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Acute ischemic stroke (AIS) poses a substantial risk of permanent disability and death globally, with neuroinflammation being a key driver of secondary brain damage post-stroke. Proprotein convertase subtilisin/kexin type 9 (PCSK9), beyond its well-accepted role in cholesterol metabolism through low-density lipoprotein receptor (LDLR) degradation, has emerged as an important mediator of neuroinflammation, making it an attractive new therapeutic target. This has sparked broader discussions about the potential pleiotropic effects of PCSK9 inhibitors on brain function. Proprotein convertase subtilisin/kexin type 9 mediates inflammation post-ischemia directly and indirectly by disrupting mTOR pathways. This stimulates signaling cascades associated with inflammation. For example, the nuclear factor-κB (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinase (MAPK) pathways in microglia activation. It also brings about reaction in astrocytes and increases the release of cytokines like interleukin-1β, interleukin-6, and tumor necrosis factor-α. Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein E receptor 2 (ApoER2) present on neurons cells, leading to further inflammatory effects. Proprotein convertase subtilisin/kexin type 9 indirectly increases lipoprotein(a) [Lp(a)], which promotes inflammation through the Lp(a)-TLR4 axis and induces endothelial dysfunction. Monoclonal antibodies (evolocumab, alirocumab) and small interfering RNA (siRNA) agents (inclisiran) are examples of PCSK9 inhibitors. According to preclinical studies, these inhibitors can mitigate neuroinflammation by blocking the M1 polarization of microglia and downregulating key pro-inflammatory factors while preserving the blood-brain barrier (BBB). They also inhibit neuronal apoptosis via the Bcl-2/Bax-caspase cascade and reduce the aggregation of β-amyloid (Aβ). Evidently, the findings from cardiac ischemia-reperfusion models show that pretreatment with PCSK9 inhibitors is effective with optimal neuroprotection. Recent clinical data support these mechanisms: PCSK9 inhibitors not only lower LDL-C and Lp(a) but also reduce systemic inflammatory markers (e.g., high-sensitivity C-reactive protein [hs-CRP], interleukin-6). Early adjunctive use of evolocumab in AIS is associated with reduced early neurological deterioration, highlighting that its effects extend beyond lipid lowering to modulating immune pathways in both the central and peripheral systems. As a promising multitarget therapeutic strategy for AIS, PCSK9 inhibitors target the interconnected pathways of lipid metabolism and neuroinflammation. Future studies should address critical challenges such as defining the optimal therapeutic time window, improving BBB penetrability, and refining patient stratification to translate their neuroprotective effects into clinical benefits for stroke patients. Show less

PIK3CA is one of the most frequently mutated genes in cervical cancer (CC). However, its clinical utility is hampered by paradoxical treatment-dependent outcomes, restricting its application in precision oncology. To address this issue, we constructed a high-resolution single-cell transcriptomic atlas of the CC tumor microenvironment. It was found that PIK3CA mutations induce a dichotomous TME, simultaneously associated with marked T-cell inflammation and resistance to adaptive immune responses. Malignant epithelial subsets induce CD8 Show less

Although recommended for cardiovascular (CV) risk stratification in adults, the role of lipoprotein(a) [Lp(a)] in hypertension is not fully established. To evaluate Lp(a) levels in adult outpatients with essential arterial hypertension. A retrospective, observational study was conducted in outpatients of both sexes, aged ≥ 18 years, with treated or untreated essential hypertension, who were consecutively evaluated at the Hypertension Unit, Excellence Hypertension Center, Sant'Andrea Hospital, Rome, Italy. Participants underwent office and out-of-office blood pressure (BP) measurements, as well as assessment of hypertension-mediated organ damage (HMOD). BP measurements were performed, and hypertension phenotypes were classified according to 2023 European hypertension guidelines. Lp(a) levels were measured, and the study population was stratified according to a Lp(a) cut-off value of ≥50 mg/dl. Due to the non-uniform distribution, absolute Lp(a) values were logarithmically transformed. A total of 230 patients with available Lp(a) values were included (42.6% women, mean age 66.3 ± 11.5 years, BMI 27.1 ± 4.5 kg/m2, office BP 137.1 ± 18.1/83.7 ± 11.0 mmHg, 24-hour BP 129.8 ± 14.5/79.6 ± 9.8 mmHg, Lp(a) 51.4 ± 65.3 mg/dL), among whom 32.2% had Lp(a) ≥50 mg/dl. There were significantly higher proportions of men (74.3% vs. 49.4%; P < 0.001), dyslipidaemia (97.3% vs. 75.0%; P < 0.001) and comorbidities (55.4% vs. 30.8%; P < 0.001) in patients with high Lp(a) than in those with normal Lp(a), who also received more frequently lipid lowering therapies (P < 0.001) and aspirin (P = 0.003). However, lower office systolic BP values (133.5±18.8 vs. 138.8±17.6 mmHg: P = 0.036) were observed in patients with Lp(a) ≥50 mg/dL than in those with < 50 mg/dl. Also, no significant differences for Lp(a) levels were observed among various hypertension phenotypes, as defined by office (P = 0.156) or out-of-office BP values (P = 0.065). No significant correlations were found between Lp(a) and office or out-of-office BP levels, both in treated and untreated hypertensive outpatients. In our population, Lp(a) levels were not associated with either office or out-of-office BP values, irrespective of antihypertensive treatment status. The role of Lp(a) in hypertension warrants further investigation. Show less

Amyloid-beta (Aβ) aggregation is the key component of neuritic plaques that drives Alzheimer's disease (AD) progression and cognitive decline. Although synaptic dysfunction strongly correlates with cognitive impairment, its underlying mechanisms remain unclear. Recently, the kynurenine pathway (KP) of tryptophan metabolism has emerged as a key contributor to AD pathology, and xanthurenic acid (XA), a naturally occurring end-product of the KP, has been implicated in neuroprotection. In this study, we investigated the neuroprotective effects of intranasally administered XA in an Aβ-induced AD mouse model. AD-like pathology was induced in mice by intracerebroventricular injection of Aβ Show less

Lipoprotein(a) (Lp(a)) is a genetically determined causal risk factor for cardiovascular disease, with approximately 20% of the population exhibiting elevated levels. While there are promising drugs in development, there are currently no approved therapies specifically designed to lower Lp(a) levels. For high-risk individuals with extreme levels of Lp(a), liver-directed genome editing could be an effective one-time solution. Genome editing approaches such as CRISPR and TALENs can reduce Lp(a) in LPA-transgenic mouse models, but they frequently induce large and potentially harmful genomic deletions. Here, we report the first application of TadA-derived cytosine base editing (CBE), delivered via helper-dependent adenovirus (HDAdV) and adeno-associated virus (AAV) vectors, to introduce premature stop codons into LPA. This strategy produced robust and durable lowering of circulating apolipoprotein(a) (apo(a)) in LPA-transgenic mice. Using SMRT-seq with single-molecule unique molecular identifiers, we quantified deletion events and found that CBE did not induce large deletions when targeting a single LPA site and produced only a small fraction (<4%) of large deletions when editing across multiple sites. In contrast, CRISPR-Cas9 cutting of LPA resulted primarily in large deletions. These findings demonstrate that CBE enables sustained reduction of circulating apolipoprotein(a) in an LPA-transgenic mouse model while largely preserving genomic integrity. Show less

Preclinical atherosclerosis and prediabetes are key targets of preventive medicine as their prevalence rises. Therefore, it is crucial to identify early processes and limit confounders such as lipid-lowering or antidiabetic therapy and advanced atherosclerosis. Proteomics enables the identification of biomarkers and molecular pathways related to atherogenesis in prediabetes. To investigate the relationship between prediabetes and preclinical atherosclerosis in apparently healthy individuals using a comprehensive proteomic approach. This cross-sectional, population-based study included 389 participants (mean age 49 ± 10 years; 47% males) from the Białystok PLUS cohort in Poland. Individuals with known diabetes, major cardiovascular, inflammatory, or malignant diseases, or those receiving steroidal or lipid-lowering therapy were excluded. Carotid ultrasound was used to assess preclinical atherosclerosis, and prediabetes was defined as impaired fasting glucose, impaired glucose tolerance, or HbA1c 5.7–6.4%. Proteomic profiling was performed using the Olink® Reveal platform, enabling deep profiling of 1050 proteins with the Proximity Extension Assay and next-generation sequencing readout, yielding log2-scaled NPX (Normalized Protein eXpression) values. In preliminary analyses, we identified proteins associated with prediabetes and then linked them to early atherosclerotic lesions. A block-sPLS-DA model integrating clinical and proteomic data revealed clear separation between participants with and without prediabetes. The clinical block comprised eight variables reflecting cardiometabolic status, whereas the proteomic block retained 45 proteins across two components. The heatmap shows pairwise Pearson correlations between selected serum proteins and clinical variables (Fig. 1). Vascular and age measures cluster together and share correlation patterns distinct from those of BMI and glycaemic parameters. A protein module including the ectodysplasin A2 receptor (EDA2R) and leiomodin 1 (LMOD1) correlates positively with age and vascular parameters, and inversely with GFR and HDL-C. Multivariable linear regression analyses were performed with selected vascular parameters as dependent variables and clinical covariates, together with proteins identified in Component 2, which are weakly related to clinical parameters and thus may represent novel biomarkers associated with prediabetes (Fig. 2). Expression of EDA2R (B = 0.05; An integrative block-sPLS-DA approach separated individuals with prediabetes from those without and revealed a proteomic signature independent of clinical covariates. Within this signature, the expression of LMOD1, EDA2R, and C16orf89 showed robust associations with atherosclerosis-related vascular traits. Enrichment analyses highlighted proteins involved in neuronal processes as candidate pathways linking early glucose disturbances with preclinical atherosclerosis. The online version contains supplementary material available at 10.1186/s12933-026-03128-w. Show less

This study aims to elucidate the role of Enterococcusin the progression from inflammatory bowel disease to colorectal cancer (CRC), with a focus on identifying key metabolites and host genes regulated by Enterococcusand their influence on CRC development. Using the database gutMGene, gutMDisorder and MACdb, we mined the key metabolites and human genes. We acquired the activated genes (panel 1) and inhibited genes (panel 2), and metabolite associated genes (MAGs, panel 3). Subsequent analyses included protein-protein interaction (PPI) network construction, functional enrichment, differential expression and survival analysis in CRC, and immune infiltration assessment. We screened 12 activated genes (Panel1: Show less

This study used a group-based multi-trajectory model (GBMTM) to identify distinct muscle health trajectories and examine their associations with physical activity (PA) in middle-aged and older adults. Data were obtained from 2818 middle-aged and older adults (aged ≥40 years) in the China Health and Retirement Longitudinal Study (2011-2015). Muscle health was assessed using muscle mass (appendicular skeletal muscle mass index), muscle strength (handgrip strength), and physical performance (5-time chair stand test). PA was assessed using the International Physical Activity Questionnaire Short Form. A GBMTM was applied to jointly identify longitudinal trajectories of muscle mass, muscle strength, and physical performance, and to evaluate their associations with PA. In this study, four muscle health trajectories were identified: low-function declining, moderate-function declining, moderate-function stable, and high-function stable group. Engaging in ≥150 min/wk of light PA (LPA), moderate PA (MPA), or vigorous PA (VPA) was associated with the moderate-function stable group (LPA: aOR = 3.44, 95% CI: 1.94 - 6.11; MPA: aOR = 2.83, 95% CI: 1.67 - 4.96; VPA: aOR = 2.88, 95% CI: 1.61 - 5.13) and the high-function stable group (LPA: aOR = 5.20, 95% CI: 2.44 - 11.19; MPA: aOR = 4.10, 95% CI: 1.92 - 8.73; VPA: aOR = 3.42, 95% CI: 1.55 - 8.55). In older adults aged ≥70 years, associations persisted for MPA and VPA. Distinct muscle health trajectories highlight individualized muscle aging and inform personalized PA guidance. Regular PA ≥150 min/wk across intensities was associated with more favorable longitudinal muscle health. Show less

Although the specific reasons for exercise motivation and the emotions felt during it are both important for physical activity (PA), little is known about how they combine to form distinct psychological profiles. This study used a person-centered approach to identify these latent profiles based on specific exercise motives and exercise-induced emotions among Chinese college students, and examined their associations with gender and PA. We recruited 1,586 undergraduates from a university in southern China ( Show less

This study aims to investigate the underlying pathophysiological relationship between obesity and osteoporosis (OP) in obese individuals, involving lipid metabolism, inflammation, and bone mineral density (BMD). Data from 318 patients diagnosed OP at our hospital between January 2023 to December 2025 were collected and analyzed. The basic information of the patient included gender, age, BMI, drinking and smoking history, diabetes, hypertension and bone mineral density (T-scores) were recorded. Baseline peripheral blood was employed to calculate lipid markers and inflammatory cytokines. Linear regression and mediation analyses were employed to assess the relevance and differences. Increased level of blood lipids and inflammatory cytokines were associated with increased risks of OP in obesity. Compared to normal-weight individuals, obese subjects exhibited significantly lower BMD. Dysregulated lipids (TC, TG, HDL-C, ApoB) negatively correlated with BMD in obesity. Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8) inversely associated with BMD, while anti-inflammatory IL-10 showed positive association. Hyperlipidemic obese individuals had elevated inflammatory cytokines (TNF-α, IL-1β) and exacerbated BMD loss. Mediation analysis revealed TNF-α mediated 41.91% and IL-6 mediated 33.20% of the TC-BMD association; TNF-α and IL-6 mediated 28.76% and 37.38% of HDL-C-BMD effects, respectively. Obesity-associated dyslipidemia drives BMD loss partly through inflammation-mediated pathways. Key inflammatory cytokines significantly mediate lipid metabolism’s impact on bone health. Targeting lipid-inflammatory crosstalk may optimize OP management in obese populations. Show less

To use compositional data analysis to examine the associations of daily movement behaviors with body composition, and to predict changes in body composition after reallocating time among behaviors in preschool-aged children. 268 preschoolers were included in the cross-sectional study. An accelerometer was used to assess sedentary behavior (SB), light and moderate-to-vigorous physical activity (LPA and MVPA). A parental report was used to collect sleep time. Bioelectrical impedance analysis was employed to assess body composition. Compositional linear regression analysis was employed to explore how daily movement behaviors were associated with body composition. Compositional isotemporal substitution analysis was employed to estimate changes in body composition after reallocating time among behaviors. 24-h movement behaviors composition significantly predicted fat-free mass index (FFMI), soft lean mass index (SLMI), and skeletal muscle mass index (SMMI), but not fat mass index, percent body fat, and bone mineral content index. The compositional isotemporal substitution analyses consistently showed that increasing MVPA at the expenses of SB was positively associated with FFMI (+0.328 kg/m The findings highlight the importance of MVPA in improving preschoolers' body composition. Increasing MVPA at the expenses of SB may be a strategy to improve body composition in preschoolers. Show less

Atherosclerotic cardiovascular disease (ASCVD) continues to be a major global health burden, with substantial residual cardiovascular risk remaining. Growing evidence highlights the liver’s pivotal role in the onset and development of ASCVD through multiple interconnected pathways. As the metabolic center of the body, the liver regulates the synthesis, secretion, and clearance of several atherogenic lipoproteins while simultaneously serving as a systemic inflammation amplifier, producing cytokines, acute-phase proteins, and coagulation factors. Traditional liver-targeted therapies, such as statins, have demonstrated that regulating liver metabolism can confer significant cardiovascular benefits. Subsequently, advances in nucleic acid-based drugs and in vivo gene-editing tools have broadened this strategy, enabling accurate and durable modulation of hepatic gene expression. However, recent clinical trials suggest that improvements in laboratory biomarkers do not always translate into proportional reductions in major adverse cardiovascular events. Moreover, the long-term safety and durability of lipid nanoparticles and gene-editing platforms remain ongoing concerns. Future research should focus on the classification of patients based on multiple omics data, and distinguish those whose main problem is metabolic disorder from those who are mainly at high risk of inflammation, thereby facilitating personalized therapeutic targeting. Overall, current evidence indicates that the liver represents a convergent therapeutic target for modulating both lipid metabolism and inflammation, offering a promising opportunity for deeper and more durable cardiovascular risk reduction. Show less

While typhoid fever affects both sexes at an equal rate, males are at a higher risk for intestinal perforation, which increases mortality. The mechanisms behind the increased morbidity of typhoid fever in human males remain an important but understudied question. Using a 129X1/SvJ (NRAMP Show less

Neurodegenerative diseases such as Huntington's Disease (HD) have a significant impact on healthcare accessibility and costs. A fatal genetic condition, characterized by the progressive loss of striatal neurons, HD is hindered by the lack of endogenous repair in the adult brain. Recent efforts toward protecting neural circuits through neurotrophic support using brain-derived neurotrophic factor (BDNF) have been suboptimal due to the protein's short half-life and limited diffusion. Addressing this, adeno-associated viral vectors (AAV) can be employed as a delivery tool to spatially transduce cells, enabling the localised production of BDNF with consequential neuron protection and/or plasticity, yet present their own constraints. To overcome these known challenges of AAV gene delivery, an injectable, physiologically stable hydrogel-mimic of the brain's extracellular matrix was fabricated to encapsulate the AAVs. This smart system both shielded and constrained the AAV; optimising transfection and therefore elevated and sustained BDNF presentation at the target site. Here, we achieved high neuroprotection using AAVDJ-BDNF delivered through a hydrogel formed via self-assembling peptide nanoscaffolds. These findings support the notion that the spatiotemporal release of BDNF to striatal neurons, facilitated by engineered biomaterial delivery systems, demonstrates tremendous promise by enhancing the efficacy of gene therapy targeted at slowing neurodegenerative disease progression. Show less

Atherosclerosis (AS) is the main pathological basis of atherosclerosis-related cardiovascular and cerebrovascular diseases. The phenotypic conversion and death mechanisms of vascular smooth muscle cells (VSMCs) are crucial during its development. This study reveals the molecular mechanisms of the C1qbp-DLAT axis and the U2AF2 (U2 Small Nuclear RNA Auxiliary Factor 2)-NEAT1 network in regulating cuproptosis in AS. In this study, an ApoE The study revealed elevated copper ion levels and dysregulated cuproptosis-related genes in an AS model. U2AF2 stabilized C1qbp mRNA, enhancing C1qbp protein expression, which promoted DLAT oligomerization to regulate cuproptosis. LncRNA NEAT1 facilitated this process by scaffolding U2AF2-C1qbp mRNA interaction. Targeted inhibition of U2AF2 significantly improved AS pathological characteristics, reduced lipid deposition, collagen deposition and macrophage infiltration within the plaque, increased smooth muscle cell content and lowered serum levels of total cholesterol (TC), total triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). This study revealed the role of the U2AF2-C1qbp-copper death regulatory axis in the development of AS, providing new targets and a theoretical basis for the treatment of AS. Targeted inhibition of U2AF2 may become an effective strategy to delay progression of AS. Show less

This study evaluated the efficacy of combining personalized acupuncture with accelerated deep transcranial magnetic stimulation (adTMS) for mild cognitive impairment (MCI). In this randomized, double-blind, controlled trial, 120 MCI patients were assigned to a Combined group (personalized acupuncture + active adTMS), a Single Stimulation group (active adTMS + sham acupuncture), or a Placebo group (sham TMS + sham acupuncture). The primary outcome was the change in Montreal Cognitive Assessment (MoCA) score at 12 weeks. Secondary outcomes included P300 latency, magnetic resonance spectroscopy (MRS) NAA/Cr ratio, serum brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), interleukin-6 (IL-6), and the Modified Barthel Index (MBI). The Combined group showed a significantly greater improvement in MoCA scores (3.2 ± 1.3 points) compared to the Single Stimulation (1.9 ± 1.2 points; mean difference 1.3, 95 % CI 0.4 to 2.2) and Placebo groups (1.1 ± 1.0 points; mean difference 2.1, 95 % CI 1.2 to 3.0). The Combined group also demonstrated greater reductions in P300 latency and increases in NAA/Cr ratio and serum BDNF levels than the other groups. The combination of personalized acupuncture and adTMS significantly improves cognitive function in MCI patients, supported by positive changes in electrophysiological and metabolic markers. This integrative approach represents a promising non-pharmacological strategy for MCI.Trial registration: International Traditional Medicine Clinical Trials Registry (ITMCTR2025000652). 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 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

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of early onset atherosclerosis. Evinacumab, an angiopoietin-like protein 3 (ANGPTL3)-inhibiting monoclonal antibody, lowers LDL-C independently of LDL receptor activity. However, its effects on other lipid-related markers remain poorly investigated in real-world clinical practice. We herein report a 54-year-old Japanese woman with genetically confirmed compound heterozygous familial hypercholesterolemia (FH) treated with evinacumab in combination with other lipid-lowering agents. Lipoprotein apheresis was continued every two weeks throughout the treatment. Serum sampling before and after evinacumab administration found that, following evinacumab initiation, LDL-C decreased from 324 to 205 mg/dL (reduction of 119 mg/dL, -36.7%) and triglycerides from 155 to 51 mg/dL (reduction of 103 mg/dL, -66.8%). Notably, atherosclerosis-related markers showed substantial reductions, with remnant-like particle cholesterol (RLP-C) decreasing from 10.5 to ＜2.0 mg/dL, small dense LDL-C (sdLDL-C) from 80.2 to 22.1 mg/dL, and malondialdehyde-modified LDL (MDA-LDL) from 105 to 87 mg/dL. Apolipoproteins (ApoB, ApoC2, ApoC3, ApoE, and ApoA5) decreased as well. No significant changes were observed in lipoprotein (a), free fatty acids, interleukin-6, or high-sensitivity C-reactive protein levels. This is the first clinical report to comprehensively evaluate the lipid-modifying effects of evinacumab in a Japanese HoFH patient. In this case, evinacumab was highly efficacious against atherosclerosis-related markers and apolipoproteins, beyond simple LDL-C reduction, suggesting additional cardiovascular benefits. These findings provide mechanistic insights that may inform therapeutic strategies for the management of HoFH. Show less

Public responses to climate change are influenced by interpretations of scientific information and individual differences. Understanding these factors can improve targeted climate communication. We conducted a nationally representative survey of Lithuanian adults ( LPA using three climate-belief indicators supported a two-class solution among respondents with complete data ( The findings reveal heterogeneity in climate-change beliefs in Lithuania and suggest that audience segmentation and psychologically informed communication strategies may enhance climate-related science communication. Show less

Cholinergic dysfunction is a key contributor to cognitive impairment observed in aging and neurodegenerative disorders such as Alzheimer's disease (AD). Although acetylcholinesterase (AChE) inhibitors have been the mainstay of symptomatic treatment for over two decades, their limited efficacy and adverse effects underscore the need for alternative therapeutic approaches. Recent evidence indicates that mechanical stimulation can modulate neuronal and glial signaling through mechanotransduction, suggesting a potential strategy to enhance cognitive function via non-pharmacological means. Here, we developed a head-mounted vibrotactile stimulation system (HVSS) that delivers controlled vibration to the cranium and evaluated its effects in a pharmacological model of acute cholinergic dysfunction induced by scopolamine. To this end, male C57BL/6 mice received scopolamine (1 mg/kg, i.p.; on days 7, 14, and 28) and were exposed to daily vibrotactile stimulation at 20, 40, or 80 Hz for 28 days. Behavioral performance was assessed using passive avoidance and Morris water maze tests, followed by biochemical and histological analyses. HVSS at 40 Hz and 80 Hz significantly improved cognitive performance, enhanced hippocampal cholinergic function, reduced oxidative damage, and upregulated memory-related signaling genes, including BDNF, PI3K, AKt, ERK1/2, CREB, and CAMK4. These findings suggest that high-frequency HVSS improves memory hippocampal cholinergic function via activation of memory-related signaling pathways, highlighting its potential as a safe, non-pharmacological neuromodulatory strategy for cholinergic dysfunction-related cognitive decline. Show less

To assess the feasibility of intravoxel incoherent motion imaging (IVIM) for detecting renal injury in an obese rat model and monitoring renal function after weight-loss therapy. Forty-two male rats were randomly divided into high-fat diet (HF) and standard diet (St) groups ( The D, D* and IVIM is a potential tool for noninvasive and longitudinally detection of early obesity-related renal injury and renal function improvement after weight-loss therapy. The online version contains supplementary material available at 10.1186/s12880-026-02288-1. Show less

Luteolin, a flavonoid naturally present in a variety of fruits, vegetables, and medicinal plants, has been recognized as a potentially effective neuroprotective nutraceutical because of its remarkable anti-inflammatory, antioxidant, and neurotrophic properties. Increasing evidence suggests that neuroinflammation and oxidative stress are major contributors to cognitive decline and neuronal degeneration in several prominent neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). Luteolin significantly inhibits microglial activation, reduces pro-inflammatory cytokine production, modulates the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, and enhances Nrf2-mediated antioxidant mechanisms. Furthermore, it promotes synaptic plasticity through brain-derived neurotrophic factor (BDNF)-associated pathways and mitigates the aggregation of pathological proteins, including Aβ, tau, α-synuclein, and mutant huntingtin. Preclinical studies consistently demonstrate substantial improvements in cognitive function, motor performance, demyelination, and neuronal viability in models of AD, PD, MS, and HD. Preliminary clinical observations also indicate prospective advantages for cognitive function, regulation of inflammatory responses, and alleviation of symptoms, particularly concerning AD and MS. Notwithstanding these encouraging outcomes, obstacles persist due to luteolin's restricted bioavailability, ideal dosing parameters, and the translational discrepancies between experimental models and human pathophysiological conditions. In summary, luteolin emerges as a noteworthy candidate for nutraceutical-oriented approaches designed to alleviate neuroinflammation and cognitive deterioration in the context of neurodegenerative diseases. Show less

TyHGB is a novel insulin resistance (IR)-related indicator, and its association with coronary heart disease (CHD) remains unclear. Additionally, studies have shown a close correlation between the diagonal earlobe crease (DELC) and CHD, yet it has not been fully applied in clinical practice to date. Therefore, this study constructed and validated a diagnostic model for CHD by combining TyHGB and DELC. A total of 1664 patients suspected of CHD who underwent coronary angiography (CAG) in the Department of Cardiology, Chengde Central Hospital from September 2021 to April 2025 were recruited for this study. Participants were categorized into a CHD group ( Age, sex, hypertension, diabetes, CR, Lp(a), TyHGB, and DELC were identified as independent risk factors for CHD through multivariate logistic regression analysis ( Both TyHGB and DELC have been identified as independent risk factors for CHD, with a linear relationship observed between TyHGB levels and CHD risk. A diagnostic model for CHD, developed by integrating TyHGB, DELC, and traditional risk factors, demonstrates strong diagnostic efficacy. The online version contains supplementary material available at 10.1186/s12944-026-02880-y. Show less

Health apps designed to monitor, motivate, and educate people towards their health goals are getting more users and features each time. These apps offer valuable support for self-managing health behaviors and achieving long-term objectives. However, there is limited understanding of user preferences regarding essential app features. The aim of the study is to get insights about potential users' preferences, in order to tailor better apps for lifestyle management. We conducted a three-part web survey with 389 respondents from four countries as part of the DigiCare4You European Union (EU) project. In the first part, we collected the socioeconomic characteristics and health status of each respondent. In the following stage, we asked five questions on a Likert scale to ascertain the individual level of usage and general attitude towards technology. Finally, we performed a discrete choice experiment (DCE) using an unlabeled design and estimated the odds ratio for each feature using conditional logit analysis. We also ran alternative estimations stratifying by non-communicable disease (NCD) patients and non-NCD patients, and explored latent profile analysis (LPA) to understand whether the general attitude towards technology impacts the preference pattern between users. The DCE revealed that respondents showed a clear preference for monitoring physical health over emotional status. They favored receiving lifestyle achievement notifications weekly rather than daily, and daily rather than more frequently. Similarly, respondents preferred uploading body weight measurements on a weekly or monthly basis rather than daily. Users expressed a preference for collaborating with their doctors to set exercise and diet goals, rather than either deciding independently or delegating entirely to their doctors. End-users also show a pattern of preferring notifications for goals instead of challenging other users. Preferences regarding the subjects of health content between workout routines, food recipes, and new scientific evidence were not significant; also, no statistical significance was found for the decision between follow-up visits with their doctor in person or remotely. LPA returned two groups regarding their general attitude towards technology: a lower, an intermediate, and a higher usage in their private life based on their responses to the questionnaire. Stratified DCEs have shown heterogeneity of users' preferences according to their specific attitude towards technology. Our study indicates that potential mobile health (mHealth) app users managing chronic conditions prefer platforms that enable shared responsibility with their doctors in defining health goals while having an intermediate level of interaction frequency with the app. These findings are key to tailoring mHealth apps that can optimize motivation triggers, support healthier lifestyles, and empower patients with chronic conditions. Show less