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
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Gene Show more
Lewy body dementia (LBD), encompassing dementia with Lewy bodies and Parkinson's disease dementia, is neuropathologically defined by neuronal accumulation of α-synuclein encoded by the SNCA gene. Genetic risk factors strongly influence LBD susceptibility, including SNCA multiplication, particularly triplication, and the apolipoprotein E ε4 allele (APOE4), the strongest common genetic risk factor for LBD. While SNCA is predominantly expressed in neurons and APOE primarily in glial cells, how these genetic factors converge to impact neuronal vulnerability and regional pathology in the human brain remains poorly understood. Here, we applied spatial transcriptomics to postmortem temporal cortex tissue from LBD cases with SNCA triplication or different APOE genotypes, alongside age- and sex-matched controls, to map gene expression within intact cortical architecture. We identified layer 5 of the gray matter as a particularly vulnerable region, characterized by elevated SNCA expression, pronounced synaptic and metabolic dysregulation, and exacerbation of these alterations in APOE4 carriers. Reelin signaling emerged as a core Lewy body-associated pathway disrupted across cortical layers, validated in independent postmortem cohorts and human-induced pluripotent stem cell (iPSC)-derived cortical organoids. In contrast, white matter exhibited distinct molecular alterations, including disrupted myelination pathways, with APOE4 carriers showing increased myelin debris and glial responses compared with non-carriers. Cell-type deconvolution informed by single-nucleus RNA sequencing further revealed APOE4-associated impairments in neuronal vulnerability and intercellular communication. Together, these findings define spatially and cell-type-specific mechanisms through which SNCA dosage and APOE4 genotype impact LBD pathology, providing insight into regionally distinct disease processes and potential targets for genetically stratified therapeutic interventions. 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
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
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
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence sugges Show more
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence suggests that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play central and interrelated roles in its pathogenesis. In this review we examine the bidirectional functions of 5-HT and BDNF in both the reproductive and nervous systems, highlighting their importance in regulating ejaculation, emotional stability, and synaptic plasticity. A comprehensive literature search (2010-2025) was conducted across multiple databases using relevant Medical Subject Headings (MeSH) terms, including pertinent original research and review articles, to synthesize the roles and regulatory pathways of 5-HT and BDNF in PE with comorbid anxiety or depression. We summarize the shared and distinct roles of 5-HT and BDNF in maintaining physiological balance across these systems and focus on their involvement in the major pathological processes underlying PE with anxiety or depression, including neurotransmitter imbalance, neuroendocrine dysregulation, inflammation, and oxidative stress. Furthermore, we outline the related signaling pathways through which 5-HT and BDNF exert their effects and interact. We also evaluate current pharmacological and non-pharmacological interventions targeting these molecules, demonstrating their potential to improve both ejaculatory control and emotional symptoms, and critically appraise selective serotonin reuptake inhibitor (SSRI)-related risks and highlighted the need for individualized dosing and monitoring. Emerging evidence suggests that Traditional Chinese Medicine formulations can extend intravaginal ejaculatory latency and mitigate mood symptoms and may serve as stand-alone or adjunctive options to reduce reliance on selective serotonin reuptake inhibitors (SSRIs). Overall, 5-HT and BDNF are not only deeply involved in the biological mechanisms of PE with comorbid psychological disorders, but also represent promising biomarkers and therapeutic targets, and their integrative neuro-reproductive regulatory functions provide new insights into the diagnosis and treatment of this multifaceted condition. 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
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, w Show more
Autophagy supports clear cell renal cell carcinoma (ccRCC) progression, yet its upstream regulatory mechanisms remain to be fully defined. Integrating bulk, single-cell, and spatial transcriptomics, we identify a regulatory axis wherein the transcription factor ZBED6 activates the expression of the autophagy-initiating kinase PIK3C3 via the repression of IGF2, thereby driving pro-tumorigenic autophagy. Spatial analysis confirms the co-localization of ZBED6 and PIK3C3 in tumor tissues. Using genes associated with this axis, we develop a six-gene prognostic signature that stratifies patients with distinct survival outcomes and differential responses to immunotherapy and targeted therapy. Functional assays show that ZBED6 promotes ccRCC cell proliferation, migration, and invasion. This work elucidates a pathway governing autophagy in ccRCC and provides a framework for prognostic assessment and precision therapy. 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
Chao Chen, Fang Lv · 2026 · British journal of hospital medicine (London, England : 2005) · added 2026-04-24
Lipoprotein(a) [Lp(a)] is recognized as a cardiovascular risk indicator; however, its connection to peripheral arterial disease (PAD) in individuals with type 2 diabetes mellitus (T2DM) is not well es Show more
Lipoprotein(a) [Lp(a)] is recognized as a cardiovascular risk indicator; however, its connection to peripheral arterial disease (PAD) in individuals with type 2 diabetes mellitus (T2DM) is not well established. This research seeks to explore how Lp(a) concentrations relate to the occurrence of PAD in T2DM patients. A retrospective analysis was conducted on 590 patients diagnosed with T2DM who were admitted to Hefei First People's Hospital from January 2022 to August 2024. Participants were grouped into tertiles according to their Lp(a) levels. The diagnosis of PAD was made using the ankle-brachial index (ABI), with an ABI <0.9 considered indicative of PAD. The association between Lp(a) concentrations and PAD was examined using multivariate logistic regression models, subgroup analyses, receiver operating characteristic (ROC) curves, and restricted cubic spline (RCS) plotting. Compared to lower Lp(a) levels, the group with higher Lp(a) levels exhibited a higher prevalence of PAD ( A significant correlation was observed between elevated Lp(a) levels and an increased risk of PAD in patients with T2DM. 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 alcohol consumption drives systemic damage through metabolites such as acetaldehyde, which trigger oxidative stress, inflammation, and gut dysbiosis. This study evaluated the protective effe Show more
Long-term alcohol consumption drives systemic damage through metabolites such as acetaldehyde, which trigger oxidative stress, inflammation, and gut dysbiosis. This study evaluated the protective effects of fermented red quinoa (FRQ) in an alcohol-exposed mouse model, with a focus on cognitive function. Male C57BL/6J mice were randomized into three groups for a 28-day study: a normal control, an alcohol-treated group gavaged with ethanol (1 mL/100 g·BW), and a group receiving the same ethanol dose co-administered with FRQ powder (human equivalent dose: 9 g/60 kg·BW). Our results demonstrated that fermentation with Lactobacillus kisonensis significantly increased the content of phenolic compounds (e.g., quercetin and veratric acid) in FRQ. FRQ intervention improved cognitive function, ameliorated synaptic structural impairment and blood-brain barrier disruption, and attenuated hepatic steatosis. The protective mechanisms involved three pathways: 1) The specific phenolic compounds in FRQ promoted alcohol metabolism by regulating ADH/ALDH activity, leading to reduced acetaldehyde levels. As a primary initiating pathway, this metabolic enhancement dominantly attenuated subsequent oxidative stress and inflammation, mitigating injury in the liver, brain, and colon. 2) It directly modulated AP-1 subunits (ΔFOSB/JUND), restored BDNF, and rebalanced the glutamate/GABA systems. 3) It regulated the gut-liver-brain axis by remodeling the gut microbiota (e.g., enriching butyrate-producing Butyricicoccus), reinforcing intestinal barrier integrity, and thereby suppressing systemic LPS translocation and inflammation. In conclusion, FRQ mitigates alcohol-induced cognitive and hepatic damage via multiple mechanisms, highlighting its promise as an integrative dietary intervention. 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
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative i Show more
We recently showed that METRNL (Meteorin-like) protects against atherosclerosis. However, the mechanism for METRNL in atherosclerosis is largely unclear. This study aimed to demonstrate the relative importance of endothelial METRNL in atherosclerosis by comparing the effects of whole-body METRNL deficiency to endothelial-specific deficiency, and to show the subcellular distribution of endothelial METRNL and its role in mitochondrial homeostasis against atherosclerosis. Our study demonstrated that a deficiency in either endothelial or global METRNL exacerbated atherosclerosis to a similar degree in both spontaneous (age-related) and high fat diet-induced atherosclerosis, suggesting that endothelial METRNL is pivotal in the progression of atherosclerosis due to METRNL deficiency. Endothelial METRNL was diffusely distributed in the cytoplasm with subcellular localization to mitochondria, nucleus, endoplasmic reticulum, and Golgi apparatus (especially enriched in mitochondria and nucleus). In both an in vivo apolipoprotein E-deficient (ApoE Show less
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN Show more
Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve (RLN) injury is a common cause of dysphonia. No biotherapeutic injectable exists that directs laryngeal reinnervation after RLN injury. Placental-derived connective tissue matrix (pd-CTM) could fill this need, as it contains a plethora of cytokines with potential UVFP therapeutic benefits. This study aimed to identify and quantify the factors in a commercially available pd-CTM (CTM Flow, CTM Biomedical, Lake Worth, Florida) and to study the effects of pd-CTM on vocal fold microenvironment and glottic function in a mouse model of unilateral RLN injury. Cytokine expression (ng/mL) in pd-CTM was characterized using a cytokine array and ELISA. In a separate experiment, C57/BL6 mice were divided into three groups: uninjured negative controls (n = 12), RLN transection with ipsilateral saline thyroarytenoid (TA) injection (n = 16), and RLN transection with ipsilateral pd-CTM TA injection. Outcomes included laryngeal electromyography (L-EMG) and video laryngoscopy after 7 and 28 days, with larynges then harvested and analyzed via immunohistochemistry (IHC) and qPCR. pd-CTM characterization showed moderate-to-high levels of neurotrophic (BDNF, CNTF, GDNF, NTF-3), angiogenic (Angiogenin, VEGF-D), tissue remodeling (bFGF, IGF-1, HGF, TGF-β3), and anti-inflammatory factors (IL-10, IL-1Rα). L-EMG demonstrated increased mean normalized area under the curve ratio in pd-CTM treated mice compared to saline treated mice at the 28-day time point indicating reinnervation (p < 0.001). IHC detected innervated neuromuscular junctions 28 days after pd-CTM treatment. pd-CTM may be a novel treatment option for patients with UVFP based on the neurotrophic, angiogenic, tissue remodeling, and anti-inflammatory factors present. NA. Show less
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the w Show more
To determine the prevalence of CHD7, FGFR1 and ANOS1 variants and the impacts of their splicing variants on mis-splicing in patients with congenital hypogonadotropic hypogonadism (CHH). Based on the whole-exome sequencing data from 280 CHH probands, we identified 15 potential splice-site variants in CHD7, ANOS1 and FGFR1 by using in silico software. The functional consequences of these variants were analyzed by the minigene assay or RT-PCR analyses of RNA taken from the peripheral lymphocytes. Detailed phenotyping was performed in the CHH patients harboring deleterious variants and their available family members. 11 out of 15 potential splice-site variants were demonstrated to cause mis-splicing, resulting in loss of function through deletion, insertion or frameshift of amino acids in the proteins. Most patients with deleterious splice-site variants in CHD7, ANOS1, FGFR1 presented with gene-specific non-reproductive phenotypes, confirming the pathogenic contribution of these variants to CHH. Our study indicated that splice-site variants in CHD7, ANOS1, FGFR1 underlie the genetic basis of ~3.9% of CHH patients, warranting the inclusion of potential splice-site variants for genetic diagnosis and counseling of CHH. 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
Serous endometrial cancer (SEC) is an aggressive subtype of endometrial cancer (EC) with poor prognosis and limited treatment options. Here, we developed a clinically relevant, immunocompetent serous- Show more
Serous endometrial cancer (SEC) is an aggressive subtype of endometrial cancer (EC) with poor prognosis and limited treatment options. Here, we developed a clinically relevant, immunocompetent serous-like mouse model incorporating oncogenic Show less
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. 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 aims to identify the latent profiles of sense of coherence (SOC) in patients with advanced cancer and explore its influencing factors encompassing sociodemographic and clinical characterist Show more
This study aims to identify the latent profiles of sense of coherence (SOC) in patients with advanced cancer and explore its influencing factors encompassing sociodemographic and clinical characteristics, and generalized resistance resources (GRRs). A cross-sectional study of 262 patients with advanced cancer was conducted by convenience sampling in Guangzhou, China, from September 2023 to July 2024. Data were collected including sociodemographic and clinical characteristics, SOC-13, Revised Life Orientation Test (LOT-R), Rosenberg Self-Esteem Scale (RSES), Inner Peace State Scale (IPSS), Gratitude Questionnaire-6 (GQ-6), and Social Support Rating Scale (SSRS). Statistical analysis was performed using latent profile analysis (LPA) and multivariate logistic regression analysis. Three latent profiles of SOC were identified: low SOC and low comprehensibility group (29.01%), moderate SOC and high meaningfulness group (40.08%), and high SOC and high manageability group (30.91%). This study found that SOC was impacted by self-perceived severity of the disease and GRRs including optimism, self-esteem, and inner peace ( SOC in patients with advanced cancer exhibited different characteristics. Enhancing positive disease perception and GRRs including optimism, self-esteem, and inner peace may be effective strategies for improving their SOC. Healthcare professionals can formulate strategies such as tailored health education, symptom management, and positive psychological interventions to enhance SOC in patients with advanced cancer. 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
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
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