Excess phosphate promotes SARS­CoV­2 N protein­induced NLRP3 inflammasome activation via the SCAP­SREBP2 signaling pathway.

Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS­CoV­2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS­CoV­2 N protein­induced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). The expression levels of SARS­CoV­2 N protein, SREBP cleavage­activating protein (SCAP), mature N­terminal SREBP2, NLRP3, procaspase­1, cleaved caspase­1, IL­1ß and IL­18 were examined by western blotting. The expression levels of SREBP2, HMG­CoA reductase, HMGCS1, low density lipoprotein receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), SREBP1c, fatty acid synthase, stearyl coenzyme A desaturase 1, acetyl­CoA carboxylase α and ATP­citrate lyase were determined by reverse transcription­quantitative PCR. The translocation of SCAP or NLRP3 from the endoplasmic reticulum to the Golgi was detected by confocal microscopy. The results showed that excess PI promoted SCAP­SREBP and NLRP3 complex translocation to the Golgi, potentially leading to NLRP3 inflammasome activation and lipogenic gene expression. Furthermore, PI amplified SARS­CoV­2 N protein­induced inflammation via the SCAP­SREBP pathway, which facilitates NLRP3 inflammasome assembly and activation. Inhibition of phosphate uptake with phosphonoformate sodium alleviated NLRP3 inflammasome activation and reduced SREBP­mediated lipogenic gene expression in VSMCs stimulated with PI and with SARS­CoV­2 N protein overexpression. Inhibition of SREBP2 or small interfering RNA­induced silencing of SREBP2 effectively suppressed the effect of PI and SARS­CoV­2 N protein on NLRP3 inflammasome activation and lipogenic gene expression. In conclusion, the present study identified that PI amplified SARS­CoV­2 N protein­induced NLRP3 inflammasome activation and lipogenic gene expression via the SCAP­SREBP signaling pathway.

SARS-CoV-2 nucleocapsid protein promotes TMAO-induced NLRP3 inflammasome activation by SCAP-SREBP signaling pathway.

The sterol regulatory element-binding protein (SREBP) activation and cytokine level were significantly increased in coronavirus disease-19. The NLRP3 inflammasome is an amplifier for cellular inflammation. This study aimed to elucidate the modulatory effect of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP) on trimethylamine N-oxide (TMAO)-induced lipogenesis and NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs). Our data indicated that SARS-CoV-2 NP activates the dissociation of the SREBP cleavage activating protein (SCAP) from the endoplasmic reticulum, resulting in SREBP activation, increased lipogenic gene expression, and NLRP3 inflammasome activation. TMAO was applied to VSMC-induced NLRP3 inflammasome by promoting the SCAP-SREBP complex endoplasmic reticulum-to-Golgi translocation, which facilitates directly binding of SARS-CoV-2 NP to the NLRP3 protein for NLRP3 inflammasome assembly. SARS-CoV-2 NP amplified the TMAO-induced lipogenic gene expression and NLRP3 inflammasome. Knockdown of SCAP-SREBP2 can effectively reduce lipogenic gene expression and alleviate NLRP3 inflammasome-mediated systemic inflammation in VSMCs stimulated with TMAO and SARS-CoV-2 NP. These results reveal that SARS-CoV-2 NP amplified TMAO-induced lipogenesis and NLRP3 inflammasome activation via priming the SCAP-SREBP signaling pathway.

Worldwide scientific efforts on nursing in the field of SARS-CoV-2: a cross-sectional survey analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a global public health issue. This study aimed to characterize global nursing research on SARS-CoV-2. METHODOLOGY: Nursing-related publications through December 31, 2022, were identified using Scopus. The number of studies, study types, countries, institutions, journals, authors, h-index, total confirmed cases, total deaths, and the highest-cited studies were investigated. RESULTS: In total, 12,427 studies were identified. The number of studies increased rapidly, particularly between 2020 and 2021, with a 2.36-fold increase. The United States published the most studies (3,289, 26.47%), followed by the United Kingdom (1,059, 8.52%) and China (877, 7.06%). Scientific productivity significantly correlated with the total confirmed cases (r = 0.701, p = 0.024) and total deaths (r = 0.804, p = 0.005). The United States had the highest h-index (80), followed by China (59), and the United Kingdom (57). The University of Toronto published the most studies (181), followed by Harvard Medical School (165), and the University of São Paulo (107). Gravenstein S (23) was the most prolific author, followed by Mor V (22), and Rosa WE (19). The International Journal of Environmental Research and Public Health published the most papers (436), followed by PLOS ONE (219), and BMJ Open (185). CONCLUSIONS: Several countries, institutions, journals, and authors contributed greatly to SARS-CoV-2-related nursing studies. Countries with larger numbers of confirmed cases and deaths tended to publish more nursing studies. The United States, United Kingdom, and China had the highest quantity and quality of studies.

Advancing Insights into Probiotics during Vegetable Fermentation.

Fermented vegetables have a long history and are enjoyed worldwide for their unique flavors and health benefits. The process of fermentation improves the nutritional value, taste, and shelf life of foods. Microorganisms play a crucial role in this process through the production of metabolites. The flavors of fermented vegetables are closely related to the evaluation and succession of microbiota. Lactic acid bacteria (LABs) are typically the dominant bacteria in fermented vegetables, and they help inhibit the growth of spoilage bacteria and maintain a healthy gut microbiota in humans. However, homemade and small-scale artisanal products rely on spontaneous fermentation using bacteria naturally present on fresh vegetables or from aged brine, which may introduce external microorganisms and lead to spoilage and substandard products. Hence, understanding the role of LABs and other probiotics in maintaining the quality and safety of fermented vegetables is essential. Additionally, selecting probiotic fermentation microbiota and isolating beneficial probiotics from fermented vegetables can facilitate the use of safe and healthy starter cultures for large-scale industrial production. This review provides insights into the traditional fermentation process of making fermented vegetables, explains the mechanisms involved, and discusses the use of modern microbiome technologies to regulate fermentation microorganisms and create probiotic fermentation microbiota for the production of highly effective, wholesome, safe, and healthy fermented vegetable foods.

Hydrogen sulfide attenuates TMAO­induced macrophage inflammation through increased SIRT1 sulfhydration.

Chronic inflammation is a key factor that accelerates the progression of inflammatory vascular disease. Hydrogen sulfide (H2S) has potent anti­inflammatory effects; however, its underlying mechanism of action has not been fully elucidated. The present study aimed to investigate the potential effect of H2S on sirtuin 1 (SIRT1) sulfhydration in trimethylamine N­oxide (TMAO)­induced macrophage inflammation, and its underlying mechanism. Pro­inflammatory M1 cytokines (MCP­1, IL­1ß, and IL­6) and anti­inflammatory M2 cytokines (IL­4 and IL­10) were detected by RT­qPCR. CSE, p65 NF­κB, p­p65 NF­κB, IL­1ß, IL­6 and TNF­α levels were measured by Western blot. The results revealed that cystathionine γ­lyase protein expression was negatively associated with TMAO­induced inflammation. Sodium hydrosulfide (a donor of H2S) increased SIRT1 expression and inhibited the expression of inflammatory cytokines in TMAO­stimulated macrophages. Furthermore, nicotinamide, a SIRT1 inhibitor, antagonized the protective effect of H2S, which contributed to P65 NF­κB phosphorylation and upregulated the expression of inflammatory factors in macrophages. H2S ameliorated TMAO­induced activation of the NF­κB signaling pathway via SIRT1 sulfhydration. Moreover, the antagonistic effect of H2S on inflammatory activation was largely eliminated by the desulfhydration reagent dithiothreitol. These results indicated that H2S may prevent TMAO­induced macrophage inflammation by reducing P65 NF­κB phosphorylation via the upregulation and sulfhydration of SIRT1, suggesting that H2S may be used to treat inflammatory vascular diseases.

Spatiotemporal Variation in Groundwater Quality and Source Apportionment along the Ye River of North China Using the PMF Model.

Groundwater quality deterioration has attracted widespread concern in China. In this research, the water quality index (WQI) and a positive matrix factorization (PMF) model were used to assess groundwater quality and identify pollution sources in the Ye River area of northern China. Research found that TH, SO42-, and NO3- were the main groundwater pollution factors in the Ye River area, since their exceeding standard rates were 78.13, 34.38, and 59.38%, respectively. The main groundwater hydrochemical type has changed from HCO3-Ca(Mg) to HCO3·SO4-Ca(Mg). These data indicated that the groundwater quality was affected by anthropogenic activities. Spatial variation in groundwater quality was mainly influenced by land use, whereas temporal variation was mainly controlled by rainfall. The WQI indicated that the groundwater quality was better in the flood season than in the dry season due to the diluting effect of rainfall runoff. Notably, farmland groundwater quality was relatively poor as it was affected by various pollution sources. Based on the PMF model, the main groundwater pollution sources were domestic sewage (52.4%), industrial wastewater (24.1%), and enhanced water-rock interaction induced by intensely exploited groundwater (23.6%) in the dry season, while in the flood season they were domestic sewage and water-rock interaction (49.6%), agriculture nonpoint pollution (26.1%), and industrial wastewater and urban nonpoint pollution (23.9%). In addition, the mean contribution of domestic sewage and industrial sewage to sampling sites in the dry season (1489 and 322.5 mg/L, respectively) were higher than that in the flood season (1158 and 273.6 mg/L, respectively). To sum up, the point sources (domestic sewage and industrial wastewater) remain the most important groundwater pollution sources in this region. Therefore, the local government should enhance the sewage treatment infrastructure and exert management of fertilization strategies to increase the fertilizer utilization rate and prevent further groundwater quality deterioration.

Research Advances in the Analysis of Nitrate Pollution Sources in a Freshwater Environment Using δ15N-NO3- and δ18O-NO3.

Nitrate is usually the main pollution factor in the river water and groundwater environment because it has the characteristics of stable properties, high solubility and easy migration. In order to ensure the safety of water supply and effectively control nitrate pollution, it is very important to accurately identify the pollution sources of nitrate in freshwater environment. At present, as the most accurate source analysis method, isotope technology is widely used to identify the pollution sources of nitrate in water environment. However, the complexity of nitrate pollution sources and nitrogen migration and transformation in the water environment, coupled with the isotopic fractionation, has changed the nitrogen and oxygen isotopic values of nitrate in the initial water body, resulting in certain limitations in the application of this technology. This review systematically summarized the typical δ15N and δ18O-NO3- ranges of NO3- sources, described the progress in the application of isotope technique to identify nitrate pollution sources in water environment, analyzed the application of isotope technique in identifying the migration and transformation of nitrogen in water environment, and introduced the method of quantitative source apportionment. Lastly, we discussed the deficiency of isotope technique in nitrate pollution source identification and described the future development direction of the pollution source apportionment of nitrate in water environment.

Spatiotemporal Patterns in River Water Quality and Pollution Source Apportionment in the Arid Beichuan River Basin of Northwestern China Using Positive Matrix Factorization Receptor Modeling Techniques.

Deteriorating surface water quality has become an important environmental problem in China. In this study, river water quality was monitored in July (wet season) and October (dry season) 2019 at 26 sites, and a water quality index (WQI) and positive matrix factorization (PMF) model were used to assess surface water quality and identify pollution sources in the Beichuan River basin, Qinghai Province, China. The results showed that 53.85% and 76.92% of TN, 11.54% and 34.62% of TP, 65.38% and 76.92% of Fe, and 11.54% and 15.38% of Mn samples in the dry and wet seasons, respectively, exceeded the Chinese Government's Grade III standards for surface water quality. The spatial variation in water quality showed that it gradually deteriorated from upstream to downstream as a result of human activity. The temporal variation showed that water quality was poorer in the wet season than in the dry season because of the rainfall runoff effect. The PMF model outputs showed that the primary sources of pollution in the wet season were mineral weathering and organic pollution sources, domestic and industrial sewage, and agricultural and urban non-point pollution sources. However, in the dry season, the primary sources were mineral weathering and organic pollution sources, industrial sewage, and domestic sewage. Our results suggest that the point pollution sources (domestic and industrial sewage) should be more strictly controlled, as a priority, in order to prevent the continued deterioration in water quality.

Synthesis of porous carbon material based on biomass derived from hibiscus sabdariffa fruits as active electrodes for high-performance symmetric supercapacitors.

Carbon-based materials are manufactured as high-performance electrodes using biomass waste in the renewable energy storage field. Herein, four types of hierarchical porous activated carbon using hibiscus sabdariffa fruits (HBFs) as a low-cost biomass precursor are synthesized through carbonization and activation. NH4Cl is used as a chemical blowing agent to form carbon nanosheets, which are the first types of hibiscus sabdariffa fruit-based carbon (HBFC-1) sample, and KOH also forms a significant bond in the activation process. The prepared HBFC-1 is chosen to manufacture the symmetric supercapacitor due to its rough surface and high surface area (1720.46 m2 g-1), making it show a high specific capacity of 194.50 F g-1 at a current density of 0.5 A g-1 in a three-electrode system. Moreover, the HBFC-1 based symmetric supercapacitor devices display a high energy density of 13.10 W h kg-1 at a power density of 225.00 W kg-1, and a high specific capacity of 29 F g-1 at 0.5 A g-1. Additionally, excellent cycle life is observed (about 96% of capacitance retained after 5000 cycles). Therefore, biomass waste, especially hibiscus sabdariffa fruit based porous carbon, can be used as the electrode for high-performance supercapacitor devices.

FGF21 protects human umbilical vein endothelial cells against high glucose-induced apoptosis via PI3K/Akt/Fox3a signaling pathway.

AIMS: Diabetic macroangiopathy is the main cause of morbidity and mortality in patients with diabetes. Endothelial cell injury is a pathological precondition for diabetic macroangiopathy. Fibroblast growth factor 21 (FGF21) is a key metabolic regulator which has recently been suggested to protect cardiac myocytes and vascular cells against oxidative stress-induced injury in vitro and vivo. In this study, we aimed to investigate the protective capacity of FGF21 in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)-induced apoptosis via phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway. METHODS: The cell viability was examined by CCK-8 assay, Intracellular ROS levels were measured by the detection of the fluorescent product formed by the oxidation of DCFH-DA, Apoptosis was analyzed using Hoechst 33258 nuclear staining and Flow Cytometry Analysis (FCA), the expression of protein were detected by Western blot. RESULTS: Results show that pretreating HUVECs with FGF21 before exposure to HG increases cell viability, while decreasing apoptosis and the generation of reactive oxygen species. Western blot analysis shows that HG reduces the phosphorylation of Akt and FoxO3a, and induces nuclear localization of FoxO3a. The effects were significantly reversed by FGF21 pre-treatment. Furthermore, the protective effects of FGF21 were prevented by PI3K/Akt inhibitor LY294002. CONCLUSIONS: Our data demonstrates that FGF21 protects HUVECs from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.

Role of PCSK9 in lipid metabolism and atherosclerosis.

Elevated plasma low-density lipoprotein cholesterol (LDL-C) is an important risk factor for cardiovascular diseases. Statins are the most widely used therapy for patients with hyperlipidemia. However, a significant residual cardiovascular risk remains in some patients even after maximally tolerated statin therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new pharmacologically therapeutic target for decreasing LDL-C. PCSK9 reduces LDL intake from circulation by enhancing LDLR degradation and preventing LDLR recirculation to the cell surface. Moreover, PCSK9 inhibitors have been approved for patients with either familial hypercholesterolemia or atherosclerotic cardiovascular disease, who require additional reduction of LDL-C. In addition, PCSK9 inhibition combined with statins has been used as a new approach to help reduce LDL-C levels in patients with either statin intolerance or unattainable LDL goal. This review will discuss the emerging anti-PCSK9 therapies in the regulation of cholesterol metabolism and atherosclerosis.

Molecular mechanisms of autophagy in cardiac ischemia/reperfusion injury (Review).

Autophagy is a maintenance process for recycling long-lived proteins and cytoplasmic organelles. The level of this process is enhanced during ischemia/reperfusion (I/R) injury. Autophagy can trigger survival signaling in myocardial ischemia, whereas defective autophagy during reperfusion is detrimental. Autophagy can be regulated through multiple signaling pathways in I/R, including Beclin­1/class III phosphatidylinositol­3 kinase (PI­3K), adenosine monophosphate activated protein kinase/mammalian target of rapamycin (mTOR), and PI­3K/protein kinase B/mTOR pathways, which consequently lead to different functions. Thus, autophagy has both protective and detrimental functions, which are determined by different signaling pathways and conditions. Targeting the activation of autophagy can be a promising new therapeutic strategy for treating cardiovascular disease.

GIS-based groundwater potential analysis using novel ensemble weights-of-evidence with logistic regression and functional tree models.

The aim of the current study was to produce groundwater spring potential maps using novel ensemble weights-of-evidence (WoE) with logistic regression (LR) and functional tree (FT) models. First, a total of 66 springs were identified by field surveys, out of which 70% of the spring locations were used for training the models and 30% of the spring locations were employed for the validation process. Second, a total of 14 affecting factors including aspect, altitude, slope, plan curvature, profile curvature, stream power index (SPI), topographic wetness index (TWI), sediment transport index (STI), lithology, normalized difference vegetation index (NDVI), land use, soil, distance to roads, and distance to streams was used to analyze the spatial relationship between these affecting factors and spring occurrences. Multicollinearity analysis and feature selection of the correlation attribute evaluation (CAE) method were employed to optimize the affecting factors. Subsequently, the novel ensembles of the WoE, LR, and FT models were constructed using the training dataset. Finally, the receiver operating characteristic (ROC) curves, standard error, confidence interval (CI) at 95%, and significance level P were employed to validate and compare the performance of three models. Overall, all three models performed well for groundwater spring potential evaluation. The prediction capability of the FT model, with the highest AUC values, the smallest standard errors, the narrowest CIs, and the smallest P values for the training and validation datasets, is better compared to those of other models. The groundwater spring potential maps can be adopted for the management of water resources and land use by planners and engineers.

Comprehensive Identification and Bread-Making Quality Evaluation of Common Wheat Somatic Variation Line AS208 on Glutenin Composition.

High molecular weight glutenin subunits (HMW-GSs) are important seed storage proteins in wheat (Triticum aestivum) that determine wheat dough elasticity and processing quality. Clarification of the defined effectiveness of HMW-GSs is very important to breeding efforts aimed at improving wheat quality. To date, there have no report on the expression silencing and quality effects of 1Bx20 and 1By20 at the Glu-B1 locus in wheat. A wheat somatic variation line, AS208, in which both 1Bx20 and 1By20 at Glu-B1 locus were silenced, was developed recently in our laboratory. Evaluation of agronomic traits and seed storage proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and reversed-phase high performance liquid chromatography (RP-HPLC) indicated that AS208 was highly similar to its parental cultivar Lunxuan987 (LX987), with the exception that the composition and expression of HMW-GSs was altered. The 1Bx20 and 1By20 in AS208 were further identified to be missing by polymerase chain reaction (PCR) and quantitative real-time RT-PCR (qRT-PCR) assays. Based on the PCR results for HMW-GS genes and their promoters in AS208 compared with LX987, 1Bx20 and 1By20 were speculated to be deleted in AS208 during in vitro culture. Quality analysis of this line with Mixograph, Farinograph, and Extensograph instruments, as well as analysis of bread-making quality traits, demonstrated that the lack of the genes encoding 1Bx20 and 1By20 caused various negative effects on dough processing and bread-making quality traits, including falling number, dough stability time, mixing tolerance index, crude protein values, wet gluten content, bread size, and internal cell structure. AS208 can potentially be used in the functional dissection of other HMW-GSs as a plant material with desirable genetic background, and in biscuit making industry as a high-quality weak gluten wheat source.

Production and identification of haploid dwarf male sterile wheat plants induced by corn inducer.

BACKGROUND: Using the cross of wheat and maize is a very useful way to produce wheat haploid plants by chromosome elimination. Dwarf male sterile wheat (DMSW) and corn inducer are potential important germplasm for wheat breeding by recurrent selection and doubled haploid strategies. There is no report yet to achieve the haploid plants from DMSW induced by maize inbred line and especially the corn inducer. RESULTS: Haploid plants of DMSW were successfully obtained in this study induced by both maize pollens of inducer line and normal inbred line. The efficiencies for wheat embryos formation and plantlets production induced by the two corn lines had no significant difference. All the eleven haploid wheat plants derived from the male sterile material were identified by botanic appearance, cytology, cytogenetics, and molecular markers. They were all haploid based on their guard cell length of 42.78-42.90 µm compared with the diploid control of 71.52 µm, and their chromosome number of 21 compared with the diploid control of 42. In addition, according to anthers, plant height, and molecular markers, the haploid plants were divided into two types. Eight of them showed dwarf, having no anthers, and the special band of Rht10, and the other three plants displayed normal plant height, having anthers, and not containing the special band of Rht10, indicating that they were originated from the MS2/Rht10 and ms2/rht10 female gametes, respectively. CONCLUSIONS: MS2/Rht10 haploid plants were successfully obtained in this study by using corn inducer and inbred line, and will be employed as candidate materials for the potential cloning of MS2 dominant male gene.