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The Late Triassic Carnian pluvial event (CPE) was an interval marked by global climatic and environmental changes that occurred simultaneously with enhancement of the hydrological cycle. This event is characterized by multiple negative carbon isotope excursions (NCIEs). However, the driving mechanism behind these multiple NCIEs remains elusive because each of the NCIEs had different magnitudes in different geological settings. In this study, we present a high-resolution record of carbonate carbon isotope (δ 13Ccarb) and major and trace element data from Well QZ-8 in the Qiangtang Basin, eastern Tethys. The carbon isotope profile from this well displays a similar trend to those for contemporaneous strata in the NW Tethys and South China. This trend is characterized by a distinct negative excursion during the CPE, supporting a global event. Interestingly, our results reveal five NCIEs for the first time in the marine sedimentary succession. Furthermore, each of these NCIEs corresponds well to changes in Ti/Al, Sr/Al and Sr/Ba, suggesting a regional effect of the hydrological cycle on carbon isotope excursions. This study emphasizes that each of the NCIEs was influenced by regional hydrological cycles although the long carbon isotope excursion during the CPE was driven by the global carbon cycle. Supplementary material: Tables showing major element, isotope and trace element data and element ratios, and a supplementary figure are available at https://doi.org/10.6084/m9.figshare.c.6805266 [ABSTRACT FROM AUTHOR]

Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus(Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the Traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com).Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines.Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat’s iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.

ABSTRACTThis study was done to observe the safety and effect of Xiaoyaosan (XYS) on the stimulated depressive disorder (DD) related dry eye disease (DED) in mice. Normal control (NC) group, Vehicle group, and drug treatment groups, including Sertraline Hydrochloride (SH), XYS low-dose (XYS-LD), medium-dose (XYS-MD), and high-dose (XYS-HD), were established. The drug quality of XYS was assessed by high-performance liquid chromatography (HPLC). XYS toxicity in kidney and liver was assessed with Hematoxylin & Eosin (H&E) staining. Serum enzyme-linked immunosorbent assay (ELISA) and body weights were used to evaluate the depression status of mice. Tear production, corneal sensitivity, Oregon Green Dye (OGD) staining, and corneal confocal microscopy were used to assess ocular surface changes. H&E staining was also used to assess pathological cornea and lacrimal gland changes. HPLC results showed that XYS complied with Chinese drug quality standards. The drug treatment groups observed no drug toxicity reactions in the liver and kidney. SH and XYS groups improved DD-related serological indices as compared with Vehicle. Body weight was enhanced in mice with XYS groups compared to Vehicle and SH. Mice with XYS treatments showed increased tear production and corneal sensitivity, decreased corneal OGD staining scores, improved morphology, and decreased inflammatory cell infiltration in the cornea and lacrimal gland. In conclusion, XYS had no drug toxicity, improved serological indices, and ocular surface pathological changes in DD-related DED mice. XYS is safe and may have a therapeutic effect on DD-related DED.

The purpose of this study was to comprehensively understand the formation mechanism of nutrient components and flavor compounds during the fermentation process of high-quality highland barley wine (HHBW). The dynamic changes of physicochemical properties, non-volatile compounds and volatile flavor compounds in HHBW at different fermentation times were investigated. The results indicated that the nutrient components and physiologically active substances in HHBW, such as proteins, β-glucan, total phenols and total flavonoids were higher than those in commercial highland barley wine (HBW). In addition, the analysis results of HS-SPME-GC-MS revealed significant differences in flavor compounds at each fermentation stage, with alcohol being the main flavor compound. The contents of aldehydes and ketones decreased rapidly with the progress of fermentation. Lactic acid was the most important organic acid in HHBW. Correlation analysis revealed a negative association between citric acid and most alcohols and esters, while tartaric acid and succinic acid exhibited positive correlations with alcohols. Bitter amino acids, such as valine, isoleucine, leucine, arginine and lysine, were positively correlated with most of the ester flavor compounds. The study can provide a reference for a deep understanding of the mechanism of the formation of the characteristic flavor of HHBW.

ABSTRACTRetinoblastoma (RB) is commonly-seen cancer in children. The p53 pathway dysfunction, which can lead to elevated MDM2 or MDM4 (p53 antagonists) protein expression, is frequently observed in almost all human cancers, including RB. The present study attempted to investigate the underlying mechanism from the perspective of non-coding RNA regulation. Here, we demonstrated that p53 and miR-129 were positively correlated with each other in RB. miR-129 directly targeted MDM2/4 to inhibit expression, therefore counteracting MDM2/4-mediated p53 signaling suppression and modulating RB cell proliferation and apoptosis. Moreover, p53 could activate the transcription of miR-129 via binding to the miR-129 promoter region, therefore forming a regulatory loop with MDM2/4 to affect RB progression. Altogether, the p53/miR-129/MDM2/4/p53 regulatory loop can modulate RB cell growth. We provide a solid experimental basis for developing novel therapies for RB.

Atractylodes macrocephalaKoidz, a traditional Chinese medicine, contains atractylenolide I (ATR-I), which has potential anticancer, anti-inflammatory, and immune-modulating properties. This study evaluated the therapeutic potential of ATR-I for indomethacin (IND)-induced gastric mucosal lesions and its underlying mechanisms. Noticeable improvements were observed in the histological morphology and ultrastructures of the rat gastric mucosa after ATR-I treatment. There was improved blood flow, a significant decrease in the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-18, and a marked increase in prostaglandin E2(PGE2) expression in ATR-I-treated rats. Furthermore, there was a significant decrease in the mRNA and protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and nuclear factor-κB (NF-κB) in rats treated with ATR-I. The results show that ATR-I inhibits the NLRP3 inflammasome signaling pathway and effectively alleviates local inflammation, thereby improving the therapeutic outcomes against IND-induced gastric ulcers in rats.

Helicobacter pylori (H pylori) infection is a crucial element in chronic gastritis progression towards precancerous lesions of gastric cancer (PLGC) formation and, potentially, gastric cancer; however, screening for and eliminating H pylorihas several challenges. This study aimed to assess the present research status, prominent themes, and frontiers of H pylori-related PLGC and to provide impartial evaluations of the developmental trends in this domain. This study extracted articles and review papers concerning H pylori-related PLGC published from 2013 to 2023 from the Web of Science Core Collection. The data was analyzed and visualized using VOSviewer and CiteSpace. The study encompassed 1426 papers, with a discernible upward trend in publications between 2013 and 2023. China emerged as the most productive country, whereas the United States exerted the greatest influence. Baylor College of Medicine was the most prolific institution. World Journal of Gastroenterologyfeatured the highest number of published papers, whereas Gastroenterologywas the most frequently cited journal. Kim N. from South Korea was the most prolific author. Co-cited literature pertained to various aspects such as gastritis classification, H pyloriinfection management, gastric cancer prevention, and managing patients with PLGC. Future research will focus on the Kyoto classification, cancer incidence, and gastric intestinal metaplasia. The results of this study indicate a persistent increase in attention directed toward H pylori-associated PLGC. The research emphasis has transitioned from molecular mechanisms, epidemiology, monitoring, and diagnosis to clinical prevention and treatment methodologies. The forthcoming research direction in this area will concentrate on controlling and preventing malignant PLGC transformation.

Objective: Sijunzi decoction (SJZD) has been used for alleviating peptic ulcer or gastric discomfort, and treating spleen disorders since the Song Dynasty, but its pharmacological effect on human gastric cancer (GC) is still unclear. In this research, a network pharmacology-based strategy was applied to explore active ingredients, potential targets, and molecular mechanisms of SJZD against GC.Methods: The active compounds and potential targets of SJZD, as well as GC-associated gene targets, were retrieved from publicly available databases. Bioinformatics approaches were used to assess the network interaction, functional regulation, and signaling pathways between SJZD ingredients and GC targets. The anticancer effects of SJZD against GC were verified in vivoby a mouse subcutaneous model.Results: The results of network analysis showed that quercetin was the most active ingredient in SJZD. Several prominent target genes of SJZD were identified, such as AKT1 and STAT3. Gene ontology analysis revealed that the core anti-GC targets of SJZD included transcription factor activity and kinase activity. Pathway enrichment analysis indicated that GC patients could be benefited from SJZD treatment via modulation of signaling pathways related to endocrine system, cancer, and infectious disease. Furthermore, in vivoexperiments showed that high-dose SJZD could inhibit GC xenograft tumor growth, reduce GC cell proliferation, induce GC cell apoptosis, and decrease the expression of p-AKT1 and p-STAT3.Conclusions: Taken together, our results suggest that SJZD can serve as an effective adjuvant therapeutic agent for GC patients.

Background: The studies about the correlation between bone mineral density (BMD) and coronary arterial calcification (CAC) were still controversial. The aim of this study was to conduct a meta-analysis to evaluate the association between BMD and CAC.Methods: We systematically searched PubMed, Embase, Google scholar and Cochrane library for observational studies. We pooled odds ratio (OR) or correlation coefficient, and 95% confidence interval (CI) of the studies. Continuous data were pooled by mean difference (MD). Sub-group analysis was applied to investigate sources of heterogeneity. Funnel plots for publication bias was also performed.Results: Seventeen studies met the inclusion criteria. Pooled ORs for the prevalence of CAC in patients with low BMD versus patients with normal BMD was 2.11 (95% CI: 1.11 - 4.02, P= 0.02). The data pooled for comparing CAC score of low BMD and normal BMD patients is 33.77 (95% CI: 23.77 - 43.77, p= 0.000). The pooled ORs of multivariate logistic regression to predict the association were 1.00 (95% CI: 0.92 - 1.10, p= 0.95, age-adjusted), and 0.95 (95% CI: 0.86 - 1.05, p= 0.33, multivariable-adjusted). Cohort category and BMD assessment method were the main sources of heterogeneity.Conclusions: Low BMD is associated with higher prevalence and severity of CAC, especially in postmenopausal women. But the relation is not significant after adjusting age and other confounding variables. Low BMD and CAC may be two independent processes with aging. More large-scale studies with high-quality design are still needed to increase the understanding of them.

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