Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable s Show more
Effective real-time monitoring and tracking of lipid droplets (LDs) are essential for the precise diagnosis of atherosclerotic plaques and the assessment of pathological progression. However, viable strategies for Show less
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroup Show more
Anxiety and depression are highly comorbid mental health disorders with heterogeneous symptom patterns and poorly understood transdiagnostic mechanisms. This study aims to characterize latent subgroups, risk factors, and symptom-level interactions underlying depression-anxiety comorbidity across adolescents and adults in multi-ethnic Southwest China. The study included a total of 41,394 adolescents (aged 9-19) and 17,345 adults (aged 18-80). Adolescents were recruited using multistage stratified cluster sampling, whereas adults were recruited by convenience sampling. All participants completed a self-designed sociodemographic questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). Latent profile analysis identified subgroups, logistic regression analyzed risk/protective factors, and network analysis mapped symptom interactions and bridge nodes. This study found that three adolescent profiles emerged: high (11.66 %), moderate (31.95 %), and low/no depression-anxiety (56.39 %). Adults were classified into low/no comorbidity (90.63 %) and comorbid depression-anxiety (9.37 %). Risk factors for adolescents included female gender (OR = 2.77, 95 %CI: 2.55-3.00; OR = 1.59, 95 %CI: 1.52-1.67), higher grade levels (OR = 3.45, 95 %CI: 3.10-3.84; OR = 3.56, 95 %CI: 3.33-3.80), smoking (OR = 1.72, 95 %CI: 1.51-1.96; OR = 1.28, 95 %CI: 1.17-1.41),drinking (OR = 2.45, 95 %CI: 2.23-2.70; OR = 1.66, 95 %CI: 1.55-1.77), family instability (OR = 1.16, 95 %CI: 1.02-1.31; OR = 1.33, 95 %CI: 1.14-1.56) and "other" ethnic minority (OR = 1.15, 95 %CI: 1.04-1.26). For adults, female gender(OR = 1.68; 95 %CI: 1.44-1.97), living alone(OR = 1.37; 95 %CI: 1.14-1.65), poor self-rated health (OR = 0.13, 95 %CI: 0.11-0.15), and Dai ethnicity (OR = 0.70, 95 %CI: 0.49-0.96) predicted comorbidity. Network analysis revealed distinct bridge symptoms: adolescents in the high depression-anxiety group had five symptoms: depressed or sad mood (phq2), psychomotor agitation/retardation (phq8), nervousness or anxiety (gad1), restlessness (gad5), and irritable (gad6); however, adults with comorbidity had one symptom: afraid something will happen (gad7). This study identified three patterns of depression-anxiety comorbidity in adolescents and two in adults. Efforts should prioritize adolescents from "other" ethnic minorities, strengthening family and peer support, as well as smoking and drinking interventions for adolescents, and addressing social isolation, physical health, and catastrophizing cognition in adults may mitigate the comorbidity burden. Show less
BackgroundPredicting cognitive function across dementia stages remains challenging. Plasma biomarkers and electroencephalogram (EEG) features may provide complementary information, but their combined Show more
BackgroundPredicting cognitive function across dementia stages remains challenging. Plasma biomarkers and electroencephalogram (EEG) features may provide complementary information, but their combined predictive value requires further study.ObjectiveTo evaluate the feasibility of integrating plasma biomarkers and EEG features to predict cognitive function in dementia and examine their correlations.MethodsFrom September 2023 to October 2024, 75 patients from two medical centers with mild cognitive impairment, mild dementia, or moderate dementia were enrolled. Resting-state 19-channel EEG data yielded 2737 time-frequency and connectivity features. Plasma biomarkers included tau, p-Tau181, Aβ Show less
Atherosclerosis is fundamentally a pathology of unresolved inflammation perpetuated by the collapse of Regulatory T cell (Treg)-mediated tolerance. Emerging evidence indicates that Treg functional int Show more
Atherosclerosis is fundamentally a pathology of unresolved inflammation perpetuated by the collapse of Regulatory T cell (Treg)-mediated tolerance. Emerging evidence indicates that Treg functional integrity is intrinsically dictated by mitochondrial fatty acid oxidation (FAO), a metabolic checkpoint often compromised under systemic metabolic stress. Current lipid-lowering therapies, such as statins, often fall short in correcting this maladaptive immunometabolic defect and may introduce collateral metabolic perturbations. This study aimed to elucidate the immunometabolic therapeutic mechanism of Dingxin Recipe III (DXR III) in ameliorating atherosclerosis. We employed an integrated systems pharmacology strategy-combining serum pharmacochemistry, multi-omics profiling, and extensive high-dimensional flow cytometry-to elucidate the therapeutic mechanism of DXR III, a traditional Chinese herbal formula in an in vivo study. ApoE DXR III treatment effectively attenuating atherosclerotic progression. Serum pharmacochemistry identified 254 prototypical absorbed constituents, including Tanshinone I (a potential Peroxisome Proliferator-Activated Receptor Gamma agonist), as bioactive candidates. Multi-omics analysis revealed that DXR III modulated the metabolic environment, coinciding with restored FAO flux. This shift was associated with a favorable metabolic niche characterized by increased FAO substrates, which correlated with the rescue of Treg differentiation and phenotypic stability. Specifically, DXR III facilitated the redistribution of Tregs from the spleen to plaque sites and significantly inhibited their trans-differentiation into Th1-like or Th17-like phenotypes. Conversely, Simvastatin treatment, despite lowering lipids, resulted in peripheral Th17 accumulation and failed to alleviate hyperglycemia. In contrast, DXR III maintained Th17 homeostasis-abolishing the pathogenic non-classical Th17 subset-and exerted dual-regulatory effects on both lipid and glucose metabolism. DXR III ameliorates atherosclerosis, a process closely associated with the modulation of the FAO metabolic checkpoint to correct the immune imbalance driving plaque progression. By rescuing the Treg differentiation, functional integrity, and phenotypic fidelity while avoiding the immunological trade-offs associated with Th1/Th17, DXR III represents a promising candidate for comprehensive cardiovascular protection. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis with cardiometabolic disorders. Due to the complicated pathophysiological processes, current ther Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis with cardiometabolic disorders. Due to the complicated pathophysiological processes, current therapeutic strategies for MASLD remain limited. Previous studies revealed that miR-320 was a regulator of systemic lipid metabolism with multi-targets. However, whether treatments against miR-320 would be benefit to MASLD was unclear. Mice with MASLD were induced by high-fat diet (HFD) treatment. Tough Decoy or sponge against miR-320 was delivered by recombinant adeno-associated virus (serotype 8) vectors in vivo. Hepatic steatosis and plasma lipids were assessed by histopathology, biochemical assays and LC-MS. Moreover, LC-MS, Western blotting, real-time PCR, immunofluorescence and luciferase reporter were performed to investigate the underlying mechanisms. Knockdown of miR-320 attenuated HFD-induced MASLD by alleviating hepatic lipid accumulation and hyperlipidemia. Mechanistically, palmitic acid (PA) combined with oleic acid (OA) treatment promoted the translocation of miR-320 from the cytoplasm into the nucleus of hepatocytes. Especially, increased nuclear miR-320 activated the transcription of APOE by targeting its promoter, which in turn aggravated triglyceride accumulation and secretion in hepatocytes. Our study revealed that treatments against miR-320 attenuated hepatic steatosis and hyperlipidemia simultaneously, which might be a potential strategy of MASLD. Show less
TBCK syndrome is a severe neurodevelopmental disorder characterized by hypotonia, intellectual disability, and progressive neurodegeneration. While the
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impa Show more
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined. Using a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment. MCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (E Our findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy. Show less
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibili Show more
Early-life stress is a critical determinant of vulnerability to later-life affective and cognitive dysfunction, yet the mechanisms through which adolescent adversity enhances adult stress susceptibility remain incompletely understood. Here, we employed a two-hit model combining adolescent social isolation stress (SIS) with adult chronic restraint stress (CRS) to examine how developmental stress interacts with adult stress exposure. SIS alone or CRS alone exerted minimal behavioral effects, whereas SIS followed by CRS markedly potentiated depression-like behaviors and impaired spatial and object recognition memory. Two-hit stress produced robust hippocampal neuroinflammatory responses, including increased astrocytic and microglial activation and elevated TNF-α, IL-1β, IL-6, and IL-17A levels. These inflammatory alterations were accompanied by pronounced suppression of the BDNF/TrkB/p-CREB signaling cascade, reduced synaptic protein expression, and diminished dendritic spine density and branching complexity in CA1 pyramidal neurons. Notably, light treatment (LT) administered during CRS exposure significantly reversed two-hit induced behavioral deficits, attenuated glial activation and cytokine upregulation, enhanced BDNF/TrkB and p-CREB signaling, and restored synaptic and structural plasticity. Together, these findings indicate that adolescent SIS primes the hippocampus for exaggerated neuroinflammatory and neuroplastic impairments following adult stress, thereby amplifying stress vulnerability. Furthermore, LT emerges as a safe non-pharmacological intervention capable of mitigating combined stress-induced emotional and cognitive dysfunction by targeting neuroinflammatory and neurotrophic pathways. Show less
This study explored the therapeutic potential of puerarin in diabetic atherosclerosis (DA) by targeting endothelial dysfunction and lipid metabolism in apolipoprotein E (APOE)-/- mice. In vitro, human Show more
This study explored the therapeutic potential of puerarin in diabetic atherosclerosis (DA) by targeting endothelial dysfunction and lipid metabolism in apolipoprotein E (APOE)-/- mice. In vitro, human aortic endothelial immortalized cells cultured under high glucose conditions were treated with puerarin. Cell viability was quantified using cell counting kit-8 (CCK-8) assay. Apoptosis rates were measured via Annexin V/PI flow cytometry. Lipid accumulation was assessed through Oil Red O staining. iNOS levels were detected by ELISA. In vivo, diabetic APOE-/- mice fed a high-fat diet received daily puerarin administration. Aortic collagen deposition was evaluated using Masson trichrome staining. Plaque burden was analyzed via hematoxylin-eosin staining. Serum lipid profiles, including low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were determined by enzymatic assays. Follistatin-like 1 (Fstl1) protein expression and downstream inflammatory mediators were examined through Western blot and immunofluorescence. Puerarin significantly improved endothelial cell survival and reduced apoptosis under high glucose. Lipid droplet formation decreased alongside iNOS suppression. In diabetic mice, puerarin attenuated aortic plaque area and collagen content while improving dyslipidemia. Fstl1 expression and associated inflammatory markers were downregulated. Puerarin alleviates DA progression through dual modulation of endothelial protection and Fstl1-mediated inflammatory pathways. Show less
This study aims to identify distinct subgroups of digital resilience among nursing students and examine the factors associated with these subgroups. Digital resilience, the ability to adapt to technol Show more
This study aims to identify distinct subgroups of digital resilience among nursing students and examine the factors associated with these subgroups. Digital resilience, the ability to adapt to technological changes and overcome challenges in higher education, is crucial for protecting students' psychological health and improving academic performance. In the context of Artificial Intelligence (AI) and digital transformation in nursing education, this resilience is essential for students to navigate virtual learning and integrate advanced technologies into their practice. A cross-sectional study. This study was conducted in eight universities in China guided by ecological systems theory and nursing students were recruited through convenience sampling. Latent profile analysis (LPA) identified subgroups and logistic regression examined related factors. A total of 331 (81.73 %) participants were included in the final analysis. The average age of participants was 20.41SD0.67 years, with 283 female (85.55 %). Latent profile analysis revealed two subgroups: the "High Digital Resilience Group" (n = 278, 83.99 %) and the "Low Digital Resilience Group" (n = 53, 16.01 %). Participants who were male (OR = 3.47, p = 0.02), had low household income (OR = 0.23, p = 0.01, low professional identity (OR = 0.86, p < 0.001) and low friend support (OR = 0.82, p < 0.001) were more likely to belong to the low digital resilience group. Educators should focus on enhancing students' professional identity and providing social support, especially for those with low digital resilience. The findings provide practical guidance for integrating AI into nursing education to enhance digital resilience. Show less
Protocatechuic acid (PCA), a natural compound found in a variety of Chinese herbal medicines and plant foods, has been documented to inhibit atherosclerosis partially by reducing inflammation burden i Show more
Protocatechuic acid (PCA), a natural compound found in a variety of Chinese herbal medicines and plant foods, has been documented to inhibit atherosclerosis partially by reducing inflammation burden in arterial endothelial cells. Interestingly, in vitro studies showed that PCA at physiologically reachable concentrations does not affect inflammation burden in TNF-α-stimulated aortic endothelial cells, whereas it increases the content of exosomal miR-10b secreted by macrophages that have engulfed apoptotic cells (efferocytic macrophages). This study was aimed at investigating whether the in vivo anti-inflammatory effect of PCA in arterial endothelial cells was due to the uptake of efferocytic macrophage exosomal miR-10b. A transwell co-culture system of aortic endothelial cells with efferocytic macrophages was used to evaluate the effect of PCA on NF-κB-mediated inflammation in aortic endothelial cells. An inhibitor of exosome secretion, GW4869, was applied to confirm the role of exosomes played in the anti-inflammatory effect of PCA. The aortic endothelial cells were administrated with exosomes isolated from PCA-treated efferocytic macrophages or miR-10b mimic or antagomir to ascertain the role of miR-10b in downregulating inflammation effect of PCA. Bioinformatics analyses, loss-of- and gain-of-function assays and luciferase reporter gene assays were performed to identify targeting relationship between miR-10b and mitogen-activated protein kinase kinase kinase 7 (MAP3K7)/β-transducin repeat-containing protein (β-TrCP). Besides, Apoe PCA at physiologically reachable concentrations inhibited NF-κB-mediated inflammation in TNF-α-stimulated aortic endothelial cells co-cultured with efferocytic macrophages, in which treatment of GW4869 reversed this effect. Exosomes isolated from PCA-treated efferocytic macrophages inhibited inflammation and increased miR-10b levels in aortic endothelial cells. Mechanistically, exosomal miR-10b post-transcriptionally repressed MAP3K7 and β-TrCP, both of which promote NF-κB activation. Knockdown of Map3k7 and Btrc with siRNA in aortic endothelial cells abolished the inhibitory effects of exosomes isolated from PCA-treated efferocytic macrophages on NF-κB-mediated inflammation. Consistently, oral administration of PCA increased miR-10b level and inhibited Map3k7 and Btrc mRNA expression as well as inflammation in aortic endothelial cells in Apoe Our current findings suggest that PCA could transfer exosomal miR-10b from efferocytic macrophages to endothelial cells and thus inhibit NF-κB-mediated inflammation in arterial endothelial cells through repressing MAP3K7 and β-TrCP, two new targets of miR-10b. Show less
To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health litera Show more
To investigate the dose-response relationship between e-health literacy and light physical activity (LPA) in older adults is to provide evidence for targeted interventions that enhance e-health literacy and promote LPA, thereby advancing healthy aging. This study used a convenience sampling method to select two residential neighborhoods. Subsequently, a random cluster sampling approach was employed, resulting in a total final sample of 105 community-dwelling older adults (aged 60 and above) from these neighborhoods. A three-axis accelerometer (ActiGraph wGT3X-BT) recorded the older adults' LPA, and the Electronic Health Literacy Scale assessed their e-health literacy. Multiple linear regression was used to explore the dose-response relationship between LPA and e-health literacy and sub-dimension scores. Multiple linear regression revealed that both the overall e-health literacy score and its components were positively associated with daily LPA (Tables 2 and 3). However, the empirical impact varied substantially across components. For each 1-point increase, LPA increased by 2.8 min for the overall score, 11 min for judgment ability, and 19.4 min for decision-making ability, whereas the effect of application ability was statistically significant but minimal. Notably, the effect sizes of all e-health literacy components were substantially smaller than that of educational attainment (β = 0.638-0.947), which was the strongest predictor in all models. This study provides empirical evidence that higher e-health literacy and its specific sub-dimensions are positively associated with light physical activity (LPA) among community-dwelling older adults, with educational attainment emerging as a key independent predictor. These findings suggest that public health interventions aimed at promoting LPA could be enhanced by incorporating strategies to improve e-health literacy, particularly targeting older adults with lower educational backgrounds. The development of tailored, theory-informed programs based on these insights holds promise for fostering healthy aging at the community level. Show less
Apolipoprotein B-100 (apoB-100) is the main structural protein of apoB-containing lipoproteins including low-density lipoprotein (LDL). Its organization or lipidation process in an apoB-containing lip Show more
Apolipoprotein B-100 (apoB-100) is the main structural protein of apoB-containing lipoproteins including low-density lipoprotein (LDL). Its organization or lipidation process in an apoB-containing lipoprotein particle is still unclear. To understand its organization in a LDL particle, the combination of atomic force microscopy (AFM) with lipid depletion by Nonidet P-40 (NP-40) or methyl-β-cyclodextrin (MβCD) was utilized for the first time to in situ visualize LDL delipidation process and lipid-poor/-free apoB-100 at a physiological condition. During LDL delipidation process, different morphologies/structures were visualized successively including spheroidal structure with a smaller size than native LDL, spheroidal structure with one or more holes, closed annular/circular structure, opened annular/circular structure, C/U-shaped (or horseshoe-shaped) structure, and V/S/I-shaped structure. Based on the concentration-dependent structural distributions, these structures probably reflect 5 stages of LDL delipidation (e.g., a slightly delipidated LDL stage, a partially delipidated LDL stage, a neutral lipid-poor/-free apoB-100 stage, a lipid-poor apoB-100 stage, and a lipid-free apoB-100 stage, respectively). Our findings could provide structural evidence to reconcile the previous controversy and provide potential evidence/clues/implications for understanding apoB-100 lipidation and the organization of apoB-100 in apoB-containing lipoprotein particles. Potentially, this study also can provide new structural insights into the design of food-grade lipid carriers. Moreover, the combination of AFM with lipid depletion, which has many advantages over traditional electron microscopy (e.g., label-free, in situ, and real-time imaging under physiological conditions, etc.), is a potentially ideal novel strategy for studying the structure of apolipoproteins or lipoproteins. Show less
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic Show more
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic characteristics, health literacy, confidence in self-care contributions, family intimacy, and profile membership. We recruited 275 dyads of patients with COPD and their family caregivers from five tertiary hospitals between May and November 2022 using convenience sampling. Latent profile analysis (LPA) was used to identify distinct profiles of caregiver self-care contributions. Univariate analysis and multinomial logistic regression were subsequently conducted to examine associations between participant characteristics and profile membership. LPA identified four distinct profiles of caregiver self-care contributions: low-contributing, under-monitored, maintenance-prioritized, and high-contributing. Significant differences were observed across these profiles in terms of patients' symptom severity, exacerbation frequency, number of hospitalizations, caregivers' education levels, caregiving duration, health literacy, confidence in self-management contributions, and family intimacy using univariate analysis. Multinomial logistic regression analysis revealed that caregivers' education levels, caregiving duration, confidence in self-management contributions, and health literacy were significant predictors of profile membership. Caregiver self-care contributions for patients with COPD can be characterized by four distinct profiles, with caregivers' educational level, health literacy, and confidence in self-management identified as key factors associated with profile membership. Show less
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in Show more
To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in preschool-aged children. 268 preschoolers were included in the cross-sectional study. An accelerometer was used to assess sedentary behavior (SB), light and moderate-to-vigorous physical activity (LPA and MVPA). A parental report was used to collect sleep time. Bioelectrical impedance analysis was employed to assess body composition. Compositional linear regression analysis was employed to explore how daily movement behaviors were associated with body composition. Compositional isotemporal substitution analysis was employed to estimate changes in body composition after reallocating time among behaviors. 24-h movement behaviors composition significantly predicted fat-free mass index (FFMI), soft lean mass index (SLMI), and skeletal muscle mass index (SMMI), but not fat mass index, percent body fat, and bone mineral content index. The compositional isotemporal substitution analyses consistently showed that increasing MVPA at the expenses of SB was positively associated with FFMI (+0.328 kg/m The findings highlight the importance of MVPA in improving preschoolers' body composition. Increasing MVPA at the expenses of SB may be a strategy to improve body composition in preschoolers. Show less
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological Show more
Obstructive sleep apnea (OSA) is characterized by recurrent intermittent hypoxia (IH) and has been increasingly associated with lung cancer incidence and mortality. However, how IH-related biological programs relate to immune remodeling, stemness-associated phenotypes, and therapeutic resistance in lung cancer remains incompletely understood. We integrated single-cell RNA sequencing data from IH-exposed murine lung tissues (GSE301350) with bulk transcriptomic datasets from TCGA-LUAD and GSE31210 to examine hypoxia-associated cellular and transcriptional patterns. Stemness was quantified using CytoTRACE and transcriptome-based stemness scoring, and its associations with immune infiltration, immune checkpoint expression, TIDE scores, predicted drug sensitivity, and immunotherapy response were evaluated. A stemness-based prognostic model was constructed using LASSO Cox regression and validated in independent cohorts. Single-cell analysis revealed marked immune remodeling under intermittent hypoxia (IH), including expansion of effector T cells, and monocytes/macrophages, populations alongside reduced B cells and dendritic cells. In human LUAD cohorts, stemness-high tumors were associated with mitochondrial and metabolic stress-related transcriptional programs, and increased expression of immune checkpoint genes (PD-1, PD-L1, CTLA4, LAG3). Elevated stemness scores correlated with higher TIDE scores, poorer overall survival, and reduced predicted responsiveness to immunotherapy. LASSO modeling identified a six-gene stemness signature (EIF5A, MELTF, SEMA3C, CPS1, TCN1, SELENOK), that consistently stratified patients into high- and low-risk groups across TCGA and GSE31210 cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Drug sensitivity analyses further suggested that stemness-high tumors may exhibit increased susceptibility to selected kinase inhibitors (Dasatinib, A-770041) and metabolic modulators (Phenformin, Salubrinal). OSA-associated IH is linked to stemness-associated transcriptional plasticity, immune suppression, and adverse clinical outcomes in lung cancer. The identified stemness-based gene signature provides a robust prognostic biomarker and highlights potential therapeutic vulnerabilities, supporting integrative strategies that combine stemness and immune -targeted approaches with immunotherapy in OSA-associated lung cancer. Show less
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating Show more
Cancer-associated fibroblasts (CAF) are abundant stromal cells in the tumor microenvironment (TME) that play a vital role in promoting tumor progression and drug resistance. The mechanisms regulating heterogeneity of CAFs in renal cell carcinoma (RCC) could represent potential targets for reprogramming the TME. In this study, we conducted single-cell RNA sequence and flow cytometry analyses that identified a CAF subset overexpressing apolipoprotein E (ApoE), which was correlated with poor survival in patients with RCC. Mechanistically, NRF1 activation in CAFs induced formation of ApoEhigh CAFs and secretion of NRG1. ApoEhigh CAFs potentiated stemness properties in the surrounding RCC cells by secreting NRG1 and subsequently activating the HER2/NF-κB pathway. Interfering with NRG1 expression or inhibiting NF-κB signaling reduced ApoEhigh CAF-induced stemness of RCC cells. Furthermore, neutralizing NRG1 enhanced the efficacy of sunitinib in RCC models in vivo. Together, these findings highlight targeting the tumor-promoting functions of ApoEhigh CAFs as a promising approach for treating advanced RCC. NRF1 drives formation of ApoEhigh cancer-associated fibroblasts that secrete NRG1 to stimulate stemness of renal cell carcinoma, revealing a stromal-mediated mechanism that can be inhibited to improve treatment of advanced kidney cancer. Show less
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 Show more
Atherosclerosis (AS), a chronic inflammatory disorder initiated by vascular endothelial dysfunction (ED), is prominently triggered by hemodynamic low-shear stress (LSS). Interferon regulatory factor 6 (IRF6) is a transcription factor that regulates the inflammatory response following injury. In this work, the LSS-induced AS model was induced by the partial ligation of the left carotid artery in high-fat diet-fed ApoE Show less
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclero Show more
Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclerotic cardiovascular diseases, their effects are limited in those with homozygous familial hypercholesterolemia. It is essential to seek new lipid-lowering targets. YAP (Yes-associated protein) may be involved in lipid metabolism in the liver; therefore, we investigated the function of hepatocyte YAP in hyperlipidemia and atherosclerosis. Hyperlipidemia models were generated in apoE knockout (apoE High-cholesterol diet-fed apoE Taken together, our findings revealed a novel role for the YAP-TEAD4-ANGPTL3 axis in lipid metabolism independent of LDLR. Inhibition of hepatocyte YAP may be an effective lipid-lowering strategy for homozygous familial hypercholesterolemia. Show less
Vascular smooth muscle cell (VSMC)-derived foam cell formation is a major contributor to atherosclerosis progression and plaque instability. Meteorin-like protein (METRNL), a secreted organokine with Show more
Vascular smooth muscle cell (VSMC)-derived foam cell formation is a major contributor to atherosclerosis progression and plaque instability. Meteorin-like protein (METRNL), a secreted organokine with known metabolic and anti-inflammatory effects, has been linked to cardiovascular protection, but its role in atherosclerosis is not well defined. This study investigated the function of METRNL in VSMC-derived foam cell formation and atherosclerosis and explored the underlying signaling mechanisms. ApoE METRNL levels declined during atherosclerosis progression and were restored during regression. METRNL selectively inhibited foam cell formation in VSMCs-but not in macrophages-by downregulating CD36-mediated cholesterol uptake and suppressing endoplasmic reticulum stress through KIT signaling. Deletion of KIT specifically in smooth muscle cells abolished these protective effects. The transcription factor SP1 was found to bind directly to the METRNL promoter and enhance its expression. Clinically, lower serum METRNL levels were independently associated with increased risk and severity of acute coronary syndrome. METRNL protects against VSMC foam cell formation and atherosclerosis by enhancing KIT signaling, thereby reducing ER stress and subsequent cholesterol uptake. These findings position METRNL as a potential therapeutic target and biomarker for atherosclerotic cardiovascular disease. Show less
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, usi Show more
The Hedgehog (Hh) signaling pathway is a key regulator of adipogenesis and lipid metabolism. However, the specific role of its receptor, Patched2 (Ptch2), in these processes remains unclear. Here, using a CRISPR/Cas9-mediated Show less
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no es Show more
Cognitive reserve (CR) refers to differences in the adaptability of cognitive processes that modify the impact of Alzheimer's disease (AD) pathology on cognitive performance. Currently there are no established blood-based biomarkers of CR in prodromal AD. In this study, we operationalize CR as memory reserve, defined as moderation (attenuation) of the CSF pTau181-memory association. DNA methylation (DNAm) integrates genetic and environmental influences and may capture biological processes that mitigate the impact of AD pathology on memory. We aimed to identify blood DNAm loci that moderate the association between cerebrospinal fluid (CSF) phosphorylated tau (pTau181) and memory in mild cognitive impairment (MCI). We also sought to determine if a DNAm-based signature of memory reserve predicts future memory decline. We analyzed 92 amyloid positive MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with blood DNAm, CSF pTau181, and memory scores (PHC_MEM) collected at the same visit. We first regressed memory scores on covariates (age, sex, number of After removing CpGs with low variability, we identified 6 CpGs with suggestive significance for DNAm×pTau181 interaction ( Blood DNAm patterns that moderate the pTau-memory relationship capture biology underlying memory reserve involving synaptic, vascular, immune, and metabolic pathways, and can be summarized into an MRS that predicts longitudinal memory trajectories in MCI. These findings support blood DNAm as a promising, non-invasive biomarker of cognitive resilience to AD pathology. Show less
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively Show more
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated. PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN. Show less
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonst Show more
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonstrated that 5'tRF-GlyGCC is overexpressed in BC tissues and negatively associated with patients' survival. Mechanistically, 5'tRF-GlyGCC binds to lactate dehydrogenase A (LDHA), enhancing its enzymatic activity and promoting glycolysis, which drives BC cell malignancy. This binding is mediated by the phosphorylation of LDHA at tyrosine 10, and facilitated by fibroblast growth factor receptor 1 (FGFR1), through the formation of a ternary complex that amplifies oncogenic signaling. Furthermore, 5'tRF-GlyGCC/LDHA axis induces macrophage infiltration and polarization toward an M2 phenotype, mediated by the chemokine CCL7, thereby reshaping the tumor microenvironment. Additionally, it is uncovered that the biogenesis of 5'tRF-GlyGCC is regulated by ALKBH3 and ANG, which also modulate LDHA activity. In vivo, targeting 5'tRF-GlyGCC/LDHA signaling significantly suppresses tumor growth and enhances the efficacy of immunotherapy. Collectively, these findings elucidate the pivotal role of 5'tRF-GlyGCC in BC progression, highlighting its potential as therapeutic target for BC treatment. Show less
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To addre Show more
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To address this, we performed multi-tissue metabolomic profiling (liver, heart, and serum) in apolipoprotein E-deficient (ApoE-/-) mice subjected to CR. Metabolomic analyses of the multiple tissues revealed that glycerophospholipid metabolism pathway was consistently modulated by CR. To explore its relevance in vascular diseases, we performed serum metabolomic profiling in an abdominal aortic aneurysm (AAA) model induced by angiotensin Ⅱ (AngⅡ) infusion in ApoE-/- mice. The level of lysophosphatidylethanolamine (LPE) (16:0/0:0), a metabolite in the glycerophospholipid metabolism pathway, was elevated during AAA progression and significantly reduced by CR intervention, suggesting its potential as a vascular disease risk factor. Notably, glycerophospholipid metabolism and LPE (16:0) were significantly associated with vascular diseases and aging-related indicators in human multi-omics data, including public transcriptomic and lipidomic, and our serum multi-omics profiling of 76 healthy aged individuals. Collectively, our findings establish glycerophospholipid metabolism and LPE (16:0) as systemic signatures of CR with diagnostic potential. They highlight a crucial link between systemic metabolism and vascular remodeling and remodeling-associated vascular diseases, while also functioning as indicators of systemic aging. Show less
Ting Fang, Xinyu Yang, Xiaoqing Deng+5 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tu Show more
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tubules. However, the role of its active form, ChREBP-β, was previously unclear. In this study, ChREBP-β overexpression and ChREBP knockout mouse models were utilized to investigate the effects of excessive fructose intake in vivo. In addition, primary renal tubular epithelial cells from mice and human kidney-2 (HK2) cells were applied for further validation in vitro. We found that ChREBP-β leads to increased transcription to mediate endoplasmic reticulum stress and mitochondrial dysfunction, which ultimately impairs renal function. Our findings underscore the critical role of ChREBP-β in fructose-related renal disorders. Show less
(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure t Show more
(1) Background: The increasing environmental concentration of polystyrene nanoplastics (PS-NPs) may pose a risk of human exposure and health threats. Previous studies have demonstrated that exposure to PS-NPs poses a threat to neural synaptic plasticity, yet the underlying mechanisms remain unclear. (2) Methods: Hippocampal astrocytes and neurons were co-cultured, exposed to PS-NPs at concentrations of 10, 50, and 100 μg/mL, and cytotoxicity was assessed. We investigated PS-NP-induced impairment of synaptic plasticity by regulating the brain-derived neurotrophic factor (BDNF). (3) Results: Calmodulin-dependent protein kinase II (CaMKII) is a central molecular organizer of synaptic plasticity, learning, and memory, and its activity is intrinsically linked to intracellular calcium ion concentration. Our research indicates that PS-NPs may interfere with calcium ion signaling and CaMKIIα activity, thereby reducing CaMKIIα activity. This subsequently downregulates the expression of cAMP response element-binding protein (CREB), modulates BDNF expression, and impacts synaptic plasticity. (4) Conclusions: In summary, this study primarily focused on the effects of PS-NPs exposure on hippocampal synaptic plasticity. Show less
Older adults typically have higher sedentary behaviour (SB) and lower physical activity (PA) than younger adults. Studies on replacing SB with PA in relation to all-cause mortality in racially diverse Show more
Older adults typically have higher sedentary behaviour (SB) and lower physical activity (PA) than younger adults. Studies on replacing SB with PA in relation to all-cause mortality in racially diverse older adults remain limited. This study included 122 966 older adults from the China Kadoorie Biobank (CKB) and 207 212 older adults from the UK Biobank (UKB). SB and PA were assessed using baseline questionnaires, with PA classified as light (LPA), moderate (MPA) or vigorous (VPA) based on metabolic equivalents. Cox proportional hazards models and isotemporal substitution models were used to examine the associations between replacing SB with different PA intensities and all-cause mortality. Longer SB (per 30 min/day increase) was associated with a higher risk of all-cause mortality in both cohorts (CKB: HR 1.013, 95% CI 1.010 to 1.017; UKB: HR 1.012, 95% CI 1.009 to 1.015). PA of any intensity was associated with a reduced risk of all-cause mortality. In the CKB, replacing 30 min/day of SB with an equivalent duration of PA showed comparable protective associations (LPA: HR 0.963, 95% CI 0.958 to 0.968; MPA: HR 0.967, 95% CI 0.961 to 0.972; VPA: HR 0.965, 95% CI 0.960 to 0.971). In the UKB, replacing 30 min/day of SB with VPA was associated with the largest reduction in mortality risk (HR: 0.950, 95% CI 0.931 to 0.970). Replacing SB with PA of any intensity was associated with reduced all-cause mortality risk in older adults, with variations across populations. These findings highlight the need for population-specific PA recommendations to promote healthy ageing. Show less
Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thorou Show more
Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like Lactobacillus and Bifidobacterium. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/β-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy. Show less