👤 Yan-ling Gao

Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders appear progressively more severe after ADR-based chemotherapy in the obese state, and the specific molecular mechanism needs to be further clarified. This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high-fat diet (HFD). We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce an in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on the regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology, and in vitro approaches. Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF receptor-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor 4 alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy. Show less

Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function. Show less

Mammalian scent glands mediate species-specific chemical communication, yet the mechanistic basis for convergent musk production remain incompletely understood. Forest musk deer and muskrat have independently evolved specialized musk-secreting glands, representing a striking case of convergent evolution. Through an integrated multi-omics approach, this study identified cyclopentadecanone as a shared key metabolic precursor in musk from both forest musk deer and muskrat, although downstream metabolite profiles diverged between the two lineages. Single-cell RNA sequencing revealed that these specialized apocrine glands possessed unique secretory architecture and exhibited transcriptional profiles associated with periodic musk production, distinct from those in conventional apocrine glands. Convergent features were evident at the cellular level, where acinar, ductal, and basal epithelial subtypes showed parallel molecular signatures across both taxa. Notably, acinar cells in both species expressed common genes involved in fatty acid and glycerolipid metabolism (e.g., Show less

This study aims to investigate how Bifidobacterium breve BBr60 improves obesity-related metabolic disorders by modulating the gut microbiota-SCFAs axis, thereby affecting inflammatory factors and metabolic hormones. A randomized, double-blind, placebo-controlled trial was conducted. A total of 75 individuals with obesity subjects (BMI ≥ 28) were enrolled and randomly assigned to either the BBr60 intervention group (10 billion CFU daily) and the placebo group. After the 12-week intervention, 65 participants (BBr60: n = 33; placebo: n = 32) completed the study and were included in the primary analysis. All participants received standardized nutritional counseling aimed at a moderate energy intake (~ 1800 kcal/day, including a daily intake of 25 g of dietary fiber.). Every week, we call participants at a fixed time to inquire about their weekly diet and weight changes, and provide dietary suggestions for the following week based on the inquiry results. Participants were instructed to maintain their usual physical activity levels throughout the study. The composition of the gut microbiota was analyzed by 16 S sequencing, fecal SCFAs were detected by GC-MS, and serum levels of IL-27, IL-1β, and metabolic hormones were measured using ELISA technology. Metabolic indicators such as body weight, body fat percentage, and HOMA-IR were also assessed. The BBr60 intervention significantly increased fecal butyrate levels (p < 0.001), accompanied by a decrease in IL-1β levels (p < 0.05) and an upregulation of IL-27 (p < 0.01). In terms of metabolic hormones, leptin (LEP), adiponectin (ADPN), connecting peptide (C-P), pancreatic polypeptide (PP), peptide YY (PYY), Glucose-dependent insulinotropic polypeptide (GIP), and Glucagon-Like Peptide-1 (GLP-1) were all significantly elevated (p < 0.05), while Homeostasis Model Assessment for Insulin Resistance(HOMA-IR) was significantly reduced in the BBr60 group (p < 0.05). In the control group, C-P, PP, and GIP were significantly increased (p < 0.05), whereas LEP, ADPN, PYY, GLP-1, and HOMA-IR showed no difference before and after the 12-week period. Correlation analysis indicated that butyrate levels were significantly positively correlated with GLP-1 and IL-27, and negatively correlated with IL-1β. Bifidobacterium breve BBr60, by remodeling the gut microbiota-SCFAs axis, inhibits the pro-inflammatory factor IL-1β, activates the anti-inflammatory signal IL-27, and synergistically regulates the metabolic hormone network (such as GLP-1, ADPN), significantly improving obesity-related metabolic disorders. This study provides a theoretical basis and intervention targets for the clinical application of probiotics targeting the "microbiota-SCFAs-inflammation/hormone axis," and future research can explore precise probiotic treatment regimens based on individual microbiota characteristics. Show less

The interleukin-6 (IL-6) family of cytokines includes IL-6, IL-11, IL-27, IL-31, etc. These cytokines are intimately linked with inflammatory diseases and exhibit pleiotropic properties. Several factors, including air pollution, smoking, and an aging population, are contributing to the changing epidemiology of respiratory diseases. A high incidence of respiratory disease represents a significant burden on society and the economy. The prominent role of IL-6 family members in respiratory diseases has been extensively studied, and they influence the disease process through multiple mechanisms and has significant clinical relevance in respiratory diseases. Here, we describe the role of IL-6 family cytokines and their signaling pathways on various immune cells, as well as the research progress on IL-6 family cytokines in respiratory diseases in recent years. The aim of this review is to provide an in-depth analysis of the key role of the IL-6 family in respiratory diseases and to provide a solid theoretical basis for further research and clinical practice in this field. Show less

Tuberculous pleural effusion (TPE) diagnosis still faces many difficulties and challenges. Some studies have shown that pleural interleukin -27 (IL-27) had a diagnostic potential for TPE. However, their findings are not always consistent. This study aimed to investigate the diagnostic accuracy of pleural IL-27 for TPE. We prospectively enrolled 211 patients with undiagnosed pleural effusion. Effusion Mycobacterium tuberculosis (Mtb) culture, Ziehl-Neelsen staining, biopsy, and response to antituberculosis therapy were used to define TPE. The pleural IL-27 levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) with the area under the curve (AUC) was used to evaluate the diagnostic accuracy of IL-27 for TPE. In addition, we investigated the influence of age on the diagnostic performance of IL-27 by resampling patients with different upper age limits in the inclusion criteria. Among the 211 enrolled participants, 33 were TPE and 178 were non-TPE. The mean concentration of IL-27 in TPE patients was significantly higher than that of non-TPE patients. The AUC of IL-27 was 0.76 (95 %CI: 0.67-0.86). At the threshold of 500 pg/mL, the sensitivity and specificity of IL-27 were 0.26 (95 %CI: 0.20-0.33) and 0.91 (95 %CI:0.76-0.97), respectively. The AUC of IL-27 is 0.84 in patients with an upper age limit of 70. Still, it decreased to 0.76 in patients with an upper age limit of 75. Age can affect the diagnostic performance of IL-27 for TPE. Show less

Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isolated from both cerebellum and frontal cortex of AD/ADRD patients and normal controls. Using peak-to-gene linkage analysis, we identified 431,834 significant linkages between gene expression and cell subtype-specific chromatin accessibility regions enriched for candidate cis-regulatory elements (cCREs). These cCREs were associated with AD/ADRD-specific transcriptomic changes and disease-related gene regulatory networks, especially for RAR Related Orphan Receptor A (RORA) and E74 Like ETS Transcription Factor 1 (ELF1) in cerebellar Purkinje cells and granule cells, respectively. Trajectory analysis of granule cell populations further identified disease-relevant transcription factors, such as RORA, and their regulatory targets. Finally, we pinpointed two likely causal genes, Seizure Related 6 Homolog Like 2 (SEZ6L2) in Purkinje cells and KAT8 Regulatory NSL Complex Subunit 1 (KANSL1) in granule cells, through integrative analysis of cCREs derived from snATAC-seq, genome-wide AD/ADRD loci, and three-dimensional (3D) genome data. Via CRISPRi experiments, we found that perturbation of rs4788201 and rs62056801 significantly inhibited the expression of their target genes, SEZ6L2 and KANSL1, in human iPSC-derived neurons. This cell subtype-specific regulatory landscape in the human cerebellum identified here offers novel genomic and epigenomic insights into the neuropathology and pathobiology of AD/ADRD and other neurological disorders if broadly applied. Show less

Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising intervention for Autism Spectrum Disorder (ASD), but objective markers for rTMS tolerance remain lacking. This case-control study explored gaze behavior variability toward emotional faces in ASD children undergoing rTMS, focusing on identifying subgroups associated with rTMS intolerance. Eye-tracking data (Tobii technology, preferential-looking paradigm) were collected from 104 ASD children (48 intolerant, 56 tolerant) receiving DLPFC-targeted rTMS (left high-frequency, right low-frequency). Latent Profile Analysis (LPA) identified fixation subgroups across eight conditions. Demographic (sex, age), clinical (CARS scores) differences, and profile-tolerance associations were analyzed. LPA revealed three gaze profiles: moderate non-preferential fixation (80.76%), low diverse fixation (9.62%), and increased fixation with mild variability (9.62%). Sex and CARS scores differed across profiles (age did not). Intolerance rates were 38.1%, 60.0%, and 100%, with profiles predicting rTMS intolerance (OR = 0.210, 95% CI: 0.079-0.557). ASD children exhibit heterogeneous emotional face gaze patterns. Findings highlight the need for personalized rTMS interventions, especially for those with higher CARS scores and increased emotional face fixation-at elevated intolerance risk. Show less

Cardiovascular-kidney-metabolic (CKM) syndrome significantly increases cancer and mortality risks, but the combined effects of CKM syndrome and physical activity (PA) on these outcomes remain poorly understood. This prospective study included 66,650 UK Biobank participants with accelerometry data. CKM syndrome was classified into five stages based on metabolic, kidney, and cardiovascular health. PA was categorized by intensity into light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) levels, and further divided into tertiles by daily duration. Multivariable Cox models were used to estimate hazard ratios. Over a median follow-up of 8.03 years, 4,301 incident cancer cases and 2,442 deaths occurred. Advancing CKM stages were associated with elevated risks of both cancer incidence and all cause mortality, while increasing PA levels reduced these risks. Significant interactions were observed between CKM syndrome and both MPA and MVPA on cancer and mortality risks (P interaction < 0.05). In participants with the lowest tertile of MPA or MVPA, those in stages 2 and 4 had higher cancer risk, while in the highest tertile, this risk was no longer elevated. For all-cause mortality, in participants with the lowest tertile of MPA or MVPA, CKM stage 3 exhibited higher risks, while those in the highest tertile did not. CKM stage 4 remained associated with higher mortality across all PA intensity levels, but risks decreased with increasing MVPA levels. Higher levels of MPA and MVPA may mitigate the elevated risks of both cancer incidence and all-cause mortality associated with CKM stages 2 to 4. Show less

Cardiovascular-Kidney-Metabolic (CKM) syndrome is characterized by the interrelatedness of chronic kidney disease, cardiovascular disease, and metabolic disorders. Although physical activity is widely acknowledged as an effective intervention for improving the prognosis of chronic diseases, its impact on all-cause mortality among patients with CKM syndrome remains unclear. To investigate the impact of physical activity on all-cause mortality among patients with CKM syndrome. Data from the 2011 wave of the China Health and Retirement Longitudinal Study were used as the baseline, with follow-up conducted until 2013. According to the International Physical Activity Questionnaire criteria, weekly physical activity levels were divided into three categories: light-volume physical activity (LPA), moderate-volume physical activity (MPA), and vigorous-volume physical activity (VPA). Cox proportional hazards regression models were employed to assess the impact of varying levels of physical activity on all-cause mortality. Restricted cubic spline analysis was used to explore possible nonlinear relationships. A total of 3343 patients with CKM syndrome were enrolled in this study. During the 2-year follow-up period, 44 deaths were recorded. After adjusting for potential confounders, VPA was associated with a 54% lower risk of all-cause mortality (adjusted hazard ratios, 0.46; 95% confidence interval: 0.24-0.89). Dose-response relationships demonstrated that all-cause mortality decreased as physical activity increased, with a 5.8% reduction in all-cause mortality risk for every 1000 MET-min/week increment in physical activity levels. VPA was significantly associated with reduced all-cause mortality in patients with CKM syndrome. Encouraging patients with CKM syndrome to engage in increased physical activity may improve clinical outcomes. Key messages What is already known on this topic: Cardiovascular-Kidney-Metabolic (CKM) syndrome involves a complex interplay between cardiovascular disease, metabolic disorders, and chronic kidney disease. While prior studies have established that physical activity can decrease mortality risk in the general population as well as in patients with cardiovascular and metabolic syndromes, the evidence regarding its impact on individuals with CKM syndrome remains limited. Additionally, there is a lack of detailed dose-response analyses of physical activity specifically targeting this high-risk population. What this study adds: This study provides novel evidence indicating that vigorous-volume physical activity (>3000 MET-minutes/week) significantly decreases all-cause mortality by 54% among patients with CKM syndrome, whereas moderate-volume, and light-volume physical activities show no significant effects. Notably, a linear dose-response relationship was established, demonstrating that each 1000-MET increment corresponds to a 5.8% reduction in mortality risk. These findings address a critical knowledge gap by quantifying both the threshold and incremental benefits of physical activity specifically for individuals with CKM syndrome, a population characterized by unique multisystem pathophysiology. How this study might affect research, practice, or policy: The findings of this study have the potential to substantially impact clinical practice by offering evidence-based thresholds for physical activity recommendations in the management of CKM syndrome. The benefits associated with vigorous-volume physical activity (>3000 MET-minutes/week) may encourage guideline committees to formulate more precise exercise prescriptions tailored to this high-risk population. Additionally, these results can be incorporated into a multidisciplinary care framework designed for managing complex chronic conditions. Show less

Human papillomavirus (HPV) infection is a global public health issue, and HPV-related stigma can affect cervical cancer prevention. But no validated tools exist to assess HPV stigma in Chinese adult women infected with HPV. This study aimed to adapt and validate the HPVsStigma scale (HPV-SS) in the Chinese context. A cross-sectional study was conducted from December 2024 to February 2025 among 501 HPV-infected women in Shenzhen, China. The HPV-SS was adapted from a 12-item HIV stigma scale. Demographic characteristics, HPV-related variables, and data on mental health were collected. Factor analyses (FA) were used to assess the scale's factorial structure, reliability, and validity. The bi-factor model was used to determine the score-reporting method of the scale. Item response theory (IRT) was employed to assess the relationship between participants' stigma levels and scale scores. Latent profile analysis (LPA) was conducted to classify the participants with different HPV stigma characteristics and determine the optimal cut-off value for HPV-SS. FA showed that the 3-factor model (personalized stigma, public-disclosure concerns, and negative self-image) had the best fit among the nested models, with good reliability and validity. The bi-factor model analysis indicated that the total scale score was more meaningful than dimension scores. IRT analysis confirmed that higher HPV-SS scores represented higher stigma levels. LPA identified a 2-class model as optimal, and the optimal cut-off value of the scale for high HPV stigma was 35. This study validated the 12-item HPV-SS for Chinese women infected with HPV, with good reliability and validity. The scale can be used to evaluate HPV stigma levels, facilitating targeted interventions to improve cervical cancer prevention and the psychological well-being of affected women. Show less

Inflammation and hyperlipidaemia contribute with similar magnitude to the risk of future atherothrombotic events. However, the relative importance of high-sensitivity CRP (hsCRP) and lipoprotein(a) (Lp[a]) as determinants of risk of major adverse cardiovascular events (MACE) are not well defined among patients aged 75 years or older with established atherosclerotic cardiovascular disease (ASCVD). The present study prospectively enrolled 2,333 patients aged 75 years or older diagnosed with ASCVD with measurement of hsCRP and Lp(a) at Fuwai Hospital. The primary endpoint was MACE, defined as a composite of all-cause death, myocardial infarction (MI), stroke or ischaemia-driven coronary revascularisation. The median follow-up time was 3.0 years (interquartile range [IQR]: 2.5-3.2 years). hsCRP was significantly associated with an increased risk of MACE (adjusted hazard ratio [aHR]: 1.05, 95% confidence interval [CI]: 1.03-1.08 per 1 mg/l increment, P < 0.001; highest versus lowest quartile: aHR: 1.70 [1.22-2.38]), whereas there was no significant association between Lp(a) and MACE risk (aHR: 1.02 [0.98-1.06] per 10 mg/dl increment, P = 0.341; highest versus lowest quartile: aHR: 1.06 [0.77-1.47]). Risks of MACE were significantly higher in participants with hsCRP ≥2 mg/l than in those with hsCRP <2 mg/l, irrespective of Lp(a) strata (aHR: 1.41 [1.12-1.79]; P = 0.004). Concomitant elevation of hsCRP (≥2 mg/l) and Lp(a) (≥30 mg/dl) was associated with the greatest risk of MACE (aHR, 1.54 [1.13-2.12]; P = 0.007). Inflammation assessed by hsCRP predicted risk of future cardiovascular events more strongly than Lp(a) in patients aged 75 years or older with established ASCVD. These results provided real-world evidence on older patients potentially benefit by targeted anti-inflammatory strategies for secondary ASCVD prevention. Show less

The direct current (DC) in optical orthogonal frequency division multiplexing (DCO-OFDM) scheme is commonly adopted in light fidelity (Li-Fi) technology as it offers a spectrally efficient solution. A prior study adopted a machine learning (ML)-based solution to predict the optimum DC bias using key parameters, including the statistical properties of the OFDM transmitted signal and a polynomial regression model. However, the model's robustness decreased when the data structure was shuffled, indicating limited generalization to unseen data. This study builds upon that work by utilizing the same dataset and improving the prediction model with advanced ML tools, such as the LazyPredict algorithm (LPA), to systematically evaluate and select a regression model. A robust ML regressor selection process is proposed to ensure the reliability of predictions. Additionally, a comprehensive data analysis is conducted to assess the importance of features affecting the optimum DC bias. The results demonstrate that the ensemble learning algorithm, Random Forest (RF), outperforms other models with an R-squared of 0.953 and an RMSE of 0.233. A Friedman statistical test was applied to validate the results over five iterations of model training. Furthermore, hyperparameter tuning and bootstrap sampling were employed to conduct a deeper investigation into the model's performance and stability. The proposed model significantly enhances the accuracy and robustness of DC bias prediction compared to previous approaches, ensuring consistent performance across different data distributions. Show less

Previous studies showed that obstructive sleep apnea (OSA) is associated with dyslipidemia. However, whether micro-arousals during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep independently associated with dyslipidemia were unknown. 4472 participants with OSA-related symptoms were finally included in our cohort. Various sleep variables including micro-arousal index (MAI) were obtained from standard polysomnography (PSG) recordings. Fasting serum lipid levels were assessed at our hospital laboratory. Linear regression models were employed to investigate relationships between micro-arousals in REM and NREM sleep and lipid profile with adjusting for multiple confounding factors. Fully adjusted models demonstrated a significant dose-dependent positive correlation between the MAI during REM sleep (MAI MAI Show less

The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect of 24-hour physical activities components on changing Life expectancy among patients with type 2 diabetes diagnosed. To address the abovementioned research gap, the study has a two-fold aims: first, to examine the mediation effect of 24-hour physical activities in type 2 diabetes and mortality; and second, to address how reallocating time on different daily activities would affect life expectancy. Analysis was conducted on the accelerometer data of 103,359 participants in the UK Biobank, with a median age of 57 years (range 39 to 70). Compositional mediation cox model was conducted to analyze the mediating effects of 24-hour physical activities. Additionally, the cohort Life table method was utilized to estimate the changes of Life-years over the next 10 years resulting from the substitution effect of different physical activities. During a mean follow-up of 13.95 (range 2.95-16.28) years, 2,649 deaths were recorded. Diabetes was significantly associated with increased time spent engaging in sedentary behavior (SB), and reduced time spent on moderate-to-vigorous physical activity (MVPA) and light-intensive physical activity (LPA), thereby demonstrating an association with higher mortality risk. The indirect effect of physical activity (HR = 1.27, 95% CI 1.23-1.30) accounted for 41.9% of the total effect of diabetes on mortality. Furthermore, the Life expectancy gains with a maximum of 1.32 years over the next 10 years was found when reallocating SB time to MVPA. The results revealed that 24-hour physical activities might mediate the association between diabetes and mortality. Therefore, promoting participation in MVPA and reducing sedentary activities among diabetes patients was expected to have a positive effect on Life expectancy over the next 10 years. Show less

This study aimed to explore the career adaptability status of cardiovascular specialist nurses (CSNs) through latent profile analysis (LPA), identify distinct subgroups and their demographic features, and determine factors influencing different adaptability categories. CSNs play a vital role in treating and rehabilitating patients with cardiovascular conditions. However, the existing literature offers limited insights into the career adaptability of CSNs in China. A multicenter, cross-sectional survey involving 659 Chinese CSNs was conducted. LPA was utilized to classify career adaptability profiles based on responses to the Career Adaptation Abilities Scale Short Form (CAAS-SF). Influencing factors were assessed using the Conditions of Work Effectiveness Questionnaire-II (CWEQ-II) and the General Self-Efficacy Scale (GSES). Differences among identified profiles were analyzed through ANOVA, chi-square tests, and multinomial logistic regression to explore relevant socio-demographic characteristics and influencing variables. A four-profile model provided the best fit, identifying groups labeled as “high adaptability” (Class 4, These findings provide evidence to assist nursing administrators in developing training programs to enhance CSNs’ career adaptability. The variables identified as associated with profile membership may enable more tailored training strategies. Show less

Low physical activity (LPA) significantly heightens the susceptibility of both type 2 diabetes mellitus (T2DM) and chronic renal disease. Nearly half of population diagnosed with T2DM globally worsen into diabetic kidney disease (DKD). Focusing on physically inactive populations, we aimed to comprehensively evaluate the trends over time and regional changes in T2DM-associated DKD attributable to LPA burden. We utilized data of the 2021 Global Burden of Disease (GBD) Study to initially assess the worldwide effects of T2DM-associated DKD attributable to LPA by computing the numbers and age-standardized rates (ASRs) of death, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs), categorized by subtypes in 2021. Linear regression model was applied to analyze the illness burden from 1990 to 2021. Furthermore, cluster analysis was performed to assess the regional differences in disease burden across GBD regions. Lastly, to forecast the illness burden for the next 25 years, we utilized the autoregressive Integrated Moving Average (ARIMA) and Excess Risk (ER) models. In 2021, the fatalities attributed to T2DM-related DKD attributable to LPA amounted to 30835 (95%UI: 12346-51646) cases, with 698484 (95%UI: 275039-1158032) DALYs. The ASRs of death and DALYs were 0.38 (95%UI: 0.15-0.63) and 8.19 (95%UI: 3.21-13.6) per 100000 individuals, respectively. Between 1990 and 2021, there was a notable escalation in deaths, DALYs, YLDs, and YLLs, as well as their ASRs. The highest burden was observed among males, older adults (aged 70 years and above), and middle Socio-demographic Index (SDI). Significant differences were noted in the disease burden among various regions and countries as defined by the GBD study. Predictive analyses indicate a continued escalation of this burden by the year 2050. The global impact of DKD attributable to LPA remains considerable, with significant disparities noted across different genders, ages, and regions. To mitigate this burden, it is crucial to implement effective interventions aimed at addressing physical inactivity, specifically designed for targeted demographic groups. Show less

This study aimed to investigate the association between objectively and subjectively measured 24-hour movement behaviors and physical fitness, and explore how the reallocation of time between 24-hour movement behaviors is associated with changes in physical fitness in adolescents. A total of 690 adolescents aged 14-17 years (55% girls) were included in this cross-sectional study conducted in Foshan, China. Moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, and sleep were assessed using accelerometers in combination with a questionnaire. Physical fitness was tested through body mass index, forced vital capacity, 50-m sprint, standing long jump, sit-and-reach, gender-specific 800/1000-m run, and pull-ups/sit-ups. MVPA was significantly associated with better performance in the 50-m sprint ( Show less

In school settings, nomophobia-a newly identified form of problematic mobile phone use characterized by anxiety and discomfort experienced when an individual is unable to use or access their smartphone-poses significant challenges to students' learning and daily life. Prior research on nomophobia has predominantly adopted a variable-centered perspective. However, if nomophobia is heterogeneous across subgroups, acknowledging this heterogeneity may inform the advancement of more tailored and productive therapeutic methods. Latent profile analysis (LPA) was conducted separately among high school students (N = 446) and college students (N = 667) to identify potential subgroup heterogeneity in nomophobia. To examine cross-group similarities in nomophobia profiles, a multi-group LPA was employed. Based on multiple model fit criteria, a three-profile solution-high nomophobia, moderate nomophobia, and low nomophobia-was identified for both groups. However, the multi-group LPA provided only partial support for the similarity of nomophobia profiles across educational stages, specifically in terms of configural and dispersion similarity. While similar nomophobia profiles emerged across groups, the partial equivalence suggests that intervention strategies for nomophobia may not be universally applicable across different educational levels. Additional studies should investigate the mechanisms underlying students' nomophobia profiles and to inform differentiated interventions for educators, institutions, and policymakers. Show less

Intensive poultry farming has significantly increased the incidence of lipid metabolic disorders, severely compromising the economic benefits of poultry industry. Currently, gamma-aminobutyric acid (GABA) is primarily used to mitigate adverse effects of heat stress in poultry, while the effects and mechanisms of GABA on lipid metabolism disorders remain underexplored. Lactobacillus plantarum (L. plantarum) serves as a significant source of GABA and is widely used in the livestock industry. This study therefore examines the effects of postbiotic GABA and the GABA-producing probiotic L. plantarum 1-2-3 on abdominal adipose tissue of laying hens following corticosterone-induced stress. To this end, hens subjected to corticosterone subcutaneous injections (4 mg/kg of body weight) were respectively received GABA (100 mg/kg BW) or L. plantarum 1-2-3 (1 × 10⁹ CFU/day). Results demonstrated that both GABA and L. plantarum 1-2-3 alleviated corticosterone-induced lipid metabolism disorders and reduced adipocyte size in abdominal fat. Additionally, expression analyses of genes and proteins related to lipid metabolism (PPARγ, C/EBPα, CD36, LPL, ATGL, and HSL) further showed that GABA and L. plantarum 1-2-3 inhibited excessive deposition of abdominal lipids in laying hens by suppressing adipogenesis and lipogenesis, while promoting lipolysis. Moreover, GABA and L. plantarum 1-2-3 both mitigated lipid deposition-induced inflammation and oxidative damage by normalizing macrophage infiltration and improving antioxidative enzyme activities (GSH-Px, T-SOD, CAT). These findings demonstrate the efficacy of GABA and L. plantarum 1-2-3 in alleviating lipid metabolism disorders in the abdominal adipose tissue of laying hens, suggesting their promise as nutritional supplements for counteracting stress-induced metabolic dysfunction. Show less

This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Liangshan black sheep were randomly divided into four groups of five replicate pens (four sheep per pen). Sheep were fed a basal diet supplemented with 0 (control), 10, 20% or 30% fermented onion. Compared to that of the control group, dietary supplementation with 20% fermented onion improved final body weight, ADG and ADFI; enhanced GPT and GOT activities and increased IgA, IgG, IgM, C3, and C4 levels; increased the levels of IL-4, IL-10, TGF- Show less

Lymphoplasmacytic Lymphoma (LPL) with immunoglobulin (Ig)A paraprotein is rare. When plasma cells dominate, the diagnosis becomes more challenging. We reported a case of a 71-year-old male with elevated creatinine, splenomegaly, monoclonal IgA, and MYD88 mutation. Only monoclonal plasma cells were detected first, leading to a misdiagnosis of multiple myeloma. When progressive spleen enlargement was observed, re-evaluation revealed the emergence of monoclonal lymphocytes and the diagnosis was revised to LPL. The addition of rituximab to DVD regimen led to a partial response. For cases where an initial definitive diagnosis cannot be established, close follow-up is required for timely diagnosis revision and therapeutic adjustment. Show less

Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and promote glycolipid metabolism in animals. In a preliminary study, we revealed that trans-10, cis-12-CLA (10,12-CLA) plays an important role in modulating lipid metabolism in chickens. However, the underlying mechanism remains unclear. In this study, we constructed an isolated in vitro model with primary chicken hepatocytes to investigate the effect of 10,12-CLA on lipid metabolism. 10,12-CLA inhibited lipid accumulation by decreasing the mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c), SREBP2, 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS), adipose triacylglyceride lipase (ACC), and lipoprotein lipase (LPL) and increasing the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1 (CPT1) and adipose triacylglyceride lipase (ATGL). Furthermore, 10,12-CLA treatment activated the protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2) and AMP-activated protein kinase (AMPK), whereas treatment with the ERK1/2 inhibitor U0126 reversed the inhibitory effects of 10,12-CLA on lipid accumulation by blocking the ERK1/2-AMPK pathway, leading to increased lipid accumulation and triglyceride content in primary chicken hepatocytes. These findings suggest that in chicken hepatocytes, 10,12-CLA alleviates hepatocyte lipid deposition by activating the ERK1/2-AMPK pathway, promoting fatty acid oxidation and reducing lipid synthesis, revealing the potential mechanism through which 10,12-CLA regulates hepatic lipid metabolism in chickens. Show less

Third-generation EGFR tyrosine kinase inhibitors (TKI) have revolutionized the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance remains a significant challenge. This study investigates the metabolic mechanisms driving third-generation EGFR-TKI resistance. We conducted plasma metabolomics analysis on 216 longitudinal samples from 186 patients with NSCLC enrolled in the clinical trial of rezivertinib (NCT03386955). Additionally, multiomics profiling of rezivertinib-resistant cell lines, functional in vitro experiments, and single-cell RNA sequencing analyses of 215 patients with NSCLC were integrated to reveal underlying mechanisms. Nonresponder patients exhibited elevated glycerophospholipids and dysregulated lysophospholipid (LPL) metabolism. Unsupervised clustering identified two patient subgroups, with cluster 1 (characterized by high LPL levels) associated with poorer survival (P = 0.022). A metabolite-based predictive model achieved robust performance [AUC: 0.7762 (training) and 0.7485 (test)]. Longitudinal analyses demonstrated LPLs and lysophosphatidic acid (LPA) accumulation during the resistance process. Integrated multiomics analyses highlighted epithelial-mesenchymal transition and glycerophospholipid reprogramming in rezivertinib-resistant cells. Functional assays confirmed that LPA promoted cell migration and invasion and attenuated the efficacy of third-generation EGFR-TKI, whereas disruption of the LPA-LPA receptor signaling axis reversed LPA-mediated resistance. Single-cell RNA sequencing identified an LPA-secreting malignant subset (cluster c4), characterized by enhanced epithelial-mesenchymal transition activation and extensive microenvironmental cross-talk through Wnt, TGF-β, and extracellular matrix signals. Our study highlights the pivotal role of LPA-mediated signaling and metabolic reprogramming in third-generation EGFR-TKI resistance. Targeting LPA production or its downstream pathways may offer novel therapeutic strategies to overcome resistance. This study provides critical metabolic insights for managing EGFR-mutant NSCLC. Show less

The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epithelial cells are the precursors of milk fat globules (MFG). However, it is unclear what happens to proteins during the transformation process from LD to MFG, and little is known about the regulation of LD diameter in vivo. In this study, 12 mid-lactation Saanen dairy goats were randomly divided into 2 groups: a control group fed a basal diet and an experimental group fed a basal diet supplemented with CLA at 90 g/d. Goat milk was collected for analysis of composition and MFG size. Mammary gland tissue was collected for analysis of LD diameter and proteins. The size of MFG was found to depend on LD diameter in the mammary glands of dairy goats. The regression equations for MFG size (Y) and LD diameter (x) were Y Show less

Membrane lipids play a crucial role in brain function and cell signalling, and they serve as key biological substrates in inflammatory responses, thrombosis, and energy metabolism. Multiple clinical and molecular evidences suggest that membrane lipids are probably involved in the pathogenesis of ischemic stroke (IS). However, current knowledge about the membrane lipid landscape and its involvement in IS pathophysiology is limited. We performed untargeted lipidomic analysis on erythrocyte membranes from 56 IS patients and 55 healthy controls. Integrated with gene expression and weighted gene co-expression network analysis, we identified dysregulated lipid signalling pathways and their contributions to IS pathophysiology. A total of 1392 erythrocyte membrane lipids were detected and quantified. Our results revealed significant impairment of membrane lipid homeostasis in IS patients, characterized by a marked reduction in glycerophospholipids (GPLs) and lysophospholipids (LPLs). Further analysis indicated that the impaired lipids were primarily concentrated in three disturbed signalling pathways, including the phospholipase A2-mediated GPL-LPL pathway, the phospholipase C-mediated inositol 1,4,5-trisphosphate/diglyceride pathway, and the sphingosine-1-phosphate (S1P)-S1P receptors pathway. Gene expression results indicated that these pathways were inhibited during the subacute phase of IS. Furthermore, these lipid signalling pathways form a highly interconnected network that collaboratively contributes to inflammation and thrombosis in IS, thereby influencing the progression and prognosis of the disease. Our findings reveal impaired erythrocyte membrane lipid homeostasis in IS, which implicates inflammatory processes and thrombosis in IS. This research offers new insights into the role of membrane lipids in IS pathogenesis, potentially informing future monitoring and therapeutic strategies. Show less

To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: ① Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; ② Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; ③ Type III, the LPL was absent in 16 cases; ④ Type IV, the LPL was inserted at TPT in 6 cases; ⑤ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; ⑥ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; ⑦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; ⑧ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62 ± 3.83) mm and female (28.07 ± 3.46) mm (t=-3.050, P = 0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, P > 0.05), and no statistical significance in the types between left and right sides (Z=-0.026, P > 0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less

The clinical application of cyclosporine A (CsA) is limited due to nephrotoxicity. Lipid metabolism disorders play important roles in renal injury, but their role in CsA nephrotoxicity is not yet clear. Huangqi (Astragalus mongholicus Bunge) and Danshen (Salvia miltiorrhiza Bunge) (HD) play roles in ameliorating the nephrotoxicity of CsA, but their mechanisms still need to be fully clarified. This study innovatively aimed to analyse the coexpression of renal proteins and serum metabolites for the identification of key pathways and targets. This study provides novel insight into the mechanism by which HD ameliorates CsA-induced nephrotoxicity. We utilized HD to intervene in both in vivo and in vitro nephrotoxicity models induced by CsA. For the in vivo experiments, we constructed a coexpression network of renal proteins and serum metabolites, which was used to screen for key pathways. To validate these findings, we knocked down key proteins in vivo. For the in vitro studies, we employed MTT, Transwell, flow cytometry, and immunofluorescence assays to monitor the epithelial-mesenchymal transition (EMT) of HK-2 cells. Additionally, we used electron microscopy and Seahorse assays to examine the effects of HD on mitochondrial structure and function. Furthermore, we overexpressed Ppara to further confirm the mechanism by which HD improves renal function. HD can improve renal pathological damage and function; regulate blood lipids, inflammation and oxidative stress indicators; and reduce apoptosis in renal tissues. Joint protein and metabolomics analyses revealed that two lipid metabolism-related pathways (the PPAR signalling pathway and linoleic acid metabolism pathway) were coenriched, involving six differential proteins (Cyp2e1, Cyp4a10, Gk, Lpl, Ppara, and Pck1) and two differentially abundant metabolites (alpha-Dimorphecolic acid and 12,13-EpOME). Western blot was used to verify differentially expressed proteins. HD improved mitochondrial damage and lipid accumulation, as demonstrated by transmission electron microscopy (TEM) analysis and Oil Red O staining. Knockdown of the key protein Ppara affected the expression of ACOX1 and exacerbated RF. In vitro verification demonstrated that HD significantly inhibited CsA-induced EMT in HK-2 cells and improved mitochondrial structure and function. Ppara overexpression promoted HD-mediated regulation of mitochondrial function, reduced apoptosis, and improved HK-2 RF. HD can ameliorate CsA nephrotoxicity through renal protein-serum metabolism coexpression, the PPAR signalling pathway, and linoleic acid metabolism. HD-induced upregulation of Ppara to regulate lipid metabolism, improve mitochondrial function and reduce apoptosis are important mechanisms. The Ppara/ACOX1/TGF-β1 axis may play an important role in this process. These findings offer potential targets for the future development of therapeutic strategies and novel drugs. Show less