Clinical and experimental studies have highlighted the significance of inflammation in coordinating wound repair and regeneration.However,it remains challenging to control the inflammatory response and tolerance at sy...Clinical and experimental studies have highlighted the significance of inflammation in coordinating wound repair and regeneration.However,it remains challenging to control the inflammatory response and tolerance at systemic levels without causing toxicity to injured tissues.Mesenchymal stem cells(MSCs) possess potent immunomodulatory properties and facilitate tissue repair by releasing exosomes,which generate a suitable microenvironment for inflammatory resolution.Exosomes contain several effective bioactive molecules and act as a cell-cell communication vehicle to influence cellular activities in recipient cells.During this process,the horizontal transfer of exosomal microRNAs(miRNAs) to acceptor cells,where they regulate target gene expression,is of particular interest for understanding the basic biology of inflammation ablation,tissue homeostasis,and development of therapeutic approaches.In this review,we describe a signature of three specific miRNAs(miR-21,miR-146 a,and miR-181) present in human umbilical cord MSC-derived exosomes(MSC-EXO) identified microarray chip analysis and focus on the inflammatory regulatory functions of these immune-related miRNAs.We also discuss the potential mechanisms contributing to the resolution of wound inflammation and tissue healing.展开更多
Background and purpose The ideal stroke classification system needs to have validity,high reliability and applicability among different stroke research settings.The Chinese Ischemic Stroke Subclassification(CISS)and t...Background and purpose The ideal stroke classification system needs to have validity,high reliability and applicability among different stroke research settings.The Chinese Ischemic Stroke Subclassification(CISS)and the Subtypes of Ischemic Stroke Classification System(SPARKLE)have emerged recently but have not been tested using agreement analysis.As a result,the objective of this study is to investigate the level of agreement among stroke subtype classifications using CISS,SPARKLE and Trial of Org 10172 in Acute Stroke Treatment(TOAST).We also analyse the inter-rater reliability of CISS.Methods The data include 623 inpatients who have had an ischaemic stroke,accrued from Beijing Tiantan Hospital between 1 October 2015 and 19 April 2016.According to the diagnostic standards of the three subtype classification systems,299 inpatients who satisfied the requirements of our study were independently classified with etiological subtypes,and we compared the three subclassifications.Results There was substantial overall agreement among the three classification systems:CISS versus SPARKLE(kappa value=0.684,p<0.001),CISS versus TOAST(kappa value=0.615,p<0.001)and SPARKLE versus TOAST(kappa value=0.675,p<0.001).The inter-rater reliability of CISS was excellent(kappa value=0.857,p<0.001).Furthermore,among the three subtype classification systems,the variance analysis results of the etiological subtypes were not uniform.Conclusion There were generally substantial agreements among three ischaemic stroke etiological classification systems.CISS is a valid and reliable classification system,with which different stroke research centres can apply and compare data.展开更多
Landslide identification is critical for risk assessment and mitigation.This paper proposes a novel machinelearning and deep-learning method to identify natural-terrain landslides using integrated geodatabases.First,l...Landslide identification is critical for risk assessment and mitigation.This paper proposes a novel machinelearning and deep-learning method to identify natural-terrain landslides using integrated geodatabases.First,landslide-related data are compiled,including topographic data,geological data and rainfall-related data.Then,three integrated geodatabases are established;namely,Recent Landslide Database(Rec LD),Relict Landslide Database(Rel LD)and Joint Landslide Database(JLD).After that,five machine learning and deep learning algorithms,including logistic regression(LR),support vector machine(SVM),random forest(RF),boosting methods and convolutional neural network(CNN),are utilized and evaluated on each database.A case study in Lantau,Hong Kong,is conducted to demonstrate the application of the proposed method.From the results of the case study,CNN achieves an identification accuracy of 92.5%on Rec LD,and outperforms other algorithms due to its strengths in feature extraction and multi dimensional data processing.Boosting methods come second in terms of accuracy,followed by RF,LR and SVM.By using machine learning and deep learning techniques,the proposed landslide identification method shows outstanding robustness and great potential in tackling the landslide identification problem.展开更多
Soil microorganisms play crucial roles in soil nutrient cycling,carbon sequestration,fertility maintenance and crop health and production.To date,the responses of microorganisms,such as microbial activity,diversity,co...Soil microorganisms play crucial roles in soil nutrient cycling,carbon sequestration,fertility maintenance and crop health and production.To date,the responses of microorganisms,such as microbial activity,diversity,community structure and nutrient cycling processes,to biochar addition have been widely reported.However,the relationships between soil microbial groups(bacteria,fungi and microscopic fauna)and biochar physicochemical properties have not been summarized.In this review,we conclude that biochar affects soil microbial growth,diversity and community compositions by directly provid-ing growth promoters for soil biota or indirectly changing soil basic properties.The porous structure,labile C,high pH and electrochemical properties of biochar play an important role in determining soil microbial abundance and communities,and their mediated N and P cycling processes,while the effects and underlying mechanisms vary with biochar types that are affected by pyrolysis temperature and feedstock type.Finally,we highlight some issues related to research methodology and subjects that are still poorly understood or controversial,and the perspectives for further research in microbial responses to biochar addition.展开更多
Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies...Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.展开更多
Skin,the largest organ in the human body,is sensitive to external stimuli.In recent years,an increasing number of skin-inspired electronics,including wearable electronics,implantable electronics,and electronic skin,ha...Skin,the largest organ in the human body,is sensitive to external stimuli.In recent years,an increasing number of skin-inspired electronics,including wearable electronics,implantable electronics,and electronic skin,have been developed because of their broad applications in healthcare and robotics.Physical sensors are one of the key building blocks of skin-inspired electronics.Typical physical sensors include mechanical sensors,temperature sensors,humidity sensors,electrophysiological sensors,and so on.In this review,we systematically review the latest advances of skin-inspired mechanical sensors,temperature sensors,and humidity sensors.The working mechanisms,key materials,device structures,and performance of various physical sensors are summarized and discussed in detail.Their applications in health monitoring,human disease diagnosis and treatment,and intelligent robots are reviewed.In addition,several novel properties of skin-inspired physical sensors such as versatility,self-healability,and implantability are introduced.Finally,the existing challenges and future perspectives of physical sensors for practical applications are discussed and proposed.展开更多
The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) ...The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored.We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment.Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled.Conventional echocardiographic measurements were obtained,and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%).Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified,and their changes with time were monitored in 14 FM patients.All patients had severely impaired cardiac function.Steep improvement in LVEF and GLS were observed within 6 days.Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal.In conclusion,FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days.The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.展开更多
MXene has shown distinctive advantages as anode materials of lithium-ion batteries. However, local surface chemistry, which was confirmed that can block ion transfer and limit redox reaction, has a significant effect ...MXene has shown distinctive advantages as anode materials of lithium-ion batteries. However, local surface chemistry, which was confirmed that can block ion transfer and limit redox reaction, has a significant effect on electrochemical performance. Herein, annealing MXene under hydrogen was employed for removing-F and turning-OH to-O terminations. We demonstrate that it improves the kinetics of Li-ion transport between the electrolyte and electrode. As a result, a lower interfacial charge transfer impedance was obtained. The electrochemical measurement exhibited that a nearly 2-fold increase of specific capacity was achieved for the annealed MXene.展开更多
Microwave has been widely used in many fields,including communication,medical treatment and military industry;however,the corresponding generated radiations have been novel hazardous sources of pollution threating hu...Microwave has been widely used in many fields,including communication,medical treatment and military industry;however,the corresponding generated radiations have been novel hazardous sources of pollution threating human’s daily life.Therefore,designing high-performance microwave absorption materials(MAMs)has become an indispensable requirement.Recently,metal-organic frameworks(MOFs)have been considered as one of the most ideal precursor candidates of MAMs because of their tunable structure,high porosity and large specific surface area.Usually,MOF-derived MAMs exhibit excellent electrical conductivity,good magnetism and sufficient defects and interfaces,providing obvious merits in both impedance matching and microwave loss.In this review,the recent research progresses on MOF-derived MAMs were profoundly reviewed,including the categories of MOFs and MOF composites precursors,design principles,preparation methods and the relationship between mechanisms of microwave absorption and microstructures of MAMs.Finally,the current challenges and prospects for future opportunities of MOF-derived MAMs are also discussed.展开更多
Hybrid perovskite possesses excellent photoelectric properties,including large light-absorption capacity and high carrier mobility,and is an ideal light-absorbing material for photoelectric devices.The grain size and ...Hybrid perovskite possesses excellent photoelectric properties,including large light-absorption capacity and high carrier mobility,and is an ideal light-absorbing material for photoelectric devices.The grain size and compactness of hybrid perovskite are key factors affecting the performance of photoelectric devices.The photocurrent and photoresponsivity of these devices are relatively low because of the rapidly recombined photoexcited electron-hole pairs in hybrid perovskite.Herein,we develop a facile two-step chemical vapor deposition(CVD)method to synthesize a high-quality van der Waals(vd Ws)MAPb I3/graphene heterostructure for high-performance image sensor.We introduced inorganic sources(PbI2)to vd Ws epitaxially grown Pb I2 film on a seamless graphene monolayer film template through CVD.Methylammonium iodide(MAI)was then reintroduced to prepare the vd Ws MAPb I3/graphene heterostructure.The MAPb I3 layer is composed of densely packed,large-size grains and displays a smooth surface.High photoresponsivity of 107A/W is achieved in the corresponding photodetector.Inspired by the human visual system,we designed a flexible photodetector array containing(24?24)pixels,achieving perfect image recognition and color discrimination.Our study may greatly facilitate the construction of high-performance optoelectronic devices in artificial retina,biomedical imaging,remote sensing,and optical communication.展开更多
Compared with the traditional atm ospheric carburization, low-pressure carburization has the benefits of producing no surface oxidation and leaving fine, uniformly dispersed carbides in the carburized layer. However, ...Compared with the traditional atm ospheric carburization, low-pressure carburization has the benefits of producing no surface oxidation and leaving fine, uniformly dispersed carbides in the carburized layer. However, the process param eters for low-pressure carburization of 16Cr3NiWMoVNbE steel have yet to be optimized. Thus, we use the saturation-value method to optimize these parameters for aviation-gear materials. Toward this end, the m icrostructure and properties of 16Cr3NiWMoVNbE steel after different carburization processes are studied by optical microscopy, scanning electron microscopy, transm ission electron microscopy, and electron probe microanalysis. Considering the saturated austenite carbon concentration, we propose a model of carbon flux and an alloy coefficient for low -pressure carburization to reduce the carbon concentration in austenite and avoid the surface carbide network. At the early stage of carburization (30 s), the gas-solid interface has a higher concentration gradient. The averaging method is not ideal in practical applications, but the carbon flux measured by using the segm ented average m ethod is 2.5 times that measured by the overall average method, which is ideal in practical applications. The corresponding carburization tim e is reduced by 60%. By using the integral average method, the actual carburization time increases, which leads to the rapid form ation of carbide on the surface and affects the entire carburization process. Nb and Wcombine with C to form carbides, which hinders carbon diffusion and consumes carbon, resulting in a sharp decrease in the rate of C diffusion in austenite (the diffusion rate is reduced by 52% for 16Cr3NiWMoVNbE steel). By changing the diffusion coefficient model and comparing the hardness gradient of different processes, the depth of the actual layer is found to be very similar to the design depth.展开更多
Dear Editor, Schisandra chinensis （Turcz.） Baill. belongs to family Schisandraceae. Its fruit called ＂Wu Wei Zi＂ in Chinese is a well-known medicinal material, which is used to treat chronic cough and dyspnea, noc...Dear Editor, Schisandra chinensis （Turcz.） Baill. belongs to family Schisandraceae. Its fruit called ＂Wu Wei Zi＂ in Chinese is a well-known medicinal material, which is used to treat chronic cough and dyspnea, nocturnal emission, enuresis, etc. （National Pharmacopoeia Committee, 2015）. Except for S. chinensis, many species of Schisandraceae, such as S. sphenanthera, S. lancifolia and S. rubriflora, are used as the original olants of folk medicines.展开更多
With the rapid development in advanced industries,such as microelectronics and optics sectors,the functional feature size of devises/components has been decreasing from micro to nanometric,and even ACS for higher perf...With the rapid development in advanced industries,such as microelectronics and optics sectors,the functional feature size of devises/components has been decreasing from micro to nanometric,and even ACS for higher performance,smaller volume and lower energy consumption.By this time,a great many quantum structures are proposed,with not only an extreme scale of several or even single atom,but also a nearly ideal lattice structure with no material defect.It is almost no doubt that such structures play critical role in the next generation products,which shows an urgent demand for the ACSM.Laser machining is one of the most important approaches widely used in engineering and scientific research.It is high-efficient and applicable for most kinds of materials.Moreover,the processing scale covers a huge range from millimeters to nanometers,and has already touched the atomic level.Laser–material interaction mechanism,as the foundation of laser machining,determines the machining accuracy and surface quality.It becomes much more sophisticated and dominant with a decrease in processing scale,which is systematically reviewed in this article.In general,the mechanisms of laser-induced material removal are classified into ablation,CE and atomic desorption,with a decrease in the scale from above microns to angstroms.The effects of processing parameters on both fundamental material response and machined surface quality are discussed,as well as theoretical methods to simulate and understand the underlying mechanisms.Examples at nanometric to atomic scale are provided,which demonstrate the capability of laser machining in achieving the ultimate precision and becoming a promising approach to ACSM.展开更多
The formed characteristics of thin-wall part is studied when it is in the process of MPAW. Finite element method is used to sinmlate the temperature field coupling flow field in the welding of thin-wall part. It is fo...The formed characteristics of thin-wall part is studied when it is in the process of MPAW. Finite element method is used to sinmlate the temperature field coupling flow field in the welding of thin-wall part. It is found that because of the obvious effect of heat accumution in cross-section, where the distribution of temperature field area presents trapezoidal inverted approximately in the molten pool and the non-molten pool area presents level. The surface tension, the electromagnetic force and buoyancy are considered for analyzing the effects on the fluid flow of welding-pool. It can be obtained that the surface tension is the main driving force in the welding pool, which is far greater than electromagnetic force and buoyancy.展开更多
The rational construction of microstructure and composition with enhanced Maxwell-Wagner-Sillars effect(MWSE)is still a challenging direction for reinforcing electromagnetic wave(EMW)absorption performance,and the rel...The rational construction of microstructure and composition with enhanced Maxwell-Wagner-Sillars effect(MWSE)is still a challenging direction for reinforcing electromagnetic wave(EMW)absorption performance,and the related EMW attenuation mechanism has rarely been elucidated.Herein,MWSE boostedβ-chitin/carbon nano-onions/Ni–P composites is prepared according to the heterointerface engineering strategy via facile layer-by-layer electrostatic assembly and electroless plating techniques.The heterogeneous interface is reinforced from the aspect of porous skeleton,nanomaterials and multilayer construction.The composites exhibit competitive EMW response mechanism between the conductive loss and the polarization/magnetic loss,as describing like the story of“The Hare and the Tortoise”.As a result,the composites not only achieve a minimum reflection loss(RL_(min))of−50.83 dB and an effective bandwidth of 6.8 GHz,but also present remarkable EMW interference shielding effectiveness of 66.66 dB.In addition,diverse functions such as good thermal insulation,infrared shielding and photothermal performance were also achieved in the hybrid composites as a result of intrinsic morphology and chemicophysics properties.Therefore,we believe that the boosted MWSE open up a novel orientation toward developing multifunctional composites with high-efficient EMW response and thermal management.展开更多
Reliable assessment of uplift capacity of buried pipelines against upheaval buckling requires a valid failure mechanism and a reliable real-time monitoring technique.This paper presents a sensing solution for evaluati...Reliable assessment of uplift capacity of buried pipelines against upheaval buckling requires a valid failure mechanism and a reliable real-time monitoring technique.This paper presents a sensing solution for evaluating uplift capacity of pipelines buried in sand using fiber optic strain sensing(FOSS)nerves.Upward pipe-soil interaction(PSI)was investigated through a series of scaled tests,in which the FOSS and image analysis techniques were used to capture the failure patterns.The published prediction models were evaluated and modified according to observations in the present study as well as a database of 41 pipe loading tests assembled from the literature.Axial strain measurements of FOSS nerves horizontally installed above the pipeline were correlated with the failure behavior of the overlying soil.The test results indicate that the previous analytical models could be further improved regarding their estimations in the failure geometry and mobilization distance at the peak uplift resistance.For typical slip plane failure forms,inclined shear bands star from the pipe shoulder,instead of the springline,and have not yet reached the ground surface at the peak resistance.The vertical inclination of curved shear bands decreases with increasing uplift displacements at the post-peak periods.At large displacements,the upward movement is confined to the deeper ground,and the slip plane failure progressively changes to the flow-around.The feasibility of FOSS in pipe uplift resistance prediction was validated through the comparison with image analyses.In addition,the shear band locations can be identified using fiber optic strain measurements.Finally,the advantages and limits of the FOSS system are discussed in terms of different levels in upward PSI assessment,including failure identification,location,and quantification.展开更多
Secreted proteins are important sources for early detection and diagnosis of disease, and as such have received considerable attention. The extraction of low concentration proteins from large volumes of culture media,...Secreted proteins are important sources for early detection and diagnosis of disease, and as such have received considerable attention. The extraction of low concentration proteins from large volumes of culture media, which are rich in salts and other compounds that interfere with most proteomics techniques, presents a problem for secretome studies. Ultrafiltration, precipitation, and dialysis are three major extraction methods that can be used to overcome this problem. The present study for the first time, compared the merits and shortcomings of these three methods, without bias. Centrifugal ultrafiltration provided the best extraction efficiency, and precipitation provided the highest number of identifiable proteins. The three methods yielded closely related, but different, information on the secretome; thus, they should be considered complementary or, at least, supplementary methods. Three hundred and sixty unique proteins were identified, including 211 potential secreted proteins. Compared with previous studies, this study also identified 42 new secreted proteins. The present study not only offers a reference for the selection of secretome extraction methods, but also expands the secretome database for the investigation of hepatocellular carcinoma.展开更多
The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strat...The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs.In particular,third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition,exhibiting a perfect balance between anticancer efficacy and general toxicity.To date,three selective CDK4/6 inhibitors have received approval from the U.S.Food and Drug Administration(FDA),and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers.In this perspective,we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells,analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment,review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds,explain the mechanisms associated with CDK4/6inhibitor resistance and describe solutions to overcome this issue,and briefly introduce proteolysis targeting chimera(PROTAC),a new and revolutionary technique used to degrade CDK4/6.展开更多
OBJECTIVE： To assess the efficacy and safety of Re- duning injection for fever, rash, and ulcers in chil- dren with mild hand, foot, and mouth disease （HFMD）. METHODS： A stratified-block randomized, dou- ble-blind...OBJECTIVE： To assess the efficacy and safety of Re- duning injection for fever, rash, and ulcers in chil- dren with mild hand, foot, and mouth disease （HFMD）. METHODS： A stratified-block randomized, dou- ble-blind, parallel-controlled, and multicenter clini- cal trial was conducted with 360 patients in five hospitals across China： Quanzhou Children＇s Hospi- tal, Shijiazhuang No. 5 Hospital, Shanghai Public Health Centre, Hunan Provincial Children＇s Hospi- tal, and Kaifeng Children＇s Hospital. Patients were randomized into three groups with 120 in each. Group A was treated with Western Medicine, group B with Reduning injection, a Chinese herbal medi- cine, and group C with both Reduning injection and Western Medicine. Results were compared for treatment efficacy and safety on HFMD. The clinical outcomes were observed as follows： fever and on- set time of antifebrile effect （time to bring the body temperature down 〉0.5~C after medication）; cumu- lative time for fever recovery （body temperature re- covering to normal and lasting more than 24 h without medication）; cumulative time for rash dis- appearance （without new rashes or ulcers appear- ing and the original ones fading away）; and cumula- tive time for mouth ulcer disappearance. RESULTS： For the onset time of the antifebrile ef- fect, there was no statistical difference between groups A and B （P〉O.05） and groups B and C （P〉 0.05）. However, there was a statistical difference be- tween groups A and C （P〈0.05）, and the effect ingroup C was the best. For the cumulative time for rash disappearance, there was no statistical differ- ence between groups A and B （P〉0.05）. There were statistical differences between groups A and C, and groups B and C （P〈0.05）, and the effect in group C was the best. For the cumulative time for mouth ul- cers disappearance, there were no statistical differ- ences among the three groups （P〉0.05）. CONCLUSION： Reduning injection with Western Medicine for symptomatic treatm展开更多
Prostate cancer(PCa)affects millions of men globally.Due to advances in understanding genomic landscapes and biological functions,the treatment of PCa continues to improve.Recently,various new classes of agents,which ...Prostate cancer(PCa)affects millions of men globally.Due to advances in understanding genomic landscapes and biological functions,the treatment of PCa continues to improve.Recently,various new classes of agents,which include next-generation androgen receptor(AR)signaling inhibitors(abiraterone,enzalutamide,apalutamide,and darolutamide),bone-targeting agents(radium-223 chloride,zoledronic acid),and poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib,rucaparib,and talazoparib)have been developed to treat PCa.Agents targeting other signaling pathways,including cyclin-dependent kinase(CDK)4/6,Ak strain transforming(AKT),wingless-type protein(WNT),and epigenetic marks,have successively entered clinical trials.Furthermore,prostate-specific membrane antigen(PSMA)targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy.Advanced clinical studies with immune checkpoint inhibitors(ICIs)have shown limited benefits in PCa,whereas subgroups of PCa with mismatch repair(MMR)or CDK12 inactivation may benefit from ICIs treatment.In this review,we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms,and further discussed their limitations and future directions.展开更多
基金supported by the National Basic Science and Development Program(2012CB518103,2012CB518105)National High Technology Research and Development Program of China (2013AA020105,2012AA020502)National Natural Science Foundation of China(81121004,81501682,81230041)
文摘Clinical and experimental studies have highlighted the significance of inflammation in coordinating wound repair and regeneration.However,it remains challenging to control the inflammatory response and tolerance at systemic levels without causing toxicity to injured tissues.Mesenchymal stem cells(MSCs) possess potent immunomodulatory properties and facilitate tissue repair by releasing exosomes,which generate a suitable microenvironment for inflammatory resolution.Exosomes contain several effective bioactive molecules and act as a cell-cell communication vehicle to influence cellular activities in recipient cells.During this process,the horizontal transfer of exosomal microRNAs(miRNAs) to acceptor cells,where they regulate target gene expression,is of particular interest for understanding the basic biology of inflammation ablation,tissue homeostasis,and development of therapeutic approaches.In this review,we describe a signature of three specific miRNAs(miR-21,miR-146 a,and miR-181) present in human umbilical cord MSC-derived exosomes(MSC-EXO) identified microarray chip analysis and focus on the inflammatory regulatory functions of these immune-related miRNAs.We also discuss the potential mechanisms contributing to the resolution of wound inflammation and tissue healing.
文摘Background and purpose The ideal stroke classification system needs to have validity,high reliability and applicability among different stroke research settings.The Chinese Ischemic Stroke Subclassification(CISS)and the Subtypes of Ischemic Stroke Classification System(SPARKLE)have emerged recently but have not been tested using agreement analysis.As a result,the objective of this study is to investigate the level of agreement among stroke subtype classifications using CISS,SPARKLE and Trial of Org 10172 in Acute Stroke Treatment(TOAST).We also analyse the inter-rater reliability of CISS.Methods The data include 623 inpatients who have had an ischaemic stroke,accrued from Beijing Tiantan Hospital between 1 October 2015 and 19 April 2016.According to the diagnostic standards of the three subtype classification systems,299 inpatients who satisfied the requirements of our study were independently classified with etiological subtypes,and we compared the three subclassifications.Results There was substantial overall agreement among the three classification systems:CISS versus SPARKLE(kappa value=0.684,p<0.001),CISS versus TOAST(kappa value=0.615,p<0.001)and SPARKLE versus TOAST(kappa value=0.675,p<0.001).The inter-rater reliability of CISS was excellent(kappa value=0.857,p<0.001).Furthermore,among the three subtype classification systems,the variance analysis results of the etiological subtypes were not uniform.Conclusion There were generally substantial agreements among three ischaemic stroke etiological classification systems.CISS is a valid and reliable classification system,with which different stroke research centres can apply and compare data.
基金supported by the Research Grants Council of the Hong Kong SAR Government(Nos.16205719,AoE/E-603/18 and 16206217)。
文摘Landslide identification is critical for risk assessment and mitigation.This paper proposes a novel machinelearning and deep-learning method to identify natural-terrain landslides using integrated geodatabases.First,landslide-related data are compiled,including topographic data,geological data and rainfall-related data.Then,three integrated geodatabases are established;namely,Recent Landslide Database(Rec LD),Relict Landslide Database(Rel LD)and Joint Landslide Database(JLD).After that,five machine learning and deep learning algorithms,including logistic regression(LR),support vector machine(SVM),random forest(RF),boosting methods and convolutional neural network(CNN),are utilized and evaluated on each database.A case study in Lantau,Hong Kong,is conducted to demonstrate the application of the proposed method.From the results of the case study,CNN achieves an identification accuracy of 92.5%on Rec LD,and outperforms other algorithms due to its strengths in feature extraction and multi dimensional data processing.Boosting methods come second in terms of accuracy,followed by RF,LR and SVM.By using machine learning and deep learning techniques,the proposed landslide identification method shows outstanding robustness and great potential in tackling the landslide identification problem.
基金This study was supported by the National Science Foundation of China(41520104001,41807033)the Young Elite Scientists Sponsorship Program by CAST(2018QNRC001)+1 种基金the Serving Local Economic Development Project of Shandong(Linyi)Institute of Modern Agriculture,Zhejiang University(ZDNY-2020-FWLY01006)the Fundamental Research Funds for the Central Universities in China.
文摘Soil microorganisms play crucial roles in soil nutrient cycling,carbon sequestration,fertility maintenance and crop health and production.To date,the responses of microorganisms,such as microbial activity,diversity,community structure and nutrient cycling processes,to biochar addition have been widely reported.However,the relationships between soil microbial groups(bacteria,fungi and microscopic fauna)and biochar physicochemical properties have not been summarized.In this review,we conclude that biochar affects soil microbial growth,diversity and community compositions by directly provid-ing growth promoters for soil biota or indirectly changing soil basic properties.The porous structure,labile C,high pH and electrochemical properties of biochar play an important role in determining soil microbial abundance and communities,and their mediated N and P cycling processes,while the effects and underlying mechanisms vary with biochar types that are affected by pyrolysis temperature and feedstock type.Finally,we highlight some issues related to research methodology and subjects that are still poorly understood or controversial,and the perspectives for further research in microbial responses to biochar addition.
基金supported by National Natural Science Foundation of China(Nos.81872877,81730100,91853109,82073975)School of Life Science(NJU)-Sipimo Joint Funds,Characteristic Innovation Project of Guangdong Provincial Education Department(Nos.2019GKTSCX039,2020KTSCX295,China),School-Level Scientific Research Project of Shenzhen Polytechnic(No.6021310023K,China)+1 种基金Natural Science Research of Jiangsu Higher Education Institutions of China(No.22KJB360005)Fundamental Research Funds for the Central Universities(No.020814380174,China).
文摘Natural products, and especially the active ingredients found in traditional Chinese medicine(TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such,traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and singlecell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.
基金National Key Basic Research and Development Program,Grant/Award Number:2016YFA0200103National Natural Science Foundation of China,Grant/Award Numbers:21975141,51672153National Program for Support of Top-notch Young Professionals,Grant/Award Number:N/A。
文摘Skin,the largest organ in the human body,is sensitive to external stimuli.In recent years,an increasing number of skin-inspired electronics,including wearable electronics,implantable electronics,and electronic skin,have been developed because of their broad applications in healthcare and robotics.Physical sensors are one of the key building blocks of skin-inspired electronics.Typical physical sensors include mechanical sensors,temperature sensors,humidity sensors,electrophysiological sensors,and so on.In this review,we systematically review the latest advances of skin-inspired mechanical sensors,temperature sensors,and humidity sensors.The working mechanisms,key materials,device structures,and performance of various physical sensors are summarized and discussed in detail.Their applications in health monitoring,human disease diagnosis and treatment,and intelligent robots are reviewed.In addition,several novel properties of skin-inspired physical sensors such as versatility,self-healability,and implantability are introduced.Finally,the existing challenges and future perspectives of physical sensors for practical applications are discussed and proposed.
基金The project was supported by the grant from the National Natural Science Foundation of China(Nos.81873535 and 81570367)We thank Dr.Jonathan R.Linder who gave us helpful suggestions in writing the manuscript.
文摘The features of myocardial strains from speckle-tracking echocardiography (STE) have not been well defined in fulminant myocarditis (FM) patients.In this study,changes in the left ventricular ejection fraction (LVEF) and global and layer-specific myocardial strains over time were monitored.We aimed to determine the echocardiographic patterns of FM and ascertain their significance in FM treatment.Twenty patients who were clinically diagnosed with FM and received mechanical life support were prospectively enrolled.Conventional echocardiographic measurements were obtained,and serial strain echocardiography was performed from admission to hospital discharge until LVEF recovery (> 50%).Global/regional peak systolic longitudinal strains (GLS/RLS) and layer-specific longitudinal strains were quantified,and their changes with time were monitored in 14 FM patients.All patients had severely impaired cardiac function.Steep improvement in LVEF and GLS were observed within 6 days.Layer-specific strain analysis showed that reduction at admission or recovery at discharge in the endocardium and epicardium strains were equal.In conclusion,FM patients who received mechanical circulatory supports exhibited steep improvement in ventricular function within 6 days.The patchy and diffused distribution pattern of reduced RLS and equally and severely impaired strain in the endocardium and epicardium are valuable features in the diagnosis of FM.
基金financial support provided by the National Key R&D Program of China (2016YFA0200400)the Jilin Province/Jilin University co-Construction Project-Funds for New Materials (SXGJSF2017-3, Branch-2/440050316A36)+4 种基金the National Natural Science Foundation of China (Grant nos. 91545119, 21761132025, 21773269 and 51372095)the Youth Innovation Promotion Association CAS (Grant no. 2015152)Strategic Priority Research Program of the Chinese Academy of Sciences Chinese Academy of Sciences (Grant nos. XDA09030103 and XDA09040203)the Program for JLU Science and Technology Innovative Research Team (JLUSTIRT)"Double-First Class" Discipline for Materials Science & Engineering
文摘MXene has shown distinctive advantages as anode materials of lithium-ion batteries. However, local surface chemistry, which was confirmed that can block ion transfer and limit redox reaction, has a significant effect on electrochemical performance. Herein, annealing MXene under hydrogen was employed for removing-F and turning-OH to-O terminations. We demonstrate that it improves the kinetics of Li-ion transport between the electrolyte and electrode. As a result, a lower interfacial charge transfer impedance was obtained. The electrochemical measurement exhibited that a nearly 2-fold increase of specific capacity was achieved for the annealed MXene.
基金Open access funding provided by Shanghai Jiao Tong University.
文摘Microwave has been widely used in many fields,including communication,medical treatment and military industry;however,the corresponding generated radiations have been novel hazardous sources of pollution threating human’s daily life.Therefore,designing high-performance microwave absorption materials(MAMs)has become an indispensable requirement.Recently,metal-organic frameworks(MOFs)have been considered as one of the most ideal precursor candidates of MAMs because of their tunable structure,high porosity and large specific surface area.Usually,MOF-derived MAMs exhibit excellent electrical conductivity,good magnetism and sufficient defects and interfaces,providing obvious merits in both impedance matching and microwave loss.In this review,the recent research progresses on MOF-derived MAMs were profoundly reviewed,including the categories of MOFs and MOF composites precursors,design principles,preparation methods and the relationship between mechanisms of microwave absorption and microstructures of MAMs.Finally,the current challenges and prospects for future opportunities of MOF-derived MAMs are also discussed.
基金supported by the Ministry of Science and Technology of China(2016YFA0200103)the National Natural Science Foundation of China(51672153,21975141)the National Program for Support of Top-notch Young Professionals.
文摘Hybrid perovskite possesses excellent photoelectric properties,including large light-absorption capacity and high carrier mobility,and is an ideal light-absorbing material for photoelectric devices.The grain size and compactness of hybrid perovskite are key factors affecting the performance of photoelectric devices.The photocurrent and photoresponsivity of these devices are relatively low because of the rapidly recombined photoexcited electron-hole pairs in hybrid perovskite.Herein,we develop a facile two-step chemical vapor deposition(CVD)method to synthesize a high-quality van der Waals(vd Ws)MAPb I3/graphene heterostructure for high-performance image sensor.We introduced inorganic sources(PbI2)to vd Ws epitaxially grown Pb I2 film on a seamless graphene monolayer film template through CVD.Methylammonium iodide(MAI)was then reintroduced to prepare the vd Ws MAPb I3/graphene heterostructure.The MAPb I3 layer is composed of densely packed,large-size grains and displays a smooth surface.High photoresponsivity of 107A/W is achieved in the corresponding photodetector.Inspired by the human visual system,we designed a flexible photodetector array containing(24?24)pixels,achieving perfect image recognition and color discrimination.Our study may greatly facilitate the construction of high-performance optoelectronic devices in artificial retina,biomedical imaging,remote sensing,and optical communication.
基金financially supported by the National Key R&D Program of China (Grant No. 2016YFB0300600)the National Natural Science Foundation of China (Grant No. 51604074)
文摘Compared with the traditional atm ospheric carburization, low-pressure carburization has the benefits of producing no surface oxidation and leaving fine, uniformly dispersed carbides in the carburized layer. However, the process param eters for low-pressure carburization of 16Cr3NiWMoVNbE steel have yet to be optimized. Thus, we use the saturation-value method to optimize these parameters for aviation-gear materials. Toward this end, the m icrostructure and properties of 16Cr3NiWMoVNbE steel after different carburization processes are studied by optical microscopy, scanning electron microscopy, transm ission electron microscopy, and electron probe microanalysis. Considering the saturated austenite carbon concentration, we propose a model of carbon flux and an alloy coefficient for low -pressure carburization to reduce the carbon concentration in austenite and avoid the surface carbide network. At the early stage of carburization (30 s), the gas-solid interface has a higher concentration gradient. The averaging method is not ideal in practical applications, but the carbon flux measured by using the segm ented average m ethod is 2.5 times that measured by the overall average method, which is ideal in practical applications. The corresponding carburization tim e is reduced by 60%. By using the integral average method, the actual carburization time increases, which leads to the rapid form ation of carbide on the surface and affects the entire carburization process. Nb and Wcombine with C to form carbides, which hinders carbon diffusion and consumes carbon, resulting in a sharp decrease in the rate of C diffusion in austenite (the diffusion rate is reduced by 52% for 16Cr3NiWMoVNbE steel). By changing the diffusion coefficient model and comparing the hardness gradient of different processes, the depth of the actual layer is found to be very similar to the design depth.
基金supported by the National Natural Science Foundation of China (813 73913)CAMS Initiative for Innovative Medicine (CAMS-I2M-1-010)
文摘Dear Editor, Schisandra chinensis （Turcz.） Baill. belongs to family Schisandraceae. Its fruit called ＂Wu Wei Zi＂ in Chinese is a well-known medicinal material, which is used to treat chronic cough and dyspnea, nocturnal emission, enuresis, etc. （National Pharmacopoeia Committee, 2015）. Except for S. chinensis, many species of Schisandraceae, such as S. sphenanthera, S. lancifolia and S. rubriflora, are used as the original olants of folk medicines.
基金supported by the National Natural Science Foundation of China(Nos.52035009,52105475).
文摘With the rapid development in advanced industries,such as microelectronics and optics sectors,the functional feature size of devises/components has been decreasing from micro to nanometric,and even ACS for higher performance,smaller volume and lower energy consumption.By this time,a great many quantum structures are proposed,with not only an extreme scale of several or even single atom,but also a nearly ideal lattice structure with no material defect.It is almost no doubt that such structures play critical role in the next generation products,which shows an urgent demand for the ACSM.Laser machining is one of the most important approaches widely used in engineering and scientific research.It is high-efficient and applicable for most kinds of materials.Moreover,the processing scale covers a huge range from millimeters to nanometers,and has already touched the atomic level.Laser–material interaction mechanism,as the foundation of laser machining,determines the machining accuracy and surface quality.It becomes much more sophisticated and dominant with a decrease in processing scale,which is systematically reviewed in this article.In general,the mechanisms of laser-induced material removal are classified into ablation,CE and atomic desorption,with a decrease in the scale from above microns to angstroms.The effects of processing parameters on both fundamental material response and machined surface quality are discussed,as well as theoretical methods to simulate and understand the underlying mechanisms.Examples at nanometric to atomic scale are provided,which demonstrate the capability of laser machining in achieving the ultimate precision and becoming a promising approach to ACSM.
基金supported by the National Natural Science Foundation of China(Grant No.U1333128,U1733125)Science and Technology Project of Tianjin(Grant No.14ZCDZGX00802,17JCZDJC38700)
文摘The formed characteristics of thin-wall part is studied when it is in the process of MPAW. Finite element method is used to sinmlate the temperature field coupling flow field in the welding of thin-wall part. It is found that because of the obvious effect of heat accumution in cross-section, where the distribution of temperature field area presents trapezoidal inverted approximately in the molten pool and the non-molten pool area presents level. The surface tension, the electromagnetic force and buoyancy are considered for analyzing the effects on the fluid flow of welding-pool. It can be obtained that the surface tension is the main driving force in the welding pool, which is far greater than electromagnetic force and buoyancy.
基金This work was supported by the National Key Research and Development Program of China(Grant No.2019YFE0122900)the National Natural Science Foundation of China(No 51971162,U1933112,51671146)+1 种基金China Postdoctoral Science Foundation(Grant No.2020M671208)Open access funding provided by Shanghai Jiao Tong University
文摘The rational construction of microstructure and composition with enhanced Maxwell-Wagner-Sillars effect(MWSE)is still a challenging direction for reinforcing electromagnetic wave(EMW)absorption performance,and the related EMW attenuation mechanism has rarely been elucidated.Herein,MWSE boostedβ-chitin/carbon nano-onions/Ni–P composites is prepared according to the heterointerface engineering strategy via facile layer-by-layer electrostatic assembly and electroless plating techniques.The heterogeneous interface is reinforced from the aspect of porous skeleton,nanomaterials and multilayer construction.The composites exhibit competitive EMW response mechanism between the conductive loss and the polarization/magnetic loss,as describing like the story of“The Hare and the Tortoise”.As a result,the composites not only achieve a minimum reflection loss(RL_(min))of−50.83 dB and an effective bandwidth of 6.8 GHz,but also present remarkable EMW interference shielding effectiveness of 66.66 dB.In addition,diverse functions such as good thermal insulation,infrared shielding and photothermal performance were also achieved in the hybrid composites as a result of intrinsic morphology and chemicophysics properties.Therefore,we believe that the boosted MWSE open up a novel orientation toward developing multifunctional composites with high-efficient EMW response and thermal management.
基金support provided by the National Natural Science Foundation of China(Grant No.42077235)the Science and Technology Plan Project of Xuzhou,China(Grant No.KC21310)the Open Fund of the State Key Laboratory for Geomechanics and Deep Underground Engineering(Grant No.SKLGDUEK 1902).
文摘Reliable assessment of uplift capacity of buried pipelines against upheaval buckling requires a valid failure mechanism and a reliable real-time monitoring technique.This paper presents a sensing solution for evaluating uplift capacity of pipelines buried in sand using fiber optic strain sensing(FOSS)nerves.Upward pipe-soil interaction(PSI)was investigated through a series of scaled tests,in which the FOSS and image analysis techniques were used to capture the failure patterns.The published prediction models were evaluated and modified according to observations in the present study as well as a database of 41 pipe loading tests assembled from the literature.Axial strain measurements of FOSS nerves horizontally installed above the pipeline were correlated with the failure behavior of the overlying soil.The test results indicate that the previous analytical models could be further improved regarding their estimations in the failure geometry and mobilization distance at the peak uplift resistance.For typical slip plane failure forms,inclined shear bands star from the pipe shoulder,instead of the springline,and have not yet reached the ground surface at the peak resistance.The vertical inclination of curved shear bands decreases with increasing uplift displacements at the post-peak periods.At large displacements,the upward movement is confined to the deeper ground,and the slip plane failure progressively changes to the flow-around.The feasibility of FOSS in pipe uplift resistance prediction was validated through the comparison with image analyses.In addition,the shear band locations can be identified using fiber optic strain measurements.Finally,the advantages and limits of the FOSS system are discussed in terms of different levels in upward PSI assessment,including failure identification,location,and quantification.
基金supported by the National Natural Science Foundation of China (Grant No. 209750240)the National Basic Research Program of China (Grant No. 2010CB912700)
文摘Secreted proteins are important sources for early detection and diagnosis of disease, and as such have received considerable attention. The extraction of low concentration proteins from large volumes of culture media, which are rich in salts and other compounds that interfere with most proteomics techniques, presents a problem for secretome studies. Ultrafiltration, precipitation, and dialysis are three major extraction methods that can be used to overcome this problem. The present study for the first time, compared the merits and shortcomings of these three methods, without bias. Centrifugal ultrafiltration provided the best extraction efficiency, and precipitation provided the highest number of identifiable proteins. The three methods yielded closely related, but different, information on the secretome; thus, they should be considered complementary or, at least, supplementary methods. Three hundred and sixty unique proteins were identified, including 211 potential secreted proteins. Compared with previous studies, this study also identified 42 new secreted proteins. The present study not only offers a reference for the selection of secretome extraction methods, but also expands the secretome database for the investigation of hepatocellular carcinoma.
基金supported by the Project Program of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZRC07,China)111 Project(B16046,China)+2 种基金“Double First-Class”University Project(CPU2018GF04,China)Jiangsu Key Laboratory of Drug Design and Optimization(DDORC201801,China)65th China Postdoctoral Science Foundation(2019M652030)
文摘The sustained cell proliferation resulting from dysregulation of the cell cycle and activation of cyclin-dependent kinases(CDKs)is a hallmark of cancer.The inhibition of CDKs is a highly promising and attractive strategy for the development of anticancer drugs.In particular,third-generation CDK inhibitors can selectively inhibit CDK4/6 and regulate the cell cycle by suppressing the G1 to S phase transition,exhibiting a perfect balance between anticancer efficacy and general toxicity.To date,three selective CDK4/6 inhibitors have received approval from the U.S.Food and Drug Administration(FDA),and 15 CDK4/6 inhibitors are in clinical trials for the treatment of cancers.In this perspective,we discuss the crucial roles of CDK4/6 in regulating the cell cycle and cancer cells,analyze the rationale for selectively inhibiting CDK4/6 for cancer treatment,review the latest advances in highly selective CDK4/6 inhibitors with different chemical scaffolds,explain the mechanisms associated with CDK4/6inhibitor resistance and describe solutions to overcome this issue,and briefly introduce proteolysis targeting chimera(PROTAC),a new and revolutionary technique used to degrade CDK4/6.
基金Supported by Grants from the Special Planning Project of the State Administration of Traditional Medicine in 2009(200907001-3)
文摘OBJECTIVE： To assess the efficacy and safety of Re- duning injection for fever, rash, and ulcers in chil- dren with mild hand, foot, and mouth disease （HFMD）. METHODS： A stratified-block randomized, dou- ble-blind, parallel-controlled, and multicenter clini- cal trial was conducted with 360 patients in five hospitals across China： Quanzhou Children＇s Hospi- tal, Shijiazhuang No. 5 Hospital, Shanghai Public Health Centre, Hunan Provincial Children＇s Hospi- tal, and Kaifeng Children＇s Hospital. Patients were randomized into three groups with 120 in each. Group A was treated with Western Medicine, group B with Reduning injection, a Chinese herbal medi- cine, and group C with both Reduning injection and Western Medicine. Results were compared for treatment efficacy and safety on HFMD. The clinical outcomes were observed as follows： fever and on- set time of antifebrile effect （time to bring the body temperature down 〉0.5~C after medication）; cumu- lative time for fever recovery （body temperature re- covering to normal and lasting more than 24 h without medication）; cumulative time for rash dis- appearance （without new rashes or ulcers appear- ing and the original ones fading away）; and cumula- tive time for mouth ulcer disappearance. RESULTS： For the onset time of the antifebrile ef- fect, there was no statistical difference between groups A and B （P〉O.05） and groups B and C （P〉 0.05）. However, there was a statistical difference be- tween groups A and C （P〈0.05）, and the effect ingroup C was the best. For the cumulative time for rash disappearance, there was no statistical differ- ence between groups A and B （P〉0.05）. There were statistical differences between groups A and C, and groups B and C （P〈0.05）, and the effect in group C was the best. For the cumulative time for mouth ul- cers disappearance, there were no statistical differ- ences among the three groups （P〉0.05）. CONCLUSION： Reduning injection with Western Medicine for symptomatic treatm
基金supported by grants from the Science and Technology Commission of Shanghai Municipality(18410750200 to R.S.)National Natural Science Foundation of China(82125025 to R.S.,81872105 to R.S.)National Major R&D Program(2017YFC0908002).
文摘Prostate cancer(PCa)affects millions of men globally.Due to advances in understanding genomic landscapes and biological functions,the treatment of PCa continues to improve.Recently,various new classes of agents,which include next-generation androgen receptor(AR)signaling inhibitors(abiraterone,enzalutamide,apalutamide,and darolutamide),bone-targeting agents(radium-223 chloride,zoledronic acid),and poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib,rucaparib,and talazoparib)have been developed to treat PCa.Agents targeting other signaling pathways,including cyclin-dependent kinase(CDK)4/6,Ak strain transforming(AKT),wingless-type protein(WNT),and epigenetic marks,have successively entered clinical trials.Furthermore,prostate-specific membrane antigen(PSMA)targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy.Advanced clinical studies with immune checkpoint inhibitors(ICIs)have shown limited benefits in PCa,whereas subgroups of PCa with mismatch repair(MMR)or CDK12 inactivation may benefit from ICIs treatment.In this review,we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms,and further discussed their limitations and future directions.
