In accordance with the feature of pure delay in monitor AGC system for cold rolling mill, a new fuzzy selftuning PID Smith prediction controller is developed. The position control model is deduced based on a single st...In accordance with the feature of pure delay in monitor AGC system for cold rolling mill, a new fuzzy selftuning PID Smith prediction controller is developed. The position control model is deduced based on a single stand cold rolling mill, and the fuzzy controller for monitor AGC system is designed. The analysis of dynamic performance for traditional PID Smith prediction controller and fuzzy self-tuning PID Smith prediction controller is done by MAT- LAB toolbox. The simulation results show that fuzzy self-tuning PID Smith controller has stronger robustness, faster response and higher static accuracy than traditional PID Smith controller.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existin...Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that micro RNAs（mi RNAs）, known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression,and growing numbers of novel mi RNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis,and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of mi RNAs in regulating bone remodeling as well as novel applications for mi RNAs in biomaterials for therapeutic purposes.展开更多
AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of t...AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of Tgondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on Tgondii tachyzoites under electromicroscope. RESULTS： The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-y, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-α were undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION： SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against Tgondii may be regulated by both hormone- and cell-mediated immune response.展开更多
Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming...Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor progression.This study aims to elucidate how PDK1 pro-motes breast cancer progression.We found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)pathway.Further investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase activity.Furthermore,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells.The phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase domain.We also found that PDK1 enhanced HIF-1αtranscriptional ac-tivity.In summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto P300.PDK1 and HIF-1αform a positive feedback loop to promote breast cancer progression.展开更多
BACKGROUND Post-transplant lymphoproliferative disorder(PTLD)is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation(allo-HCT)or solid organ transplantation(SOT).Unlike SO...BACKGROUND Post-transplant lymphoproliferative disorder(PTLD)is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation(allo-HCT)or solid organ transplantation(SOT).Unlike SOT,PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism.CASE SUMMARY We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma(DLBCL)with significantly decreased T-cell chimerism early after allo-HCT.A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission.Nearly 3 mo after transplantation,the patient developed cervical lymph node enlargement and gastric lesions,both of which were pathologically suggestive of DLBCL.Meanwhile,the patient experienced a significant and persistent decrease in T-cell chimerism.A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy.CONCLUSION The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient.展开更多
The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt ...The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the gen展开更多
Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI...Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.展开更多
基金Item Sponsored by National Natural Science Foundation of China (50634030)
文摘In accordance with the feature of pure delay in monitor AGC system for cold rolling mill, a new fuzzy selftuning PID Smith prediction controller is developed. The position control model is deduced based on a single stand cold rolling mill, and the fuzzy controller for monitor AGC system is designed. The analysis of dynamic performance for traditional PID Smith prediction controller and fuzzy self-tuning PID Smith prediction controller is done by MAT- LAB toolbox. The simulation results show that fuzzy self-tuning PID Smith controller has stronger robustness, faster response and higher static accuracy than traditional PID Smith controller.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
基金supported by grants from the Science and Technology Fund of Sichuan Province (Grant No. 2011SZ0096)the National Natural Science Foundation of China (Grant No. 31470904)
文摘Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that micro RNAs（mi RNAs）, known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression,and growing numbers of novel mi RNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis,and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of mi RNAs in regulating bone remodeling as well as novel applications for mi RNAs in biomaterials for therapeutic purposes.
基金Supported by China Ministry of Human Affairs and Department of Science and Technology of Shandong Province, No. 031050115
文摘AIM： To analyze the biological role of the surface antigen of Toxoplasma gondii（Tgondii） in development of vaccine. METHODS： The surface antigen of Tgondii （SAG1） was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of Tgondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on Tgondii tachyzoites under electromicroscope. RESULTS： The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-y, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-α were undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION： SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against Tgondii may be regulated by both hormone- and cell-mediated immune response.
基金supported by grants from the National Natural Science Foundation of China(No.82073255)the Foundation of Chongqing Municipal Education Commission(China)(No.HZ2021006).
文摘Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor progression.This study aims to elucidate how PDK1 pro-motes breast cancer progression.We found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)pathway.Further investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase activity.Furthermore,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells.The phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase domain.We also found that PDK1 enhanced HIF-1αtranscriptional ac-tivity.In summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto P300.PDK1 and HIF-1αform a positive feedback loop to promote breast cancer progression.
文摘BACKGROUND Post-transplant lymphoproliferative disorder(PTLD)is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation(allo-HCT)or solid organ transplantation(SOT).Unlike SOT,PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism.CASE SUMMARY We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma(DLBCL)with significantly decreased T-cell chimerism early after allo-HCT.A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission.Nearly 3 mo after transplantation,the patient developed cervical lymph node enlargement and gastric lesions,both of which were pathologically suggestive of DLBCL.Meanwhile,the patient experienced a significant and persistent decrease in T-cell chimerism.A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy.CONCLUSION The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient.
基金supported by the National Natural Science Foundation of China(31901462)the Natural Science Foundation of the Jiangsu Higher Education Institutions,China(22KJA210005)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD)the Brand Professional Construction Program of Jiangsu Higher Education Institutions,China。
文摘The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the gen
基金supported by the National Natural Science Foundation of China(32288101)the National Key Research and Development Program of China(2021YFC2701400)Shenkang Clinical Technology Innovation Project(SHDC22021219)。
文摘Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of 40.It represents a significant detriment to female fertility.However,the known POI-causative genes currently account for only a fraction of cases.To elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in RNF111.In a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 variants.These variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 variants.Notably,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling pathway.Our analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and humans.To further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian reserve.Additionally,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse ovaries.In conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.
