How Does Risk Management Improve Farmers’ Green Production Level? Organic Fertilizer as an Example

With increases in the frequency of various natural and social risks, effectively coping with uncertainty is necessary for the sustainable development of individuals and the society, particularly smallholder farmers with vulnerable livelihoods. Using survey data from farmers in China, we constructed a risk management capability index system for farmers at the individual, collective, and government levels to empirically analyze the impact of risk management on green production behavior through the Heckman model for two-stage sample selection. The results showed that risk management is a key factor affecting green production behavior. Membership status (membership in an organization), government subsidies, and income levels significantly promote green production levels. Moreover, risk management not only directly affects the green production level but also promotes green production behavior by expanding the scale of operation, improving the sense of responsibility, and enhancing the behavioral responsibility. Additionally, the mediating effect of these factors on farmers in the low-risk perception group was more obvious. Therefore, the risk management level of farmers should be improved at the individual, collective, and government levels to promote sustainable agriculture

Microvascular Endothelial Cells-Derived Microvesicles Imply in Ischemic Stroke by Modulating Astrocyte and Blood Brain Barrier Function and Cerebral Blood Flow

Background Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage. Results EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score. Conclusions Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke

Based on Network Pharmacology and Molecular Docking to Discuss the Mechanism of Antitussive and Expectorant Action of Ruanerli

The antitussive and expectorant effects of Ruanerli and its mechanism were investigated by methods of network pharmacology. The outcomes predicted were verified by molecular docking and animal experiments. The components and targets of Ruanerli were obtained by literature investigation and TCMSP database screen. Mapping with two groups of genes related to "cough" and "sputum" from GeneCards database, the target genes of antitussive and expectorant effects of Ruanerli were obtained. GO and KEGG enrichment analysis of the target genes was performed by Metascape platform. The PPI network among the target genes was constructed through STRING data platform. Cytoscape plugin CytoHubba was used to screen the Top10 genes related to antitussive and expectorant effects of Ruanerli, and KEGG pathway enrichment was performed on the Top10 genes through Metascape data platform to predict the possible signal pathways involved in antitussive and expectorant effects of Ruanerli. Autodock Vina was used for molecular docking between the predicted Top10 gene proteins and the Top 3 active ingredients of Ruanerli. Finally, the predicted results were verified by ammonia induced cough test and phenol red excretion test. According to the analysis of multiple databases, 51 chemical components and 282 corresponding targets have been reported, eighty of them were related to the antitussive and expectorant effects of Ruanerli. The Top10 genes selected by Degree value were mainly concentrated in infection and immune-related pathways. Molecular docking test showed that the Top10 genes had strong binding activity with the Top3 chemical components (Caffeic acid, Rutin and Valeraldehyde) in PPI network. Animal experiments showed that the cough induced by ammonia was significantly inhibited when treated with Ruanerli in mice. The levels of IL-6 and IL-13 in serum were reduced and the excretion of phenol red in mice trachea was increased. PCR and WB detection showed that the mRNA levels and protein expressions of inflammatory genes IL6, IL1B, VEGFA, PTGS2 and MAPK3 were decreased, suggesting that the antitussive and expectorant effects of Ruanerli might be related to decreasing the expression of inflammatory genes and the release of inflammatory factors

Study of Aerosol Influence on Nighttime Land Surface Temperature Retrieval Based on Two Methods

The aim of this study is to evaluate the aerosol influence on LST retrieval with two algorithms (split-window (SW) method and a four-channel based method) using simulated data under typical conditions. The results show that the root mean square error (RMSE) decreases to approximately 2.3 K for SW method and 1.5 K for four channel based method when VZA = 60° and visibility = 3 km; an RMSE would be increased by approximately 1.0 K when visibility varies from 3 km to 23 km. Moreover, a detailed sensitivity analysis under a visibility of 3 km and 23 km is performed in terms of uncertainties of land surface emissivity (LSE), water vapor content (WVC), and instrument noise, respectively. It is noted that the four-channel based method is more sensitive to LSE than SW method, especially for dry atmosphere; LST error caused by a WVC uncertainty of 20% is within 1.5 K for SW method and within 0.8 K for four-channel based method; the instrument noise would introduce LST error with a maximum standard deviation of 0.5 K and 0.04 K for the four-channel based method and SW method, respectively

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction

Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.Peer reviewe

Muc2 Protects against Lethal Infectious Colitis by Disassociating Pathogenic and Commensal Bacteria from the Colonic Mucosa

Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2−/−) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2−/− mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10–100 fold greater C. rodentium burdens in Muc2−/− vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2−/− mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2−/− vs. WT mice, with overt pathogen and commensal translocation into the Muc2−/− colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2−/− mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets