Results 171 to 180 of about 487,432 (309)

Metabolic Regulation of Dimethylsulfoniopropionate Cleavage and Dimethyl Sulfide Production in Halomonas sp. D47

open access: yesAdvanced Science, EarlyView.
Dimethylsulfoniopropionate (DMSP) is a major marine organosulfur compound central to climate‐relevant dimethyl sulfide (DMS) production. In Halomonas sp. D47, DMSP catabolism is revealed to be coordinated by two transcriptional regulators, AcuR and AcuZ, which control gene expression by sensing DMSP and its metabolites.
Li‐Yuan Zheng   +16 more
wiley   +1 more source

Endogenous “Time Bomb” – Mislocalized Phospholipase A2 as a Critical Mediator of Ultra‐Rapid Mortality in Sepsis and Acute Lung Injury

open access: yesAdvanced Science, EarlyView.
Phospholipase A2 (PLA2), a dormant enzyme, becomes lethal when activated—collapsing lungs in minutes. Our dual therapy (DOPS + varespladib) boosts survival from 0% to >90% in sepsis/ALI. A breakthrough for acute lung injury treatment. ABSTRACT This study reveals that phospholipase A2 (PLA2), normally stable and nontoxic, can be activated specifically ...
Jianyu Wang   +7 more
wiley   +1 more source

UBE2T‐Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation‐Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
This study integrates multi‐omics to reveal the critical role of UBE2T in driving malignancy and stromal co‐evolution in PDAC. UBE2T potentiates glycolysis by regulating p53 degradation via a positive feedback loop, thereby promoting histone H3 lysine 18 lactylation in CAFs and stromal deposition. The UBE2T inhibitor PGG represents a potential strategy
Yong Ma   +16 more
wiley   +1 more source

Cuproptosis and Disulfidptosis Converge to Empower PD‐L1 Checkpoint Therapy via Cadict‐Induced PD‐L1 Translation

open access: yesAdvanced Science, EarlyView.
This study introduces Cadict, an EGFR‐targeted nanodrug that co‐delivers cuproptosis and disulfidptosis inducers to overcome immune resistance. Cadict synergistically enhances tumor cytotoxicity and sensitizes cancers to ICIs by upregulating PD‐L1 via an Eif5b‐dependent translation mechanism, fostering a potent antitumor immune response and ...
Shaoqing Huang   +12 more
wiley   +1 more source

Understanding and Overcoming Antibody‐Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer

open access: yesAdvanced Science, EarlyView.
Antibody–drug conjugates (ADCs) transform breast cancer therapy, yet resistance limits their durability. Emerging evidence reveals that ADC failure is not solely tumor‐intrinsic but shaped by dynamic tumor–microenvironment interactions that alter drug delivery, processing, and response.
Minji Seo, Jangsoon Lee, Naoto T. Ueno
wiley   +1 more source

Deciphering and Targeting the Schwannoma‐Neuron‐Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain

open access: yesAdvanced Science, EarlyView.
We established patient‐derived SWN cell lines and orthotopic PDX models that recapitulate patient pain phenotypes, alongside a novel intravital DRG imaging platform to track macrophage infiltration and neuronal pain responses. Using these models, we define HMGB1–CCL2–IL‐6 signaling crosstalk driving pain and identify EGF signaling as a key regulator of
Zhenzhen Yin   +17 more
wiley   +1 more source

An Insulin‐Exosome‐TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
In pancreatic ductal adenocarcinoma (PDAC), insulin is associated with activation of PI3K/AKT–RAB3A signaling and enhanced secretion of TNFAIP8‐enriched exosomes from tumor cells. Uptake of these exosomes by fibroblasts is linked to TRIM21‐dependent STAT1 degradation and the emergence of myofibroblastic CAF–associated features, accompanied by increased
Zhenyu Li   +15 more
wiley   +1 more source

Embedded CRISPRi Enhances Gene‐Silencing Efficiency in Drosophila

open access: yesAdvanced Science, EarlyView.
Current CRISPR interference (CRISPRi) technology in Drosophila has limited efficiency. This study introduces the emCRISPRi platform, which significantly enhances transcriptional silencing efficacy by embedding inhibitory domains within the dCas9 architecture.
Pengchong Fu   +7 more
wiley   +1 more source

Engineering Compact Base Editors by AlphaFold‐Guided Mutation Scan and Escherichia coli‐Based Tri‐Selection

open access: yesAdvanced Science, EarlyView.
A miniaturized deaminase SsdAtox was scanned with AlphaFold to identify DNA binding pocket hot spots. Site‐saturation mutagenesis at gatekeeper residue K31 yielded ten‐fold activity enhancement. Trinity Screen, an E. coli‐based three‐in‐one platform selecting for high activity and reduced double‐strand breaks, enabled combinatorial evolution at DNA ...
Ryeo Gang Son   +2 more
wiley   +1 more source

A Testis‐Specific Aralkylamine N‐Acetyltransferase Regulates Dimorphic Sperm Function and Male Fertility in Moths

open access: yesAdvanced Science, EarlyView.
We identify a Lepidoptera‐conserved testis‐specific arylalkylamine N‐acetyltransferase (LTNAT) that governs male moth fertility via a novel mechanism. LTNAT loss disrupts eupyrene sperm mitochondrial derivatives and impairs apyrene sperm motility, offering a safe molecular target for innovative pesticides and genetic pest control.
Hao Sun   +5 more
wiley   +1 more source

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