Nano-composite particles can be synthesized by a hydrogen arc plasma method, which possesses the advantages of high productivity, controllable size distribution and low electric energy consumption comparing with conve...Nano-composite particles can be synthesized by a hydrogen arc plasma method, which possesses the advantages of high productivity, controllable size distribution and low electric energy consumption comparing with conventional gas condensation method. With this method, not only the nanoparticles of metals and alloys, but also the nano-composite particles with shell structure can be synthesized. The microstructures, compositions and the formation mechanism of the nano composite particles were studied展开更多
A Cul-catalyzed three-component coupling of trifluoromethyl ketone N-tosylhydrazones, alkynes and azides has been developed. The reaction represents a straightforward method to access difluoromethylene substituted 1,2...A Cul-catalyzed three-component coupling of trifluoromethyl ketone N-tosylhydrazones, alkynes and azides has been developed. The reaction represents a straightforward method to access difluoromethylene substituted 1,2,3-triazoles. Mechanistically, it has been proposed that the reaction follows a pathway involving the formation of Cu（1） triazolide intermediate, Cu（I） carbene formation, migratory insertion, and β-fluoride elimination. The trans- formation is featured by mild conditions, wide substrate scope and high efficiency.展开更多
Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality.In this study,we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant...Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality.In this study,we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine a-1,3-galactose epitopes(a Gal)and endorphin extracellular domains(END)with dendritic cells(DCs)from healthy volunteers.END^(+)/Gal^(+)-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes(CTLs)and secretion of interferon-gamma(IFN-γ).CTLs targeted cells expressing a Gal and END and tumor angiogenesis.The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice,indicating the high clinical potential of this new cell based vaccine.展开更多
Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle di...Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.展开更多
Rh（I）-C.atalyzed synthesis of 1,1-difluoro-2,2-diarylalkenes from trifluoromethylketone N-tosylhydrazones and arylboronates is presented in this communication. This new synthetic method is based on the Rh（l）-carbe...Rh（I）-C.atalyzed synthesis of 1,1-difluoro-2,2-diarylalkenes from trifluoromethylketone N-tosylhydrazones and arylboronates is presented in this communication. This new synthetic method is based on the Rh（l）-carbene migra- tory insertion followed by fl-fluoride elimination. In one particular case the protonation occurs instead offl-fluoride elimination, affording 2,2-diaryl trifluoroethane product.展开更多
Non-human primates(NHPs)represent the most valuable animals for drug discovery.However,the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simu...Non-human primates(NHPs)represent the most valuable animals for drug discovery.However,the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases,such as cancer.This study gen erated an in situ gen e-editi ng approach to in duce efficie nt loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cyno molgus mon key.Un der ultraso und guida nee,the CRISPR/Cas9 was injected into the cyno molgus mon key liver through the in trahepatic portal vein.The results showed that the ultraso un d-guided CRISPR/Cas9 resulted in in dels of the Pten and p53 genes in seve n out of eight monkeys.The best mutation efficiencies for Pten and p53 were up to 74.71%and 74.68%,respectively.Furthermore,the morbidity of primary and exte nsively metastatic(lung,splee n,lymph nodes)hepatoma in CRISPR-treated mon keys was 87.5%.The ultraso un d-guided CRISPR system could have great potential to successfully pursue the desired target genes,thereby reducing possible side effects associated with hitting no n-specific off-target genes,and sign ifica ntly in creasing more efficie ncy as well as higher specificity of in situ gene editi ng in vivo,which holds promise as a powerful,yet feasible tool,to edit disease genes to build corresp on ding huma n disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.展开更多
文摘Nano-composite particles can be synthesized by a hydrogen arc plasma method, which possesses the advantages of high productivity, controllable size distribution and low electric energy consumption comparing with conventional gas condensation method. With this method, not only the nanoparticles of metals and alloys, but also the nano-composite particles with shell structure can be synthesized. The microstructures, compositions and the formation mechanism of the nano composite particles were studied
文摘A Cul-catalyzed three-component coupling of trifluoromethyl ketone N-tosylhydrazones, alkynes and azides has been developed. The reaction represents a straightforward method to access difluoromethylene substituted 1,2,3-triazoles. Mechanistically, it has been proposed that the reaction follows a pathway involving the formation of Cu（1） triazolide intermediate, Cu（I） carbene formation, migratory insertion, and β-fluoride elimination. The trans- formation is featured by mild conditions, wide substrate scope and high efficiency.
基金supported,in part,by grants from the State Project for Essential Drug Research and Development(No.2019ZX09301132,China)National Natural Science Foundation of China(Nos.82060562 and 82072340)+2 种基金the Scientific and Technological Innovation Major Base of Guangxi(No.2018-15Z04,China)Guangxi Key Research and Development Project(No.AB20117001,China)Guangxi Natural Science Foundation(No.2018JJA140524,China)。
文摘Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality.In this study,we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine a-1,3-galactose epitopes(a Gal)and endorphin extracellular domains(END)with dendritic cells(DCs)from healthy volunteers.END^(+)/Gal^(+)-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes(CTLs)and secretion of interferon-gamma(IFN-γ).CTLs targeted cells expressing a Gal and END and tumor angiogenesis.The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice,indicating the high clinical potential of this new cell based vaccine.
基金supported by the Scientific and Technological Innovation Major Base of Guangxi (No. 2018–15-Z04)Guangxi Key Research and Development Project (No. AB20117001)+1 种基金Guangxi Science and Technology Bases and Talent Special Project (No. AD17129062)Guangxi Natural Science Foundation (No. 2018JJA140524)。
文摘Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.
文摘Rh（I）-C.atalyzed synthesis of 1,1-difluoro-2,2-diarylalkenes from trifluoromethylketone N-tosylhydrazones and arylboronates is presented in this communication. This new synthetic method is based on the Rh（l）-carbene migra- tory insertion followed by fl-fluoride elimination. In one particular case the protonation occurs instead offl-fluoride elimination, affording 2,2-diaryl trifluoroethane product.
基金This work was supported in part by Scientific and Technological Innovation Major Base of Guangxi(No.2018-15-Z04)Changjiang Scholars and Innovative Research Team in University(No.IRT_15R13)+2 种基金Guangxi Science and Technology Base and Talent Special Project(No.AD17129062)Guangxi Key Research and Development Project(No.AB20117001)Guangxi Science Foundation Project(No.2018JJA140524).
文摘Non-human primates(NHPs)represent the most valuable animals for drug discovery.However,the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases,such as cancer.This study gen erated an in situ gen e-editi ng approach to in duce efficie nt loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cyno molgus mon key.Un der ultraso und guida nee,the CRISPR/Cas9 was injected into the cyno molgus mon key liver through the in trahepatic portal vein.The results showed that the ultraso un d-guided CRISPR/Cas9 resulted in in dels of the Pten and p53 genes in seve n out of eight monkeys.The best mutation efficiencies for Pten and p53 were up to 74.71%and 74.68%,respectively.Furthermore,the morbidity of primary and exte nsively metastatic(lung,splee n,lymph nodes)hepatoma in CRISPR-treated mon keys was 87.5%.The ultraso un d-guided CRISPR system could have great potential to successfully pursue the desired target genes,thereby reducing possible side effects associated with hitting no n-specific off-target genes,and sign ifica ntly in creasing more efficie ncy as well as higher specificity of in situ gene editi ng in vivo,which holds promise as a powerful,yet feasible tool,to edit disease genes to build corresp on ding huma n disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.
