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Immune-stimulating cocktail could shield against diverse bacterial and viral infections

Features of recently identified influenza D point to possible pandemic threat

Mild cognitive impairment (MCI) is the prodromal stage of dementia involving complex interactions between the brain and peripheral organs. Emerging evidence indicates that heart dysfunction and gut microbiota dysbiosis contribute to MCI pathogenesis. Here, we present a framework integrating brain-heart-gut interactions using whole-body positron emission tomography (PET) to enhance brain-only diagnostic performance. Our brain-only model achieves diagnostic performance comparable to that of...

CONCLUSIONS: The anti-ASC N-terminal and C-terminal antibodies may have neuroprotective effects, which are manifested as reducing cell apoptosis, improving cognitive function, and alleviating AD-like pathology in AD mice. Immunotherapies targeting ASC are promising for treating AD.

Mitochondrial dysfunction is increasingly recognized as a central driver of Alzheimer's disease (AD), contributing to neuroinflammation, synaptic failure, and energy collapse.Emerging preclinical evidence suggests that classic hallucinogens, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, may restore mitochondrial integrity by activating Serotonin 2A (5-HT2A) and sigma-1(Sig-1R) receptors. In experimental models, these pathways are associated with...

Formation of new amyloid fibrils and oligomers from monomeric protein on the surfaces of existing fibrils is an important driver of many disorders such as Alzheimer's and Parkinson's diseases. The structural basis of this secondary nucleation process, however, is poorly understood. Here, we ask whether secondary nucleation sites are found predominantly at rare growth defects: irregularities in the fibril core structure incorporated during their original assembly. We first demonstrate using the...

Aging is a major risk factor for diabetic kidney disease (DKD), with both conditions exhibiting similar renal pathology. We identify the energy-sensing molecule Retinoic acid-related orphan receptor γ (RORγ) as significantly downregulated in diabetic and aged kidneys. Tubule-specific RORγ deficiency exacerbates kidney injury, whereas its overexpression protects. Mechanistically, RORγ stabilizes insulin-induced gene 1 (INSIG1) by upregulating the deubiquitinase YOD1 and enhancing AMPK activity...

Skeletal muscle aging causes loss of both muscle mss and strength, often leading to sarcopenia. Clinical manifestation of sarcopenia has been found to improve with exercise intervention. The molecular mechanisms in response to exercise intervention in aged skeletal muscles are not fully understood. We performed transcriptomic profiling of aged animal model with exercise intervention for identifying the plausible mechanism leading to enhanced muscle function. Expression levels of 43,629 RNAs were...

We leveraged allele frequencies from gnomAD, Regeneron Genetics Center Million Exome and Turkish Variome for 4591 disease genes from PanelApp and OMIM, and identified 97,135 pathogenic and 478,263 likely pathogenic variants using an American College of Medical Genetics and Genomics-based classifier. This expanded pathogenic and likely pathogenic variants nearly six-fold. On average, an individual is born with 4.70 pathogenic or likely pathogenic variants, of which 1.66 are compatible with a...