In recent years, the progress of NAFLD has become an important health problem, and the prevention or delay of progress in NAFLD is a major key point. Whether or not to combine T2MD, people are interested in the mechan...In recent years, the progress of NAFLD has become an important health problem, and the prevention or delay of progress in NAFLD is a major key point. Whether or not to combine T2MD, people are interested in the mechanisms and efficacy of SGLT2i for NAFLD. In this review, we summarized the current clinical research on SGLT2i for the combination of T2MD’s NAFLD patients, and the latest evidence of external or animal experiments. These evidences will help us to more accurately understand the protective effects of SGLT2i in NAFLD. Lifestyle changes are still essential to prevent and treat NAFLD, and for all kinds of drugs that treat NAFLD in clinical trials, SGLT2i may be one of the promising treatments.展开更多
针对河道实时流速测量系统存在的电源有限功率约束和河道的声传输噪声复杂问题,设计了一种基于m序列相关法的声层析河道实时流速测量系统,系统采用m序列码作为扩频发送信号来解决背景噪声干扰,在接收端使用正交解调(In-Phase and Quadra...针对河道实时流速测量系统存在的电源有限功率约束和河道的声传输噪声复杂问题,设计了一种基于m序列相关法的声层析河道实时流速测量系统,系统采用m序列码作为扩频发送信号来解决背景噪声干扰,在接收端使用正交解调(In-Phase and Quadrature Demodulation,IQ解调)解决同步解调信噪比低的问题。在有限电源功率下,分析了m序列的阶数、扩频倍数对时间测量的影响。系统使用了国产的RT-Thread操作系统和北斗卫星导航系统,实现各站点定位和授时。选择10阶m序列调制信号,在长江流域进行现场验证,所测流速与多普勒流速仪验证比对,两者平均误差为1.2%。展开更多
酶功能的识别对理解生命活动的机制、推进生命科学的发展有重要作用。然而现有的酶EC编号预测方法,并未充分利用蛋白质序列信息,在识别精度上仍有所不足。针对上述问题,本研究提出一种基于层级特征和全局特征的EC编号预测网络(EC number...酶功能的识别对理解生命活动的机制、推进生命科学的发展有重要作用。然而现有的酶EC编号预测方法,并未充分利用蛋白质序列信息,在识别精度上仍有所不足。针对上述问题,本研究提出一种基于层级特征和全局特征的EC编号预测网络(EC number prediction network using hierarchical features and global features,ECPN-HFGF)。该方法首先通过残差网络提取蛋白质序列通用特征,并通过层级特征提取模块和全局特征提取模块进一步提取蛋白质序列的层级特征和全局特征,之后结合两种特征信息的预测结果,采用多任务学习框架,实现酶EC编号的精确预测。计算实验结果表明,ECPN-HFGF方法在蛋白质序列EC编号预测任务上性能最佳,宏观F1值和微观F1值分别达到95.5%和99.0%。ECPN-HFGF方法能有效结合蛋白质序列的层级特征和全局特征,快速准确预测蛋白质序列EC编号,比当前常用方法预测精确度更高,能够为酶学研究和酶工程应用的发展提供一种高效的思路和方法。展开更多
The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary chola...The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.展开更多
Robots are widely used,providing significant convenience in daily life and production.With the rapid development of artificial intelligence and neuromorphic computing in recent years,the realization of more intelligen...Robots are widely used,providing significant convenience in daily life and production.With the rapid development of artificial intelligence and neuromorphic computing in recent years,the realization of more intelligent robots through a pro-found intersection of neuroscience and robotics has received much attention.Neuromorphic circuits based on memristors used to construct hardware neural networks have proved to be a promising solution of shattering traditional control limita-tions in the field of robot control,showcasing characteristics that enhance robot intelligence,speed,and energy efficiency.Start-ing with introducing the working mechanism of memristors and peripheral circuit design,this review gives a comprehensive analysis on the biomimetic information processing and biomimetic driving operations achieved through the utilization of neuro-morphic circuits in brain-like control.Four hardware neural network approaches,including digital-analog hybrid circuit design,novel device structure design,multi-regulation mechanism,and crossbar array,are summarized,which can well simulate the motor decision-making mechanism,multi-information integration and parallel control of brain at the hardware level.It will be definitely conductive to promote the application of memristor-based neuromorphic circuits in areas such as intelligent robotics,artificial intelligence,and neural computing.Finally,a conclusion and future prospects are discussed.展开更多
Polymer dielectrics capable of operating efficiently at high electric fields and elevated temperatures are urgently demanded by next-generation electronics and electrical power systems.While inorganic fillers have bee...Polymer dielectrics capable of operating efficiently at high electric fields and elevated temperatures are urgently demanded by next-generation electronics and electrical power systems.While inorganic fillers have been extensively utilized to improved high-temperature capacitive performance of dielectric polymers,the presence of thermodynamically incompatible organic and inorganic components may lead to concern about the long-term stability and also complicate film processing.Herein,zero-dimensional polymer dots with high electron affinity are introduced into photoactive allyl-containing poly(aryl ether sulfone)to form the all-organic polymer composites for hightemperature capacitive energy storage.Upon ultraviolet irradiation,the crosslinked polymer composites with polymer dots are efficient in suppressing electrical conduction at high electric fields and elevated temperatures,which significantly reduces the high-field energy loss of the composites at 200℃.Accordingly,the ultraviolet-irradiated composite film exhibits a discharged energy density of 4.2 J cm^(−3)at 200℃.Along with outstanding cyclic stability of capacitive performance at 200℃,this work provides a promising class of dielectric materials for robust high-performance all-organic dielectric nanocomposites.展开更多
BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,ofte...BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,often failing to capture the complexity of the disease.The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.AIM To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.METHODS This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2,PLAU,and CCNA2.The results were validated in an independent dataset.This study also examined the correlations between the model risk score and various clinical features,components of the immune microenvironment,chemotherapeutic drug sensitivity,and metabolism-related pathways.Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.RESULTS The prognostic model demonstrated significant predictive value,with the risk score showing a strong correlation with clinical features:It was significantly associated with tumor grade(G)(bP<0.01),moderately associated with tumor stage(T)(aP<0.05),and significantly correlated with residual tumor(R)status(bP<0.01).There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs.Furthermore,the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.CONCLUSION The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.展开更多
The positive structure belts surrounding the Taibei Sag,Turpan-Hami Basin,have been the main targets for oil and gas exploration for years and are now left with remaining resources scattering in reservoirs adjacent to...The positive structure belts surrounding the Taibei Sag,Turpan-Hami Basin,have been the main targets for oil and gas exploration for years and are now left with remaining resources scattering in reservoirs adjacent to source rocks in the sag,where the Shuixigou Group with substantial oil and gas potential constitutes the primary focus for near-source exploration.Consequently,characterization of development and key controlling factors of reservoir space becomes a must for future exploration in the area.This study investigates the development traits,genesis,and controlling factors of the Xishanyao and Sangonghe formations in the Shengbei and Qiudong Sub-sags of the Taibei Sag with techniques such as cast thin-section observation,porosity and permeability tests,high-pressure mercury injection,and saturation fluid NMR analysis of reservoir rocks.The findings reveal that the Shuixigou Group in the Taibei Sag consists of lithic sandstone.Reservoirs in the group are mostly poor in terms of physical properties,with undeveloped primary pores dominated by intergranular dissolved pores as a result of a strong compaction.Comparative analysis of key controlling factors of the Sangonghe Formation reveals significant distinctions in sandstone particle size,sand body thickness,genesis and distribution,provenance location,and source rock type between the Qiudong area and Shengbei area.Vertically,the coal seams of the Xishanyao Formation exhibit heightened development with shallower burial depth and lower maturity compared to those of the Sangonghe Formation.Consequently,this environment fosters the formation of organic acids,which have a stronger dissolution effect on minerals to develop secondary dissolution pores,and ultimately resulting in better reservoir physical properties.Overall,the reservoirs within the Qiudong area of the Taibei Sag demonstrate superior characteristics compared to those in the Shengbei area.Furthermore,the reservoir physical properties of the Xishanyao Formation are better than those of the Sangonghe Formation.The research findings will provide valuable guidance for the exploration and development of lithological oil and gas reservoirs within the Taibei Sag.展开更多
BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflamm...BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.展开更多
Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among ...Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among children and adolescents can help identify areas of success,stagnation and emerging threats,thereby facilitating effective improvement strategies.Aims To estimate the incidence and burden trends of anxiety disorders in children and adolescents from 1990 to 2019 in 204 countries and compare the incidence and disease burden in different countries.To examine the association between anxiety disorders and social indicators(healthcare access and quality of life).Methods Data were obtained from the Global Burden of Disease Study 2019.The age-standardised incidence rates(ASIRs)and disability-adjusted life years(DALYs)were reported to assess the burden of anxiety disorders,and the estimated annual percentage change was calculated to quantify the temporal trends.Pearson’s correlation was used to investigate country-level risk factors for incidence and DALYs.Results Globally,there were 932 million incident cases of anxiety disorders in children and adolescents,739.29 per 100000 ASIRs and 380.62 million DALYs in 2019.From 1990 to 2019,the estimated annual percentage change of incidence of anxiety disorders decreased by 2.2%.Significant variations were observed in the age-standardised burden rate and the changing trend of anxiety disorders among countries.Portugal reported the highest ASIR of anxiety disorders,while Mexico had the largest increase rate of ASIR.In 2019,Portugal reported the highest number of DALYs(1001.71 million),and India(212.09 million)reported the lowest number of DALYs.The burden of anxiety disorders was positively correlated with the average number of psychiatrists,psychologists and nurses in the mental health sector(per 100000),and quality of life and the correlation coefficients were 0.58,0.67,0.43 and 0.53,respectively.Conclusions The incidence and global burden of anxiety disorders in adolescents have continued to decrease over the past 30 years.However,the incidence and disease burden in developed countries are still increasing steadily.Policymakers should design and implement mental health strategies for adolescents based on their specific developmental status,as well as the cultural and regional characteristics of each country.展开更多
文摘In recent years, the progress of NAFLD has become an important health problem, and the prevention or delay of progress in NAFLD is a major key point. Whether or not to combine T2MD, people are interested in the mechanisms and efficacy of SGLT2i for NAFLD. In this review, we summarized the current clinical research on SGLT2i for the combination of T2MD’s NAFLD patients, and the latest evidence of external or animal experiments. These evidences will help us to more accurately understand the protective effects of SGLT2i in NAFLD. Lifestyle changes are still essential to prevent and treat NAFLD, and for all kinds of drugs that treat NAFLD in clinical trials, SGLT2i may be one of the promising treatments.
文摘针对河道实时流速测量系统存在的电源有限功率约束和河道的声传输噪声复杂问题,设计了一种基于m序列相关法的声层析河道实时流速测量系统,系统采用m序列码作为扩频发送信号来解决背景噪声干扰,在接收端使用正交解调(In-Phase and Quadrature Demodulation,IQ解调)解决同步解调信噪比低的问题。在有限电源功率下,分析了m序列的阶数、扩频倍数对时间测量的影响。系统使用了国产的RT-Thread操作系统和北斗卫星导航系统,实现各站点定位和授时。选择10阶m序列调制信号,在长江流域进行现场验证,所测流速与多普勒流速仪验证比对,两者平均误差为1.2%。
文摘酶功能的识别对理解生命活动的机制、推进生命科学的发展有重要作用。然而现有的酶EC编号预测方法,并未充分利用蛋白质序列信息,在识别精度上仍有所不足。针对上述问题,本研究提出一种基于层级特征和全局特征的EC编号预测网络(EC number prediction network using hierarchical features and global features,ECPN-HFGF)。该方法首先通过残差网络提取蛋白质序列通用特征,并通过层级特征提取模块和全局特征提取模块进一步提取蛋白质序列的层级特征和全局特征,之后结合两种特征信息的预测结果,采用多任务学习框架,实现酶EC编号的精确预测。计算实验结果表明,ECPN-HFGF方法在蛋白质序列EC编号预测任务上性能最佳,宏观F1值和微观F1值分别达到95.5%和99.0%。ECPN-HFGF方法能有效结合蛋白质序列的层级特征和全局特征,快速准确预测蛋白质序列EC编号,比当前常用方法预测精确度更高,能够为酶学研究和酶工程应用的发展提供一种高效的思路和方法。
基金the supports of the National Natural Science Foundation of China (No. 51901153)Natural Science Foundation of Shanxi Province,China (No. 201901D211096)。
文摘The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.
文摘Robots are widely used,providing significant convenience in daily life and production.With the rapid development of artificial intelligence and neuromorphic computing in recent years,the realization of more intelligent robots through a pro-found intersection of neuroscience and robotics has received much attention.Neuromorphic circuits based on memristors used to construct hardware neural networks have proved to be a promising solution of shattering traditional control limita-tions in the field of robot control,showcasing characteristics that enhance robot intelligence,speed,and energy efficiency.Start-ing with introducing the working mechanism of memristors and peripheral circuit design,this review gives a comprehensive analysis on the biomimetic information processing and biomimetic driving operations achieved through the utilization of neuro-morphic circuits in brain-like control.Four hardware neural network approaches,including digital-analog hybrid circuit design,novel device structure design,multi-regulation mechanism,and crossbar array,are summarized,which can well simulate the motor decision-making mechanism,multi-information integration and parallel control of brain at the hardware level.It will be definitely conductive to promote the application of memristor-based neuromorphic circuits in areas such as intelligent robotics,artificial intelligence,and neural computing.Finally,a conclusion and future prospects are discussed.
基金the National Natural Science Foundation of China(No.51973080,92066104).
文摘Polymer dielectrics capable of operating efficiently at high electric fields and elevated temperatures are urgently demanded by next-generation electronics and electrical power systems.While inorganic fillers have been extensively utilized to improved high-temperature capacitive performance of dielectric polymers,the presence of thermodynamically incompatible organic and inorganic components may lead to concern about the long-term stability and also complicate film processing.Herein,zero-dimensional polymer dots with high electron affinity are introduced into photoactive allyl-containing poly(aryl ether sulfone)to form the all-organic polymer composites for hightemperature capacitive energy storage.Upon ultraviolet irradiation,the crosslinked polymer composites with polymer dots are efficient in suppressing electrical conduction at high electric fields and elevated temperatures,which significantly reduces the high-field energy loss of the composites at 200℃.Accordingly,the ultraviolet-irradiated composite film exhibits a discharged energy density of 4.2 J cm^(−3)at 200℃.Along with outstanding cyclic stability of capacitive performance at 200℃,this work provides a promising class of dielectric materials for robust high-performance all-organic dielectric nanocomposites.
基金Supported by National Natural Science Foundation of China,No.82100581。
文摘BACKGROUND Pancreatic cancer is one of the most lethal malignancies,characterized by poor prognosis and low survival rates.Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy,often failing to capture the complexity of the disease.The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment.This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer.AIM To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules.METHODS This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2,PLAU,and CCNA2.The results were validated in an independent dataset.This study also examined the correlations between the model risk score and various clinical features,components of the immune microenvironment,chemotherapeutic drug sensitivity,and metabolism-related pathways.Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines.RESULTS The prognostic model demonstrated significant predictive value,with the risk score showing a strong correlation with clinical features:It was significantly associated with tumor grade(G)(bP<0.01),moderately associated with tumor stage(T)(aP<0.05),and significantly correlated with residual tumor(R)status(bP<0.01).There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs.Furthermore,the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer.CONCLUSION The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.
基金funded by the National Natural Science Foundation of China(No.U22B6002)the“14th Five-Year”Forward-looking Basic Science and Technology Project of China National Petroleum Company Limited(No.2022DJ2107).
文摘The positive structure belts surrounding the Taibei Sag,Turpan-Hami Basin,have been the main targets for oil and gas exploration for years and are now left with remaining resources scattering in reservoirs adjacent to source rocks in the sag,where the Shuixigou Group with substantial oil and gas potential constitutes the primary focus for near-source exploration.Consequently,characterization of development and key controlling factors of reservoir space becomes a must for future exploration in the area.This study investigates the development traits,genesis,and controlling factors of the Xishanyao and Sangonghe formations in the Shengbei and Qiudong Sub-sags of the Taibei Sag with techniques such as cast thin-section observation,porosity and permeability tests,high-pressure mercury injection,and saturation fluid NMR analysis of reservoir rocks.The findings reveal that the Shuixigou Group in the Taibei Sag consists of lithic sandstone.Reservoirs in the group are mostly poor in terms of physical properties,with undeveloped primary pores dominated by intergranular dissolved pores as a result of a strong compaction.Comparative analysis of key controlling factors of the Sangonghe Formation reveals significant distinctions in sandstone particle size,sand body thickness,genesis and distribution,provenance location,and source rock type between the Qiudong area and Shengbei area.Vertically,the coal seams of the Xishanyao Formation exhibit heightened development with shallower burial depth and lower maturity compared to those of the Sangonghe Formation.Consequently,this environment fosters the formation of organic acids,which have a stronger dissolution effect on minerals to develop secondary dissolution pores,and ultimately resulting in better reservoir physical properties.Overall,the reservoirs within the Qiudong area of the Taibei Sag demonstrate superior characteristics compared to those in the Shengbei area.Furthermore,the reservoir physical properties of the Xishanyao Formation are better than those of the Sangonghe Formation.The research findings will provide valuable guidance for the exploration and development of lithological oil and gas reservoirs within the Taibei Sag.
基金Project of the National Natural Science Foundation of China,No.82172398Key Research Project of the Department of Education of Liaoning Province,No.LJKZZ20220148+1 种基金Dalian Medical Science Research Project,No.2111038Dalian Dengfeng Plan Medical Key Specialty Construction Project(2021),No.243.
文摘BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examination results showed that the blank control group had the fastest progression of arthritis,the normal extracellular vesicle group had a relatively slower progression,and the engineered extracellular vesicle group had the slowest progression.Gross histological observation results showed that the blank control group had the most obvious signs of arthritis,the normal extracellular vesicle group showed signs of arthritis,and the engineered extracellular vesicle group showed no significant signs of arthritis.Using the Pelletier gross score evaluation,the engineered extracellular vesicle group had the slowest progression of arthritis.Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group,and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition.Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group.Compared to the normal extracellular vesicle group,the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells.CONCLUSION Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability,thereby protecting articular cartilage,and slowing the progression of KOA.
基金This work was supported by the National Natural Science Foundation of China(82173636)the International Institute of Population Health,Peking University Health Science Center(Number:JKGL202302)the National Key Research and Development Plan Project(2022YFC3600904).The funders had no role in study design,data collection and analysis,decision to publish or preparation of the manuscript.
文摘Background Anxiety disorders are the most common psychiatric problems,affecting approximately 1 in 12 children and 1 in 4 adolescents.Understanding the incidence,burden and correlated risks of anxiety disorders among children and adolescents can help identify areas of success,stagnation and emerging threats,thereby facilitating effective improvement strategies.Aims To estimate the incidence and burden trends of anxiety disorders in children and adolescents from 1990 to 2019 in 204 countries and compare the incidence and disease burden in different countries.To examine the association between anxiety disorders and social indicators(healthcare access and quality of life).Methods Data were obtained from the Global Burden of Disease Study 2019.The age-standardised incidence rates(ASIRs)and disability-adjusted life years(DALYs)were reported to assess the burden of anxiety disorders,and the estimated annual percentage change was calculated to quantify the temporal trends.Pearson’s correlation was used to investigate country-level risk factors for incidence and DALYs.Results Globally,there were 932 million incident cases of anxiety disorders in children and adolescents,739.29 per 100000 ASIRs and 380.62 million DALYs in 2019.From 1990 to 2019,the estimated annual percentage change of incidence of anxiety disorders decreased by 2.2%.Significant variations were observed in the age-standardised burden rate and the changing trend of anxiety disorders among countries.Portugal reported the highest ASIR of anxiety disorders,while Mexico had the largest increase rate of ASIR.In 2019,Portugal reported the highest number of DALYs(1001.71 million),and India(212.09 million)reported the lowest number of DALYs.The burden of anxiety disorders was positively correlated with the average number of psychiatrists,psychologists and nurses in the mental health sector(per 100000),and quality of life and the correlation coefficients were 0.58,0.67,0.43 and 0.53,respectively.Conclusions The incidence and global burden of anxiety disorders in adolescents have continued to decrease over the past 30 years.However,the incidence and disease burden in developed countries are still increasing steadily.Policymakers should design and implement mental health strategies for adolescents based on their specific developmental status,as well as the cultural and regional characteristics of each country.
