Results 101 to 110 of about 198,410 (265)

Caveolin‐1 Stabilizes SERCA2 to Counteract Acute Kidney Injury via Suppression of Ca2+‐Dependent Endoplasmic Reticulum Stress in Distal Tubules

open access: yesAdvanced Science, EarlyView.
In AKI, initial kidney injury upregulates the expression of Cav‐1, which subsequently binds to and stabilizes SERCA2 via its scaffolding domain and through deubiquitination, thereby regulating Ca2+ homeostasis and ER stress. Conversely, Cav‐1 deficiency accelerates SERCA2 degradation, triggering Ca2+ overload and ER stress, and ultimately exacerbating ...
Yan Zhang   +19 more
wiley   +1 more source

A Virus‐Inducible E3–RLCK–MADS Module Coordinates Suppression of Plant Immunity and Fertility in Rice

open access: yesAdvanced Science, EarlyView.
ABSTRACT Viruses often hijack host developmental programs to promote infection, but the mechanistic links between reproductive regulation and antiviral immunity remain incompletely understood. Here, we identify a virus‐triggered hierarchical degradation cascade that links antiviral immunity and fertility regulation in rice. We show that the rice grassy
Yuansheng Wu   +13 more
wiley   +1 more source

GLS1 Orchestrates Exosome‐Mediated Tumor‐Endothelial Communication to Facilitate Angiogenesis

open access: yesAdvanced Science, EarlyView.
This study reveals a previously unappreciated, non‐metabolic function of GLS1 in the control of tumor angiogenesis via exosome‐mediated CAV1‐TNC signaling, indicating that therapeutic targeting of GLS1 may offer a dual benefit by simultaneously suppressing tumor metabolic activity and angiogenic processes in head and neck cancer. ABSTRACT Glutaminase 1
Jianqiang Yang   +9 more
wiley   +1 more source

Light‐Switched Mesenchymal Stem Cells for In Situ Exosome Amplification in Craniofacial Bone Defect Reconstruction

open access: yesAdvanced Science, EarlyView.
Light‐switchable MSCs (MSC‐UCNPs) were constructed by intracellular incorporation of UCNPs. Upon 980 nm irradiation, UCNPs emitted localized ultraviolet light (365 nm), activating the ROS/HEXB/LAMP1 signaling pathway to suppress lysosome–multivesicular body fusion and thereby enhance exosome biogenesis. Embedded within an injectable hydrogel, MSC‐UCNPs
Tingting Wu   +7 more
wiley   +1 more source

Drug‐Induced Cuproptosis Defines the Therapeutic Window of Celecoxib in Intervertebral Disc Degeneration via the HSP90‐RBX1 Axis

open access: yesAdvanced Science, EarlyView.
This study reveals the dual role of celecoxib in intervertebral disc degeneration. While low concentrations are protective, high concentrations induce toxicity by upregulating HSP90, which synergizes with USP15 to deubiquitinate and stabilize RBX1. This leads to degradation of COMMD1/ATP7B, copper dyshomeostasis, and ultimately, cuproptosis.
Youfeng Guo   +11 more
wiley   +1 more source

“Membrane‐Guided” Repair Strategy: Precision Delivery of GGT1 Degrader for Targeted Repair and Regeneration of Spinal Cord Neurons

open access: yesAdvanced Science, EarlyView.
This study confirms that GGT1 is a key driver of neuronal ferroptosis following spinal cord injury. We developed NSCm@EA, a biomimetic delivery system coated with neural stem cell membranes, for precise delivery of enocyanin to injured neurons. By combining targeted delivery with ubiquitination degradation mechanisms, this system promotes MGRN1 ...
Tao Yang   +14 more
wiley   +1 more source

ZDHHC18‐Mediated Palmitoylation of ORF3a Promotes SARS‐CoV‐2 Pathogenesis by Antagonizing TRIM16‐Mediated Ubiquitination and Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
Palmitoylation by ZDHHC18 blocks ORF3a K27‐linked ubiquitination mediated by TRIM16, thereby preventing its proteasomal degradation and strengthening viral pathogenesis. Targeting palmitoylation through a pharmacological inhibitor (2‐BP), a competitive inhibitory peptide (OPIP), or adenovirus‐mediated knockdown of ZDHHC18 expression presents a ...
Sidi Yang   +17 more
wiley   +1 more source

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

open access: yesAdvanced Science, EarlyView.
Membrane proteins remain challenging targets for conventional TPD approaches. Here, the authors develop UPTAB, a modular platform leveraging ultrahigh‐affinity orthogonal Im/CL protein pairs for lysosomal degradation of membrane proteins. Mono‐targeted (Type‐I), dual‐targeted (Type‐II), and tri‐targeted (Type‐III) UPTABs enable simultaneous degradation
Mengqing Zhao   +7 more
wiley   +1 more source

Lactoferrin Deficiency During Lactation Causes Adult Obesity‐Related Metabolic Disease Through Persistent Adipose Dysfunction Driven by Impaired Adipocyte Development

open access: yesAdvanced Science, EarlyView.
Lactational lactoferrin deficiency exerts lasting effects on epididymal adipose tissue development from lactation into adulthood: it impairs adipocyte hyperplasia and induces pathological hypertrophy, resulting in lower body weight yet exacerbated metabolic dysfunction under a high‐fat diet in adulthood.
Qin An   +11 more
wiley   +1 more source

BCMA‐Engineered Dendritic Cell‐Derived Exosomes as Bi‐Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma

open access: yesAdvanced Science, EarlyView.
A dual‐function cell‐free therapeutic based on DC2.4 cell‐derived exosomes engineered to display BCMA. (Left) Soluble Ligand Sequestration (Decoy Function): DB Exo act as molecular decoys that predominantly sequester soluble APRIL with partial BAFF attenuation, effectively disrupting the NF‐κB survival signaling axis and suppressing myeloma cell ...
Yuqing Zeng   +5 more
wiley   +1 more source

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