Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2α (HIF-2α)1. Here we show that monotherapy with casdatifan—an orally bioavailable, potent and selective HIF-2α inhibitor2—produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100 mg once daily (QD) cohort (n = 32) and the total cohort (n = 127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19–55%; 100 mg QD) and 31% (95% CI = 23–40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7–not estimable; 100 mg QD) and 12.2 months (9.4–20.6; total). Greater maximal reductions in serum

AbstractBackground. Overwhelming presence of immunoregulatory myeloid cells and dysfunctional T cells is a major barrier to effective immunotherapies in gl

Abstract. Extreme flooding driven by climate change demands strategies to enhance plant tolerance to low-oxygen stress. We investigated the ability of bioa

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

TNF-driven metabolic reprogramming enhances glucose utilization in monocytes through inducible nitric oxide synthase (iNOS) and hypoxia-inducible factor 1α (HIF-1α), promoting parasite control and host...

Obstructive sleep apnea (OSA) is a prevalent chronic respiratory condition characterized by repetitive upper airway collapse during sleep, leading to transient hypoxemia and arousals from sleep. Multiple risk factors heighten susceptibility to OSA. Intermittent hypoxia caused by OSA can increase the risk of end-organ morbidity. Key mechanisms include mitochondrial dysfunction, excessive production of ROS, and inflammation driven by NF-κB. HIF-1α responses vary by tissue and exposure pattern and may be attenuated during chronic intermittent hypoxia.

TNF-driven metabolic reprogramming enhances glucose utilization in monocytes through inducible nitric oxide synthase (iNOS) and hypoxia-inducible factor 1α (HIF-1α), promoting parasite control and host...

Hypoxia in marine systems is expanding worldwide due to anthropogenic activities. Deep waters of the St. Lawrence Estuary and Gulf are rapidly deoxygenating (∼1 mmol O2 m−3 y−1), driven by changes in Atlantic water-mass intrusion and nutrient‐fueled remineralization, and are simultaneously acidifying (∼0.004 pH unit y−1). These changes alter biogeochemical cycles and degrade habitats, causing biotic and economic consequences. Using a coupled physical-biogeochemical model, we tested whether watershed-scale nitrate reductions could mitigate deep‐water deoxygenation and carbonate-system degradation. Three nitrate‐reduction scenarios reduced riverine St. Lawrence River nitrate loads by about 11%, 30%, and 50% (−2.8, −7.5, and −11.7 mmol N m−3, respectively). Relative to the baseline simulation, these scenarios increased dissolved oxygen concentrations (DO) (+1.6, +4.3, and +6.7 mmol O2 m−3), pH (+0.004, +0.010, and +0.016), and aragonite saturation state (Ωarag) (+0.003, +0.009, and +0.015) in the deep Laurentian Channel (⩾175 m). The volume of deep waters with DO saturation

Abstract. Extreme flooding driven by climate change demands strategies to enhance plant tolerance to low-oxygen stress. We investigated the ability of bioa

Abstract. Extreme flooding driven by climate change demands strategies to enhance plant tolerance to low-oxygen stress. We investigated the ability of bioa

Abstract. Osteocytes regulate skeletal homeostasis and respond to oxygen deprivation via hypoxia inducible factors (HIFs), the principal transcriptional me

Wu et al. show that endothelial FGF13 functions as a potent suppressor of hypoxia-driven angiogenesis. Endothelial FGF13 functions as a potent suppressor of hypoxia-driven angiogenesis. By facilitating RACK1-dependent, oxygen-independent degradation of HIF-1α, FGF13 limits vascular growth, whereas FGF13 endothelial deficiency stabilizes this pathway and enhances angiogenic repair.

Eutrophication and warming in Lake Erie create two microbial threats: cyanobacterial harmful algal blooms (cHABs) that can produce toxins, and seasonal hypoxia driven by microbial respiration. These p...

Why transposable elements (TEs) persisted or expanded in genomes remains a mystery. Using integrated analysis of TE macro- and microevolution in locusts, our results showed that thousands of TE inser...

Background Subretinal fibrosis (SRF), a severe vision-threatening complication secondary to neovascular age-related macular degeneration (nAMD), remains a major clinical challenge due to its complex pathogenesis and prolonged disease course. The fibrotic process is driven by multiple synergistic factors, including chronic inflammation, hypoxia, epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and pathological neovascularization, which collectively lead to the ineffectiveness of conventional anti-vascular endothelial growth factor (VEGF) monotherapies in halting disease progression. Results This study developed a sequential dual-drug delivery system based on the terpolymer P(NIPAM-co-AA-co-HEMA) hydrogel (NAHGel), designed to achieve multi-targeted regulation from the pathological microenvironment to downstream fibrotic processes. NAHGel exhibits excellent thermal responsiveness, biomechanical stability, and biodegradability, and is co-loaded with

Wang et al. identify an immunoregulatory subset of IGFBP2+ NK cells in liver cancer, driven by hypoxia-induced histone lactylation. NK-secreted IGFBP2 helps tumors evade immunity by suppressing stress ligand expression. Blocking IGFBP2 restores tumor sensitivity to cytotoxicity and synergizes with checkpoint therapy, revealing a therapeutic target.

Abstract. Extreme flooding driven by climate change demands strategies to enhance plant tolerance to low-oxygen stress. We investigated the ability of bioa

As critical transitional zones between land and sea, estuaries are confronting the dual threats of increasing acidification and hypoxia driven by human activities and climate change. However, the comb...

Recurrent retinal detachment (RD) is a major determinant of vision loss following primary RD repair, largely driven by proliferative vitreoretinopathy, a fibroinflammatory wound-healing process in which hypoxia-inducible factor (HIF)–regulated transcriptional programs have been implicated. Statins possess anti-inflammatory and anti-fibrotic properties and are indirect HIF inhibitors. Our aim was to evaluate whether preoperative statins reduced the risk of recurrent RD repair within one year after primary repair.

Glucose deprivation in the primary CNS lymphoma (PCNSL) tumor microenvironment drives SLC2A5 (encoding GLUT5)-dependent fructose metabolism in tumor cells, while hypoxia induces HIF-mediated SLC2A5 expression in tumor-supportive macrophages, revealing SLC2A5 -driven fructose utilization as a shared and targetable metabolic vulnerability across malignant and microenvironmental compartments. ABSTRACT Primary central nervous system lymphoma (PCNSL) exhibits distinct molecular features and a unique tumor microenvironment (TME) characterized by hypoxia and reduced cerebrospinal fluid glucose levels. However, the extent to which the PCNSL TME shapes the metabolic and functional states of tumor and non-tumor microenvironment cells remains largely unexplored. Utilizing single-cell multi-omic approaches, we systematically dissected tumor-TME interactions in PCNSL and showed that glucose deprivation within the TME leads to enhanced SLC2A5 -mediated fructose metabolism in tumor cells and contributes to T cell dysfunction. Furthermore, hypoxia within the TME induces SLC2A5 expression in tumor-supportive macrophages through HIF-dependent transcriptional regulation, establishing SLC2A5 and its associated fructose metabolism as potential metabolic vulnerabilities in both tumor cells and tumor-supportive macrophages. In vitro and in vivo functional assays further demonstrated that genetic and pharmacologic inhibition of SLC2A5 -mediated fructose uptake markedly suppressed lymphoma growth. Collectively, our study uncovers a novel potential metabolic liability targeting tumor–TME interactions in PCNSL.