Based on single-cell sequencing of the hippocampi of 5×familiar Alzheimer's disease(5×FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzhe...Based on single-cell sequencing of the hippocampi of 5×familiar Alzheimer's disease(5×FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C−C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communication in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5×FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.展开更多
SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to fa...SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to facilitate analysis of data from complex survey studies. On the other hand, PROC MEANS and many other classic SAS procedures also provide an option for including weights and yield identical point estimates, but different standard errors (SEs), as their corresponding survey procedures. This paper takes an in-depth look at different types of weights and provides guidance on use of different SAS procedures.展开更多
SETD2 is the main transferase for the trimethylation of histone H3 at lysine 36 (H3K36me3) in mammals. SETD2 plays important role in repairing DNA double strand breaks and maintaining chromatin integrity.1 In renal ca...SETD2 is the main transferase for the trimethylation of histone H3 at lysine 36 (H3K36me3) in mammals. SETD2 plays important role in repairing DNA double strand breaks and maintaining chromatin integrity.1 In renal carcinoma, SETD2 deficiency caused DNA replication fork instability and DNA damage.2 The absence of SETD2 was also reported to have strong tumor-promoting effects in lung adenocarcinomas (LUAD).3 However, the other roles of SETD2 remain poorly understood in LUAD. In this study, we utilized comprehensive omics-data analysis to determine that SETD2 was associated with DNA damage and immune-related signals in LUAD. SETD2 knockdown induced DNA damage and cGAS activation in LUAD cells, and reduced the number of cells at the G1 phase. Moreover, SETD2 deficiency was conducive to mutation burden, immune cell infiltration, and immunotherapy responses. High SETD2 expression was associated with high radiocurability. These findings suggest that SETD2 may be a promising biomarker of therapeutic responses for LUAD patients, and offer novel insights into immunotherapy and radiotherapy.展开更多
基金supported by grants from the Key R&D Plan of the Science and Technology Plan of Tibet Autonomous Region,China(Grant No.:XZ202201ZY0026G)the Science and Technology Cooperation Project of Shandong Provincial Department of Science and Technology for Counterpart Assistance to Tibet,China(Grant No.:YDZX2021083)+1 种基金the National Natural Science Foundation of China(Grant No.:82205078)the Natural Science Foundation of Shandong Province,China(Grant No.:ZR2021QH157).
文摘Based on single-cell sequencing of the hippocampi of 5×familiar Alzheimer's disease(5×FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C−C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communication in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5×FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.
文摘SAS and other popular statistical packages provide support for survey data with sampling weights. For example, PROC MEANS and PROC LOGISTIC in SAS have their counterparts PROC SURVEYMEANS and PROC SURVEYLOGISTIC to facilitate analysis of data from complex survey studies. On the other hand, PROC MEANS and many other classic SAS procedures also provide an option for including weights and yield identical point estimates, but different standard errors (SEs), as their corresponding survey procedures. This paper takes an in-depth look at different types of weights and provides guidance on use of different SAS procedures.
基金supported by National Natural Science Foundation,China(No.81972852,81800429)Key Research&Development Project of Hubei Province,China(No.2020BCA069)+3 种基金Nature Science Foundation of Hubei Province,China(No.2020CFB612)Young and Middle-Aged Medical Backbone Talents of Wuhan,China(No.WHQG201902)Application Foundation Frontier Project of Wuhan,China(No.2020020601012221)Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,China(No.ZNJC201922,ZNJC202007).
文摘SETD2 is the main transferase for the trimethylation of histone H3 at lysine 36 (H3K36me3) in mammals. SETD2 plays important role in repairing DNA double strand breaks and maintaining chromatin integrity.1 In renal carcinoma, SETD2 deficiency caused DNA replication fork instability and DNA damage.2 The absence of SETD2 was also reported to have strong tumor-promoting effects in lung adenocarcinomas (LUAD).3 However, the other roles of SETD2 remain poorly understood in LUAD. In this study, we utilized comprehensive omics-data analysis to determine that SETD2 was associated with DNA damage and immune-related signals in LUAD. SETD2 knockdown induced DNA damage and cGAS activation in LUAD cells, and reduced the number of cells at the G1 phase. Moreover, SETD2 deficiency was conducive to mutation burden, immune cell infiltration, and immunotherapy responses. High SETD2 expression was associated with high radiocurability. These findings suggest that SETD2 may be a promising biomarker of therapeutic responses for LUAD patients, and offer novel insights into immunotherapy and radiotherapy.
