As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resti...As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resting membrane potential and modulate membrane excitability. It has been reported that residue E224 plays a key role in regulating inward rectification. The mutant Kir2.1 (E224G) displays weaker inward rectification than the WT channel. Gating of Kir2.1 depends on the membrane lipid, PIP<sub>2</sub>, such that the channel gates are closed in the absence of PIP<sub>2</sub>. Here we perform electrophysiological and computational approaches, and demonstrate that E224 also plays an important role in the PIP<sub>2</sub>-dependent activation of Kir2.1 in addition to its influence on inward rectification. The E224G mutant takes 4.5 times longer to be activated by PIP<sub>2</sub>. To probe the mechanism by which E224G slows the channel opening kinetics, we perform targeted molecular dynamics simulations and find that the mutant weakens the interactions between CD-loop and C-linker (H221-R189) and the adjacent G-loops (R312-E303) which are thought to stabilize the open state of the channel in our previous work. These data provide new insights into the regulation of Kir2.1 channel activity and suggest that a common mechanism may be involved in the distinct biophysical processes, such as inward rectification and PIP<sub>2</sub>-induced gating.展开更多
Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its im...Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.展开更多
To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidatio...To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.展开更多
In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using ...In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using the hybrid kinetic-magnetohydrodynamic model in the NIMROD code,we have identified such a transition between the fishbone instability and theβ-induced Alfvén eigenmode(BAE)for the NBI heated plasmas on HL-2 A.When the safety factor at magnetic axis is well below one,typical kink-fishbone transition occurs as the EP fraction increases.When q0 is raised to approaching one,the fishbone mode is replaced with BAE for sufficient amount of EPs.When q0 is slightly above one,the toroidicity-induced Alfvén eigenmode dominates at lower EP pressure,whereas BAE dominates at higher EP pressure.展开更多
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant...Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.展开更多
In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of su...In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.展开更多
基金Supported by the National Natural Science Foundation for Distinguished Young Scholars of Hebei Province under Grant Nos C2015202340 and C2013202244the Foundation for Outstanding Talents of Hebei Province under Grant No C201400305+3 种基金the National Natural Science Foundation of China under Grant Nos 11247010,11175055,11475053,11347017,31400711 and 11647121the NIH R01 under Grant No HL059949-18the Foundation for the Science and Technology Program of Higher Education Institutions of Hebei Province under Grant No QN2016113the Scientific Innovation Fund for Excellent Young Scientists of Hebei University of Technology under Grant No 2015010
文摘As a member of the inwardly rectifying channel (Kir) family, Kir2.1 allows to influx the cell more easily than to efflux, a biophysical phenomenon named inward rectification. The function of Kir2.1 is to set the resting membrane potential and modulate membrane excitability. It has been reported that residue E224 plays a key role in regulating inward rectification. The mutant Kir2.1 (E224G) displays weaker inward rectification than the WT channel. Gating of Kir2.1 depends on the membrane lipid, PIP<sub>2</sub>, such that the channel gates are closed in the absence of PIP<sub>2</sub>. Here we perform electrophysiological and computational approaches, and demonstrate that E224 also plays an important role in the PIP<sub>2</sub>-dependent activation of Kir2.1 in addition to its influence on inward rectification. The E224G mutant takes 4.5 times longer to be activated by PIP<sub>2</sub>. To probe the mechanism by which E224G slows the channel opening kinetics, we perform targeted molecular dynamics simulations and find that the mutant weakens the interactions between CD-loop and C-linker (H221-R189) and the adjacent G-loops (R312-E303) which are thought to stabilize the open state of the channel in our previous work. These data provide new insights into the regulation of Kir2.1 channel activity and suggest that a common mechanism may be involved in the distinct biophysical processes, such as inward rectification and PIP<sub>2</sub>-induced gating.
基金partially supported by the National Natural Science Foundation of China(42177164,52474121)the Outstanding Youth Project of Hunan Provincial Department of Education(23B0008).
文摘Given the growing concern over global warming and the critical role of carbon dioxide(CO_(2))in this phenomenon,the study of CO_(2)-induced alterations in coal strength has garnered significant attention due to its implications for carbon sequestration.A large number of experiments have proved that CO_(2) interaction time(T),saturation pressure(P)and other parameters have significant effects on coal strength.However,accurate evaluation of CO_(2)-induced alterations in coal strength is still a difficult problem,so it is particularly important to establish accurate and efficient prediction models.This study explored the application of advancedmachine learning(ML)algorithms and Gene Expression Programming(GEP)techniques to predict CO_(2)-induced alterations in coal strength.Sixmodels were developed,including three metaheuristic-optimized XGBoost models(GWO-XGBoost,SSA-XGBoost,PO-XGBoost)and three GEP models(GEP-1,GEP-2,GEP-3).Comprehensive evaluations using multiple metrics revealed that all models demonstrated high predictive accuracy,with the SSA-XGBoost model achieving the best performance(R2—Coefficient of determination=0.99396,RMSE—Root Mean Square Error=0.62102,MAE—Mean Absolute Error=0.36164,MAPE—Mean Absolute Percentage Error=4.8101%,RPD—Residual Predictive Deviation=13.4741).Model interpretability analyses using SHAP(Shapley Additive exPlanations),ICE(Individual Conditional Expectation),and PDP(Partial Dependence Plot)techniques highlighted the dominant role of fixed carbon content(FC)and significant interactions between FC and CO_(2) saturation pressure(P).Theresults demonstrated that the proposedmodels effectively address the challenges of CO_(2)-induced strength prediction,providing valuable insights for geological storage safety and environmental applications.
文摘To investigate and compare the inhibitory properties of free and bound phenolic extracts of clove bud against carbohydrate hydrolyzing enzymes (alpha-amylase & alpha-glucosidase) and Fe2+-induced lipid peroxidation in rat pancreas in vitro. Methods: The free phenolics were extracted with 80% (v/v) acetone, while bound phenolics were extracted from the alkaline and acid hydrolyzed residue with ethyl acetate. Then, the interaction of the extracts with alpha-amylase and alpha-glucosidase was subsequently assessed. Thereafter, the total phenolic contents and antioxidant activities of the extracts were determined. Results: The result revealed that both extracts inhibited alpha-amylase and alpha-glucosidase in a dose-dependent manner. However, the alpha-glucosidase inhibitory activity of the extracts were significantly (P<0.05) higher than their alpha-amylase inhibitory activity. The free phenolics (31.67 mg/g) and flavonoid (17.28 mg/g) contents were significantly (P<0.05) higher than bound phenolic (23.52 mg/g) and flavonoid (13.70 mg/g) contents. Both extracts also exhibited high antioxidant activities as typified by their high reducing power, 1,1 diphenyl-2- picrylhydrazyl (DPPH) and 2, 2-azinobis-3-ethylbenzo-thiazoline-6-sulfonate (ABTS) radical scavenging abilities, as well as inhibition of Fe2+-induced lipid peroxidation in rat pancreas in vitro. Conclusions: This study provides a biochemical rationale by which clove elicits therapeutic effect on type 2 diabetes.
基金supported by the National Magnetic Confinement Fusion Science Program of China(No.2019YFE03050004)National Natural Science Foundation of China(Nos.11875253,11775221,51821005)+3 种基金the Fundamental Research Funds for the Central Universities at University of Science and Technology of China(No.WK3420000004)Huazhong University of Science and Technology(No.2019kfy XJJS193)the Collaborative Innovation Program of Hefei Science Center,CAS(No.2019HSC-CIP015)the U.S.Department of Energy(Nos.DE-FG02-86ER53218 and DE-SC0018001)。
文摘In the presence of energetic particles(EPs)from auxiliary heating and burning plasmas,fishbone instability and Alfvén modes can be excited and their transition can take place in certain overlapping regimes.Using the hybrid kinetic-magnetohydrodynamic model in the NIMROD code,we have identified such a transition between the fishbone instability and theβ-induced Alfvén eigenmode(BAE)for the NBI heated plasmas on HL-2 A.When the safety factor at magnetic axis is well below one,typical kink-fishbone transition occurs as the EP fraction increases.When q0 is raised to approaching one,the fishbone mode is replaced with BAE for sufficient amount of EPs.When q0 is slightly above one,the toroidicity-induced Alfvén eigenmode dominates at lower EP pressure,whereas BAE dominates at higher EP pressure.
基金supported by the Russian Foundation for Basic Research (Grant No. 20-04-00526А)
文摘Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.
基金the DFG research training group GRK 1896 at Erlangen University and from the Joint Project Helmholtz-Institute Erlangen-Nürnberg(HI-ERN)for Renewable Energy Production under Project DBF01253,respectivelyfinancial support through the“Aufbruch Bayern”initiative of the state of Bavaria(EnCN and Solar Factory of the Future)and the“Solar Factory of the Future”with the Energy Campus Nürnberg(EnCN).
文摘In this report,we show that hyperspectral high-resolution photoluminescence mapping is a powerful tool for the selection and optimiz1ation of the laser ablation processes used for the patterning interconnections of subcells on Cu(Inx,Ga1-x)Se2(CIGS)modules.In this way,we show that in-depth monitoring of material degradation in the vicinity of the ablation region and the identification of the underlying mechanisms can be accomplished.Specifically,by analyzing the standard P1 patterning line ablated before the CIGS deposition,we reveal an anomalous emission-quenching effect that follows the edge of the molybdenum groove underneath.We further rationalize the origins of this effect by comparing the topography of the P1 edge through a scanning electron microscope(SEM)cross-section,where a reduction of the photoemission cannot be explained by a thickness variation.We also investigate the laser-induced damage on P1 patterning lines performed after the deposition of CIGS.We then document,for the first time,the existence of a short-range damaged area,which is independent of the application of an optical aperture on the laser path.Our findings pave the way for a better understanding of P1-induced power losses and introduce new insights into the improvement of current strategies for industry-relevant module interconnection schemes.
