Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study

Background Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. Methods Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro. Results SS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro. Conclusion Our results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury

Can LLMs Express Their Uncertainty? An Empirical Evaluation of Confidence Elicitation in LLMs

The task of empowering large language models (LLMs) to accurately express their confidence, referred to as confidence elicitation, is essential in ensuring reliable and trustworthy decision-making processes. Previous methods, which primarily rely on model logits, have become less suitable for LLMs and even infeasible with the rise of closed-source LLMs (e.g., commercialized LLM APIs). This leads to a growing need to explore the untapped area of \emph{non-logit-based} approaches to estimate the uncertainty of LLMs. Hence, in this study, we investigate approaches for confidence elicitation that do not require model fine-tuning or access to proprietary information. We introduce three categories of methods: verbalize-based, consistency-based, and their hybrid methods for benchmarking, and evaluate their performance across five types of datasets and four widely-used LLMs. Our analysis of these methods uncovers several key insights: 1) LLMs often exhibit a high degree of overconfidence when verbalizing their confidence; 2) Prompting strategies such as CoT, Top-K and Multi-step confidences improve calibration of verbalized confidence; 3) Consistency-based methods outperform the verbalized confidences in most cases, with particularly notable improvements on the arithmetic reasoning task; 4) Hybrid methods consistently deliver the best performance over their baselines, thereby emerging as a promising state-of-the-art approach; 5) Despite these advancements, all investigated methods continue to struggle with challenging tasks, such as those requiring professional knowledge, leaving significant scope for improvement of confidence elicitation.Comment: 11 Page

Ensemble Learning Independent Component Analysis of Normal Galaxy Spectra

In this paper, we employe a new statistical analysis technique, Ensemble Learning for Independent Component Analysis (EL-ICA), on the synthetic galaxy spectra from a newly released high resolution evolutionary model by Bruzual & Charlot. We find that EL-ICA can sufficiently compress the synthetic galaxy spectral library to 6 non-negative Independent Components (ICs), which are good templates to model huge amount of normal galaxy spectra, such as the galaxy spectra in the Sloan Digital Sky Survey (SDSS). Important spectral parameters, such as starlight reddening, stellar velocity dispersion, stellar mass and star formation histories, can be given simultaneously by the fit. Extensive tests show that the fit and the derived parameters are reliable for galaxy spectra with the typical quality of the SDSS.Comment: 41 pages, 23 figures, to be published in A

Towards Detecting The 2175-{\AA} Dust Feature Associated With Strong High Redshift Mg {\ss}II Absorption Lines

We report detections of 39 2175-{\AA} dust extinction bump candidates associated with strong Mg II absorption lines at z$\sim$ 1--1.8 on quasar spectra in Sloan Digital Sky Survey (SDSS) DR3. These strong Mg II absorption line systems are detected among 2,951 strong Mg II absorbers with the rest equivalent width $W_r\lambda2796 >$ 1.0{\AA} at $1.0 < z < 1.86$, which is part of a full sample of 7,421 strong Mg II absorbers compiled by Prochter et al. (2006). The redshift range of the absorbers is chosen to allow the 2175-{\AA} extinction features to be completely covered within the SDSS spectrograph operation wavelength range. An upper limit of the background quasar emission redshift at z$=$2.1 is set to prevent the Ly$\alpha$ forest lines from contaminating the sensitive spectral region for the 2175-{\AA} bump measurements. The FM90 (Fitzpatrick & Massa 1990) parameterization is applied to model the Optical/UV extinction curve in the rest frame of Mg II absorbers of the 2175-{\AA} bump candidates. The simulation technique developed by Jiang et al. (2010a, b) is used to derive the statistical significance of the candidate 2175-{\AA} bumps. A total of 12 absorbers are detected with 2175-{\AA} bumps at a 5$\sigma$ level of statistical significance, 10 are detected at a 4$\sigma$ level and 17 are detected at a 3$\sigma$ level. Most of the candidate bumps in this work are similar to the relatively weak 2175-{\AA} bumps observed in the Large Magellanic Clouds (LMC) LMC2 supershell rather than the strong ones observed in the Milky Way (MW). This sample has greatly increased the total number of 2175-{\AA} extinction bumps measured on SDSS quasar spectra. Follow-up observations may rule out some of possible false detections and reveal the physical and chemical natures of 2175-{\AA} quasar absorbers.Comment: 71 pages, 6 tables, 49 figures, accepted by ApJ, Table 1 is available entirely at http://home.ustc.edu.cn/~jpaty/dataset/qso_dr7.dat ;Table 2 is available entirely at http://home.ustc.edu.cn/~jpaty/dataset/rejected.lis

MiR-130a inhibition protects rat cardiac myocytes from hypoxia-triggered apoptosis by targeting Smad4

Background: Cardiomyocyte death facilitates the pathological process underlying ischaemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs play a critical role in the pathological process underlying myocardial infarction by regulating cardiomyocyte apoptosis. However, the relevance of miR-130a in regulating cardiomyocyte apoptosis and the underlying mechanism are still uncertain. Aim: We sought to explore the regulatory effect of miR-130a on hypoxic cardiomyocyte apoptosis. Methods: The expression of miR-130a was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell survival was determined by the MTT assay. The lactate dehydrogenase (LDH) assay was performed to deter­mine the severity of hypoxia-induced cell injury. Apoptosis was assessed via caspase-3 analysis. Protein expression level was determined by Western blotting. The genes targeted by miR-130a were predicted using bioinformatics and were validated via the dual-luciferase reporter assay system. Results: We found that miR-130a expression was greatly increased in hypoxic cardiac myocytes, and that the downregulation of miR-130a effectively shielded cardiac myocytes from hypoxia-triggered apoptosis. In bioinformatic analysis the Smad4 gene was predicted to be the target of miR-130a. This finding was validated through the Western blot assay, dual-luciferase reporter gene assay, and qRT-PCR. MiR-130a inhibition significantly promoted the activation of Smad4 in hypoxic cardiomyocytes. Inter­estingly, knockdown of Smad4 markedly reversed the protective effects induced by miR-130a inhibition. Moreover, we found that the inhibition of miR-130a promoted the activation of transforming growth factor-b1 signalling. Blocking of Smad4 signal­ling significantly abrogated the protective effects of miR-130a inhibition. Conclusions: The findings indicate that inhibition of miR-130a, which targets the Smad4 gene, shields cardiac myocytes from hypoxic apoptosis. This study offers a novel perspective on the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a possible drug target for the treatment of myocardial infarction

Caffeine intake and anxiety: a meta-analysis

The results from studies on relationship between caffeine intake and risk of anxiety remains controversial, so we conducted a meta-analysis to summarize the evidence about the association between caffeine intake and risk of anxiety. Relevant articles were identified by researching PubMed, Web of Science, Cochrane library, Embase, CNKI, WANFANG DATA, SinoMed and VIP from the inception to December, 2022. Three investigators independently sifted through the literature, extracted the data, and evaluated the quality of the included studies based on predetermined selection criteria and assessed articles with Risk of bias assessment tool for Cochrane systematic reviews and analytical cross-sectional study quality assessment tool from JBI PACES. After assessing the quality of the literature, meta-analysis was performed using Revman 5.4 and Stata 12.0. Data were obtained from eight articles, and 546 participants from 14 studies in eight articles from healthy populations were included in the caffeine-anxiety analyses. As the scales used to assess anxiety vary in the literature, we chose standardized mean difference as the outcome indicator. In terms of overall effect, the results of the meta-analysis showed that caffeine intake increased the risk of anxiety [SMD = 0.94, 95% Cl = (0.28, 1.60), p &lt; 0.05]. After suspecting that dose size might be responsible for the heterogeneity by sensitivity analysis, we performed subgroup analysis according to dose size and found that low-dose caffeine intake moderately increased the risk of anxiety [SMD = 0.61, 95%Cl = (0.42, 0.79), p &lt; 0.05], whereas high-dose caffeine intake had a highly significant increase in the risk of anxiety [SMD = 2.86, 95%Cl = (2.50, 3.22), p &lt; 0.05]. The results confirm that caffeine intake is associated with an elevated risk of anxiety in healthy individuals without psychiatric disorders, especially when the intake dose is greater than 400 mg

A reference-grade wild soybean genome

Efficient crop improvement depends on the application of accurate genetic information contained in diverse germplasm resources. Here we report a reference-grade genome of wild soybean accession W05, with a final assembled genome size of 1013.2 Mb and a contig N50 of 3.3 Mb. The analytical power of the W05 genome is demonstrated by several examples. First, we identify an inversion at the locus determining seed coat color during domestication. Second, a translocation event between chromosomes 11 and 13 of some genotypes is shown to interfere with the assignment of QTLs. Third, we find a region containing copy number variations of the Kunitz trypsin inhibitor (KTI) genes. Such findings illustrate the power of this assembly in the analysis of large structural variations in soybean germplasm collections. The wild soybean genome assembly has wide applications in comparative genomic and evolutionary studies, as well as in crop breeding and improvement programs

A reference-grade wild soybean genome

Wild relatives of crop plants are invaluable germplasm for genetic improvement. Here, Xie et al. report a reference-grade wild soybean genome and show that it can be used to identify structural variation and refine quantitative trait loci