Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular mat...Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.展开更多
Objective： The aim of this study was to investigate whether astrecyte elevated gene 1 （AEG1） regulates COX-2 expression in human hepatoma HepG2 cells and related pathways involved in this process. Methods： Human h...Objective： The aim of this study was to investigate whether astrecyte elevated gene 1 （AEG1） regulates COX-2 expression in human hepatoma HepG2 cells and related pathways involved in this process. Methods： Human hepatoma HepG2 cells were transfected with pcDNA3.1（-）-AEG1 plasmid or psilencer2.0-AEGl-shRNA1 plasmid to up/down-regulate AEG1 expression, pcDNA3.1（-） and psilencer 2.0 empty vector plasmids were transfected respectively as control. Real-time RT-PCR was carried out to measure the expression levels of AEG1 and COX-2 mRNA. The expression levels of AEG1 and COX-2 protein were detected by Western blot. NF-KB signaling was blocked by PDTC, and AP-1 signaling was blocked by curcumin. Results： AEG1 mRNA and protein levels were increased after pcDNA3.1（-）-AEG1 transfection, and decreased after psilencer2.0-AEGl-shRNAs transfection. COX-2 mRNA and protein levels were increased in AEGl-overexpressing cells and decreased in AEGl-knockdown cells. Phosphorylations of p65 and c-jun were up-regulated in AEGl-overexpressing cells. Both PDTC and curoumin reduced COX-2 expression in HepG2 cells with AEG1 overexpression. Conclusion： AEG1- overexpressing and -knockdown HepG2 cells are established successfully. AEG1 could induce COX-2 expression though activating NF-KB and AP-1 in human hepatoma HepG2 cells.展开更多
HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major ...HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel chemotypes of anti-HIV-1 agents with improved drugresistance profiles,reduced toxicity,and excellent druggability.A series of diarylpyrimidine(DAPY)derivatives were prepared via structural modifications of the leads K-5a2 and 25a.Among them,15a with dimethylphosphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel,being 1.6-fold(WT,EC_(50) Z 1.75 nmol/L),3.0-fold(L100I,EC_(50) Z 2.84 nmol/L),2.4-fold(K103N,EC_(50) Z 1.27 nmol/L),3.3-fold(Y181C,EC50 Z 5.38 nmol/L),2.9-fold(Y188L,EC_(50) Z 7.96 nmol/L),2.5-fold(E138K,EC_(50) Z 4.28 nmol/L),4.8-fold(F227L/V106A,EC_(50) Z 3.76 nmol/L)and 5.3-fold(RES056,EC_(50) Z 15.8 nmol/L)more effective than that of the marketed drug ETR.Molecular docking results illustrated the detailed interactions formed by compound 15a and WT,F227L/V106A,and RES056 RT.Moreover,15a-HCl carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profiles(LD_(50)>2000 mg/kg),which demonstrated that 15a HCl is a potential anti-HIV-1 drug candidate.展开更多
Luminescent materials often suffer from thermal quenching(TQ),limiting the continuation of their applications under high temperatures up to 473 K.The formation of defect levels could suppress TQ,but rational synthesis...Luminescent materials often suffer from thermal quenching(TQ),limiting the continuation of their applications under high temperatures up to 473 K.The formation of defect levels could suppress TQ,but rational synthesis and deep understanding of multiple defects-regulated luminescent materials working in such a wide temperature range still remain challenging.Here,we prepare a negative thermal quenching(NTQ)phosphor LiTaO_(3)∶Tb^(3+)by introducing gradient defects V_(Ta)^(5−),Tb_(Li)^(2+),and(V_(Ta)Tb_(Li))^(3−)as identified by advanced experimental and theoretical studies.Its photoluminescence significantly becomes intense with rising temperatures and then slowly increases at 373 to 473 K.The mechanism studies reveal that gradient defects with varied trapping depths could act as energy buffer layers to effectively capture the carriers.Under thermal disturbance,the stored carriers could successively migrate to the activators in consecutive and wide temperature zones,compensating for TQ to enhance luminescence emission.This study initiates the synthesis of multi-defect NTQ phosphors for temperature-dependent applications.展开更多
Purpose–Since many global path planning algorithms cannot achieve the planned path with both safety and economy,this study aims to propose a path planning method for unmanned vehicles with a controllable distance fro...Purpose–Since many global path planning algorithms cannot achieve the planned path with both safety and economy,this study aims to propose a path planning method for unmanned vehicles with a controllable distance from obstacles.Design/methodology/approach–First,combining satellite image and the Voronoi field algorithm(VFA)generates rasterized environmental information and establishes navigation area boundary.Second,establishing a hazard function associated with navigation area boundary improves the evaluation function of the A*algorithm and uses the improved A*algorithm for global path planning.Finally,to reduce the number of redundant nodes in the planned path and smooth the path,node optimization and gradient descent method(GDM)are used.Then,a continuous smooth path that meets the actual navigation requirements of unmanned vehicle is obtained.Findings–The simulation experiment proved that the proposed global path planning method can realize the control of the distance between the planned path and the obstacle by setting different navigation area boundaries.The node reduction rate is between 33.52%and 73.15%,and the smoothness meets the navigation requirements.This method is reasonable and effective in the global path planning process of unmanned vehicle and can provide reference to unmanned vehicles’autonomous obstacle avoidance decision-making.Originality/value–This study establishes navigation area boundary for the environment based on the VFA and uses the improved Aalgorithm to generate a navigation path that takes into account both safety and economy.This study also proposes a method to solve the redundancy of grid environment path nodes and large-angle steering and to smooth the path to improve the applicability of the proposed global path planning method.The proposed global path planning method solves the requirements of path safety and smoothness.展开更多
Mixed crystal strategy is an effective approach of improving the luminescence properties of optical materials and has been adopted widely in many systems.In this paper,the La-mixed Gd_(2)Si_(2)O_(7):Ce polycrystalline...Mixed crystal strategy is an effective approach of improving the luminescence properties of optical materials and has been adopted widely in many systems.In this paper,the La-mixed Gd_(2)Si_(2)O_(7):Ce polycrystalline samples were successfully synthesized by a sol-gel method.The crystal structure and luminescence properties were confirmed and discussed by XRD,UV-Vis luminescence spectra,and XEL,respectively.The vacuum ultraviolet excitation spectra and thermoluminescence glow curves were also systematically investigated and discussed at varied temperature.A combination of the first-principles calculations and optical characterization experiments was employed to study the electronic band structure of host material,revealing that the band gap is narrowed and the 5d_(1) level of Ce^(3+) shifts to higher energy as the La content increases.The luminescence the rmo-stability and activation energy were also measured and calculated.It indicates that thermo-stability is strongly dependent on the La concentration.An effective approach is developed to tune the electronic band structure,luminescence properties and thermostability of(Gd_(1-x)La_(x))_(2)Si_(2)O_(7):Ce scintillator by adjusting La/Gd ratio.展开更多
文摘Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.
基金Supported by grants from the National Science Foundation of China (No.81070333)the Natural Science Foundation of Hubei Province of China (No.2012FFB02318)
文摘Objective： The aim of this study was to investigate whether astrecyte elevated gene 1 （AEG1） regulates COX-2 expression in human hepatoma HepG2 cells and related pathways involved in this process. Methods： Human hepatoma HepG2 cells were transfected with pcDNA3.1（-）-AEG1 plasmid or psilencer2.0-AEGl-shRNA1 plasmid to up/down-regulate AEG1 expression, pcDNA3.1（-） and psilencer 2.0 empty vector plasmids were transfected respectively as control. Real-time RT-PCR was carried out to measure the expression levels of AEG1 and COX-2 mRNA. The expression levels of AEG1 and COX-2 protein were detected by Western blot. NF-KB signaling was blocked by PDTC, and AP-1 signaling was blocked by curcumin. Results： AEG1 mRNA and protein levels were increased after pcDNA3.1（-）-AEG1 transfection, and decreased after psilencer2.0-AEGl-shRNAs transfection. COX-2 mRNA and protein levels were increased in AEGl-overexpressing cells and decreased in AEGl-knockdown cells. Phosphorylations of p65 and c-jun were up-regulated in AEGl-overexpressing cells. Both PDTC and curoumin reduced COX-2 expression in HepG2 cells with AEG1 overexpression. Conclusion： AEG1- overexpressing and -knockdown HepG2 cells are established successfully. AEG1 could induce COX-2 expression though activating NF-KB and AP-1 in human hepatoma HepG2 cells.
基金financial support from the National Natural Science Foundation of China(NSFC Nos.81973181,82273773)Shandong Provincial Natural Science Foundation(ZR2020YQ61,ZR2020JQ31,China)Qilu Young Scholars Program of Shandong University and Taishan Scholar Program at Shandong Province.
文摘HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel chemotypes of anti-HIV-1 agents with improved drugresistance profiles,reduced toxicity,and excellent druggability.A series of diarylpyrimidine(DAPY)derivatives were prepared via structural modifications of the leads K-5a2 and 25a.Among them,15a with dimethylphosphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel,being 1.6-fold(WT,EC_(50) Z 1.75 nmol/L),3.0-fold(L100I,EC_(50) Z 2.84 nmol/L),2.4-fold(K103N,EC_(50) Z 1.27 nmol/L),3.3-fold(Y181C,EC50 Z 5.38 nmol/L),2.9-fold(Y188L,EC_(50) Z 7.96 nmol/L),2.5-fold(E138K,EC_(50) Z 4.28 nmol/L),4.8-fold(F227L/V106A,EC_(50) Z 3.76 nmol/L)and 5.3-fold(RES056,EC_(50) Z 15.8 nmol/L)more effective than that of the marketed drug ETR.Molecular docking results illustrated the detailed interactions formed by compound 15a and WT,F227L/V106A,and RES056 RT.Moreover,15a-HCl carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profiles(LD_(50)>2000 mg/kg),which demonstrated that 15a HCl is a potential anti-HIV-1 drug candidate.
基金the National Key Research and Development Program of China(Grant No.2018YFB0704103)the Natural Science Foundation of Shanghai(Grant Nos.22ZR1472100 and 20ZR1465900)+3 种基金the National Natural Science Foundation of China(Grant Nos.92163117 and 62175210)the State Key Laboratory of ASIC&System(Grant No.2020KF002)the Innovation Project of Shanghai Institute of Ceramics(Grant No.E21ZC1770G)L.L.thanks the Taiwan Light Source for technical support.J.W.thanks the Program of Shanghai Academic Research Leader(Grant No.20XD1424300)for financial support.The authors thank Professor Zhijun Zhang for providing valuable assistance in stress luminescence testing.
文摘Luminescent materials often suffer from thermal quenching(TQ),limiting the continuation of their applications under high temperatures up to 473 K.The formation of defect levels could suppress TQ,but rational synthesis and deep understanding of multiple defects-regulated luminescent materials working in such a wide temperature range still remain challenging.Here,we prepare a negative thermal quenching(NTQ)phosphor LiTaO_(3)∶Tb^(3+)by introducing gradient defects V_(Ta)^(5−),Tb_(Li)^(2+),and(V_(Ta)Tb_(Li))^(3−)as identified by advanced experimental and theoretical studies.Its photoluminescence significantly becomes intense with rising temperatures and then slowly increases at 373 to 473 K.The mechanism studies reveal that gradient defects with varied trapping depths could act as energy buffer layers to effectively capture the carriers.Under thermal disturbance,the stored carriers could successively migrate to the activators in consecutive and wide temperature zones,compensating for TQ to enhance luminescence emission.This study initiates the synthesis of multi-defect NTQ phosphors for temperature-dependent applications.
文摘Purpose–Since many global path planning algorithms cannot achieve the planned path with both safety and economy,this study aims to propose a path planning method for unmanned vehicles with a controllable distance from obstacles.Design/methodology/approach–First,combining satellite image and the Voronoi field algorithm(VFA)generates rasterized environmental information and establishes navigation area boundary.Second,establishing a hazard function associated with navigation area boundary improves the evaluation function of the A*algorithm and uses the improved A*algorithm for global path planning.Finally,to reduce the number of redundant nodes in the planned path and smooth the path,node optimization and gradient descent method(GDM)are used.Then,a continuous smooth path that meets the actual navigation requirements of unmanned vehicle is obtained.Findings–The simulation experiment proved that the proposed global path planning method can realize the control of the distance between the planned path and the obstacle by setting different navigation area boundaries.The node reduction rate is between 33.52%and 73.15%,and the smoothness meets the navigation requirements.This method is reasonable and effective in the global path planning process of unmanned vehicle and can provide reference to unmanned vehicles’autonomous obstacle avoidance decision-making.Originality/value–This study establishes navigation area boundary for the environment based on the VFA and uses the improved Aalgorithm to generate a navigation path that takes into account both safety and economy.This study also proposes a method to solve the redundancy of grid environment path nodes and large-angle steering and to smooth the path to improve the applicability of the proposed global path planning method.The proposed global path planning method solves the requirements of path safety and smoothness.
基金Project supported by the National Natural Science Foundation of China(11975220,51972291)the National Key Research and Development Program of China(2016YFB0700204)Natural Science Foundation of Shanghai(16ZR1441100)。
文摘Mixed crystal strategy is an effective approach of improving the luminescence properties of optical materials and has been adopted widely in many systems.In this paper,the La-mixed Gd_(2)Si_(2)O_(7):Ce polycrystalline samples were successfully synthesized by a sol-gel method.The crystal structure and luminescence properties were confirmed and discussed by XRD,UV-Vis luminescence spectra,and XEL,respectively.The vacuum ultraviolet excitation spectra and thermoluminescence glow curves were also systematically investigated and discussed at varied temperature.A combination of the first-principles calculations and optical characterization experiments was employed to study the electronic band structure of host material,revealing that the band gap is narrowed and the 5d_(1) level of Ce^(3+) shifts to higher energy as the La content increases.The luminescence the rmo-stability and activation energy were also measured and calculated.It indicates that thermo-stability is strongly dependent on the La concentration.An effective approach is developed to tune the electronic band structure,luminescence properties and thermostability of(Gd_(1-x)La_(x))_(2)Si_(2)O_(7):Ce scintillator by adjusting La/Gd ratio.
