Asparaginase and Autophagy Inhibitors Effectively Remove Senescent Cells by Synergistically Limiting Asparagine Supply.

The accumulation of senescent cells (SNCs) contributes to tissue dysfunction and age-related diseases, creating an urgent need for effective senolytic strategies. We identified a metabolic vulnerability in SNCs characterized by marked downregulation of asparagine synthetase (ASNS), rendering them uniquely dependent on exogenous asparagine (Asn). This vulnerability was exploited through combined treatment with L-asparaginase (ASNase) and autophagy inhibitors, which synergistically deplete Asn via complementary mechanisms: ASNase degrades extracellular Asn pools, while autophagy inhibition blocks intracellular protein recycling as an alternative Asn source.

GLUT3 enhances chemosensitivity in glioblastoma by transporting temozolomide and capecitabine.

Glioblastoma multiforme (GBM), the most aggressive brain cancer, is highly resistant to chemotherapy, which profoundly affects patient survival and prognosis. Temozolomide (TMZ), the sole first-line chemotherapeutic agent for GBM, faces substantial challenges in overcoming this resistance. Despite the belief that TMZ is well-absorbed in the small intestine and can effectively cross the blood-brain barrier due to its small molecular size, emerging evidence suggests that its uptake is not merely through passive diffusion across the lipid bilayer but is regulated by Wnt signaling.

Synthesis of Highly Functionalized Indolizines via NIS-Promoted Spiroannulation/Ring-Opening Aromatization of Alkylidene Oxindoles with 2-(Pyridin-2-yl)acetate Derivatives.

A novel NIS-promoted domino reaction of alkylidene oxindoles with 2-(pyridin-2-yl)acetate derivatives has been established, enabling the efficient and straightforward synthesis of a vast variety of highly functionalized indolizines via sequential spiroannulation and ring-opening aromatization processes. The protocol features mild reaction conditions, broad substrate scope, high efficiency, scalability, and applicability for the preparation of CF-containing indolizines. Furthermore, the functional groups in the indolizine framework provide the feasibility for follow-up derivatization.

SIRT7 knockdown promotes gemcitabine sensitivity of pancreatic cancer cell via upregulation of GLUT3 expression.

Gemcitabine serves as a first-line chemotherapeutic treatment for pancreatic cancer (PC), but it is prone to rapid drug resistance. Increasing the sensitivity of PC to gemcitabine has long been a focus of research. Fasting interventions may augment the effects of chemotherapy and present new options.

Facile Preparation of Ultrathin Co O /Nanocarbon Composites with Greatly Improved Surface Activity as a Highly Efficient Oxygen Evolution Reaction Catalyst.

The efficient catalytic oxidation of water to dioxygen plays a significant role in solar fuel and artificial photosynthetic systems. It remains highly challenging to develop oxygen evolution reaction (OER) catalysts with high activity and low cost under mild conditions. Here, a new composite material is reported based on ultrathin 2D Co O nanosheets and reduced graphene oxides (rGO) by means of a one-pot hydrothermal strategy.