The relationship between actin dynamics and remyelination after intracerebral hemorrhage (ICH) remains unclear. This study aims to investigate the mechanism by which scalp acupuncture (SA) regulates remyelination in acute ICH rats through the PAK1/LIMK1/CFL1 signaling pathway. The Male Sprague-Dawley rats were used to establish the ICH model by autologous blood injection. The treatment group SA intervention, with the selective inhibitor of PAK1, IPA-3, used as a positive control. The regulatory effect of SA on the PAK1/LIMK1/CFL1 signaling pathway after ICH was evaluated using neurological function assessment, Luxol fast blue staining, Western blot, and immunofluorescence staining. On the third day after ICH, there is a peak in p-PAK1 levels, and SA intervention has the best therapeutic effect. Therefore, the third day was chosen for the IPA-3 positive control experiment. The study found that the PAK1/LIMK1/CFL1 signaling pathway is activated after ICH, leading to the inhibition of filamentous actin depolymerization, resulting in severe myelin sheath loss and neurological dysfunction. Following SA or IPA-3 intervention, the PAK1/LIMK1/CFL1 pathway is inhibited, leading to the depolymerization of actin filaments and a reduction in the degree of myelin sheath loss, as well as improvement in symptoms of neurological dysfunction. SA regulates the homeostasis of actin proteins by inhibiting the PAK1/LIMK1/CFL1 signaling pathway, promoting neuronal myelin sheath regeneration after acute ICH, and improving neurological behavioral disorders.

Sepsis-induced acute myocardial injury (AMI) is a major contributor to mortality in septic patients, yet its molecular underpinnings remain incompletely understood. While previous studies have largely focused on transcriptional changes, the role of alternative splicing (AS) in septic cardiomyopathy has not been systematically explored.

We employed two widely used murine models of sepsis-cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection-to investigate transcriptomic dysregulation in the heart. Through RNA sequencing, we analyzed both differentially expressed genes (DEGs) and differentially alternative splicing events (DAS), followed by bioinformatic enrichment analysis. Key AS events were validated via RT-PCR and qPCR.

We identified hundreds of sepsis-induced DAS events, with skipped exon (SE) being the most prominent subtype in both CLP and LPS models. Integration of DEG and DAS datasets revealed 127 overlapping genes involved in inflammatory and stress-related pathways, including MAPK, AMPK, and JAK-STAT signaling. Splicing factors such as Cirbp, Rbm3, Cir1 were dysregulated under septic conditions. Validation experiments confirmed model-specific AS events in genes including Per1, Map3k6, and Septin4, which are implicated in circadian regulation, inflammation, and cytoskeletal remodeling, respectively.

This study is the first to comprehensively map AS changes in the septic myocardium using dual models. Our integrative approach reveals that alternative splicing represents a critical and underappreciated regulatory layer in septic cardiac injury, supported by both transcript- and protein-level evidence. These findings broaden the understanding of transcriptomic complexity in sepsis and highlight new molecular targets for therapeutic intervention.

Sepsis represents a life-threatening syndrome driven by dysregulated host responses in which inflammation, coagulation, and endothelial dysfunction intersect. Increasing evidence suggests that endotheliopathy is a dynamically interacting component linking systemic inflammation, immunothrombosis, and microvascular dysfunction. Rather than acting as a singular upstream trigger, endothelial dysfunction evolves in parallel with platelet, neutrophil, and monocyte activation, forming a self-amplifying thromboinflammatory network that drives organ failure.

The vascular endothelium maintains hemostatic balance through anticoagulant pathways mediated by thrombomodulin, endothelial protein C receptor (EPCR), and antithrombin, supported by a protective glycocalyx layer. During sepsis, pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) trigger the degradation of the glycocalyx, deactivation of the vascular stabilizing regulator Tie2, and shedding of thrombomodulin and EPCR, ultimately leading to capillary leakage and a procoagulant endothelial phenotype. Concurrently, excessive immunothrombosis, characterized by tissue factor expression, platelet activation, and neutrophil extracellular trap (NET) formation, amplifies endothelial injury and impairs microcirculation. Sepsis occurs across a spectrum of clinical states, with sepsis-induced coagulopathy (SIC) representing an early, potentially reversible stage marked by thrombin generation and suppressed fibrinolysis, whereas progression to overt disseminated intravascular coagulation (DIC) entails consumptive coagulopathy and organ failure. Biomarker-based phenotyping using syndecan-1, soluble thrombomodulin, angiopoietin-2, and NET-related markers enables mechanistic stratification and therapeutic targeting.

Recognition of endotheliopathy as an interacting component of SIC provides a unifying framework for understanding disease progression and identifying temporally appropriate therapeutic targets. Emerging endothelial-directed therapies, including heparanase inhibitors, Tie2 agonists, antithrombin and thrombomodulin supplementation, and NET-targeted interventions, represent a paradigm shift toward precision medicine in managing sepsis. Integrating endothelial biomarkers and immunothrombotic phenotyping into adaptive trial designs will be critical to advancing approaches for personalized vascular and immune modulation. Recognition of endotheliopathy as the central driver of sepsis-induced coagulopathy provides a unifying framework for understanding the mechanisms involved and driving therapeutic innovation.

Mitochondrial ferritin (FtMt), first identified by Levi et al., is an iron-storage protein with high homology with cytoplasmic ferritin. It is mainly expressed in metabolically active tissues and exhibits distinct physiological and biochemical properties compared cytoplasmic ferritin. Over the past few decades, significant attention has been drawn to the unique structural and functional characteristics of FtMt that differentiates it from conventional ferritin. Mitochondrial ferritin specifically located on the mitochondrial exhibits unique advantages in mitochondrial redox balance through isolating iron within mitochondria, reducing oxidative stress and maintaining mitochondrial homeostasis. Moreover, it modulates the labile iron pool within mitochondria, facilitating the biosynthesis of iron-sulfur clusters and supporting cellular respiration. This review comprehensively discusses the pivotal function of FtMt in regulating mitochondrial redox homeostasis and its impact on cell fate decisions, specifically, its influence on apoptosis, ferroptosis through alterations in mitochondrial integrity. We also summarize recent advances in understanding the association between FtMt dysregulation and various diseases, emphasizing its implications in neurodegenerative diseases, cardiovascular disorders and cerebrovascular pathologies. By critically evaluating emerging evidence, this article aims to provide translational insights into targeting FtMt and mitochondrial redox homeostasis as therapeutic strategies for mitigating these clinically significant diseases.

Long-term domestication and cultivation have led to the differentiation of Salvia miltiorrhiza genetic resources in different regions of China, accompanied by differences in the accumulation of pharmacological components represented by tanshinones in the roots. Tanshinone, as a key biomarker with significant therapeutic effects on cardiovascular and cerebrovascular diseases, has become the primary target for improvement in S. miltiorrhiza breeding. It is particularly important to deeply analyze the differentiation of tanshinones biosynthetic pathways in S. miltiorrhiza of different ecotypes, systematically revealing the evolution mechanism of geoherbs driven by metabolic networks. Based on integrated omics strategies, the metabolic regulatory network of tanshinones was constructed in different ecotypes, and WRKY70 was identified as a core transcription factor in the regulatory network of tanshinones metabolism. Transgene, Yeast-one-hybrid, EMSA, and Dual-LUC demonstrated that WRKY70 positively regulates tanshinones biosynthesis by targeting the promoter of CYP76AK1 and ABCG1. Yeast-two-hybrid, BiFC, Luciferase complementation, and Co-IP confirmed that WRKY70 formed a stable protein complex with SnRK2.6, which in turn mediated the ABA signaling pathway dependent tanshinones metabolic regulation and drought stress adaptation. Overall, we report that a bifunctional transcription factor, WRKY70, promotes tanshinones synthesis while enhancing plant adaptation to drought, which is expected to be used as a breeding target to save the deficiency of tanshinones and enhance stress resistance in specific ecotype S. miltiorrhiza.

Regulation of LDLR gene expression plays an important role in the development of atherosclerotic diseases including heart attack and stroke. Although LDLR regulation by sterol response elements has been well characterized, the functional significance of other noncoding regions at the LDLR locus remains poorly defined. In this study, we developed and applied a high throughput CRISPR screen to test the functional importance of candidate LDLR cis-regulatory elements (CREs) in their native genomic context. In total, we found 25 discrete regions to exhibit a significant impact on LDLR expression. For one of these regions with particularly strong activity in the first intron, we validated the presence of an enhancer by confirming that its disruption reduced endogenous LDLR expression while its insertion upstream of a minimal promoter augmented reporter gene expression. We then applied a massively parallel reporter assay to fine map enhancer activity within this region to a 129 bp interval that is highly conserved among vertebrates, exhibits biochemical hallmarks of enhancer activity, is enriched for transcription factor binding motifs, and contains a common genetic variant (rs57217136) that has been associated with human LDL cholesterol levels by genome-wide association studies. Overall, these findings demonstrate the power of CRISPR screening to interrogate candidate CREs and clarify the functional landscape of noncoding sequences at the LDLR locus.

Hearing loss (HL) negatively impacts all aspects of health, yet poor access to hearing healthcare (HHC) among adults is a pervasive public health problem. The inaccessibility of HHC is amplified in rural adults. Rural health clinics (RHC) are a critical healthcare system tasked with improving health in rural communities and the objective of this study is to assess the prevalence of HL and the utilization of HHC within RHCs.

Using cross-sectional study design, adults were recruited from 10 RHC throughout rural Kentucky, mostly within Appalachia. The primary outcomes were (1) presence of HL on screening and (2) history of a hearing test within the last year and within the last 5 years. Additional outcomes included sociodemographic and overall health status. Descriptive, univariate, and multivariate analyses were conducted.

A total of 403 participants (mean age 51.1) were recruited. A total of 388 participants completed a hearing screening and 271 (70%) screened positive for HL, yet only 3.4% and 13.4% of participants had undergone a hearing test in the past 1 and 5 years, respectively. Adults with higher education levels were less likely to have HL (OR 0.47; 95% CI 0.26-0.86; p = 0.02). HL in this sample was associated with noise exposure (OR 1.97; CI 1.08 to 3.61; p = 0.03) and poorer mental health (OR 3.48; 95% CI 1.74-7.18; p = 0.001).

Rural adults in RHC have a high prevalence of HL and low utilization of HHC. Promoting and expanding access to HHC within RHCs may improve hearing health among rural adults.

As global populations age, interpersonal age discrimination has emerged as a critical barrier to mental health and well-being in older adults. The team examined the adverse effects of interpersonal age discrimination on older adults' psychological well-being, including self-rated health, mental health, social adaptability, and life satisfaction.

Using nationally representative data from the China Longitudinal Ageing Social Survey (CLASS), the analysis quantified the impact of ageism on multidimensional health outcomes.

Results indicated that age discrimination significantly worsened mental health and subjective well-being, partly by fostering negative ageing attitudes and limiting social engagement. Mechanism analyses further revealed that discrimination hindered older adults' access to smart ageing technologies, thereby impeding health management and social connectivity. Heterogeneity analyses showed that rural residents, pension recipients, and employed older adults experienced relatively attenuated effects, while gender and education level had no significant moderating influence. Moreover, age discrimination was associated with increased medical expenditures and decreased spending on cultural and recreational activities.

The findings highlighted the importance of enhancing intergenerational interactions to mitigate the psychological harms of age discrimination. These results suggested that nursing professionals play a vital role in addressing interpersonal ageism, particularly by facilitating digital inclusion and identifying ageism-related distress to support older adults' comprehensive well-being.

Rapid population aging and the intensifying digitalization of everyday life are unfolding simultaneously in China. While prior studies have largely examined pairwise associations among digital inclusion, social engagement, mental health, and overall health status, few have evaluated an integrated, theoretically grounded pathway linking these domains in later life.

This study aims to quantify the direct and indirect pathways through which digital inclusion influences older adults' overall health status, social engagement, and mental health, specified as sequential mediators.

We analyzed the newly released, nationally representative data from the 2023 wave of the China Longitudinal Aging Social Survey, comprising 9918 adults aged 60 years or older. Overall health status was assessed using 3 self-rated health (SRH) indicators: current SRH, SRH relative to age peers, and SRH relative to last year. Digital inclusion was measured through digital access, device proficiency, and digital ability. Social engagement captured social support, frequency of participation in community or voluntary activities, and nononline activities. Mental health included depressive symptoms, social adaptation, and life satisfaction. Analyses included descriptive statistics, multivariable hierarchical linear regressions, and structural equation modeling to estimate direct and mediated effects (2-sided; α=.05).

Older age, chronic disease, and functional limitations were associated with poorer overall health status, whereas higher education and current employment were associated with better health status. Digital inclusion was positively associated with social engagement (β=.50), which in turn was positively associated with mental health. Mental health showed the strongest association with SRH (β=.74). The direct path from social engagement to overall health status was nonsignificant (P=.34), indicating that participation influences health primarily through psychological pathways. In regression analyses, digital inclusion modestly improved model fit for health status outcomes, while adding mental health produced a greater increase.

Digital inclusion promoted active aging indirectly, by expanding social engagement and enhancing mental health, thereby improving overall health status. Policy efforts should prioritize narrowing the digital divide by improving digital skills and capability, rather than access alone. Meaningful opportunities for social engagement should also be expanded to strengthen community-based mental health support. In addition, strategies should be tailored to the differing needs of urban and rural settings.

Cardiovascular risk factors and depressive symptoms are common in adolescents and young adults with type 1 diabetes (T1D). While exercise improves cardiovascular health and metabolic control, its mental health benefits remain unclear. High intensity interval training (HIIT) has shown an improvement in aerobic capacity without a detrimental decline in blood glucose and home-based HIIT has reduced barriers towards exercise in adults with T1D. There is scant evidence in children with T1D.

Evaluate metabolic effects of HIIT (time in range, glycemic variability, HbA1c, lipid profile, blood pressure, and body composition). Secondary outcomes included assessing aerobic capacity, strength endurance, depressive symptoms, and barriers towards physical activity.

Prospective, longitudinal, multicenter study involving adolescents (aged 12 and 19) with T1D diagnosed for ≥1 year, at least Tanner stage III, HbA1c between 7-11.5%, and a total daily insulin dose ≥0.7 units/kg/day. Outcomes were assessed at baseline, 1, 3, and 3 months after intervention.

22 participants completed intervention (mean age: 14.32±1.62 years) showing no changes in HbA1c or time in range. Mean blood glucose significantly declined during sessions (191.61±13.69 to 159.95±13.04 mg/dL, p<0.001), with no increase in time in hypoglycemia. Body lean mass increase and fat mass decline after 3 months of training (40.84 ± 8.53 to 42.35 ± 8.34, p<0.001 and 29.94 ± 8.99 to 28.85 ± 9.20, p=0.010, respectively). Maximal oxygen consumption improved once the intervention was completed (33.86±4.00 to 36.43±3.64, <0.001). Lack of motivation and concerns regarding weather decreased after training (73% vs. 59% and 27% vs 14%, respectively).

HIIT improved physical fitness and body composition maintaining glycemic stability, being a safe regimen to encourage physical activity in adolescents with TD1.