Results 101 to 110 of about 98,151 (252)

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

Repurposing a Small Molecule Plant Hormone as a Tunable ON‐Switch for CAR‐T Cell Immunotherapy

open access: yesAdvanced Science, EarlyView.
By engineering a receptor system integrating the plant auxin receptor AFB1 with its co‐receptor IAA7, we enable ligand‐dependent interactions triggered by the plant hormone auxins. This design allows rapid, reversible, and dose‐dependent T cell activation, resulting in potent cytotoxicity against B‐cell lymphoma in vitro and in vivo.
Hongxiang Zeng   +16 more
wiley   +1 more source

VlPAG/DRN Microglia Drive Neuropathic Pain‐Induced Depression via a Defined Neuroimmune Axis

open access: yesAdvanced Science, EarlyView.
Peripheral nerve injury (SNI) induces neuropathic pain, activates midbrain microglia, and triggers an NLRP3–IL‐1β–dependent inflammatory cascade. IL‐1β signals through IL‐1R1 on vlPAG/DRN VGLUT2+ neurons (vlPAG/DRNGlu), inducing hyperexcitability and driving the vlPAG/DRNGlu→BNSTGABA circuit to produce the affective component of neuropathic pain ...
Jing Yang   +7 more
wiley   +1 more source

Nucleoside‐Modified mRNA Encoding Alpha‐Galactosidase A Ameliorates Fabry Disease Phenotypes in Human IPSC‐Derived Cardiomyocytes

open access: yesAdvanced Science, EarlyView.
Human iPSC‐derived Fabry cardiomyocytes exhibited broad transcriptional dysregulation, apoptosis, mitochondrial dysfunction, impaired reactive oxygen species handling, altered contractility, and abnormal calcium transient decay, potentially mediated by phospholamban hyperphosphorylation.
Malte Juchem   +24 more
wiley   +1 more source

S9 protease WprP2 catalyzes uniform cleavage on the precursor peptide in RiPP biosynthesis

open access: yesCommunications Chemistry
Serine proteases in ribosomally synthesized and post-translationally modified peptides (RiPPs) catalyze the cleavage on the precursor peptides in the biosynthesis of RiPP natural products. Here, we identified an uncharacterized serine protease WprP2 from
Jabal Rahmat Haedar   +4 more
doaj   +1 more source

Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy

open access: yesAdvanced Science, EarlyView.
This work positions the versatile performance of the peptide‐based bioPhosTAC platform for dissecting phosphorylation‐dependent biology and expanding the scope of induced‐proximity technologies. We demonstrated that selective manipulation of a tyrosine phosphorylation site is sufficient to propagate coordinated cellular consequences.
Seung Un Seo   +7 more
wiley   +1 more source

Uncoupling Type I Interferon Benefits From Inflammatory Toxicity: Transformer‐Prioritized Precision Agonists for Potent and Safer Cancer Immunotherapy

open access: yesAdvanced Science, EarlyView.
A Transformer‐based AI framework, DLINP, screens millions of compounds to identify Co68, a cobalt‐pincer organometallic complex that biases TLR4‐MD2 signaling toward antitumor interferon activation while suppressing inflammatory toxicity through an early TLR4‐SYK‐STAT1 axis.
Xuefei Guo   +10 more
wiley   +1 more source

Natural‐Inspired Engineered Microalgae With Selenium Enrichment Enabled Potent Anti‐Tumor Immunity

open access: yesAdvanced Science, EarlyView.
Se‐Ssp was engineered as a potent immunomodulator for activating innate immunity via the TLR and cGAS‐STING pathways, therefore converting “cold” tumors into “hot” tumors to achieve high efficacy and long‐term therapeutic outcomes. ABSTRACT Immunotherapy has shed light on clinical oncology for several decades.
Yuqi Yang   +11 more
wiley   +1 more source

Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A

open access: yesAdvanced Science, EarlyView.
Corynoxine exerts potent broad‐spectrum anticancer activity by directly targeting NQO1. This interaction dissociates the oncogenic NQO1‐PTPA complex, releasing PTPA to robustly activate the tumor suppressor PP2A. Consequently, downstream Raf/MEK/ERK and PI3K/AKT signaling pathways are suppressed, downregulating c‐Myc and driving tumor regression ...
Guoqing Hou   +6 more
wiley   +1 more source

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