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Movement-responsive deep brain stimulation for Parkinson's disease using a remotely optimized neural decoder

3 days 13 hours ago
Deep brain stimulation (DBS) has garnered widespread use as an effective treatment for advanced Parkinson's disease. Conventional DBS (cDBS) provides electrical stimulation to the basal ganglia at fixed amplitude and frequency, yet patients' therapeutic needs are often dynamic with residual symptom fluctuations or side effects. Adaptive DBS (aDBS) is an emerging technology that modulates stimulation with respect to real-time clinical, physiological or behavioural states, enabling therapy to...
Tanner C Dixon

A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation

3 days 13 hours ago
The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal...
Mingyue Wang

Pancreatic beta-Cell Remodeling in Health and Aging: Lessons from Rodents and Humans

3 days 13 hours ago
Pancreatic β-cells are essential for maintaining glucose homeostasis throughout life. Although rodent models have been instrumental in elucidating β-cell biology, notable differences exist between rodents and humans across fetal, postnatal and adult stages. This review provides a comparative analysis of β-cell development, proliferation and regenerative capacity between these two species, highlighting critical divergences that must be considered when translating preclinical findings to human...
Radwan Darwish

Age-dependent accumulation of mitochondrial tRNA mutations in mouse kidneys linked to mitochondrial kidney diseases

3 days 13 hours ago
Heteroplasmic pathogenic mitochondrial DNA (mtDNA) mutations are key drivers of mitochondrial diseases, yet their tissue-specific and cell-specific accumulation patterns during aging and the mechanistic links to pathology remain poorly understood. In this study, we employed DddA-derived cytosine base editor technology to generate three mouse models harboring distinct pathogenic mitochondrial tRNA mutations. These mutations exhibited age-dependent accumulation in the kidneys, leading to severe...
Leping Zhang

Senescent macrophages induce ferroptosis in skeletal muscle and accelerate osteoarthritis-related muscle atrophy

3 days 13 hours ago
Muscle atrophy around joints is a common issue for people with osteoarthritis (OA), but its causes are poorly understood. Here we demonstrate that chronic inflammation in quadriceps muscle coincides with OA in mice, characterized by an increase in macrophages, activation of inflammatory pathways and tissue vascularization. We show that, during OA progression, macrophages progressively exhibit increasing phenotypes of senescence and promote muscle atrophy through paracrine induction of...
Wei Xiang

Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells

3 days 13 hours ago
RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5'...
Neha Nagpal

Stem cell therapies for diabetes

3 days 13 hours ago
Diabetes has long-term, potentially severe implications for healthspan and lifespan and imposes an immense burden on global healthcare, the economy and society. Although a repertoire of medications is available to treat diabetes, these do not properly address the eventual lack of functional pancreatic beta cells that are needed to secrete insulin and maintain glucose homeostasis. Human islet cell transplantation from deceased donors is an established treatment for insulin-requiring type 1...
Juin Ting Chen

Cholesterol's hidden impact: the nonlinear link between remnant cholesterol (RC) and phenotypic age acceleration (PhenoAgeAccel)

3 days 13 hours ago
Cholesterol metabolism disorders have been shown to correlate with multiple physiopathologic aspects of cellular aging. However, whether indicators reflecting cholesterol metabolism [e.g., remnant cholesterol (RC)] can serve as biomarkers for biological aging remains unclear. To address this gap, this study aimed to explore the relationship between RC and phenotypic age acceleration (PhenoAgeAccel) using data from the National Health and Nutrition Examination Survey (NHANES) database. First,...
QianKun Yang

Acute corticospinal and reticulospinal responses to strength training in ageing

3 days 13 hours ago
Ageing is associated with declines in neuromuscular function, yet the neural mechanisms underlying strength adaptations in older adults remain unclear. While the corticospinal tract (CST) is the primary pathway for voluntary movement, the reticulospinal tract (RST) may play a compensatory role with age. This study investigated CST and RST responses following a single session of high-intensity metronome-paced strength training (MPST) in young and older adults. Thirty-five participants (17 young,...
Ummatul Siddique