The lung, a key organ for oxygen exchange, is particularly susceptible to high-altitude hypoxic stress. Hypoxia induces vascular impairment, which is characterized by vascular inflammatory responses and aging-like changes. Lipid metabolism has been shown to be closely associated with cellular homeostasis and membrane balance. However, the alterations in pulmonary lipid metabolism in response to high-altitude hypoxia are not fully characterized. In this study, model mice were subjected to a hypobaric chamber at an altitude of 5500m for 3 days, and pulmonary microvascular endothelial cells (PMVECs) were cultured under 1% oxygen for 18h to simulate the effects of acute severe hypoxia. High-altitude hypoxia significantly disrupted lung sphingolipid metabolism, accompanied by inflammation and aging-like changes in mice. Moreover, C24-Ceramide (Cer) and its synthase (CERS2) were significantly increased in PMVECs. C24-Cer was identified to bind to voltage-dependent anion channel 1 (VDAC1) (a mitochondrial outer membrane protein), which promoted mitochondrial DNA (mtDNA) release and subsequently induced the inflammation and aging-like changes by activating the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway. Inhibition of C24-Cer or VDAC1 oligomerization by si-Cers2 or VBIT-4 could significantly reduce mtDNA release and alleviate inflammation and aging-like changes in the PMVECs and lung tissue under hypoxia. Our present work provides a novel and potential therapeutic target for high-altitude hypoxia-related vascular diseases.

Intensified water column hypoxia drives disproportionate benthic P release and N:P imbalance via enhanced sedimentary sulfate reduction.

Solid tumors present formidable barriers to immunotherapy due to low immunogenicity and a highly suppressive microenvironment. This study introduces Hb-DD@SRF, a mutually reinforcing nanoplatform comprising a sorafenib (SRF)-loaded core coated with a dual-targeting hemoglobin (Hb) shell. Upon targeting iron transporters on tumor cells, Fe2+ derived from Hb catalyzes reactive oxygen species (ROS) generation, while acidic conditions trigger SRF release to inhibit glutathione peroxidase 4 (GPX4), synergistically amplifying ferroptosis. This robust process elicits immunogenic cell death to prime T cells. Crucially, Hb-mediated oxygenation precisely offsets the severe hypoxia resulting from SRF, establishing a complementary loop that prevents drug resistance. Furthermore, the platform targets M2 macrophages via the haptoglobin pathway, where oxygen and SRF jointly reprogram them to reverse immunosuppression. This remodeled immunostimulatory microenvironment synergizes with anti-PD-L1 therapy to achieve pronounced suppression of primary and metastatic tumors. Collectively, Hb-DD@SRF orchestrates ferroptosis amplification and comprehensive microenvironment modulation to potentiate antitumor immunotherapy.

Abstract Mangroves host many marine species and support fisheries in developing (sub)tropical countries. The suitability of mangrove habitats depends strongly thier the water chemistry. Here, we show how global warming and rising atmospheric CO 2 will reduce dissolved oxygen and increase CO 2 in mangrove waters. Observations from 23 mangrove‐lined estuaries worldwide revealed that most sites already experience mild (34%–43% of the time) or severe (6%–32%) hypercapnic hypoxia, that is, high CO 2 and low oxygen conditions. Hypercapnic hypoxia mostly occurs during low tide, at low‐salinity sites, and in warm tropical regions. Climate change will decrease oxygen concentrations by 5%–35% and increase CO 2 concentrations by 8%–60% in mangrove waters by 2100. Overall, hypercapnic hypoxia events will occur more frequently, last longer, and become more severe. These shifts will reduce mangrove biodiversity and deteriorate habitat quality for commercially valuable fish. The strongest impact is expected in tropical developing countries.

Distinct roles of PINK1 autophosphorylation in neonatal hypoxia with or without convulsions.

Populations in managed care are valuable resources that complement in situ conservation efforts, but adaptation to captive conditions and other domestication effects present concerns for conservation. Many populations of fish adapted to sulfide springs are highly endemic and imperiled, potentially benefiting from ex situ conservation efforts. However, it is challenging to maintain natural conditions in the laboratory as hydrogen sulfide (H2S) is highly toxic and coincides with severe hypoxia. Here, we tested whether long-term standardized rearing of sulfide spring fishes leads to the loss of H2S and hypoxia tolerances. We compared the tolerances of Poecilia mexicana (Poeciliidae) from sulfidic and non-sulfidic habitats that were reared in the laboratory for 18 years and wild-caught fish from the same sites. Both H2S and hypoxia tolerances were maintained in laboratory-reared fish from the sulfidic habitat. Additionally, fish from a non-sulfidic cave site, evolutionarily derived from a sulfidic population, exhibited higher H2S and hypoxia tolerances than fish from the non-sulfidic surface site. While domestication can lead to the loss of adaptations to extreme environmental conditions, our research indicates this is not a concern in laboratory stocks of P. mexicana, which retained tolerance of H2S and hypoxia despite not experiencing these stressors for approximately 40 generations.

To compare the incidence of hypoxia and other sedation-related adverse events (AEs) in overweight patients undergoing gastrointestinal (GI) endoscopy who were sedated using ciprofol or propofol. A randomized, controlled trial was conducted in five hospitals in China between September 2022 and August 2023. Patients were randomized into either ciprofol or propofol sedation. The primary outcome was the total incidence of hypoxia and severe hypoxia. The secondary outcomes were hypoxia incidence, severe hypoxia incidence, subclinical respiratory depression incidence, endoscopy success rate, injection pain incidence, and corrective hypoxic measures proportion. A total of 1018 patients were randomized into either ciprofol group (n = 506) or propofol group (n = 512). The mean BMI was 26.23 kg/m2 in the ciprofol group and 26.17 kg/m2 in the propofol group. Compared with propofol, ciprofol showed lower incidences of total hypoxia and severe hypoxia in both the full analysis set (FAS) and per-protocol analysis set (PPS). The lower incidence was particularly significant for severe hypoxia (4.35% vs. 7.62%, p = 0.028 in FAS). The injection pain incidence was significantly lower in the ciprofol group than in the propofol group (2.57% vs. 13.28%, p < 0.001 in FAS). Moreover, fewer patients in the ciprofol group required oxygen-correction therapy (20.40% vs. 25.70%, p = 0.047 in PPS), and ciprofol had a lower incidence of AEs associated with sedation. During GI endoscopy, overweight patients are significantly less prone to hypoxia when sedated with ciprofol than with propofol, offering a safer alternative. ClinicalTrials.gov (NCT05518929).

Clinical and Microbiological Characteristics of macrolide-resistant Bordetella pertussis Infection: A case series in Osaka, Japan (2024-2025).

Limited intensity and duration of high-intensity focused ultrasound (HIFU)-induced immune response largely hinder postoperative immunotherapy due to low immunogenicity and immunosuppression of tumor microenvironment (TME). In this study, effect-specific metal-organic frameworks (MOFs) were designed based on the severe hypoxia of postoperative tumors through regulating TME to enhance body's antitumor immune response. The combination of iron ions, hypoxic-activated prodrug banoxantrone, and indoleamine 2,3-dioxygenase (IDO) signaling pathway inhibitor NLG919 is utilized to construct MOFs loaded with CaCO3, which achieves intraoperative monitoring via photoacoustic imaging for precise ablation of tumors. Ingeniously, banoxantrone, within the severely hypoxic environment of tumors induced by HIFU, is activated in the manner of converting enemies into friends and cooperates with iron ions to effectively trigger immunogenic cell death (ICD) in tumors. In addition, the immunosuppressive microenvironment exacerbated by postoperative hypoxia is degraded via the cooperation of NLG919, which blocks the IDO-1 signaling pathway and CaCO3, which consumes lactic acid. Based on these improvements, well-designed MOFs effectively inhibit bilateral tumor growth/metastasis and offer a successful paradigm for improving the overall prognosis of HIFU.

Hypoxia-induced regulatory changes are well understood across aquatic and terrestrial systems. These changes are normally initiated by elements belonging to hypoxia inducible factor (HIF) pathway. These elements generate responses that help organisms survive hypoxia, such as protein stabilization, antioxidant activity, or the switch from aerobic to anaerobic metabolism. The HIF pathway is initiated by the transcription factor HIF-α via deactivation of its repressor EGLN. However, recent work revealed that many aquatic invertebrates do not possess HIF-α or EGLN. Among these is the intertidal copepod Tigriopus californicus. Although this copepod experiences daily bouts of hypoxia, T. californicus tolerates even extended anoxia with minimal mortality. Because T. californicus lacks HIF-α, it is unclear how the transcriptional response proceeds on a fine timescale in this species and which physiological strategies they use to cope with severe hypoxia. In this study, we captured gene expression over a species-typical course of hypoxia including normoxia, mild hypoxia (∼3.5 mg O2 l-1), at critical oxygen tension (Pcrit; ∼0.5 mg O2 l-1), anoxia (0 mg O2 l-1), and recovery. We identified and clustered genes affected by this hypoxia course and tested for enrichment of gene ontology and transcription factor binding site motifs. We identified genes with known responses to hypoxia, including genes with interactions with HIF-α in other systems. We also identified genes related to functions unique to T. californicus, including exoskeletal modifications that could represent a specialized response allowing T. californicus to persist in extreme hypoxic environments despite lacking HIF-α.

Rigorous pre-clinical research in male rodents defined the cellular mechanisms of respiratory neuroplasticity following brief exposures to hypoxia (acute, intermittent hypoxia; AIH). AIH elicits phrenic long-term facilitation (pLTF), a progressive increase in phrenic nerve amplitude over time. Mechanisms to AIH-induced pLTF are complex and variable depending on the severity of hypoxemia during AIH. Moderate AIH (mAIH; PaO2 ~35-45mmHg) triggers spinal serotonin receptor activation to induce pLTF expression. More severe AIH (sAIH; PaO2 ~25-30mmHg) induces pLTF through an adenosine receptor-dependent pathway. Here we assessed: 1) if sAIH-induced pLTF is expressed in female rats, and whether sAIH-pLTF is impacted by the estrous cycle; 2) if the magnitude of sAIH-induced pLTF in female rats is similar to male rats; and 3) whether GDX alters the magnitude of sAIH-induced pLTF. We hypothesized that female rats would express sAIH-induced pLTF, and that circulating steroid hormone levels would have minimal impact on sAIH-induced pLTF in either sex. Our findings reveal that female rats express robust pLTF (~106% above baseline phrenic amplitudes) in response to sAIH, with minimal effects of estrous cycle stage. Female rats also showed a nearly 100% higher magnitude in sAIH-pLTF than males (p=0.006). Following GDX, pLTF magnitude was reduced in female rats (p=0.04), while males were unable to express pLTF. These findings predict unique cellular mechanisms to pLTF in female rats following sAIH, and sex-specific impacts of steroid hormone signaling on the expression of respiratory neuroplasticity.

Sudden unexpected death in epilepsy (SUDEP) is a devastating consequence of some generalized convulsive seizures (GCS). Recent work has focused on seizure related apnea as a biomarker of SUDEP risk, frequently without characterizing the adequacy of non-apneic ventilation or identifying other dysfunctional breathing patterns. We hypothesized that GCS frequently induce immediate, severe, non-apneic respiratory dysfunction that can induce critical hypoxia and bradycardia and sought to characterize breathing patterns after GCS. Adult patients admitted to an epilepsy monitoring unit were studied. The effects of GCS on breathing and heart rate were analyzed using nasal pressure transducers, chest and abdominal respiratory inductance plethysmography, capillary oxygen saturation, transcutaneous CO2, electrocardiogram, electroencephalogram, and expert audiovisual analysis. Correlation analyses, the Mann-Whitney test, and an unpaired t test were used to analyze relationships between dysfunctional breathing patterns and both the severity of postictal hypoxemia and the heart rate. Thirty-two GCS from 22 patients were analyzed and 31 exhibited 1 or more of the following breathing patterns: disordered rhythmicity (n = 28/32, 87.5%), shallow breathing (n = 12/32, 37.5%), thoracoabdominal asynchrony (n = 24/30, 80.0%), and upper airway obstruction (n = 30/32, 93.8%). Oxygen desaturation was more severe when postictal breathing was shallow or irregular in amplitude. The latter was associated with absolute or relative bradycardia. Nonfatal GCS frequently induce immediate, severe, non-apneic respiratory dysfunction temporally associated with severe hypoxia and bradycardia. Our study suggests that postictal respiratory and cardiac function are tightly coupled and highlights the importance of including all the relevant pathologic variables in studies of SUDEP pathogenesis. ANN NEUROL 2026.

Objective : To evaluate the diagnostic value of biomarkers of inflammation, lipid peroxidation, hypoxia and intraabdominal hypertension in gynecological peritonitis. Material and methods . Forty-four women with gynecologic peritonitis who underwent emergency laparoscopic peritoneal lavage were examined. Biomarkers of inflammation, oxidative stress, hypoxia and intra-abdominal pressure were determined before the operation, their values were compared with intraoperative findings. Results: Generalized peritonitis was accompanied by severe inflammatory and metabolic disorders. Levels of malondialdehyde (4.35 [4.00; 4.60] vs 3.25 [2.90; 3.50] nmol/ml) and conjugated dienes (2.92 [2.59; 3.18] vs 2.18 [1.93; 2.43] nmol/ml, p &lt; 0.001) were higher, indicating increased lipid peroxidation. Elevated levels of CRP, IL-6, procalcitonin PCT, and lactate (p &lt; 0.001) indicated activation of the inflammatory cascade and hypoxia. Intra-abdominal pressure in generalized peritonitis (22.70 [21.80; 23.68] vs 11.95 [11.40; 12.97] mmHg, p &lt; 0.001) confirmed the risk of intra-abdominal hypertension and organ dysfunction. More severe systemic inflammation and hypoxia were noted in severe intestinal dilation (p &lt; 0.001). Conclusion . The severity of gynecological peritonitis correlates with changes in biomarkers of inflammation, lipid peroxidation, hypoxia and intra-abdominal pressure, which emphasizes their diagnostic significance.

Urban rivers worldwide are increasingly exposed to multiple stressors from industrial, agricultural, and domestic activities; however, sensitive indicators to assess their ecological status remain limited. This study evaluated the potential of natural biofilms as bioindicators of environmental quality in two impacted river basins in Argentina: the Luján and Reconquista rivers. Biofilm and water samples were collected from upstream, urban, and industrial sites, and from controlled outdoor ponds used as a control. We analysed water physicochemical parameters, biofilm community composition, oxidative stress biomarkers (reduced glutathione, GSH; catalase, CAT; glutathione S-transferase, GST; and thiobarbituric acid reactive substances, TBARS), and extracellular enzyme activities (alkaline phosphatase, β-glucosidase). Results revealed clear water quality gradients, with downstream Luján sites and the mid-Reconquista showing severe deterioration, nutrient enrichment, hypoxia, and heavy metal exceedances. Biofilm communities mirrored these conditions: diverse and balanced assemblages dominated reference sites, while degraded ones showed reduced richness and tolerant taxa dominance. Biomarker responses also displayed consistent alterations, with high CAT activity (11,87 mmoles H2O2 cons x min-1 × mg prot-1 in L3 and 16,04 in R2), reduced GSH (0,007 mmoles GSH x g ww-1 in R2), and imbalances in GST and TBARS, indicating enhanced oxidative stress. Multivariate analyses integrated these datasets, consistently separating less-impacted from highly degraded sites. Overall, biofilms proved to be sensitive and cost-effective indicators, integrating structural and functional responses to contamination gradients, and offering a robust tool for monitoring urban rivers.

Abstract Metastasis accounts for the majority of cancer-related deaths, yet only a rare subset of tumor cells can successfully complete this process. Among these, polyaneuploid cancer cells (PACCs), which arise via endoreplication in response to stressors such as hypoxia, have been implicated as stress-resistant drivers of metastasis. In prostate cancer, the presence of PACCs within primary tumors correlates with poor prognosis and reduced metastasis-free survival, and these cells are consistently detected in metastatic lesions from patients. However, identifying PACCs and reproducibly modeling their formation in vitro remain major challenges to understanding their metastatic potential. Here, we build upon our validated in vitro model of tumor hypoxia to develop a reliable system for PACC induction and detection within prostate cancer. This membrane-based culture system permits the self-generated development of hypoxia as prostate cancer cells consume a limited amount of oxygen, while a phosphorescent oxygen-sensing film enables real-time, spatially resolved mapping of oxygen distribution across the culture. Under these conditions, heterogeneous populations of PACC and non-PACC cells emerge along an oxygen gradient, with cells at the core of the system experiencing the most severe hypoxia, thus effectively recapitulating the tumor microenvironment. This approach represents a marked departure from traditional PACC models, which rely on high doses of chemotherapy or hypoxia-mimetic agents to artificially induce their formation. To validate PACC induction, we performed flow cytometric DNA content analysis following 16 hours of hypoxia and observed a nearly threefold increase in the proportion of cells exceeding 4N genomic content. These results suggest that the tumor model promotes the emergence of prostate cancer-derived PACCs. To enable live detection of PACCs without DNA-binding dyes that may interfere with replication and cause phototoxicity, we established a morphology-based criterion. Cells exceeding 1500 µm2 in area and demonstrating ≥3-fold growth over 16 hours corresponded to the polyaneuploid population identified by conventional nuclear area analysis following DNA dye staining. Preliminary single-cell tracking using this classification showed that PACCs exhibit greater net and total displacements than non-PACCs under hypoxia, which are behaviors consistent with successful invasion during metastasis. Altogether, this system provides a physiologically-relevant model for inducing and identifying prostate cancer-derived PACCs in vitro. Coupled with the robust criteria for real-time PACC detection, this model establishes a foundation for future work to investigate the mechanisms by which PACCs may promote metastatic progression in prostate cancer. Citation Format: Noreen Hosny, Shengkai Li, Sarah Amend, Robert Gatenby, Kenneth J. Pienta, Joel Brown, Junle Qu, Robert H. Austin. In vitro tumor hypoxia model enables induction and real-time detection of polyaneuploid cancer cells (PACCs) in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B030.

This study aimed to examine the physiological mechanisms associated with Voluntary Isocapnic Hyperpnoea (VIH) in severe hypoxia and evaluated whether such respiratory modulation may attenuate hypoxemia and Acute Mountain Sickness (AMS). Eighteen healthy participants (8 females) completed two 2-hour sessions in a normobaric hypoxic chamber simulating 4200m above sea level, in randomized order: an experimental session including a 5-minute VIH intervention after 1h, and a control session without VIH. AMS symptoms, arterial oxygen saturation (SpO₂), heart rate, blood pressure and gases were monitored before and during the hypoxic exposure. Separate repeated-measures ANOVAs were employed to analyze the effects of VIH and differences between the sessions. VIH decreased clinical hypoxemia (from 83.3% to 22.2%) and reduced AMS incidence (from 11.1% to 5.5%). This was associated with an increase in SpO₂ (p = 0.011, ηp2 = 0.341, ω2 = 0.159) and blood oxygen partial pressure (p = 0.027, ηp2 = 0.271, ω2 = 0.112). SpO₂ kinetics differed between sessions (p = 0.011, ηp2 = 0.132, ω2 = 0.061), with higher values during the experimental session. This benefit was acute as differences in SpO₂ were not noted at the final timepoint. Substantial intra-individual variability and no sex-related interactions were observed. These preliminary findings suggest that VIH is a feasible method for transiently improving blood oxygen saturation under hypoxia, and has the potential to attenuate AMS. Further research is nevertheless warranted to clarify the role of VIH within the framework of altitude medicine and address potential mechanistic explanations. Methodological insights from the present study should inform future investigations.

ObjectiveTo quantify the relationship between the longest apnea duration (LAD) and the lowest oxygen saturation (LSaO2) in patients with obstructive sleep apnea (OSA) and to develop a predictive model for the risk of LSaO2 decline.MethodsA total of 1716 OSA patients were enrolled and grouped by severity (236 non-OSA, 395 mild, 365 moderate, and 720 severe). Multiple linear regression was used to analyze the dose-effect relationship between LAD and LSaO2. A logistic regression model was developed to predict LSaO2 grade, with the dataset partitioned into a training set (n = 1,372) and a testing set (n = 344) using random sampling.Results(1) For every 1-s increase in LAD, LSaO2 decreased by 0.280% (95% CI: −0.291%∼-0.269%) in a univariate model and still decreased by 0.183% (95% CI: −0.197%∼-0.170%) after adjusting for sex, age, BMI, and AHI; (2) Critical points were identified: LSaO2 was 85% when LAD was 34.20 s and 80% when LAD was 52.07 s; (3) The predictive model showed excellent identification performance for severe (AUC = 0.93) and moderate-severe LSaO2 (AUC = 0.96).ConclusionThe study first quantifies the dose-response relationship between LAD and LSaO2 and establishes relevant clinical thresholds. The developed model can accurately identify patients at risk of severe and moderate-severe hypoxia, offering a new tool for individualized intervention.

Abstract Severe hypoxia within thick bioengineered tissues critically impairs cell viability and function, limiting their application in organ-scale engineering and regenerative medicine. Current methods for oxygen delivery often fall short of providing sustained oxygenation before neovascularization. Here, we introduce a smart self-oxygenating tissue (SSOT) platform that leverages a bio-ionic liquid (BIL)-functionalized biocompatible hydrogel electrolyte for localized and controlled oxygen generation via electrolysis. Comprehensive characterization of the system confirmed stability and electrochemical properties, with molecular dynamics simulations demonstrating that BIL enhances oxygen release. In vitro, the SSOT platform maintains cell viability and promotes vascularization under severe hypoxic conditions. Diabetic wound healing studies using mouse models showed that an SSOT patch accelerates wound closure in chronic and non-chronic wounds. These findings highlight the potential of electrolysis-driven methods for providing on-demand and sustained oxygen delivery, essential for the development of functional living tissues and ultimately organs.

Historical and future water quality risks driven by climate change: Strategic management and overcoming challenges.

Hemoglobin adduction and impaired oxygen transport define the etiology of pyrrolizidine alkaloid-induced pulmonary arterial hypertension.