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Scientists have discovered that pantethine, a readily available vitamin B5 derivative, can calm overactive immune cells and may help fight psoriasis. The supplement prevented psoriasis in mice and showed promising results in a small human trial, revealing an unexpected connection between cholesterol and autoimmune inflammation.

Scientists have discovered that gut bacteria can feed on the protective mucus lining your intestines, producing potentially harmful compounds, but fiber helps keep this activity in check. Overlooked proteins in plant foods also help shift gut bacteria toward producing beneficial substances, revealing a surprising new reason plant-based diets may be good for you.

Univariate differential expression analysis dominates single-cell transcriptomic studies of Alzheimer's disease, yet marginal testing alone cannot resolve multivariate disease-associated structure or distinguish clinical from neuropathological signatures. Here we introduce TriSCOPE, a framework integrating multivariate predictive modeling, donor-aware differential expression, and pseudotime inference, applied to six Alzheimer's disease snRNA-seq datasets comprising ~4.2 million nuclei from 627...

Tau propagation is a key driver of Alzheimer's disease (AD), yet selective markers of seeding-competent tau remain elusive. Ubiquitin phosphorylated at Serine-65 (pS65-Ub) is a PINK1-derived cellular stress signal that accumulates in AD with elevated tau pathology, but its relationship to tau seeding is unknown. Here, using postmortem brain tissue from female and male donors, we show that a subset of tau is covalently modified by pS65-Ub in AD brain. The pS65-Ub-associated tau population is...

Neurotoxic intermediates formed during amyloid-β (Aβ) aggregation are thought to drive Alzheimer's disease, yet their rarity and transient nature have obscured their identity and formation pathways in the human brain. Here, we combine super-resolution microscopy and single-molecule functional imaging with kinetic modelling to classify Aβ intermediates according to their membrane-disrupting activity and connect their damaging effects to the aggregation pathways that generate them. Applying this...

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder characterized by variable progression and treatment response. Over the past three decades, genetic discoveries have reshaped our understanding of PD biology, identifying rare monogenic forms, strong genetic risk variants and a large set of common and rare genetic variants variably contributing to PD heritability. These findings led to the identification of key pathways implicated in the neurodegenerative process, including...

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Spatial omics technologies provide unprecedented opportunities to investigate how molecular programs are organized within tissues. However, existing analytical frameworks primarily focus on identifying cellular states and characterizing differentially expressed molecular features across these states. The relational spatial organization of molecular features and its dynamics across biological contexts therefore remain largely unexplored. Here we present Gene SPatial Optimal Transport (GeneSPOT),...

Timely removal of defective or superfluous cellular components, including misfolded proteins, aberrant protein complexes and damaged organelles, is essential for maintaining cellular homeostasis and adaptation to stress. This process is controlled by an intricate interplay between two principal degradation systems, the ubiquitin-proteasome system and autophagy, which together mediate the recognition, selection and elimination of diverse substrates. In this Review, we discuss how proteins and...

Diabetes is a major risk factor for developing cognitive impairment and studies have shown that poor glycemic control can increase this risk, but the neural mechanisms are poorly understood. Many studies have linked altered spontaneous cortical activity during the resting-state to Alzheimer's disease and other neurological conditions associated with cognitive impairment. Herein, we examine whether the strength of spontaneous activity during the resting-state is differentially related to glycemic...

Single-cell genomics is transformative for characterizing cellular heterogeneity, but many biological questions require comparing samples rather than individual cells. Typical analyses compare "case" and "control" groups, ignoring sample-level variation within them. Here, we present scSLIDE (single-cell sample-level inference using density estimation), a framework that transforms each sample's single-cell data into a compact profile describing where its cells are distributed in high-dimensional...

Region-specific synapse loss is an early hallmark of Alzheimer's disease, yet the upstream signals that render synapses vulnerable remain unclear. In a mouse model of amyloidosis, we identify an early astrocyte state that emerges in vulnerable brain regions before widespread plaque deposition and overt gliosis. These astrocytes exhibit bulbous-looking perisynaptic processes enriched in p62 and glycogen, impaired autophagic flux and calcium signaling, and diminished astrocyte-synapse coverage....

CONCLUSION: Probiotics or synbiotics may improve cognitive test performance, but the certainty of evidence is very low because of risk of bias, substantial heterogeneity, and imprecision. Exploratory subgroup analyses did not provide clear evidence that disease category, intervention duration, intervention type, study-level mean age, strain composition, dosage, or cognitive assessment instrument modified the treatment effect. Larger, well-designed randomized trials are needed.

Ribophagy plays a critical role in maintaining ribosome quality, yet how ribosomes are marked for autophagic recognition remains poorly understood. Here, we identify the methyltransferase Dot1/DOT1L as a conserved regulator of ribophagy that generates an "eat-me" signal through methylation of Rpl12, thereby regulating ribosome quality. Under nutrient deprivation, Dot1 methylates Rpl12 at K41 and K48 in Saccharomyces cerevisiae, enhancing its interaction with Atg11 and initiating ribophagy...

Vascular endothelial cell (VEC) senescence is a key contributor to vascular aging and atherosclerosis. Increasing evidence suggests that long non-coding RNAs (lncRNAs) can encode functional micropeptides involved in cellular regulation. In this study, we investigated whether 17β-estradiol (17β-E2) delays endothelial senescence through an lncRNA-encoded peptide associated with autophagy. RNA sequencing was performed in H(2)O(2)-induced senescent human umbilical vein endothelial cells (HUVECs)...

The motion of liquid droplets on solid surfaces is commonly described by contact-line friction, which is generally assumed to increase monotonically with instantaneous velocity. However, such a velocity-only description cannot explain why static droplet friction can exceed dynamic friction or why contact-line friction can become velocity-weakening. Here, we demonstrate that contact-line friction depends jointly on sliding velocity and contact history. Using self-assembled alkylsilane monolayers...

Most vertebrates and insects undergo senescence: as they age, their rate of mortality increases while reproduction declines. We present data from a 34-y study on 3,285 colonies of known age in the western harvester ant, Pogonomyrmex occidentalis, that show the reverse pattern, negative senescence, in which mortality decreases and reproduction increases with age. Theoretical models have identified indeterminate growth and a lack of reproductive cost to growth as the key traits favoring the...

Blood-brain barrier (BBB) dysfunction is an early feature of brain aging, but the endothelial mechanisms preserving barrier resilience remain unclear. Although we have reported α-synuclein (SNCA) supports vascular endothelial homeostasis, its role in the brain microvascular endothelium is unknown. Because SNCA loss suppresses eNOS/NO signaling and promotes endothelial β-site amyloid precursor protein cleaving enzyme 1 (BACE1) induction, we investigated whether senescence-associated SNCA decline...

After more than 35 years of research, scientists have uncovered surprising clues about what really drives Lyme disease risk. Contrary to longstanding assumptions, deer populations appear less important than mice, which can fuel a 40% increase in tick numbers the following year. Even acorn production can predict tick population surges two years in advance, while extreme temperatures may be far less deadly to ticks than scientists once believed.

A surprising new study from UCLA suggests that a naturally occurring molecule could help breast cancer survivors overcome the frustrating brain fog and exhaustion that can linger long after treatment ends. Researchers found that women taking an oxaloacetate supplement for eight weeks experienced substantial improvements in memory, concentration, mental clarity, and fatigue.