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The degradation mechanism of multi-resonance thermally activated delayed fluorescence materials
1,4-Azaborine-based arenes are promising electroluminescent emitters with thermally activated delayed fluorescence (TADF), offering narrow emission spectra and high quantum yields due to a multi-resonance (MR) effect. However, their practical application is constrained by their limited operational stability. This study investigates the degradation mechanism of MR-TADF molecules. Electroluminescent devices incorporating these compounds display varied operational lifetimes, uncorrelated with...
Osteoarthritis
Osteoarthritis is a heterogeneous disorder that is increasingly prevalent largely due to aging and obesity, resulting in a major disease burden worldwide. Knowledge about the underlying aetiology has improved, with increased understanding of the role of genetic factors, the microbiome, and existence of different pain mechanisms. However, this knowledge has not yet been translated into new treatment options. New evidence has questioned the efficacy of recommended treatments, such as therapeutic...
Effect of pre-hospital living setting on nutritional intake route upon discharge in older adults with aspiration pneumonia: a prospective cohort study
CONCLUSIONS: The pre-hospital living setting could serve as a good indicator of the nutritional intake route upon discharge. It is essential to optimize care in both nursing facilities and hospital settings when caring for older patients with aspiration pneumonia.
Negotiating a physically active life in tune with ageing: a grounded theory study of older persons' experiences of participating in high-intensity interval training
CONCLUSIONS: Our grounded theory underscores that physical activity and exercise should be regarded as multifaceted processes, which must be considered when promoting physical activity initiatives for older persons. By considering the older person and societal norms and values, we can gather knowledge to design physical exercise interventions that are not only effective but also enjoyable and capable of transforming how individuals perceive themselves as exercising persons.
Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice
Aging is a major risk factor for poor outcomes following respiratory infections. In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced...
John Deutch recalls how Jimmy Carter left his mark on energy research
Longtime MIT professor served as the first director of research in the Department of Energy
Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease
Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples. Expression of the herpesvirus...
regionalpcs improve discovery of DNA methylation associations with complex traits
We have developed the regionalpcs method, an approach for summarizing gene-level methylation. regionalpcs addresses the challenge of deciphering complex epigenetic mechanisms in diseases like Alzheimer's disease. In contrast to averaging, regionalpcs uses principal components analysis to capture complex methylation patterns across gene regions. Our method demonstrates a 54% improvement in sensitivity over averaging in simulations, providing a robust framework for identifying subtle epigenetic...
Analysis of multi-condition single-cell data with latent embedding multivariate regression
Identifying gene expression differences in heterogeneous tissues across conditions is a fundamental biological task, enabled by multi-condition single-cell RNA sequencing (RNA-seq). Current data analysis approaches divide the constituent cells into clusters meant to represent cell types, but such discrete categorization tends to be an unsatisfactory model of the underlying biology. Here, we introduce latent embedding multivariate regression (LEMUR), a model that operates without, or before,...
A nucleolar mechanism suppresses organismal proteostasis by modulating TGFβ/ERK signalling
The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Alas, ageing-associated decline in the efficiency of this network enables protein aggregation and consequently the development of late-onset neurodegenerative disorders, such as Alzheimer's disease. Accordingly, the maintenance of proteostasis through late stages of life bears the...
Using a sex- and gender-informed lens to enhance care in Parkinson's disease
No abstract
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction
Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross...
Therapy-induced senescent cancer cells contribute to cancer progression by promoting ribophorin 1-dependent PD-L1 upregulation
Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its...
A cell atlas of the human fallopian tube throughout the menstrual cycle and menopause
The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and...
Circadian clock communication during homeostasis and ageing
Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs. Numerous...
A nucleolar mechanism suppresses organismal proteostasis by modulating TGFβ/ERK signalling
The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Alas, ageing-associated decline in the efficiency of this network enables protein aggregation and consequently the development of late-onset neurodegenerative disorders, such as Alzheimer's disease. Accordingly, the maintenance of proteostasis through late stages of life bears the...
Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases
Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases....
Development of a digital memory and learning test for elderly individuals
CONCLUSION: The DMLT is a promising tool for cognitive assessment in the elderly, offering an accessible alternative. The high acceptance among elderly participants suggests that the test has potential for clinical and research use, although further studies are needed to validate its effectiveness in broader clinical settings.
The interactive use of augmented reality for educating the elderly on common age-related eye disease
CONCLUSIONS: Our study revealed the potential of the use of AR technology in facilitating health education on eye diseases in the elderly. The specific backgrounds and characteristics of target participants and the combination of AR with other pedagogical approaches warrant further investigation to maximize the impact of AR-based workshops in health education in broader healthcare contexts.
Comprehensive characterization of the transcriptional landscape in Alzheimer's disease (AD) brains
Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts,...