SubclassⅢsucrose nonfermenting1-related protein kinase 2s(SnRK2s)function in ABA and abiotic stress responses by unknown mechanisms.We found that osmotic stress/ABA-activated protein kinase 10(SAPK10),a member of ric...SubclassⅢsucrose nonfermenting1-related protein kinase 2s(SnRK2s)function in ABA and abiotic stress responses by unknown mechanisms.We found that osmotic stress/ABA-activated protein kinase 10(SAPK10),a member of rice SnRK2s,physically interacted with CBL-interacting protein kinase 1(OsCIPK1).OsCIPK1 expression was up-regulated by ABA and PEG treatment,and overexpression increased the ABA sensitivity of seed germination and root growth and plant osmotic stress tolerance.Osmotic stress or ABA-induced activation of OsCIPK1 is dependent on SAPK10.SAPK10 phosphorylates Thr-24 of OsCIPK1 in vitro,and this phosphorylation increases the activity of OsCIPK1 and positively regulates the function of OsCIPK1 in ABA responses and plant osmotic stress tolerance.This study suggests that OsCIPK1 is a direct phosphorylated substrate of SAPK10,and SAPK10-mediated phosphorylation of OsCIPK1 functions in ABA signaling and increases rice osmotic stress tolerance.展开更多
Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies ...Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).展开更多
The corrosion behavior of BFe10-1-1 alloy with different rare earth （RE） contents in simulated flowing marine water was investigated by X-ray diffractometer and scanning electron microscope （SEM）. It was demonstra...The corrosion behavior of BFe10-1-1 alloy with different rare earth （RE） contents in simulated flowing marine water was investigated by X-ray diffractometer and scanning electron microscope （SEM）. It was demonstrated that the corrosion rate of BFel0-1-1 alloy with the same chemical compositions in faster flow velocity of marine water was higher than that in a lower flow velocity of marine water. Fixing the flow velocity, BFe 10-1-1 alloy had the best flushing corrosion resistance when the RE content was 0.04wt.%. The consequence of such good corrosion resistance was attributed to the formation of compact protective film on alloy surface containing RE phase such as CeNis. The RE-contained film combines with other corrosion products firmly, which was difficult to fall off from the alloy surface in the flowing marine water. Additionally, SEM analysis confirmed that pitting mechanism, which would be transformed to spalling mechanism gradually with further increasing RE content, was the prevalent mechanism when the alloy contained 0.04wt.%RE.展开更多
The aim of this study was to investigate the expression of PD-1 on peripheral blood mononuclear cells (PBMCs) and the serum level of CXCL10 and those of roles in the pathogenesis in SLE patients. The expression of PD-...The aim of this study was to investigate the expression of PD-1 on peripheral blood mononuclear cells (PBMCs) and the serum level of CXCL10 and those of roles in the pathogenesis in SLE patients. The expression of PD-1 on PBMCs was tested by flow cytometry and the serum level of CXCL10 was determined by ELISA in 47 SLE patients and 21 healthy controls. The correlation between PD-1, CXCL10 and ANA, anti-dsDNA antibody and SLEDAI (SLE disease activity index) were evaluated. The expression of PD-1 on PBMCs in SLE patients was significantly different from that of controls. The percentage of PD-1 on neutrophiles in SLE patients was decreased compared with that of healthy controls (P<0.01), and that on lymphocyte from inactive SLE was significantly lower than that of controls (P<0.02). However, the PD-1 expression and the level of serum CXCL10 in active SLE were significantly increased (P<0.01) than those of controls. Positive correlations were found between PD-1, CXCL10 and anti-dsDNA antibody, SLEDAI in active SLE. The abnormal expression of PD-1 on PBMCs and serum level of CXCL10 in SLE patients may impair the auto-immunological tolerance, and play an important role in the pathogenesis of SLE.展开更多
To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and inter...To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats＇ pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of IL-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients（p 〈0.01 and p 〈0.05, respectively） ; the blood glucose concentration decreased （p 〈 0. 05 ） ; both the functional β cell in islets and the insulin content in pancreatic tissue increased （p 〈 0. 05 and p 〈0. 01 ） ; the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively（p 〈0. 01 and p 〈 0. 05）. The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats .展开更多
ZTE Corporation announced on April 29, 2009 that its terminal products recorded 10 million units shipped globally in Q1 2009, representing an increase of 30% compared with
AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibro...AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.展开更多
AIM： To investigate the regulation of lipoxygenase （LOX）-1 and Dectin-1 on interleukin-10 （IL-10） production in mice with Aspergillus fumigatus （A. fumigatus） keratitis. METHODS： The corneas of C57BL/6 mice we...AIM： To investigate the regulation of lipoxygenase （LOX）-1 and Dectin-1 on interleukin-10 （IL-10） production in mice with Aspergillus fumigatus （A. fumigatus） keratitis. METHODS： The corneas of C57BL/6 mice were pretreated with LOX-1 inhibitor Poly（I） or Dectin-1 siRNA separately before the infection of A. fumigatus. Polymerase chain reaction （PCR） and Western blot were used to detect the expression of IL-10. RESULTS： The mRNA and protein expressions of IL-10 were significantly increased in mice with A. fumigatus keratitis. Compared with the group pretreated with sterile water before infection, Poly（I） pretreatment suppressed IL-10 expression significantly. Compared with the group pretreated with scrambled siRNA before infection, Dectin-1 siRNA pretreatment significantly reduced IL-10 expression in response to A. fumigatus infection. CONCLUSION： LOX-1 and Dectin-1 regulate IL-10 production in mouse A. fumigatus keratitis.展开更多
基金supported by grants from the National Natural Science Foundation of China(31971824,32170316)。
文摘SubclassⅢsucrose nonfermenting1-related protein kinase 2s(SnRK2s)function in ABA and abiotic stress responses by unknown mechanisms.We found that osmotic stress/ABA-activated protein kinase 10(SAPK10),a member of rice SnRK2s,physically interacted with CBL-interacting protein kinase 1(OsCIPK1).OsCIPK1 expression was up-regulated by ABA and PEG treatment,and overexpression increased the ABA sensitivity of seed germination and root growth and plant osmotic stress tolerance.Osmotic stress or ABA-induced activation of OsCIPK1 is dependent on SAPK10.SAPK10 phosphorylates Thr-24 of OsCIPK1 in vitro,and this phosphorylation increases the activity of OsCIPK1 and positively regulates the function of OsCIPK1 in ABA responses and plant osmotic stress tolerance.This study suggests that OsCIPK1 is a direct phosphorylated substrate of SAPK10,and SAPK10-mediated phosphorylation of OsCIPK1 functions in ABA signaling and increases rice osmotic stress tolerance.
基金funded by Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A)National Natural Science Foundation of China(Grant No.82103677)National Science and Technology Major Projects of China(Grant No.2019ZX09732-001)。
文摘Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).
基金supported by the Science and Technology Payoffs Transformation Program of Jiangsu Province (DA2006034)the Program of National College Student Creative Experiment (081053309)
文摘The corrosion behavior of BFe10-1-1 alloy with different rare earth （RE） contents in simulated flowing marine water was investigated by X-ray diffractometer and scanning electron microscope （SEM）. It was demonstrated that the corrosion rate of BFel0-1-1 alloy with the same chemical compositions in faster flow velocity of marine water was higher than that in a lower flow velocity of marine water. Fixing the flow velocity, BFe 10-1-1 alloy had the best flushing corrosion resistance when the RE content was 0.04wt.%. The consequence of such good corrosion resistance was attributed to the formation of compact protective film on alloy surface containing RE phase such as CeNis. The RE-contained film combines with other corrosion products firmly, which was difficult to fall off from the alloy surface in the flowing marine water. Additionally, SEM analysis confirmed that pitting mechanism, which would be transformed to spalling mechanism gradually with further increasing RE content, was the prevalent mechanism when the alloy contained 0.04wt.%RE.
文摘The aim of this study was to investigate the expression of PD-1 on peripheral blood mononuclear cells (PBMCs) and the serum level of CXCL10 and those of roles in the pathogenesis in SLE patients. The expression of PD-1 on PBMCs was tested by flow cytometry and the serum level of CXCL10 was determined by ELISA in 47 SLE patients and 21 healthy controls. The correlation between PD-1, CXCL10 and ANA, anti-dsDNA antibody and SLEDAI (SLE disease activity index) were evaluated. The expression of PD-1 on PBMCs in SLE patients was significantly different from that of controls. The percentage of PD-1 on neutrophiles in SLE patients was decreased compared with that of healthy controls (P<0.01), and that on lymphocyte from inactive SLE was significantly lower than that of controls (P<0.02). However, the PD-1 expression and the level of serum CXCL10 in active SLE were significantly increased (P<0.01) than those of controls. Positive correlations were found between PD-1, CXCL10 and anti-dsDNA antibody, SLEDAI in active SLE. The abnormal expression of PD-1 on PBMCs and serum level of CXCL10 in SLE patients may impair the auto-immunological tolerance, and play an important role in the pathogenesis of SLE.
基金Supported Partly by the National Natural Science Foundation of China(No.39870667)the Program for Scientific ResearchFoundation of Jilin Province,China(No.2002-714)the Key Scientific Research Project from the Third Clinical College of Jilin University,China.
文摘To observe the effects of the micronutrients on oxidative and autoimmune destruction of islets so as to prevent a person from the onset and development of type 1 Diabetes Mellitus （T1DM）, the interleukin-4 and interleukin-10 expressions of lymphocytes in peripheral blood and spleen of T1DM rats were determined by flow cytometry. GSH-Px activity and MDA level in the rats＇ pancreas were measured using biochemical methods. The insulin contents in serum and β cell insulin secret storage were tested by RIA and IHC, respectively. There was an increase in the percentages of IL-4 and IL-10 positive lymphocytes in the peripheral blood and spleen of the groups of rats supplemented with various combinations of micronutrients（p 〈0.01 and p 〈0.05, respectively） ; the blood glucose concentration decreased （p 〈 0. 05 ） ; both the functional β cell in islets and the insulin content in pancreatic tissue increased （p 〈 0. 05 and p 〈0. 01 ） ; the GSH-Px activity and MDA level of pancreas in the rats enhanced and decreased respectively（p 〈0. 01 and p 〈 0. 05）. The results suggest that micronutrients may alleviate the islet lesions by upregulating the expressions of IL-4 and IL-10 and lowering oxidative stress in diabetic rats .
文摘ZTE Corporation announced on April 29, 2009 that its terminal products recorded 10 million units shipped globally in Q1 2009, representing an increase of 30% compared with
基金Supported by the Science and Technology Project of Fujian Educational Committee, No. JA04198
文摘AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCI4 administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCI4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7th wk, MMP-2 and TIMP-1 mRNA increased in group C (P= 0.001/0.001) and group I (P= 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P= 0.001) while decreased in group I (P = 0.042) compared with that in the 7th wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.
基金Supported by the National Natural Science Foundation of China(No.81470609No.81300730+4 种基金No.81500695)China Postdoctoral Science Foundation(No.2018M630482)the National Natural Science Foundation of Shandong(No.ZR2017BH025)Key Research Project of Shandong(No.2018GSF118193)Applied Basic Research Project of Qingdao(No.16-5-1-65-jch)
文摘AIM： To investigate the regulation of lipoxygenase （LOX）-1 and Dectin-1 on interleukin-10 （IL-10） production in mice with Aspergillus fumigatus （A. fumigatus） keratitis. METHODS： The corneas of C57BL/6 mice were pretreated with LOX-1 inhibitor Poly（I） or Dectin-1 siRNA separately before the infection of A. fumigatus. Polymerase chain reaction （PCR） and Western blot were used to detect the expression of IL-10. RESULTS： The mRNA and protein expressions of IL-10 were significantly increased in mice with A. fumigatus keratitis. Compared with the group pretreated with sterile water before infection, Poly（I） pretreatment suppressed IL-10 expression significantly. Compared with the group pretreated with scrambled siRNA before infection, Dectin-1 siRNA pretreatment significantly reduced IL-10 expression in response to A. fumigatus infection. CONCLUSION： LOX-1 and Dectin-1 regulate IL-10 production in mouse A. fumigatus keratitis.
