Primary nephrotic syndrome (NS) is associated with systemic effects that may impact cardiac function, although several studies have explored left ventricle in children with NS. Few studies investigated right ventricle (RV) in this disease. Therefore, the study aimed to provide a comprehensive evaluation of RV functions in children with primary NS using echocardiography.

A case-control observational study was conducted from January 2022 to August 2024 on 40 primary NS patients with steroid-resistant nephrotic syndrome (SRNS) and steroid-sensitive nephrotic syndrome (SSNS), alongside 40 healthy controls. All participants underwent RV assessments using conventional parameters, tissue Doppler imaging (TDI), two-dimensional speckle-tracking echocardiography (2D STE), and three-dimensional echocardiography (3DE).

Significantly lower s', e' in NS patients compared to controls, especially lower in SRNS compared to SSNS. Significantly higher E/e' and Tei index was detected in the NS group compared to controls (p = < 0.001) and more pronounced in SRNS. RV free wall strain longitudinal strain (RVFWLS) and RV four chamber longitudinal strain (RV4CSL) were significantly reduced in NS group compared to controls. 3D auto RV-derived ejection fraction (EF), TAPSE, stroke volume and septal strain were lower in NS compared to controls(p = < 0.001); however, there are no significant differences between SSNS and SRNS. Significant correlations were detected between some echocardiographic parameters and serum cholesterol, albumin, and creatinine.

Integrative use of variable echocardiographic modalities allows detection of subclinical alterations in RV function in children with primary NS, with more affected parameters in SRNS. Therefore, regular surveillance of RV functions in primary NS should be considered.

Medical payment plans shape financial protection and access to care, but their associations with costs, disease progression and survival in hypertension remain poorly characterised. We analyse 8,004,039 inpatient admissions among 4,675,738 patients in Henan, China, from 2019 to 2024 using mixed-effects, multistate and survival models, and externally validate the non-mortality findings in Xinjiang. Compared with self-pay, urban employee, urban-rural resident and commercial or other insurance are associated with 24.95%, 8.71% and 16.64% higher total inpatient expenditure, respectively, while all non-self-pay plans are associated with 89.47-97.56% lower out-of-pocket spending. Urban employee insurance shows the most favourable survival (adjusted hazard ratio for all-cause mortality, 0.72; 95% confidence interval, 0.68-0.76), whereas government-supported or medical assistance arrangements show the poorest survival (1.33; 1.23-1.43) and the greatest expected time in multimorbidity. Sensitivity analyses and external validation support the direction of the main non-mortality findings. These observational associations do not isolate payment-plan effects and may reflect differences in benefit scope, care access and participants' underlying health and social vulnerability. Narrowing reimbursement gaps alone may therefore be insufficient without broader improvements in service coverage and access.

Despite the female predominance in age- and immune-associated diseases, the pathways underlying sex differences in healthy immune aging remain incompletely understood. Here, we analyze a multi-ethnic single-cell transcriptome of healthy human immune aging (35% Asian), comprising 3.8 million peripheral blood mononuclear cells (PBMCs) from 1,828 individuals aged 19-97 years. Prominent peaks of differential gene expression around 40 (mainly CD4 T cells) and after 60 (mainly CD8 T cells) years of age were accompanied by an age-dependent decline in RNA/protein homeostasis and inflammatory PBMC polarization with sex-dependent kinetics. While females displayed sustained CD8 T cell activation and late-life aging signatures in CD4 T, NK, and B cells, males exhibited early-life fluctuations in CD4 T cell immunometabolism associated with hypomethylation of SSH3 at chromosome 11q13. Deep learning-based biological age clocks stratified for sex outperformed sex-combined models, learning from transcriptional immune trajectories. We thus unravel a nonlinear PBMC aging whereby targeting sex-specific pathways might allow precision geromedicine.

Conventional critical-sized bone defect (CSD) implants frequently suffer from geometric mismatches and interfacial gaps with the host bone, leading to suboptimal osteogenesis and poor osseointegration. Herein, inspired by kirigami and origami concepts, we propose a novel approach for fabricating bioceramic scaffolds from pliable, trimmable hydrogel-based ceramic precursors composed of photosensitive hydrogel components and nano-hydroxyapatite. The hydrogel precursor exhibits superior ductility and elasticity, enabling convenient tailoring to the contours of complex bone defects, such as cranium. After sintering, the hydrogel-derived bioceramic scaffolds exhibit ultra-low linear shrinkage (∼10%), well-defined structural fidelity, and moderate mechanical properties. In vitro experiments confirmed that the bioceramic scaffolds possess superior biocompatibility and promote osteogenic differentiation, as evidenced by the upregulation of osteogenic genes (Runx2, Alp, Ocn, and Col I). In a rat CSD model, Micro-CT and histological analyses demonstrated that the hydrogel-derived bioceramic scaffolds promoted substantial new bone formation compared with the control group, which was further corroborated by immunohistochemical staining showing upregulated expression of osteogenic-related proteins, including RUNX2, OPN, and OCN. Overall, this work provides a viable strategy for fabricating bioceramic scaffolds that match the geometric contours of bone defects while effectively promoting bone regeneration.

There are an estimated 9.5 million people living with type 1 diabetes (T1D) globally, with cardiovascular disease (CVD) remaining a major cause of morbidity and mortality despite advances in care. Atherosclerosis occurs earlier in people with T1D and those with T1D-onset in early childhood are at particularly high lifetime risk of CVD. Multiple traditional risk factors (e.g., glycaemia, lipids, blood pressure, obesity and smoking) and novel risk factors (e.g., social determinants of health, inflammation and genetics) can promote CVD in people with T1D. This highlights the need for a life-course approach to managing overall cardiovascular risk and preventing or mitigating end-stage complications such as atherosclerotic events, cardiac autonomic neuropathy and heart failure. However, most people with T1D do not meet all recommended risk factor targets. Whilst T1D-specific risk calculators for CVD are available to guide shared decision-making and risk factor management, greater awareness and further data are needed to inform their use in different T1D populations. However, there remains a relative paucity of T1D-specific clinical trial data to inform the management and therapies for CVD risk factors such as dyslipidaemia, hypertension and chronic kidney disease (CKD), and for clinically evident CVD. There is now increasing interest in the use of adjunct glucose-lowering drugs initially developed for use in type 2 diabetes, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 agonists, and whilst some weight, glycaemia, blood pressure and albuminuria benefits have been shown, cardiovascular outcome trials (CVOT) in T1D are currently lacking. This review by a multidisciplinary team provides an overview of CVD pathophysiology, risk factor care, risk prediction and management in people with T1D.

We aimed to examine the mediating role of accelerated aging in the association between diet quality and CVD incidence and mortality. Data were obtained from the UK Biobank cohort. Diet quality was evaluated using four established indices: the Healthy Eating Index-2020, the Alternative Healthy Eating Index, the Dietary Approaches to Stop Hypertension index, and the Mediterranean Diet Score. Accelerated aging was assessed by the Phenotypic Age Acceleration and Biological Age Acceleration. Outcomes included incident CVD and CVD mortality. Multivariable linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. Subgroup analyses were conducted according to sex, age, and CVD subtypes. This analysis comprised 52,718 UK Biobank participants who were followed for a mean of 12 years. Accelerated aging significantly mediated the associations between diet quality and both incident CVD and CVD mortality across the four indices. The proportion mediated ranged from 21.81 to 40.84% for incident CVD and from 16.67 to 35.87% for CVD mortality. Our study indicates that accelerated biological aging may serve as a potential intermediate pathway linking diet quality to CVD. These findings suggest that aging-related physiological dysregulation may be a potential target for future dietary intervention research. Incorporating population stratification by sex, age, and disease subtype is essential to develop more precise and effective dietary guidelines to improve cardiovascular health.

Post-stroke cognitive impairment (PSCI) affects nearly 30% of stroke survivors and substantially limits functional recovery. Brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase-β (Trkβ) signalling plays an important role in synaptic plasticity and cognitive function; however, the contribution of individual NTRK2/Trkβ isoforms to PSCI remains poorly understood. This study investigated (a) isoform-specific NTRK2 mRNA expression, (b) genetic association of the isoform-specific variant rs6559833 with post-stroke cognitive outcomes and (c) DNA methylation patterns potentially regulating NTRK2 expression using blood as primary biosource. Isoform-specific expression was analysed in 50 subjects, rs6559833 was genotyped in 280 ischemic stroke patients, and DNA methylation was assessed in 10 samples using whole-genome bisulfite sequencing. The TRKβ-FL expression was significantly reduced in stroke patients compared with healthy controls, whereas TRKβ-SHC expression was higher in PSCN individuals than in PSCI patients. The latter showed positive correlation with MEK2 expression and memory performance. The 'TT' genotype of the rs6559833 variant showed marginal associations with post-stroke memory status and overall BMSE scores (p = 0.0442 and 0.0488, respectively). Furthermore, hypermethylation was observed within the NTRK2 gene body and in genes encoding its splicing regulators, whereas no evident difference in promoter methylation was observed. Collectively, these findings suggest that Trkβ-SHC expression may be associated with preserved cognitive function after stroke and indicate a potential relationship between isoform-specific NTRK2 expression, genetic regulation and cognitive outcomes in PSCI.

Breast cancer treatment remains limited by therapeutic resistance, recurrence, and incomplete responses to immunotherapy, largely because tumor cells continuously adapt to the dynamic tumor microenvironment (TME). Mitochondria are central regulators of energy metabolism, redox balance, cell death, inflammatory signaling, and immune modulation. Stressors within the breast cancer TME, including hypoxia, nutrient deprivation, acidosis, matrix stiffening, oxidative stress, and treatment pressure, can remodel mitochondrial metabolism and dynamics, thereby promoting tumor survival, invasion, immune evasion, and therapy resistance. Conversely, stressed mitochondria reshape the TME through metabolic byproducts, reactive oxygen species, mitochondrial DNA release, inflammatory mediators, and stromal or vascular remodeling signals. This reciprocal mitochondria-TME crosstalk forms a self-reinforcing pathological loop that supports breast cancer progression. Biomaterial-based mitochondria-targeted nanomedicine offers a strategy to intervene in this loop by integrating multilevel delivery, microenvironment-responsive release, mitochondrial targeting, metabolic regulation, and immune activation. This review summarizes how the breast cancer TME remodels mitochondrial function, how mitochondrial stress reciprocally reshapes the TME, and how biomaterial-based therapeutic platforms can be designed to target this axis. We further discuss translational challenges, including tumor specificity, intratumoral penetration, long-term biosafety, subtype-specific intervention, and clinically relevant combination strategies.

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-associated systems have emerged as powerful tools for next-generation molecular diagnostics, particularly for nucleic acid detection. However, ultrasensitive protein detection is equally critical across diverse applications in biology and medicine, especially for diagnosing and prognosing diseases such as cancer, traumatic brain injury (TBI), Alzheimer's disease, and cardiovascular diseases. Despite recent efforts to adapt CRISPR/Cas systems for protein detection, these methods have typically achieved sensitivity in the femtomolar to picomolar range, underscoring the need for enhanced detection capabilities. Here, we developed CRISPR-AMPED, a CRISPR/Cas-based immunoassay enhanced by magnetic proximity extension and detection. This approach combines proximity extension assay (PEA) with magnetic beads to convert protein targets into DNA barcodes while enabling effective washing to reduce background noise. The resulting DNA barcodes are detected through recombinase polymerase amplification (RPA) coupled with CRISPR/Cas12a, eliminating thermocycling and providing simultaneous target and signal amplification. CRISPR-AMPED achieves attomolar-level sensitivity, surpassing ELISA by over three orders of magnitude and outperforming existing immunoassays and CRISPR/Cas-based protein detection systems. As an initial demonstration of clinical utility, we applied CRISPR-AMPED to detect the inflammatory biomarker interleukin-8 (IL-8) in serum samples from patients with TBI and healthy controls. Further integration with a smartphone-based detection device demonstrates its potential for portable testing, while the digital format extends the dynamic range and enhances quantitation precision. Together, these results establish CRISPR-AMPED as a sensitive protein detection approach using IL-8 as an initial model target and provide a framework for future adaptation to additional protein biomarkers.