Background:The study was conducted with the interest of exploring the effects of Qingre Yangyin Chushi pill as anti-inflammatory agent in gout treatment based on the NLRP3/GSDMD coke death pathway.Methods:In this stud...Background:The study was conducted with the interest of exploring the effects of Qingre Yangyin Chushi pill as anti-inflammatory agent in gout treatment based on the NLRP3/GSDMD coke death pathway.Methods:In this study,48 male SD rats were randomly divided into 6 groups,namely model group,blank control group(BC),Qingre Yangyin Chushi pill low-dose treatment group(MSD1),medium-dose treatment group(MSD2),high-dose treatment group(MSD3),and colchicine group(PC),with eight members in each group.The BC and model groups were administered with saline twice a day.The MSD1,MSD2,and MSD3 groups were administered with Qingre Yangyin Chushi pill at a dose of 1.8 g·kg^?1,3.6 g·kg^?1,and 7.2 g·kg^?1 twice a day.The colchicine group was administered with a colchicine suspension at a dose of 0.6×10^?3 g kg^?1 twice a day for 7 days.After gavage of animals in each group for 4 days,the rats'ankle joints were injected with sodium urate suspension×3 days to induce a gouty arthritis model.Then,serum and tissue samples were collected on the third and seventh day after gavage.The synovial tissue from the rat ankle joints was taken,and immunohistochemical technique was used to detect NOD-like receptor protein 3(NLRP3),inflammatory bodies,cysteine protease-1(Caspase-1),and Gasdermin-D protein(GSDMD)expression.Image-Pro Plus image analysis system was used to measure the average integrated absorbance and calculate IHS.Integral enzyme-linked immunosorbent assay was used to determine the interleukin 1β(IL-1β)and interleukin 18(IL-18)expression of tumor necrosis factor-α(TNF-α).Western blot was used to detect NLRP3,Caspase-1,GSDMD,and apoptosis-associated speck-like protein containing a CARD(ASC)expression levels.Results:After 48 hours of modeling,compared with the PC group,the arthritis indices of the MSD1,MSD2,and MSD3 groups were insignificant(P>0.05).The levels of IL-1β,IL-18,and TNF-αwere lower in the PC and MSD2 groups compared with the BC group.However,compared with the control group,MSD1,MSD2,and PC groups had lower levels of IL-1βand IL-18.Regarding TNF-αlevels(P<0.05);compared with the PC group,the levels of IL-1β,IL-18,and TNF-αin MSD2 decreased more significantly(P<0.05).The levels of NLRP3,Caspase-1,GSDMD,ASC,IHS score,and mRNA were lower in the PC and MSD2 groups(P<0.05)compared with the control group.The MSD1 and MSD2 groups had lower levels of NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels(P<0.05)compared with the PC group.Moreover,NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels were more reduced in the MSD2 group(P<0.05).Conclusion:Qingre Yangyin Chushi pill can inhibit the activation of the NLPR3 inflammatory complex,reduce the production of GSDMD protein,regulate the occurrence of pyroptosis,reduce the expression of inflammatory factors,and thus reduce arthritis.All these processes are achieved through the NLRP3/GSDMD pathway.展开更多
MXene,a transition metal carbide/nitride,has been prominent as an ideal electrochemical active material for supercapacitors.However,the low MXene load limits its practical applications.As environmental concerns and su...MXene,a transition metal carbide/nitride,has been prominent as an ideal electrochemical active material for supercapacitors.However,the low MXene load limits its practical applications.As environmental concerns and sustainable development become more widely recognized,it is necessary to explore a greener and cleaner technology to recycle textile by-products such as cotton.The present study proposes an effective 3D fabrication method that uses MXene to fabricate waste denim felt into ultralight and flexible supercapacitors through needling and carbonization.The 3D structure provided more sites for loading MXene onto Z-directional fiber bundles,resulting in more efficient ion exchange between the electrolyte and electrodes.Furthermore,the carbonization process removed the specific adverse groups in MXenes,further improving the specific capacitance,energy density,power density and electrical conductivity of supercapacitors.The electrodes achieve a maximum specific capacitance of 1748.5 mF cm-2 and demonstrate remarkable cycling stability maintaining more than 94%after 15,000 galvanostatic charge/discharge cycles.Besides,the obtained supercapacitors present a maximum specific capacitance of 577.5 mF cm^(-2),energy density of 80.2μWh cm^(-2)and power density of 3 mW cm^(-2),respectively.The resulting supercapacitors can be used to develop smart wearable power devices such as smartwatches,laying the foundation for a novel strategy of utilizing waste cotton in a high-quality manner.展开更多
This article proposes an integral-based event-triggered attack-resilient control method for the aircraft-on-ground(AoG) synergistic turning system with uncertain tire cornering stiffness under stochastic deception att...This article proposes an integral-based event-triggered attack-resilient control method for the aircraft-on-ground(AoG) synergistic turning system with uncertain tire cornering stiffness under stochastic deception attacks. First, a novel AoG synergistic turning model is established with synergistic reverse steering of the front and main wheels to decrease the steering angle of the AoG fuselage, thus reducing the steady-state error when it follows a path with some large curvature. Considering that the tire cornering stiffness of the front and main wheels vary during steering, a dynamical observer is designed to adaptively identify them and estimate the system state at the same time.Then, an integral-based event-triggered mechanism(I-ETM) is synthesized to reduce the transmission frequency at the observerto-controller end, where stochastic deception attacks may occur at any time with a stochastic probability. Moreover, an attackresilient controller is designed to guarantee that the closed-loop system is robust L2-stable under stochastic attacks and external disturbances. A co-design method is provided to get feasible solutions for the observer, controller, and I-ETM simultaneously. An optimization program is further presented to make a tradeoff between the robustness of the control scheme and the saving of communication resources. Finally, the low-and high-probability stochastic deception attacks are considered in the simulations. The results have illustrated that the AoG synergistic turning system with the proposed control method follows a path with some large curvature well under stochastic deception attacks. Furthermore,compared with the static event-triggered mechanisms, the proposed I-ETM has demonstrated its superiority in saving communication resources.展开更多
Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary inju...Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary injury,immunization,and potential infections).However,three-dimensional(3D)printing technology as an emerging field can serve as an effective approach to achieve satisfactory revascularization while making up for the above limitations.A wide variety of methods can be used to facilitate blood supply during the design of a 3D-printed scaffold.Importantly,the scaffold structure lays a foundation for the entire printing object;any method to promote angiogenesis can be effective only if it is based on well-designed scaffolds.In this review,different designs related to angiogenesis are summarized by collecting the literature from recent years.The 3D-printed scaffolds are classified into four major categories and discussed in detail,from elementary porous scaffolds to the most advanced bone-like scaffolds.Finally,structural design suggestions to achieve rapid angiogenesis are proposed by analyzing the above architectures.This review can provide a reference for organizations or individual academics to achieve improved bone defect repair and regeneration using 3D printing.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver.Understanding the molecular mechanisms underlying the CCA progression will likely yield th...BACKGROUND Cholangiocarcinoma(CCA)is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver.Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease.AIM To determine the molecular pathogenesis in CCA progression.METHODS In silico analysis,in vitro cell culture,CCA transgenic animals,histological,and molecular assays were adopted to determine the molecular pathogenesis.RESULTS The transcriptomic data of human CCA samples were retrieved from The Cancer Genome Atlas(TGCA,CHOL),European Bioinformatics Institute(EBI,GAD-00001001076),and Gene Expression Omnibus(GEO,GSE107943)databases.Using Gene set enrichment analysis,the cell cycle and Notch related pathways were demonstrated to be significantly activated in CCA in TCGA and GEO datasets.We,through differentially expressed genes,found several cell cycle and notch associated genes were significantly up-regulated in cancer tissues when compared with the non-cancerous control samples.The associated genes,via quantitative real-time PCR and western blotting assays,were further examined in normal human cholangiocytes,CCA cell lines,mouse normal bile ducts,and mouse CCA tumors established by specifically depleting P53 and expressing KrasG12D mutation in the liver.Consistently,we validated that the cell cycle and Notch pathways are up-regulated in CCA cell lines and mouse CCA tumors.Interestingly,targeting cell cycle and notch pathways using small molecules also exhibited significant beneficial effects in controlling tumor malignancy.More importantly,we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank test.CONCLUSION In summary,our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are potential therapeutic targets in this deadly disease.展开更多
基金This study was supported by the General Project of Beijing Natural Science Foundation(No.7172101)the Beijing Municipal Hospital Research and Cultivation Project(No.PZ2017015)the Beijing Hospital of Traditional Chinese Medicine Gospital-Level Project(No.YJ-201807).
文摘Background:The study was conducted with the interest of exploring the effects of Qingre Yangyin Chushi pill as anti-inflammatory agent in gout treatment based on the NLRP3/GSDMD coke death pathway.Methods:In this study,48 male SD rats were randomly divided into 6 groups,namely model group,blank control group(BC),Qingre Yangyin Chushi pill low-dose treatment group(MSD1),medium-dose treatment group(MSD2),high-dose treatment group(MSD3),and colchicine group(PC),with eight members in each group.The BC and model groups were administered with saline twice a day.The MSD1,MSD2,and MSD3 groups were administered with Qingre Yangyin Chushi pill at a dose of 1.8 g·kg^?1,3.6 g·kg^?1,and 7.2 g·kg^?1 twice a day.The colchicine group was administered with a colchicine suspension at a dose of 0.6×10^?3 g kg^?1 twice a day for 7 days.After gavage of animals in each group for 4 days,the rats'ankle joints were injected with sodium urate suspension×3 days to induce a gouty arthritis model.Then,serum and tissue samples were collected on the third and seventh day after gavage.The synovial tissue from the rat ankle joints was taken,and immunohistochemical technique was used to detect NOD-like receptor protein 3(NLRP3),inflammatory bodies,cysteine protease-1(Caspase-1),and Gasdermin-D protein(GSDMD)expression.Image-Pro Plus image analysis system was used to measure the average integrated absorbance and calculate IHS.Integral enzyme-linked immunosorbent assay was used to determine the interleukin 1β(IL-1β)and interleukin 18(IL-18)expression of tumor necrosis factor-α(TNF-α).Western blot was used to detect NLRP3,Caspase-1,GSDMD,and apoptosis-associated speck-like protein containing a CARD(ASC)expression levels.Results:After 48 hours of modeling,compared with the PC group,the arthritis indices of the MSD1,MSD2,and MSD3 groups were insignificant(P>0.05).The levels of IL-1β,IL-18,and TNF-αwere lower in the PC and MSD2 groups compared with the BC group.However,compared with the control group,MSD1,MSD2,and PC groups had lower levels of IL-1βand IL-18.Regarding TNF-αlevels(P<0.05);compared with the PC group,the levels of IL-1β,IL-18,and TNF-αin MSD2 decreased more significantly(P<0.05).The levels of NLRP3,Caspase-1,GSDMD,ASC,IHS score,and mRNA were lower in the PC and MSD2 groups(P<0.05)compared with the control group.The MSD1 and MSD2 groups had lower levels of NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels(P<0.05)compared with the PC group.Moreover,NLRP3,Caspase-1,GSDMD,ASC protein levels,IHS points,and mRNA levels were more reduced in the MSD2 group(P<0.05).Conclusion:Qingre Yangyin Chushi pill can inhibit the activation of the NLPR3 inflammatory complex,reduce the production of GSDMD protein,regulate the occurrence of pyroptosis,reduce the expression of inflammatory factors,and thus reduce arthritis.All these processes are achieved through the NLRP3/GSDMD pathway.
基金The authors acknowledge the financial support from the National Natural Science Foundation of China(Nos.52073224,32201491)the Textile Vision Basic Research Program of China(No.J202110)+3 种基金the Scientific Research Project of Shaanxi Provincial Education Department,China(No.22JC035)the Advanced Manufacturing Technology Program of Xi’an Science and Technology Bureau,China(No.21XJZZ0019)the Research Fund for the Doctoral Program of Xi’an Polytechnic University(No.BS202053)the Youth Innovation Team of Shaanxi Universities and Institute of Flexible electronics and Intelligent Textile.
文摘MXene,a transition metal carbide/nitride,has been prominent as an ideal electrochemical active material for supercapacitors.However,the low MXene load limits its practical applications.As environmental concerns and sustainable development become more widely recognized,it is necessary to explore a greener and cleaner technology to recycle textile by-products such as cotton.The present study proposes an effective 3D fabrication method that uses MXene to fabricate waste denim felt into ultralight and flexible supercapacitors through needling and carbonization.The 3D structure provided more sites for loading MXene onto Z-directional fiber bundles,resulting in more efficient ion exchange between the electrolyte and electrodes.Furthermore,the carbonization process removed the specific adverse groups in MXenes,further improving the specific capacitance,energy density,power density and electrical conductivity of supercapacitors.The electrodes achieve a maximum specific capacitance of 1748.5 mF cm-2 and demonstrate remarkable cycling stability maintaining more than 94%after 15,000 galvanostatic charge/discharge cycles.Besides,the obtained supercapacitors present a maximum specific capacitance of 577.5 mF cm^(-2),energy density of 80.2μWh cm^(-2)and power density of 3 mW cm^(-2),respectively.The resulting supercapacitors can be used to develop smart wearable power devices such as smartwatches,laying the foundation for a novel strategy of utilizing waste cotton in a high-quality manner.
基金supported in part by the National Science Fund for Excellent Young Scholars of China (62222317)the National Natural Science Foundation of China (61973319)+4 种基金the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (61860206014)111 Project of China (B17048)Science and Technology Innovation Program of Hunan Province (2022WZ1001)the Natural Science Foundation of Changsha (kq2208287)the Postdoctoral Fund of Central South University (22022136)。
文摘This article proposes an integral-based event-triggered attack-resilient control method for the aircraft-on-ground(AoG) synergistic turning system with uncertain tire cornering stiffness under stochastic deception attacks. First, a novel AoG synergistic turning model is established with synergistic reverse steering of the front and main wheels to decrease the steering angle of the AoG fuselage, thus reducing the steady-state error when it follows a path with some large curvature. Considering that the tire cornering stiffness of the front and main wheels vary during steering, a dynamical observer is designed to adaptively identify them and estimate the system state at the same time.Then, an integral-based event-triggered mechanism(I-ETM) is synthesized to reduce the transmission frequency at the observerto-controller end, where stochastic deception attacks may occur at any time with a stochastic probability. Moreover, an attackresilient controller is designed to guarantee that the closed-loop system is robust L2-stable under stochastic attacks and external disturbances. A co-design method is provided to get feasible solutions for the observer, controller, and I-ETM simultaneously. An optimization program is further presented to make a tradeoff between the robustness of the control scheme and the saving of communication resources. Finally, the low-and high-probability stochastic deception attacks are considered in the simulations. The results have illustrated that the AoG synergistic turning system with the proposed control method follows a path with some large curvature well under stochastic deception attacks. Furthermore,compared with the static event-triggered mechanisms, the proposed I-ETM has demonstrated its superiority in saving communication resources.
基金supported by the Zhejiang Province Key Research and Development Program(No.2021C03059)。
文摘Large bone defect regeneration has always been recognized as a challenging clinical problem due to the difficulty of revascularization.Conventional treatments exhibit certain inherent disadvantages(e.g.,secondary injury,immunization,and potential infections).However,three-dimensional(3D)printing technology as an emerging field can serve as an effective approach to achieve satisfactory revascularization while making up for the above limitations.A wide variety of methods can be used to facilitate blood supply during the design of a 3D-printed scaffold.Importantly,the scaffold structure lays a foundation for the entire printing object;any method to promote angiogenesis can be effective only if it is based on well-designed scaffolds.In this review,different designs related to angiogenesis are summarized by collecting the literature from recent years.The 3D-printed scaffolds are classified into four major categories and discussed in detail,from elementary porous scaffolds to the most advanced bone-like scaffolds.Finally,structural design suggestions to achieve rapid angiogenesis are proposed by analyzing the above architectures.This review can provide a reference for organizations or individual academics to achieve improved bone defect repair and regeneration using 3D printing.
基金Supported by 2017 AASLD Pinnacle Research Career Development Award.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver.Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease.AIM To determine the molecular pathogenesis in CCA progression.METHODS In silico analysis,in vitro cell culture,CCA transgenic animals,histological,and molecular assays were adopted to determine the molecular pathogenesis.RESULTS The transcriptomic data of human CCA samples were retrieved from The Cancer Genome Atlas(TGCA,CHOL),European Bioinformatics Institute(EBI,GAD-00001001076),and Gene Expression Omnibus(GEO,GSE107943)databases.Using Gene set enrichment analysis,the cell cycle and Notch related pathways were demonstrated to be significantly activated in CCA in TCGA and GEO datasets.We,through differentially expressed genes,found several cell cycle and notch associated genes were significantly up-regulated in cancer tissues when compared with the non-cancerous control samples.The associated genes,via quantitative real-time PCR and western blotting assays,were further examined in normal human cholangiocytes,CCA cell lines,mouse normal bile ducts,and mouse CCA tumors established by specifically depleting P53 and expressing KrasG12D mutation in the liver.Consistently,we validated that the cell cycle and Notch pathways are up-regulated in CCA cell lines and mouse CCA tumors.Interestingly,targeting cell cycle and notch pathways using small molecules also exhibited significant beneficial effects in controlling tumor malignancy.More importantly,we demonstrated that several cell cycle and Notch associated genes are significantly associated with poor overall survival and disease-free survival using the Log-Rank test.CONCLUSION In summary,our study comprehensively analyzed the gene expression pattern of CCA samples using publicly available datasets and identified the cell cycle and Notch pathways are potential therapeutic targets in this deadly disease.
