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
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by whi Show more
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by which these dual agonists affect systemic metabolism remain elusive. To investigate the effects of a novel dual-receptor agonist, THDBH120, on systemic metabolism in obese individuals and the specific roles of GIPR and GLP-1R in modulating systemic and adipose tissue metabolism. To evaluate the intrinsic properties of THDBH120, we conducted a potency assay by using HEK293 cell lines overexpressing either human GIPR or GLP-1R and measured the accumulation of cAMP as a downstream second messenger following receptor activation. To evaluate the efficacy of THDBH120 on systemic metabolism, we used obese rodents and nonhuman primate species that received various doses and frequencies of THDBH120. To determine the metabolic roles of GLP-1R and GIPR in mediating the beneficial effects of THDBH120, we used GLP-1R- and GIPR-knockout mouse models treated with THDBH120, the GLP-1R agonist semaglutide, or the GIPR agonist LAGIPRA and performed transcriptomic sequencing analyses of adipose tissues. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has superior weight loss and metabolic improvement effects in rodents and mammals. The activation of GLP-1R by semaglutide or THDBH120 improved lipid metabolism, whereas the activation of GIPR by LAGIPRA or THDBH120 alleviated inflammation. THDBH120 improved lipid metabolism via GLP-1R-mediated pathways and mitigated inflammation by activating GIPR-associated pathways in the adipose tissues of obese mice. Both GLP-1R and GIPR are important in mediating the beneficial effects of dual receptors on systemic metabolism. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has potential clinical applications. Show less
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies Show more
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE Show less
Jianyi Li, Luyao Zhang, Jiapei Xu+7 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, s Show more
Chronic stress is associated with inflammatory activation and oxidative stress responses leading to endothelial dysfunction, which promotes the development of atherosclerosis (AS). SGLT2 inhibitors, such as Dapagliflozin (DAPA), exhibit a protective effect against cardiovascular diseases. However, the effects and mechanisms of DAPA on chronic stress-induced AS are largely unknown. The aim of this study was to determine whether DAPA confers a protective effect against chronic stress-induced AS and to elucidate its further molecular mechanisms. The combined high-fat diet-fed and chronic unpredictable mild stress in ApoE-/- mice and lipopolysaccharides- and corticosterone-induced human umbilical vein endothelial cells (HUVECs) were employed to evaluate the antiatherosclerotic effect of DAPA under chronic stress in vivo and in vitro. Histological staining, western blot analysis, siRNA transfection, reactive oxygen species (ROS) staining, and apoptosis assessment were used to investigate the potential mechanisms of DAPA against AS under chronic stress. The results indicate that DAPA significantly improved plaque size and increased plaque stability in the aorta under chronic stress and reduced inflammation and oxidative stress and inhibited apoptosis in the aorta and HUVECs. Chronic stress upregulated regulated in development and DNA damage response 1 (REDD1) expression, which exacerbated cellular inflammation, oxidative stress, and apoptosis levels, leading to endothelial dysfunction. In contrast, DAPA downregulated REDD1 expression and activated the AKT/FoxO1 pathway. In addition, p53 was a transcriptional regulator of REDD1 under chronic stress. More importantly, p53 agonists prevented DAPA from downregulating REDD1 and inhibited AKT/FoxO1 activation, thereby exacerbating chronic stress-induced endothelial dysfunction. These results suggest that DAPA effectively attenuates chronic stress-induced endothelial dysfunction and AS by downregulating REDD1 to activate the AKT/FoxO1 pathway. 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
Norethindrone (NET) and levonorgestrel (LNG) are synthetic progestins frequently detected in aquatic environments, have unclear effects on lipid metabolic homeostasis during the early life stages of a Show more
Norethindrone (NET) and levonorgestrel (LNG) are synthetic progestins frequently detected in aquatic environments, have unclear effects on lipid metabolic homeostasis during the early life stages of aquatic organisms. Although progestins commonly occur as mixtures, their combined impacts remain unclear. In this study, we investigated the individual and combined impacts of NET and LNG at environmentally relevant concentrations (2-200 ng/L) on lipid metabolism in zebrafish larvae. NET and LNG significantly disrupted early development in zebrafish. It also altered lipid profiles, as indicated by elevated triglyceride (TG) levels, reduced total cholesterol (TC), as well as alterations in key metabolic enzymes (FASN, LPL) and lipid-regulatory genes (pparγ, fasn, lpl, pparα). Co-exposure with LNG resulted in non-additive responses across multiple endpoints. Antagonistic interactions were predominant at medium and high concentrations, while occasional synergism was observed at low doses. These complex patterns were further supported by Bliss independence model analysis. Notably, combined exposure suppressed both lipid synthesis and degradation pathways more strongly than individual treatments, leading to lipid accumulation and altered energy regulation. This study advanced understanding of the ecological risks caused by progestins in aquatic environments and highlighted the necessity of mixture-based risk assessment of endocrine-disrupting compounds. Show less
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoin Show more
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoints that can be therapeutically targeted to restore M2 bias remain poorly defined. Here, we aimed to determine whether the RNA-binding protein TAF15 acts as a post-transcriptional stabilizer of the M2-promoting CEBPB/APOE/PTX3 axis, thereby accelerating DFU healing. First, we confirmed that APOE positively regulates PTX3, which supports M2 polarization and the proliferation and migration of HDF. CEBPB transcriptionally activated APOE and promoted M2 macrophage polarization. TAF15 stabilized CEBPB mRNA and affected HDF cell proliferation and migration by promoting M2 macrophage polarization. Additionally, TAF15 overexpression partially counteracted the disruption of M2 macrophage polarization caused by APOE silencing and facilitated DFU wound healing. Collectively, our findings establish TAF15-driven stabilization of CEBPB mRNA as a target point that sequentially activates APOE/PTX3 signaling to enforce M2 polarization and accelerate DFU closure. This study provides a preclinical rationale for the development of TAF15-targeted oligonucleotides or small-molecule strategies to reprogram wound macrophages and improve DFU outcomes in patients with diabetes. Show less
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To addre Show more
Caloric restriction (CR) improves metabolic health and reduces the risk of aging-related vascular diseases. However, the systematic metabolic reprogramming associated with CR remains unclear. To address this, we performed multi-tissue metabolomic profiling (liver, heart, and serum) in apolipoprotein E-deficient (ApoE-/-) mice subjected to CR. Metabolomic analyses of the multiple tissues revealed that glycerophospholipid metabolism pathway was consistently modulated by CR. To explore its relevance in vascular diseases, we performed serum metabolomic profiling in an abdominal aortic aneurysm (AAA) model induced by angiotensin Ⅱ (AngⅡ) infusion in ApoE-/- mice. The level of lysophosphatidylethanolamine (LPE) (16:0/0:0), a metabolite in the glycerophospholipid metabolism pathway, was elevated during AAA progression and significantly reduced by CR intervention, suggesting its potential as a vascular disease risk factor. Notably, glycerophospholipid metabolism and LPE (16:0) were significantly associated with vascular diseases and aging-related indicators in human multi-omics data, including public transcriptomic and lipidomic, and our serum multi-omics profiling of 76 healthy aged individuals. Collectively, our findings establish glycerophospholipid metabolism and LPE (16:0) as systemic signatures of CR with diagnostic potential. They highlight a crucial link between systemic metabolism and vascular remodeling and remodeling-associated vascular diseases, while also functioning as indicators of systemic aging. Show less
Calcific aortic valve disease (CAVD) is a cardiovascular disease closely associated with aging. The role of lipoprotein(a) [Lp(a)] has attracted considerable attention in recent years. However, limite Show more
Calcific aortic valve disease (CAVD) is a cardiovascular disease closely associated with aging. The role of lipoprotein(a) [Lp(a)] has attracted considerable attention in recent years. However, limited research has simultaneously explored the relationships between Lp(a), age, and CAVD. This study sought to assess the relationship linking Lp(a), time-weighted Lp(a), and CAVD. A total of 5,156 inpatients with comprehensive clinical data were recruited for this study. The associations of Lp(a) and time-weighted Lp(a) with CAVD were examined via multivariate logistic regression analysis, alongside the application of restricted cubic spline analysis. The diagnostic utility of Lp(a) and time-weighted Lp(a) for CAVD was assessed by constructing receiver operating characteristic (ROC) curves. CAVD prevalence rose with age, whereas the rate of increase diminished with advancing age. The average Lp(a) level in the young populations with CAVD was more than twice that in the No-CAVD group, particularly among those aged 55 years or younger. The prevalence of CAVD in non-elderly populations was markedly 2–4 fold greater in the higher Lp(a) group (> 30 mg/dL) than in the lower Lp(a) group (≤ 30 mg/dL). Multivariate adjusted odds ratios (ORs) for CAVD increased with advancing Lp(a) or age. Time-weighted Lp(a), which takes into account both age and Lp(a), was more strongly linked to elevated CAVD risk than Lp(a) alone. Time-weighted Lp(a) enhanced the diagnostic value of CAVD, improving both sensitivity and specificity. The risk of CAVD is strongly associated with both age and elevated Lp(a) levels. Time-weighted Lp(a), which integrates these factors, serves as a superior indicator that better captures cumulative long-term Lp(a) variation and yields stronger CAVD risk stratification. The online version contains supplementary material available at 10.1186/s12944-026-02884-8. Show less
Gallbladder adenosquamous carcinoma (GBASC) is an uncommon, highly aggressive neoplasm characterized by the coexistence of both glandular and squamous cells. Representing fewer than 5% of gallbladder Show more
Gallbladder adenosquamous carcinoma (GBASC) is an uncommon, highly aggressive neoplasm characterized by the coexistence of both glandular and squamous cells. Representing fewer than 5% of gallbladder malignancies, GBASC demonstrates a more aggressive behavior and has poorer prognosis, posing considerable challenges for early diagnosis and effective management. We present a case of GBASC in a 52-year-old woman who achieved long-term tumor-free survival by surgery, as well as targeted and immunotherapy after the operation. Targeted gene sequencing and bioinformatics analysis tools, including STRING, GeneMANIA, Metascape, TRRUST, Sangerbox, and cBioPortal, were used to analyze the biological functions and features of the mutated genes in GBASC. A total of 16 mutations ( Comparative analyses with other gallbladder carcinoma subtypes revealed GBASC to have distinct clinical phenotypes, molecular alterations, functional characteristics, and enriched signaling pathways. Moreover, there is an urgent need for standardized treatment protocols. Show less
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its act Show more
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its active components and underlying mechanisms of action remain largely unexplored. Bauhinia brachycarpa Benth (BBB), an ethnic medicine in China, has antinociceptive effect on neuropathic pain (NP). In this study, an effective portion from BBB was screened and its antinociceptive mechanism was investigated. After the preparation of ethanolic extract from BBB (EEBb) and different soluble portion from EEBb (peEEBb, eaEEBb, nbEEBb), the total content of flavonoids and phenolic acids were measured. A partial sciatic nerve ligation (PSNL) model in vivo was applied to evaluate the antinociceptive effect and the influence on microglia function of these samples. The possible acting target of BBB was predicted by network pharmacology. And the mechanism of nbEEBb, the most effective antinociceptive portion, were studied by PSNL model in vivo and ATP-induced activation of BV2 model in vitro. nbEEBb had the strongest ability of alleviating NP as well as the obvious effect on microglia polarization. The action of nbEEBb was positively correlated to the total content of flavonoids or phenolic acids. nbEEBb inhibited the protein and gene expressions of most key components in P2X4-BDNF-TrkB signaling pathway. nbEEBb is the most effective portion from BBB on NP, and its mechanism refers to the inhibition of P2X4-BDNF-TrkB signaling pathway, which involved in neuron-microglia interaction. Show less
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impa Show more
Post-stroke seizures are a common and debilitating complication with limited therapeutic options, underscoring the need to identify novel molecular targets. Disruption of chloride homeostasis via impaired potassium chloride cotransporter 2 (KCC2) activity is a key driver of neuronal hyperexcitability. While microglia are a predominant source of brain-derived neurotrophic factor (BDNF) in the acute phase after brain injury, the role of microglial BDNF and its signaling in KCC2 dysregulation and early post-stroke seizure susceptibility remain poorly defined. Using a middle cerebral artery occlusion-reperfusion (MCAO-R) mouse model and oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons, we assessed KCC2 function, neuronal excitability, and seizure susceptibility. Pharmacological tools, including the microglial inhibitor minocycline, the TrkB antagonist K252a, the loop diuretic furosemide (FUR), repurposed here as a KCC2-stabilizing agent, and the KCC2 activator CLP290, were employed. Techniques included immunofluorescence, Western blotting, patch-clamp electrophysiology, electroencephalography (EEG), and behavioral seizure assessment. MCAO-R and OGD/R significantly reduced membrane KCC2 expression, leading to a depolarizing shift in the GABA equilibrium potentials (E Our findings identify microglia-derived BDNF/TrkB signaling as a critical upstream pathway mediating KCC2 dysfunction in early post-stroke seizure. Targeting this axis by inhibiting microglial activation, blocking TrkB, or directly enhancing KCC2 function with activators like CLP290 represents a promising therapeutic strategy for stroke-related epilepsy. Show less
To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implica Show more
To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implications for 90-day outcomes. In a prospective cohort, 266 hospitalized AECOPD patients were stratified into worsened ( Compared with controls, AECOPD patients exhibited higher IL-6, TNF-α, PD-1, and MMP-9, alongside reduced BDNF and IL-10. Stable patients demonstrated partial biomarker normalization, whereas worsened patients retained a pro-inflammatory profile. Corticosteroids and antibiotics attenuated cytokine elevations, and oxygen therapy facilitated BDNF recovery. Low BDNF and high MMP-9 predicted spirometric decline, while elevated PD-1 and MMP-9 were associated with increased 90-day readmission risk. A dual-axis model incorporating neurotrophic and immune exhaustion markers outperformed GOLD classification for risk prediction. Neuroimmune biomarkers capture recovery heterogeneity in AECOPD. The proposed dual-axis model improves prognostic accuracy and may inform personalized management strategies. Show less
Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor pro Show more
Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored. We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis. ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-κB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis. The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC. Show less
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients ha Show more
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients have a relatively high risk of infection during the treatment process. Hemodialysis nurses, who are the main executors of the treatment operations and have the most contact with patients, have a close relationship with the infection risk of patients. The level of their hospital infection prevention and control literacy is closely related to the infection risk of patients. To explore the current level of knowledge, attitudes, and practices (KAP) of hospital infection prevention and control among haemodialysis nurses in the Sichuan Province, China, and identified their potential categories. This provided evidence-based recommendations for improving infection control management in hemodialysis departments. A cross-sectional study was conducted From July 15 to August 15, 2025 using a convenience sampling method to survey 470 hemodialysis nurses from 78 hospitals in Sichuan Province. Participants were licensed nurses with over 3 months of hemodialysis experience. Data were collected using the A total of 460 valid questionnaires were collected, with an effective response rate of 97.87%. The average scores for knowledge, attitudes, and practices related to hospital infection prevention and control among haemodialysis nurses were 4.67 ± 0.43, 4.59 ± 0.43, and 4.74 ± 0.34, respectively. Three latent profile models were constructed, with the two-class model identified as the optimal solution, which were defined as the "Low KAP Group" (25.9%) and "High KAP Group" (74.1%). Logistic regression analysis revealed that sex, responsibility for infection control, hospital level, annual number of infection control training sessions, organizational support, and work engagement were significant influencing factors ( The KAP level of haemodialysis nurses in hospital infection prevention and control was relatively high. Hospital managers should tailor supportive work environments on the basis of the individual characteristics and work engagement of haemodialysis nurses to improve the KAP level of nosocomial infection prevention and control among haemodialysis nurses. Show less
Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to Show more
Lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are independent risk factors for worse outcomes in coronary artery disease (CAD) patients. Evidence of their joint association is limited. We aimed to investigate the combined effect of elevated Lp(a) and DM on survival outcomes in CAD patients. This study included 65 547 CAD patients (62.6 ± 10.7 years, 27.7% female) from CIN-II and RED-CARPET cohorts. Patients were stratified into four groups by Lp(a) levels (< or ≥ 30 mg/dL) and DM status. Multivariable Cox regression models estimated associations with cardiovascular and all-cause mortality, examining additive and multiplicative interactions. During a median follow-up of 5.5 years, 10 686 (16.3%) patients died from all causes and 5106 (7.8%) died from cardiovascular causes. Patients with Lp(a) ≥ 30 mg/dL and DM were independently associated with cardiovascular mortality (adjusted hazard ratio [aHR]: 1.28, 95% CI: 1.20-1.35; aHR: 1.53, 95% CI: 1.44-1.62, all p < 0.001, respectively). Compared to patients with Lp(a) < 30 mg/dL without DM, the aHRs were 1.26 (95% CI: 1.16-1.36, p < 0.001), 1.51 (95% CI: 1.40-1.62, p < 0.001) and 2.00 (95% CI: 1.83-2.18, p < 0.001) for those with Lp(a) ≥ 30 mg/dL without DM, Lp(a) < 30 mg/dL with DM and Lp(a) ≥ 30 mg/dL with DM, respectively. Significant additive interaction between elevated Lp(a) and DM on cardiovascular mortality was observed, with 12% of the excess risk attributed. Similar associations were observed in all-cause mortality. In patients with CAD, elevated Lp(a) and DM act synergistically to increase the risk of cardiovascular and all-cause mortality, suggesting that both risks should be considered to integrate management. Show less
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to c Show more
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to cancer progression remain poorly understood. Here, we identified a lung cancer-specific chimeric RNA KANSL1-ARL17A (chKANSARL) and its circular variant fusion circular RNA KANSL1-ARL17 A (F-circKA), both derived from the fusion gene KANSARL. Functional assays revealed that overexpression of either chKANSARL or F-circKA significantly enhanced lung cancer cell proliferation, migration, and invasion, while their knockdown suppressed these malignant phenotypes. In vivo experiments demonstrated that chKANSARL overexpression accelerated tumor growth in immunodeficient mice. Notably, coexpression experiments uncovered a synergistic regulatory interaction between F-circKA and chKANSARL, amplifying oncogenic effects. Mechanistically, miRNA sequencing and dual-luciferase assays revealed that F-circKA acts as a molecular sponge for miR-6860, thereby derepressing chKANSARL expression. Rescue experiments further validated this regulatory axis, wherein miR-6860 inhibition reversed the tumor-suppressive effects of F-circKA knockdown. Collectively, our study identifies and characterizes a novel F-circKA/miR-6860/chKANSARL regulatory axis, revealing how dual transcriptional outputs from the KANSARL fusion gene can synergistically drive lung cancer progression. These findings highlight a previously unrecognized layer of cooperative regulation between linear and circular fusion RNAs in oncogenesis and provide a new framework for understanding fusion gene-mediated tumorigenesis. Show less
Atherosclerosis is a chronic and progressive inflammatory disease that can lead to adverse cardiovascular and cerebrovascular events. Phenotypic switching of vascular smooth muscle cells (VSMCs) plays Show more
Atherosclerosis is a chronic and progressive inflammatory disease that can lead to adverse cardiovascular and cerebrovascular events. Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a pivotal role in its development and progression, but the upstream regulatory mechanisms remain incompletely defined. Here, we identify ubiquitin-fold modifier 1 (UFM1), a ubiquitin-like protein, as a critical regulator of VSMCs plasticity and atherogenesis. In VSMCs stimulated with oxidized low-density lipoprotein (ox-LDL), UFM1 overexpression markedly attenuated phenotypic switching, restoring contractile features and suppressing synthetic activation, accompanied by reduced proliferation and migration. In contrast, UFM1 knockdown further exacerbated these phenotypic alterations. In ApoE Show less
Given the heterogeneous nature of Alzheimer's disease (AD) and its higher prevalence in females, it is crucial to understand sex-related differences in AD presentation and changes in the brain. This s Show more
Given the heterogeneous nature of Alzheimer's disease (AD) and its higher prevalence in females, it is crucial to understand sex-related differences in AD presentation and changes in the brain. This systematic review investigates sex differences in AD and summarizes key findings from neuroimaging studies over the past two decades to examine how genetics, hormones, and lifestyle factors influence neuroimaging biomarkers and their correlation with cognitive decline and AD progression. A comprehensive literature search was conducted across several databases for human studies from 2004 to 2024 related to AD, biological sex differences, and neuroimaging. After a 3-step review process, the final extraction included 120 peer-reviewed studies using various neuroimaging modalities, such as MRI, amyloid-beta PET, tau-PET, and fluorodeoxyglucose (FDG) PET, to investigate sex as a biological predictor variable in adults with or at risk for AD. Over 90% of the reviewed studies identified clear sex-specific patterns of imaging biomarkers related to cognitive reserve, hormonal changes, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle factors. Machine learning studies increasingly incorporate sex as a key variable, revealing sex-specific biomarkers and improving model performance in predicting disease status and progression. Considering biological sex in AD research is essential for improving diagnostic accuracy, tailoring interventions, and health outcomes. This systematic review identifies sex-specific patterns in neuroimaging biomarkers of AD, influenced by cognitive reserve, hormones, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle. Recognizing these differences is crucial for understanding, diagnosis, and treatment efficacy. Show less
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic Show more
Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein that has been established as an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Structurally composed of a low-density lipoprotein (LDL)-like particle covalently linked to apolipoprotein(a) [apo(a)], Lp(a) exhibits unique atherogenic, thrombogenic, and inflammatory properties, largely due to its role as a carrier of oxidized phospholipids (OxPL). Plasma Lp(a) concentrations are predominantly determined by the number of kringle IV type 2 (KIV-2) repeats in the LPA gene, with minimal influence from lifestyle or environmental factors. Despite substantial evidence linking elevated Lp(a) to cardiovascular risk, clinical testing remains underutilized, especially in East Asian countries. In Taiwan, although population-level Lp(a) concentrations are comparatively low, a significant subset exceeds risk thresholds, with local studies confirming its prognostic value in coronary artery disease and ischemic stroke. Barriers, including limited physician awareness, implementation barriers, and therapeutic nihilism, contribute to its under-recognition. This review highlights the molecular features of Lp(a), its pathogenesis of cardiovascular disorders, epidemiology, and current barriers and future advances in diagnostic testing, with a particular focus on implications for cardiovascular risk management in Taiwan. Show less
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key Show more
Keratoconus (KC) is a progressive disorder of corneal thinning characterized by responses in the extracellular matrix and cellular interactions. This study used bioinformatics methods to identify key genes involved in KC development and in anoikis and endoplasmic reticulum (ER) stress. KC and control datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). These were cross-referenced with anoikis and ER stress-related genes from Genecards. Functional enrichment, immune infiltration analysis, and machine learning techniques (LASSO, Random Forest) were used to identify candidate molecular signatures, which were then validated in an animal model. We identified 46 DEGs associated with anoikis and 41 DEGs related to ER stress. Functional analysis linked them to apoptosis and IL-17 signaling. Five key molecular signatures were identified: CDKN1A, MCL1, PTGS2, PTHLH, and ANGPTL4. The expression of ANGPTL4, CDKN1A, and MCL1 was consistent in the animal model. These genes are associated with inflammatory and oxidative stress responses. Twelve potential therapeutic drugs were predicted. This study identifies five candidate molecular signatures for KC related to anoikis and ER stress, offering insights into KC pathogenesis and potential targeted therapies. Show less
This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify t Show more
This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children. Clinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted. The proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G>A (p.Trp2002*), in the spectrin beta chain ( The heterozygous mutations Show less
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show prom Show more
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show promise, their mechanisms in mitigating neuropsychiatric comorbidities remain unclear. Here, we investigated the therapeutic potential of Show less
Interleukin-27 (IL-27) is an immunoregulatory cytokine, but its role in B-cell haematopoiesis and B-cell acute lymphoblastic leukaemia (B-ALL) within the bone marrow (BM) niche remains unclear. IL-27 Show more
Interleukin-27 (IL-27) is an immunoregulatory cytokine, but its role in B-cell haematopoiesis and B-cell acute lymphoblastic leukaemia (B-ALL) within the bone marrow (BM) niche remains unclear. IL-27 was delivered in vivo using adeno-associated virus. B-cell reconstitution, mixed BM chimeras, and an N-myc-driven B-ALL model were analysed by flow cytometry, transcriptional profiling, and survival studies. Group comparisons were assessed using Student's t-test, and survival was evaluated by Kaplan-Meier analysis with log-rank tests. Sustained IL-27 expression selectively impaired B-cell reconstitution while preserving overall haematopoietic recovery, with marked reductions in CLPs and early B-cell subsets. IL-27 directly inhibited early B-lineage differentiation and concurrently remodelled the BM microenvironment by downregulating VCAM-1, ICAM-2, CXCL12, and IGF-1. These niche alterations were associated with reduced BM-resident B-ALL burden, enhanced chemotherapy efficacy, and improved survival in B-ALL-bearing mice. IL-27 showed no direct cytotoxicity toward B-ALL cells, supporting an indirect, niche-mediated mechanism. IL-27 constrains B-cell haematopoiesis and B-ALL progression through coordinated progenitor inhibition and BM niche remodelling, revealing a cytokine-driven strategy with the potential to enhance leukaemia therapy. This work was supported by the National Key R&D Program of China (Grant No. 2021YFA1100800 to A.-B.L.) and the National Natural Science Foundation of China (Grant No. 82100180). Show less
Gary Chen, Adrienne Sexton · 2026 · Patient education and counseling · Elsevier · added 2026-04-24
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinic Show more
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinical practice. Rigorous scoping review methodology was followed. Ovid Medline, Embase, PsycINFO, and CINAHL were searched with keywords and MeSH terms related to "genetic testing", "genetic counseling", "dementia", "decision making", and "patient outcomes" for peer-reviewed studies with adult participants published over the last ten years. Thirty-six articles met inclusion criteria. Narrative synthesis organized findings into temporal categories including motivations for genetic testing, experiences during the testing/counseling process, and outcomes after testing. Common motivators included reducing uncertainty, reproductive planning, life planning, and the prospect of a treatment becoming available in the future. A lack of current treatments and fear that knowledge of genetic risk would be difficult to cope with were common barriers to testing. Patient-centered communication improved satisfaction. Genetic testing was generally psychologically well tolerated, and a wide range of practical responses were reported including changes to lifestyle, diet, advanced care and financial planning, and engaging in clinical trials. This review maps the experiences and outcomes of genetic testing or counseling for people with or at potentially increased genetic risk of dementia. Genetic testing and counseling for directly causal dementia genes and APOE genotype appears well tolerated but long-term outcome data is lacking. Motivations, concerns and perceived benefits of knowing genetic results vary depending on personal, familial and cultural viewpoints. Genetic counseling can help patients and families prepare, reduce decisional regret, and adapt to results. Motivations varied, and a patient-centered approach addressing both information and psychological aspects improves satisfaction. Future longitudinal research should ascertain ways to support individuals from a wide range of demographics with understanding and adjusting to genetic risk information regarding dementia. Show less
Carotid atherosclerosis is a significant risk factor for cardiovascular and cerebrovascular diseases. Maintaining plaque stability can prevent plaque rupture and thrombus formation, slow disease progr Show more
Carotid atherosclerosis is a significant risk factor for cardiovascular and cerebrovascular diseases. Maintaining plaque stability can prevent plaque rupture and thrombus formation, slow disease progression, and is critically important for preventing cerebrovascular events (such as stroke, transient ischemic attack (TIA), and similar events). Mechanisms influencing plaque stability are still unclear. In this study, stable plaques (n = 5) and unstable plaques (n = 5) were collected from patients and analyzed using RNA-sequencing. 594 differently expressed genes were found by RNA-seq. Pathways enriched by KEGG analysis of differentially expressed genes included inflammation related pathway, cell adhesion related pathway and TGFβ signaling pathway. Especially, we found AMIGO1 was significantly upregulated in stable plaques. Functional assays including cell adhesion, and inflammation-related factor detection revealed that AMIGO1 significantly promotes endothelial cell adhesion while downregulating inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) production, thereby mitigating inflammatory responses. Co-immunoprecipitation (Co-IP) experiments further found that AMIGO1 interacts with transforming growth factor beta receptor II (TGFRII), stabilizing TGFRII protein levels and subsequently activating the TGFβ signaling pathway. AMIGO1 overexpression with AAV9 virus tail vein injection markedly stabilized plaques in ApoE Show less
Spinal cord injury (SCI) remains difficult to treat, and current interventions provide limited functional restoration and often require invasive procedures. Existing cell- or extracellular vesicles (E Show more
Spinal cord injury (SCI) remains difficult to treat, and current interventions provide limited functional restoration and often require invasive procedures. Existing cell- or extracellular vesicles (EV)-based approaches are frequently administered alongside surgery, limiting therapeutic reach and overall efficacy. In this study, we developed an engineered extracellular vesicle (EV) platform by displaying a single-chain variable fragment (scFv) against integrin αvβ8 (αITGEV) and loading brain-derived neurotrophic factor mRNA (mBDNF). The construct maintained canonical EV identity and morphology, and showed predominant single particle co-positivity for targeting ligand and cargo. In neuron-microglia co-culture, mBDNF@αITGEV preferentially entered both cell types under injury-relevant stress, shifted microglia toward a repair-associated phenotype, reduced TNF-α and IL-1β, increased IL-4 and IL-10, and preserved neuronal architecture. Our results indicate that mBDNF@αITG-EVs significantly promote functional motor recovery by modulating the inflammatory microenvironment and inhibiting neuronal ferroptosis. Mechanistically, the delivery of BDNF mRNA bolstered GPX4 expression and stabilized mitochondrial dynamics, thereby mitigating secondary oxidative damage. This study provides a non-invasive strategy for precision nanomedicine in neuro-regeneration. Collectively, this study supports a non-invasive systemically administered, targeted EV-mRNA therapeutic strategy for spinal cord injury with translational potential. Show less
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stres Show more
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stress among Chinese female clinical nurses using latent profile analysis, compare sociodemographic differences across these subgroups, and examine their associations with premenstrual syndrome (PMS). A cross-sectional study was conducted among female nurses in tertiary hospitals in Huai'an City, Jiangsu Province, China, from November to December 2023. We recruited participants via convenience sampling, and 400 valid questionnaires were collected. Data were collected using a researcher-developed general information questionnaire, the standardized Chinese Nurses Stressor Scale (35 items), and the Premenstrual Syndrome Scale. Latent profile analysis (LPA) was performed with Mplus 8.0 to identify occupational stress subtypes. Sociodemographic predictors of these subtypes were explored using chi-square tests and multivariate logistic regression in SPSS 25.0. The association between stress subtypes and PMS symptoms was assessed using ANOVA. A Three clinical female nurse occupational stress subtypes were identified: overall low-stress (38.3%, This study identified significant heterogeneity in occupational stress among clinical female nurses, categorized into three distinct subtypes differing in stress levels and demographic characteristics. These findings highlight the importance of considering individual differences when developing interventions to address occupational stress. The study advocates for the implementation of intervention strategies targeting different types of stress in nursing education and organizational reform to better support nurses in fulfilling their responsibilities. Show less
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the ef Show more
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE Show less
The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable o Show more
The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable of altering the functionality of foods. This research investigated the effects of fermentation with different LAB, such as Lactobacillus acidophilus (LAC), Lactobacillus casei (LCA), Lactobacillus rhamnosus (LRH), Lactobacillus plantarum (LPL), and Lactobacillus bulgaricus (LBU), on the hypoglycemic activity and mechanism of polyphenols in highland barley. The hypoglycemic activity of the fermentation products was measured by in vitro antioxidant, enzyme activity, and glucose consumption experiments. Untargeted metabolomic analysis used UHPLC-Q Exactive HF-X/MS to reveal distinct metabolic profiles among the fermented groups. Molecular docking and western blot experiments were conducted to elucidate the mechanism underlying the hypoglycemic effect of fermentation products. Polyphenolic antioxidant activity in highland barley and its inhibitory activities against α-glucosidase and α-amylase were increased after LAC fermentation. Furthermore, the fermented extracts improved glucose consumption in HepG2 cells. The content determination and metabolomic analysis showed that fermented highland barley polyphenols were increased, and 113 differential phenolic metabolites were identified and annotated, among which 44 exhibited a significant upregulation compared with raw highland barley polyphenols. At the molecular level, the polyphenol extract upregulated PI3K and phosphorylated Akt expression in HepG2 cells. Overall, the results indicate that fermentation by LAC biotransformed highland barley polyphenols into smaller molecules with improved hypoglycemic activities, thereby enhancing their bioavailability. Show less