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BACKGROUND: The brown planthopper (BPH) is a kind of piercing-sucking insect specific to rice, with the damage tops the list of pathogens and insects in recent years. microRNAs (miRNAs) are pivotal regulators of plant-environment interactions, while the mechanism underlying their function against insects is largely unknown. RESULTS: Here, we confirmed that OsmiR319, an ancient and conserved miRNA, negatively regulated resistance to BPHs, with overexpression of OsmiR319 susceptible to BPH, while suppression of OsmiR319 resistant to BPH in comparison with wild type. Meanwhile, we identified several targets of OsmiR319 that may mediate BPH resistance. Among them, OsPCF5 was the most obviously induced by BPH feeding, and over expression of OsPCF5 was resistance to BPH. In addition, various biochemical assays verified that OsPCF5 interacted with several MYB proteins, such as OsMYB22, OsMYB30, and OsMYB30C.Genetically, we revealed that both OsMYB22 and OsMYB30C positively regulated BPH resistance. Genetic interaction analyses confirmed that OsMYB22 and OsMYB30C both function in the same genetic pathway with OsmiR319b to mediate BPH resistance. CONCLUSIONS: Altogether, we revealed that OsPCF5 regulates BPH resistance via association with several MYB proteins downstream of OsmiR319, these MYB proteins might function as regulators of BPH resistance through regulating the phenylpropane synthesis.
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Hemípteros , MicroRNAs , Oryza , Animais , Oryza/fisiologia , Hemípteros/genética , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Singlet oxygen (1O2) species generated in peroxymonosulfate (PMS)-based advanced oxidation processes offer opportunities to overcome the low efficiency and secondary pollution limitations of existing AOPs, but efficient production of 1O2 via tuning the coordination environment of metal active sites remains challenging due to insufficient understanding of their catalytic mechanisms. Herein, an asymmetrical configuration characterized by a manganese single atom coordinated is established with one S atom and three N atoms (denoted as Mn-S1N3), which offer a strong local electric field to promote the cleavage of OâH and SâO bonds, serving as the crucial driver of its high 1O2 production. Strikingly, an enhanced the local electric field caused by the dynamic inter-transformation of the Mn coordination structure (Mn-S1N3 â Mn-N3) can further downshift the 1O2 production energy barrier. Mn-S1N3 demonstrates 100% selective product 1O2 by activation of PMS at unprecedented utilization efficiency, and efficiently oxidize electron-rich pollutants. This work provides an atomic-level understanding of the catalytic selectivity and is expected to guide the design of smart 1O2-AOPs catalysts for more selective and efficient decontamination applications.
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In this study, we present an ultralow noise single-frequency fiber laser operating at 1550â nm, utilizing a traveling-wave ring cavity configuration. The frequency noise of the laser approaches the thermal noise limit, achieving a white noise level of 0.025â Hz2/Hz, resulting in an instantaneous linewidth of 0.08â Hz. After amplification, the output power reaches 4.94 W while maintaining the same low white noise level as the laser oscillator. The integration linewidths of the laser oscillator and amplifier are 221â Hz and 665â Hz, respectively, with both exhibiting relative intensity noises that approach the quantum shot noise limit. To the best of our knowledge, this work shows the lowest frequency noise combined with relatively high power for this type of ring cavity fiber laser.
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Sunlight may lead to changes in disinfection byproducts (DBPs) formation potentials of source water via transforming dissolved organic matter (DOM); however, the underlying mechanisms behind these changes remain unclear. This work systematically investigated the effect of photochemical transformation of DOM from reservoir water (DOMRe) and micropolluted river water (DOMRi) after 36 h of simulated sunlight irradiation (equivalent to one month under natural sunlight) on DBPs formation. Upon irradiation, high molecular weight (MW) and aromatic molecules tended to be mineralized or converted into low-MW and highly oxidized (O/C > 0.5) ones which might react with chlorine to generate high levels of DBPs, resulting in an elevation in the yields (µg DBP/mg C) of almost all the measured DBPs and the quantities of unknown DBPs in both DOM samples after chlorination. Additionally, DOMRi contained more aromatic molecules susceptible to photooxidation than DOMRe. Consequently, irradiated DOMRi exhibited a greater increase in the formation potentials of haloacetonitriles, halonitromethanes, and specific regulated DBPs, with nitrogenous DBPs being responsible for the overall rise in the calculated cytotoxicity following chlorination. This work emphasized the importance of a comprehensive removal of phototransformation products that may serve as DBPs precursors from source waters, especially from micropolluted source waters.
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Layered VS2 has been widely used as a battery anode material owing to its large specific surface area and controllable ion-transport channel. However, its semiconductor properties and poor cycling stability seriously limit its further applications. Herein, a two-dimensional BN/VS2 heterostructure (BVH) was constructed as an anode material for rechargeable metal-ion batteries (RMIBs). Demonstrated using first principles calculations, BVH exhibits a metallic property due to lattice stress between monolayer BN and VS2. BVH displays low ion diffusion energy barriers (0.13, 0.43, and 0.56 eV) and high theoretical capacities (447, 553.5, and 340.7 mA h g-1) for Li+, Na+, and Mg2+ storage. In BVH, the VS2 layer as the main redox center supports charge transfer, while the inactive BN layer enables high structural stability. This synergistic effect is expected to simultaneously achieve a high rate, high capacity, and long life. This design provides an important insight into developing new anode materials for RMIBs.
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Type A aortic dissection (TAAD) is a life-threatening disease with high mortality and poor prognosis, usually treated by surgery. There are many complications in its perioperative period, one of which is oxygenation impairment (OI). As a common complication of TAAD, OI usually occurs throughout the perioperative period of TAAD and requires prolonged mechanical ventilation (MV) and other supportive measures. The purpose of this article is to review the risk factors, mechanisms, and treatments of type A aortic dissection-related oxygenation impairment (TAAD-OI) so as to improve clinicians' knowledge about it. Among risk factors, elevated body mass index (BMI), prolonged extracorporeal circulation (ECC) duration, higher inflammatory cells and stored blood transfusion stand out. A reduced occurrence of TAAD-OI can be achieved by controlling these risk factors such as suppressing inflammatory response by drugs. As for its mechanism, it is currently believed that inflammatory signaling pathways play a major role in this process, including the HMGB1/RAGE signaling pathway, gut-lung axis and macrophage, which have been gradually explored and are expected to provide evidences revealing the specific mechanism of TAAD-OI. Numerous treatments have been investigated for TAAD-OI, such as nitric oxide (NO), continuous pulmonary perfusion/inflation, ulinastatin and sivelestat sodium, immunomodulation intervention and mechanical support. However, these measures are all aimed at postoperative TAAD-OI, and not all of the therapies have shown satisfactory effects. Treatments for preoperative TAAD-OI are not currently available because it is difficult to correct OI without correcting the dissection. Therefore, the best solution for preoperative TAAD-OI is to operate as soon as possible. At present, there is no specific method for clinical application, and it relies more on the experience of clinicians or learns from treatments of other diseases related to oxygenation disorders. More efforts should be made to understand its pathogenesis to better improve its treatments in the future.
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Phytohormones, epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined. In this study, bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light, correlating with reduced abscisic acid (ABA) accumulation. Transcription of the key ABA catabolism gene, ABA 8'-hydroxylase FaCYP707A4, was induced in bagged fruit. With light exclusion whole genome DNA methylation levels were up-regulated, corresponding to a delayed ripening process, while DNA methylation levels in the promoter of FaCYP707A4 were suppressed, correlating with increases in transcript and decreased ABA content. Experiments indicated FaCRY1, a blue light receptor repressed in bagged fruit and FaAGO4, a key protein involved in RNA-directed DNA methylation, could bind to the promoter of FaCYP707A4. The interaction between FaCRY1 and FaAGO4, and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter. Furthermore, transient overexpression of FaCRY1, or an increase in FaCRY1 transcription by blue light treatment, increases the methylation level of the FaCYP707A4 promoter, while transient RNA interference of FaCRY1 displayed opposite phenotypes. These findings reveal a mechanism by which DNA methylation influences ABA catabolism, and participates in light-mediated strawberry ripening.
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Ácido Abscísico , Metilação de DNA , Fragaria , Frutas , Regulação da Expressão Gênica de Plantas , Luz , Proteínas de Plantas , Regiões Promotoras Genéticas , Ácido Abscísico/metabolismo , Fragaria/genética , Fragaria/metabolismo , Fragaria/crescimento & desenvolvimento , Metilação de DNA/genética , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regiões Promotoras Genéticas/genéticaRESUMO
To investigate the heavy metals (HMs) contamination of surface farmland soil along the river in the southeast of a mining area in southwest China and identify the contamination sources, 54 topsoil samples were collected and the concentrations of seven elements (Zn, Ni, Pb, Cu, Hg, Cr, and Co) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic fluorescence spectrometry (AFS). The geo-accumulation index ([Formula: see text]) and comprehensive potential ecological risk index ([Formula: see text]) were used for analysis to determine the pollution degree of HMs and the risk level of the study area. Meanwhile, the Positive Matrix Factorization (PMF) model was combined with a variety of statistical methods to determine the sources of HMs. To explore the influence of the river flowing through the mining area on the concentrations of HMs in the farmland soil, 15 water samples were collected and the concentrations of the above seven elements were determined. The results showed that the concentrations of Pb, Cu, and Zn in soil all exceeded the risk screening value, and Pb in soil of some sampling sites exceeded control value of "Agricultural Land Soil Pollution Risk Control Standard".[Formula: see text] showed that Pb was heavily contaminated, while Cu and Zn were moderately contaminated. RI showed that the study area was at moderate risk. PMF and various statistical methods showed that the main source of HMs was the industrial source. In the short term, the river flowing through the mine has no significant influence on the concentration of HMs in the soil. The results provide a reference for the local government to control contamination and identify the sources of HMs.
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Metais Pesados , Solo , Fazendas , Rios , Chumbo , Medição de Risco , ChinaRESUMO
Exposure to stress early in life has been associated with adult-onset comorbidities such as chronic pain, metabolic dysregulation, obesity, and inactivity. We have established an early-life stress model using neonatal maternal separation (NMS) in mice, which displays evidence of increased body weight and adiposity, widespread mechanical allodynia, and hypothalamic-pituitary-adrenal axis dysregulation in male mice. Early-life stress and consumption of a Western-style diet contribute to the development of obesity; however, relatively few preclinical studies have been performed in female rodents, which are known to be protected against diet-induced obesity and metabolic dysfunction. In this study, we gave naïve and NMS female mice access to a high-fat/high-sucrose (HFS) diet beginning at 4 wk of age. Robust increases in body weight and fat were observed in HFS-fed NMS mice during the first 10 wk on the diet, driven partly by increased food intake. Female NMS mice on an HFS diet showed widespread mechanical hypersensitivity compared with either naïve mice on an HFS diet or NMS mice on a control diet. HFS diet-fed NMS mice also had impaired glucose tolerance and fasting hyperinsulinemia. Strikingly, female NMS mice on an HFS diet showed evidence of hepatic steatosis with increased triglyceride levels and altered glucocorticoid receptor levels and phosphorylation state. They also exhibited increased energy expenditure as observed via indirect calorimetry and expression of proinflammatory markers in perigonadal adipose. Altogether, our data suggest that early-life stress exposure increased the susceptibility of female mice to develop diet-induced metabolic dysfunction and pain-like behaviors.
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Dieta Hiperlipídica , Sacarose Alimentar , Estresse Psicológico , Animais , Feminino , Camundongos , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Sistema Hipotálamo-Hipofisário/metabolismo , Privação Materna , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Sacarose Alimentar/efeitos adversosRESUMO
Atherosclerosis is the main pathological basis of cardiovascular disease and involves damage to vascular endothelial cells (ECs) that results in endothelial dysfunction (ED). The vascular endothelium is the key to maintaining blood vessel health and homeostasis. ED is a complex pathological process involving inflammation, shear stress, vascular tone, adhesion of leukocytes to ECs, and platelet aggregation. The activation of P2X4, P2X7, and P2Y2 receptors regulates vascular tone in response to shear stress, while activation of the A2A, P2X4, P2X7, P2Y1, P2Y2, P2Y6, and P2Y12 receptors promotes the secretion of inflammatory cytokines. Finally, P2X1, P2Y1, and P2Y12 receptor activation regulates platelet activity. These purinergic receptors mediate ED and participate in atherosclerosis. In short, P2X4, P2X7, P2Y1, and P2Y12 receptors are potential therapeutic targets for atherosclerosis.
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Aterosclerose , Receptores Purinérgicos P2 , Humanos , Células Endoteliais , Receptores Purinérgicos , Endotélio Vascular , Receptores Purinérgicos P2Y1RESUMO
Rechargeable magnesium batteries (RMBs) are considered as highly promising energy storage systems. However, the lack of cathode materials with fast Mg2+ diffusion kinetics and high energy density severely hinders the development of RMBs. Herein, a two-dimensional (2D) VO2/VS2 heterostructure as a RMB cathode material is proposed by introducing an O-V-O layer in VS2 to improve the discharge voltage and specific capacity while keeping the fast Mg2+ diffusion kinetics. Based on first principle calculations, the geometric structures, electronic characteristics of the VO2/VS2 heterostructure, and the adsorption properties and diffusion behaviors of Mg2+ in VO2/VS2 are systematically studied. The metallic properties of VO2/VS2 and a relatively low diffusion barrier of Mg2+ (0.6 eV) in VO2/VS2 enable a large potential in delivering high rate performance in actual RMBs. Compared with traditional VS2 materials (1.25 V), the average discharge platform of VO2/VS2 could be increased to 1.7 V. The theoretical capacities of the layered VS2 and VO2/VS2 are calculated as 233 and 301 mA h g-1, respectively. Thus, the VO2/VS2 heterostructure exhibits a high theoretical energy density of 511.7 W h kg-1, significantly surpassing that of VS2 (291.3 W h kg-1). This work provides important guidance for designing high-energy and high-rate 2D heterostructure cathode materials for RMBs and other multivalent ion batteries.
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OBJECTIVE: To explore the differences and characteristics of cardiorespiratory fitness (CRF) among children and adolescents in regions with different latitudes in China. METHODS: A total of 9892 children and adolescents aged 7-22 years were selected from seven administrative regions in China by the stratified cluster random sampling method. CRF was measured by performance on the 20 m shuttle run test (20mSRT) and estimated maximal oxygen consumption (VO2max ). One-way ANOVA, one-way ANCOVA, and the Lambda Mu and Sigma methods were used to analyze the data. RESULTS: Overall, the VO2max of children and adolescents at high latitudes was significantly lower than that of children at low and middle latitudes. The P10 , P50 , and P90 20mSRT values for children and adolescents of most age groups in high latitudes were less than those in low and middle latitudes. The 20mSRT-Z and VO2max -Z scores among children and adolescents aged 7-22 in high latitudes were lower than those in middle and low latitudes after adjusting for age, per capita gross domestic product (GDP), and per capita disposable income. CONCLUSION: In general, the CRF of children and adolescents at high latitudes was less than that at low and middle latitudes. Effective measures should be taken to improve CRF in children and adolescents at high latitudes.
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Aptidão Cardiorrespiratória , Humanos , Criança , Adolescente , Renda , China , Coleta de Dados , Teste de Esforço/métodosRESUMO
As an important forestry biomass resource, rosin has a wide range of applications in medicine, adhesives, surfactants and other fields. Using natural dehydroabietic acid as a raw material, dehydroabietic acid-based phosphorus monoester (DPM) and diester (DPD) surfactants were designed and synthesized. The chemical structures and self-assembly properties were characterized by FT-IR, NMR and TEM, and the effects of pH on critical micelle concentration, γCMC, emulsifying properties, foam properties and micelle morphology were studied. The results showed that the CMC, γCMC value and aggregate morphology had certain pH responsiveness. The γCMC value under acidic conditions was smaller than γCMC under alkaline conditions, and the foaming performance and foam stability under acidic conditions were better than those under alkaline conditions. TEM micelle morphology studies have shown that DPM and DPD surfactants can self-assemble into rod-shaped and spherical micelle morphologies with a pH change in an aqueous solution. At the same pH, the foaming and emulsification properties of DPD were better than those of DPM. The best foaming and emulsification ability of DPD were 11.8 mL and 175 s, respectively. At the same time, the foaming ability of DPD is also affected by pH. DPD has excellent foaming properties in acidic conditions, but these disappeared in neutral conditions.
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microRNAs (miRNAs) are promising targets for crop improvement of complex agricultural traits. Coordinated activity between/among different miRNAs may fine-tune specific developmental processes in diverse organisms. Grain size is a main factor determining rice (Oryza sativa L.) crop yield, but the network of miRNAs influencing this trait remains uncharacterized. Here we show that sequestering OsmiR396 through target mimicry (MIM396) can substantially increase grain size in several japonica and indica rice subspecies and in plants with excessive tillers and a high panicle density. Thus, OsmiR396 has a major role related to the regulation of rice grain size. The grain shape of Growth Regulating Factor8 (OsGRF8)-overexpressing transgenic plants was most similar to that of MIM396 plants, suggesting OsGRF8 is a major mediator of OsmiR396 in grain size regulation. A miRNA microarray analysis revealed changes to the expression of many miRNAs, including OsmiR408, in the MIM396 plants. Analyses of gene expression patterns and functions indicated OsmiR408 is an embryo-specific miRNA that positively regulates grain size. Silencing OsmiR408 expression (miR408KO) using CRISPR technology resulted in small grains. Moreover, we revealed the direct regulatory effects of OsGRF8 on OsMIR408 expression. A genetic analysis further showed that the large-grain phenotype of MIM396 plants could be complemented by miR408KO. Also, several hormone signaling pathways might be involved in the OsmiR396/GRF-meditated grain size regulation. Our findings suggest that genetic regulatory networks comprising various miRNAs, such as OsmiR396 and OsmiR408, may be crucial for controlling rice grain size. Furthermore, the OsmiR396/GRF module may be important for breeding new high-yielding rice varieties.
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Grão Comestível/crescimento & desenvolvimento , MicroRNAs/metabolismo , Oryza/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , RNA de Plantas/metabolismo , Grão Comestível/genética , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/metabolismoRESUMO
OBJECTIVE: This study aimed to assess the role of age, sex, and weight status in the development of muscular fitness in a large sample of Chinese Tibetan children and adolescents aged 7-18 years living in areas over 3600 m. METHOD: A sample of 4673 Chinese Tibetan children and adolescents aged 7-18 years were recruited from 21 schools in three cities (Lhasa, Naqu, and Anduo) of Tibet, China. Grip strength, standing long jump, 30-s sit-ups, and 50-m dash were conducted to determine muscular fitness. Independent sample t tests were conducted to compare muscular fitness between boys and girls for each age group. The changes in mean scores on each muscular fitness test were estimated. The influence of weight status on muscular strength level was also estimated using one-way ANOVA and LSD tests. We also compared the average muscular fitness between Chinese Tibetan and Chinese average level. RESULTS: The muscular fitness of Chinese Tibetan boys aged 7-18 years was higher than that of girls, with older children outperforming younger children. Among the Chinese Tibetan boys, those in the normal-weight group showed the best performance, whereas overweight group showed the best performance among the girls. The performance of Chinese Tibetan children and adolescents in standing long jump and 50-m dash was lower while that in sit-ups was higher than the performance of their Chinese counterparts. CONCLUSION: Chinese Tibetan children and adolescents have relatively strong abdominal strength, but lower limb strength, which needs to be improved. Age, sex, and weight status should be considered when designing interventions to improve muscular fitness.
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Altitude , Exercício Físico , Adolescente , Índice de Massa Corporal , Criança , China , Estudos Transversais , Feminino , Humanos , Masculino , Aptidão Física , TibetRESUMO
As a typical triazole fungicide, prothioconazole (Pro) has been used extensively due to its broad spectrum and high efficiency. However, as a racemic mixture of two enantiomers (R-Pro and S-Pro), the enantiomer-specific outcomes on the bioactivity have not been fully elucidated. Here, we investigate how chirality affects the activity and mechanism of action of Pro enantiomers on Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), the notorious virulent strain causing Fusarium wilt of banana (FWB). The Pro enantiomers were evaluated in vivo and in vitro with the aid of three bioassay methods for their fungicidal activities against TR4 and the results suggested that the fungicidal activities of Pro enantiomers are stereoselective in a dose-dependent manner with R-Pro making a major contribution to the treatment outcomes. We found that R-Pro led to more severe morphological changes and impairment in membrane integrity than S-Pro. R-Pro also led to the increase of more MDA contents and the reduction of more SOD and CAT activities compared with the control and S-Pro groups. Furthermore, the expression of Cytochrome P450 14α-sterol demethylases (CYP51), the target for triazole fungicides, was significantly increased upon treatment with R-Pro rather than S-Pro, at both transcriptional and translational levels; so were the activities of the Cytochrome P450 enzymes. In addition, surface plasmon resonance (SPR) and molecular docking illuminated the stereoselective interactions between the Pro enantiomers and CYP51 of TR4 at the target site, and R-Pro showed a better binding affinity with CYP51 than S-Pro. These results suggested an enantioselective mechanism of Pro against TR4, which may rely on the enantioselective damages to the fungal cell membrane and the enantiospecific CYP51 binding affinity. Taken together, our study shed some light on the mechanisms underlying the differential activities of the Pro enantiomers against TR4 and demonstrated that Pro can be used as a potential candidate in the treatment of FWB.
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Antifúngicos/farmacologia , Fusarium/efeitos dos fármacos , Estresse Oxidativo , Esterol 14-Desmetilase/genética , Triazóis/farmacologia , Catalase , Regulação Fúngica da Expressão Gênica , Isomerismo , Simulação de Acoplamento Molecular , Esterol 14-Desmetilase/efeitos dos fármacos , Superóxido Dismutase , Triazóis/químicaRESUMO
Synthesis and implementation of highly active, stable, and affordable electrocatalysts for the oxygen evolution reaction (OER) is a major challenge in developing energy efficient and economically viable energy conversion devices such as electrolyzers, rechargeable metal-air batteries, and regenerative fuel cells. The current benchmark electrocatalyst for OER is based on iridium oxide (IrOx) due to its superior performance and excellent stability. However, large scale applications using IrOx are impractical due to its low abundance and high cost. Herein, we report a highly active hafnium-modified iridium oxide (IrHfxOy) electrocatalyst for OER. The IrHfxOy electrocatalyst demonstrated ten times higher activity in alkaline conditions (pH = 11) and four times higher activity in acid conditions (pH = 1) than a IrOx electrocatalyst. The highest intrinsic mass activity of the IrHfxOy catalyst in acid conditions was calculated as 6950 A gIrOx-1 at an overpotential (η) of 0.3 V. Combined studies utilizing operando surface enhanced Raman spectroscopy (SERS) and DFT calculations revealed that the active sites for OER are the Ir-O species for both IrOx and IrHfxOy catalysts. The presence of Hf sites leads to more negative charge states on nearby O sites, shortening of the bond lengths of Ir-O, and lowers free energies for OER intermediates that accelerate the OER process.
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INTRODUCTION: This multicenter, randomized, noninferiority trial compared electroacupuncture with prucalopride for the treatment of severe chronic constipation (SCC). METHODS: Participants with SCC (≤ 2 mean weekly complete spontaneous bowel movements [CSBMs]) were randomly assigned to receive either 28-session electroacupuncture over 8 weeks with follow-up without treatment over 24 weeks or prucalopride (2 mg/d before breakfast) over 32 weeks. The primary outcome was the proportion of participants with ≥3 mean weekly CSBMs over weeks 3-8, based on the modified intention-to-treat population, with -10% as the noninferior margin. RESULTS: Five hundred sixty participants were randomized, 280 in each group. Electroacupuncture was noninferior to prucalopride for the primary outcome (36.2% vs 37.8%, with a difference of -1.6% [95% confidence interval, -8% to 4.7%], P < 0.001 for noninferiority); almost the same results were found in the per-protocol population. The proportions of overall CSBM responders through weeks 1-8 were similar in the electroacupuncture and prucalopride groups (24.91% vs 25.54%, with a difference of -0.63% [95% confidence interval, -7.86% to 6.60%, P = 0.864]). Except during the first 2-week treatment, no between-group differences were found in outcomes of excessive straining, stool consistency, and quality of life. Adverse events occurred in 49 (17.69%) participants in the electroacupuncture group and 123 (44.24%) in the prucalopride group. One non-treatment-related serious adverse event was recorded in the electroacupuncture group. DISCUSSION: Electroacupuncture was noninferior to prucalopride in relieving SCC with a good safety profile. The effects of 8-week electroacupuncture could sustain for 24 weeks after treatment. Electroacupuncture is a promising noninferior alternative for SCC (see Visual Abstract, http://links.lww.com/AJG/B776).
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Benzofuranos/uso terapêutico , Constipação Intestinal/terapia , Eletroacupuntura/métodos , Laxantes/uso terapêutico , China , Doença Crônica , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Platelet activation by stimulatory factors leads to an increase in intracellular calcium concentration ([Ca2+]i), which is essential for almost all platelet functions. Modulation of Ca2+ influx and [Ca2+]i in platelets has been emerging as a possible strategy for preventing and treating platelet-dependent thrombosis. Voltage-gated potassium 1.3 channels (Kv1.3) are highly expressed in platelets and able to regulate agonist-evoked [Ca2+]i increase. However, the role of Kv1.3 channels in regulating platelet functions and thrombosis has not yet been elucidated. In addition, it is difficult to obtain a specific blocker for this channel, since Kv1.3 shares identical drug-binding sites with other K+ channels. Here, we investigate whether specific blockade of Kv1.3 channels by monoclonal antibodies affects platelet functions and thrombosis. Approach and Results: In this study, we produced the anti-Kv1.3 monoclonal antibody 6E12#15, which could specifically recognize both human and mouse Kv1.3 proteins and sufficiently block Kv1.3 channel currents. We found Kv1.3 blockade by 6E12#15 inhibited platelet aggregation, adhesion, and activation upon agonist stimulation. In vivo treatment with 6E12#15 alleviated thrombus formation in a mesenteric arteriole thrombosis mouse model and protected mice from collagen/epinephrine-induced pulmonary thromboembolism. Furthermore, we observed Kv1.3 regulated platelet functions by modulating Ca2+ influx and [Ca2+]i elevation, and that this is mediated in part by P2X1. Interestingly, Kv1.3-/- mice showed impaired platelet aggregation while displayed no abnormalities in in vivo thrombus formation. This phenomenon was related to more megakaryocytes and platelets produced in Kv1.3-/- mice compared with wild-type mice. CONCLUSIONS: We showed specific inhibition of Kv1.3 by the novel monoclonal antibody 6E12#15 suppressed platelet functions and platelet-dependent thrombosis through modulating platelet [Ca2+]i elevation. These results indicate that Kv1.3 could act as a promising therapeutic target for antiplatelet therapies.
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Anticorpos Monoclonais/farmacologia , Plaquetas/efeitos dos fármacos , Fibrinolíticos/farmacologia , Canal de Potássio Kv1.3/antagonistas & inibidores , Inibidores da Agregação Plaquetária/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Embolia Pulmonar/prevenção & controle , Trombose/prevenção & controle , Animais , Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/metabolismo , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Canal de Potássio Kv1.3/sangue , Canal de Potássio Kv1.3/deficiência , Canal de Potássio Kv1.3/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ativação Plaquetária/efeitos dos fármacos , Embolia Pulmonar/sangue , Embolia Pulmonar/genética , Embolia Pulmonar/metabolismo , Transdução de Sinais , Trombose/sangue , Trombose/genética , Trombose/metabolismoRESUMO
BACKGROUND: This study assessed the correlation between latitude and the cardiorespiratory fitness (CRF) of children and adolescents. METHODS: In 16 provinces and autonomous regions in China, 25,941 children and adolescents aged 10-18 were included. CRF was measured using the 20 m shuttle run test (20 m SRT) and estimated peak oxygen uptake (VO2peak). One-way ANOVA and multiple regression analysis were used to explore the correlation between CRF and latitude in children and adolescents. RESULTS: The VO2peak values of the low (south), middle, and high (north) latitude groups for boys were 43.1, 43.1, and 40.7 mL/kg/min, respectively, and 40.0, 40.0, and 38.5 mL/kg/min for girls, respectively. After adjusting for confounding factors, the regression coefficients (ß) between VO2peak-Z and both latitude-Z and (latitude-Z)2 for boys were -0.151 and -0.043, respectively. For girls, they were -0.142 and -0.020, respectively. The Partial correlation coefficient (r) for latitude-Z and (latitude-Z)2 were -0.14 and -0.04 for boys, and -0.13 and -0.02 for girls, respectively. CONCLUSION: The CRF among children and adolescents in high latitude regions is significantly lower than that in middle and low latitude region, and it generally shows a "parabolic" trend between Latitude-Z and VO2peak-Z.