Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)sig...Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.展开更多
This paper describes the design and control of a portable and lightweight knee exoskeleton for people with knee dysfunction.The knee exoskeleton is designed based on our custom quasi-direct drive actuation composed of...This paper describes the design and control of a portable and lightweight knee exoskeleton for people with knee dysfunction.The knee exoskeleton is designed based on our custom quasi-direct drive actuation composed of a DC motor unit and a transmission mechanism encompassing three gears.An online gait generation method based on gait step calculation and direct measurement using Inertial Measurement Unit(IMU)sensors is proposed to provide continuous assistance during walking.Based on the generated gait trajectory online,Active Disturbance Rejection Control(ADRC)incorporating the feedforward compensation approach is proposed to help the human leg move in consideration of external disturbances.The developed knee exoskeleton has been employed successfully to assist impaired users with knee dysfunction to walk in a health recovery center.The experimental results indicate that the online gait generation method and the proposed control method are suitable for the knee exoskeleton.The maximum value of the target knee angular position is approximately 50°and the mean of the control torque for the knee joint is located in the interval of[−2 Nm,4 Nm].The developed knee exoskeleton has the potential to regain normal gait to improve strength and endurance during walking in their activities of daily life.展开更多
Background:Podocyte injury is crucial in diabetic kidney disease(DKD)progression,and the mechanism remains unclear.The previous studies indicated Diosgenin played a key role in inhibiting podocyte injury progression.H...Background:Podocyte injury is crucial in diabetic kidney disease(DKD)progression,and the mechanism remains unclear.The previous studies indicated Diosgenin played a key role in inhibiting podocyte injury progression.However,more research is needed to explore Diosgenin in inhibiting-molecular mechanisms in the process of podocyte injury.Methods:The content of Diosgenin in HeShenwan was detected by High-Performance Liquid Chromatography-mass spectrometry(HPLC-MS)method.The podocyte injury model was constructed by high glucose(HG)-induced mpc5 cells.The Cell Counting Kit-8(CCK-8)assay was utilized to evaluate the activity of mpc5 cells.Pyroptosis in mpc5 cells was assessed using flow cytometry.Molecular docking studies of Diosgenin and Nrf2 were carried out using VINA 1.1.2 software.The levels of Superoxide dismutase(SOD),Malondialdehyde(MDA),Reactive oxygen species(ROS),Interleukin 1β(IL-1β),Interleukin 18(IL-18),Lactate dehydrogenase(LDH)and High mobility group protein B1(HMGB1)were assessed using related kits.The levels of Nod-like receptor protein 3(NLRP3),Nuclear factor erythroid-2-related factor 2(Nrf2),Cysteinyl aspartate specific proteinase 1(Caspase-1),Gasdermin(GSDMD),and Apoptosis-associated speck-like protein contain a CARD(ASC)were detected.Results:The Diosgenin content was the highest in HeShenwan.The addition of Diosgenin enhanced HG-induced mpc5 cell activity and reduced oxidative stress and pyroptosis.Molecular docking results showed that Diosgenin bound to the Nrf2 through hydrogen bonds and hydrophobic interactions,regulating the Nrf2 expression.Overexpression of Nrf2 reduced the levels of NLRP3,reducing oxidative stress and inhibiting pyroptosis in mpc5 cells.Knockdown of Nrf2 reduced HG-induced mpc5 cell activity and increased pyroptosis and oxidative stress.Diosgenin inhibited pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway.Conclusion:Diosgenin inhibited HG-induced pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway.展开更多
Chinese sprangletop (Leptochloa chinensis), belonging to the grass subfamily Chloridoideae, is one of the most notorious weeds in rice ecosystems. Here, we report a chromosome-scale reference genome assembly and a gen...Chinese sprangletop (Leptochloa chinensis), belonging to the grass subfamily Chloridoideae, is one of the most notorious weeds in rice ecosystems. Here, we report a chromosome-scale reference genome assembly and a genomic variation map of the tetraploid L. chinensis. The L. chinensis genome is derived from two diploid progenitors that diverged ∼10.9 million years ago, and its two subgenomes display neither fractionation bias nor overall gene expression dominance. Comparative genomic analyses reveal substantial genome rearrangements in L. chinensis after its divergence from the common ancestor of Chloridoideae and, together with transcriptome profiling, demonstrate the important contribution of tetraploidization to the gene sources for the herbicide resistance of L. chinensis. Population genomic analyses of 89 accessions from China reveal that L. chinensis accessions collected from southern/southwestern provinces have substantially higher nucleotide diversity than those from the middle and lower reaches of the Yangtze River, suggesting that L. chinensis spread in China from the southern/southwestern provinces to the middle and lower reaches of the Yangtze River. During this spread, L. chinensis developed significantly increased herbicide resistance, accompanied by the selection of numerous genes involved in herbicide resistance. Taken together, our study generated valuable genomic resources for future fundamental research and agricultural management of L. chinensis, and provides significant new insights into the herbicide resistance as well as the origin and adaptive evolution of L. chinensis.展开更多
Weeds pose a significant threat to crop production,resulting in substantial yield reduction.In addition,they possess robust weedy traits that enable them to survive in extreme environments and evade human con-trol.In ...Weeds pose a significant threat to crop production,resulting in substantial yield reduction.In addition,they possess robust weedy traits that enable them to survive in extreme environments and evade human con-trol.In recent years,the application of multi-omics biotechnologies has helped to reveal the molecular mechanisms underlying these weedy traits.In this review,we systematically describe diverse applications of multi-omics platforms for characterizing key aspects of weed biology,including the origins of weed spe-cies,weed classification,and the underlying genetic and molecular bases of important weedy traits such as crop–weed interactions,adaptability to different environments,photoperiodicflowering responses,and herbicide resistance.In addition,we discuss limitations to the application of multi-omics techniques in weed science,particularly compared with their extensive use in model plants and crops.In this regard,we provide a forward-looking perspective on the future application of multi-omics technologies to weed science research.These powerful tools hold great promise for comprehensively and efficiently unraveling the intricate molecular genetic mechanisms that underlie weedy traits.The resulting advances will facilitate the development of sustainable and highly effective weed management strategies,promoting greener practices in agriculture.展开更多
基金National Natural Science Foundation of China(U21A20411)Innovative Research Group Program of Hunan Provincial Natural Science Foundation (2024JJ1007)Hunan Provincial Natural Science Foundation(2023JJ30473)。
文摘Objective To investigate the effects of Zuogui Jiangtang Yishen Formula(左归降糖益肾方,ZGJTYSF)in regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling axis on pyroptosis in rats with diabetic kidney disease(DKD).Methods Fifty male specific pathogen-free(SPF)grade Goto-Kakizaki(GK)rats(12 weeks old)were fed a high-fat diet for one month to establish an early DKD model.Model establishment was confirmed when fasting blood glucose(FBG)≥11.1 mmol/L and urinary albuminto-creatinine ratio(uACR)≥30 mg/g.The successfully modeled early DKD rats were randomly divided by random number table into five groups(n=10 per group):model group;dapagliflozin group(1.0 mg/kg,by gavage,served as positive control);and low-,medium-,and high-dose of ZGJTYSF groups(4.9,9.9,and 19.9 g/kg,respectively,by gavage).Age-matched male SPF Wistar rats(n=10)served as control group.Rats in control and model groups were gavaged with equivalent volumes of distilled water.Treatment lasted 12 weeks.Changes in uACR,FBG,and renal function were observed in all groups.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe renal histopathological changes.Immunohistochemistry was performed to detect the localization and expression of caspase-1,GSDMD,and NLRP3 in rat renal tissues.Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP)nick end labeling(TUNEL)was utilized to detect pyroptosis in renal tissues.Quantitative real-time polymerase chain reaction(qPCR)and Western blot were applied to detect mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,interleukin(IL)-1β,and IL-18.Results Compared with model group,all doses of ZGJTYSF showed reductions in FBG,with medium-and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12(P<0.05).For uACR,all doses of ZGJTYSF groups exhibited a decreasing trend,with high-dose of ZGJTYSF group being significantly lower than low-and medium-dose of ZGJTYSF groups at week 12(P<0.05)and showing no significant difference from dapagliflozin group(P>0.05).No significant differences in renal function parameters(serum creatinine,blood urea nitrogen,and uric acid)were observed among groups(P>0.05).Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group,with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group.Immunohistochemistry demonstrated significantly reduced expression of caspase-1,GSDMD,and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group(P<0.05 or P<0.01),while the differences in low-and medium-dose of ZGJTYSF groups were not statistically significant(P>0.05).TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups(P<0.01),indicating a marked reduction in pyroptotic cells.Molecular analysis revealed that compared with model group,both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3,caspase-1,GSDMD,IL-1β,and IL-18 in renal tissues(P<0.01),while low-and medium-dose of ZGJTYSF groups showed downward trends without statistical significance(P>0.05).Conclusion ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis,thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
基金We are grateful to the Natural Science Foundation of Guangdong Province(2020A1515110121)the Fundamental Research Funds for the Central Universities(N2129002)for all support provided to realize this project.
文摘This paper describes the design and control of a portable and lightweight knee exoskeleton for people with knee dysfunction.The knee exoskeleton is designed based on our custom quasi-direct drive actuation composed of a DC motor unit and a transmission mechanism encompassing three gears.An online gait generation method based on gait step calculation and direct measurement using Inertial Measurement Unit(IMU)sensors is proposed to provide continuous assistance during walking.Based on the generated gait trajectory online,Active Disturbance Rejection Control(ADRC)incorporating the feedforward compensation approach is proposed to help the human leg move in consideration of external disturbances.The developed knee exoskeleton has been employed successfully to assist impaired users with knee dysfunction to walk in a health recovery center.The experimental results indicate that the online gait generation method and the proposed control method are suitable for the knee exoskeleton.The maximum value of the target knee angular position is approximately 50°and the mean of the control torque for the knee joint is located in the interval of[−2 Nm,4 Nm].The developed knee exoskeleton has the potential to regain normal gait to improve strength and endurance during walking in their activities of daily life.
基金General Funded Project of Hunan Provincial Health Commission(No.202203054238)Hunan University of Chinese Medicine Campus Joint Fund Project(Nos.2023XYLH022,2023XYLH028)Project of Key Specialties of Chinese Medicine in Hunan Province(axm-sbk-2023001,cxm-nfmnk-2023001).
文摘Background:Podocyte injury is crucial in diabetic kidney disease(DKD)progression,and the mechanism remains unclear.The previous studies indicated Diosgenin played a key role in inhibiting podocyte injury progression.However,more research is needed to explore Diosgenin in inhibiting-molecular mechanisms in the process of podocyte injury.Methods:The content of Diosgenin in HeShenwan was detected by High-Performance Liquid Chromatography-mass spectrometry(HPLC-MS)method.The podocyte injury model was constructed by high glucose(HG)-induced mpc5 cells.The Cell Counting Kit-8(CCK-8)assay was utilized to evaluate the activity of mpc5 cells.Pyroptosis in mpc5 cells was assessed using flow cytometry.Molecular docking studies of Diosgenin and Nrf2 were carried out using VINA 1.1.2 software.The levels of Superoxide dismutase(SOD),Malondialdehyde(MDA),Reactive oxygen species(ROS),Interleukin 1β(IL-1β),Interleukin 18(IL-18),Lactate dehydrogenase(LDH)and High mobility group protein B1(HMGB1)were assessed using related kits.The levels of Nod-like receptor protein 3(NLRP3),Nuclear factor erythroid-2-related factor 2(Nrf2),Cysteinyl aspartate specific proteinase 1(Caspase-1),Gasdermin(GSDMD),and Apoptosis-associated speck-like protein contain a CARD(ASC)were detected.Results:The Diosgenin content was the highest in HeShenwan.The addition of Diosgenin enhanced HG-induced mpc5 cell activity and reduced oxidative stress and pyroptosis.Molecular docking results showed that Diosgenin bound to the Nrf2 through hydrogen bonds and hydrophobic interactions,regulating the Nrf2 expression.Overexpression of Nrf2 reduced the levels of NLRP3,reducing oxidative stress and inhibiting pyroptosis in mpc5 cells.Knockdown of Nrf2 reduced HG-induced mpc5 cell activity and increased pyroptosis and oxidative stress.Diosgenin inhibited pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway.Conclusion:Diosgenin inhibited HG-induced pyroptosis in mpc5 cells by regulating the Nrf2/NLRP3 pathway.
基金supported by grants from the National Key R&D Program of China(No.2021YFD1700101)the National Natural Science Foundation of China(No.32130091 and No.32001923)+2 种基金the science And and Technology Innovation Program of Hunan Province (No.2020WK2014 and No.2020WK2023)the Training Program for Excellent Young Innovators of Changsha(kg2106079)the China Agriculture Research System of MOF and MARA(CARS-16-E19)。
文摘Chinese sprangletop (Leptochloa chinensis), belonging to the grass subfamily Chloridoideae, is one of the most notorious weeds in rice ecosystems. Here, we report a chromosome-scale reference genome assembly and a genomic variation map of the tetraploid L. chinensis. The L. chinensis genome is derived from two diploid progenitors that diverged ∼10.9 million years ago, and its two subgenomes display neither fractionation bias nor overall gene expression dominance. Comparative genomic analyses reveal substantial genome rearrangements in L. chinensis after its divergence from the common ancestor of Chloridoideae and, together with transcriptome profiling, demonstrate the important contribution of tetraploidization to the gene sources for the herbicide resistance of L. chinensis. Population genomic analyses of 89 accessions from China reveal that L. chinensis accessions collected from southern/southwestern provinces have substantially higher nucleotide diversity than those from the middle and lower reaches of the Yangtze River, suggesting that L. chinensis spread in China from the southern/southwestern provinces to the middle and lower reaches of the Yangtze River. During this spread, L. chinensis developed significantly increased herbicide resistance, accompanied by the selection of numerous genes involved in herbicide resistance. Taken together, our study generated valuable genomic resources for future fundamental research and agricultural management of L. chinensis, and provides significant new insights into the herbicide resistance as well as the origin and adaptive evolution of L. chinensis.
基金supported by grants from the National Natural Science Foundation of China (no.32272564 and no.32302387)the National Key R&D Program of China (no.2023YFD1401100 and no.2021YFD1700101)+3 种基金the Science and Technology Innovation Program of Hunan Province (no.2022RC1017)Hunan Outstanding Youth Fund Project (no.2023JJ10025)the Training Program for Excellent Young Innovators of Changsha (kq2106079)the Hunan Agricultural Science and Technology Innovation Fund Project (2022CX01 and 2023CX02).
文摘Weeds pose a significant threat to crop production,resulting in substantial yield reduction.In addition,they possess robust weedy traits that enable them to survive in extreme environments and evade human con-trol.In recent years,the application of multi-omics biotechnologies has helped to reveal the molecular mechanisms underlying these weedy traits.In this review,we systematically describe diverse applications of multi-omics platforms for characterizing key aspects of weed biology,including the origins of weed spe-cies,weed classification,and the underlying genetic and molecular bases of important weedy traits such as crop–weed interactions,adaptability to different environments,photoperiodicflowering responses,and herbicide resistance.In addition,we discuss limitations to the application of multi-omics techniques in weed science,particularly compared with their extensive use in model plants and crops.In this regard,we provide a forward-looking perspective on the future application of multi-omics technologies to weed science research.These powerful tools hold great promise for comprehensively and efficiently unraveling the intricate molecular genetic mechanisms that underlie weedy traits.The resulting advances will facilitate the development of sustainable and highly effective weed management strategies,promoting greener practices in agriculture.
