upregulated, 382 downregulated). • The predicted target mRNAs of lncRNAs of silicosis involves in 13 pathways. • "Proteoglycans in cancer" signaling pathway in pulmonary fibrosis is valuable to study. • LncRNA-miRNA-mRNA ceRNA network may play an important role in pulmonary fibrosis. Silicosis is a kind of chronic and incurable lung fibrotic disease with pathogenesis and molecular mechanisms largely unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of silicosis. However, how many lncRNAs involved in the pulmonary fibrosis remains to be elucidated. In this study, Wistar rats were exposed to silicon dioxide by an improved tracheal intubation method. Rats in the control group were treated with normal saline solution. Results showed that 28 days after exposure, there were significant differences in body weight and lung coefficient of rats treated with silica compared with control rats. The formation of lung fibrosis in silica-induced rats was confirmed by histologic examination. We then investigated the lncRNAs expression changes in lung tissues of silica-exposed rats and compared that with the rats in the control group using microarray. The results indicated that silica exposure leads to altered expression profile in 682 lncRNAs (300 upregulated and 382 downregulated). Seventy-three ceRNA pairs were acquired by predicted analysis. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses were used to predict the biological pathway and functional classification of lncRNAs. The results showed that silica exposure affected 13 lncRNAs pathways. The functional classification mainly involved in protein binding, cell shape and extracellular exosome. This study indicated that alteration of lncRNAs may play a role in silica-induced pulmonary fibrosis through regulation of expressions of functional genes in lungs of rat. Our results provide more insights into the mechanism of silicosis. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Silica induced EMT and pulmonary fibrosis in rats. • TGF-β1/Smad2/3 was involved at 14 days and 28 days after silica instillation. • Pirfenidone inhibited EMT and silicosis fibrosis in rats. • The effects of PFD on silicosis rats may be related to TGF-β1/Smad2/3 pathway. Abstract To study the role of pirfenidone in rats exposed to silica dust, we established the rat silicosis model with 50 mg/ml silica by intratracheal instillation. From the first day after silica instillation, rats were given pirfenidone (50, 100 mg/kg/day) and rats were sacrificed at 14 days and 28 days to observe the histopathology of lungs, to analyze the level of TNF-α, IL-1β, IL-6 in lung tissues and to measure the expression of TGF-β1, Smad2/3, vimentin, and E-cadherin in lung tissues. Results showed that pirfenidone (50, 100 mg/kg/day) reduced the silica-induced alveolar inflammation, the damage of alveolar structure and the blue areas of collagen fibers in the lungs of rats. At the same time, pirfenidone also reduced the level of TNF-α, IL-1β, IL-6 in lung tissues and the protein expression of collagen I. After pirfenidone intervention for 14 days and 28 days, the protein expression of vimentin was down-regulated and the protein expression of E-cadherin was up-regulated in lung tissues. In addition, the TGF-β1/smad2/3 pathway was activated at 14 days and 28 days after silica instillation, and pirfenidone reduced the expression of TGF-β1 and smad2/3 in the lungs. These results indicated that pirfenidone intervention inhibited the epithelial-mesenchymal transition and pulmonary fibrosis in rat silicosis model, which effects may be related to the TGF-β1/smad pathway. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (MI/R) injury is a major cause of cardiac dysfunction during cardiovascular surgery and heart transplantation and characterized by hyperactive oxidative stress and inflammatory response. Barbaloin (BAR) is the main medicinal composition of the Chinese traditional medicine aloe vera. BAR has strong anti-oxidant, anti-inflammatory and anti-tumor properties. However, the effect of BAR on MI/R-induced myocardial injury is not explored. This study aims to investigate whether BAR provides cardio-protection against MI/R injury and the underlying mechanisms. BAR (20 mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for 5 days before MI/R operation. BAR pretreatment conferred cardio-protective effects against MI/R injury by improving hemodynamic function and limiting infarction size. Moreover, BAR pretreatment effectively inhibited I/R-induced myocardial oxidative stress and inflammatory response. Furthermore, BAR pretreatment activated adenosine monophosphate-activated protein kinase (AMPK) signaling in MI/R hearts. AMPK inhibitor compound C inhibited BAR-induced AMPK activation, and blunted BAR-mediated anti-oxidative, anti-inflammatory effects and cardio-protection. Taken together our study has identified a novel function of BAR and provided a molecular basis for BAR potential applications in the treatment of MI/R injury and other ischemic disorders. [ABSTRACT FROM AUTHOR]

This article has been retracted at the request of the authors. The Editor in Chief has agreed to retract this article and the publisher supports the decision. The authors have indicated that their initial results were not reproducible when conducted by their colleagues. They indicated that the levels of autophagy were significantly different in the MI/R mice model in the respective results. The authors of this article would like to apologize to all affected parties. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal . [ABSTRACT FROM AUTHOR]

Helicobacter pylori ( H. pylori ) infect nearly half of the global population, contributing to upper digestive tract diseases. This 2019 cross-sectional study included 3,867 patients undergoing esophagogastroduodenoscopy (EGD) and 2,875 undergoing both colonoscopy and EGD. Subjects were categorized into H. pylori positive and negative groups by rapid urease test (RUT). In addition to exploring the relationship between H. pylori infection and upper gastrointestinal diseases, this study further revealed that H. pylori infection was closely related to lower digestive tract diseases, including colorectal polyp (63.28%) and colorectal cancer (75.76%), as well as upper and lower gastrointestinal comorbidities, including chronic atrophic gastritis with colorectal polyp (79.85%), peptic ulcer with colorectal polyp (79.72%), gastric polyp with colorectal polyp (66.24%), and chronic atrophic gastritis with colorectal cancer (92.86%). Besides, a univariate logistic regression analysis was conducted to compare the differences between the two groups (including gender, nationality, marital status, smoking history, drinking history, living area, age, BMI, glycosylated hemoglobin, fasting blood glucose, total cholesterol, and triglyceride levels), the results identified marital status and age as independent risk factors for H. pylori infection (OR, 1.435; 95% CI, 1.042 to 1.977; OR, 1.007; 95% CI, 1.001 to 1.013). Further clarification of the correlation between the prevalence of gastrointestinal diseases and H. pylori infection will be important for H. pylori infection management strategies and the treatment and prevention of gastrointestinal diseases.

Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), as a typical tumor marker, has been found to exert immunomodulatory effects in many diseases. We previously reported the clinical and molecular evidences supporting that SARS-Cov-2 infected the gastrointestinal (GI) tract and found a reduction of CEACAM5 in COVID-19 patients' feces which associated with gut dysbiosis. Yet the role of CEACAM5 in GI infection is ill-defined., Methods: Mice models were established through intraperitoneally injecting with recombinant viral spike-Fc to mimic the intestinal inflammation. We collected duodenum, jejunum, ileum and colon samples after 6h, 2 days, 4 days and 7 days of spike-Fc or control-Fc injection to perform proteomic analysis. Blood was collected from healthy donors and peripheral blood mononuclear cells (PBMC) were separated by density gradient centrifugation, then CD4+ T cells were isolated with magnetic beads and co-cultured with Caco-2 cells., Results: In addition to intestinal CEACAM5, the expression of tight junction and the percent of CD4+ T lymphocytes were significantly decreased in spike-Fc group compared to control (p < 0.05), accompanied with increased level of inflammatory factors. The KEGG analysis revealed differentially expressed proteins were mainly enriched in the coronavirus disease (COVID-19), tight junction, focal adhesion, adherens junction and PI3K-Akt signaling pathway. Protein-protein interaction (PPI) network analysis identified the interaction between CEACAM5 and Galectin-9 that was also verified by molecular docking and co-IP assay. We further confirmed a reduction of CEACAM5 in SARS-CoV-2 spike stimulated enterocytes could promote the expression of Galectin-9 protein in CD4+T cells. Then it gave rise to the increasing release of inflammatory factors and increased apoptosis of CD4+T cells by inhibition of PI3K/AKT/mTOR pathway. Ultimately intestinal barrier dysfunction happened., Conclusion: Our results indicated that CEACAM5 overexpression and Galectin-9 knockdown played a protective role in intestinal barrier injury upon spike-Fc stimulation. Collectively, our findings identified firstly that SARS-CoV-2 spike induced intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9. The result provides potential therapeutic targets in intestinal barrier dysfunction for treating severe COVID patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Zhang, Ren, Dou, Wen, Yang, Li, Yan and Han.)

Objective: To detect the chemical constituents in Jianqu samples under different fermentated states by using UPLC-QTOF-MS/MS technology, to conduct preliminary analyses, and to establish an HPLC method for the simultaneous determination of hesperidin and naringenin in Jianqu, and the variation of the two components during fermentation were compared., Methods: Waters ACQUITYTM UPLC HSST3 column (2.1 mm × 100 mm, 1.8 μm) was used; the mobile phase was 0.1% formic acid aqueous solution (A)-0.1% formic acid acetonitrile (B); The flow rate was 0.4 mL·min -1 with gradient elution; the column temperature was 45 °C; injection volume was 5 μL. The mass spectra of the samples were collected by negative ion mode under the electrospray ion source, and the data were screened and matched by UNIFI software. Hypersil gold C18 column (100 mm × 2.1 mm, 1.9 μm) was used; the mobile phase was acetonitrile (A)-0.1% acetic acid (B);; the flow rate with gradient elution was 0.3 mL·min -1 ; the column temperature was 30 °C; the injection volume was 2 μL. The content changes of hesperetin and naringenin in Jianqu at different fermentation time were detected., Results: A total of 54 compounds were identified, including flavonoids, amino acids, organic acids, terpenoids, coumarins, lignans, and other compounds. Under the selected HPLC conditions, the linear relationship between hesperidin and naringenin was discovered (r 2 = 0.9996). The content of hesperidin and naringenin changed significantly in the whole fermentation process. The highest concentration of content was observed at 36 h of fermentation and then decreased to varying degrees., Conclusion: This experiment can effectively identify various chemical components in Jianqu during different fermentation periods, and determine the content of the characteristic components, so as to provide a scientific basis for further study of Jianqu fermentation processing technology as well as a sound pharmacodynamic material basis.

Background: Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss., Materials and Methods: We induced gut leakiness by injecting carbon tetrachloride (CCl 4 ) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor- α (TNF- α ) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro ., Results: Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF- α levels; upregulated tight junction (TJ) expression; and inhibited epithelial I κ B- α degradation and phosphorylation, NF- κ B p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl 4 . Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro , using Caco-2 cells with gain- or loss-of-HO-1-function after TNF- α . Pretreated with JSH-23 (NF- κ B inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF- α -induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF- κ B p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury., Conclusion: HO-1/CO maintains intestinal barrier integrity through the NF- κ B/MLCK pathway. Therefore, the intestinal HO-1/CO-NF- κ B/MLCK system is a potential therapeutic target for diseases with a leaky gut., Competing Interests: All authors declare that they have no conflict of interests., (Copyright © 2021 Zhenling Zhang et al.)

The mitogen-activated protein kinase (MAPK) pathway controls intestinal epithelial barrier permeability by regulating tight junctions (TJs) and epithelial cells damage. Heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal epithelial barrier function, but the molecular mechanism is not yet clarified. MAPK activation and barrier permeability were studied using monolayers of Caco-2 cells treated with tissue necrosis factor α (TNF-α) transfected with FUGW-HO-1 or pLKO.1-sh-HO-1 plasmid. Intestinal mucosal barrier permeability and MAPK activation were also investigated using carbon tetrachloride (CCl 4 ) administration with CoPP (a HO-1 inducer), ZnPP (a HO-1 inhibitor), CO releasing molecule 2 (CORM-2), or inactived-CORM-2-treated wild-type mice and mice with HO-1 deficiency in intestinal epithelial cells. TNF-α increased epithelial TJ disruption and cleaved caspase-3 expression, induced ERK, p38, and JNK phosphorylation. In addition, HO-1 blocked TNF-α-induced increase in epithelial TJs disruption, cleaved caspase-3 expression, as well as ERK, p38, and JNK phosphorylation in an HO-1-dependent manner. CoPP and CORM-2 directly ameliorated intestinal mucosal injury, attenuated TJ disruption and cleaved caspase-3 expression, and inhibited epithelial ERK, p38, and JNK phosphorylation after chronic CCl 4 injection. Conversely, ZnPP completely reversed these effects. Furthermore, mice with intestinal epithelial HO-1 deficient exhibited a robust increase in mucosal TJs disruption, cleaved caspase-3 expression, and MAPKs activation as compared to the control group mice. These data demonstrated that HO-1-dependent MAPK signaling inhibition preserves the intestinal mucosal barrier integrity by abrogating TJ dysregulation and epithelial cell damage. The differential targeting of gut HO-1-MAPK axis leads to improved intestinal disease therapy.

Background: No consensus exists regarding which procedures should be performed to disinfect endoscopes and working platforms after COVID-19 patients have undergone endoscopy., Methods: We analyzed the disinfection quality of endoscopes and working platforms after 11 COVID-19 patients had undergone endoscopy., Conclusions: For endoscopic preprocessing at the bedside, a key disinfection step is using a multienzyme stock solution. The nucleic acid tests for endoscopists, washers, endoscopes, and working platforms were all negative. Based on our experience with the 11 COVID-19 patients who had undergone endoscopy, we provide an endoscopic reprocessing method for the bedside endoscopic diagnosis and treatment of COVID-19 patients for reference., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Xianqi Lin et al.)

Objective: To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients., Design: We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues., Results: Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients., Conclusions: GI tract may be a potential transmission route and target organ of SARS-CoV-2., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the mechanisms of α-zearalanol (Zeranol)-induced male reproductive toxicity, the effects of Zeranol on spermatogenesis and sex hormone levels of male mice were studied., Methods: Forty healthy sexually mature male Kunming mice were randomly divided into four groups. The mice were mock-treated or treated with Zeranol 25, 50 or 100 mg/kg via oral gavage for 35 days. The epididymal sperms were counted and their morphology and motility were analyzed. The testicles were examined by light and electron microscopy. The levels of serum/testicular testosterone (T), serum follicle stimulating hormone (FSH) and serum luteinizing hormone (LH) were determined by radioimmunoassay., Results: Zeranol decreased the epididymal sperm count and sperm motility in a dose depend manner. While there were not significant differences in the sperm malformation rates between the Zeranol treated groups and the control group. Furthermore, Zeranol could decrease the weight and the organ coefficient of the seminal vesicles and the testicles and lead to significant pathological changes of the testicles. Zeranol could also decrease the levels of serum T, FSH, LH as well as the levels of testicular T of male mice., Conclusions: Zeranol induced reproductive toxicity in adult male mice. It could damage spermatogenesis via its direct effects on the testicles and interfere with sex hormone levels of male mice through its effects on the hypothalamic-pituitary-testicular axis.

Objective: To study the effects of zeranol on spermiogenesis function of mice and its possible mechanism., Methods: 40 healthy mature male mice were randomly divided into four groups: negative group and zeranol exposure groups (25, 50, 100 mg/kg). Male mice were respectively administered with zeranol at the doses of 25, 50, and 100 mg/kg for 35 days and killed. The weights of spermary, epididymis and spermatocyst were measured. The sperm counting, motility and the percent of abnormal sperms were observed. Pathological changes of testicle tissue were also observed., Results: In comparison with control group, the visceral coefficient of spermatocysts and sperm counting of zeranol exposure groups were all decreased ( P < 0.05). Sperm motility were significantly decreased in the median and high exposure groups (P < 0.05). Pathological alterations of testes were also observed. Seminiferous epithelium was reduced in exposure groups, loose and anomalistic organization. Sperm counts were also reduced in the lumina of seminiferous tubules with glair., Conclusion: Zeranol have toxicity effect on spermigenesis function of male mice.

Objective: To describe serum homocysteine distribution and its associated factors in population of urban and rural areas in Beijing., Methods: The study population was represented by a randomly selected sample with 1 168 subjects, including both males and females aged 35 - 64. The levels of serum homocycteine were compared and the correlation with other risk factors were analyzed statistically., Results: (1) Geometric mean of serum homocycteine was 15.4 micromol/L in males and 12.2 micromol/L in females (P < 0.001). (2) There was a significant difference in homocysteine levels between urban population and rural population. Men from rural area had 1.5 times higher homocyteine than from urban (18.0 micromol/L vs 12.0 micromol/L, P < 0.001), while the rural women had 1.3 times higher homocysteine level than urban women did. (3) The prevalence rate of hyperhomocysteinemia was 15.3% in population aged 35 - 64 in Beijing area. (4) Gender, residential location (urban or rural), smoking and education had independent effects on level of serum homocysteine by multivariate analysis., Conclusion: Population in Beijing had higher serum level and prevalence rate of homocysteine than some western countries. Gender, geographic distribution, smoking and education had some influence on homocysteine level.