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Primary biliary cholangitis (PBC) is an autoimmune liver disease. During the diagnostic process, the patient’s autoimmune antibodies are routinely examined. Approximately 20% of PBC patients have positive anti-centromere antibody (ACA). We evaluated the clinical characteristics of ACA-positive and ACA-negative PBC patients to explain the differences in disease progression between these two groups. Retrospective data from 961 PBC patients at Beijing Youan Hospital from 2010 to 2019 were gathered and separated into two groups based on ACA positivity. We collected and evaluated clinical laboratory indices, gastroscopy findings, and liver function assessments. In addition, 60 liver biopsies were available for comparison between the 2 groups. Pathologists staged the histological findings using the Ludwig staging criteria and Nakanuma staging and grading. Immunohistochemical staining was also performed on liver biopsies to examine the expression of cytokeratin 7 (CK7) in the tissue. A synthesis of clinical indicators in the large cohort showed that alanine transaminase, aspartate aminotransferase, total bilirubin, IgG, white blood cell, and platelet were significantly lower in the ACA-positive group, indicating that the overall status of liver injury was more moderate in the ACA-positive group. Additionally, ACA-positive patients in the non-cirrhotic group were more likely to present with gastroesophageal varices related to portal hypertension. Finally, analysis of pathologic findings showed that parameters were mostly comparable in the two groups, but CK7 differed and was more significantly lower in the ACA-positive group in albumin–bilirubin grade 2 and 3 patients. In summary, we characterized and compared the clinical features of ACA-positive and ACA-negative PBC patients, corroborating previous studies on the relationship between ACA positivity and portal hypertension cross-sectionally. It suggested that gastroesophageal varices might happen in the earlier course of PBC natural progression in the ACA-positive group.

BACKGROUND: Widespread resistance of insect pests to insecticides and transgenic crops in the field is a significant challenge for sustainable agriculture, and calls for the development of novel alternative strategies to control insect pests. One potential resource for the discovery of novel insecticidal molecules is natural toxins, particularly those derived from the venoms of insect predators. RESULTS: In this study, we identified three insecticidal proteinaceous toxins from the venom glands (VGs) of the predatory stink bug, Arma custos (Hemiptera: Asopinae). Transcriptomic analysis of A. custos VGs revealed 151 potentially secreted VG‐rich venom proteins. Three VG‐rich venom proteins (designated AcVP1 ~ 3) were produced by overexpression in Escherichia coli. Injection of the recombinant proteins into tobacco cutworm (Spodoptera litura) larvae showed that all of the three recombinant proteins caused paralysis, liquefaction and death. Injection of recombinant proteins into rice brown planthopper (Nilaparvata lugens) nymphs showed higher insecticidal activities, among which a trypsin (AcVP2) caused 100% mortality postinjection at 1.27 pmol mg−1 body weight. CONCLUSION: A natural toolkit for the discovery of insecticidal toxins from predatory insects has been revealed by the present study. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: The Albumin-Bilirubin (ALBI) score and grade are widely used to stratify patients with primary biliary cholangitis (PBC) into different disease statuses and risk levels. Recent studies have increasingly highlighted the role of gut microbiota in autoimmune liver diseases. This study aimed to investigate the differences in gut microbiota among PBC patients with varying ALBI grades. Methods: Clinical data and stool samples were collected from outpatient and inpatient PBC patients between 2019 and 2022. Gut microbiota profiles were obtained using 16S rDNA sequencing of stool samples. We analyzed alpha diversity, beta diversity, LEfSe analysis and pathway function prediction. Additionally, various machine learning methods—including random forest (RF), lasso, gradient boosting machine (GBM) and support vector machine (SVM)—were employed to identify key features and to build and validate predictive models using bootstrap techniques. Results: Clinical characteristics of ALBI grade 1 patients were comparatively better than those of ALBI grade 2 and 3 patients, including multiple laboratory indices. Gut microbiota analysis revealed that species richness and balance were higher in ALBI grade 1 patients. Both the comparison of the most abundant genera and the linear discriminant analysis (LDA) in LEfSe demonstrated that Lachnospira had a higher abundance and better discriminative ability in ALBI grade 1. Pathway function prediction indicated that sulfur metabolism was upregulated in higher ALBI grades. Furthermore, RF identified 10 specific genera, which were then used to build and validate models for discriminating PBC patients according to their ALBI grades. All three models, developed using different machine learning methods, demonstrated good discrimination ability (mean AUC 0.75–0.80). Conclusion: This study highlights significant differences in gut microbiota profiles among PBC patients with different ALBI grades. The increased abundance of Lachnospira and upregulation of sulfur metabolism pathways are notable in patients with lower ALBI grades. The machine learning models developed based on gut microbiota features offer promising tools for discriminating between PBC patients with varying disease severities, which could enhance the precision of treatment strategies. [ABSTRACT FROM AUTHOR]

Background. Sepsis remains a major health condition with a high mortality rate that may be related to immunosuppression. T lymphocyte subsets may reflect the immune function of sepsis patients. The purpose of this study was to investigate the predictive value of CD4+ T lymphocyte counts of ICU patients for their short‐term prognosis. Methods. We conducted a prospective, observational cohort study in a general ICU and enrolled patients with sepsis using the Sepsis‐3 criteria. Peripheral blood samples were collected within 24 hours of enrollment or measurement of blood cell analysis and biomarkers of CD4+ T lymphocytes and CD8+ T lymphocytes. Severity was classified by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores. The primary outcome was 28‐day mortality. Results. A total of 100 patients with sepsis were enrolled and analyzed. CD4+ T lymphocyte counts gradually decreased based on 28‐day mortality (p < 0.001). Similarly, multivariate logistic regression analysis showed that only CD4+ T lymphocyte counts were an independent predictor of 28‐day mortality in sepsis patients. The area under the receiver operating characteristic curve of the combination of CD4+ T lymphocyte counts and the SOFA score was 0.78. Conclusion. Our study demonstrated that CD4+ T lymphocyte counts are associated with 28‐day mortality. A combination of CD4+ T lymphocyte counts with the SOFA score increased the predictive accuracy for 28‐day mortality. [ABSTRACT FROM AUTHOR]

Gradient grain structure materials with superior mechanical properties of high strength and high toughness have attracted widespread attention. Gradient materials can effectively improve toughness by constructing a microstructure from fine to coarse crystals inside the material, which has gradually become a hotspot of attention in the academic and engineering communities. In this paper, based on the crystal plasticity intrinsic theory, dislocation density is introduced as a characterization quantity, and cohesive units are added at grain boundaries to simulate damage fractures. The results of this study reveal the fracture damage mechanism of gradient crystal structure materials, providing new ideas and methods for the design of gradient materials. [ABSTRACT FROM AUTHOR]

The self-digestive solution (SDS) of the biocontrol bacterium Lysobacter enzymogenes LE16 shows strong antagonistic activities against multiple soil-borne phytopathogens but the positive evidence of this bacterium against plant foliar disease is still scanty. Thus, laboratory, greenhouse, and field experiments were carried out to estimate the efficacies of SDS, S-SDS (stored at room temperature for 12 months), and H-SDS (heated at 100°C for 30 min) against plant powdery mildew. This bacterium produced hydrolases (phosphatase, protease, lysozyme, chitinase, and β-1,3-glucanase) that degrade pathogen cell components and siderophores that compete for iron with phytopathogens. The top five antimicrobial metabolites identified in SDS were pyroglutamic acid, deoxycytidine, pyrrole-2-carboxylic acid, 13-oxo-9,11-tridecadienoic acid, and 3'-amino-3'-deoxythimidine. Among them, pyroglutamic acid may play a vital role in powdery mildew control. As a result, SDS, S-SDS, and H-SDS strongly inhibited the conidial germination of Erysiphe cichoracearum and Sphaerotheca fuliginea. The application of SDS significantly increased the activity of antioxidant enzymes in crop leaves and effectively controlled tobacco and cucumber powdery mildew in the greenhouse and the field. Therefore, L. enzymogenes LE16 can effectively control powdery mildew. The underlying mechanisms may be attributed to the induction of plant systemic resistance and the production of antifungal substances. [ABSTRACT FROM AUTHOR]