BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure.7,8-Dihydroxyflavone(7,8-DHF)is a flavonoid derivative that acts as a smal...BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure.7,8-Dihydroxyflavone(7,8-DHF)is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic.The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy.METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol(ISO)with or without 7,8-DHF,respectively.F-actin staining was performed to calculate the cell area.Transcriptional levels of hypertrophic markers,including ANP,BNP,andβ-MHC,were detected.Echocardiography,hematoxylin-eosin staining,and transmission electron microscopy were used to examine the cardiac function,histology,and ultrastructure of ventricles.Protein levels of mitochondria-related factors,such as adenosine monophosphate-activated protein kinase(AMPK),and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),were detected.RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy,diminished the cross-sectional area,and alleviated the mitochondrial disorders of cardiomyocytes.Meanwhile,7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes.In addition,7,8-DHF activated AMPK and PGC-1αsignals without affecting the protein levels of mitochondrial dynamics-related molecules.The effects of 7,8-DHF were eliminanted by Compound C,an AMPK inhibitor.CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling,providing a potential agent for the treatment of pathological cardiac hypertrophy.展开更多
As a subtask of information extraction (IE), which aims to extract structured information from texts, event extraction is to recognize event trigger mentions of a predefined event type and their arguments. In general,...As a subtask of information extraction (IE), which aims to extract structured information from texts, event extraction is to recognize event trigger mentions of a predefined event type and their arguments. In general, event extraction can be divided into two subtasks: trigger extraction and argument extraction. Currently, the frequent existences of unannotated trigger mentions and poor-context trigger mentions impose critical challenges in Chinese trigger extraction. This paper proposes a novel three-layer joint model to integrate three components in trigger extraction, i.e., trigger identification, event type determination, and event subtype determination. In this way, different kinds of evidence on distinct pseudo samples can be well captured to eliminate the harmful effects of those un-annotated trigger mentions. In addition, this paper introduces various types of linguistically driven constraints on the trigger and argument semantics into the joint model to recover those poor-context trigger mentions. The experimental results show that our joint model significantly outperforms the state-of-the-art Chinese trigger extraction and Chinese event extraction as a whole.展开更多
Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious ba...Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency.A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases.However,strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking,and nonviral vectors with target recognition functions may be the focus of future research.Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing.Diseases are both varied and complex,and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important.Meanwhile,there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment.This paper reviews the current developments in three aspects,namely,gene-editing type,delivery vector,and disease characteristics.Additionally,this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.展开更多
Early studies on discourse rhetorical structure parsing mainly adopt bottom-up approaches,limiting the parsing process to local information.Although current top-down parsers can better capture global information and h...Early studies on discourse rhetorical structure parsing mainly adopt bottom-up approaches,limiting the parsing process to local information.Although current top-down parsers can better capture global information and have achieved particular success,the importance of local and global information at various levels of discourse parsing is differ-ent.This paper argues that combining local and global information for discourse parsing is more sensible.To prove this,we introduce a top-down discourse parser with bidirectional representation learning capabilities.Existing corpora on Rhetorical Structure Theory(RST)are known to be much limited in size,which makes discourse parsing very challenging.To alleviate this problem,we leverage some boundary features and a data augmentation strategy to tap the potential of our parser.We use two methods for evaluation,and the experiments on the RST-DT corpus show that our parser can pri-marily improve the performance due to the effective combination of local and global information.The boundary features and the data augmentation strategy also play a role.Based on gold standard elementary discourse units(EDUs),our pars-er significantly advances the baseline systems in nuclearity detection,with the results on the other three indicators(span,relation,and full)being competitive.Based on automatically segmented EDUs,our parser still outperforms previous state-of-the-artwork.展开更多
This systematic review assessed the safety and efficacy of the disposable circumcision suture device （DCSD） and conventional circumcision （CC） in the treatment of redundant prepuce and phimosis. Two independent re...This systematic review assessed the safety and efficacy of the disposable circumcision suture device （DCSD） and conventional circumcision （CC） in the treatment of redundant prepuce and phimosis. Two independent reviewers conducted a literature search for randomized controlled trials （RCTs） using the DCSD and CC for the treatment of redundant prepuce or phimosis in China and abroad. Nine RCTs （1898 cases） were included. Compared with the CC group, the DCSD group had a shorter operative time （standardized mean difference [SMD] = -21.44; 95% confidence intervals [95% CIs] [-25.08, -17.79]; P 〈 0.00001）, shorter wound healing time （SMD = -3.66; 95% CI [-5.46, -1.85]; P 〈 0.0001）, less intraoperative blood loss （SMD = -9.64; 95% CI [-11.37, -7.90]; P 〈 0.00001）, better cosmetic penile appearance （odds ratio [OR] =8.77; 95% CI [5.90, 13.02]; P 〈 0.00001）, lower intraoperative pain score, lower 24-h postoperative pain score, lower incidence of infection, less incision edema, and fewer adverse events. There were no differences between the CC and DCSD groups in the incidences of dehiscence, or hematoma. The results of this meta-analysis indicate that the DCSD appears to be safer and more effective than CC. However, additional high-quality RCTs with larger study populations are needed.展开更多
Mitochondria are subcellular organelles that provide energy for the cell.They form a dynamic tubular network and play an important role in maintaining the cell function and integrity.Heart is a powerful organ that sup...Mitochondria are subcellular organelles that provide energy for the cell.They form a dynamic tubular network and play an important role in maintaining the cell function and integrity.Heart is a powerful organ that supplies the motivation for circulation,thereby requiring large amounts of energy.Thus,the healthiness of cardiomyocytes and mitochondria is necessary for the normal cardiac function.Mitochondria not only lie in the center of the cell apoptotic pathway,but also are the major source of reactive oxygen species(ROS)generation.Mitochondrial morphological change includes fission and fusion that are regulated by a large number of proteins.In this review we discuss the regulators of mitochondrial fission/fusion and their association with cell apoptosis,autophagy and ROS production in the heart.展开更多
基金supported by the National Natural Science Foundation of China (No. 82070309, 8187 0191, and 82073838)“333 Project” of Jiangsu Provincethe Lvyangjinfeng Talent Program of Yangzhou
文摘BACKGROUND Pathological cardiac hypertrophy is a compensated response to various stimuli and is considered a key risk factor for heart failure.7,8-Dihydroxyflavone(7,8-DHF)is a flavonoid derivative that acts as a small-molecule brain-derived neurotrophic factor mimetic.The present study aimed to explore the potential role of 7,8-DHF in cardiac hypertrophy.METHODS Kunming mice and H9c2 cells were exposed to transverse aortic constriction or isoproterenol(ISO)with or without 7,8-DHF,respectively.F-actin staining was performed to calculate the cell area.Transcriptional levels of hypertrophic markers,including ANP,BNP,andβ-MHC,were detected.Echocardiography,hematoxylin-eosin staining,and transmission electron microscopy were used to examine the cardiac function,histology,and ultrastructure of ventricles.Protein levels of mitochondria-related factors,such as adenosine monophosphate-activated protein kinase(AMPK),and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α),were detected.RESULTS 7,8-DHF inhibited compensated and decompensated cardiac hypertrophy,diminished the cross-sectional area,and alleviated the mitochondrial disorders of cardiomyocytes.Meanwhile,7,8-DHF reduced the cell size and repressed the mRNA levels of the hypertrophic markers of ISO-treated cardiomyocytes.In addition,7,8-DHF activated AMPK and PGC-1αsignals without affecting the protein levels of mitochondrial dynamics-related molecules.The effects of 7,8-DHF were eliminanted by Compound C,an AMPK inhibitor.CONCLUSIONS These findings suggest that 7,8-DHF inhibited cardiac hypertrophy and mitochondrial dysfunction by activating AMPK signaling,providing a potential agent for the treatment of pathological cardiac hypertrophy.
文摘As a subtask of information extraction (IE), which aims to extract structured information from texts, event extraction is to recognize event trigger mentions of a predefined event type and their arguments. In general, event extraction can be divided into two subtasks: trigger extraction and argument extraction. Currently, the frequent existences of unannotated trigger mentions and poor-context trigger mentions impose critical challenges in Chinese trigger extraction. This paper proposes a novel three-layer joint model to integrate three components in trigger extraction, i.e., trigger identification, event type determination, and event subtype determination. In this way, different kinds of evidence on distinct pseudo samples can be well captured to eliminate the harmful effects of those un-annotated trigger mentions. In addition, this paper introduces various types of linguistically driven constraints on the trigger and argument semantics into the joint model to recover those poor-context trigger mentions. The experimental results show that our joint model significantly outperforms the state-of-the-art Chinese trigger extraction and Chinese event extraction as a whole.
基金This work was supported by The National Natural Science Foundation of China(No.81870331,China)Natural Science Foundation of Shandong Province(No.ZR2021MH280)the Qingdao Municipal Science and Technology Bureau Project(No.21-1-4-rkjk-12-nsh,China).
文摘Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency.A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases.However,strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking,and nonviral vectors with target recognition functions may be the focus of future research.Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing.Diseases are both varied and complex,and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important.Meanwhile,there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment.This paper reviews the current developments in three aspects,namely,gene-editing type,delivery vector,and disease characteristics.Additionally,this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.
基金supported by the National Natural Science Foundation of China under Grant No.62276178。
文摘Early studies on discourse rhetorical structure parsing mainly adopt bottom-up approaches,limiting the parsing process to local information.Although current top-down parsers can better capture global information and have achieved particular success,the importance of local and global information at various levels of discourse parsing is differ-ent.This paper argues that combining local and global information for discourse parsing is more sensible.To prove this,we introduce a top-down discourse parser with bidirectional representation learning capabilities.Existing corpora on Rhetorical Structure Theory(RST)are known to be much limited in size,which makes discourse parsing very challenging.To alleviate this problem,we leverage some boundary features and a data augmentation strategy to tap the potential of our parser.We use two methods for evaluation,and the experiments on the RST-DT corpus show that our parser can pri-marily improve the performance due to the effective combination of local and global information.The boundary features and the data augmentation strategy also play a role.Based on gold standard elementary discourse units(EDUs),our pars-er significantly advances the baseline systems in nuclearity detection,with the results on the other three indicators(span,relation,and full)being competitive.Based on automatically segmented EDUs,our parser still outperforms previous state-of-the-artwork.
文摘This systematic review assessed the safety and efficacy of the disposable circumcision suture device （DCSD） and conventional circumcision （CC） in the treatment of redundant prepuce and phimosis. Two independent reviewers conducted a literature search for randomized controlled trials （RCTs） using the DCSD and CC for the treatment of redundant prepuce or phimosis in China and abroad. Nine RCTs （1898 cases） were included. Compared with the CC group, the DCSD group had a shorter operative time （standardized mean difference [SMD] = -21.44; 95% confidence intervals [95% CIs] [-25.08, -17.79]; P 〈 0.00001）, shorter wound healing time （SMD = -3.66; 95% CI [-5.46, -1.85]; P 〈 0.0001）, less intraoperative blood loss （SMD = -9.64; 95% CI [-11.37, -7.90]; P 〈 0.00001）, better cosmetic penile appearance （odds ratio [OR] =8.77; 95% CI [5.90, 13.02]; P 〈 0.00001）, lower intraoperative pain score, lower 24-h postoperative pain score, lower incidence of infection, less incision edema, and fewer adverse events. There were no differences between the CC and DCSD groups in the incidences of dehiscence, or hematoma. The results of this meta-analysis indicate that the DCSD appears to be safer and more effective than CC. However, additional high-quality RCTs with larger study populations are needed.
文摘Mitochondria are subcellular organelles that provide energy for the cell.They form a dynamic tubular network and play an important role in maintaining the cell function and integrity.Heart is a powerful organ that supplies the motivation for circulation,thereby requiring large amounts of energy.Thus,the healthiness of cardiomyocytes and mitochondria is necessary for the normal cardiac function.Mitochondria not only lie in the center of the cell apoptotic pathway,but also are the major source of reactive oxygen species(ROS)generation.Mitochondrial morphological change includes fission and fusion that are regulated by a large number of proteins.In this review we discuss the regulators of mitochondrial fission/fusion and their association with cell apoptosis,autophagy and ROS production in the heart.
