Background:The relationship between microRNA(miRNA)expression patterns and tumor mutation burden(TMB)in uterine corpus endometrial carcinoma(UCEC)was investigated in this study.Methods:The UCEC dataset from The Cancer...Background:The relationship between microRNA(miRNA)expression patterns and tumor mutation burden(TMB)in uterine corpus endometrial carcinoma(UCEC)was investigated in this study.Methods:The UCEC dataset from The Cancer Genome Atlas(TCGA)database was used to identify the miRNAs that differ in expression between high TMB and low TMB sample sets.The total sample sets were divided into a training set and a test set.TMB levels were predicted using miRNA-based signature classifiers developed by Lasso Cox regression.Test sets were used to validate the classifier.This study investigated the relationship between a miRNA-based signature classifier and three immune checkpoint molecules(programmed cell death protein 1[PD-1],programmed cell death ligand 1[PD-L1],cytotoxic T lymphocyte-associated antigen 4[CTLA-4]).For the miRNA-based signature classifier,functional enrichment analysis was performed on the miRNAs.An analysis of the relationship between PD-1,PD-L1,and CTLA-4 immune checkpoint genes was carried out using the miRNA-based signature classifier.Results:We identified 27 differentially expressed miRNAs in miRNA-base signature.For predicting the TMB level,27-miRNA-based signature classifiers had accuracies of 0.8689 in the training cohort,0.8276 in the test cohort,and 0.8524 in the total cohort.The correlation between the miRNA-based signature classifier and PD-1 was negative,while the correlation between PD-L1 and CTLA4 was positive.Based on the miRNA profiling described above,we validated the expression levels of 9 miRNAs in clinical samples by quantitative reverse transcription PCR(qRT-PCR).Four of them were highly expressed and many cancer-related and immune-associated biological processes were linked to these 27 miRNAs.Thus,the developed miRNA-based signature classifier was correlated with TMB levels that could also predict TMB levels in UCEC samples.Conclusion:In this study,we investigated the relationship between a miRNAbased signature classifier and TMB levels in Uterine Corpus Endometrial Carcinoma.Further,this is the first study to confirm their relationship in clinical samples,which may provide more evidence support for immunotherapy of endometrial cancer.展开更多
Cerebral venous sinus thrombosis(CVST)is a rare condition in early pregnancy.A22-year-old Chinese woman at10weeks of pregnancy requested induced abortion and was diagnosed as CVST for a severe headache accompanying wi...Cerebral venous sinus thrombosis(CVST)is a rare condition in early pregnancy.A22-year-old Chinese woman at10weeks of pregnancy requested induced abortion and was diagnosed as CVST for a severe headache accompanying with nausea and vomiting.The patient was treated successfully with anticoagulation,followed by amniocentesis,and finally succeeded in induction of labor safely.The diagnosis,treatment and prognosis for this rare condition are discussed in this paper.展开更多
The Neogene fluvial reservoir in the Bohai oilfield is one of the leading development horizons for increasing reserves and production in the Bohai oilfield. However, the development of offshore fluvial reservoirs is f...The Neogene fluvial reservoir in the Bohai oilfield is one of the leading development horizons for increasing reserves and production in the Bohai oilfield. However, the development of offshore fluvial reservoirs is faced with the problems of thin reservoir thickness, narrow plane width, rapid lateral change, and thin well pattern. Taking the KLA oilfield as an example, this paper discusses the nuanced characterization and configuration of a single channel controlled by sedimentary facies to guide developing offshore river facies’ narrow channel main control oilfield. Firstly, based on a large number of core data, the acceptable sedimentary facies identification is realized, the sedimentary model of the study area is established, the delicate calibration of logging facies and seismic facies is realized under the constraint of the sedimentary model, and a set of technical methods for nuanced reservoir characterization guided by seismic sedimentology is summarized, to realize the boundary identification of composite channel configuration and further realize the nuanced characterization of the single narrow channel. Based on this set of technology, it guides the smooth implementation of horizontal wells in the oilfield. The drilling encounter rate of the reservoir in the horizontal section of the single well exceeds 90%, ensuring the injection production connectivity and increasing the reserve production rate by more than 10%.展开更多
Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mamma...Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mammals,MARylation is mainly catalyzed by ADP-ribosyltransferases(ARTs),which consist of two groups:ART cholera toxin-like(ARTCs)and ART diphtheria toxin-like(ARTDs,also known as PARPs).The human ARTC(hARTC)family is composed of four members:two active mono-ADP-ARTs(hARTC1 and hARTC5)and two enzymatically inactive enzymes(hARTC3 and hARTC4).In this study,we systematically examined the homology,expression,and localization pattern of the hARTC family,with a particular focus on hARTC1.Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1.We also identified vesicle-associated membrane protein-associated protein B(VAPB)as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site.Furthermore,we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis,highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis.In summary,our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.展开更多
基金the National Natural Science Foundation(81803877,82104705)the Natural Science Foundation of Guangdong Province of China(2017A030310178)+5 种基金the Guangdong Sci-Tech Commissioner(20211800500322)the China Postdoctoral Science Foundation(2020M682817)Guangdong Basic and Applied Basic Research Foundation(2020A1515110651,2020B1515120063)Guangdong Medical Science and Technology Research Foundation(A2021476)Traditional Chinese Medicine Research Project of Guangdong Province Traditional Chinese Medicine Bureau(20221256)the Dongguan Social Technology Development Fund(202050715001207).
文摘Background:The relationship between microRNA(miRNA)expression patterns and tumor mutation burden(TMB)in uterine corpus endometrial carcinoma(UCEC)was investigated in this study.Methods:The UCEC dataset from The Cancer Genome Atlas(TCGA)database was used to identify the miRNAs that differ in expression between high TMB and low TMB sample sets.The total sample sets were divided into a training set and a test set.TMB levels were predicted using miRNA-based signature classifiers developed by Lasso Cox regression.Test sets were used to validate the classifier.This study investigated the relationship between a miRNA-based signature classifier and three immune checkpoint molecules(programmed cell death protein 1[PD-1],programmed cell death ligand 1[PD-L1],cytotoxic T lymphocyte-associated antigen 4[CTLA-4]).For the miRNA-based signature classifier,functional enrichment analysis was performed on the miRNAs.An analysis of the relationship between PD-1,PD-L1,and CTLA-4 immune checkpoint genes was carried out using the miRNA-based signature classifier.Results:We identified 27 differentially expressed miRNAs in miRNA-base signature.For predicting the TMB level,27-miRNA-based signature classifiers had accuracies of 0.8689 in the training cohort,0.8276 in the test cohort,and 0.8524 in the total cohort.The correlation between the miRNA-based signature classifier and PD-1 was negative,while the correlation between PD-L1 and CTLA4 was positive.Based on the miRNA profiling described above,we validated the expression levels of 9 miRNAs in clinical samples by quantitative reverse transcription PCR(qRT-PCR).Four of them were highly expressed and many cancer-related and immune-associated biological processes were linked to these 27 miRNAs.Thus,the developed miRNA-based signature classifier was correlated with TMB levels that could also predict TMB levels in UCEC samples.Conclusion:In this study,we investigated the relationship between a miRNAbased signature classifier and TMB levels in Uterine Corpus Endometrial Carcinoma.Further,this is the first study to confirm their relationship in clinical samples,which may provide more evidence support for immunotherapy of endometrial cancer.
文摘Cerebral venous sinus thrombosis(CVST)is a rare condition in early pregnancy.A22-year-old Chinese woman at10weeks of pregnancy requested induced abortion and was diagnosed as CVST for a severe headache accompanying with nausea and vomiting.The patient was treated successfully with anticoagulation,followed by amniocentesis,and finally succeeded in induction of labor safely.The diagnosis,treatment and prognosis for this rare condition are discussed in this paper.
文摘The Neogene fluvial reservoir in the Bohai oilfield is one of the leading development horizons for increasing reserves and production in the Bohai oilfield. However, the development of offshore fluvial reservoirs is faced with the problems of thin reservoir thickness, narrow plane width, rapid lateral change, and thin well pattern. Taking the KLA oilfield as an example, this paper discusses the nuanced characterization and configuration of a single channel controlled by sedimentary facies to guide developing offshore river facies’ narrow channel main control oilfield. Firstly, based on a large number of core data, the acceptable sedimentary facies identification is realized, the sedimentary model of the study area is established, the delicate calibration of logging facies and seismic facies is realized under the constraint of the sedimentary model, and a set of technical methods for nuanced reservoir characterization guided by seismic sedimentology is summarized, to realize the boundary identification of composite channel configuration and further realize the nuanced characterization of the single narrow channel. Based on this set of technology, it guides the smooth implementation of horizontal wells in the oilfield. The drilling encounter rate of the reservoir in the horizontal section of the single well exceeds 90%, ensuring the injection production connectivity and increasing the reserve production rate by more than 10%.
基金This work was supported by grants from the National Natural Science Foundation of China(32071277,82002594,81874160,and 32171295)the Natural Science Foundation of Hebei Province(C2021201012)+3 种基金S&T Program of Hebei(216Z2602G)the Interdisciplinary Research Program of Natural Science of Hebei University(DXK202006 and DXK202007)Hebei Natural Science Foundation for Outstanding Young Scholars(H2020201017)the High-level Talents Research Start-up Project of Hebei University(521000981352).
文摘Mono-ADP-ribosylation(MARylation)is a post-translational modification that regulates a variety of biological processes,including DNA damage repair,cell proliferation,metabolism,and stress and immune responses.In mammals,MARylation is mainly catalyzed by ADP-ribosyltransferases(ARTs),which consist of two groups:ART cholera toxin-like(ARTCs)and ART diphtheria toxin-like(ARTDs,also known as PARPs).The human ARTC(hARTC)family is composed of four members:two active mono-ADP-ARTs(hARTC1 and hARTC5)and two enzymatically inactive enzymes(hARTC3 and hARTC4).In this study,we systematically examined the homology,expression,and localization pattern of the hARTC family,with a particular focus on hARTC1.Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1.We also identified vesicle-associated membrane protein-associated protein B(VAPB)as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site.Furthermore,we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis,highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis.In summary,our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.