Effect of Hb conformational changes on oxygen transport physiology. / Hb构象变化对氧转运生理功能的影响.

Red blood cells (RBCs) are the primary mediators of oxygen transport in the human body, and their function is mainly achieved through conformational changes of hemoglobin (Hb). Hb is a tetramer composed of four subunits, with HbA being the predominant Hb in healthy adults, existing in two forms: tense state (T state) and relaxed state (R state). Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid, carbon dioxide, protons, and chloride ions, while exogenous regulators include inositol hexaphosphate, inositol tripyrophosphate, benzabate, urea derivative L35, and vanillin, each with different mechanisms of action. The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Integrated SEAWAT model and GALDIT method for dynamic vulnerability assessment of coastal aquifer to seawater intrusion.

Seawater intrusion (SI) has become a global issue exacerbated by intense anthropogenic activities and climate change. It is imperative to seek a synergistic strategy to reconcile environmental and economic benefits in the coastal regions. However, the intricate SI process and data scarcity present formidable challenges in dynamically assessing the coastal groundwater vulnerability. To address the challenge, this study proposed a novel framework that integrates the existing vulnerability assessment method (GALDIT) and variable-density groundwater model (SEAWAT). The future scenarios from 2019 to 2050 were investigated monthly under climate change (SSP1-2.6, SSP2-4.5, SSP3-7.0 and SSP5-8.5) and human activities (80 % and 50 % of current groundwater abstraction) in Longkou city, China, a typical coastal region subject to extensive SI, compared with the status quo in 2018. Results indicated that by 2050, the high vulnerability area, is in a narrow buffer within 1.2 km from the shoreline and exhibits minor changes while the salt concentration here increased by about 2700 mg/L compared with the current situation. The moderate vulnerability zone expands by about 30 km2, and the low vulnerable area decreases proportionally. The groundwater over-abstraction is identified as a more critical factor compared to the regional precipitation under climate change. When groundwater abstraction is reduced to 80 % of the current scale, the expansion rate of the moderate-vulnerable area slows down significantly, with an expansion area of only 18 km2 by 2050. Further reducing groundwater abstraction to 50 % of the current scale shifts the evolution trend of the medium-vulnerable area from expansion to contraction, with the area shrinking by about 11 km2 by 2050. The integrated vulnerability assessment framework can be applied not only in the similar coastal regions but also provides insights into other natural hazards.

The role and mechanism of miR-425-3p regulating neuronal pyroptosis -mediated inorganic arsenic-induced generalized anxiety disorder.

Pyroptosis plays a critical role in the pathogenesis of mental disorders. However, its specific role and mechanism in arsenic (As)-induced generalized anxiety disorder (GAD) remain elusive. We utilized the data from CtdBbase, Phenopedia and DisGeNet to analyze genes that interact with arsenic poisoning and GAD. Subsequently KEGG and GO enrichment analysis were conducted to preliminatively predict the mechanism of inorganic arsenic-induced GAD. Male Wistar rats were administered water containing NaAsO2 (50, 100 µg/L) to evaluate GAD-like behavior through open field test and elevated plus maze. The expression of differential miRNAs including miR-425-3p, and pyroptosis in the prefrontal cortex of rats were detected. Furthermore, SKNSH cells were stimulated with NaAsO2 to examine the molecular changes, and then miR-425-3p mimic was transfected into SKNSH cells to detect pyroptosis in order to verify the function of miR-425-3p. Inorganic arsenic was confirmed to induce GAD-like behavior in rats, characterized by decreased locomotor activity and exploratory activities. Rats with inorganic arsenic-induced GAD exhibited reduced miR-425-3p expression levels in the prefrontal cortex and increased expression of pyroptosis-related proteins, including NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Treating with different concentrations of NaAsO2 showed that inorganic arsenic exposure downregulates miR-425-3p expression in SKNSH cells and upregulates the expression levels of pyroptosis-related proteins. Dual-luciferase reporter gene experiments demonstrated that miR-425-3p targets the NFKB1. Overexpressing miR-425-3p reversed the inorganic arsenic-induced pyroptosis in SKNSH cells by inhibiting the expression of NF-κB, NLRP3, Caspase-1, GSDMD, IL-1ß, and IL-18. Our findings suggest that inorganic arsenic exposure may induce GAD-like behavior in rats by downregulating miR-425-3p in prefrontal cortex, which targets NF-κB and regulates pyroptosis in neuronal cells.

Protective effect of heme chloride on hypoxia-induced tissue injury in mice. / æ°¯åŒ–è¡€çº¢ç´ å¯¹ç¼ºæ°§å¯¼è‡´å°é¼ ç»„ç»‡æŸä¼¤çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: Heme chloride (Hemin) is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs. This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice, and explore its role in anti-plateau hypoxia. METHODS: Thirty male BALB/c mice were randomly divided into a blank group, a positive drug group (acetazolomide, 200 mg/kg), a Hemin low-dose group (15 mg/kg), a Hemin medium-dose group (30 mg/kg), and a Hemin high-dose group (60 mg/kg) with intraperitoneal injection. The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened. Thirty-six male BALB/c mice were randomly divided into a blank group, a hypoxia group, a positive drug group, and a Hemin high-dose group. The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde (MDA), glutataione (GSH), and superoxide dismutase (SOD) levels of myocardium, brain, lung, and liver tissues were measured in different groups with hypoxia for 24 h. The degree of histopathological damage of mice was observed with HE staining. The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. RESULTS: Compared with the blank group, the survival time of mice in the positive drug group, the Hemin medium-dose group, and high-dose group was significantly extended (all P<0.05), with the highest prolongation rate in the Hemin high-dose group. Compared with the hypoxia group, mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue, and a significant decrease in MDA content of lung tissue (all P<0.05). The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver, heart, brain and lung tissues of mice with hypoxia, and the most obvious effect on that of the brain tissue. CONCLUSIONS: Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia, and has obvious protective effect on tissue damage caused by hypoxia.

Multi-objective optimization-based reactive nitrogen transport modeling for the water-environment-agriculture nexus in a basin-scale coastal aquifer.

The quantification of trade-offs between social-economic and environmental effects is of great importance, especially in the semi-arid coastal areas with highly developed agriculture. The study presents an integrated multi-objective simulation-optimization (S-O) framework to evaluate the basin-scale water-environment-agriculture (WEA) nexus. First, the variable-density groundwater model (SEAWAT) is coupled to the reactive transport model (RT3D) for the first attempt to simulate the environmental effects subject to seawater intrusion (SWI) and nitrate pollution (NP). Then, the surrogate assisted multi-objective optimization algorithm is utilized to investigate the trade-offs between the net agricultural benefits and extents of SWI and NP while considering the water supply, food security, and land availability simultaneously. The S-O modeling methodology is applied to the Dagu River Basin (DRB), a typical SWI region with intensive agricultural irrigation in China. It is shown that the three-objective space based on Pareto-optimal front can be achieved by optimizing planting area in the irrigation districts, indicating the optimal evolution of the WEA nexus system. The Pareto-optimal solutions generated by multi-objective S-O model are more realistic and pragmatic, avoiding the decision bias that may often lead to cognitive myopia caused by the low-dimensional objectives. Although the net agricultural benefits in Pareto-optimal solutions are declined to some extent, the environmental objectives (the extents of SWI and NP) are improved compared to those in the pre-optimized scheme. Therefore, the proposed multi-objective S-O framework can be applied to the WEA nexus in the river basin with intensive agriculture development, which is significant to implement the integrated management of water, food, and environment, especially for the semi-arid coastal aquifers.