Aberrant RNA alternative splicing in cancer generates varied novel isoforms and protein variants that facilitate cancer progression.Here,we employed the advanced long-read full-length transcriptome sequencing on gallb...Aberrant RNA alternative splicing in cancer generates varied novel isoforms and protein variants that facilitate cancer progression.Here,we employed the advanced long-read full-length transcriptome sequencing on gallbladder normal tissues,tumors,and cell lines to establish a comprehensive full-length gallbladder transcriptomic atlas.It is of note that receptor tyrosine kinases were one of the most dynamic components with highly variable transcript,with Erb-B2 receptor tyrosine kinase 2(ERBB2)as a prime representative.A novel transcript,designated ERBB2 i14e,was identified for encoding a novel functional protein,and its protein expression was elevated in gallbladder cancer and strongly associated with worse prognosis.With the regulation of splicing factors ESRP1/2,ERBB2 i14e was alternatively spliced from intron 14 and the encoded i14e peptide was proved to facilitate the interaction with ERBB3 and downstream signaling activation of AKT.ERBB2 i14e was inducible and its expression attenuated anti-ERBB2 treatment efficacy in tumor xenografts.Further studies with patient derived xenografts models validated that ERBB2 i14e blockage with antisense oligonucleotide enhanced the tumor sensitivity to trastuzumab and its drug conjugates.Overall,this study provides a gallbladder specific long-read transcriptome profile and discovers a novel mechanism of trastuzumab resistance,thus ultimately devising strategies to improve trastuzumab therapy.展开更多
The solvent-free and catalyst-free(SFCF)reaction has gamered significant interestamongchemists due to its alignment with many of the 12 principles of green chemistry.In recent years,numerous innovative techniques have...The solvent-free and catalyst-free(SFCF)reaction has gamered significant interestamongchemists due to its alignment with many of the 12 principles of green chemistry.In recent years,numerous innovative techniques have been employedto expand thescope ofSFCFreactions and diversify the range of substrates.This paper presents an exhaustive examination of these transformations involving various functional groups,including alkenes,alkynes,aldehydes,ketones,imines,carboxylic acids,anhydrides,amides,amines,epoxides,aziridines,and organoselenides.Our review primarily seeks to elucidate the impact of solvent and concentration effects on these reactions by applying novel theories,such as the aggregate effect,multi-body effect,and multiple weak interactions,to ascertain how solvents impede these reactions.Additionally,different reaction mechanisms are con trasted under catalytic versus non-catalytic as well as solvent versus non-solvent conditions.Furthermore,the applications of such environmentally friendly re-actions in fields such as material synthesis and drug synthesis are emphasized.展开更多
In recent years,the synthesis and application of alkenes have attracted increased attention.Triphenylethenes(TriPEs)have lower molecular torsion than tetraphenylethenes(TPEs),which helps to balance the degree of conju...In recent years,the synthesis and application of alkenes have attracted increased attention.Triphenylethenes(TriPEs)have lower molecular torsion than tetraphenylethenes(TPEs),which helps to balance the degree of conjugation and the aggregation-induced emission(AIE)effect.The geometry of double bonds has a significant impact on luminescence.Therefore,it is essential to provide a comprehensive summary of the stereoselective synthetic strategies for trisubstituted alkenes.In this review,common strategies for the stereoselective synthesis of alkenes are described,with an emphasis on the origin of stereoselectivity and the types of substrates.In addition,the AIE properties of TriPE and its applications in optoelectronic devices,stimuli-responsive materials,sensors,and therapies were discussed.展开更多
Molecular aggregation affects the electronic interactions between molecules and has emerged as a powerful tool in material science.Aggregate effect finds wide applications in the research of new physical phenomena;how...Molecular aggregation affects the electronic interactions between molecules and has emerged as a powerful tool in material science.Aggregate effect finds wide applications in the research of new physical phenomena;however,its value for chemical reaction development has been far less explored.Herein,we report the development of aggregation-enabled alkene insertion into carbon–halogen bonds.The spontaneous cleavage of C–X(X=Cl,Br,or I)bonds generates an intimate ion pair,which can be quickly captured by alkenes in an aggregated state.Additional catalysts or promoters are not necessary under such circumstances,and solvent quenching experiments indicate that the aggregated state is critical for achieving such sequences.The ionic insertion mode is supported by mechanistic studies,density functional theory calculations,and symmetry-adapted perturbation theory analysis.Results also show that the non-aggregated state may quench the transition state and terminate the insertion process.展开更多
基金supported by grants from National Natural Science Foundation of China(No.32130036,82403148,82303937,82073206)Shanghai Shenkang Clinical Technology Innovation Project(No.SHDC12021101)+8 种基金Basic Research Project of Science and Technology Commission of Shanghai Municipality(No.20JC1419100)National Key Research and Development Program of China(No.2021YFE0203300)Science and Technology Innovation Action Plan Technical Standards Project of Science and Technology Commission of Shanghai Municipality(23DZ2202800)Cooperative Research Projects of Shanghai Jiao Tong University(2022LHA13)Major Science and Technology R&D Project of the Science and Technology Department of Jiangxi Province(20213AAG01013)Shanghai Outstanding Academic Leader(23XD1450700),Shanghai Rising-Star Program(23QA1408500)Young Talents Project of Shanghai Municipal Health Commission(2022YQ061)Shanghai Municipal Health Commission health Industry clinical research special project(No.20224Z0014)the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(No.20SG14).
文摘Aberrant RNA alternative splicing in cancer generates varied novel isoforms and protein variants that facilitate cancer progression.Here,we employed the advanced long-read full-length transcriptome sequencing on gallbladder normal tissues,tumors,and cell lines to establish a comprehensive full-length gallbladder transcriptomic atlas.It is of note that receptor tyrosine kinases were one of the most dynamic components with highly variable transcript,with Erb-B2 receptor tyrosine kinase 2(ERBB2)as a prime representative.A novel transcript,designated ERBB2 i14e,was identified for encoding a novel functional protein,and its protein expression was elevated in gallbladder cancer and strongly associated with worse prognosis.With the regulation of splicing factors ESRP1/2,ERBB2 i14e was alternatively spliced from intron 14 and the encoded i14e peptide was proved to facilitate the interaction with ERBB3 and downstream signaling activation of AKT.ERBB2 i14e was inducible and its expression attenuated anti-ERBB2 treatment efficacy in tumor xenografts.Further studies with patient derived xenografts models validated that ERBB2 i14e blockage with antisense oligonucleotide enhanced the tumor sensitivity to trastuzumab and its drug conjugates.Overall,this study provides a gallbladder specific long-read transcriptome profile and discovers a novel mechanism of trastuzumab resistance,thus ultimately devising strategies to improve trastuzumab therapy.
基金supported by the National Natural Science Foundation of China(Nos.52171075,91940305).The authors would like to thank Shiyanjia Lab(www.shiyanjia.com)for the language editing service.
文摘The solvent-free and catalyst-free(SFCF)reaction has gamered significant interestamongchemists due to its alignment with many of the 12 principles of green chemistry.In recent years,numerous innovative techniques have been employedto expand thescope ofSFCFreactions and diversify the range of substrates.This paper presents an exhaustive examination of these transformations involving various functional groups,including alkenes,alkynes,aldehydes,ketones,imines,carboxylic acids,anhydrides,amides,amines,epoxides,aziridines,and organoselenides.Our review primarily seeks to elucidate the impact of solvent and concentration effects on these reactions by applying novel theories,such as the aggregate effect,multi-body effect,and multiple weak interactions,to ascertain how solvents impede these reactions.Additionally,different reaction mechanisms are con trasted under catalytic versus non-catalytic as well as solvent versus non-solvent conditions.Furthermore,the applications of such environmentally friendly re-actions in fields such as material synthesis and drug synthesis are emphasized.
基金supported by the National Natural Science Foundation of China(81874181,21871284)the Major Scientific and Technological Special Project for“Significant New Drugs Creation”(2019ZX09301158)+2 种基金the Emerging Frontier Program of Hospital Development Centre(SHDC12018107)the Science&Technology Department of Shanghai(18401933500)the State Key Laboratory of Bioorganic and Natural Products Chemistry。
文摘In recent years,the synthesis and application of alkenes have attracted increased attention.Triphenylethenes(TriPEs)have lower molecular torsion than tetraphenylethenes(TPEs),which helps to balance the degree of conjugation and the aggregation-induced emission(AIE)effect.The geometry of double bonds has a significant impact on luminescence.Therefore,it is essential to provide a comprehensive summary of the stereoselective synthetic strategies for trisubstituted alkenes.In this review,common strategies for the stereoselective synthesis of alkenes are described,with an emphasis on the origin of stereoselectivity and the types of substrates.In addition,the AIE properties of TriPE and its applications in optoelectronic devices,stimuli-responsive materials,sensors,and therapies were discussed.
基金National Natural Science Foundation of China,Grant/Award Numbers:91940305,21933009,81874181,22271195,21871284Natural Science Foundation of Fujian Province,Grant/Award Number:2021J01525+3 种基金Major Scientific and Technological Special Project for“Significant New Drugs Creation”,Grant/Award Number:2019ZX09301158The Emerging Frontier Program of Hospital Development Centre,Grant/Award Number:SHDC12018107Shanghai Science and Technology Development Fund from Central Leading Local Government,Grant/Award Number:YDZX20223100001004Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine,Grant/Award Number:ZY(2021-2023)−0501。
文摘Molecular aggregation affects the electronic interactions between molecules and has emerged as a powerful tool in material science.Aggregate effect finds wide applications in the research of new physical phenomena;however,its value for chemical reaction development has been far less explored.Herein,we report the development of aggregation-enabled alkene insertion into carbon–halogen bonds.The spontaneous cleavage of C–X(X=Cl,Br,or I)bonds generates an intimate ion pair,which can be quickly captured by alkenes in an aggregated state.Additional catalysts or promoters are not necessary under such circumstances,and solvent quenching experiments indicate that the aggregated state is critical for achieving such sequences.The ionic insertion mode is supported by mechanistic studies,density functional theory calculations,and symmetry-adapted perturbation theory analysis.Results also show that the non-aggregated state may quench the transition state and terminate the insertion process.
