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Parkinson's disease (PD) is a multisystemic disorder that manifests through motor and non-motor symptoms. Motor dysfunction results from the degeneration of dopamine-producing neurons in the substantia nigra pars compacta. Increasing evidence suggests that synapse dysfunction precedes neuronal loss by years. Still, early synaptic alterations in PD remain poorly understood. Here, we integrate literature meta-analysis and multi-omics with biochemical, imaging, and electrophysiological measurements...

SQSTM1/p62 (sequestosome 1) is an important receptor protein involved in many cellular signaling processes, including macroautophagy/autophagy. It is a molecular hub for cellular homeostasis and cellular responses. Within autophagy, SQSTM1 targets ubiquitinated cargo for degradation, maintaining cellular proteostasis. Structurally, SQSTM1 consists of several domains that facilitate its binding to ubiquitinated cargo, the formation of SQSTM1 aggregate inclusions, interactions with MAP1LC3/LC3,...

Scalable clinical markers of neurocognitive vulnerability in aging are needed, particularly in settings where biomarker access remains limited. Instrumental activities of daily living (IADLs) capture cognitively demanding everyday behavior and may provide a low-cost, repeatable functional marker of elevated risk. We harmonized longitudinal data from four population-based aging cohorts-CHARLS, ELSA, HRS, and SHARE-including adults aged ≥50 years with eligible baseline assessments. IADL impairment...

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative condition that is characterized by an increasing incidence rate due to global population aging, resulting in a significant social and economic burden. Current pharmacological interventions offer only limited relief and are unable to halt neuronal loss and cognitive decline. Therefore, safe and effective non-pharmacological interventions (NPIs) are needed for the management of AD. This review systematically synthesizes...

High-fidelity single-nucleotide-resolution mapping of abasic (AP) sites in mammalian genomes remains technically challenging due to low abundance and high background. Here we present DEPACE-seq (Dual-End PAB-Conjugated Endo IV-Cleaved Sequencing), a robust and easy-to-implement method for precise genome-wide profiling of AP sites. DEPACE-seq employs an N-pyrrolyl-alanine-2,2'-(ethylenedioxy)bis(ethylamine)-biotin (PAB) probe that selectively conjugates AP sites via a mild Pictet-Spengler...

Genetic changes may set off a chain reaction that causes the spine’s natural shock absorbers to harden and deteriorate. Zebrafish with a faulty collagen-related gene developed mineral buildup and spinal fusion similar to human disc disease. Researchers were able to reduce the damage using an existing osteoporosis drug and by targeting fat metabolism. The discovery points to several exciting possibilities for future back pain treatments.

Tiny pollution particles from smoke, soot, and dust may worsen rheumatoid arthritis and raise the risk of painful flares, particularly after prolonged exposure. The findings suggest that avoiding poor air quality could become an important part of managing the disease.

A prescription form of THC helped many people with PTSD escape recurring trauma-related nightmares, with more than one-third reporting that the nightmares disappeared completely after ten weeks. The results could point toward a long-awaited treatment for one of PTSD’s most distressing and stubborn symptoms.

Pioneering study projects rural heat will edge closer to city swelter

Scientists are racing to conserve what remains of these majestic animals’ genetic diversity

A simple change in posture may subtly affect how people feel and make decisions. Participants who sat upright reported greater feelings of pride and took more successful risks in a virtual balloon game than those who hunched over. Most did not realize researchers had influenced their posture, helping rule out the possibility that they were merely responding to expectations. The results suggest workplace ergonomics could influence more than physical comfort.