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Multiple myeloma (MM) remains an incurable disease despite therapeutic advancements extending survival. Relapses driven by drug resistance and minimal residual disease underscore the need for novel treatment strategies. Natural Killer (NK) cells play a key role in MM immunity, yet their function is suppressed by inhibitory cytokines and metabolites from the tumor microenvironment. Developing anticancer drugs with immunomodulatory properties, such as enhancing tumor sensitivity to NK cell...

Endometrial cancer (EC) is one of the most common gynecologic malignancies amongst women worldwide. Its incidence and mortality rates have been increasing in the last decade. In the present work, we built a patient EC-derived organoid (PDOs) platform that faithfully recapitulated tumor phenotype, genomic alterations, and expression profiles of matched-primary cancer tissues. Interestingly, we found that the response of EC-derived PDOs to both standard therapy and a wide range of targeted drugs...

Neural hyperexcitability and network dysfunction are neurophysiological hallmarks of Alzheimer's disease (AD) in animal studies, but their presence and clinical relevance in humans remain poorly understood. We introduce a perturbation-based approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), alongside resting-state EEG (rsEEG), to investigate neurophysiological basis of default mode network (DMN) dysfunction in early AD. While rsEEG revealed global neural...

Intermittent fasting (IF) offers a potential strategy to counteract Alzheimer's disease (AD) progression. In our 16-week study on AD transgenic mice, IF positively affected cognitive function and reduced amyloid-β (Aβ) accumulation, verifying the IF's role in modulating neuroinflammation. Multiomics integration revealed strong links between IF-induced hippocampal gene expression, gut microbiota, and serum metabolites beneficial for cognition. Indole-3-propionic acid (IPA) emerged as a pivotal...

Autophagy preserves neuronal integrity by clearing damaged proteins and organelles, but its efficiency declines with aging and neurodegeneration. Depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD^(+)) is a hallmark of this decline, yet how metabolic restoration enhances autophagic control has remained obscure. Meanwhile, alternative RNA splicing errors accumulate in aging brains, compromising proteostasis. Here, we identify a metabolic - transcriptional mechanism linking...

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CONCLUSIONS: Given the complexity and significant unmet needs among older adults, AI's potential benefits and harms are both heightened in this population. Appropriate guardrails are needed to leverage the benefits of AI while mitigating potential harms. Our findings have implications for technology developers to design innovations that align with the stakeholders' perceived roles for AI, for regulatory bodies to incorporate stakeholders' concerns when developing AI regulations, and for health...

Autophagy preserves neuronal integrity by clearing damaged proteins and organelles, but its efficiency declines with aging and neurodegeneration. Depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD^(+)) is a hallmark of this decline, yet how metabolic restoration enhances autophagic control has remained obscure. Meanwhile, alternative RNA splicing errors accumulate in aging brains, compromising proteostasis. Here, we identify a metabolic - transcriptional mechanism linking...

CONCLUSION: Frailty serves as a critical mediator between disability, anxiety and depression in older adults with chronic disease comorbidity. Targeted interventions addressing disability and frailty may significantly mitigate anxiety and depression, thereby improving mental health and quality of life in this vulnerable population.

CONCLUSION: This study suggests that clear guidance regarding postoperative rehabilitation exercises and multidisciplinary management protocols including individualized exercise plans, collaborative multidisciplinary rehabilitation strategies, and the development of smart devices may be important for healthcare providers in supporting patients' rehabilitation management. Based on participants' experiences, these approaches show potential for contributing to the alleviation of postoperative...

CONCLUSIONS: This study developed interpretable, gender-specific machine learning models for CVD risk prediction in the oldest old population using routine biomarkers. The models demonstrated good discrimination and calibration, offering a practical tool for identifying high-risk individuals who may benefit from targeted preventive interventions. These findings suggest the potential utility of biomarker-based machine learning approaches in cardiovascular risk assessment for the rapidly growing...

There is a growing contradiction between the rising demand for mechanical ventilation among the elderly and their heightened sensitivity to ventilator-induced lung injury (VILI). This discrepancy compels us to explore therapeutic targets for VILI in elderly patients. Our research revealed that aging increases the sensitivity of pulmonary endothelial cells to low-magnitude mechanical stretch. By analyzing transcriptome sequencing data from lung tissues of humans and mice at different ages, as...

A daily pill can prevent the crippling disease, but its maker won’t bring it to market

CONCLUSION: The study shows that higher healthcare utilisation among older adults, but public healthcare utilisation remains low. The public healthcare utilisation, mostly by poorer population, highlights equity concerns.

This review delves into the intricate relationship between serotonin signaling, mitophagy and mitochondrial dysfunction in Alzheimer's disease (AD), with a focus on the mechanistic pathways that link these processes and their potential therapeutic implications. A neurodegenerative condition called Alzheimer's disease is marked by cognitive deterioration. It is increasingly recognized as being influenced by impaired mitochondrial function and mitophagy, the selective degradation of damaged...

Alzheimer's disease (AD), the most common cause of dementia, is characterized by amyloid-β deposition, tau hyperphosphorylation, neuroinflammation, and progressive neuronal loss, with no curative therapy currently available. Dental pulp stem cells (DPSCs) derived from third molars represent an ethically accessible, minimally invasive, neural crest-derived mesenchymal stem cell source with self-renewal and multi-lineage differentiation potential. Preclinical evidence suggests that DPSCs exert...