Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity effica...Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity efficacies from 11 teas.In vitro experiments revealed that lipid accumulation in L02 cells and lipid synthesis in 3T3-L1 cells were significantly better inhibited by Tea-B than Tea-A.Further in vivo experiments using model mice revealed that the differences in chemical components generated two pathways in the anti-obesity efficacy and mechanism of Pu-erh teas.Tea-A changes the histomorphology of brown adipose tissue(BAT)and increases the abundance of Coriobacteriaceae_UCG_002 and cyclic AMP in guts through high chemical contents of cyclopentasiloxane,decamethyl,tridecane and 1,2,3-trimethoxybenzene,eventually increasing BAT activation and fat browning gene expression;the high content of hexadecane and 1,2-dimethoxybenzene in Tea-B reduces white adipose tissue(WAT)accumulation and the process of fatty liver,increases the abundance of Odoribacter and sphinganine 1-phosphate,inhibits the expression of lipid synthesis and transport genes.These mechanistic findings on the association of the representative bioactive components in Pu-erh teas with the anti-obesity phenotypes,gut microbes,gut metabolite structure and anti-obesity pathways,which were obtained for the first time,provide foundations for developing functional Pu-erh tea.展开更多
Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,r...Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.展开更多
Ulcerative colitis(UC)is a chronic systematic inflammation disorder with increasing incidence,unknown pathogenesis,limited drug treatment,and abundant medical expenses.Dietary intake,as a daily indispensable environme...Ulcerative colitis(UC)is a chronic systematic inflammation disorder with increasing incidence,unknown pathogenesis,limited drug treatment,and abundant medical expenses.Dietary intake,as a daily indispensable environment factor,is closely related to UC pathogenesis and prevention.The underlying interactions between dietary intake and UC progression are implicated with the modulation of gut microbiome as well as microbial metabolites,suggesting the complex and systematic characteristics of UC.However,the triangular relationships with dietary intake,gut microbiota homeostasis,and UC have not been well summarized so far.Here we review the recent studies of dietary intake on the regulation of gut microbiome homeostasis as well as modulation of UC progression.These findings suggest that varieties in dietary patterns result in the production of diverse microbial fermentation metabolites,which contribute to gut microbiome homeostasis through multiple manipulations including immune modulation,inftammation restriction as well as epithelial barrier maintenance,thus finally determine the fate of UC progression and give implications for functional food development for prevention and treatment of UC patients.展开更多
With the rapid development of chemical engineering and biotechnology,polypeptide,as a promising candidate in the biomedical field,has been thoroughly investigated and extensively used as the drug delivery vehicle for ...With the rapid development of chemical engineering and biotechnology,polypeptide,as a promising candidate in the biomedical field,has been thoroughly investigated and extensively used as the drug delivery vehicle for diseases treatment,especially cancer,owing to the high biocompatibility,good biodegradability,versatile con-structions,and diverse functions.Engineered polypeptide-based drug delivery system(so-called EPP-DDS)can deliver the cargos to the target site via a specific recognition effect,followed by overcoming the barriers like blood brain barrier(BBB)and releasing them by responding to the microenvironment cues,to improve the therapeutic efficacy and reduce the side-effect.Herein,it's of great importance to conclude and summarize the updates on EPP-DDS developed by chemical engineering methods.In this review,we first summarized the recent updates in the manufacturing of polypeptide and preparation of EPP-DDS based on green biochemical engineering and/or synthetic processes for cancer therapy,including chemotherapy,immunotherapy,photodynamic therapy(PDT),gene therapy,and combination therapy.Then,we surveyed the research progress of inflammation-mediated cancer treatment strategies based on EPP-DDS with high anti-inflammation activity.Finally,we concluded the discovery and green production process of engineered polypeptide,challenges,and perspectives of EPP-DDS.Overall,the EPP-DDS has great potential for cancer therapy in the clinic with improved therapeutic efficacy and reduced adverse effect,which needs the innovation of green biochemical engineering for customized design and production of polypeptides.展开更多
MicroRNAs(miRNAs)are a class of endogenous short noncoding RNA.They regulate gene expression and function,essential to biological processes.It is necessary to develop an efficient detection method to determine these v...MicroRNAs(miRNAs)are a class of endogenous short noncoding RNA.They regulate gene expression and function,essential to biological processes.It is necessary to develop an efficient detection method to determine these valuable biomarkers for the diagnosis of cancers.In this paper,we proposed a general and rapid method for sensitive and quantitative detection of miRNA by combining CRISPR–Cas12a and rolling circle amplification(RCA)with the precircularized probe.Eventually,the detection of miRNA-21 could be completed in 70 min with a limit of detection of 8.1 pM with high specificity.The reaction time was reduced by almost 4 h from more than 5 h to 70 min,which makes detection more efficient.This design improves the efficiency of CRISPR–Cas and RCA-based sensing strategy and shows great potential in lab-based detection and point-of-care test.展开更多
基金The financial support received from the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022,WDZC20200821141349001)Shenzhen Bay Laboratory Startup Fund(21310041,S234602003)。
文摘Pu-erh tea,a traditional Chinese beverage,performs an anti-obesity function,but the correlation between its components and efficacy remains unknown.Here,we screened two Pu-erh teas with significant anti-obesity efficacies from 11 teas.In vitro experiments revealed that lipid accumulation in L02 cells and lipid synthesis in 3T3-L1 cells were significantly better inhibited by Tea-B than Tea-A.Further in vivo experiments using model mice revealed that the differences in chemical components generated two pathways in the anti-obesity efficacy and mechanism of Pu-erh teas.Tea-A changes the histomorphology of brown adipose tissue(BAT)and increases the abundance of Coriobacteriaceae_UCG_002 and cyclic AMP in guts through high chemical contents of cyclopentasiloxane,decamethyl,tridecane and 1,2,3-trimethoxybenzene,eventually increasing BAT activation and fat browning gene expression;the high content of hexadecane and 1,2-dimethoxybenzene in Tea-B reduces white adipose tissue(WAT)accumulation and the process of fatty liver,increases the abundance of Odoribacter and sphinganine 1-phosphate,inhibits the expression of lipid synthesis and transport genes.These mechanistic findings on the association of the representative bioactive components in Pu-erh teas with the anti-obesity phenotypes,gut microbes,gut metabolite structure and anti-obesity pathways,which were obtained for the first time,provide foundations for developing functional Pu-erh tea.
基金supported by the National Key Research and Development Program of China (2018YFA0901500)the National Natural Science Foundation of China (U2032210)。
文摘Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.
基金the National Key Research and Development Plan,China(2016YFD0400203-4).
文摘Ulcerative colitis(UC)is a chronic systematic inflammation disorder with increasing incidence,unknown pathogenesis,limited drug treatment,and abundant medical expenses.Dietary intake,as a daily indispensable environment factor,is closely related to UC pathogenesis and prevention.The underlying interactions between dietary intake and UC progression are implicated with the modulation of gut microbiome as well as microbial metabolites,suggesting the complex and systematic characteristics of UC.However,the triangular relationships with dietary intake,gut microbiota homeostasis,and UC have not been well summarized so far.Here we review the recent studies of dietary intake on the regulation of gut microbiome homeostasis as well as modulation of UC progression.These findings suggest that varieties in dietary patterns result in the production of diverse microbial fermentation metabolites,which contribute to gut microbiome homeostasis through multiple manipulations including immune modulation,inftammation restriction as well as epithelial barrier maintenance,thus finally determine the fate of UC progression and give implications for functional food development for prevention and treatment of UC patients.
基金supported by the Scientific Research Startup Funds(No.QD2021020C)at Shenzhen International Graduate School at Tsinghua Universitythe grant from the Shenzhen Science and Technology Innovation Commission(No.KCXFZ20201221173207022).
文摘With the rapid development of chemical engineering and biotechnology,polypeptide,as a promising candidate in the biomedical field,has been thoroughly investigated and extensively used as the drug delivery vehicle for diseases treatment,especially cancer,owing to the high biocompatibility,good biodegradability,versatile con-structions,and diverse functions.Engineered polypeptide-based drug delivery system(so-called EPP-DDS)can deliver the cargos to the target site via a specific recognition effect,followed by overcoming the barriers like blood brain barrier(BBB)and releasing them by responding to the microenvironment cues,to improve the therapeutic efficacy and reduce the side-effect.Herein,it's of great importance to conclude and summarize the updates on EPP-DDS developed by chemical engineering methods.In this review,we first summarized the recent updates in the manufacturing of polypeptide and preparation of EPP-DDS based on green biochemical engineering and/or synthetic processes for cancer therapy,including chemotherapy,immunotherapy,photodynamic therapy(PDT),gene therapy,and combination therapy.Then,we surveyed the research progress of inflammation-mediated cancer treatment strategies based on EPP-DDS with high anti-inflammation activity.Finally,we concluded the discovery and green production process of engineered polypeptide,challenges,and perspectives of EPP-DDS.Overall,the EPP-DDS has great potential for cancer therapy in the clinic with improved therapeutic efficacy and reduced adverse effect,which needs the innovation of green biochemical engineering for customized design and production of polypeptides.
基金the National Key Research and Development Program of China(Grant No.2019YFA0904800)the Project supported by the Joint Funds of the National Natural Science Foundation of China(Grant U2032210)the National Natural Science Foundation of China(NSFC)(Grant 21938004).
文摘MicroRNAs(miRNAs)are a class of endogenous short noncoding RNA.They regulate gene expression and function,essential to biological processes.It is necessary to develop an efficient detection method to determine these valuable biomarkers for the diagnosis of cancers.In this paper,we proposed a general and rapid method for sensitive and quantitative detection of miRNA by combining CRISPR–Cas12a and rolling circle amplification(RCA)with the precircularized probe.Eventually,the detection of miRNA-21 could be completed in 70 min with a limit of detection of 8.1 pM with high specificity.The reaction time was reduced by almost 4 h from more than 5 h to 70 min,which makes detection more efficient.This design improves the efficiency of CRISPR–Cas and RCA-based sensing strategy and shows great potential in lab-based detection and point-of-care test.
