👤 Wenjin Zou

Nurses in traditional Chinese medicine (TCM) departments face significant sleep challenges associated with occupational stressors. However, person-centered analyses classifying these sleep patterns remain scarce. This study aimed to identify heterogeneous sleep disturbance subgroups via latent profile analysis (LPA) and evaluate the performance of explainable machine learning models in discriminating these subgroups based on demographic and occupational features. A cross-sectional survey enrolled 7721 nurses from 130 TCM healthcare institutions in Liaoning Province (December 2024). Data encompassed demographic, occupational, and psychological variables obtained via self-administered questionnaires, including the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance short form 8a. LPA was employed to categorize sleep disturbance patterns. Recursive feature elimination with random forest (RFE-RF) was used to select features associated with subgroup membership for five machine learning models. Models were trained on 70% of the data and evaluated on a 30% independent test set. The optimal classification model (XGBoost) underwent interpretability analysis using Shapley additive explanations (SHAP). LPA identified three subgroups: mild-stable (29.8%), moderate-fluctuating (60%), and severe-persistent (10.2%). Machine learning models achieved test AUCs of 0.71-0.84, with XGBoost demonstrating the highest discriminatory performance (AUC = 0.84, 95%CI: 0.83-0.85) in classifying subgroups. SHAP analysis indicated that monthly income, organizational support, hospital level, self-compassion, and resilience were the top five features contributing to the model's classification output. This study characterized three distinct sleep disturbance subgroups among TCM nurses, with the majority exhibiting moderate symptoms. The sequential application of LPA and explainable machine learning demonstrated robust performance in distinguishing sleep disturbance patterns. Identifying correlates-such as lower income and resilience-may assist nurse managers in stratifying risk and tailoring interventions for those most likely to fall into the severe subgroup. Future longitudinal studies are required to validate the stability of these subgroups and establish causal relationships. Show less

At present, the research on the effective teaching behaviors of clinical nursing teachers mainly focuses on the overall level of effective teaching behaviors and their relationship with other variables, ignoring the individual heterogeneity of the effective teaching behaviors of clinical nursing teachers. This study through latent profile analysis (LPA), aims to identify different effective teaching behavior profiles of clinical nursing teachers and explore the demographic and personal factors associated with these different effective teaching behavior profiles. This is a cross-sectional study. A survey was conducted among 842 clinical nursing teachers through demographic questionnaires, the Effective Teaching Behavior Scale, and the Self-Efficacy Scale. LPA analyzes the potential characteristics of effective teaching behaviors of clinical nursing teachers. The multiple logistic regression method was used to explore the predictors of different spectra. Three potential characteristics were identified: Profile 1- high effective teaching behavior group, Profile 2- moderate effective teaching behavior group, and Profile 3 - low effective teaching behavior group. Marital status, years of teaching experience and self-efficacy are predictive factors for different profiles. Most clinical nursing teachers are classified as type 1, and they have relatively good effective teaching behavior ability. Strategies such as enhancing self-efficacy, paying attention to the marital status of clinical nursing teachers, and focusing on training clinical nursing teachers with shorter tenure may be effective ways to improve the effective teaching behaviors of clinical nursing teachers in different situations. Show less

The abuse of methamphetamine (METH) is associated with an increased risk of Parkinson's disease (PD), whereas microglial polarization and glucose metabolism disorders are closely related to the progression of PD. This study aimed to investigate the specific molecular mechanism underlying the promotion of PD progression by METH through the regulation of microglial polarization and glycolysis. METH-induced C57BL/6 mice and BV2 cells were used to construct PD-like neurotoxicity animal and cell models for experimental investigation. Behavioral tests, immunohistochemistry and Nissl staining were used to assess the behavioral ability and neuronal damage of the animals. The levels of related proteins, inflammatory cytokines and glycolysis were detected using immunofluorescence, ELISA, Western blotting, and CCK-8 assays. METH treatment significantly promoted behavioral disorders in PD mice, reduced the number of TH-positive neurons, and aggravated neuronal damage in the substantia nigra (SN). In addition, METH decreased the M2 marker proteins Arg-1 and CD206 and increased the M1 marker proteins iNOS and CD86; the proinflammatory cytokines TNF-α, IL-β, and IL-6; and glucose uptake, glucose consumption and lactic acid production, thus promoting M1 polarization and glycolytic activity in BV2 cells. In terms of the underlying molecular mechanism, METH treatment significantly increased the level of LPA. METH promotes LPA expression via upregulation of LIPH expression, and activates the PI3K/AKT pathway. Knockdown of LIPH or treatment with BrP-LPA reduces the ability of METH to promote M1 microglial polarization and glycolytic activity. Furthermore, the addition of the PI3K/AKT signaling pathway activator 740 YP weakened the inhibitory effect of BrP-LPA on the above process. METH may promote M1 polarization and glycolytic activity in microglia by activating LIPH/LPA/PI3K/AKT signaling, thus promoting the progression of PD. Show less

Social isolation has emerged as an increasingly critical public health issue among adolescents with depression. This study aimed to identify latent subgroups of social isolation based on its manifestations among adolescent patients with depression and to explore the associated influencing factors. A cross-sectional study was conducted from August 2024 to March 2025 at a specialized psychiatric hospital in Nanjing, China. Data were collected using paper-based questionnaires, which included demographic characteristics, the General Social Alienation Scale (GSAS), the Patient Health Questionnaire for Adolescents (PHQ-A), and the Resilience Scale for Chinese Adolescents (RSCA). Latent profile analysis (LPA) was used to classify patterns of social isolation. Chi-square tests, analysis of variance (ANOVA), lasso regression, and multinomial logistic regression were used to analyze profile characteristics and their influencing factors. A total of 412 adolescent patients with depression were included. This study identified three distinct profiles of social isolation: "Low isolation - Fluctuating group" (24.7 %, n = 102), "Moderate isolation - Skeptical group" (39.6 %, n = 163), and "High isolation - Avoidant group" (35.7 %, n = 147). Patients were significantly more likely to be classified into the "High isolation - Avoidant group" if they had siblings, a longer duration of mental illness, more severe depressive symptoms, or lower psychological resilience (all p < 0.05). This study revealed the heterogeneity of social isolation among adolescents with depression through LPA and identified key influencing factors. These findings provide a theoretical foundation for the development of tailored intervention strategies. Show less

Organic and organic-inorganic hybrid materials exhibiting room-temperature phosphorescence (RTP) and long persistent luminescence (LPL) materials have attracted growing attention for various time-resolved optoelectronic applications. To date, realizing intrinsically distinct RTP and LPL emissions within a single material system remains elusive, yet it is crucial for unlocking multifunctional applications such as multilevel optical encryption. Here, a Mn Show less

Achieving long persistent luminescence (LPL) in fully organic materials with both hour-level duration and high thermal stability remains a fundamental challenge attributable to rapid exciton quenching and poor resistance to thermal disturbances. Herein, a trap engineering strategy is reported based on rigidified triphenylamine derivatives and boronic ester functionalization embedded in recycled poly(ethylene terephthalate) (PET), enabling the first fully organic polymer-based LPL system that exhibits simultaneously ultralong LPL and exceptional thermal robustness. Molecular conformation locking and optimized donor-acceptor charge transfer lead to deep trap states (≈1.03 eV), resulting in ambient LPL lifetimes exceeding 12 h. Remarkably, the luminescence is thermally enhanced by over 56 times at 500 K, rivaling high-performance inorganic phosphors. In addition, 980 nm near-infrared photo excitation further amplifies the emission, showcasing strong photo-stimulated luminescence capability. Taking advantage of PET's processability, 3D-printed luminescent structures are fabricated that retain LPL functionality and enable spatially resolved thermal sensing and real-time damage detection. This work not only introduces a sustainable and scalable platform for advanced thermal imaging and optoelectronics, but also sets a new benchmark in the design of heat-resistant organic LPL materials, bridging the gap between high-performance functionality and environmental compatibility. Show less

In this study, we used optical genome mapping (OGM), conventional karyotyping, and next-generation sequencing to analyze cytogenomic alterations in 91 cases of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Whereas karyotyping detected abnormal karyotypes in 55% of cases, OGM identified cytogenetic abnormalities in 97.8% of the cases and provided clinically relevant information beyond karyotyping in ∼70% of cases. OGM detected gene rearrangements in 80% of cases, including 24 recurrent gene fusions and 21 previously unreported putative gene fusions in T-ALL. Copy number variants were detected in 93% of cases, with interstitial deletions the most common. Gene mutations were detected in 93% of cases, with NOTCH1 being most frequent (in 57% of cases). Combining all data, most T-ALL cases harbored 3 or more cytogenomic aberrations. Specific cytogenomic alterations differed among T-ALL subtypes as follows: rearrangements of BCL11B and PICALM::MLLT10, deletions of 7p, and mutations involving DNMT3A, WT1, TET2, IDH2, and FLT3 were common in early T-precursor and near-early T-precursor subtypes. Rearrangements of TLX1, KMT2A, STIL::TAL1, and NUP214::ABL1, deletions of 9p, and FBXW7 mutations were frequently associated with the cortical subtype. We conclude that integration of OGM and next-generation sequencing with karyotyping enables comprehensive cytogenomic profiling of T-ALL that improves detection of clinically relevant genomic alterations and may inform disease classification and future studies of risk stratification. Show less

Transitions of cancer cells between distinct cell states, which are typically driven by transcription reprogramming, fuel tumor plasticity, metastasis, and therapeutic resistance. Whether the transitions between cell states can be therapeutically targeted remains unknown. Here, using the epithelial-to-mesenchymal transition (EMT) as a model, we show that the transcription reprogramming during a cell-state transition induces genomic instability through R-loops and transcription-replication conflicts, and the cell-state transition cannot occur without the ATR kinase, a key regulator of the replication stress response. ATR inhibition during EMT not only increases transcription- and replication-dependent genomic instability but also disrupts transcription reprogramming. Unexpectedly, ATR inhibition elevates R-loop-associated DNA damage at the SNAI1 gene, a key driver of the transcription reprogramming during EMT, triggering ATM- and Polycomb-mediated transcription repression of SNAI1. Beyond SNAI1, ATR also suppresses R-loops and antagonizes repressive chromatin at a subset of EMT genes. Importantly, inhibition of ATR in tumors undergoing EMT reduces tumor growth and metastasis, suggesting that ATR inhibition eliminates cancer cells in transition. Thus, during EMT, ATR not only protects genome integrity but also enables transcription reprogramming, revealing that ATR is a safeguard of cell-state transitions and a target to suppress tumor plasticity. Show less

Defects in mitochondrial energy metabolism in injured tubular epithelial cells (TECs) are a well-recognized hallmark of kidney injury pathogenesis; however, the key target leading to this defect during the acute kidney injury (AKI)-to-chronic kidney disease (CKD) transition remains elusive. Here, we found that during the AKI-to-CKD transition, the increased WW domain containing E3 ubiquitin protein ligase 2 (WWP2) was shuttled to the mitochondria and disabled TEC mitochondrial energy metabolism by ubiquitinating and degrading complex II subunit succinate dehydrogenase complex subunit C (SDHC), leading to oxidative phosphorylation (OXPHOS) disability and aggravated TEC maladaptive repair. Preemptive and late depletion of Wwp2 both ameliorated unilateral ischemia-reperfusion (UIR) injury-induced AKI-to-CKD transition, and tubular-specific Wwp2 depletion resulted in the same protective phenotype. Furthermore, Sdhc knockdown abolished the protective effects of Wwp2 deletion in UIR mice. Conversely, SDHC overexpression attenuated OXPHOS impairment and TEC injury following WWP2 overexpression. Finally, we leveraged high-throughput virtual screening, enzyme activity assays, and binding affinity assays to identify two candidate WWP2 inhibitors. Both inhibitors significantly improved TEC maladaptive repair and deferred the AKI-to-CKD transition. Overall, we identified WWP2 as a critical regulator of mitochondrial OXPHOS integrity in maladaptive repairing TECs and identified two WWP2 inhibitors as potential drug candidates for interrupting the AKI-to-CKD transition. Show less

Polycystic ovary syndrome (PCOS) is a prevalent metabolic and reproductive endocrine disorder with strong heritability. However, the independent role of oocytes in mediating this heritability remains unclear. Utilizing in vitro fertilization-embryo transfer and surrogacy, we demonstrated that oocytes from androgen-exposed mice (F1) transmitted PCOS-like traits to F2 and F3 generations. Notably, caloric restriction (CR) in F1 or F2 effectively prevented this transmission by restoring disrupted DNA methylation in oocyte genes related to insulin secretion and AMPK signaling pathways. Further detection in adult tissues of offspring revealed dysregulated DNA methylation and expression of those genes (e.g., Adcy3, Gnas, and Srebf1) were reversed by maternal CR. Moreover, similar benefits of CR were observed in aberrant embryonic methylome of women with PCOS. These findings elucidate the essential role of CR in preventing PCOS transmission via methylation reprogramming, emphasizing the importance of preconception metabolic management for women with PCOS. Show less

GLP-1 has become a prime target for medical treatment due to its significant therapeutic efficacy. However, the activation mechanisms of class B1 GPCRs, including glucagon-like peptides (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), remain poorly understood. This study focuses on understanding the activation mechanisms of the GLP-1 receptor (GLP-1R) by investigating its conformational changes from activated/inactivated to inactivated/activated states. By analyzing the dynamic conformational changes of the receptor during activation, a closure-open transition in the extracellular domain (ECD) and a movement trend of the transmembrane helices are observed, which indicates a similarity to the activation mechanism of class A GPCRs. Furthermore, the binding characteristics of a dual agonist Tirzepatide (LY3298176) is studied in detail and it is revealed that the conserved residues contribute in a similar fashion toward binding to both GLP-1R and GIPR. Mutations in non-conserved residues in Tirzepatide affect the binding affinity, with C-terminal mutations weakening the binding affinity toward GLP-1R, while N-terminal mutations enhancing the affinity to GIPR, resulting in a biased binding mode. These findings enriched our fundamental understanding of GLP-1R/GIPR activation and provided theoretical guidance for the design and development of future peptide-based agonists and offer insights into the optimization of other dual or multi-target agonists. Show less

Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers. A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once-weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration. A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once-weekly administration. It was observed that C BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity. Show less

Diabetic kidney disease (DKD) is a common and serious complication in patients with diabetes mellitus (DM). This study was aimed to reveal the validity of seven emerging novel biomarkers of angiopoietin-like-4 (ANGPTL4), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), growth differentiation factor-15 (GDF15), fibroblast growth factor-23 (FGF23), n-terminal osteopontin (ntOPN) and pyruvate kinase muscle isozyme M2 (PKM2) in detecting DM patients at high risk of DKD and establish prediction models for DKD onset in DM patients. This was a cross-sectional study of 348 adult patients with Type 1 DM for at least 5 years, or Type 2 DM, followed by a prospective observational cohort of 141 adult DM patients without renal involvement at baseline and follow-up for at least 2 years. We performed logistic regression analysis to analyze the relationship between the variables and the risk of DKD occurrence, and receiver operator characteristic (ROC) analysis to assess the predictive ability of multi-biomarker panels for DKD onset. In the cross-sectional cohort, the seven urinary biomarkers were all elevated in DKD patients, of which the high levels of urinary ntOPN, GDF15, NGAL, MCP-1 and FGF23 significantly increased the risk of DKD diagnosis; the urinary MCP-1 alone performed best in DKD detection with the largest area under the ROC curve (AUC). In the prospective cohort, the high levels of urinary GDF15, MCP-1, ANGPTL4 and FGF23 significantly increased the risk of DKD development, and the model constructed based on the above four biomarkers had the largest AUC (0.873) for predicting the 2-year risk of DKD occurrence. Our study demonstrated that the four-biomarker model performed the best in predicting DKD, which could provide more accurate tools for DKD risk prediction, thereby improving the prognosis in DM patients. Show less

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using hematoxylin and eosin staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression. Show less

Abnormalities in lipid metabolism play an important role in diabetic macular edema (DME), and the aim of this study was to investigate the correlation between ApoB/A1 levels and best corrected visual acuity (BCVA) and macular microstructural changes in DME patients after anti-VEGF treatment. Through a retrospective cohort analysis of 61 patients (61 eyes) with non-proliferative diabetic retinopathy combined with macular edema treated with 3 + PRN anti-VEGF regimen and followed up for three months, grouped by median ApoB/A1, the differences between the efficacy indexes of the two groups were compared. The results showed that the macular edema regression rate was significantly higher in the high ApoB/A1 ratio group than in the low ratio group at one month after treatment(P < 0.05), and at three months after treatment, the high ApoB/A1 ratio group was better than the low ratio group in BCVA improvement (58.1% vs. 26.7%), inner retinal layer restoration (38.7% vs. 10.0%), and hyperreflective foci (HF) reduction (41.9% vs. 6.7%). aspects were better than those in the low ratio group (P < 0.05). The results of ordered logistic regression analysis showed that the ApoB/A1 ratio was significantly correlated with the change in macular edema at one month after treatment and the change in the number of HF at three months after treatment. Conclusions showed that the ApoB/A1 ratio was significantly correlated with short-term improvement of BCVA and macular microstructure after anti-VEGF treatment in DME patients, and it is expected to be used as an objective biomarker for assessing the efficacy of anti-VEGF treatment in DME patients. Show less

Emerging lipid-modifying agents show potential but lack evidence for the management of uric acid and gout. We aimed to explore the causal effects of lipid traits, lipid-modifying drugs on uric acid levels and risk of gout. Two-sample MR analyses were performed to investigate the associations of genetically predicted lipid traits (LDL-C, HDL-C and TG) and lipid-modifying drug targets (PCSK9, HMGCR, NPC1L1, CETP, ABCG5/G8, APOB, LDLR, LPL, ANGPTL3, and APOC3) with uric acid levels and gout risk. Validation analyses were performed using the independent cohort of the UK Biobank. Summary-data-based MR was further conducted to estimate the associations of the expression of drug target genes with the outcomes. Genetically predicted lower HDL-C and higher TG were significantly associated with elevated uric acid levels ( The online version contains supplementary material available at 10.1007/s43657-024-00212-7. Show less

Calcific aortic valve stenosis (CAVS) is steadily rising worldwide with no effective pharmacological agents available. Observational studies implicated dyslipidaemia as a risk factor for CAVS. Whether dyslipidaemia is causative for CAVS and the therapeutic potential of different lipid-modifying drug targets for CAVS treatment remains unclear. We appraised the relationship of genetically-proxied lipid traits and 12 lipid-modifying drug targets with CAVS risk using Mendelian randomization (MR). Genetic variants associated with lipid traits and variants in genes encoding lipid-modifying drug targets were retrieved from GLGC. Summary-level data for CAVS were obtained from the TARGET consortium and FinnGen. Validation analyses were performed using genetic instruments retrieved from liver-derived gene expression and circulation plasma levels of targets. Colocalisation and mediation analyses were performed to evaluate the robustness of our findings and explore potential mediators (i.e., lipoprotein a (Lp(a)), body mass index, apolipoprotein B (ApoB)). The MR analyses supported that total cholesterol and LDL-cholesterol level were independent causal risk factors. The drug-target MR analysis suggested that genetic mimicry of PCSK9 inhibition should reduce CAVS risk (OR = 0.63, 95% CI = 0.56-0.70), which was corroborated by colocalisation analysis. Secondary analyses supported a genetically proxied effect of liver-specific PCSK9 expression (OR = 0.94 per SD reduction in PCSK9 expression, 95% CI = 0.88-1.00) and circulating plasma levels of PCSK9 (OR = 0.86 per SD reduction in PCSK9 protein, 95% CI = 0.83-0.88) on CAVS risk. ApoB and Lp(a) mediated 55.9% and 4.5%, respectively, of the total effect of PCSK9 on CAVS risk. Multiple sensitivity analyses supported this observation. Our study supports total cholesterol, LDL-cholesterol as a causal factor for CAVS, and genetically proxied inhibition of PCSK9 may reduced its risk. Show less

This cross-sectional study retrospectively analyzed data from 9,218 patients who underwent physical examinations at Shanghai Health and Medical Center in 2022. HP infection status was determined using the carbon-13 breath test, and clinical data, biochemical indicators, and lipid metabolism-related data were collected. Multiple regression analysis was employed to investigate the relationship between HP infection and the ApoB/ApoA1 ratio. Patients in the HP-positive group were older and had a higher proportion of males. Their body mass index (BMI), blood pressure, γ-glutamyl transpeptidase (γ-GT), total cholesterol (TC), fasting blood glucose (FBG), Creatinine and White blood Cell were significantly higher than those in the HP-negative group. The HP-positive group exhibited a higher prevalence of underlying diseases (e.g., hypertension, diabetes, coronary heart disease) and significant abnormalities in glucose and lipid metabolism, uric acid, high-sensitivity C-reactive protein (hs-CRP), and other indicators. The ApoB/ApoA1 ratio was significantly elevated in the HP-positive group and was not influenced by gender. Multiple regression analysis revealed that the ApoB/ApoA1 ratio is an independent risk factor for HP infection. HP infection is closely associated with abnormal lipid metabolism, and the ApoB/ApoA1 ratio is an independent risk factor for HP infection, demonstrating significant advantages over other lipid indicators. This large-scale study highlights a significant association between HP infection and an elevated ApoB/ApoA1 ratio. The findings suggest that HP may contribute to cardiovascular risk via dyslipidemia, with the ApoB/ApoA1 ratio serving as a potential biomarker. Further research should explore whether HP eradication could mitigate these metabolic disturbances. Show less

Observational studies have identified a possible connection between lipid-lowering medications and respiratory illnesses. However, it remains unclear whether lipid-lowering drugs is causative for respiratory diseases, and we aimed to answer this question. We performed Mendelian randomization (MR) analyses by integrating data from genome-wide association studies (GWAS). Three statistical approaches were employed for MR analysis: inverse variance weighting (IVW), MR-Egger, and weighted median. The purpose was to evaluate the causal relationships between 10 drug targets that lower lipid levels and the likelihood of developing 7 respiratory diseases. Additional sensitivity analyses were conducted to ensure the robustness and validity of the results. After adjusting for multiple testing, our MR analysis identified APOB (odd ratios [OR]: 0.86; 95% confidence interval [CI]: 0.77 to 0.97; P Our findings suggest a likely causal relationship between respiratory diseases and lipid-lowering drug targets. Further mechanistic and clinical research is needed to confirm and validate these findings. Show less

At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia. Show less

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options, thus necessitating novel strategies targeting upstream fibrogenic drivers; the exact impact of apolipoprotein E (apoE) on IPF and its therapeutic potential remain unexplored. This study aims to identify novel therapeutic targets for pulmonary fibrosis and elucidate the mechanism by which plasma apoE alleviates this condition. We conducted an integrated meta-analysis of seven plasma cohorts and two-sample Mendelian randomization to assess apoE's association with IPF risk. CRISPR-engineered APOE-deficient canines and Apoe Plasma apoE was identified as a robust protective factor against IPF, with genetically elevated levels correlating with improved pulmonary function, and its deficiency in plasma showed potential diagnostic value for IPF. APOE-deficient canines developed spontaneous pulmonary fibrosis, and Apoe Plasma apoE is a causal guardian against pulmonary fibrogenesis, inhibiting TGF-β/Smad signaling through dual receptor (LRP1/PLAU) engagement. Cross-species validation and mechanistic elucidation position RGX-104, a small-molecule LXR agonist, as a potential therapeutic candidate for clinical translation in IPF. Show less

Extensive research has demonstrated that gut microbiota and its metabolites-including short-chain fatty acids, trimethylamine N-oxide (TMAO), and bile acids-play a crucial role in the pathophysiology of coronary artery disease (CAD).The bidirectional interaction between the gut microbiota and the cardiovascular system significantly influences host metabolic and inflammatory homeostasis. As a result, targeted modulation of the gut microbiota emerges as a promising adjunctive therapeutic strategy for CAD, offering potential benefits with minimal side effects. This study aims to elucidate the therapeutic mechanisms of the clinically validated Chinese medicine formula HJ11 in mitigating coronary heart disease (CHD), with a particular focus on its regulation of the heart-gut axis and associated atherosclerotic processes. This study established an ApoE-/- mouse model of atherosclerosis and treated with HJ11 via gavage.We investigated the effects of HJ11 on the gut microenvironment in these atherosclerotic mice. Gut microbial composition and faecal metabolite profiles were analyzed using 16S rDNA sequencing and metabolomics. Additionally, an in vitro model of atherosclerosis was used to examine whether HJ11 exerts anti-inflammatory effects by modulating the TLR4/MYD88/IκB-α signaling pathway. HJ11 exerted protective effects on coronary atherosclerosis by reducing systemic serum lipid levels and inhibiting plaque formation, vascular inflammation, and collagen deposition, while also alleviating aortic injury. It suppressed endothelial inflammation and inhibited the proliferation of vascular smooth muscle cells. In the gut, HJ11 alleviated intestinal structural damage and enhanced barrier integrity. Notably, it promoted the function of Akkermansia, a beneficial bacterium known to influence TLR4 expression. Finally, in an in vitro atherosclerosis model, HJ11 decoction inhibited cell proliferation and migration by inactivating the TLR4/MYD88/IκB-α signaling pathway-an effect that was abolished by TLR4 overexpression. Show less

Rupture of vulnerable atherosclerotic plaques is a major cause of acute cardiovascular events. Vascular smooth muscle cell (VSMC) senescence promotes plaque vulnerability by impairing fibrous cap integrity. Although melatonin exhibits atheroprotective potential, its capacity to stabilize plaques by targeting VSMC senescence along with the underlying mechanisms, remains unclear. In this study, a vulnerable plaque model was established in ApoE Show less

Branched-chain amino acids (BCAAs), including valine, leucine and isoleucine, are essential nutrient signals that influence mammalian animal metabolism. Many enzymes are involved in the metabolism of BCAAs, such as branched-chain amino acid transaminases (BCATs), branched-chain α-keto acid dehydrogenase (BCKDH), and BCKDH kinase (BCKDK). The aberrant expression of enzymes involved in BCAA metabolism and an imbalance in BCAA amino acid intake can lead to disordered metabolism. Aberrant BCAA metabolism can lead to several diseases, such as human ovarian disease, including ovarian cancer (OC), polycystic ovary syndrome (PCOS), and premature ovarian failure (POF), which are common gynaecological diseases. The overexpression of BCATs is found in OC, which promotes BCAA catalysis to provide a large amount of energy for tumorigenesis. However, BCKDK is overexpressed in epithelial ovarian cancer (EOC), which promotes proliferation and migration via MEK-ERK. In addition, several studies have reported that high levels of BCAAs are increased in the plasma of PCOS and POF patients. This review focuses on the role of BCAA metabolism and potential management methods for OC, PCOS and POF. Show less

Pathological cardiac hypertrophy is an independent risk factor for heart failure (HF). Early identification and timely treatment are crucial for significantly delaying the progression of HF. Targeted amino acid metabolomics and RNA sequencing (RNA-seq) were combined to explore the underlying mechanism. In vitro, H9c2 cells were stimulated with angiotensin II (Ang II) or were incubated with extra valine after Ang II stimulation. The branched chain alpha-ketoate dehydrogenase kinase (Bckdk) inhibitor 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) and rapamycin were utilized to confirm the role of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in this process. A significant accumulation of valine was detected within hypertrophic hearts from spontaneously hypertensive rats (SHR). When branched chain amino acid (BCAA) degradation was increased by BT2, the most pronounced decrease was observed in the valine level (Δ = 0.185 μmol/g, p < 0.001), and cardiac hypertrophy was ameliorated. The role of imbalanced mitochondrial quality control (MQC), including the suppression of mitophagy and excessive mitochondrial fission, was revealed in myocardial hypertrophy. In vitro, high concentrations of valine exacerbated cardiomyocyte hypertrophy stimulated by Any II, resulting in the accumulation of impaired mitochondria and respiratory chain dysfunction. BT2, rapamycin, and mitochondrial division inhibitor 1 (Mdivi-1) all ameliorated MQC imbalance, mitochondrial damage and oxidative stress in hypertensive models with high valine concentration. Valine exacerbated pathological cardiac hypertrophy by causing a MQC imbalance, probably as an early biomarker for cardiac hypertrophy under chronic hypertension. Show less

Gut microbiota not only biosynthesizes branched-chain amino acids (BCAA) but also catabolizes and utilizes them, while the effects of dietary BCAA supplementation on intestinal microbiota and metabolism remain largely elusive. Therefore, the present study aimed to investigate the impacts of dietary BCAA supplementation on productive performance, egg quality, gut microbiota and metabolism in laying hens. A total of 180 Fengda No.1 laying hens aged 41 weeks were randomly assigned to five groups, with each group consisting of six replicates of six hens, and the experiment lasted for 8 weeks. The control group (Ctrl AA) was fed a basal diet, while the other four groups were supplemented with 67% leucine (High Leu), isoleucine (High Ile), both leucine and isoleucine (High Leu + Ile), or a combination of the three BCAA (High BCAA), respectively, based on the Ctrl AA. The results demonstrated that compared with Ctrl AA, both High Ile and High BCAA significantly decreased egg mass and laying rate ( Show less