Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may Show more
Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol-related behaviors. We investigated the effects of pitolisant, an FDA-approved H3R antagonist, on ethanol (EtOH)-related behaviors in mice. Adult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted. Pitolisant administration reduced acute EtOH-induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression-like behavior during 24-h withdrawal (Post-EtOH). Mechanistically, the Post-EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra-LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol-related behavior. These findings highlight the HAergic system as a critical regulator of alcohol-related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD. 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
Chemical investigation of the soft coral Sclerophytum humesi led to the discovery of (±)-norsclerohumin A (1), a pair of enantiomeric norsesquiterpenoids possessing an unprecedented oxatricyclo[7.2.1. Show more
Chemical investigation of the soft coral Sclerophytum humesi led to the discovery of (±)-norsclerohumin A (1), a pair of enantiomeric norsesquiterpenoids possessing an unprecedented oxatricyclo[7.2.1.0 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
Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and a Show more
Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. The mechanisms driving this transition from acute immune activation to chronic inflammatory remodeling under viral suppression remain incompletely understood. Here, we leveraged a nonhuman primate model to characterize the longitudinal transcriptomic changes across key stages of SIV infection and ART. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-κB signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-κB, and inflammasome (NLRP3/NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-κB activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART-treated macaque revealed macrophage-rich plaques with p21⁺ senescent cells with intraluminal thrombus formation, recapitulating key features of HIV-associated atherogenesis. While ART normalizes acute infection-induced immune dysregulation, chronic SIV infection sustains a chronic, macrophage- and TLR-driven inflammatory state linked to vascular injury and aging process regardless of long-term suppression of viremia. Targeting inflammasome, NF-κB, and senescence pathways may mitigate non-AIDS comorbidities in PLWH. 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
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfun Show more
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27 Show less
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly r Show more
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs. Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibited comparable HFpEF susceptibility regardless of genotype, developing hallmark phenotypes including diastolic dysfunction (E/E'), myocardial hypertrophy (heart weight/tibia length), cardiac fibrosis, and hepatic steatosis. Particularly, due to the reduced ejection fraction in KO mice, combined with HFD/L-NAME, the HF phenotype was ultimately manifested as impaired diastolic function and slightly reduced ejection fraction (with the characteristics of HFpEF and HFmrEF). Mechanistically, KO-HF females displayed significant estrogen axis disruption (plasma estradiol and the expression of ERα, ERβ, ESRRA, and PELP1 expression). OVX in WT females validated the importance of estrogen for HFpEF resistance. Transcriptomic profiling identified convergent targets across cardiac (ITGAD, ITGAM, FGA, and FGB) and hepatic tissues (APOA1 and APOB), revealing miR-30a-5p's orchestration of extracellular matrix remodeling (via ITGAD/ITGAM mechanotransduction),fibrinogen-mediated microvascular homeostasis, and APOB-driven metabolic dysregulation. Notably, OE intervention failed to mitigate OVX-induced cardiac/hepatic pathology, implicating estrogen-dependent miR-30a-5p functionality. These findings establish miR-30a-5p as a crucial sex-specific regulator of HF (mainly HFpEF), operating through estrogen signaling to balance cardiac compliance and metabolic adaptation. Show less
Xin Huang, Yan-Yun Sun, Yi-Ren Qin+15 more · 2026 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Toll-like receptor 9 (TLR9), expressed in both microglia and neurons of the CNS, represents a promising therapeutic target for Alzheimer's disease (AD). While either microglial or neuronal TLR9 activa Show more
Toll-like receptor 9 (TLR9), expressed in both microglia and neurons of the CNS, represents a promising therapeutic target for Alzheimer's disease (AD). While either microglial or neuronal TLR9 activation exerts neuroprotective effects that ameliorate AD pathology and preserve cognitive function, CpG oligodeoxynucleotides (ODNs), the synthetic agonists, cannot cross the blood-brain barrier (BBB). To overcome this, we developed tNCpG, an apolipoprotein E (ApoE)-functionalized polymersome nanocarrier for brain-targeted delivery of CpG ODNs. APP/PS1 transgenic mice, which overexpress human mutant APP/PS1 and are widely used in AD mouse models for preclinical studies, were administered tNCpG intravenously biweekly for 3 months, starting at 4 months of age. tNCpG achieved efficient brain delivery while specifically targeting microglia and neurons. tNCpG treatment enhanced microglial recruitment to and phagocytosis of Aβ plaques, suppressed Aβ production while promoting its degradation, and improved BBB integrity and Aβ efflux. Collectively, these effects significantly reduced cerebral Aβ burden, neuroinflammation, and neurodegeneration, leading to the rescue of cognitive deficits. Our study establishes targeted TLR9 activation via tNCpG as a disease-modifying therapeutic strategy for AD. Show less
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the Show more
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the interaction between the gut microbiota and the central nervous system (CNS). The gut-brain axis (GBA), as a bidirectional communication pathway, plays an increasingly recognized role in regulating cognitive functions. Ganoderma lucidum polysaccharides (GLP), a traditional medicinal and edible substance, can regulate gut microbiota homeostasis and short-chain fatty acid (SCFAs) levels through the GBA. GLP reduces the Firmicutes/Bacteroidetes ratio, significantly increases the abundance of Lactobacillus, and further suppresses oxidative stress and inflammatory responses by controlling microglial overactivation and neuroinflammation, thereby enhancing the expression of synapse-associated proteins and brain-derived neurotrophic factor (BDNF). Consequently, GLP shows potential for improving cognitive dysfunction. This review systematically summarizes the bioactivities of GLP, explores the neurodegenerative mechanisms of aging, and proposes the possibility that GLP mitigates aging-induced inflammation and improves cognitive function via modulation of the gut microbiota. Show less
Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide, and an urgent need exists to discover new therapeutic strategies. Isolinderalactone (ISO) is a sesquiter Show more
Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide, and an urgent need exists to discover new therapeutic strategies. Isolinderalactone (ISO) is a sesquiterpene compound derived from the Lindera aggregata root with significant anti-inflammatory effects. Given that atherosclerosis (AS) is a chronic inflammatory condition, the efficacy and mechanism of ISO on atherosclerotic disease are still unclear. The study aims to evaluate the therapeutic potential of ISO as an NLRP3 inhibitor in the management of AS. For in vivo study, ApoE Our data show that ISO reduced atherosclerotic plaque formation by inhibiting NLRP3 inflammasome activation and inflammatory responses. Network pharmacology analyses showed that ISO might alleviate AS by suppressing the NOD-like receptor (NLR) pathway, leading to reduced inflammatory mediators. ISO dose-dependently suppressed IL-1β secretion through inhibiting NLRP3 inflammasome activation, displaying an IC Collectively, ISO emerges as a novel NLRP3 inhibitor and a potential therapeutic candidate for atherosclerotic disease. 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
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms rema Show more
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of autophagic proteins including ATG5, BECN1 and MAP1LC3/LC3 as well as LAMP1. Accordingly, silencing of 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
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
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
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
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
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonst Show more
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonstrated that 5'tRF-GlyGCC is overexpressed in BC tissues and negatively associated with patients' survival. Mechanistically, 5'tRF-GlyGCC binds to lactate dehydrogenase A (LDHA), enhancing its enzymatic activity and promoting glycolysis, which drives BC cell malignancy. This binding is mediated by the phosphorylation of LDHA at tyrosine 10, and facilitated by fibroblast growth factor receptor 1 (FGFR1), through the formation of a ternary complex that amplifies oncogenic signaling. Furthermore, 5'tRF-GlyGCC/LDHA axis induces macrophage infiltration and polarization toward an M2 phenotype, mediated by the chemokine CCL7, thereby reshaping the tumor microenvironment. Additionally, it is uncovered that the biogenesis of 5'tRF-GlyGCC is regulated by ALKBH3 and ANG, which also modulate LDHA activity. In vivo, targeting 5'tRF-GlyGCC/LDHA signaling significantly suppresses tumor growth and enhances the efficacy of immunotherapy. Collectively, these findings elucidate the pivotal role of 5'tRF-GlyGCC in BC progression, highlighting its potential as therapeutic target for BC treatment. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent disease, yet its genetic architecture remains incompletely characterized. We integrated genome-wide association Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent disease, yet its genetic architecture remains incompletely characterized. We integrated genome-wide association study data from multiple cohorts totaling nearly 3 million individuals of European ancestry and applied cross-trait genomic modeling of hepatic fat and seven cardiometabolic traits to construct an MASLD-specific polygenic architecture. We identified 128 risk variants across 100 loci and prioritized 55 effector genes, including established (e.g., 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
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
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
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. 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