Results 181 to 190 of about 580,571 (256)

PolyG Fibrils Coalesce Into Nuclear Ribbons That Engage Proteostasis Machinery in Neuronal Intranuclear Inclusion Disease

open access: yesAdvanced Science, EarlyView.
In NIID, expanded NOTCH2NLC repeats give rise to nuclear polyG inclusions. Tracer‐guided in situ cryo‐electron tomography enables cross‐scale structural analysis from mouse brain to native neuronal nuclei, revealing dense‐core/peripheral‐halo inclusions built from compact polyG ribbons.
Hui Dong   +13 more
wiley   +1 more source

Self‐Assembly of Antigenic Peptide Nanofibrils Templates the Growth of Silica Nanoparticles for Nanovaccines

open access: yesAdvanced Science, EarlyView.
Antigenic peptides Aβ42 and E7 self‐assemble into nanofibrils; APTES and TEOS induce SiO2 NP formation on these fibrils to form SiO2@fibril nanovaccines, which activate BMDCs in vitro. In vivo, SiO2@Aβ42 fibril nanovaccines alleviate AD symptoms and clear Aβ42 plaques in APP/PS1 mice, and SiO2@E7 fibril nanovaccines inhibit tumor growth and promote ...
Xuecheng Yang   +6 more
wiley   +1 more source

Renal Clearable Luminogenic Reporter for Ultrasensitive Influenza Virus Imaging and Efficient Antiviral Therapies Monitoring in Living Mice

open access: yesAdvanced Science, EarlyView.
A viral luminogenic reporter with chemiluminescence/fluorescence dual‐response and efficient renal clearance was developed for non‐invasive imaging and urinalysis of H1N1 virus protease, allowing for remote detection of H1N1 virus infections and monitoring of antiviral therapeutic efficacy in living mice.
Bankang Ruan   +9 more
wiley   +1 more source

Harmonizing Rigidity and Flexibility: Embedding COF Quantum Dots Into Extracellular Matrix Gel as Carbon Monoxide Depot for Acoustically Triggered Time‐Programmable Anti‐Infective Therapy

open access: yesAdvanced Science, EarlyView.
A rigid‑flexible integrated CO depot is engineered by embedding rigid COFQDs into a flexible ECM gel network. The rigid framework enables high‑capacity CO storage and sonodynamic bacterial killing, while the flexible ECM gel controls sustained CO release, collectively eradicating multidrug‑resistant infection and promoting scarless healing.
Baohong Sun   +13 more
wiley   +1 more source

Programmable Nanobody‐Targeting Chimeras Enable Intracellular Viral Protein Degradation

open access: yesAdvanced Science, EarlyView.
Nab‐TAC enables targeted degradation of HBV surface antigen (HBsAg) in vivo. By fusing nanobody‐based recognition domains with programmable proteasome‐recruiting degradation signals, Nab‐TAC reduces HBsAg levels in a hydrodynamic HBV mouse model. ABSTRACT Chronic hepatitis B virus (HBV) infection remains a major global health challenge, largely because
Max Yu‐Chen Pan   +11 more
wiley   +1 more source

Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance

open access: yesAdvanced Science, EarlyView.
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer   +9 more
wiley   +1 more source

A Second Pathogenic Protein, PolyGN2C‐iso2, Reveals a Dual‐Protein Pathology in Neuronal Intranuclear Inclusion Disease

open access: yesAdvanced Science, EarlyView.
This study reveals that NOTCH2NLC transcript variant 2 generates PolyGN2C‐iso2, an aggregating protein present within intranuclear inclusions of NIID patient tissues. A novel mouse model expressing PolyGN2C‐iso2 recapitulates white matter abnormalities and cognitive deficits, mechanistically linked to mitochondrial dysfunction. These findings support a
Kang Zhang   +22 more
wiley   +1 more source

Immediate Growth Control in Response to Boiling Histotripsy is Prognostic for Intratumoral Immune Activation

open access: yesAdvanced Science, EarlyView.
Boiling Histrotripsy (BH), a mechanical form of focused ultrasound (FUS), allows for non‐invasive and non‐ionizing tissue destruction. Utilizing a BH treatment protocol that yielded bifurcating primary tumor growth responses, we found that immediate BH‐induced tumor growth control identifies tumors with acute reductions in antigen‐presenting cells (APC)
Lydia E. Kitelinger   +8 more
wiley   +1 more source

Integrated Single‐Cell and TCR Profiling Reveals Protection‐Associated CD8+ T Cell Subsets Linked to Viral Control in PRRSV

open access: yesAdvanced Science, EarlyView.
PRRSV vaccine‐mediated protection is associated with clonally expanded cytotoxic CD8+ T cell subsets driven by viral structural proteins and supported by innate TLR4/TLR8 signaling and CD4+ T cell help, whereas non‐protective responses are characterized by dysfunctional exhausted‐like CD8+ T cells linked to poor viral control.
Can Kong   +14 more
wiley   +1 more source

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

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