Results 211 to 220 of about 489,988 (278)

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

Integrated Single‐Nucleus Multi‐Omics Atlases Reveal Lineage Plasticity and Regulatory Networks of Luminal Epithelial Cells During Mammary Gland Lactation and Involution

open access: yesAdvanced Science, EarlyView.
This study integrates single‐cell multi‐omics, spatial transcriptomics, and cross‐species comparative analyses to systematically characterize the cellular composition and differentiation trajectories of goat mammary epithelial cells, along with the gene regulatory networks and intercellular communication mechanisms governing these trajectories, thereby
Xiaoru Yan   +12 more
wiley   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

open access: yesAdvanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng   +19 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

YAP1‐Driven Pathogenic Fibro‐Adipogenic Progenitors Secrete IL‐6 and FGF21 to Mediate Muscle‐Bone Crosstalk and Promote Bone Loss

open access: yesAdvanced Science, EarlyView.
Fibro‐adipogenic progenitors (FAPs) in atrophic muscle undergo YAP1‐driven pathogenic activation, secreting IL‐6 and FGF21 as bone‐catabolic myokines that mediate muscle‐bone crosstalk and promote bone loss. Genetic or pharmacological targeting of this YAP1‐FAP‐myokine axis rescues skeletal deterioration, identifying FAP‐derived myokines as therapeutic
Xiaoyu Cai   +16 more
wiley   +1 more source

Deltacoronavirus Modulates circRNA cGLIS3 Metabolism to Evade Host Antiviral Response

open access: yesAdvanced Science, EarlyView.
This study reveals that both deltacoronavirus nucleocapsid protein and host RNA binding protein IGF2BP2 promote circular RNA GLIS3 (cGLIS3) biogenesis by binding to GLIS3 pre‐mRNA. The m6A modification‐mediated cGLIS3‐IGF2BP2 interaction weakens RNase L‐mediated degradation of cGLIS3 while facilitates a ubiquitin‐dependent degradation of IGF2BP2, thus ...
Liuyang Du   +10 more
wiley   +1 more source

Miro1 Protects Against Acute Kidney Injury Through Modulating Mitochondrial Homeostasis via Interaction With Sirt6

open access: yesAdvanced Science, EarlyView.
Ischemia‐reperfusion reduces Sirt6 activity, thereby increasing Miro1 acetylation. Hyperacetylated Miro1 exhibits perinuclear distribution and degradation, thereby inducing mitochondrial dysfunction and promoting apoptosis in renal tubular epithelial cells. This pathway reveals a mechanistic link between Sirt6‐mediated deacetylation and Miro1 stability
Lin Wu   +12 more
wiley   +1 more source

AI Designed Conformation Locking Peptides Target STING to Restore Diabetic Wound Healing

open access: yesAdvanced Science, EarlyView.
A generative AI pipeline identifies SCP‐1, a conformation‐locking peptide that stabilizes inactive STING. Incorporated into a dual‐responsive hydrogel for localized, MMP‐9‐triggered release, SCP‐1 suppresses inflammation, promotes reparative macrophage polarization, and accelerates diabetic wound healing.
Xinyu Li   +8 more
wiley   +1 more source

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