Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently le...Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.展开更多
[Objectives]This study was conducted to further enrich the research on saline-alkali land improvement,and explore the effects of biological bacterial fertilizers containing Bacillus subtilis and Bacillus velezensis HM...[Objectives]This study was conducted to further enrich the research on saline-alkali land improvement,and explore the effects of biological bacterial fertilizers containing Bacillus subtilis and Bacillus velezensis HM-3 in saline-alkali land improvement and crop growth promotion.[Methods]Wheat was planted in saline-alkali land in Huanghua City,Hebei Province,and a mixed application experiment was carried out using biological agents from Hemiao Biotechnology Co.,Ltd.[Results]Compared with the field of control check(CK),water-soluble salts and pH value in the experimental fields decreased,and living bacteria count in the soil increased.Meanwhile,the economic characters of wheat in the experimental fields showed excellent performance,with yields increasing by 39.09%and 27.49%compared with the CK.It could be seen that the application of biological bacterial fertilizers achieved obvious effects of improving saline-alkali soil and increasing wheat yield.[Conclusions]In this study,the effects of biological bacterial fertilizers on saline-alkali land and wheat growth characters were clarified,providing some technical support and theoretical guidance for wheat planting in Huanghua saline-alkali land.展开更多
Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are const...Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of organs.Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors.Brain organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma research.GBM organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental models.Therefore,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision treatments.This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.展开更多
Ghrelin O-acyltransferase(GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. GOAT is expressed mainly in the stoma...Ghrelin O-acyltransferase(GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. GOAT is expressed mainly in the stomach, pancreas and hypothalamus. Levels of GOAT are altered by energy status. GOAT contains 11 transmembrane helices and one reentrant loop. Its invariant residue His-338 and conserved Asn-307 are located in the endoplasmic reticulum lumen and cytosol respectively. GOAT contributes to the regulation of food intake and energy expenditure, as well as glucose and lipids homeostasis. Deletion of GOAT blocks the acylation of ghrelin leading to subsequent impairment in energy homeostasis and survival when mice are challenged with high energy diet or severe caloric restriction. GO-Co A-Tat, a peptide GOAT inhibitor, attenuates acyl-ghrelin production and prevents weight gain induced by a medium-chain triglycerides-rich high fat diet. Further, GO-Co A-Tat increases glucose-induced insulin secretion. Overall, inhibition of GOAT is a novel strategy for treatment of obesity and related metabolic disorders.展开更多
The 2016 Albert Lasker Basic Medical Research Award honors three physician-scientists： William G. Kaelin, Jr. from Harvard Medical School, Peter J. Ratcliffe from Uni- versity of Oxford and Gregg L. Semenza, from Joh...The 2016 Albert Lasker Basic Medical Research Award honors three physician-scientists： William G. Kaelin, Jr. from Harvard Medical School, Peter J. Ratcliffe from Uni- versity of Oxford and Gregg L. Semenza, from Johns Hopkins University School of Medicine, for their discovery of the pathway by which cells from human and most animals sense and adapt to changes in oxygen availability, a process essential for survival. The Lasker Award is widely considered as America＇s mosLt prestigious honor in the biomedical field. For 71 years,展开更多
A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleava...A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleavage of the N-N bond via carbon atom insertion.This metal-free ring expansion reaction enables the late-stage diversification of indazole skeletons,assembling a diverse array of functionalized quinazolin-4(3H)-ones in decent yields with excellent functional group compatibility.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172660)Hebei Province Graduate Student Innovation Project(Grant No.CXZZBS2023001)Baoding Natural Science Foundation(Grant No.H2272P015).
文摘Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.
基金Supported by Key Research and Development Program of Hebei Province(20322911D,21322903D)Innovation Ability Promotion Program of Hebei Province(20562903D)+1 种基金Technical Innovation Guidance Program of Hebei Province(20822904D)Science and Technology Research and Development Program of Qinhuangdao City(202201B028).
文摘[Objectives]This study was conducted to further enrich the research on saline-alkali land improvement,and explore the effects of biological bacterial fertilizers containing Bacillus subtilis and Bacillus velezensis HM-3 in saline-alkali land improvement and crop growth promotion.[Methods]Wheat was planted in saline-alkali land in Huanghua City,Hebei Province,and a mixed application experiment was carried out using biological agents from Hemiao Biotechnology Co.,Ltd.[Results]Compared with the field of control check(CK),water-soluble salts and pH value in the experimental fields decreased,and living bacteria count in the soil increased.Meanwhile,the economic characters of wheat in the experimental fields showed excellent performance,with yields increasing by 39.09%and 27.49%compared with the CK.It could be seen that the application of biological bacterial fertilizers achieved obvious effects of improving saline-alkali soil and increasing wheat yield.[Conclusions]In this study,the effects of biological bacterial fertilizers on saline-alkali land and wheat growth characters were clarified,providing some technical support and theoretical guidance for wheat planting in Huanghua saline-alkali land.
基金supported by grants from the Hebei Natural Science Foundation(Grant No.H2022201062)The Science and Technology Program of Hebei(Grant No.223777115D)+1 种基金Hebei Provincial Central Leading Local Science and Technology Development Fund Project(Grant No.216Z7711G)Postgraduate’s Innovation Fund Project of Hebei Province(Grant No.CXZZBS2023002)。
文摘Glioblastomas(GBMs)are the brain tumors with the highest malignancy and poorest prognoses.GBM is characterized by high heterogeneity and resistance to drug treatment.Organoids are 3-dimensional cultures that are constructed in vitro and comprise cell types highly similar to those in organs or tissues in vivo,thus simulating specific structures and physiological functions of organs.Organoids have been technically developed into an advanced ex vivo disease model used in basic and preclinical research on tumors.Brain organoids,which simulate the brain microenvironment while preserving tumor heterogeneity,have been used to predict patients’therapeutic responses to antitumor drugs,thus enabling a breakthrough in glioma research.GBM organoids provide an effective supplementary model that reflects human tumors’biological characteristics and functions in vitro more directly and accurately than traditional experimental models.Therefore,GBM organoids are widely applicable in disease mechanism research,drug development and screening,and glioma precision treatments.This review focuses on the development of various GBM organoid models and their applications in identifying new individualized therapies against drug-resistant GBM.
基金supported by the National Natural Science Foundation of China(8133001081390354)American Diabetes Association grant(1-13-BS-225)
文摘Ghrelin O-acyltransferase(GOAT), a member of MBOATs family, is essential for octanoylation of ghrelin, which is required for active ghrelin to bind with and activate its receptor. GOAT is expressed mainly in the stomach, pancreas and hypothalamus. Levels of GOAT are altered by energy status. GOAT contains 11 transmembrane helices and one reentrant loop. Its invariant residue His-338 and conserved Asn-307 are located in the endoplasmic reticulum lumen and cytosol respectively. GOAT contributes to the regulation of food intake and energy expenditure, as well as glucose and lipids homeostasis. Deletion of GOAT blocks the acylation of ghrelin leading to subsequent impairment in energy homeostasis and survival when mice are challenged with high energy diet or severe caloric restriction. GO-Co A-Tat, a peptide GOAT inhibitor, attenuates acyl-ghrelin production and prevents weight gain induced by a medium-chain triglycerides-rich high fat diet. Further, GO-Co A-Tat increases glucose-induced insulin secretion. Overall, inhibition of GOAT is a novel strategy for treatment of obesity and related metabolic disorders.
文摘The 2016 Albert Lasker Basic Medical Research Award honors three physician-scientists： William G. Kaelin, Jr. from Harvard Medical School, Peter J. Ratcliffe from Uni- versity of Oxford and Gregg L. Semenza, from Johns Hopkins University School of Medicine, for their discovery of the pathway by which cells from human and most animals sense and adapt to changes in oxygen availability, a process essential for survival. The Lasker Award is widely considered as America＇s mosLt prestigious honor in the biomedical field. For 71 years,
基金supported by the National Natural Science Foundation of China(21931013,22271105)the Natural Science Foundation of Fujian Province(2022J02009)+1 种基金the Science and Technology Research Project of Education Department of Hubei Province(B2021133)the Hubei Key Laboratory of Pollutant Analysis&Reuse Technology(PA190109)
文摘A novel difluorocarbene promoted single-atom skeletal editing of 2H-indazoles is demonstrated herein.Ethyl bromodifluoroacetate was severed as the difluorocarbene source in the current protocol,facilitating the cleavage of the N-N bond via carbon atom insertion.This metal-free ring expansion reaction enables the late-stage diversification of indazole skeletons,assembling a diverse array of functionalized quinazolin-4(3H)-ones in decent yields with excellent functional group compatibility.
