Hydrodynamic and Biochemical Impacts on the Development of Hypoxia in the Louisiana–Texas Shelf Part I: Numerical Modeling and Hypoxia Mechanisms

A three-dimensional coupled hydrodynamic–biogeochemical model with N, P, Si cycles and multiple phytoplankton and zooplankton functional groups was developed and applied to the Gulf of Mexico to study bottom dissolved oxygen dynamics. A 15-year hindcast was achieved covering the period of 2006–2020. Extensive model validation against in situ data demonstrates that the model is capable of reproducing vertical distributions of dissolved oxygen (DO), frequency distributions of hypoxia thickness, spatial distributions of bottom DO concentration and interannual variations of hypoxic area. The impacts of river plume and along-shore currents on bottom DO dynamics were examined based on multiyear bottom DO climatology, the corresponding long-term trends, and interannual variability. Model results suggest that mechanisms of bottom hypoxia developments are different between the west and east Louisiana–Texas Shelf waters. The mid-Atchafalaya nearshore (10–20 m) region firstly suffers from hypoxia in May, followed by the west-Mississippi nearshore region in June. Hypoxic waters expand in the following months and eventually merge in August. Sediment oxygen consumption (SOC) and water stratification (measured by potential energy anomaly, PEA) are two main factors modulating the variability of bottom DO concentration. Generalized Boosted Regression Models provide analysis of the relative importance of PEA and SOC. The analysis indicates that SOC is the main regulator in nearshore regions, and water stratification outcompetes the sedimentary biochemical processes in the offshore (20–50 m) regions. A strong quadratic relationship was found between hypoxic volume and hypoxic area, which suggests that the volume mostly results from the low DO in bottom water and can be potentially estimated based on the hypoxic area.

Vascular reactivity contributes to adipose tissue remodeling in obesity

Vascular reactivity of adipose tissue (AT) is hypothesized to play an important role in the development of obesity. However, the exact role of vascular reactivity in the development of obesity remains unclear. In this study, we investigated the chronological changes in vascular reactivity and the microenvironments of the visceral AT (VAT) and subcutaneous AT (SAT) in lean and obese mice. Changes in blood flow levels induced by a β-adrenoceptor agonist (isoproterenol) were significantly lower in the VAT of the mice fed a high-fat diet (HFD) for 1 and 12 weeks, compared to those in the VAT of the mice fed a low-fat diet (LFD) for the same period; no significant change was observed in the SAT of any mouse group, suggesting depot-specific vascular reactivity of AT. Consistently, the hypoxic area and the expression of genes associated with angiogenesis and macrophage recruitment were increased in the VAT (but not in the SAT) of mice fed an HFD for 1 week, compared with mice fed an LFD. These changes occurred with no morphological changes, including those related to adipocyte size, AT vessel density, and the diameter and pericyte coverage of the endothelium, suggesting a determinant role of vascular reactivity in the type of AT remodeling. The suppression of vascular reactivity was accompanied by increased endothelin-1 gene expression and extracellular matrix (ECM) stiffness only in the VAT, implying enhanced contractile activities of the vasculature and ECM. The results suggest a depot-specific role of vascular reactivity in AT remodeling during the development of obesity.

Escherichiacoli Nissle 1917 as a Novel Microrobot for Tumor-Targeted Imaging and Therapy

Highly efficient drug delivery systems with excellent tumor selectivity and minimal toxicity to normal tissues remain challenging for tumor treatment. Although great effort has been made to prolong the blood circulation and improve the delivery efficiency to tumor sites, nanomedicines are rarely approved for clinical application. Bacteria have the inherent properties of homing to solid tumors, presenting themselves as promising drug delivery systems. Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to selectively colonize in the hypoxic area of the tumor for survival and reproduction. EcN can be engineered as a bacteria-based microrobot for molecular imaging, drug delivery, and gene delivery. This review summarizes the progress in EcN-mediated tumor imaging and therapy and discusses the prospects and challenges for its clinical application. EcN provides a new idea as a delivery vehicle and will be a powerful weapon against cancer.

Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

Oxygen-Based Nanocarriers to Modulate Tumor Hypoxia for Ameliorated Anti-Tumor Therapy: Fabrications, Properties, and Future Directions

Over the past five years, oxygen-based nanocarriers (NCs) to boost anti-tumor therapy attracted tremendous attention from basic research and clinical practice. Indeed, tumor hypoxia, caused by elevated proliferative activity and dysfunctional vasculature, is directly responsible for the less effectiveness or ineffective of many conventional therapeutic modalities. Undeniably, oxygen-generating NCs and oxygen-carrying NCs can increase oxygen concentration in the hypoxic area of tumors and have also been shown to have the ability to decrease the expression of drug efflux pumps (e.g., P-gp); to increase uptake by tumor cells; to facilitate the generation of cytotoxic reactive oxide species (ROS); and to evoke systematic anti-tumor immune responses. However, there are still many challenges and limitations that need to be further improved. In this review, we first discussed the mechanisms of tumor hypoxia and how it severely restricts the therapeutic efficacy of clinical treatments. Then an up-to-date account of recent progress in the fabrications of oxygen-generating NCs and oxygen-carrying NCs are systematically introduced. The improved physicochemical and surface properties of hypoxia alleviating NCs for increasing the targeting ability to hypoxic cells are also elaborated with special attention to the latest nano-technologies. Finally, the future directions of these NCs, especially towards clinical translation, are proposed. Therefore, we expect to provide some valued enlightenments and proposals in engineering more effective oxygen-based NCs in this promising field in this comprehensive overview.

Anticipating Ocean Deoxygenation in the Maritime Continent of Southeast Asia

Oxygen plays an essential role in the biogeochemical process and ocean productivity, especially during the recent trend of ocean warming. However, deoxygenation as a consequence of climate change receives less attention than ocean acidification and warming. Therefore, understanding the deoxygenation as an effect of ocean warming is indispensable. The maritime continent waters of Southeast Asia are well known on marine biodiversity and geolocation unique features that are inevitably impacted by climate change. This condition will suffer more due to less oxygen on the marine water. This review focuses on observing oxygen depletion changes and hypoxia in the maritime continent area, its potency, effect, and recommendation on how to monitor deoxygenation. Based on previous research, the Bay of Bengal has been affected by oxygen depletion, and climate change increases this hypoxic area. In other locations, coastal hypoxic occurred seasonally. However, dominating big cities in the coast area increase the vulnerability of hypoxic zones such as in Sangga Besar River Estuary, Bolinao and Anda Coastal, Manila Bay, Jakarta Bay, Cambodian Waters, and Bengal Bay. Deoxygenation mitigation is an initial step in anticipating global climate change. The monitoring of the hypoxic area is needed to inform the threat of the deoxygenation on the maritime continent of SEA.

Daily hypoxia forecasting and uncertainty assessment via Bayesian mechanistic model for the Northern Gulf of Mexico

Low bottom water dissolved oxygen conditions (hypoxia) occur almost every summer in the northern Gulf of Mexico due to a combination of nutrient loadings and water column stratification. Several models have been used to forecast the midsummer hypoxic area based on spring nitrogen loading from major rivers. However, sub-seasonal forecasts are needed to fully characterize the dynamics of hypoxia over the summer season, which is important for informing fisheries and ecosystem management. Here, we present an approach to forecast hypoxic conditions at daily resolution through Bayesian mechanistic modeling that allows for rigorous uncertainty quantification. Within this framework, we develop and test different representations and projections of hydro-meteorological model inputs. We find that May precipitation over the Mississippi River Basin is a key predictor of summer discharge and loading that substantially improves forecast performance. Accounting for spring wind conditions also improves forecast performance, though to a lesser extent. The proposed approach generates forecasts for two different sections of the Louisiana–Texas shelf (east and west), and it explains about 50 % of the variability in total hypoxic area when tested against historical observations (1985−2016). Results also show how forecast uncertainties build over the summer season, with longer lead times from the nominal forecast release date of 31 May, due to increasing stochasticity in riverine and meteorological inputs. Consequently, the portion of overall forecast variance associated with uncertainties in data inputs increases from 26 % to 41 % from June–July to August–September, respectively. Overall, the study demonstrates a unique approach to assessing and reducing uncertainties in dynamic hypoxia forecasting.

Implication of O2 dynamics for both N2O and CH4 emissions from soil during biological soil disinfestation

Soil O2 dynamics have significant influences on greenhouse gas emissions during soil management practice. In this study, we deployed O2-specific planar optodes to visualize spatiotemporal distribution of O2 in soils treated with biological soil disinfestation (BSD). This study aimed to reveal the role of anoxia development on emissions of N2O and CH4 from soil amended with crop residues during BSD period. The incorporation of crop residues includes wheat straw only, wheat straw with biochar and early straw incorporation. The anoxia in soil developed very fast within 3 days, while the O2 in headspace decreased much slower and it became anaerobic after 5 days, which was significantly affected by straw and biochar additions. The N2O emissions were positively correlated with soil hypoxic fraction. The CH4 emissions were not significant until the anoxia dominated in both soil and headspace. The co-application of biochar with straw delayed the anoxia development and extended the hypoxic area in soil, resulting in lower emissions of N2O and CH4. Those results highlight that the soil O2 dynamic was the key variable triggering the N2O and CH4 productions. Therefore, detailed information of soil O2 availability could be highly beneficial for optimizing the strategies of organic amendments incorporation in the BSD technique.

Hypoxia, Oxidative Stress, and Inflammation: Three Faces of Neurodegenerative Diseases

The cerebral hypoxia-ischemia can induce a wide spectrum of biologic responses that include depolarization, excitotoxicity, oxidative stress, inflammation, and apoptosis, and result in neurodegeneration. Several adaptive and survival endogenous mechanisms can also be activated giving an opportunity for the affected cells to remain alive, waiting for helper signals that avoid apoptosis. These signals appear to help cells, depending on intensity, chronicity, and proximity to the central hypoxic area of the affected tissue. These mechanisms are present not only in a large list of brain pathologies affecting commonly older individuals, but also in other pathologies such as refractory epilepsies, encephalopathies, or brain trauma, where neurodegenerative features such as cognitive and/or motor deficits sequelae can be developed. The hypoxia inducible factor 1α (HIF-1α) is a master transcription factor driving a wide spectrum cellular response. HIF-1α may induce erythropoietin (EPO) receptor overexpression, which provides the therapeutic opportunity to administer pharmacological doses of EPO to rescue and/or repair affected brain tissue. Intranasal administration of EPO combined with other antioxidant and anti-inflammatory compounds could become an effective therapeutic alternative, to avoid and/or slow down neurodegenerative deterioration without producing adverse peripheral effects.

Increasing heart vascularisation after myocardial infarction using brain natriuretic peptide stimulation of endothelial and WT1+ epicardial cells

Brain natriuretic peptide (BNP) treatment increases heart function and decreases heart dilation after myocardial infarction (MI). Here, we investigated whether part of the cardioprotective effect of BNP in infarcted hearts related to improved neovascularisation. Infarcted mice were treated with saline or BNP for 10 days. BNP treatment increased vascularisation and the number of endothelial cells in all areas of infarcted hearts. Endothelial cell lineage tracing showed that BNP directly stimulated the proliferation of resident endothelial cells via NPR-A binding and p38 MAP kinase activation. BNP also stimulated the proliferation of WT1+ epicardium-derived cells but only in the hypoxic area of infarcted hearts. Our results demonstrated that these immature cells have a natural capacity to differentiate into endothelial cells in infarcted hearts. BNP treatment increased their proliferation but not their differentiation capacity. We identified new roles for BNP that hold potential for new therapeutic strategies to improve recovery and clinical outcome after MI.