Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospect Show more
Although immune-mediated diseases (IMDs) and major depressive disorder (MDD) commonly co-occur, the bidirectional relationship between them remains to be fully elucidated. Using data from the prospective UK Biobank cohort, we evaluated the bidirectional associations by time-varying Cox proportional hazards regression models and assessed shared genetic architecture using genome-wide association study summary statistics. Additionally, we employed collagen-induced arthritis (CIA) and chronic social defeat stress (CSDS) mouse models to investigate the relationship between rheumatoid arthritis (RA) and depression. Over 5,226,841 person-years of follow-up, 23,534 incident MDD cases were identified. The presence of any IMD was associated with higher MDD risk (hazard ratio [HR]: 1.95; 95% CI: 1.89-2.01). Conversely, 59,742 incident cases of IMD were documented. MDD was associated with increased IMD risk (HR: 1.47; 95% CI: 1.40-1.54). We observed significant global genetic correlations between IMDs and MDD (r 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
The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aime Show more
The COVID-19 pandemic has significantly disrupted educational style, potentially affecting the learning adaptation of nursing freshmen who are integral to the future nursing workforce. This study aimed to identify distinct subgroups of nursing freshmen based on their bioecological attributes related to learning adaptation during the pandemic. A multicenter, cross-sectional study was conducted of 1170 first-year nursing students from six higher education institutions in China. Learning adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction, were investigated. Latent Profile Analysis (LPA) was utilized to identify distinct profiles. Descriptive statistics indicated a positive level of learning adaptation among participants, with an overall mean score of 3.51 ± 0.57. LPA revealed four distinct profiles: 'Struggling Learners' (5.47%), 'Moderate Engagers' (70.60%), 'Adaptable Strivers' (18.29%), and 'Optimal Adapters' (5.64%), which demonstrated significant differences in adaptation, resilience, parental attachment, interaction anxiety, and mobile phone addiction tendencies (P < 0.05). The study's findings emphasize the heterogeneity in learning adaptation among nursing freshmen and the importance of considering bioecological attributes when developing educational interventions during crisis. Recognizing these profiles can guide the development of targeted strategies to enhance student adaptation and academic achievement. 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
This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becom Show more
This study aims to explore the shared transcriptomic features of caloric restriction (CR) and endurance exercise in skeletal muscle among older adults. As age increases, muscle atrophy gradually becomes a common issue of functional decline in the elderly. Utilizing bioinformatics analysis, this research identified 101 overlapping differentially expressed genes (DEGs) involved in both CR and endurance exercise. These genes are primarily enriched in key biological pathways related to longevity, Apelin signaling, AMPK signaling, FoxO signaling, and cGMP-PKG signaling pathways. Additionally, we identified 10 key genes (such as LPL, PPARGC1A, and IGF1), 4 transcription factors (FOXC1, POU2F2, GATA2, and STAT3), and 4 microRNAs (miR-155-5p, miR-124-3p, miR-1-3p, and miR-16-5p) interacting with these genes. Drug-gene interaction analysis identified carotuximab as a compound with potential relevance for future investigation in the context of muscle aging. These findings provide new insights into the molecular mechanisms underlying muscle functional decline in the elderly and propose potential targets and drugs for intervention development. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive amyloid-β (Aβ) accumulation, neuroinflammation, and oxidative stress. Exosomes derived from human umbili Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive amyloid-β (Aβ) accumulation, neuroinflammation, and oxidative stress. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSC@Exo) represent promising nanoscale carriers for targeted drug delivery. In this study, Baicalein (Bac), a potent antioxidant and anti-inflammatory flavonoid, was encapsulated into hUC-MSC-derived exosomes (Exo@Bac) to enhance its therapeutic efficacy. The neuroprotective potential of Exo@Bac was evaluated in a rat model of Aβ1-42-induced AD. Rats received intraperitoneal injections of Bac, hUC-MSC@Exo, or Exo@Bac, and cognitive performance was assessed using the passive avoidance test and Morris water maze. Exo@Bac treatment significantly improved memory deficits and elevated brain-derived neurotrophic factor (BDNF) expression compared to controls. Histopathological analyses revealed reduced neuronal damage and apoptosis, alongside decreased Aβ1-42 deposition in Exo@Bac-treated rats. Furthermore, Exo@Bac enhanced antioxidant defense (increased SOD), attenuated pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and lowered lipid peroxidation (MDA). Mechanistically, Exo@Bac promoted AMPK phosphorylation while suppressing NF-κB p65 signaling, indicating modulation of both oxidative stress and neuroinflammatory pathways. These findings demonstrate that Exo@Bac acts as a nanotherapeutic agent capable of mitigating AD pathology, highlighting its potential as a novel strategy for Alzheimer's disease therapy. Show less
Luwen Hao, Xin Chen, Bo Qin · 2026 · Frontiers in cell and developmental biology · Frontiers · added 2026-04-24
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disorder characterized by unexplained left ventricular hypertrophy and represents a leading cause of morbidity and sudden cardi Show more
Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac disorder characterized by unexplained left ventricular hypertrophy and represents a leading cause of morbidity and sudden cardiac death, particularly in young adults and athletes. Early studies focused on morphological features, but advances in molecular genetics have shifted emphasis toward genetic diagnosis, mechanistic insights, and family-based management. Pathogenic variants in sarcomeric genes, especially 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 employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through c Show more
This study employed a latent profile analysis (LPA) to identify distinct subgroups of learned helplessness among Chinese breast cancer chemotherapy patients and examined influencing factors. Through convenience sampling, 260 breast cancer chemotherapy patients aged 18-74 years from a tertiary hospital in Henan Province were recruited between May 2024 and January 2025. Data were collected using a general demographic questionnaire, the Learned Helplessness Scale, the Brief Illness Perception Questionnaire, the Social Support Rating Scale, and the General Self-Efficacy Scale. An LPA was applied to classify learned helplessness patterns, followed by a multivariate logistic regression to determine the influencing factors. The latent profile analysis revealed three distinct profiles of learned helplessness among breast cancer patients undergoing chemotherapy: a "low helplessness-low hopelessness stable profile" (17.0%), a "moderate helplessness-moderate hopelessness fluctuating profile" (52.0%), and a "high helplessness-high hopelessness profile" (31.0%). The multivariable logistic regression revealed that age range 18-44 years, low monthly household income per capita, fatigue, and illness perception were significantly associated with the "high helplessness-high hopelessness profile" (P < 0.05). Conversely, the age range 45-59 years was significantly associated with the "moderate helplessness-moderate hopelessness fluctuating profile" (P < 0.001). Furthermore, experiencing ≤2 chemotherapy-related side effects, a higher level of perceived social support, and greater self-efficacy were significant predictors of membership in the "low helplessness-low hopelessness profile" (P < 0.05). Breast cancer chemotherapy patients were categorized into three distinct subgroups, which were influenced by age, income, fatigue, treatment side effects, illness perception, self-efficacy, and social support. 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
Pharmacological preconditioning of mesenchymal stem cells (MSCs) is a promising strategy to enhance their therapeutic efficacy for end-stage liver disease; however, maximizing this benefit remains a m Show more
Pharmacological preconditioning of mesenchymal stem cells (MSCs) is a promising strategy to enhance their therapeutic efficacy for end-stage liver disease; however, maximizing this benefit remains a major clinical challenge. Senkyunolide H (SNH), a small-molecule compound derived from Angelica sinensis, exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties. Nevertheless, its capacity to optimize MSCs-based therapy for liver disease has not been fully elucidated. Here, we demonstrate that SNH preconditioning significantly enhances the therapeutic efficacy of bone marrow mesenchymal stem cells (BMSCs) in a murine model of liver cirrhosis. Specifically, SNH-pretreated BMSCs markedly alleviated hepatocellular injury, promoted hepatocyte proliferation, and attenuated collagen deposition. Mechanistically, SNH augments the therapeutic potency of BMSCs by partly binding to macrophage erythroblast attacher (MAEA), a subunit of the E3 ubiquitin ligase complex. This interaction stabilizes MAEA, which in turn facilitates the ubiquitination and proteasomal degradation of dual specificity phosphatase 6 (DUSP6), thereby activating ERK/STAT3 signaling and upregulating the secretion of hepatocyte growth factor (HGF). Collectively, our findings highlight SNH preconditioning as a robust approach to enhance the paracrine function and therapeutic potential of BMSCs, and identify MAEA as a novel therapeutic target for BMSCs-based interventions in liver cirrhosis. 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
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive perfo Show more
Klotho is a longevity-associated protein with established neuroprotective properties. However, it is unclear how plasma klotho levels relate to Alzheimer's disease (AD) pathologies and cognitive performance. In this study, we examined the associations between plasma klotho levels and plasma biomarkers, as well as amyloid beta (Aβ) positron emission tomography (PET), tau PET, neurodegeneration, and cognition, in 354 older adults. Stratified association, interaction, and mediation analyses were conducted to elucidate apolipoprotein E (APOE) ε4-dependent relationships and potential underlying pathways. Higher plasma klotho levels were associated with lower AD-related biomarkers and cognitive decline in APOE ε4 carriers. Plasma klotho and APOE ε4 exhibited significant or marginal interactions with less abnormal changes in plasma phosphorylated tau217, glial fibrillary acidic protein, neurofilament light chain, Aβ PET, and cognition. These AD-related biomarkers mediated the protective effect of plasma klotho on cognitive function in APOE ε4 carriers. This study suggests that plasma klotho is an APOE ε4-dependent protective factor, which may attenuate AD-related pathology and improve cognitive performance. Show less
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a Show more
Ulcerative colitis (UC) is subtype of inflammatory bowel disease that is frequently comorbid with anxiety disorders. However, effective dual-targeting therapies are still lacking. Hyperoside (HYP), a natural flavonoid, exhibits anti-inflammatory and neuroprotective properties, yet its potential therapeutic effects on UC and associated anxiety, as well as the underlying mechanisms, remain largely unexplored. A murine model of DSS-induced colitis was established and treated with HYP. Disease activity was assessed through body weight, colon length, and histopathology. Anxiety-like behaviors were evaluated using open field and elevated plus maze tests. Neuroinflammation was examined through immunohistochemistry of BDNF expression and microglial activation. Gut microbiota composition was profiled by metagenomic sequencing, and metabolomic profiling was conducted using the Q300 Kit. Network pharmacology and molecular docking were employed to predict signaling pathways, which were further validated by Western blotting. Additionally, antibiotic depletion experiments were conducted to determine microbiota dependency. HYP administration significantly ameliorated DSS-induced colitis, as evidenced by attenuated weight loss, restored colon length, and improved histopathology. It suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and restored intestinal barrier integrity by upregulating Mucin-2 and ZO-1. Furthermore, HYP also alleviated anxiety-like behaviors and mitigated neuroinflammation by increasing BDNF levels and suppressing microglial activation. HYP treatment also restored gut microbial homeostasis, enriching beneficial bacteria such as Our findings demonstrate that HYP effectively alleviates DSS-induced colitis and comorbid anxiety-like behaviors. Its efficacy is dependent on the gut microbiota and is associated with the restoration of microbial homeostasis, enhancement of arginine metabolism, and modulation of the MAPK/PI3K-Akt/NF-κB signaling pathways. HYP represents a promising microbiota-targeting therapeutic candidate for UC and its neuropsychiatric comorbidities. Show less
Pro-inflammatory macrophage function is linked to an increase in mitochondrial fission. Melatonin has a positive impact on atherosclerosis and has a significant effect on the control of mitochondrial Show more
Pro-inflammatory macrophage function is linked to an increase in mitochondrial fission. Melatonin has a positive impact on atherosclerosis and has a significant effect on the control of mitochondrial fission and fusion. Nevertheless, it is still unclear how melatonin contributes to slowing the advancement of atherosclerosis. The ApoE The study found that melatonin treatment decreased the area of atherosclerotic plaque, decreased lipid deposition, suppressed inflammatory cytokine levels, inhibited macrophage pro-inflammatory differentiation, inhibited mitochondrial fragmentation, increased the level of Sirt3, and decreased Drp1 expression in atherosclerosis (AS) mice. However, Sirt3 inhibition abolished the protective affects of melatonin in AS mice. Melatonin therapy upregulated Sirt3 expression in RAW264.7 cells subjected to ox-LDL, blocked Drp1-mediated mitochondrial fission, and reduced inflammatory cytokine levels. On the other hand, melatonin's inhibitory effects on Drp1 expression and mitochondrial fission were lessened by Sirt3 inhibition. Additionally, DRP1 siRNA knockdown inhibited mitochondrial fission and pro-inflammatory differentiation of macrophages induced by ox-LDL. Melatonin inhibits the growth of atherosclerosis and the pro-inflammatory differentiation of macrophages by blocking the Sirt3-Drp1 pathway, which prevents mitochondria from fission. Melatonin's suppression of mitochondrial fission may be a viable strategy for postponing cardiovascular problems in atherosclerosis patients. Show less
Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor Show more
Intracerebral hemorrhage (ICH) is a devastating condition characterized by rapid onset, high rates of disability and mortality, and prolonged recovery. Dysregulated γ-aminobutyric acid type A receptor (GABAAR) signaling contributes to ICH-induced neurotoxicity, presenting a promising therapeutic target. To assess the neurorestorative effects of the GABAAR α1-selective partial positive allosteric modulator (PAM) CL218872 and the α5-selective negative allosteric modulator (NAM) MRK-016 on synaptic plasticity and neural repair following ICH. An ICH mouse model was constructed using collagenase IV, and ICH mice were administered the GABAAR modulators CL218872 or MRK-016. Differences in inflammation and neurological deficit score were compared between different groups of mice. Morphologic and functional changes in mouse neuronal cells were next determined by Nissl and Golgi-Cox staining. Synaptic structural changes in ICH mice were visualized by transmission electron microscopy, and changes in synaptic plasticity-related molecules were quantified to assess the effects of GABAAR modulators on synapses in ICH mice. Treatment with CL218872 resulted in a reduction in hemorrhage and improved neurobehavioral outcomes in ICH mice. Additionally, CL218872 mitigated inflammation by downregulating phospho-p65, IL-6 and TNF-α expression. Histological analysis revealed an increase in neuronal density, preservation of cell morphology, and enhanced synaptic connectivity following CL218872 treatment. Furthermore, synaptic structure was restored, and there was an upregulation of brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density protein 95 (PSD-95), and synaptophysin in ICH mice. However, treatment with MRK-016 yielded the opposite result. The GABAAR α1-selective PAM CL218872 exerts neuroprotective and neurorestorative effects in ICH, suggesting its therapeutic potential for ICH management. Show less
Apigenin is a bioactive flavonoid and widely found in herbs, fruits, and vegetables. Accumulated evidences have demonstrated the protective potential of apigenin on cardiovascular diseases, but its ro Show more
Apigenin is a bioactive flavonoid and widely found in herbs, fruits, and vegetables. Accumulated evidences have demonstrated the protective potential of apigenin on cardiovascular diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the therapeutic effects of apigenin on atherosclerosis in vivo and explore the potential mechanism. ApoE Apigenin obviously reduced lesion areas in both en-face aortas and aortic root in HFD fed ApoE Apigenin alleviated atherosclerosis development by inhibiting macrophage foam cell formation via PPARγ-LXRα-ABCA1/ABCG1 pathway. Show less
Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects i Show more
Prior studies indicate that allyl isothiocyanate (AITC) alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). The vitamin D receptor (VDR) is known to exert protective effects in MASLD; however, whether AITC alleviates MASLD through VDR remains unclear. To clarify the function and underlying mechanisms of AITC in MASLD AML-12 cells were exposed to 300 μM palmitate acid (PA) for 24 hours to establish an To establish an AITC provides a robust molecular basis for improving MASLD by activating hepatic VDR and driving the downstream HNF-4α/MTTP/ApoB signaling pathway. This pathway reduces hepatic lipid accumulation, promotes FA β-oxidation, and improves insulin resistance, establishing AITC as a promising treatment for MASLD. 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
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HF Show more
This study investigated the effects of high-intensity intermittent training (HIIT) Forty male Sprague-Dawley rats were randomly divided into two groups: standard diet (C, n = 10) and high-fat diet (HFD, n = 30). After 8 weeks of HFD feeding, 24 obese rats were further randomised into three subgroups: HFD (H, n = 8), HFD + moderate-intensity training (HMT, n = 8), and HFD + HIIT (HHT, n = 8). The HMT and HHT groups underwent 8 week training interventions (six sessions/week). The HMT protocol included a 10 min warm-up (treadmill speed: 10 m/min), a 40 min moderate-intensity aerobic phase (60%-70% of maximum speed), and a 10 min recovery (10 m/min). The HHT protocol featured 10 min warm-up and recovery phases (10 m/min), with 40 min of alternating treadmill training: 3 min at 50% maximum speed followed by 3 min at 90% maximum speed. No significant differences in body weight were observed between the HHT and HMT groups. HHT rats displayed significantly lower plasma triglyceride levels than H and HMT rats. Compared with HMT, HHT reduced adipose mass and adipocyte size and increased mitochondrial succinate dehydrogenase and cytochrome c oxidase (COX) activities in adipose tissue. However, HHT rats displayed lower COX activity in visceral white adipose tissue than HMT rats. Training upregulated browning-related genes and uncoupling protein 1 (UCP1) in adipose tissue, with stronger effects in HHT than in HMT. Plasma and adipose tissue IL-27 levels, as well as p38 MAPK-PGC-1α signalling pathway activation, were significantly elevated in both training groups, with greater increases in HHT. HIIT promotes adipose tissue browning by activating the IL-27 signalling pathway and ameliorates obesity-associated metabolic disorders more effectively than MAIT, supporting its potential as a therapeutic strategy for obesity. Show less
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform Show more
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform (MDQIP) that uses a model to objectively calculate and rank compound activities, addressing the limitations of traditional "experience-driven" evaluations, accelerates the screening and evaluation of potential AChE inhibitors from Red Gastrodia elata, offering a more efficient approach to drug discovery. Ultrafiltration-LC screening identified parishin A as having the most stable binding, with binding degree and recovery rates of 98.85% and 99.39%, respectively. Molecular docking revealed that parishins A and C were the strongest AChE inhibitors, exhibiting stable binding through hydrogen bonds, π-alkyl, and π-π interactions. Molecular dynamics simulations confirmed the stability of these compounds, with binding energies of -82.65 ± 4.24 and - 80.69 ± 4.19 kcal/mol. Enzyme kinetics showed that parishins A and C are mixed-type inhibitors, with IC Show less
Junjie Hu, Pei-Yang Gao, Run Di+2 more · 2026 · The Journal of neuroscience : the official journal of the Society for Neuroscience · Society for Neuroscience · added 2026-04-24
Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced co Show more
Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced cognitive dysfunction arises from a cascade of neurobiological processes, including persistent neuroinflammation, neurotransmitter dysregulation, and impaired synaptic plasticity. These mechanisms particularly affect the hippocampus and medial prefrontal cortex (mPFC)-regions essential for memory, attention, and executive function. Neuroimaging studies have documented structural atrophy and disrupted network connectivity in these brain areas in CP patients. At the molecular level, pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) impair glutamatergic and GABAergic signaling, disrupt long-term potentiation (LTP), and inhibit neurogenesis. Additionally, dysregulation of brain-derived neurotrophic factor (BDNF) signaling exacerbates synaptic vulnerability, contributing to cognitive decline. These mechanistic overlaps are particularly relevant in aging populations and in Alzheimer's disease (AD), where CP may act as a risk factor. This review integrates clinical and preclinical findings on CP-related cognitive dysfunction, outlines key molecular mechanisms, and explores emerging therapeutic strategies targeting inflammation, neurotransmitter systems, and synaptic repair. Understanding the interaction between chronic pain and cognition is critical for developing precision treatments that address both nociceptive and neurodegenerative pathways. Show less
Previous studies have reported that IGF-1 single nucleotide polymorphism is associated with milk fat traits, but they are limited to trait association analysis. We previously identified a synonymous m Show more
Previous studies have reported that IGF-1 single nucleotide polymorphism is associated with milk fat traits, but they are limited to trait association analysis. We previously identified a synonymous mutation c.258 A > G (rs322131043) in IGF-1, which influenced IGF-1 expression and caused differences in metabolism. This study aims to reveal a new regulatory function of IGF-1 c.258 A > G on milk fat metabolism. Livers transcriptomics was used to identify differentially expressed genes between wild type mice (WT) and IGF-1 c.258 A > G mice (Homozygous mutation, Ho). Subsequently, lipid phenotyping, followed by metabolomics of mammary glands was conducted to verify transcriptomic findings. Finally, the potential mechanisms underlying IGF-1 c.258 A > G-induced changes in milk fat metabolism were explored though integrated transcriptomics-metabolomics analysis and Western blot validation. IGF-1 c.258 A > G changed the expression of genes related to lipid metabolism in livers of 8-week-old mice, including a 10-fold lipoprotein lipase (LPL) expression (P < 0.01) and 80-90 % downregulation of acyl-CoA thioesterase 3 (Acot3), enoyl-Coenzyme A delta isomerase 3 (Eci3), fatty acid synthase (FASN), and sterol regulatory element binding protein1 (SREBP1) expression (P < 0.01). The milk fat content of Ho dams on the second day of lactation (L2D) was decreased 50 % than that of WT dams (P < 0.05), although there was no significant difference in adipose tissue of 8-week-old WT/Ho mice. The levels of triglycerides, sphingolipids and their related fatty acyl chains (10:0, 26:0, 14:2, 20:4, 11:3, 19:0) in mammary glands of L2D Ho dams were reduced 10-50 % observed by lipid metabolomics. And combined with transcriptomics and Western blot, the data suggested that a 2.5-fold upregulation of LPL expression (P < 0.05) may contribute to the milk fat metabolism changes mediated by the IGF-1 c.258 A > G. This study revealed new function of IGF-1 c.258 A > G on milk fat metabolism, thereby informing the development of targeted genetic breeding on milk fat trait. Show less
Aerobic exercise reduces cardiovascular events in atherosclerosis, but the causal roles of microRNAs (miRNAs) in mediating exercise-induced vascular smooth muscle cell (VSMC) phenotypic switching and Show more
Aerobic exercise reduces cardiovascular events in atherosclerosis, but the causal roles of microRNAs (miRNAs) in mediating exercise-induced vascular smooth muscle cell (VSMC) phenotypic switching and plaque stabilization remains unclear. This study investigated whether aerobic exercise stabilizes atherosclerotic plaques by reprogramming VSMC miRNA expression, focusing on the miR-15a-5p/Semaphorin-3A (Sema3A) axis. High-fat diet-fed ApoE Exercise reduced plaque vulnerability, increased collagen content, reduced lipid content, and attenuated macrophage infiltration. Integrative miRNA profiling revealed that miR-15a-5p was markedly upregulated in atherosclerotic aortas but significantly suppressed by exercise locally and in circulation. In human carotid plaques, miR-15a-5p levels positively correlated with the plaque vulnerability index. Mechanistically, miR-15a-5p directly targeted the 3'-UTR of Sema3A, repressing its expression. VSMC-specific miR-15a-5p overexpression in vivo downregulated contractile markers, accelerated phenotypic switching, and destabilized plaques, such traits resembled those in cells from sedentary mice. Aerobic exercise stabilizes plaques by downregulating miR-15a-5p, relieving Sema3A repression and preserving the contractile VSMC phenotype. The miR-15a-5p/Sema3A signaling axis mediates exercise-induced atheroprotection. Notably, elevated miR-15a-5p levels in human carotid plaques correlate positively with plaque vulnerability, supporting its potential as an atherosclerotic therapeutic target. Show less
Li Zhang, Yuting Wang, Wei Min Gao+8 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutell Show more
Coronary restenosis remains a major challenge following percutaneous coronary intervention (PCI), necessitating the development of effective stent-eluting drugs. Previous studies indicate that scutellarin protects vascular endothelial cells and exhibits anti-thrombotic and anti-platelet effects. Notably, our prior research demonstrated that scutellarin specifically counteracts oxidative stress-driven endothelial dysfunction, a key initiating event in restenosis. This combined evidence strongly suggests its potential against in-stent restenosis (ISR). Therefore, this study explores the efficacy of scutellarin in preventing ISR after PCI. We investigated scutellarin, derived from Erigeron breviscapus, for its potential to prevent ISR following PCI. The efficacy and mechanism of scutellarin were evaluated using both in vivo and in vitro models. An experimental atherosclerosis model was established in APOE In APOE This study establishes the efficacy of scutellarin in mitigating ISR using two complementary in vivo models. Scutellarin-eluting stents in atherosclerotic minipigs overcome translational barriers through full interventional simulation. Furthermore, scutellarin inhibits VSMCs proliferation, migration and promotes autophagy-coordinated apoptosis by the coordinated downregulation of both the Pl3K/AKT and lKKs/NF-κB cascades.These findings highlight scutellarin as a promising candidate for next-generation bioactive stent coatings, bridging phytopharmacology and precision interventional cardiology. Show less
Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is Show more
Non-small cell lung cancer (NSCLC) is characterized by high morbidity and lethality, causing a great physical and psychological burden on patients. Therefore, effective treatment of NSCLC patients is very important. This study analyzes the impact of a nursing intervention of case management combined with cognitive-behavioral therapy on anxiety and depression and quality of life in postoperative NSCLC patients. A single-center, non-randomized controlled study in which 80 NSCLC patients from the Hospital were enrolled from May 2023 to January 2024, and were categorized into case management (CM) and cognitive-behavioral therapy (CBT) groups depending on treatment modalities, with case management care in both groups, and cognitive-behavioral therapy care added to the CM combined with CBT (CC) group. The Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), self-perception burden scale (SPBS), life qualities (QLQ-C30), neurotransmitter levels, and clinical effectiveness were primarily assessed in both groups post-treatment. Secondary outcomes included pain level (VAS score), nursing satisfaction, adverse events, and complications. After treatment, the indicators of both groups were significantly different from those of the pre-treatment. Post-treatment, the CC group demonstrated significantly lower scores than the CM group in HAMA (10.18 ± 2.10 vs. 16.04 ± 3.89), HAMD (11.94 ± 2.91 vs. 16.81 ± 3.19), and SPBS (25.52 ± 3.17 vs. 33.50 ± 5.61) (all P < 0.05). Conversely, the CC group showed significantly higher QLQ-C30 scores and levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF). The nursing intervention of case management combined with cognitive behavioral therapy has a good improvement effect on the anxiety and depression status of NSCLC patients. It can improve the quality of life, which is worth promoting and using in the clinic. Show less
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to Show more
Retigabine (RTG) shows notable neuroprotective efficacy in multiple brain injury models; however, its interplay with endoplasmic reticulum stress (ERS) is poorly understood. This study was designed to explore the therapeutic potential of RTG against CRS-induced depression-like behaviors and cognitive deficits in mice and to uncover the associated molecular mechanisms. A depression-like and cognitive impairment model was established in C57BL/6 male mice using chronic restraint stress (CRS). Six-week-old C57BL/6 male mice were randomly assigned to the following groups: control (Con), model (CRS), RTG (10 mg/kg), XE-991 (2 mg/kg) or tunicamycin (Tm, 2 mg/kg). Behavioral tests were conducted to assess depression-like behaviors and cognitive function. Hippocampal neuronal morphology was examined by H&E and immunofluorescence staining, while changes in endoplasmic reticulum stress (ERS)-related signaling pathways were analyzed by Western blot. Retigabine treatment reduced hippocampal neuronal damage and the expression of ERS-related factors (GRP78, CHOP) and the pro-apoptotic factor BAX in CRS-induced mice, while it increased the levels of BDNF. These effects were antagonized by XE-991 and the ERS agonist tunicamycin (Tm). Retigabine may alleviate CRS-induced depressive-like behaviors and cognitive impairment by inhibiting ERS-mediated apoptosis, suggesting its potential as a novel therapeutic strategy for depression. Show less
Ting Li, Ke Chen · 2026 · Journal of affective disorders · Elsevier · added 2026-04-24
Internalizing and externalizing behavior problems co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few studies have explored this heterogeneity and its de Show more
Internalizing and externalizing behavior problems co-occur frequently and there is heterogeneity in the co-occurrence of such symptoms; however, few studies have explored this heterogeneity and its developmental mechanisms from a person-centered perspective. The primary aim of this study is to employ Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA)-person-centered statistical approaches-to explore this underlying heterogeneity, uncover its dynamic developmental trajectories, and further examine the key factors that influence class membership and transitions. A sample of 2232 Chinese college students from three universities in Chongqing was assessed at two time points spaced ten months apart. Latent Profile Analysis (LPA) and Latent Transition Analysis (LTA) were conducted on measures of internalizing and externalizing problems. LPA revealed three distinct profiles for both internalizing problems ("Low-Risk/Well-Adapted", "Moderate-Risk/Affective-Distress", "High-Risk/Comorbid") and externalizing problems ("Well-Adapted", "Adaptation Difficulties", "Maladaptive") at T1, with similar structures at T2. LTA indicated high stability for the low- and high-risk internalizing profiles, but significant fluidity in the middle, with nearly half of the moderate-risk group transitioning to the high-risk profile. For externalizing problems, there was a pronounced shift toward the "Maladaptive" profile over time. Negative parental rearing and PWU were significant risk factors for adverse transitions, while positive parenting, self-transcendence values, and objective social support served as protective factors. Co-occurring internalizing and externalizing problems among Chinese college students are heterogeneous and dynamic. The moderate-risk group represents a critical target for early intervention. Modifiable ecological factors across family, individual, and technological domains significantly predict longitudinal trajectories, informing targeted prevention strategies. Show less