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Work fatigue refers to physical, mental, and emotional exhaustion, resulting in the inability to work. Hitherto research indicate a close relationship between high-performance work systems and work fatigue, and there may be a double-edged sword effect of high-performance work systems on work fatigue. However, a comprehensive theoretical framework has not been developed to understand the relationship between them. Based on the challenge-hindrance stress model, this study employs role overload and job responsibility as mediating variables in a conceptual framework to understand the impact of high-performance work systems on work fatigue. Using the partial least square structural equation model and a sample of 360 employees in China, the mediating effects of role overload and job responsibility were confirmed. Further, the internal mechanisms of how high-performance work systems affect work fatigue are discussed, its adverse effects are confirmed, and its practical implications are proposed.

Ferroptosis is recently identified, an iron- and reactive oxygen species- (ROS-) dependent form of regulated cell death. This study was designed to determine the existence of ferroptosis in the pathogenesis of type 2 diabetic osteoporosis and confirm that melatonin can inhibit the ferroptosis of osteoblasts through activating Nrf2/HO-1 signaling pathway to improve bone microstructure in vivo and in vitro. We treated MC3T3-E1 cells with different concentrations of melatonin (1, 10, or 100 μM) and exposed them to high glucose (25.5 mM) for 48 h in vitro. Our data showed that high glucose can induce osteoblast cytotoxicity and the accumulation of lipid peroxide, the mitochondria of osteoblast show the same morphology changes as the erastin treatment group, and the expression of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11) is downregulated, but these effects were reversed by ferroptosis inhibitor ferrastatin-1 and iron chelator deferoxamine (DFO). Furthermore, western blot and real-time polymerase chain reaction were used to detect the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); osteogenic capacity was evaluated by alizarin red S staining and the expression of osteoprotegerin, osteocalcin, and alkaline phosphatase; the results showed that the expression levels of these proteins in osteoblasts with 1, 10, or 100 μM melatonins were significantly higher than the high glucose group, but after using Nrf2-SiRNA interference, the therapeutic effect of melatonin was significantly inhibited. We also performed in vivo experiments in a diabetic rat model treated with two concentrations of melatonin (10, 50 mg/kg). Dynamic bone histomorphometry and micro-CT were used to observe the rat bone microstructure, and the expression of GPX4 and Nrf2 was determined by immunohistochemistry. Here, we first report that high glucose induces ferroptosis via increased ROS/lipid peroxidation/glutathione depletion in type 2 diabetic osteoporosis. More importantly, melatonin significantly reduced the level of ferroptosis and improved the osteogenic capacity of MC3T3-E1 through activating the Nrf2/HO-1 pathway in vivo and in vitro.

The incidence of type 2 diabetic osteoporosis (T2DOP), which seriously threatens elderly people’s health, is rapidly increasing in recent years. However, the specific mechanism of the T2DOP is still unclear. Studies have shown the relationship between iron overload and T2DOP. Mitochondrial ferritin (FtMt) is a protein that stores iron ions and intercepts toxic ferrous ions in cells mitochondria. Ferroptosis, an iron-dependent cell injured way, may be related to the pathogenesis of T2DOP. In this study, we intend to elucidate the effect of FtMt on ferroptosis in osteoblasts and explain the possible mechanism. We first detected the occurrence of ferroptosis in bone tissue and the expression of FtMt after inducing T2DOP rat model. Then we used hFOB1.19 cells to study the influence of high glucose on FtMt, ferroptosis, and osteogenic function of osteoblasts. Then we observed the effect of FtMt on ferroptosis and osteoblast function by lentiviral silencing and overexpression of FtMt. We found ferroptosis in T2DOP rats bone. Overexpression of FtMt reduced osteoblastic ferroptosis under high glucose condition while silent FtMt induced mitophagy through ROS / PINK1/Parkin pathway. Then we found increased ferroptosis in osteoblasts after activating mitophagy by carbonyl cyanide-m-chlorophenyl-hydrazine (CCCP, a mitophagy agonist). Our study demonstrated that FtMt inhibited the occurrence of ferroptosis in osteoblasts by reducing oxidative stress caused by excess ferrous ions, and FtMt deficiency induced mitophagy in the pathogenesis of T2DOP. This study suggested that FtMt might serve as a potential target for T2DOP therapy.

Background: Arrhythmia after myocardial infarction, a common disease, has a high incidence and lethality in clinical practice, which seriously affects patients’ quality of life and survival time. Based on our previous study and available evidence, berberine plays a role in the treatment and prevention of arrhythmia after myocardial infarction. Thus, in order to clarify the specific mechanism and provide new clinical treatments, we conducted this study. Method: Firstly, we used bioinformatics analysis and system pharmacology to analyze the physicochemical properties and biological activities of berberine in the Molinspiration server. Secondly, we explored the potential molecular mechanism of arrhythmia after myocardial infarction treated with berberine by using network pharmacology technology: (1) obtaining common genes among berberine, myocardial infarction, and arrhythmia through TCMSP, TTD databases, and so forth; (2) constructing protein–protein interaction by using STRING database; (3) using g:Profiler database to conduct GO enrichment analysis of hub genes and pathways; and (4) performing molecular docking and visualization by using AutoDock and Pymol software. Finally, we applied Western blotting analysis and real‐time quantitative polymerase chain reaction to validate the expression of relevant proteins in the TGF‐ β 1‐induced cell models. Results: The results of bioinformatics analysis and system pharmacology of berberine indicated that it had wonderful bioavailability and high biological activities. The results of network pharmacology showed that (1) 70 genes related to berberine against arrhythmia after myocardial infarction were obtained, (2) 31 hub genes were obtained by constructing PPI network, and (3) GO enrichment analysis showed that hub genes were associated with mechanisms such as stimulus and cell death. The analysis of KEGG pathways, Wiki pathways, and Reactome pathways showed that the HIF‐1 signaling pathway and interleukin‐4 and interleukin‐13 signaling pathways were the most likely to exert therapeutic effects. (4) The results of molecular docking indicated that berberine most likely exerted therapeutic effects through acting on NGF. Western blotting analysis and real‐time quantitative polymerase chain reaction techniques showed that berberine could reduce the expression of NGF and α ‐SMA in TGF‐ β 1‐induced cell models, which confirmed the accuracy of the above findings. Conclusion: Berberine can reduce NGF secretion not only by inhibiting the conversion of cardiac fibroblasts to myofibroblasts but also by acting directly on myofibroblasts. Thus, the sympathetic nerve remodeling was inhibited, which can reduce the occurrence of arrhythmia after myocardial infarction. Considering its wonderful bioavailability and high biological activities, we believe that berberine can be a novel potential therapeutic agent with potential for the treatment of arrhythmia after myocardial infarction.

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity. Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Here the authors show that elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local bone GC activation, is associated with bone loss and obesity mice.

Background Early identification of high-risk individuals for coronary artery disease (CAD) is critical, especially in acute coronary syndrome (ACS) patients who face elevated risks of adverse cardiovascular events and are in need of intensified secondary prevention. This study aimed to investigate the combined value of the triglyceride-glucose (TyG) index—a surrogate marker of insulin resistance—and the systemic inflammatory response index (SIRI), calculated as (neutrophil count × monocyte count)/ lyphocyte count, in assessing coronary artery stenosis severity, proposing a cost-effective strategy for risk stratification in ACS management. Methods A retrospective cohort study included 415 ACS patients diagnosed by coronary angiography at Beijing University of Chinese Medicine Third Affiliated Hospital (June 2021–February 2024). Patients were stratified into low stenosis (Gensini score < 34, n  = 204) and high stenosis (Gensini score ≥ 34, n  = 211) groups based on the median Gensini score. Clinical parameters and inflammatory markers were analyzed using logistic regression and ROC curves. Results High stenosis group showed significantly higher TyG (1.95 vs. 1.42, P  < 0.001) and SIRI (1.07 vs. 0.75, P  < 0.001) than the low stenosis group. Both indices independently associated with severe stenosis (OR = 3.094 and 2.064, P  < 0.001). The combined TyG-SIRI model achieved an AUC of 0.744 (sensitivity 61.61%, specificity 72.06%), outperforming individual indices (TyG: 0.715; SIRI: 0.666; Delong's test P  < 0.05). Conclusion The combination of TyG and SIRI is strongly associated with coronary stenosis severity in ACS patients, suggesting its potential as a clinically feasible, non-invasive indicator for early risk stratification.

Polystyrene microplastics (PS MPs) are micrometer-scale items degraded from plastics and have been detected in various organisms. PS MPs have been identified as causing cognitive, cardiac, intestinal, and hepatic damage. However, their role in liver regeneration under drug-induced liver injury remains unknown. Thus, the current study aims to evaluate the impact of PS MPs on liver repair during APAP hepatotoxicity. PS MPs pretreatment exacerbates mice mortality and hepatocyte apoptosis, suppresses hepatic cell proliferation, and disturbs the inflammatory response in the APAP-induced damage model. Further mechanism exploration uncovers that prior PS MPs administration is sufficient to recruit neutrophils and macrophages, which are necessary for tissue recovery in the acute liver injury model. However, the polarization capacity of macrophages to anti-inflammatory sub-type is significantly delayed in PS MPs plus APAP group compared to the single APAP group, which is the leading cause of tissue repair suppression. Overall, the current study supports a new insight to realize the toxicity of PS MPs in acute liver injury, which should be considered in health risk assessment.

Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC. 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathologica

My orchestral work \"FROST BITTEN LOTUS\" (苍菡吟) draws inspiration from the first piece in the Yuan dynasty's song collection \"Gan He Ye (dried lotus) Eight Pieces.\" This is a set of sanqu (散曲, a form of classical Chinese poetry written to be sung) created by Liu Bingzhong, a Yuan dynasty writer. It's considered an excellent work that combines sanqu and folk songs, where the author creates meaning from the subject matter itself. This Yuan dynasty song is structured into seven distinct phrases, featuring a sophisticated rhyming pattern that includes four level-tone rhymes and two special \"xié\" rhymes (叶, pronounced in the second tone). These \"xié\" rhymes represent a unique feature in classical Chinese poetry where syllables share the same rhyme category but differ in tone.I designed the structure of my orchestral composition based on the tonal system of the Yuan dynasty, which had a fascinating linguistic characteristic: during this period, the traditional four-tone system was undergoing transformation. The entering tone (rusheng) was being merged into other tonal categories, creating a simplified system where syllables were broadly classified as either \"level\" or \"oblique\" tones. This tonal pattern creates a natural musical rhythm that I've incorporated into the piece's structure, translating these linguistic features into melodic and rhythmic elements that Western listeners can appreciate as a unique fusion of Eastern poetic structure and Western orchestral expression.Additionally, the musical mode marking for this Yuan song is Nan Lü (南吕). Although the pitch standards for ancient modes kept changing (showing a declining trend), the yin-yang division within the twelve lülü (律吕, Chinese twelve-tone musical system) remained constant. I created my pitch collections based on the level tones (平声) and oblique tones (仄声), which are fundamental to classical Chinese prosody, combined with the six yang lü and six yin lü, further incorporating post-tonal methods. Through transposition and inversion between different pitch sets, I achieved timbral transformations while avoiding repetition and overly consonant progressions.Finally, I used the varying character counts in the seven phrases of this Yuan song as the foundational template for my rhythmic design, which I then developed further. This approach translates the original poem's textual rhythm—where each Chinese character typically represents one syllable—into musical patterns that honor the source material's natural flow. I aim to portray a lotus that, though frost-bitten and withered, stands resilient and continues to emanate vitality against the harsh elements—a metaphor that resonates across cultures as a symbol of endurance and inner strength despite external challenges.

背景与目的 肺癌是全球癌症相关死亡的主要原因，患者从手术、放疗和化疗这些传统治疗方法中生存获益有限。免疫疗法作为肺癌的一种新兴治疗手段，显著延长了患者的总生存期（overall survival, OS），然而，仅有一部分患者能够从中获益，需要我们更深入地探索免疫治疗生物标志物以筛选优势人群。方法 从癌症基因组图谱（The Cancer Genome Atlas, TCGA）和基因表达综合数据库（Gene Expression Omnibus, GEO）下载原始数据，利用R软件和TIMER数据库筛选肺鳞癌（lung squamous cell carcinoma, LUSC）免疫预后相关基因。在TCGA和GEO数据库中研究了目标基因的表达情况，并通过R软件和TISIDB数据库对目标基因进行基因本体（Gene Ontology, GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析以及与肿瘤免疫特征之间的相关性分析。结果 我们筛选出cAMP依赖性蛋白激酶抑制剂γ（protein kinase inhibitor gamma, PKIG）这个免疫预后相关基因，PKIG在LUSC和正常组织中的表达有明显差异，并对LUSC的诊断和预后评估具有重要参考价值。PKIG差异基因主要集中富集在体液免疫反应的调节等过程。PKIG的表达与调节性T细胞（regulatory T cells, Tregs）的浸润水平呈正相关（r=0.340, P<0.001）。此外，PKIG还与LUSC中趋化因子配体2（chemokine C-C motif ligand 2, CCL2）（r=0.503, P<0.001）、CXC趋化因子配体12（CXC chemokine ligand 12, CXCL12）（r=0.386, P<0.001）和CXC趋化因子受体4（CXC-chemokine receptor 4, CXCR4）（r=0.492, P<0.001）等趋化因子/趋化因子受体以及细胞程序性死亡蛋白1（programmed cell death protein 1, PDCD1）（r=0.359, P<0.001）、细胞毒性T淋巴细胞相关蛋白4（cytotoxic T-lymphocyte associated antigen 4, CTLA4）（r=0.