With Hemerocallis fulva‘Golden Doll'as an experimental material,the effects of different concentrations of neutral salt( NaCl) and alkaline salt( NaHCO3) stresses on photosynthesis and chlorophyll fluorescence ch...With Hemerocallis fulva‘Golden Doll'as an experimental material,the effects of different concentrations of neutral salt( NaCl) and alkaline salt( NaHCO3) stresses on photosynthesis and chlorophyll fluorescence characteristics in H. fulva seedlings were studied. The results showed that salt stress treatment significantly reduced the photosynthetic capacity of H. fulva. Under the NaCl and NaHCO3 stresses,the photosynthetic characteristics and chlorophyll fluorescence parameters of H. fulva seedlings were basically the same,but the photosynthetic characteristics and chlorophyll fluorescence parameter values of H. fulva seedlings were significantly different under different salt types and salt concentrations. With the extension of days of salt stress and the increase of salt concentration,the initial fluorescence yield( Fo) and non-photochemical quenching coefficient( NPQ) increased;the maximum fluorescence yield( Fm),maximum photochemical efficiency( Fv/Fm),PSII actual photosynthetic quantum yield( Y) and apparent quantum efficiency( AQY) all showed a downward trend;and moreover,with the extension of days of salt stress and the increase of salt concentration,the net photosynthetic rate( Pn) decreased and the intercellular CO2 concentration( Ci) increased. It was speculated that under salt stress,the photosynthetic characteristics of H. fulva leaves were inhibited. On the one hand,the non-stomatal limiting factor,i. e.,the chlorophyll content decreased,which led to the inhibition of photosynthetic characteristics. On the other hand,the decrease in the photosynthetic performance of mesophyll cells led to a decrease in the net photosynthetic rate of H. fulva. The changes of photosynthetic characteristics and chlorophyll fluorescence parameters in H. fulva caused by salt stress were closely related to the types of salts and salt concentration. High salt stress significantly inhibited the photosynthetic capacity of H. fulva‘Golden Doll',and the effect of NaHCO3 on H. fulva seedlings was significantly greater than that of NaCl.展开更多
In recent years,the development of bispecific antibodies(bsAbs)has been rapid,with many new structures and target combinations being created.The boom in bsAbs has led to the successive issuance of industry guidance fo...In recent years,the development of bispecific antibodies(bsAbs)has been rapid,with many new structures and target combinations being created.The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China.However,there is a high degree of similarity in target selection,which could affect the development of diversity in bsAbs.This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies(mAbs).Through database research,we have identified the preferences of available bsAbs combinations,suggesting rational target selection options and warning of potential wastage of medical resources.We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.展开更多
Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibit...Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.展开更多
Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymp...Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.展开更多
基金Supported by Science and Technology Research Project of Institutions of Higher Education in Hebei Province (BJ2017102)Tangshan Normal University Doctoral Fund (2014A06)。
文摘With Hemerocallis fulva‘Golden Doll'as an experimental material,the effects of different concentrations of neutral salt( NaCl) and alkaline salt( NaHCO3) stresses on photosynthesis and chlorophyll fluorescence characteristics in H. fulva seedlings were studied. The results showed that salt stress treatment significantly reduced the photosynthetic capacity of H. fulva. Under the NaCl and NaHCO3 stresses,the photosynthetic characteristics and chlorophyll fluorescence parameters of H. fulva seedlings were basically the same,but the photosynthetic characteristics and chlorophyll fluorescence parameter values of H. fulva seedlings were significantly different under different salt types and salt concentrations. With the extension of days of salt stress and the increase of salt concentration,the initial fluorescence yield( Fo) and non-photochemical quenching coefficient( NPQ) increased;the maximum fluorescence yield( Fm),maximum photochemical efficiency( Fv/Fm),PSII actual photosynthetic quantum yield( Y) and apparent quantum efficiency( AQY) all showed a downward trend;and moreover,with the extension of days of salt stress and the increase of salt concentration,the net photosynthetic rate( Pn) decreased and the intercellular CO2 concentration( Ci) increased. It was speculated that under salt stress,the photosynthetic characteristics of H. fulva leaves were inhibited. On the one hand,the non-stomatal limiting factor,i. e.,the chlorophyll content decreased,which led to the inhibition of photosynthetic characteristics. On the other hand,the decrease in the photosynthetic performance of mesophyll cells led to a decrease in the net photosynthetic rate of H. fulva. The changes of photosynthetic characteristics and chlorophyll fluorescence parameters in H. fulva caused by salt stress were closely related to the types of salts and salt concentration. High salt stress significantly inhibited the photosynthetic capacity of H. fulva‘Golden Doll',and the effect of NaHCO3 on H. fulva seedlings was significantly greater than that of NaCl.
基金supported by the National Key Research and Development Program of China(2022YFA1303803)National Natural Science Foundation of China(82073701)+1 种基金the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202209)supported by“Double First-Class”University Project(CPU2022PZQ07,China)。
文摘In recent years,the development of bispecific antibodies(bsAbs)has been rapid,with many new structures and target combinations being created.The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China.However,there is a high degree of similarity in target selection,which could affect the development of diversity in bsAbs.This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies(mAbs).Through database research,we have identified the preferences of available bsAbs combinations,suggesting rational target selection options and warning of potential wastage of medical resources.We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
基金This study was supported by the National Natural Science Foundation of China(82073701,31900687,81973366)Natural Science Foundation of Jiangsu Province(BK2019040713,China)+3 种基金the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202013,China)This study was also supported by Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University(No.2020KFKT-5,China)the“Double First-Class”University Project(CPU2018GF04,China),and CAMS Innovation Fund for Medical Sciences(2021-I2M-1-070)The X-ray data were collected at the Shanghai Synchrotron Radiation Facility(SSRF,China)BL19U beamline.
文摘Programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1)have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy.Despite the inherent advantages of small-molecule inhibitors over antibodies,the discovery of small-molecule inhibitors has fallen behind that of antibody drugs.Based on docking studies between small molecule inhibitor and PD-L1 protein,changing the chemical linker of inhibitor from a flexible chain to an aromatic ring may improve its binding capacity to PD-L1 protein,which was not reported before.A series of novel phthalimide derivatives from structure-based rational design was synthesized.P39 was identified as the best inhibitor with promising activity,which not only inhibited PD-1/PD-L1 interaction(IC_(50)=8.9 nmol/L),but also enhanced killing efficacy of immune cells on cancer cells.Co-crystal data demonstrated that P39 induced the dimerization of PD-L1 proteins,thereby blocking the binding of PD-1/PD-L1.Moreover,P39 exhibited a favorable safety profile with a LD_(50)>5000 mg/kg and showed significant in vivo antitumor activity through promoting CD8^(+)T cell activation.All these data suggest that P39 acts as a promising small chemical inhibitor against the PD-1/PD-L1 axis and has the potential to improve the immunotherapy efficacy of T-cells.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2016ZX310182-2 and 2016ZX310176-6 to NY)the Medical Epigenetics Research Center,Chinese Academy of Medical Sciences(Grant Nos.2017PT31035 and 2018PT31035 to NY)the National Natural Science Foundation of China(Grant No.81773163 to JF)
文摘Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.
