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Psycho-socio-economic factors (PSEFs) such as income and homeownership may influence the prevalence of cardiorenal multimorbidity (CRM), yet their prospective associations with CRM risk remain unclear. This study aimed to estimate CRM incidence and examine its relationships with multiple PSEFs in a nationally representative Canadian cohort. We analyzed data from 16,557 participants (mean age: 60.4 years; 48.9% men) in the Canadian Longitudinal Study on Aging (CLSA) who were free of CRM at...

Appropriators agree instead to keep this year’s spending nearly level

No abstract

CONCLUSION: The study highlights the inequalities in the subjective physical and mental health of older adults across cities with different administrative hierarchies in China. By providing more resources, cities with higher administrative hierarchies can significantly improve older adults' life quality and subjective health. Meanwhile, marketization further strengthens the positive impact of urban administrative hierarchy on mental health. By introducing the urban administrative hierarchy as a...

Homologous recombination (HR) is traditionally portrayed as a DNA double-strand break repair pathway. However, emerging evidence positions RAD51, its partners BRCA1, BRCA2, and other HR factors at the core of a broader genome-maintenance network that operates by a "prevent and protect" strategy extending beyond repair. Here, we review how RAD51 can shield DNA from nucleolytic processing mediated by MRE11 and related nucleases, promote fork reversal, suppress replicative DNA gaps accumulation,...

CONCLUSION: The ACP training program has successfully engaged staff in care homes by increasing their capacity, opportunity, and motivation.

CONCLUSION: The findings elucidate a complex interplay between cardiovascular health and auditory function, emphasizing that heart attacks may exacerbate HL through the frailty pathway in certain older populations. These results highlight the need for tailored cardiovascular interventions and proactive measures to mitigate HL risks. Future research should focus on defining these pathophysiological associations more clearly to develop targeted interventions for vulnerable older people.

CONCLUSION: Our findings highlight that maintaining physical activity, particularly during middle adulthood, is associated with reduced risk of sarcopenia. Because physical activity was self-reported, future research should employ objective measures and longitudinal designs to confirm these associations.

Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid deposition in patients with T2D, with hIAPP fibrils believed to play a key role in the pathogenesis of T2D. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of hIAPP fibrils extracted from surgically resected pancreases of three donors with T2D. These fibrils exhibit a uniform...

We report the discovery of a chemical series that enhances ApoE secretion from human astrocytes through mechanisms independent of LXR agonism. Target deconvolution of hits from a phenotypic screen in astrocytoma cells employed chemoproteomics, photoaffinity probes, in vitro KINOMEscan analysis, and targeted siRNA knockdown experiments. Photoaffinity labeling coupled with quantitative chemical proteomics identified aryl hydrocarbon receptor (AhR), a transcription factor not previously associated...

The mechanisms for failure of neoadjuvant immune checkpoint blockade (NICB), an established therapy for patients with esophageal squamous cell carcinoma (ESCC), remain unclear. We integrated single-cell RNA data from patients with ESCC pre- and post-NICB, identifying a subset of senescent EGR1-expressing B cells that correlate with poor pathological responses. EGR1 was a key transcription factor regulating B cell senescence. EGR1^(+) B cells emerged as predictors of adverse outcomes in multiple...