Sodium oligomannate's amelioration of reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model depends on the gut microbiome†.

It has been well established that there is a connection between polycystic ovary syndrome pathology and gut microbiome dysbiosis. A marine-derived oligosaccharide, GV-971, has been reported to alter gut microbiota and alleviate Aß amyloidosis. In this study, the effects of GV-971 on polycystic ovary syndrome-like mice were explored. Mice were randomly assigned into four groups: control, letrozole, letrozole + GV-971, and control + GV-971. Glucose metabolism in polycystic ovary syndrome-like mice was ameliorated by GV-971, while the reproductive endocrine disorder of polycystic ovary syndrome-like mice was partially reversed. The messenger ribonucleic acid levels of steroidogenic enzymes in ovaries of polycystic ovary syndrome-like mice were improved. GV-971 restored the fertility of polycystic ovary syndrome-like mice and significantly increase the number of litters. Furthermore, GV-971 treatment effectively mitigated abnormal bile acid metabolism. Notably, after GV-971 intervention, gut microbiota alpha-diversity was considerably raised and the relative abundance of Firmicutes was reduced. In conclusion, the hyperinsulinemia and hyperandrogenemia of polycystic ovary syndrome-like mice were alleviated by GV-971 intervention, which was associated with mitigating bile acid metabolism and modulating gut microbiota.

Spatiotemporal transcriptomic atlas of rhizome formation in Oryza longistaminata.

Rhizomes are modified stems that grow underground and produce new individuals genetically identical to the mother plant. Recently, a breakthrough has been made in efforts to convert annual grains into perennial ones by utilizing wild rhizomatous species as donors, yet the developmental biology of this organ is rarely studied. Oryza longistaminata, a wild rice species featuring strong rhizomes, provides a valuable model for exploration of rhizome development. Here, we first assembled a double-haplotype genome of O. longistaminata, which displays a 48-fold improvement in contiguity compared to the previously published assembly. Furthermore, spatiotemporal transcriptomics was performed to obtain the expression profiles of different tissues in O. longistaminata rhizomes and tillers. Two spatially reciprocal cell clusters, the vascular bundle 2 cluster and the parenchyma 2 cluster, were determined to be the primary distinctions between the rhizomes and tillers. We also captured meristem initiation cells in the sunken area of parenchyma located at the base of internodes, which is the starting point for rhizome initiation. Trajectory analysis further indicated that the rhizome is regenerated through de novo generation. Collectively, these analyses revealed a spatiotemporal transcriptional transition underlying the rhizome initiation, providing a valuable resource for future perennial crop breeding.

Upgrading Passenger Vehicle Emission Standard Helps to Reduce China's Air Pollution Risk from Uncertainty in Electrification.

Upgrading to the CHINA 7 standard is crucial for managing air pollution from passenger vehicles in China. Meanwhile, China aims to achieve carbon neutrality by 2060, which necessitates large-scale replacement of gasoline vehicles with electric vehicles in the future. Consequently, the public might view upgrading gasoline vehicles to the CHINA 7 standard as redundant. However, the emission reduction benefits of upgrading standards in the context of uncertain electrification ambitions have not received adequate attention. Here, we show that upgrading standards will compensate for the absence of emissions reductions due to hindered electrification efforts. In the best scenario, China's CO2 emissions can be reduced to 0.047 Gt and NOx to 8.2 × 103 t in 2050. In nonextreme electrification scenarios with CHINA 7 standard, the emission intensity reduction will remain the main driver for emission reductions, outweighing the electrification contribution. In extreme electrification scenarios, upgrading standards will tackle the increased emissions from plug-in hybrid electric vehicles. Our fleet-level results advocate for early standards upgrades to enhance resilience against air pollution risks arising from uncertainties in electrification. Our evidence from China, with one of the most stringent emission standards, can provide a reference point for the world on the upgrading passenger vehicle emission standard issue.

Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs.

BACKGROUND: Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic cancer often accompany with dismal prognosis, highlighting the need to investigate mechanisms of drug resistance and develop therapies to overcome chemoresistance. METHODS: This research was filed with the Chinese Clinical Trial Registry (ChiCTR2200061320). In order to isolate primary normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) samples of pancreatic ductal adenocarcinoma (PDAC) and paracancerous pancreatic tissue from individuals diagnosed with PDAC were obtained. The exosomes were obtained using ultracentrifugation, and their characteristics were determined by Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and high-throughput sequencing. Gemcitabine (GEM) was employed to promote ferroptosis, and ferroptosis levels were determined by monitoring lipid reactive oxygen species (ROS), cell survival, and intracellular Fe2+ concentrations. To assess in vivo tumor response to GEM therapy, a xenograft tumor mouse model was utilized. RESULTS: Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, and maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells. CONCLUSION: This work demonstrates a novel mode of acquired chemoresistance in PDAC and identifies the miR-3173-5p/ACSL4 pathway as a promising treatment target for GEM-resistant pancreatic cancer.

In Situ Growth of Sodium Manganese Hexacyanoferrate on Carbon Nanotubes for High-Performance Sodium-Ion Batteries.

Sodium manganese hexacyanoferrate (NaMnHCF) has emerged as a research hotspot among Prussian blue analogs for sodium-ion battery cathode materials due to its advantages of high voltage, high specific capacity, and abundant raw materials. However, its practical application is limited by its poor electronic conductivity. In this study, we aim to solve this problem through the in situ growth of NaMnHCF on carbon nanotubes (CNTs) using a simple coprecipitation method. The results show that the overall electronic conductivity of NaMnHCF is significantly improved after the introduction of CNTs. The NaMnHCF@10%CNT sample presents a specific capacity of 90 mA h g-1, even at a current density of 20 C (2400 mA g-1). The study shows that the optimized composite exhibits a superior electrochemical performance at different mass loadings (from low to high), which is attributed to the enhanced electron transport and shortened electron pathway. Surprisingly, the cycling performance of the composites was also improved, resulting from decreased polarization and the subsequent reduction in the side reactions at the cathode/electrolyte interface. Furthermore, we revealed the evolution of potential plateau roots from the extraction of crystal water during the charge-discharge process of NaMnHCF based on the experimental results. This study is instructive not only for the practical application of NaMnHCF materials but also for advancing our scientific understanding of the behavior of crystal water during the charge-discharge process.

Human leukocyte antigen-G (HLA-G) expression plays an important role in the diagnosis and grading of endometrial cancer.

The research aimed to investigate the expression of human leukocyte antigen G (HLA-G) in cancer tissues and normal endometrium and the expression of HLA-G in the three different grades of Endometrial cancer, to determine if HLA-G expression is related with the diagnosis and grading of endometrial cancer. The expression of HLA-G protein was analysed in the primary tumour in 97 tissue samples obtained from endometrial cancer, in which 30 samples were at pathological Grade 1; 37 samples were at Grade 2; 27 samples were at Grade 3; and the other 5 samples were obtained from normal endometrium. The HLA-G protein level was measured by immunohistochemical method and analysed according to the clinicopathological parameters of patients. A statistically significant difference (p < .05) was observed in HLA-G expression between the cancerous tissue and the normal endometrium (p = .0007), and the histochemistry score (H-score) of the negative control was 0.05 ± 0.03 (mean ± SD). Statistically significant correlations were also observed between samples of pathological Grade 1 and Grade 2 (p = .0126), Grade 2 and Grade 3 (p = .0359), Grade 1 and Grade 3 (p = .0001). Endometrial cancer cells express higher levels of HLA-G probably to escape immune surveillance, and HLA-G expression level is related with the pathological grade of endometrial cancer. Therefore, HLA-G detecting and quantifying could possibly help diagnosing, grading and treatment of endometrial cancer.Impact statementWhat is already known on this subject? The expression of a member of the non-classical HLA antigens, HLA-G, is one of the main ways for tumour immune escape and progression. The significance of HLA-G in tumour biology has been intensively investigated (Carosella et al. 2015), and now it is widely acknowledged that HLA-G expression in tumours is highly linked with immune suppressive microenvironments, advanced tumour stage, poor therapeutic responses and prognosis (Lin and Yan, 2018). However, to our knowledge, no research has been conducted on the correlation between HLA-G expression and pathological grades of endometrial cancer.What do the results of this study add? Our study demonstrated that the expression of HLA-G plays an important role in the pathological grading of endometrial cancer.What are the implications of these findings for clinical practice and/or further research? Measuring the level of HLA-G expression to help pathological grading of endometrial cancer is important in determining the treatment of patients with endometrial cancer and studying the underlying mechanisms of the development of endometrial cancer, while proving or finding new targeted therapies inhibiting or modifying these processes still requires further investigation.

Computed tomography evaluation of extensive intravenous angioleiomyoma: a case report.

BACKGROUND: Uterine angioleiomyoma is a rare variant of leiomyoma, and the main therapy is complete surgery. This study introduces the benefit of three-dimensional computed tomography reconstruction for preoperative preparation. CASE PRESENTATION: A 50-year-old woman presented because of chest distress after activity, with worsening symptoms. After examination, the final diagnosis was uterine angioleiomyoma. The tumour originated in the uterus; grew into the right iliac vein; coursed along the iliac vein, inferior vena cava, and right atrium; and finally invaded the right ventricle. To best complete the surgery, a multidisciplinary surgery was selected. Before the surgery, a three-dimensional computed tomography reconstruction model was created to assess the tumour status, and this model enabled the surgery to be completed successfully. CONCLUSION: Three-dimensional computed tomography reconstruction is of great significance for the preoperative diagnosis of uterine angioleiomyoma and the formulation of surgical treatment plans. Based on its vivid images, surgeons can perform operations more effectively and safely.

Association of left atrial wall thickness with recurrence after cryoballoon ablation of paroxysmal atrial fibrillation.

BACKGROUND: Transmural injury plays a role in successful atrial fibrillation ablation. The effect of left atrial wall thickness (LAWT) on the efficacy of radiofrequency ablation has been identified, but data on the relationship between LAWT and cryoballoon for paroxysmal atrial fibrillation (PAF) are lacking. We aim to explore the relationship between LAWT and recurrence after cryoballoon ablation (CBA). METHODS: We studied 364 patients (mean age 62 years) with PAF who underwent a second-generation CBA and pre-procedure cardiac CTA. LAWT and left atrial volume index (LAVI) were obtained based on pre-procedure cardiac CTA measurements. Follow-up was at least 12 months and predictors of atrial tachyarrhythmia recurrence during follow-up were assessed. RESULTS: Patients were followed up for a median of 19 (12-28) months, with an atrial tachyarrhythmia-free rate of 77.5% after cryoablation. Greater LAVI (50.0 ± 19.6 mL/m2 vs. 44.3 ± 15.4 mL/m2, P = 0.018) and greater LAWT (1.67 ± 0.24 vs. 1.46 ± 0.25 mm, P < 0.001) were associated with atrial tachyarrhythmia recurrence. The mean LAWT of PV antrum correlated with TTI (R = 0.252, P < 0.001). Adding LAWT to the established risk model improved both the discrimination and reclassification effects (IDI: 0.099, 95% CI: 0.065-0.134, P < 0.001; NRI: 0.685, 95% CI: 0.455-0.915, P < 0.001). In a multivariable Cox proportional hazard model, the mean LAWT of PV antrum (hazard ratio [HR]:3.657, 95%CI: 2.319-5.765, P < 0.001) was an independent predictor of atrial tachyarrhythmia recurrence after cryoablation. CONCLUSIONS: The mean LAWT of PV antrum, obtained from preoperative measurements on CT, was associated with atrial tachyarrhythmia recurrence after cryoablation.

Abnormal Serum Biochemical Results and Mitochondrial Damage of Lymphocytes in Patients with Schizophrenia and SARS-CoV-2 Infection: A Retrospective Study.

Purpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia. Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed. Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS). Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.

Comparison of safety and effectiveness of different sheaths in ablation of focal atrial tachycardia: a retrospective study.

Background: A novel visualized steerable sheath, referred to as the Vizigo sheath, has been utilized in clinical interventions. The objective of this study was to evaluate and contrast the efficacy and safety of the Vizigo sheath with other sheaths in the catheter ablation (CA) for focal atrial tachycardia (FAT). Methods: A retrospective cohort study was conducted on consecutive patients with CA for FAT from March 2019 to February 2022. Objectives were to assess the impact of the Vizigo sheath on acute and long-term ablation success rates, procedural and fluoroscopy times, and contact force (CF). Results: A total of 164 patients, mean age 50±15 years, 97 (59.1%) women, underwent CA of FAT using the Vizigo sheath (N=42), non-visualized steerable sheath (N=36), or other conventional sheath (N=86). Age, sex, body mass index (BMI), presence of hypertension, heart failure, and diabetes mellitus were not significantly different among the three groups. The acute success rate of 94.0% was similar among the three groups. Over a follow-up of 14±2 months, the Vizigo sheath was associated with superior arrhythmia-free survival (88.1%) when compared to non-visualized steerable (69.4%; P=0.04) and other conventional (72.1%, P=0.046) sheaths. Procedural duration, number of ablation lesions, and ablation times were similar among the three groups. However, the Vizigo sheath was associated with lower fluoroscopy times (e.g., 145 vs. 250 s with Vizigo versus non-visualized steerable sheaths, P=0.03) and higher CF (e.g., average CF 12.0 versus 8.0 g with Vizigo versus non-visualized steerable sheaths, P=0.003). Conclusions: The application of Vizigo sheath can improve the long-term success rate of FAT and reduce the radiation exposure of patients and medical staff in our single-center limited sample study. More research may be needed in the future to confirm our findings.

Iron-Nickel synergistic catalysis growth of (Fe,Ni)9S8/Ni3S2@N,S codoped carbon bridged nanowires enhanced oxygen evolution reaction performance.

Improving the conductivity of the electrocatalyst itself is essential for enhancing its performance. In this work, N, S-rich 6-thioguanine (TG) is selected as the ligand to synthesize a Fe, Ni bimetallic porous coordination polymer (PCP), which is then derived to fabricate N,S codoped carbon (NSC)-coated (Fe,Ni)9S8/Ni3S2 bridged nanowires. The (Fe,Ni)9S8/Ni3S2@NSC bridged nanowires obtained through bimetallic synergistic catalysis and self-sulfurization processes not only introduced additional electrocatalytic active sites but also significantly enhance the overall conductivity of the catalyst due to the interconnected nanowire structure. The resulting (Fe,Ni)9S8/Ni3S2@NSC demonstrates remarkable oxygen evolution reaction (OER) performance, exhibiting an overpotential as low as 252 mV at a current density of 10 mA cm-2. This work proposes a novel strategy for enhancing the overall conductivity of catalysts by growing bridged nanowires, providing valuable insights and inspiration for the design and preparation of advanced transition metal sulfide electrocatalysts.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Early rhythm control vs. rate control in atrial fibrillation: A systematic review and meta-analysis.

Objective: It has long been debated whether rhythm control vs. rate control strategies have differing effects on mortality and morbidity for atrial fibrillation (AF). Recently, several randomized controlled studies (RCTs) and observational trials described that an early rhythm management method was linked to a lower likelihood of negative clinical outcomes in individuals with AF. We wanted to see if an early rhythm management method may help patients with AF. Methods: We performed a systematic search to retrieve studies assessing the outcomes of early rhythm control vs. rate control in AF by using PubMed, Web of Science, Cochrane Library, and Embase published between 01/01/2000 and 15/04/2022. Results: Finally, two RCTs, one retrospective analysis of RCTs, and four observational studies were identified. Compared with rate control, early rhythm control has been linked to lower all-cause mortality. [risk ratio (RR), 0.76; 95% CI 0.69-0.83; P < 0.00001; I 2 = 77%]. The early rhythm control group was also associated with a lower risk of cardiovascular mortality (RR, 0.68; 95% CI 0.63-0.74; P < 0.00001; I 2 = 33), stroke (RR, 0.77; 95% CI 0.67-0.87; P < 0.001; I 2 = 64), and heart failure hospitalization (RR, 0.74; 95% CI 0.59-0.93; P = 0.0009; I 2 = 93%). We found no significant difference in nights spent in hospital per year, acute coronary syndrome, major bleeding, and cardiac arrest/ventricular arrhythmia between the groups. Conclusion: In this meta-analysis, early rhythm therapy was linked to a lower risk of all-cause mortality, cardiovascular mortality, stroke, and heart failure hospitalization compared with the rate control group. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333592.

The role of non-coding RNAs in ferroptosis regulation.

Ferroptosis is a newly recognized form of cell death that is distinct from apoptosis, necrosis, autophagy in morphology, biochemistry, and heredity. The basic process of ferroptosis involves disordered permeability of plasma membrane, which is caused by abnormal accumulation of lipids and reactive oxygen species (ROS). The regulatory mechanism of ferroptosis is important due to its involvement in tumor progression, neurotoxicity, neurodegenerative diseases, acute renal failure, and ischemia-reperfusion injury. Recent studies have shown that in ferroptosis metabolism, non-coding RNAs (ncRNAs) can interfere with multiple signaling pathways at both the pre-transcriptional and post-transcriptional levels. Despite great progress, current research on the mechanism of ncRNAs and ferroptosis remains insufficient. This review provides an overview of the main mechanisms and targets of ferroptosis and focuses on the mechanisms of non-coding RNA regulation. Analyzing the deficiencies in current research may provide ideas for future studies to investigate.

Effects of polysaccharides from Fuzhuan brick tea on immune function and gut microbiota of cyclophosphamide-treated mice.

In this study, cyclophosphamide (Cy) was used to treat mice to establish an immunosuppressant model in mice, and the regulatory effects of polysaccharides from Fuzhuan brick tea (FBTPSs) including crude FBTPSs (CFBTPSs) and the purified fraction (FBTPSs-3) on the immune function and gut microbiota of mice were investigated. The results showed that CFBTPSs and FBTPSs-3 restored the levels of body weight, feed intake, immune organ index, cytokine and immunoglobulin A in mice. The Cy-induced injury of gut including intestinal morphology and expression of tight junction proteins were also restored. Furthermore, CFBTPSs and FBTPSs-3 could significantly modulate gut microbiota by increasing the relative abundance of Muribaculaceae and reduceing the relative abundances of Lachnospiraceae, Helicobacteraceae, Clostridaceae, Desulfovibrionaceae and Deferribacteraceae. Moreover, the gut microbiota derived short-chain fatty acids might play an important role in improvement of immune function by FBTPSs. Our results showed that FBTPSs could regulate the immune function of mice, which provided evidences for the development of FBTPSs as potentially functional foods to improve human health.

Left Atrial Appendage Closure for Atrial Fibrillation in the Elderly >75 Years Old: A Meta-Analysis of Observational Studies

Background: Left atrial appendage closure (LAAC) is an established therapy for patients with atrial fibrillation (AF); however, there is a limited understanding of LAAC in elderly patients (≥75 years old). We conducted a meta-analysis to investigate the procedural complications and long-term outcomes after LAAC in the elderly versus the non-elderly. Methods: We screened PubMed, EMBASE, Cochrane Library, and Web of Science. Procedural endpoints of interest included successful implantation LAAC rates, in-hospital mortality, major bleeding events, pericardial effusion/tamponade, stroke, and vascular access complications related to LAAC. Long-term outcomes included all-cause mortality, major bleeding events, and stroke/transient ischemic attack (TIA) during follow-up. Results: Finally, 12 studies were included in the analysis; these included a total of 25,094 people in the elderly group and 36,035 people in the non-elderly group. The successful implantation LAAC rates did not differ between the groups, while the elderly patients experienced more periprocedural mortality (OR 2.62; 95% CI 1.79−3.83, p < 0.01; I2 = 0%), pericardial effusion/tamponade (OR 1.39; 95% CI: 1.06−1.82, p < 0.01; I2 = 0%), major bleeding events (OR 1.32; 95% CI 1.17−1.48, p < 0.01; I2 = 0%), and vascular access complications (OR 1.34; 95% CI 1.16−1.55, p < 0.01; I2 = 0%) than the non-elderly patients. The long-term stroke/TIA rates did not differ between the elderly and the non-elderly at least one year after follow-up. Conclusions: Even though successful implantation LAAC rates are similar, elderly patients have a significantly higher incidence of periprocedural mortality, major bleeding events, vascular access complications, and pericardial effusion/tamponade after LAAC than non-elderly patients. The stroke/TIA rates did not differ between both groups after at least one-year follow-up.

Peri-Ulcerative Mucosal Inflammation Appearance is an Independent Risk Factor for 30-Day Rebleeding in Patients with Gastric Ulcer Bleeding: A Multicenter Retrospective Study.

Aim: The aim of this study was to identify clinical endoscopic indicators related to peri-ulcerative mucosal inflammation and to analyze whether the degree of peri-ulcerative mucosal inflammation appearance is an independent risk factor for gastric ulcer rebleeding. Methods: We conducted a retrospective study that included patients with gastric ulcer bleeding who were hospitalized at three medical centers in China from January 1, 2016 to December 31, 2019. Ulcer rebleeding that occurred within 30 days of successful initial hemostasis was analyzed to determine whether this event was related to the degree of peri-ulcerative mucosal inflammation appearance or other mucosal inflammation-related factors. Results: We enrolled 1111 patients and determined that GBS-Rebleeding-ROC (P<0.001), age (P=0.01), use of NSAIDs (P=0.001), bile reflux (P<0.001), and Helicobacter pylori (P<0.001) are all risk factors for peri-ulcerative mucosal inflammation appearance. Through multivariate analysis, we determined that severe peri-ulcerative mucosal inflammation appearance (P=0.002) was an independent risk factor for ulcer rebleeding within 30 days. Finally, we developed a risk assessment model using factors associated with mucosal inflammation that may be useful for early prediction of rebleeding. Conclusion: The risk factors for peri-ulcerative mucosal inflammation appearance were identified. Severe peri-ulcerative mucosal inflammation appearance is an independent risk factor for ulcer rebleeding.

Immunomodulatory activity of polysaccharides from the mycelium of Aspergillus cristatus, isolated from Fuzhuan brick tea, associated with the regulation of intestinal barrier function and gut microbiota.

Aspergillus cristatus is the dominant fungus involved in the fermentation of Fuzhuan brick tea (FBT). The intracellular polysaccharides (IPSs) from A. cristatus (MK346334, NCBI), isolated from FBT, exhibited immunomodulatory activity in vitro while the effects in vivo on immune system and gut microbiota remain unclear. In this study, IPSs and the purified fraction (IPSs-2) from IPSs were prepared and their immunomodulatory activities were investigated with cyclophosphamide (Cy)-induced immunosuppressive mice. As results, IPSs strengthened the immune function, manifesting in the improvement of body weight, daily intake, immune organ indices, cytokines and immunoglobulin. Meanwhile, IPSs attenuated Cy-induced intestinal barrier injury and promoted the expression of tight junction proteins and mucin, reinforcing the intestinal barrier function. Moreover, IPSs not only promoted the production of short-chain fatty acids and the expression of G protein-coupled receptor (GPR), but also balanced dysbiosis of gut microbiota through elevating the growth of beneficial bacteria while reducing pathobionts to maintain the homeostasis of the microbial ecology. These results suggested that IPSs exerted immunomodulatory activity linking with the restoration of intestinal barrier function and regulation of gut microbiota, which contributes to the development of novel probiotics and effective immunomodulators for strengthening host immunity and gut health.

Possible roles of HLA-G regulating immune cells in pregnancy and endometrial diseases via KIR2DL4.

Major histocompatibility complex (MHC) molecules bind peptides originated from cellular synthesis and present them at the cell surface for recognition by receptors on immune cells like T lymphocytes, natural killer (NK) cells or mast cells. Such recognition plays a crucial part in autoimmunity, anti-bacterial, anti-viral and anti-tumor responses. Human leukocyte antigen G (HLA-G) is a member of non-classical HLA class I molecules which has been studied deeply in recent years into its role in pregnancy and endometrial diseases, including endometrial tumor, endometriosis and adenomyosis, etc. Understanding the mechanism of the maintenance of pregnancy and immune escape of endometrial diseases in a HLA-G dependent way is of current interest. Perception from studies in the expression of HLA-G and possible pathways is a vital part of understanding mechanisms related to immune escape.

Modulation of gut homeostasis by exopolysaccharides from Aspergillus cristatus (MK346334), a strain of fungus isolated from Fuzhuan brick tea, contributes to immunomodulatory activity in cyclophosphamide-treated mice.

In this study, the crude exopolysaccharides (CEPSs) from fungus Aspergillus cristatus (MK346334, NCBI) isolated from Fuzhuan brick tea and its main purified fraction (EPSs-2) were investigated. Using the RAW264.7 cell model, EPSs-2 exhibited an excellent immunomodulatory effect in vitro. Then, the regulating effects of EPSs on immune function and gut microbiota were evaluated using a cyclophosphamide (Cy)-induced mice model. It was found that both CEPSs and EPSs-2 improved the body weight loss, immune organ indexes as well as the levels of TNF-α, IL-1ß, IFN-γ and IgA, exhibiting potent immunoregulatory activity. Moreover, CEPSs and EPSs-2 not only attenuated the intestinal tissue damage, but also promoted the production of short-chain fatty acids and modulated the microbial composition by increasing the growth of Muribaculaceae, Prevotellaceae_UCG-001, Bacteroides, Parabacteroides and Tidjanibacter, while decreasing the relative abundances of Helicobacter, Bilophila, Mucispirillum, Lachnospiraceae, Ruminococcaceae and Clostridiales. These results indicated that the EPSs, especially EPSs-2, exhibited immunomodulatory activity associated with the modulation of gut microbiota to maintain gut homeostasis, which provided evidence for the development of novel potential prebiotics and immunomodulators.