This paper explores strategies to cultivate high-level technical talents in vocational undergraduate colleges by analyzing their development,the essence of such talents,and proposing several key measures.Strategies in...This paper explores strategies to cultivate high-level technical talents in vocational undergraduate colleges by analyzing their development,the essence of such talents,and proposing several key measures.Strategies include optimizing professional settings and curricula,enhancing school-enterprise cooperation and the integration of industry-university-research,improving teaching staff quality and educational standards,and expanding international cooperation.The importance of policy support and funding and establishing robust quality assurance systems is emphasized for effectively cultivating skilled talents in vocational undergraduate colleges.展开更多
To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and P...To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC progression.After analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection list.PIGL depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell survival.Specifically,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells.PIGL phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and CCL20.Clinically,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in tumors.Clinically,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.展开更多
MicroRNAs(miRNAs)as a well-known kind of cancer marker are closely associated with the formation and metastasis of tumors.Here,a novel tetraphenylethylene(TPE)-doped covalent organic frameworks(TPE-COFs)with strong ag...MicroRNAs(miRNAs)as a well-known kind of cancer marker are closely associated with the formation and metastasis of tumors.Here,a novel tetraphenylethylene(TPE)-doped covalent organic frameworks(TPE-COFs)with strong aggregation-induced electrochemiluminescence(AIECL)response was synthesized and introduced to construct an ultrasensitive biosensor for the detection of miRNA-21.The strong aggregation-induced emission(AIE)response was obtained because the molecular motion of TPE was restricted by COFs which had the porosity and highly ordered topological structure.Meanwhile,the porous structure of COFs allowed TPE to react with electrochemiluminescence(ECL)coreactants more effectively.Furthermore,COFs significantly improved the electron transport efficiency of the entire ECL system.All of these endowed the TPE-COFs with superior AIECL performance.Then,a TPE-COFs based ECL resonance energy transfer(ECL-RET)system was constructed for ultrasensitive miRNA-21 biosensing with differential signal readout.The proposed assays exhibited excellent sensitivity with a wide dynamic range from 10 aM to 1 pM and a low detection limit of 2.18 aM.Therefore,these indicated that doping TPE in COFs was a creative way to develop functional COFs and provided an effective way for enhancing AIECL.Furthermore,this work boarded the application of AIECL in analytical chemistry.展开更多
文摘This paper explores strategies to cultivate high-level technical talents in vocational undergraduate colleges by analyzing their development,the essence of such talents,and proposing several key measures.Strategies include optimizing professional settings and curricula,enhancing school-enterprise cooperation and the integration of industry-university-research,improving teaching staff quality and educational standards,and expanding international cooperation.The importance of policy support and funding and establishing robust quality assurance systems is emphasized for effectively cultivating skilled talents in vocational undergraduate colleges.
基金supported mainly by the Guangdong Natural Science Foundation of Guangdong Province of China 2021B1515020016in part by NSFC grants No.82000616,82272714,82173149Science and Technology Program of Guangdong Province No.2020B1212060019.
文摘To improve the efficacy of lenvatinib in combination with programmed death-1(PD-1)blockade therapy for hepatocellular carcinoma(HCC),we screened the suppressive metabolic enzymes that sensitize HCC to lenvatinib and PD-1 blockade,thus impeding HCC progression.After analysis of the CRISPR‒Cas9 screen,phosphatidylinositol-glycan biosynthesis class L(PIGL)ranked first in the positive selection list.PIGL depletion had no effect on tumor cell growth in vitro but reprogrammed the tumor microenvironment(TME)in vivo to support tumor cell survival.Specifically,nuclear PIGL disrupted the interaction between cMyc/BRD4 on the distant promoter of target genes and thus decreased the expression of CCL2 and CCL20,which are involved in shaping the immunosuppressive TME by recruiting macrophages and regulatory T cells.PIGL phosphorylation at Y81 by FGFR2 abolished the interaction of PIGL with importinα/β1,thus retaining PIGL in the cytosol and facilitating tumor evasion by releasing CCL2 and CCL20.Clinically,elevated nuclear PIGL predicts a better prognosis for HCC patients and presents a positive correlation with CD8+T-cell enrichment in tumors.Clinically,our findings highlight that the nuclear PIGL intensity or the change in PIGL-Y81 phosphorylation should be used as a biomarker to guide lenvatinib with PD-1 blockade therapy.
基金National Natural Science Foundation of China(Nos.42275152,32072305,22076042)Special Project for Hubei Local Science and Technology Development Guided by the Central Government(No.2019ZYYD004)+1 种基金Open Project Funding of the State Key Laboratory of Biocatalysis and Enzyme Engineering,Knowledge Innovation Program of Wuhan-Shuguang Project(2022020801020331)Foundation for Creative Research Groups of Hubei Province of China(No.2011CDA111).
文摘MicroRNAs(miRNAs)as a well-known kind of cancer marker are closely associated with the formation and metastasis of tumors.Here,a novel tetraphenylethylene(TPE)-doped covalent organic frameworks(TPE-COFs)with strong aggregation-induced electrochemiluminescence(AIECL)response was synthesized and introduced to construct an ultrasensitive biosensor for the detection of miRNA-21.The strong aggregation-induced emission(AIE)response was obtained because the molecular motion of TPE was restricted by COFs which had the porosity and highly ordered topological structure.Meanwhile,the porous structure of COFs allowed TPE to react with electrochemiluminescence(ECL)coreactants more effectively.Furthermore,COFs significantly improved the electron transport efficiency of the entire ECL system.All of these endowed the TPE-COFs with superior AIECL performance.Then,a TPE-COFs based ECL resonance energy transfer(ECL-RET)system was constructed for ultrasensitive miRNA-21 biosensing with differential signal readout.The proposed assays exhibited excellent sensitivity with a wide dynamic range from 10 aM to 1 pM and a low detection limit of 2.18 aM.Therefore,these indicated that doping TPE in COFs was a creative way to develop functional COFs and provided an effective way for enhancing AIECL.Furthermore,this work boarded the application of AIECL in analytical chemistry.