Flavonoids are one of the principal bioactive components in Salix songarica flowers (S. songarica 'H'), and drying is critical for their preservation. To address this knowledge gap and identify the optimal processing strategy, four drying methods-freeze-drying (FD), vacuum microwave drying (WD), natural drying (ND), and hot-air drying (HD)-were systematically compared using UHPLC-MS/MS-based targeted metabolomics. A total of 673 flavonoid compounds were identified. FD most effectively preserved total flavonoid content and in vitro antioxidant capacity (DPPH, ABTS+, FRAP), with a strong positive correlation observed between them. Comparative analyses revealed 55, 95, and 67 differentially accumulated metabolites (DAMs) in the FD vs. WD, FD vs. ND, and FD vs. HD groups, respectively; these DAMs were mainly enriched in the flavonoid biosynthesis pathway. Notably, FD maintained the integrity of the flavonoid metabolic network under low-temperature, oxygen-limited conditions, thereby optimally preserving the phytochemical quality of S. songarica 'H'. This study provides the first metabolomic evidence to guide the optimization of drying processes for this distinctive botanical resource.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal hepatic lipid accumulation and is frequently driven by factors such as a high-fat diet (HFD). Total flavonoids of Apocynum venetum (TFAV), the bioactive constituents of a traditional medicinal plant, have demonstrated antioxidant and lipid-modulating properties. However, their therapeutic potential against MASLD and the underlying mechanisms are not explored. This study aims to evaluate the ameliorative effects of TFAV on HFD-induced MASLD utilizing both in vivo animal and in vitro cellular models. Methods: C57BL/6J were allocated to control, high-fat diet (HFD), TFAV (100 mg/kg/day), and TFAV intervention groups (25, 50, and 100 mg/kg/day). In vitro, WRL68 hepatocytes were stimulated with free fatty acids (FFAs) to establish a cellular model of steatosis. Liver function, serum lipid profiles, hepatic histopathology, and the AMPK signaling pathway were assessed. Results: TFAV intervention significantly improved serum biochemical profiles in the animal models; for instance, co-treatment with 100 mg/kg/day TFAV and HFD reduced TC, TG, and LDL-C levels by 20.59%, 45.26%, and 38.24% respectively (p < 0.05), and effectively alleviated hepatic steatosis and hepatocyte ballooning. Furthermore, TFAV markedly inhibited intracellular reactive oxygen species (ROS) levels and activated the AMPK signaling pathway (p < 0.05). This was accompanied by the downregulation of SREBP-1c and ACC expression (p < 0.05), as well as the upregulation of ATGL and CPT1α expression (p < 0.05). Conclusions: These results demonstrates that TFAV remodel hepatic lipid homeostasis by activating the AMPK signaling pathway, and exerting significant preventive and protective effects against the progression of HFD-induced MASLD in vivo.

More than 90% of deaths due to breast cancer (BC) are due to metastasis-related complications, with invasive ductal carcinoma (IDC) of the breast being the most common pathologic type of breast cancer and highly susceptible to metastasis to distant organs. BC patients who develop cancer metastases are more likely to have a poor prognosis and poor quality of life, so it is extremely important to recognize and diagnose whether distant metastases have occurred in IDC as early as possible. In this study, we develop a non-invasive breast cancer classification system for detecting cancer metastasis. We used Anaconda-Jupyter notebooks to develop various Python programming modules for text mining, data processing, and machine learning (ML) methods. A risk prediction model was constructed based on four algorithms: Random Forest, XGBoost, Logistic Regression, and SVM. Additionally, we developed a hybrid model based on a voting mechanism using these four algorithms as the base models. The models were compared and evaluated by the following metrics: accuracy, precision, recall, F1-score, and area under the ROC curve (AUC) values. The experimental results show that the hybrid model based on the voting mechanism exhibits the best prediction performance (accuracy: 0.867, precision: 0.929, recall: 0.805, F1-score: 0.856, AUC: 0.94). This stable risk prediction model provides a valuable reference support for doctors in assessing and diagnosing the risk of IDC hematogenous metastasis. It also improves the work efficiency of doctors and strives to provide patients with increased chances of survival.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease with a complex etiology, in which several types of cells play important roles. Sex differences in disease susceptibility and survival have been observed in PAH patients, but few studies have analyzed the effect of changes in cell type and number on sex differences in PAH at the single-cell level. In this study, we performed a series of analyses on GSE169471 and GSE228644 datasets and found significant changes in the ratio of several types of cells in male PAH lung tissues. Surprisingly, we found that the ratio of macrophages in male PAH samples was 7 times higher than that in females. Consistently, the ratio of M1 macrophages was also significantly increased in male PAH samples. The different expression genes (DEGs) in macrophages were mainly involved in the ribosome pathway, which is closely related to cell proliferation. Inhibition of ribosomal protein L39 (RPL39), a core gene in the ribosome pathway, can inhibit macrophage proliferation and attenuate the sex differences in PAH. In conclusion, our study suggests that ribosome pathway-associated cell proliferation of macrophages might be associated with sex differences in PAH.

BackgroundThe use of highly active antiretroviral therapy has transformed AIDS into a chronic infectious disease, but issues of chronic inflammation and immune system activation persist. Modulating the gut microbiome of patients may improve this situation, yet the specific association mechanisms between HIV and the gut microbiome remain unclear. This study aims to explore the research hotspots and trends of the HIV and the gut microbiome, providing direction for future research.MethodsWe conducted a search of the Web of Science Core Collection database up to April 30, 2024 to retrieve articles related to the relationship between the HIV and the gut microbiome. The scientific achievements and research frontiers in this field were analyzed using CiteSpace, VOSviewer, and Bibliometrix statistical software.ResultsAs of April 30, 2024, a total of 379 articles met the inclusion criteria. The number of publications in this field peaked in 2023, and the number of articles published after 2020 declined. The country with the highest number of publications was the United States (184 articles), and the institution with the most publications was the University of Colorado (USA) (21 articles). The author with the most publications was Routy Jean-Pierre (Canada) (14 articles). High-frequency keywords, aside from the key terms, included “HIV,” “inflammation,” “immune activation,” “gut microbiota,” and “translocation.” Keyword burst results indicated that short-chain fatty acids, T cells and obesity might become the focus of future research.ConclusionThe research hotspots in this field should prioritize examining the role of the primary gut microbiome metabolite, short-chain fatty acids, in reducing immune system activation and inflammation. Another emerging area of interest could be the investigation into the annual increase in obesity rates within this field. Furthermore, understanding the metabolic mechanisms of short-chain fatty acids in T cells is essential. Additionally, multi-omics analysis holds potential.

BackgroundType 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.ObjectiveThis study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.MethodsWe used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package “bibliometrix” were used to conduct this bibliometric analysis.ResultsEventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.ConclusionIn the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.

PURPOSE:Kidney clear cell carcinoma (KIRC) has a poor prognosis, high morbidity and mortality rates, and high invasion and metastasis rate, and effective therapeutic targets are lacking. zDHHC3 has been implicated in various cancers, but its specific role in KIRC remains unclear.METHODS:In this study, we performed a pan-cancer analysis, bioinformatics analysis, and cell experiment to detect the role of zDHHC3 in KIRC.RESULTS:zDHHC3 was significantly down-regulated in KIRC, and that its high expression was associated with favorable patient outcomes. We identified 202 hub genes that were most relevant to high zDHHC3 expression and KIRC, and found that they were involved mainly in ion transport and renal cell carcinoma. Among these hub genes, SLC9A2 was identified as a downstream gene of zDHHC3. zDHHC3 suppression led to decreased expression and S-palmitoylation of SLC9A2, which further inhibited the apoptosis of Caki-2 cells.CONCLUSION:Our findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3-SLC9A2 axis may provide a new option for the clinical treatment of KIRC.

文章采用2012-2020年沪深A股上市企业数据,基于知识基础观,研究了员工教育投资与企业技术创新的关系,并考察了企业内、外部薪酬差距对二者关系的调节作用,以及联合调节作用.研究结果表明:(1)员工教育投资显著促进企业技术创新.(2)企业内部薪酬差距对二者的关系具有倒U型的调节作用.(3)企业外部薪酬差距对二者的关系具有正向调节作用.(4)企业内、外部薪酬差距具有联合调节作用.进一步研究发现:(1)员工教育投资对国企技术创新的促进作用更小.(2)企业内、外部薪酬差距的调节效应分别在非国有企业与国有企业中更显著.(3)员工教育投资能够显著促进制造业国企和东部、中部、西部地区国企的技术创新.因此,企业应重视员工教育投资,同时关注薪酬战略的内部公平性和外部竞争性,以便充分发挥员工教育投资对技术创新的正向效益.

Several studies indicated that the gut microbiota might participate in the beneficial effect of inulin on obesity. However, the mechanisms involved were still largely unknown. Sixteen high-fat diets (HFDs)-induced obese C57BL/6 mice were converted to a normal diet and then randomized into two groups, OND (obese mice + normal diet) group gavage-fed for 10 weeks with normal saline and ONDI (obese mice + normal diet + inulin) group with inulin at 10 g/kg/day. The body weight of HFD-induced obese mice showed different degrees of decrease in both groups. However, the ONDI group lost more weight and returned to normal earlier. Compared to the OND group, inulin supplementation significantly shifted the composition and structure of gut microbiota, such as higher α diversity. The β diversity analysis also confirmed the changes in gut microbiota composition between groups. At the genus level, the abundance of Alistipes was considerably increased, and it was significantly correlated with inulin supplementation (r = 0.72, P = 0.002). Serum metabolite levels were distinctly altered after inulin supplementation, and 143 metabolites were significantly altered in the ONDI group. Among them, indole-3-acrylic acid level increased more than 500-fold compared to the OND group. It was also strongly positive correlation with Alistipes (r = 0.72, P = 0.002) and inulin supplementation (r = 0.99, P = 9.2e−13) and negatively correlated with obesity (r = −0.72, P = 0.002). In conclusion, inulin supplementation could accelerate body weight loss in obese mice by increasing Alistipes and indole-3-acrylic acid level.

Idiopathic pulmonary arterial hypertension (IPAH) is a progressive vascular disease with high mortality and heritability. Pyroptosis is a novel form of programmed cell death, and it is closely associated with IPAH. However, the roles of pyroptosis-related genes (PRGs) in IPAH are still largely unknown. In this study, we identified KIF23 as the most relevant gene for IPAH and pyroptosis, and its expression was significantly increased in pulmonary arterial smooth muscle cells (PASMCs) of IPAH. Besides, the pyroptosis level of PASMCs was also considerably upregulated in IPAH. Knockdown of KIF23 in PASMCs could significantly suppress the PASMCs' pyroptosis and proliferation and then alleviate the increase in pulmonary arterial pressure, right ventricular hypertrophy, and pulmonary vascular resistance in IPAH. KIF23 regulated the expression of Caspase3, NLRP3, and HMGB1, and they were all involved in the PI3K/AKT and MAPK pathways, indicating that PI3K/AKT and MAPK pathways might participate in regulating PASMCs pyroptosis by KIF23. In conclusion, our study suggests that KIF23 may be a new therapeutic target for IPAH, which can alleviate the symptoms of IPAH by inhibiting the pyroptosis and proliferation of PASMCs.

同事公正氛围在现代日益扁平化管理的企业中作用凸显,对员工创新及组织绩效都会产生重要影响.在此背景下,学者们对此研究逐日加深.为进一步丰富其研究,文章根据社会交换理论,以认知—情感系统理论为逻辑框架,从个体层面构建同事公正氛围对员工创新行为的链式中介模型.通过对465名员工两阶段问卷调查数据进行回归分析,研究发现:同事公正氛围对员工创新行为有显著的正向影响;职场地位和工作获得感不仅在同事公正氛围与员工创新行为之间分别起单独中介作用,并且存在链式中介作用.本研究不仅有助于丰富同事公正氛围对员工创新行为的影响研究,还可为企业人力资源管理实践提供一定借鉴意义.

基于自我一致性理论和情感事件理论,以认知—情感系统理论作为影响路径的逻辑脉络,构建员工优势使用通过组织自尊与积极情绪影响员工创新行为的链式中介模型,探讨差错反感文化的边界作用.采用问卷调查法在两个时间点进行数据收集,通过配对得到302份有效数据,相关分析结果表明:员工优势使用正向影响创新行为;组织自尊和积极情绪不仅分别在员工优势使用与创新行为间发挥部分中介作用,而且共同发挥链式中介作用;差错反感文化负向调节员工优势使用与创新行为、组织自尊与创新行为、积极情绪与创新行为的关系.

Objectives. - Our goal was to test the anti-obesity effects of supplementing inulin and compound probiotic (CP) alone or in combination on HFD-mice model. Material and methods. - Fifty C57BL/6 mice were randomly divided into five groups of varying diets as follows: normal chow diet (NCD), high-fat diet(HFD), HFD + inulin, HFD + CP, HFD + inulin + CP. Each group consisted of five males and five females. All mice were sacrificed to test obesity parameters adipocytokines blood lipid parameters and inflammatory factor after seven weeks. Results. - Compared to male mice HFD group, the supplement of inulin and CP alone significantly improved HFD-induced obesity by regulating weight gain blood lipid metabolism inflammatory cytokines and adipokines. However, inulin combined CP had a better anti-obesity effect. For the female mice, body weight blood lipids and glucose liver weight and Free fatty acid (FFA) were influenced to different degrees. Besides, the beneficial effects of inulin and CP treatment on HFD-induced obesity showed gender-difference. Conclusion. - This study demonstrated that prebiotic inulin and CP could have paly antiobesity effects on HFD male mice, respectively. The synergism of inulin combined with CP on improving HFD-induced obesity was observed in our study. Meanwhile, there were differences between male and female mice of above beneficial effects, providing a rational therapeutic method of HFD-induced obesity in the future. (C) 2020 Societe francophone nutrition clinique et metabolisme (SFNCM). Published by Elsevier Masson SAS. All rights reserved.

该文以2013—2018年深沪A股的915家上市公司为研究样本,建立PVAR动态模型,通过脉冲响应函数和方差分解等方法探究政府补贴、企业能力与创新绩效之间的动态交互效应.结果发现:从创新绩效影响因素的角度,企业营销能力对创新绩效的促进作用最大,政府补贴次之,研发能力和管理能力较弱,且促进作用均在创新绩效未来第1期达到最大值,随后逐期递减;从政府补贴对象选择的角度,创新绩效和企业能力对政府补贴有促进作用,创新绩效能够促进企业在未来第2期获得政府补贴,管理能力和营销能力能够促进企业在未来第4期获得政府补贴;从影响企业能力的角度,政府补贴和创新绩效均对企业能力有抑制作用,但作用效果较小.该研究结论丰富了企业创新系统的相关研究,为企业争取政府补贴和协同内外部要素以提升创新绩效提供了可行性思路.

BackgroundArsenic trioxide (ATO) can bind directly to the human promyelocytic leukemia (PML) protein, leading to modification of PML by SUMOs. UBC9 is the only known E2-conjugating enzyme involved in SUMOylation. PML degradation via RNF4, an E3 ubiquitin ligases family member. PML is key organizer of nuclear bodies (NBs) that regulate many biological processes such as senescence, and DNA damage. ATO can activate the TGFβ/Smad signaling pathway, causing liver fibrosis. However, the roles of PML Sumoylation in ATO-induced liver fibrosis remain unclear.ObjectiveThis study aimed to investigate the role of PML Sumoylation in the ATO-induced HSCs activation and to improve the mechanism of ATO-induced liver fibrosis.MethodsHepatic stellate cells (HSCs) were treated with 2 μmol/L ATO. Cell viability was detected by CCK-8 analysis. Immunoblot analysis and real-time quantitative PCR were used to detect the expression of IL-1β, TNF-α, TGF-β1, p-Smad2/3, α-SMA, Collagen I and PML SUMOylation after silencing PML, UBC9, and RNF4, respectively. The formation of PML-NBs was observed by immunofluorescence staining.Results2 and 5 μmol/L ATO intervention increased HSCs cell viability. ATO was able to significantly trigger PML SUMOylation and the formation of PML-NBs. Inhibition of SUMOylated PML by silencing UBC9, subsequently preventing the downregulation of HSCs activation indicators induced by ATO (P < 0.05). Conversely, enhancing SUMOylated PML accumulation by silencing RNF4, activating TGFβ/Smad signaling pathway, eventually promoting the induction of liver fibrosis.ConclusionThese results indicated that PML SUMOylation plays a critical role in the development of liver fibrosis induced by ATO.

本文以我国2013-2018年深沪A股民营制造业上市公司为研究对象,以委托代理理论为基础,探讨了CEO产出型职业经历对企业创新投资的影响以及制度性因素的调节作用.研究发现,CEO产出型职业经历与企业创新投资呈正相关关系;股权制衡、两职合一、股权激励机制和市场竞争机制在CEO产出型职业经历与企业创新投资的关系中均有一定的调节作用;薪酬激励机制并没有起到调节作用.研究结果表明,合理选择具有相关职业经历的CEO、完善内外部制度性因素对抑制CEO的道德风险,充分发挥CEO在企业创新投资中的作用具有重要意义,同时也为我国民营制造业创新驱动发展战略下寻求建设创新优势提供了有力支撑.

This study investigated the effects of proanthocyanidins (PC) on arsenic methylation metabolism and efflux in human hepatocytes (L-02), as well as the relationships between PC and GSH, MRP1 and other molecules. Cells were randomly divided into blank control group, arsenic trioxide exposure group (ATO, As2O3, 25μmol/L), and PC-treated arsenic exposure group (10, 25, 50mg/L). After 24/48h, the contents of different forms of arsenic were determined, and the methylation indexes were calculated. Intracellular S-adenosyl methionine (SAM), arsenic (+3 oxidation state) methyltransferase (AS3MT), multidrug resistance-associated protein 1 (MRP1), and reduced glutathione (GSH) were ascertained. Changing trends were observed and the correlation between arsenic metabolism and efflux related factors and arsenic metabolites was analyzed. We observed that cells showed increased levels of content/constituent ratio of methyl arsenic, primary/secondary methylation index, methylation growth efficiency/rate, and the difference of methyl arsenic content in cells and culture medium (P<0.05, resp.). Compared with ATO exposure group, the intracellular SAM content in PC-treated group decreased, and the contents of GSH, AS3MT, and MRP1 increased (P<0.05, resp.). There was a positive correlation between the content of intracellular GSH/AS3MT and methyl arsenic. The content of MRP1 was positively correlated with the difference of methyl arsenic content in cell and culture medium; conversely, the SAM content was negatively correlated with intracellular methyl arsenic content (P<0.05, resp.). Taken together, these results prove that PC can promote arsenic methylation metabolism and efflux in L-02 cells, which may be related to the upregulation of GSH, MRP1, and AS3MT levels by PC.