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Transcriptome modulation is essential for metabolic adaptation to nutrient environments. However, the role of isoform usage, a crucial transcriptome component, is not yet fully understood. This study outlines the landscape of isoform-usage modulations across major metabolic organs in both mice and monkeys, spanning diverse metabolic states. Our in-depth analysis identifies numerous isoform-usage events, intricately influenced by nutrient challenges and largely independent of gene expression...

Aging alters signaling that involves brain-derived neurotrophic factor (BDNF) in the hippocampus. An adequate level of BDNF is essential for maintaining cognitive function in older adults. Previously, we showed that repeated intraperitoneal administration of the chemokine ligand CX3CL1 modulates peritoneal immune cells and the vagal nerve to increase hippocampal BDNF, consequently improving cognitive decline in aged mice. Here, we examined the contribution of endogenous CX3CL1 in the peritoneal...

Nucleotide-binding leucine-rich repeat (NLR) receptors play crucial roles in plant immunity by sensing pathogen effectors¹. In Arabidopsis, certain sensor NLRs function as NADases to catalyse the production of second messengers^(2,3), which can be recognized by enhanced disease susceptibility 1 (EDS1) with its partner senescence-associated gene 101 (SAG101), to activate helper NLR N requirement gene 1 (NRG1)⁴. A cryoelectron microscopy structure shows that second-messenger-activated EDS1-SAG101...

The use of reactive supports to disperse metal species is crucial for constructing highly efficient interfacial catalysts, by tuning the competitive reactant adsorption-activation pattern in supported metal catalysts into a non-competitive mechanism^(1-3). However, these reactive supports are prone to deterioration during catalysis, limiting the lifespan of the catalyst and their potential practical applications⁴. New strategies are needed to simultaneously protect reactive supports and surface...

No abstract

In response to organ injury in adults, macrophages often promote scarring, yet during early life, they are required for tissue regeneration. To elucidate the mechanisms underlying age-associated regeneration, we compared the macrophage injury response in newborn versus adult hearts. Single-cell analysis revealed an accumulation of tissue-resident macrophages in neonates that were selectively polarized for apoptotic cell recognition and uptake (efferocytosis). Ablation of the apoptotic cell...

Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large aging-neutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from...

CONCLUSIONS: This Delphi study estimated that dementia already affects roughly 1 in 12 older Brazilians aged 60 and above, with slightly higher prevalence in women and significant geographical variations. These results underscore the urgency for targeted public health strategies in Brazil and offer a framework for similar challenges in other LMICs, especially given that dementia cases are projected to increase by approximately 3.6 times in 4 decades.

Cumulative silicon photovoltaic (PV) waste highlights the importance of considering waste recycling before the commercialization of emerging PV technologies^(1,2). Perovskite PVs are a promising next-generation technology³, in which recycling their end-of-life waste can reduce the toxic waste and retain resources^(4,5). Here we report a low-cost, green-solvent-based holistic recycling strategy to restore all valuable components from perovskite PV waste. We develop an efficient aqueous-based...

Alzheimer's disease (AD) affects more than 10% of the population ≥65 y of age, but the underlying biological risks of most AD cases are unclear. We show anti-poly-glycine-arginine (a-polyGR) positive aggregates frequently accumulate in sporadic AD autopsy brains (45/80 cases). We hypothesize that these aggregates are caused by one or more polyGR-encoding repeat expansion mutations. We developed a CRISPR/deactivated-Cas9 enrichment strategy to identify candidate GR-encoding repeat expansion...

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of abnormal α-synuclein (α-syn) within dopaminergic neurons in the substantia nigra region of the brain. Despite excessive accumulation of α-syn being key to the pathogenesis of PD, the mechanisms governing its clearance remain elusive. In this study, we found that the endosomal sorting complex required for transport (ESCRT) system plays a crucial role in capturing and facilitating the...

In multiple sclerosis (MS), inflammation of the central nervous system results in demyelination, neuroaxonal injury, and cell death. However, the molecular signals responsible for injury and cell death in neurons are not fully characterized. Here, we profile the transcriptome of retinal ganglion cells (RGCs) in experimental autoimmune encephalomyelitis (EAE) mice. Pathway analysis identifies a transcriptional signature reminiscent of aged RGCs with some senescent features, with a comparable...

The limited success of cancer immunotherapy has posed challenges in treating patients with cancer. However, promising strides could be made with a deeper understanding of the factors that cause T cell dysfunction within the tumor microenvironment and by developing effective strategies to counteract tumor-induced immune suppression. Here, we report that tumor-derived extracellular vesicles (tEVs) can induce senescence and suppression in T cells. Programmed death ligand 1 (PD-L1), a key component...

RNA binding proteins (RBPs) containing intrinsically disordered regions (IDRs) are present in diverse molecular complexes where they function as dynamic regulators. Their characteristics promote liquid-liquid phase separation (LLPS) and the formation of membraneless organelles such as stress granules and nucleoli. IDR-RBPs are particularly relevant in the nervous system and their dysfunction is associated with neurodegenerative diseases and brain tumor development. Serpine1 mRNA-binding protein...

Scientists say the source of a high-energy particle that zipped through the Mediterranean Sea in 2023 is a mystery

Dementia, characterized by loss of cognitive abilities in the elderly, poses a significant global health challenge. This study explores the role of astrocytes, one of most representative glial cells in the brain, in mitigating cognitive decline. Specifically, we investigated the impact of Hevin (also known as SPARC-like1/SPARCL-1), a secreted glycoprotein, on cognitive decline in both normal and pathological brain aging. By using adeno-associated viruses, we overexpressed Hevin in hippocampal...

DNA topoisomerases are essential molecular machines that manage DNA topology in the cell and play important roles in DNA replication and transcription. We found that knocking down the enzyme topoisomerase Top2 or its mammalian homolog TOP2B increases the lifespan of S. cerevisiae, C. elegans, and mice. TOP2B reduction also extends the health span of mice and alleviates the pathologies of aging in multiple tissues. At the cellular/molecular level, TOP2B reduction alleviates the major hallmarks of...

Dementia, characterized by loss of cognitive abilities in the elderly, poses a significant global health challenge. This study explores the role of astrocytes, one of most representative glial cells in the brain, in mitigating cognitive decline. Specifically, we investigated the impact of Hevin (also known as SPARC-like1/SPARCL-1), a secreted glycoprotein, on cognitive decline in both normal and pathological brain aging. By using adeno-associated viruses, we overexpressed Hevin in hippocampal...