Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway.

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1ß) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.

GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages.

Anemia is a significant complication of chronic inflammation and may be related to dysregulated activities among erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBIs, we found that the GM-CSF receptor is preferentially and highly expressed among EBI macrophages but not among erythroblasts. GM-CSF treatment significantly decreases human EBI formation in vitro by decreasing the adhesion molecule expression of CD163. RNA-sequence analysis suggests that GM-CSF treatment impairs the supporting function of human EBI macrophages during erythropoiesis. GM-CSF treatment also polarizes human EBI macrophages from M2-like type to M1-like type. In addition, GM-CSF decreases mouse bone marrow (BM) erythroblasts as well as EBI macrophages, leading to a reduction in EBI numbers. In defining the molecular mechanism at work, we found that GM-CSF treatment significantly decreases the adhesion molecule expression of CD163 and Vcam1 in vivo. Importantly, GM-CSF treatment also decreases the phagocytosis rate of EBI macrophages in mouse BM as well as decreases the expression of the engulfment-related molecules Mertk, Axl, and Timd4. In addition, GM-CSF treatment polarizes mouse BM EBI macrophages from M2-like type to M1-like type. Thus, we document that GM-CSF impairs EBI formation in mice and humans. Our findings support that targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy to treat anemia resulting from inflammatory diseases.

Reactive Nitrogen Species Generated by Gas-Liquid Dielectric Barrier Discharge for Efficient Degradation of Perfluorooctanoic Acid from Water.

Perfluorooctanoic acid (PFOA) poses a serious threat to the ecological environment and biological health because of its ubiquitous distribution, extreme persistence, and high toxicity. In this study, we designed a novel gas-liquid dielectric barrier discharge (GLDBD) reactor which could efficiently destruct PFOA. PFOA removal efficiencies can be obtained in various water matrices, which were higher than 98.0% within 50 min, with energy yields higher than 114.5 mg·kWh-1. It was confirmed that the reactive species including e-, ONOOH, •NO2, and hydroxyl radicals (•OH) were responsible for PFOA removal. Especially, this study first revealed the crucial role of reactive nitrogen species (RNS) for PFOA degradation in the plasma system. Due to the generation of a large amount of RNS, the designed GLDBD reactor proved to be less sensitive to various water matrices, which meant a broader promising practical application. Moreover, influential factors including high concentration of various ions and humic acid (HA), were investigated. The possible PFOA degradation pathways were proposed based on liquid chromatograph-mass spectrometer (LC-MS) results and density functional theory (DFT) calculation, which further confirmed the feasibility of PFOA removal with RNS. This research, therefore, provides an effective and versatile alternative for PFOA removal from various water matrices.

Omics analyses indicate the routes of lignin related metabolites regulated by trypsin during storage of pitaya (Hylocereus undatus).

The storage quality of Hylocereus undatus was significantly improved by trypsin, a novel preservative. The transcriptomic results revealed that antioxidant signal pathways were induced, while lignin catabolic process was impeded by trypsin. In addition, the results of protein-protein interaction (PPI) network networks suggested that flavone 3'-O-methyltransferase 1 (OMT1), ferulic acid 5-hydroxylase 1 (CYP84A1), cellulose synthase isomer (CEV1), and 4-coumarate-CoA ligase 3 (4CL3) act as hubs of peroxidases, lignin related proteins, and proteins involved in the phenylpropanoid metabolism (PLPs) induced by trypsin. Trypsin also regulated the biosynthesis of lignin, chlorogenic acid, and flavonoids. Caffeic acid might be the hub in the metabolic network of the early pathways of phenylpropanoid biosynthesis. It has been hypothesized that trypsin might quickly induce lignin biosynthesis and then up-regulated bioactive metabolites to enhance storage quality of H. undatus.

Rapid responses of adipocytes to iron overload increase serum TG level by decreasing adiponectin.

Iron overload is tightly connected with metabolic disorders. Excess iron in the adipose and its roles in dyslipidemia are of interest to be identified. In acute iron overload mice receiving intraperitoneal injection of 100 mg/kg/day dextran-iron for 5 days, the epididymis adipose showed a remarkable increase in iron. Serum triglyceride and low-density lipoprotein cholesterol (LDL-C) levels were increased and high-density lipoprotein cholesterol (HDL-C) level was decreased, while serum alkaline phosphatase, aspartate aminotransferase, glucose, and insulin were not affected. The serum-cytokine-microarray showed that adipocytokines, including adiponectin, leptin, and resistin were significantly decreased. Other serum cytokines, including pro-insulin cytokines, inflammatory cytokines, chemokines, and growth factors were not changed, except that ghrelin and chemokine RANTES were increased. Iron overload decreased expressions of adiponectin and leptin both in vivo and in vitro. Intraperitoneal injection of recombinant leptin at 1 µg/g in acute iron overload mice had no significant effects on serum levels of TC, TG, HDL-C, and LDL-C, while intraperitoneal injection of recombinant adiponectin at 3 µg/g partially restored serum TG level through improving activities of lipoprotein lipase and hepatic lipase, but abnormal serum LDL-C and HDL-C were not redressed, suggesting other mechanisms also existed. In conclusion, the adipose responds to iron overload at an early stage to interfere with lipid metabolism by secreting adipocytokines, which may further affect glucose metabolism, inflammation, and other iron overload-induced effects on the body.

Association between healthy eating index-2015 and various cognitive domains in US adults aged 60 years or older: the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Diet, as a modifiable factor, plays an important role in cognitive function. However, the association between adherence to the 2015-2020 Dietary Guidelines for Americans (DGA), measured by Healthy Eating Index (HEI)-2015, and cognitive function remains unclear. This study aims to explore whether HEI-2015 is associated with various cognitive domains and whether such association is modified by age, gender, or ethnicity in the US adults aged 60 years or older using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. METHODS: HEI-2015 scores were calculated from 24-h dietary recall interviews. Cognitive function was evaluated by Digit Symbol Substitution Test (DSST, a measure of processing speed), Animal Fluency Test (AFT, a measure of executive function), a subtest from Consortium to Establish a Registry for Alzheimer's disease (CERAD, a measure of memory), and a composite-z score calculated by summing z scores of individual tests. The associations between HEI-2015 scores and cognitive performance were explored using multiple linear regression models. RESULTS: A total of 2450 participants aged 60 years or older were included. Participants with higher HEI-2015 scores were more likely to have higher DSST, AFT as well as composite-z scores (P<0.05). Significant interaction effects were identified between HEI-2015 and ethnicity in specific cognitive domains (Pinteraction<0.05). Among HEI-2015 components, higher intakes of whole fruits and seafood and plant protein were associated with better cognitive performance (P<0.05). CONCLUSION: Higher adherence to DGA is associated with better cognitive performance, especially regarding processing speed and executive function among the US adults aged 60 years or older.

Association between Healthy Eating Index-2015 and physical frailty among the United States elderly adults: the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Diet plays an important role in the development of age-related chronic diseases. However, the association between diet quality assessed by Healthy Eating Index (HEI)-2015, the latest version of HEI, and physical frailty among the general United States (US) elderly adults remains unclear. AIMS: The present study aims to explore the association between HEI-2015 and physical frailty in elderly adults using data from National Health and Nutrition Examination Survey (NHANES) 2011-2014. METHODS: HEI-2015 scores were calculated from 2 days 24-h recall interviews. Physical frailty status was assessed by four criteria developed by Fried et al.: exhaustion, weakness, low body mass, and low physical activity, and then categorized into robust (0 criteria), pre-frail (1-2 criteria), or frail (3-4 criteria). The binary and multinomial logistic regressions were used to examine the odds of frailty status. RESULTS: A total of 2345 participants aged 60 years or older were included. According to the 4-items frailty criteria, 51.1% participants were robust, 42.1% were pre-frail, and 6.8% were frail. Compared to the lowest HEI-2015 quartile, the elderly adults in the higher quartile had a lower odds of physical frailty (P < 0.05). Regarding the frailty criterion separately, higher HEI-2015 was associated with lower odds of exhaustion, weakness, low physical activity and unintentional weight loss, respectively (P < 0.05). Among 13 HEI-2015 components, adherence to the recommended intake of whole fruits and total vegetables components were less likely to be physically frail (P < 0.05). CONCLUSION: Higher HEI-2015 was inversely associated with lower odds of physical frailty in the US elderly adults.

Inflammatory lncRNA AK039862 regulates paraquat-inhibited proliferation and migration of microglial and neuronal cells through the Pafah1b1/Foxa1 pathway in co-culture environments.

Emerging evidences having suggested that particular lncRNAs have a potential effect on PD progression through provoking damage and inflammatory responses of microglia/ dopaminergic cells. In addition, paraquat can be accumulated in human body through various approaches and have an increased risk for Parkinson's disease. However, the specific role and mechanism of lncRNA related to neurotoxic in the progression of PD is unclear. In our study, a mouse PD model was established induced by the intraperitoneal injection of paraquat (5 mg/kg and 10 mg/kg) every three days (10 times). We determined differential expression of lncRNA AK039862 and its potential targeted genes Pafah1b1/Foxa1 in PD mouse model, then we used fluorescence in situ hybridization (FISH) to visualize the cellular distribution of AK039862. Short interfering RNAs (siRNAs) and overexpression plasmids were designed for knockdown or overexpression of AK039862. To simulate the coexisting dopaminergic cells and microglia cells in vitro, we applied several non-contact co-culture models, including conditioned medium and Transwell co-culture systems. Cytotoxicity of PQ was evaluated using bv2 cells with the concentrations: 30, 60 µM, and mn9d cells with the concentrations: 50, 100 µM. As a result, we depicted multiple interesting individual and interactive features of inflammatory lncRNA AK039862 involved in PQ-induced cellular functional effects. First, we detected that AK039862 contributed to the neuronal injury process in PQ-treated mice and co-localization of AK039862 with dopaminergic cells in vivo. And interestingly, we demonstrated that PQ significantly inhibited microglia and dopaminergic cells proliferation and microglia migration in vitro. Further research indicated that the PQ-induced low expression of AK039862 rescued microglia proliferation and migration inhibition via the AK039862/Pafah1b1/Foxa1 pathway. Meanwhile, AK039862 also participated in the interaction between microglia and dopaminergic cells with PQ treatment in non-contact co-culture models. In summary, we found that PQ inhibited the proliferation and migration of microglial cells, and elucidated AK039862 played a key role in PQ-induced neuroinflammatory damage through Pafah1b1/Foxa1. Finally, inflammatory AK039862 is involved in the complex communication between microglia and dopaminergic cells in the environment of PQ damage.

Black carp TRAFD1 restrains MAVS-mediated antiviral signaling during the innate immune activation.

TRAFD1 negatively regulates TLR and RLR signaling in human and mammal; however, its role in teleost fish remains unknown. In this paper, the TRAFD1 homologue has been cloned and characterized from black carp (Mylopharyngodon piceus). Black carp TRAFD1 (bcTRAFD1) consists of 567 amino acids and shows low similarity to that of mammalian TRAFD1, which has been identified as a cytosolic protein through immunofluorescence staining. When co-expressed with bcTRAFD1, the IFN promoter-inducing ability of black carp MAVS (bcMAVS) was obviously dampened in the luciferase reporter assay. Accordingly, bcMAVS-mediated antiviral activity against grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV) was potently repressed by bcTRAFD1 in plaque assay. And the co-immunoprecipitation assay between bcTRAFD1 and bcMAVS has identified the association between these two molecules. Thus, our data supports the conclusion that bcTRAFD1 interacts with bcMAVS and negatively regulates bcMAVS-mediated antiviral signaling during the innate immune activation, which sheds a light on the regulation of MAVS in teleost.

Exosomal sphingosine 1-phosphate secreted by mesenchymal stem cells regulated Treg/Th17 balance in aplastic anemia.

This study was designed to explore whether exosomal sphingosine 1-phosphate (S1P) from mesenchymal stem cells (MSCs) regulate the Treg/Th17 balance in aplastic anemia (AA) patients and to validate the underlying mechanism. To address this, exosomes from human bone marrow MSCs (MSCs-Exos) were co-cultured with CD4+ T cells from AA patients (AA CD4+ T cells), which were transfected with si-S1PR1, si-S1PR3, or not. The proportion of Th17 and Treg was evaluated by flow cytometry. The levels of Th17-associated interleukin-17 (IL-17), Treg-associated IL-10, and transforming growth factor-ß were determined by ELISA. S1P content in MSCs-Exos isolated from control, si-SphK1, or si-SphK2 transfected MSCs was examined by LC-MS/MS. Hematoxylin and eosin staining of bone marrow tissues was performed to evaluate the effect of MSCs-Exos in AA mice. Our results showed that MSCs-Exos reversed the increased Th17/Treg in AA through SphK1-mediated exosomal S1P enrichment. Furthermore, the promotion of Treg differentiation by exosomal S1P from MSCs was mediated through the receptor S1PR1 expressed on CD4+ T cells. Further in vivo experiments showed that MSCs-Exos reversed the increased Th17/Treg and alleviated AA progression in AA mice. In summary, SphK1-mediated enrichment of exosomal S1P secreted by MSCs reversed the increased Treg/Th17 ratio via the receptor S1PR1 in AA patients. © 2019 IUBMB Life, 71(9):1284-1292, 2019.

STAT1a and STAT1b of black carp play important roles in the innate immune defense against GCRV.

Signal transducer and activator of transcription 1 (STAT1) plays an important role in the Janus kinase (JAK)-STAT signaling of human and mammals; however, the mechanism of STAT1 in innate immune activation of teleost fishes remains largely unknown. In this study, two STAT1 homologues (bcSTAT1a and bcSTAT1b) of black carp (Mylopharyngodon piceus) have been cloned and characterized. Both bcSTAT1a and bcSTAT1b transcription in host cells was obviously increased in response to the stimulation of poly (I:C), lipopolysaccharide (LPS), grass carp reovirus (GCRV) and interferon (IFN); however, the increase rate of bcSTAT1b transcription post stimulation was obviously higher than that of bcSTAT1a. bcSTAT1a and bcSTAT1b were distributed in both cytoplasm and nucleus in the immunofluorescence staining assay. Self-association of bcSTAT1a and bcSTAT1b, and the interaction between bcSTAT1a and bcSTAT1b have been detected through co-immunoprecipitation (co-IP) assay; and the data of native polyacrylamide gel electrophoresis (PAGE) implied that bcSTAT1a and bcSTAT1b might form homodimer and heterodimer in vivo like their mammalian counterparts. Both bcSTAT1a and bcSTAT1b presented IFN-inducing ability in report assay, and both bcSTAT1a and bcSTAT1b showed antiviral activities against GCRV in EPC cells. Our data support the conclusion that both bcSTAT1a and bcSTAT1b play important roles in host antiviral innate immune activation initiated by GCRV.

Advanced oxidation protein products aggravate cardiac remodeling via cardiomyocyte apoptosis in chronic kidney disease.

Advanced oxidation protein products (AOPPs) are independent risk factor for various cardiovascular diseases. Cardiomyocyte apoptosis has been implicated as an important mechanism in cardiac remodeling in chronic kidney disease (CKD). However, whether AOPPs affect cardiomyocyte apoptosis and subsequent cardiac remodeling in CKD is still not very clear. Here, we assessed the role of AOPPs in cardiomyocyte apoptosis in CKD. H9C2 rat cardiomyoblast cells were exposed to AOPPs. Apoptotic cells were determined by TUNEL assay. The expression of apoptotic markers (cleaved caspase-3 and Bax), JNK signaling, and endoplasmic reticulum stress were explored. Serum AOPPs were measured in male Sprague-Dawley rats that underwent sham surgery and 5/6 nephrectomy, respectively. In vitro, our findings showed that AOPPs activated JNK signaling and endoplasmic reticulum stress and significantly aggravated H9C2 rat cardiomyoblast cells apoptosis. These effects were partially ameliorated by apocynin with inhibition of oxidative stress. In vivo, serum levels of AOPPs were progressively elevated with the increasing time course in CKD rats compared with sham-operated rats ( P < 0.05). Serum AOPP levels were positively associated with cardiomyocyte apoptosis ( R2 = 0.76, P < 0.01). In conclusion, AOPPs aggravate cardiomyocyte apoptosis in vitro, and these effects are partially prevented by apocynin via suppressing JNK signaling and endoplasmic reticulum stress with oxidative stress inhibition. In vivo, AOPPs are increased in the CKD model and may contribute to the cardiac pathogenesis, but at this point it is unclear if that is true. These results suggest that pharmacological approaches to attenuate AOPP-aggravated cardiomyocyte apoptosis may be beneficial to improve cardiac remodeling in CKD. NEW & NOTEWORTHY Here, we present new evidence to show that advanced oxidation protein products aggravate cardiomyocyte apoptosis and subsequent cardiac remodeling via upregulations of JNK signaling and endoplasmic reticulum stress in chronic kidney disease. Such processes are mainly prevented by apocynin via oxidative stress inhibition.

Interleukin-18 Enhances Vascular Calcification and Osteogenic Differentiation of Vascular Smooth Muscle Cells Through TRPM7 Activation.

OBJECTIVE: Vascular calcification (VC) is an important predictor of cardiovascular morbidity and mortality. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) is a key mechanism of VC. Recent studies show that IL-18 (interleukin-18) favors VC while TRPM7 (transient receptor potential melastatin 7) channel upregulation inhibits VC. However, the relationship between IL-18 and TRPM7 is unclear. We questioned whether IL-18 enhances VC and osteogenic differentiation of VSMCs through TRPM7 channel activation. APPROACH AND RESULTS: Coronary artery calcification and serum IL-18 were measured in patients by computed tomographic scanning and enzyme-linked immunosorbent assay, respectively. Primary rat VSMCs calcification were induced by high inorganic phosphate and exposed to IL-18. VSMCs were also treated with TRPM7 antagonist 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA to block TRPM7 channel activity and expression. TRPM7 currents were recorded by patch-clamp. Human studies showed that serum IL-18 levels were positively associated with coronary artery calcium scores (r=0.91; P<0.001). In VSMCs, IL-18 significantly decreased expression of contractile markers α-smooth muscle actin, smooth muscle 22 α, and increased calcium deposition, alkaline phosphatase activity, and expression of osteogenic differentiation markers bone morphogenetic protein-2, Runx2 (runt-related transcription factor 2), and osteocalcin (P<0.05). IL-18 increased TRPM7 expression through ERK1/2 (extracellular signal-regulated kinase 1/2) signaling activation, and TRPM7 currents were augmented by IL-18 treatment. Inhibition of TRPM7 channel by 2-aminoethoxy-diphenylborate or TRPM7 small interfering RNA prevented IL-18-enhanced osteogenic differentiation and VSMCs calcification. CONCLUSIONS: These findings suggest that coronary artery calcification is associated with increased IL-18 levels. IL-18 enhances VSMCs osteogenic differentiation and subsequent VC induced by ß-glycerophosphate via TRPM7 channel activation. Accordingly, IL-18 may contribute to VC in proinflammatory conditions.

Molecular cloning and characterization of TANK of black carp Mylopharyngodon piceus.

The TRAF family member-associated NF-κB activator (TANK) is linked to the regulation of the transcription of NF-κB in mammals; however, its role in interferon induction is unclear. To elucidate the roles of TANK in teleost, the TANK homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized in this paper. The open reading frame (ORF) of black carp TANK (bcTANK) comprises 1050 nucleotides and the predicted bcTANK protein contains 350 amino acids. The transcription of bcTANK in host cells increased in response to the stimulation of LPS, poly (I:C), SVCV and GCRV. bcTANK migrated around 50 KDa in immunoblot assay and was identified as a cytosolic protein by immunofluorescent staining in both EPC and HeLa cells. bcTANK could not induce the activity of IFN promoter in luciferase reporter assay in EPC cells; however, the IFN-activation ability of bcTANK was obviously enhanced when the cells were treated with LPS, poly (I:C) or virus. Both CPE ratio and virus titer in the media of EPC cells expressing bcTANK were obviously lower than those of the control cells, which were examined by violet crystal staining and plaque assay separately. Taken together, our data support the conclusion that bcTANK plays an important role in the antiviral innate immune activation of black carp.

Seasonal variations of PCDD/Fs in fishes: inferring a hidden exposure route from Na-PCP application for schistosomiasis control.

Japanese schistosomiasis was endemic in Dongting Lake, the second largest freshwater lake in China. The technical sodium pentachlorophenate (Na-PCP) was widely used during the period between the early 1960s and early 1990s to kill oncomelania, the intermediate host of Schistosomes. However, polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) also contaminated the environment of Dongting Lake due to trace impurities of Na-PCP. In this study, 13 species of freshwater fish were collected from Dongting Lake and analyzed in wet and dry seasons. Temporal (wet and dry season) variations in PCDD/Fs in fishes from Dongting Lake were observed. The concentration of PCDD/Fs was considerably higher in the wet season than in the dry season and in areas in China where Na-PCP was not applied. The higher level of PCDD/Fs in the wet season may be attributed to the use of Na-PCP in the past and to the increase in the migration of PCDD/Fs from sediments to water in the wet season. The results indicate that the risk of PCDD/Fs contamination is connected with prior consumption of fishes that live in the Na-PCP application area. However, there was no difference in the concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) between the wet and dry seasons.

Correction to: Seasonal variations of PCDD/Fs in fishes: inferring a hidden exposure route from Na-PCP application for schistosomiasis control.

The original version of this article unfortunately contained an error in the affiliation section.

Efficacy and Safety of Ranolazine in Diabetic Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have discovered that the antiangina agent ranolazine exerts a glucometabolic effect. OBJECTIVE: This systematic review and meta-analysis aimed to further understand the efficacy and safety profile of ranolazine in patients with diabetes. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and EMBASE databases and in ClinicalTrials.gov up to July 2017. Efficacy end points were defined as the change in hemoglobin A1C (A1C) and fasting serum glucose (FSG) levels. Safety end points included the incidence of hypoglycemia, persistent hyperglycemia, and major adverse cardiovascular events (MACE). Sensitive and subgroup analyses were also conducted. RESULTS: Seven RCTs with 4461 diabetic patients were selected. Compared with placebo, the use of ranolazine significantly reduced the levels of A1C (weighted mean difference [WMD] = -0.49%; 95% CI = -0.58 to -0.40; P < 0.00001) and FSG (WMD = -6.70 mg/dL; 95% CI = -11.87 to -1.52; P = 0.01). No significant differences were observed in the rates of hypoglycemia (relative risk [RR] = 1.17; 95% CI = 0.76 to 1.80; P = 0.47), persistent hyperglycemia (RR = 0.78; 95% CI = 0.47 to 1.31; P = 0.35), and MACE (RR = 0.65; 95% CI = 0.32 to 1.32; P = 0.23). CONCLUSION: Ranolazine exerts a positive effect on glucose control and is a well-tolerated agent for patients with diabetes.

Microstructure refinement of cold-sprayed copper investigated by electron channeling contrast imaging.

The electron channeling contrast imaging technique was used to investigate the microstructure of copper coatings fabricated by cold gas dynamic spray. The high velocity impact characteristics for cold spray led to the formation of many substructures, such as high density dislocation walls, dislocation cells, deformation twins, and ultrafine equiaxed subgrains/grains. A schematic model is proposed to explain structure refinement of Cu during cold spray, where an emphasis is placed on the role of dislocation configurations and twinning.

Efficient degradation of F-53B as PFOS alternative in water by plasma discharge: Feasibility and mechanism insights.

The frequent detection of 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) in various environments has raised concerns owing to its comparable or even higher environmental persistence and toxicity than perfluorooctane sulfonate (PFOS). This study investigated the plasma degradation of F-53B for the first time using a water film plasma discharge system. The results revealed that F-53B demonstrated a higher rate constant but similar defluorination compared to PFOS, which could be ascribed to the introduction of the chlorine atom. Successful elimination (94.8-100 %) was attained at F-53B initial concentrations between 0.5 and 10 mg/L, with energy yields varying from 15.1 to 84.5 mg/kWh. The mechanistic exploration suggested that the decomposition of F-53B mainly occurred at the gas-liquid interface, where it directly reacted with reactive species generated by gas discharge. F-53B degradation pathways involving dechlorination, desulfonation, carboxylation, C-O bond cleavage, and stepwise CF2 elimination were proposed based on the identified byproducts and theoretical calculations. Furthermore, the demonstrated effectiveness in removing F-53B in various coexisting ions and water matrices highlighted the robust anti-interference ability of the treatment process. These findings provide mechanistic insights into the plasma degradation of F-53B, showcasing the potential of plasma processes for eliminating PFAS alternatives in water.