Climate effects of the Three Gorges Reservoir as simulated by a high resolution double nested regional climate model

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The Role of Antioxidant Enzymes in Adaptive Responses to Sheath Blight Infestation under Different Fertilization Rates and Hill Densities

Sheath blight of rice, caused by Rhizoctonia solani, is one of the most devastating rice diseases worldwide. No rice cultivar has been found to be completely resistant to this fungus. Identifying antioxidant enzymes activities (activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)) and malondialdehyde content (MDA) responding to sheath blight infestation is imperative to understand the defensive mechanism systems of rice. In the present study, two inoculation methods (toothpick and agar block method) were tested in double-season rice. Toothpick method had greater lesion length than agar block method in late season. A higher MDA content was found under toothpick method compared with agar block method, which led to greater POD and SOD activities. Dense planting caused higher lesion length resulting in a higher MDA content, which also subsequently stimulated higher POD and SOD activity. Sheath blight severity was significantly related to the activity of antioxidant enzyme during both seasons. The present study implies that rice plants possess a system of antioxidant protective enzymes which helps them in adaptation to sheath blight infection stresses. Several agronomic practices, such as rational use of fertilizers and optimum planting density, involved in regulating antioxidant protective enzyme systems can be regarded as promising strategy to suppress the sheath blight development

Study of Xuanhuang Pill in protecting against alcohol liver disease using ultra-performance liquid chromatography/time-of-flight mass spectrometry and network pharmacology

IntroductionXuanhuang Pill (XHP) is a traditional Chinese medicine oral formula composed of 10 herbs. This study aims to verify the hepatoprotective activity of XHP and explain its possible mechanism.MethodsThe hepatoprotective activity of XHP was evaluated by constructing a mouse model of alcoholic liver disease, and the mechanism of XHP was preliminarily explained by utilizing ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-QTOF/MS), proteomics and network pharmacology.ResultsThe current study demonstrated that treatment with XHP ameliorated acute alcohol-induced liver injury in mice by significantly reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and triglycerides (TGs) and malondialdehyde (MDA) content. Remarkably, treatment also increased superoxide dismutase (SOD) activity and glutathione (GSH) content. UPLC-QTOF/MS, 199 compounds were identified as within the make-up of the XHP. Network pharmacology analysis showed that 103 targets regulated by 163 chemical components may play an important role in the protective liver effect mediated by XHP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggest that the HIF-1, FoxO, PI3K-Akt, insulin, and thyroid hormone signaling pathways are key modulators of XHP’s effects. Finally, eight key targets including Mapk1, Mapk3, Akt1, Map2k1, Pik3ca, Pik3cg, Raf1, and Prkca were verified by molecular docking and proteomics analysis, which provide insight into the hepatoprotective effect observed with XHP treatment.ConclusionIn summary, these results improved upon knowledge of the chemical composition and the potential mechanisms of hepatoprotective action of oral XHP treatment, providing foundational support for this formulation as a viable therapeutic option for alcoholic liver disease

Bacteroides vulgatus alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance

BackgroundPatients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.MethodsWe performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography–tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut–brain communication. Evans Blue tracer dye was used to assess blood–brain barrier (BBB) permeability.ResultsOur results showed that the faecal abundance of Bacteroides vulgatus (B. vulgatus) was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the B. vulgatus group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, B. vulgatus relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of B. vulgatus was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, B. vulgatus and 4-HPAA play critical roles in gut–brain communication.ConclusionB. vulgatus and B. vulgatus-derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut–brain axis. Thus, administration of B. vulgatus or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD

Proteomics and network pharmacology of Ganshu Nuodan capsules in the prevention of alcoholic liver disease

IntroductionGanshu Nuodan is a liver-protecting dietary supplement composed of Ganoderma lucidum (G. lucidum) spore powder, Pueraria montana (Lour.) Merr. (P. montana), Salvia miltiorrhiza Bunge (S. miltiorrhiza) and Astragalus membranaceus (Fisch.) Bunge. (A. membranaceus). However, its pharmacodynamic material basis and mechanism of action remain unknown.MethodsA mouse model of acute alcohol liver disease (ALD) induced by intragastric administration of 50% alcohol was used to evaluate the hepatoprotective effect of Ganshu Nuodan. The chemical constituents of Ganshu Nuodan were comprehensively identified by UPLC-QTOF/MS, and then its pharmacodynamic material basis and potential mechanism of action were explored by proteomics and network pharmacology.ResultsGanshu Nuodan could ameliorate acute ALD, which is mainly manifested in the significant reduction of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and malondialdehyde (MDA) content in liver and the remarkably increase of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver. Totally 76 chemical constituents were identified from Ganshu Nuodan by UPLC-QTOF/MS, including 21 quinones, 18 flavonoids, 11 organic acids, 7 terpenoids, 5 ketones, 4 sterols, 3 coumarins and 7 others. Three key signaling pathways were identified via proteomics studies, namely Arachidonic acid metabolism, Retinol metabolism, and HIF-1 signaling pathway respectively. Combined with network pharmacology and molecular docking, six key targets were subsequently obtained, including Ephx2, Lta4h, Map2k1, Stat3, Mtor and Dgat1. Finally, these six key targets and their related components were verified by molecular docking, which could explain the material basis of the hepatoprotective effect of Ganshu Nuodan.ConclusionGanshu Nuodan can protect acute alcohol-induced liver injury in mice by inhibiting oxidative stress, lipid accumulation and apoptosis. Our study provides a scientific basis for the hepatoprotective effect of Ganshu Nuodan in acute ALD mice and supports its traditional application

SkyMath: Technical Report

Large language models (LLMs) have shown great potential to solve varieties of natural language processing (NLP) tasks, including mathematical reasoning. In this work, we present SkyMath, a large language model for mathematics with 13 billion parameters. By applying self-compare fine-tuning, we have enhanced mathematical reasoning abilities of Skywork-13B-Base remarkably. On GSM8K, SkyMath outperforms all known open-source models of similar size and has established a new SOTA performance

Analysis of risk factors and short-term prognostic factors of arrhythmia in patients infected with mild/moderate SARS-CoV-2 Omicron variant

BackgroundComplications, including arrhythmia, following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continue to be of concern. Omicron is the mainstream SARS-CoV-2 mutant circulating in mainland China. At present, there are few epidemiological studies concerning the relationship between arrhythmia and Omicron variant infection in mainland China.ObjectivesTo investigate the risk factors of arrhythmia in patients infected with the SARS-CoV-2 Omicron variant and the factors influencing prognosis.MethodsData from 192 Omicron infected patients with symptoms of arrhythmia (AH group) and 100 Omicron infected patients without arrhythmia (Control group) were collected. Patients in the AH group were divided into the good and poor prognosis groups, according to the follow-up results 4–6 weeks after infection. The general and clinical data between the AH and Control groups, and between the good and poor prognosis groups were compared. The variables with differences between the groups were included in the multivariate logistic regression analysis, and the quantitative variables were analyzed by receiver operating characteristic curve to obtain their cut-off values.ResultsCompared with the control group, the body mass index (BMI), proportion of patients with a history of arrhythmia, proportion of antibiotics taken, heart rate, moderate disease severity, white blood cell (WBC) count, and the aspartate aminotransferase, creatine kinase (CK), CK isoenzyme (CK-MB), myoglobin (Mb), high-sensitive troponin I (hs-cTnI), lymphocyte ratio and high sensitivity C-reactive protein (hs-CRP) levels in the AH group were significantly higher (p < 0.05). In addition, obesity (BMI ≥24 kg/m2), fast heart rate (≥100 times/min), moderate disease severity, and WBC, CK-MB and hs-cTnI levels were independent risk factors of arrhythmia for patients with Omicron infection (p < 0.05), and hs-CRP was a protective factor (p < 0.05). Compared with the good prognosis group, the age, proportion of patients with a history of arrhythmia, heart rate, proportion of moderate disease severity, and hs-CRP, CK, Mb and hs-cTnI levels were significantly higher in the poor prognosis group, while the proportion of vaccination was lower in the poor prognosis group (p < 0.05). Advanced age (≥65 years old), proportion of history of arrhythmia, moderate disease severity, vaccination, and hs-CRP, Mb and cTnI levels were independent factors for poor prognosis of patients with arrhythmia (p < 0.05).ConclusionThe factors that affect arrhythmia and the prognosis of patients infected with Omicron include obesity, high heart rate, severity of the disease, age. history of arrhythmia, WBC, hs-CRP, and myocardial injury indexes, which could be used to evaluate and prevent arrhythmia complications in patients in the future

Skywork: A More Open Bilingual Foundation Model

In this technical report, we present Skywork-13B, a family of large language models (LLMs) trained on a corpus of over 3.2 trillion tokens drawn from both English and Chinese texts. This bilingual foundation model is the most extensively trained and openly published LLMs of comparable size to date. We introduce a two-stage training methodology using a segmented corpus, targeting general purpose training and then domain-specific enhancement training, respectively. We show that our model not only excels on popular benchmarks, but also achieves \emph{state of the art} performance in Chinese language modeling on diverse domains. Furthermore, we propose a novel leakage detection method, demonstrating that test data contamination is a pressing issue warranting further investigation by the LLM community. To spur future research, we release Skywork-13B along with checkpoints obtained during intermediate stages of the training process. We are also releasing part of our SkyPile corpus, a collection of over 150 billion tokens of web text, which is the largest high quality open Chinese pre-training corpus to date. We hope Skywork-13B and our open corpus will serve as a valuable open-source resource to democratize access to high-quality LLMs

Deletion of the epigenetic regulator GcnE in Aspergillus niger FGSC A1279 activates the production of multiple polyketide metabolites

Epigenetic modification is an important regulatory mechanism in the biosynthesis of secondary metabolites in Aspergillus species, which have been considered to be the treasure trove of new bioactive secondary metabolites. In this study, we reported that deletion of the epigenetic regulator gcnE, a histone acetyltransferase in the SAGA/ADA complex, resulted in the production of 12 polyketide secondary metabolites in A. niger FGSC A1279, which was previously not known to produce toxins or secondary metabolites. Chemical workup and structural elucidation by 1D/2D NMR and high resolution electrospray ionization mass (HR-ESIMS) yielded the novel compound nigerpyrone (1) and five known compounds: carbonarone A (2), pestalamide A (3), funalenone (4), aurasperone E (5), and aurasperone A (6). Based on chemical information and the literature, the biosynthetic gene clusters of funalenone (4), aurasperone E (5), and aurasperone A (6) were located on chromosomes of A. niger FGSC A1279. This study found that inactivation of GcnE activated the production of secondary metabolites in A. niger. The biosynthetic pathway for nigerpyrone and its derivatives was identified and characterized via gene knockout and complementation experiments. A biosynthetic model of this group of pyran-based fungal metabolites was proposed. [Abstract copyright: Crown Copyright © 2018. Published by Elsevier GmbH. All rights reserved.

Water Bath Extraction Optimization of Polyphenols from Qing Brick Tea and Raw Material Selection for Tea Polyphenol Extraction

In this paper, single-factor experiments and orthogonal experiment were conducted to optimize the water bath extraction of polyphenols from Qing Brick Tea, and the optimal extraction conditions obtained were as follows: solvent of 50% ethanol, solid/liquid ratio of 1: 30, temperature of 80 ℃, and time of 6 min. Under the optimal water bath extraction conditions, polyphenols in fresh tea leaves, fresh tea petioles, fresh tea blades, finished brick tea, finished tea petioles, finished tea blades, tea dregs after brewing and tea dregs after boiling were extracted, respectively. It was found that the quality fraction of polyphenols extracted from fresh tea leaves was the highest, with the best extraction effect. The extraction effect of leaf blades was better than that of leaf petioles, and the extraction effect of tea dregs after brewing was better than that of tea dregs after boiling