Results 161 to 170 of about 298 (198)

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

open access: yesAdvanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo   +17 more
wiley   +1 more source

Hypothalamic Control of Liver Health and Disease: From Circuits to Pathophysiology and Therapies

open access: yesAdvanced Science, EarlyView.
This review delineates the hypothalamic circuits that control liver homeostasis via autonomic and neuroendocrine pathways. Dysregulation of this hypothalamus–liver axis drives disease progression across a spectrum including steatotic liver disease, liver inflammation and injury, fibrosis, cirrhosis, and hepatocellular carcinoma.
Qin Tang   +7 more
wiley   +1 more source

Engineering a 660 nm‐Responsive Optogenetic Inducer of Pyroptosis for Precision Cancer Therapy

open access: yesAdvanced Science, EarlyView.
This study reports a bioorthogonal pyroptosis inducer, PyroRACS. By using a red‐light‐responsive Cre‐On genetic switch to control the expression of highly cytotoxic GSDMDNT, PyroRACS enables the artificial induction of pyroptosis with precise spatiotemporal control.
Mengkai Zhang   +5 more
wiley   +1 more source

Computation and Structure‐Guided Arginine Scanning Engineers a Hyperactive AP Endonuclease for Multiplex Viral RNA Sensing

open access: yesAdvanced Science, EarlyView.
Computational and structure‐guided arginine scanning rewires the DNA‐binding interface of APE1 to create APE1‐Evo, a hyperactive yet specific AP endonuclease. Integrated into the NAPTUNE‐V2.0 cascade, APE1‐Evo enables amplification‐free, multiplex viral RNA sensing for dengue virus and influenza A/B, highlighting a general strategy for engineering ...
Junlan Wang   +20 more
wiley   +1 more source

Targeting the KCNC3‐Dependent Anterior Insular‐Lateral Orbitofrontal Cortex Glutamatergic Circuit Attenuates Post‐Traumatic Anxiety

open access: yesAdvanced Science, EarlyView.
Frontal lobe traumatic brain injury is associated with hyperactivity of an insular–orbitofrontal circuit in both patients and mice. By combination of integrating functional imaging, cell‐type–specific circuit manipulation, single‐cell transcriptomics, and whole‐cell recordings, this work identifies the downregulation of the potassium channel KCNC3 in ...
Meng‐Ge Li   +10 more
wiley   +1 more source

Genetic Ablation and Multi‐Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models

open access: yesAdvanced Science, EarlyView.
Genetic ablation of Cep55 in Pten‐deficient mouse models delays tumorigenesis. Integrated multi‐omics analyses (proteomics, phosphoproteomics, and spatial transcriptomics) reveal that CEP55 regulates oncogenic signaling (RAS/ERK, PI3K/AKT), integrin/FAK‐mediated adhesion, extracellular matrix (ECM) remodeling, and endocytosis.
Behnam Rashidieh   +22 more
wiley   +1 more source

Overcoming Transmission Barriers: A Dual‐Functional Adhesive Hydrogel for Direct Monkeypox Virus Neutralization and Wound Healing

open access: yesAdvanced Science, EarlyView.
MPXV infection leads to persistent viral replication and severe local inflammation, while existing treatments cannot simultaneously remove viruses and repair injured tissue. This study constructs Polymer@mPDA@Gel hydrogel via a two‐step hierarchical assembly method: mPDA anchors photothermal polymers to form antiviral photothermal subunits, which are ...
Ming Zhang   +7 more
wiley   +1 more source

Systematic Multi‐Level Analyses Decode the Arthritis‐Neurodegeneration Axis With In Vivo Validation

open access: yesAdvanced Science, EarlyView.
Arthritis and neurodegeneration are usually studied as separate disorders, but this study connects them through population evidence, genetic inference, transcriptomic mapping, and mouse models. It highlights RNF40 as a context‐dependent joint‐brain candidate, induced in inflammatory joints yet functionally linked to dopamine‐neuron vulnerability ...
Jinwen Wang   +7 more
wiley   +1 more source

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

open access: yesAdvanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu   +17 more
wiley   +1 more source

ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER–Mitochondria Contact Sites

open access: yesAdvanced Science, EarlyView.
ABSTRACT Mitochondrial transport and distribution are crucial for cellular homeostasis, yet whether and how they are regulated by endoplasmic reticulum (ER)–mitochondria contact sites remains unclear. Here, we demonstrate that the ER protein atlastin‐2 (ATL2) orchestrates mitochondrial transport and distribution by promoting assembly of the transport ...
Yiru Cheng   +9 more
wiley   +1 more source

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