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Background Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored. Results In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus , which were positively correlated with gut barrier function, while suppressing Odoribacter , Rikenella , Oscillibacter and Parasutterella , which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects. Conclusions Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella , which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter , which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF_505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry. Potential recombination of African swine fever virus genotypes is not well understood. Here, Zhao et al. report naturally occurring ASFVs carrying mosaic genomes of genotype I and II and show that the recombinant virus is lethal in pigs and evades the immunity induced by genotype II live vaccine.

Studying the spatial distribution pattern of soil organic carbon and its influencing factors is essential for understanding the carbon cycle in terrestrial ecosystems. Soil samples from four active layers of typical vegetation types (Populus, subalpine shrubs, Picea crassifolia Kom, and alpine meadow) in the upper reaches of Shiyang River basin in the Qilian Mountains were collected to determine the soil organic carbon content and physicochemical properties. The results show the following: (1) There are significant differences in the vertical distribution of Soil organic carbon in the watershed, and the Soil organic carbon content decreases significantly with increasing soil depth. (2) Mainly affected by biomass, the organic carbon content of different vegetation types in different soil layers is as follows: Alpine meadow > Picea crassifolia Kom > Populus > Subalpine shrub, and the soil organic carbon content increases with increasing altitude. Under different vegetation types, the Soil organic content is the highest in the 0–30 cm soil profile, and the maximum value often appears in the 0–10 cm layer, then gradually decreases downward. (3) When soil organic carbon is determined in different vegetation types in the study area, the change of hydrothermal factors has little effect on soil organic carbon content in the short term.

Recent investigations reveal that lactate is not a waste product but a major energy source for cells, especially in the mitochondria, which can support cellular survival under glucose shortage. Accordingly, the new understanding of lactate prompts to target it together with glucose to pursue a more efficient cancer starvation therapy. Herein, zeolitic imidazolate framework‐8 (ZIF‐8) nanoplatforms are used to co‐deliver α‐cyano‐4‐hydroxycinnamate (CHC) and glucose oxidase (GOx) and fulfill the task of simultaneous depriving of lactate and glucose, resulting in a new nanomedicine CHC/GOx@ZIF‐8. The synthesis conditions are carefully optimized in order to yield monodisperse and uniform nanomedicines, which will ensure reliable and steady therapeutic properties. Compared with the strategies aiming at a single carbon source, improved starvation therapy efficacy is observed. Besides, more than boosting the energy shortage, CHC/GOx@ZIF‐8 can block the lactate‐fueled respiration and relieve solid tumor hypoxia, which will enhance GOx catalysis activity, depleting extra glucose, and producing more cytotoxic H2O2. By the synergistically enhanced anti‐tumor effect, both in vitro and in vivo cancer‐killing efficacies of CHC/GOx@ZIF‐8 show twice enhancements than the GOx mediated therapy. The results demonstrate that the dual‐depriving of lactate and glucose is a more advanced strategy for strengthening cancer starvation therapy. Metal‐organic‐framework nanomedicines encapsulating an inhibitor of monocarboxylate transporters 1 and glucose oxidase are developed for efficient glucose depletion while inhibiting the lactate influx. At meanwhile, inhibiting the lactate influx can improve the intracellular oxygen pressure, which subsequently promotes the catalytic activity of glucose oxidase. Cancer cells are substantially killed from ATP shortage and high ROS levels.

Cadmium has been accumulating in the agricultural and ecological environment in recent years due to the release of industrial pollutants. Due to its high solubility, slow degradability and high toxicity, it is highly susceptible to occurring in agricultural fields. The presence of cadmium at low concentrations is harmful to plants. Heavy metal ATPases (HMAs) are proteins that can detoxify high concentrations of heavy metals through vacuole compartmentalization or exocytosis pathways. They have been extensively studied in plants. However, the cadmium transport function of HMAs in wheat has not been explored. In this study, a comprehensive and systematic investigation of HMA gene family members in wheat was conducted. A total of 28 putative TaHMAs were identified. Phylogenetically, these 28 putative TaHMAs were divided into two subgroups: Cu/Ag and Zn/Co/Cd/Pb. The gene structures and conserved motifs were consistent within the same branch and diverse in different branches. The TaHMA gene family is closely related to rice, B. distachyon and A. tauschii. GO analysis results suggest that TaHMAs may be involved in cation transport and membrane components. Protein interaction analysis results suggest that TaHMAs may interact with TaSOD to activate the SOD defense mechanism in wheat. Expression patterns exhibited tissue specificity. Finally, the expression patterns of TaHMAs were validated in the roots and leaves of wheat plants under cadmium stress. Our findings will be valuable for functional studies and applications of HMA gene family members in wheat.

BackgroundTo understand the involvement of micro-RNA (miRNA) in the development and progression of oesophageal squamous cell carcinoma (ESCC), miRNA profiles were compared between tumour and corresponding non-tumour tissues.MethodsmiRCURY LNA array was used to generate miRNA expressing profile. Real-time quantitative PCR was applied to detectthe expression of miR-375 in ESCC samples and its correlation with insulin-like growth factor 1 receptor (IGF1R). Methylation-specific PCR was used to study the methylation status in the promoter region of miR-375. The tumour-suppressive effect of miR-375 was determined by both in-vitro and in-vivo assays.ResultsThe downregulation of miR-375 was frequently detected in primary ESCC, which was significantly correlated with advanced stage (p=0.003), distant metastasis (p<0.0001), poor overall survival (p=0.048) and disease-free survival (p=0.0006). Promoter methylation of miR-375 was detected in 26 of 45 (57.8%) ESCC specimens. Functional assays demonstrated that miR-375 could inhibit clonogenicity, cell motility, cell proliferation, tumour formation and metastasis in mice. Further study showed that miR-375 could interact with the 3′-untranslated region of IGF1R and downregulate its expression. In clinical specimens, the expression of IGF1R was also negatively correlated with miR-375 expression (p=0.008).ConclusionsThis study demonstrates that miR-375 has a strong tumour-suppressive effect through inhibiting the expression of IGF1R. The downregulation of miR-375, which is mainly caused by promoter methylation, is one of the molecular mechanisms involved in the development and progression of ESCC.

Surfactant can improve the wettability of water to coal, which is beneficial to reduce the production of coal dust in coal seam water injection. Through the measurement and calculation of contact angle and its decay rate, the wettability differences of SDS (C 12 H 25 OSO 3 Na), AES (C 14 H 29 O 5 NaS), OP-10 (C 18 H 30 O 10 ), and JFC (RO(CH 2 CH 2 O) n H) to anthracite were compared. In addition, the wetting modification effect and infiltration rate of anthracite by water, AES, and OP-10 were studied by infrared spectroscopy and complex impedance monitoring of coal pillar immersion process. The results show that when the concentration of surfactant is 0.1%, the contact angle decay time of OP-10 is very short, and the contact angle decay rate is as high as 19°/s. The decay rate can more obviously reflect the wettability difference of surfactants. And the wetting modification effect of OP-10 on anthracite is stronger than that of AES, and the peaks of oxygen-containing functional groups such as carboxyl and hydroxyl groups are stronger. Furthermore, the capillary force between OP-10 and anthracite is much larger than that of water, which shows the characteristics of fast water absorption and wide distribution in the infiltration experiment of columnar coal. The results of complex impedance measurement indicate that the impedance decay rate of coal is well correlated with capillary rise factor F C , contact angle decay rate, and contact angle. It is hoped that the research results can provide help for coal seam water injection and dust prevention.

As raindrops fall from the cloud base to the ground, evaporation below those clouds affects the rain’s isotope ratio, reduces precipitation in arid areas, and impacts the local climate. Therefore, in arid areas with scarce water resources and fragile ecological environments, the below-cloud evaporation is an issue of great concern. Based on 406 event-based precipitation samples collected from nine stations in the Shiyang River basin (SRB) in the northwest arid area, global meteorological water line (GMWL) and local meteorological water line (LMWL) are compared, and the Stewart model is used to study the effect of spatial and temporal variation of below-cloud evaporation on isotope values in different geomorphic units at the SRB. Furthermore, factors influencing below-cloud evaporation are analyzed. The results show that 1) the change of d-excess (Δd) in precipitation at the SRB and the residual ratio of raindrop evaporation (f) vary in time and space. With regard to temporal variation, the intensity of below-cloud evaporation is described by summer < autumn < winter < spring. Regarding spatial variation, the below-cloud evaporation in mountain areas is weaker than in oases and deserts. The intensity of below-cloud evaporation in mountain areas increases with decreasing altitude, and the below-cloud evaporation in oasis and desert areas is affected by local climatic conditions. 2) Below-cloud evaporation is also affected by local transpiration evaporation, especially around reservoirs. Reservoirs increase the relative humidity of the air nearby, weakening below-cloud evaporation. This study deepens our understanding of the water cycle process in arid areas.

Mechanical force regulates bone density, modeling, and homeostasis. Substantial periosteal bone formation is generated by external mechanical stimuli, yet its mechanism is poorly understood. Here, it is shown that myeloid‐lineage cells differentiate into subgroups and regulate periosteal bone formation in response to mechanical loading. Mechanical loading on tibiae significantly increases the number of periosteal myeloid‐lineage cells and the levels of active transforming growth factor β (TGF‐β), resulting in cortical bone formation. Knockout of Tgfb1 in myeloid‐lineage cells attenuates mechanical loading‐induced periosteal bone formation in mice. Moreover, CD68+F4/80+ macrophages, a subtype of myeloid‐lineage cells, express and activate TGF‐β1 for recruitment of osteoprogenitors. Particularly, mechanical loading induces the differentiation of periosteal CD68+F4/80− myeloid‐lineage cells to the CD68+F4/80+ macrophages via signaling of piezo‐type mechanosensitive ion channel component 1 (Piezo1) for TGF‐β1 secretion. Importantly, CD68+F4/80+ macrophages activate TGF‐β1 by expression and secretion of thrombospondin‐1 (Thbs1). Administration of Thbs1 inhibitor significantly impairs loading‐induced TGF‐β activation and recruitment of osteoprogenitors in the periosteum. The results suggest that periosteal myeloid‐lineage cells respond to mechanical forces and consequently produce and activate TGF‐β1 for periosteal bone formation. Mechanical loading induces the increase in periosteal CD68+F4/80− myeloid‐lineage cells, which further differentiate into CD68+F4/80+ macrophages with the synthesis of Csf1 via Piezo1 signaling. Periosteal CD68+F4/80+ macrophages secrete TGF‐β1 and activate TGF‐β1 by producing Thbs1. Active TGF‐β1 recruits osteoprogenitors to the periosteal bone surface for cortical bone formation.