A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pHtriggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOX_(ADH) and D-DOX_(car) conjugated with acid-labil...A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pHtriggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOX_(ADH) and D-DOX_(car) conjugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOX_(ADH)(D-DOX_(ADH)-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slowrelease mixed DSDS nanoparticles.展开更多
Chiral ligand conjugated transition metal oxide nanoparticles(NPs) are a promising platform for chiral recognition, biochemical sensing, and chiroptics. Herein, we present chirality-based strategy for effective sensin...Chiral ligand conjugated transition metal oxide nanoparticles(NPs) are a promising platform for chiral recognition, biochemical sensing, and chiroptics. Herein, we present chirality-based strategy for effective sensing of mercury ions via ligand-induced chirality derived from metal-to-ligand charge transfer(MLCT) effects. The ligand competition effect between molybdenum and heavy metal ions such as mercury is designated to be essential for MLCT chirality. With this know-how, mercury ions, which have a larger stability constant(Kf) than molybdenum, can be selectively identified and quantified with a limit of detection(LOD) of 0.08 and 0.12 nmol/L for D-cysteine and L-cysteine(Cys) capped Mo O2 NPs. Such chiral chemical sensing nanosystems would be an ideal prototype for biochemical sensing with a significant impact on the field of biosensing, biological systems,and water research-based nanotoxicology.展开更多
C-aryl glycosides are an important kind of carbohydrate derivatives for drug discovery,due to their distinctive attributes of resistance to hydrolysis from enzymes.Herein,C-aryl glycosylation was established for the s...C-aryl glycosides are an important kind of carbohydrate derivatives for drug discovery,due to their distinctive attributes of resistance to hydrolysis from enzymes.Herein,C-aryl glycosylation was established for the synthesis of 2-sulfur C-aryl glycals and 1,2-dihydrobenzofuran-fused C-aryl glycosides via interrupted Pummerer process,featured with sulfonium-tethered[3,3]-sigmatropic rearrangement between sulfoxide glycals and phenols.This protocol offers a broad substrate scope with diverse glycosyl and phenols.Dapagliflozin,Empagliflozin,and Ipragliflozin analogs were straightforward achieved,respectively.展开更多
Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC...Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.展开更多
文摘A mixed drug self-delivery system(DSDS)with high drug content(>50%)was developed to regulate pHtriggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOX_(ADH) and D-DOX_(car) conjugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOX_(ADH)(D-DOX_(ADH)-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slowrelease mixed DSDS nanoparticles.
基金Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180305180553701,KQTD2015071710313656)Guangdong Basic and Applied Basic Research Foundation(2019A1515012094)+4 种基金Natural Science Foundation of Hubei Province(2020CFB200)Shenzhen Fundamental Research Foundation(JCYJ20180508162801893)National Natural Science Foundation of China(21805234,22075240)Guangdong Introducing Innovative and Enterpreneurial Teams(2019ZT08L101)Shenzhen Institute of Artificial Intelligence and Robotics for Society(AIRS)。
文摘Chiral ligand conjugated transition metal oxide nanoparticles(NPs) are a promising platform for chiral recognition, biochemical sensing, and chiroptics. Herein, we present chirality-based strategy for effective sensing of mercury ions via ligand-induced chirality derived from metal-to-ligand charge transfer(MLCT) effects. The ligand competition effect between molybdenum and heavy metal ions such as mercury is designated to be essential for MLCT chirality. With this know-how, mercury ions, which have a larger stability constant(Kf) than molybdenum, can be selectively identified and quantified with a limit of detection(LOD) of 0.08 and 0.12 nmol/L for D-cysteine and L-cysteine(Cys) capped Mo O2 NPs. Such chiral chemical sensing nanosystems would be an ideal prototype for biochemical sensing with a significant impact on the field of biosensing, biological systems,and water research-based nanotoxicology.
基金The authors are grateful for financial support provided by NSFC(22125103and21971065)STCSM(22JC1401000,20xD1421500 and 20JC1416800)the Fundamental Research FundsfortheCentral Universities.
文摘C-aryl glycosides are an important kind of carbohydrate derivatives for drug discovery,due to their distinctive attributes of resistance to hydrolysis from enzymes.Herein,C-aryl glycosylation was established for the synthesis of 2-sulfur C-aryl glycals and 1,2-dihydrobenzofuran-fused C-aryl glycosides via interrupted Pummerer process,featured with sulfonium-tethered[3,3]-sigmatropic rearrangement between sulfoxide glycals and phenols.This protocol offers a broad substrate scope with diverse glycosyl and phenols.Dapagliflozin,Empagliflozin,and Ipragliflozin analogs were straightforward achieved,respectively.
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(No.2017-I2M-1-005,2016-I2M-1-001)the National Key R&D Program of China(No.2016YFC1303201)+2 种基金the National Natural Science Foundation of China(No.81802299,81502514)the Fundamental Research Funds for the Central Universities(No.3332018070)the National Key Basic Research Development Plan(No.2018YFC1312105).
文摘Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.
