The acceleration of electrons near three-dimensional(3D)magnetic nulls is crucial to the energy conversion mechanism in the 3D magnetic reconnection process.To explore electron acceleration in a 3D magnetic null topol...The acceleration of electrons near three-dimensional(3D)magnetic nulls is crucial to the energy conversion mechanism in the 3D magnetic reconnection process.To explore electron acceleration in a 3D magnetic null topology,we constructed a pair of 3D magnetic nulls in the PKU Plasma Test(PPT)device and observed acceleration of electrons near magnetic nulls.This study measured the plasma floating potential and ion density profiles around the 3D magnetic null.The potential wells near nulls may be related to the energy variations of electrons,so we measured the electron distribution functions(EDFs)at different spatial positions.The axial variation of EDF shows that the electrons deviate from the Maxwell distribution near magnetic nulls.With scanning probes that can directionally measure and theoretically analyze based on curve fitting,the variations of EDFs are linked to the changes of plasma potential under 3D magnetic null topology.The kinetic energy of electrons accelerated by the electric field is 6 eV(v_(e)~7v_(Alfvén-e))and the scale of the region where accelerating electrons exist is in the order of serval electron skin depths.展开更多
The HIT-PSI is a linear plasma device built for physically simulating the high heat flux environment of future reactor divertors to test/develop advanced target plate materials.In this study,the geometry-modified SOLP...The HIT-PSI is a linear plasma device built for physically simulating the high heat flux environment of future reactor divertors to test/develop advanced target plate materials.In this study,the geometry-modified SOLPS-ITER program is employed to examine the effects of the magnetic field strength and neutral pressure in the device on the heat flux experienced by the target plate of the HIT-PSI device.The findings of the numerical simulation indicate a positive correlation between the magnetic field strength and the heat flux density.Conversely,there is a negative correlation observed between the heat flux density and the neutral pressure.When the magnetic field strength at the axis exceeds 1 tesla and the neutral pressure falls below 10 Pa,the HIT-PSI has the capability to attain a heat flux of 10 MW·m-2 at the target plate.The simulation results offer a valuable point of reference for subsequent experiments at HIT-PSI.展开更多
The Space Plasma Environment Research Facility(SPERF)for ground simulation of the space plasma environment is a key component of the Space Environment Simulation Research Infrastructure(SESRI),a major national science...The Space Plasma Environment Research Facility(SPERF)for ground simulation of the space plasma environment is a key component of the Space Environment Simulation Research Infrastructure(SESRI),a major national science and technology infrastructure for fundamental research.It is designed to investigate outstanding issues in the space plasma environment,such as energetic particle acceleration,transport,and interaction with electromagnetic waves,as well as magnetic reconnection processes,in magnetospheric plasmas.The Tail-Research EXperiment(TREX)is part of the SPERF for laboratory studies of space physics relevant to magnetic reconnection,dipolarization and hydromagnetic wave excitation in the magnetotail.SPERFTREX is designed to carry out three types of experiments:the tail plasmoid for magnetic reconnection,dipolarization front formation,and magnetohydrodynamic waves excited by highspeed plasma jets.In this paper,the scientific goals and three scenarios of SPERF-TREX for typical processes in space plasmas are presented,and experimental plans for SPERF-TREX are also reviewed,together with the plasma sources applied to generate the plasma with the desired parameters and various magnetic configurations.展开更多
The inward particle transport is associated with the formation of peaked density profiles,which contributes to improve the fusion rate and the realization of steady-state discharge.The active control of inward particl...The inward particle transport is associated with the formation of peaked density profiles,which contributes to improve the fusion rate and the realization of steady-state discharge.The active control of inward particle transport is considered as one of the most critical issues of magnetic confinement fusion.Recently,it is realized preliminarily by adding a biased endplate in the Peking University Plasma Test(PPT)device.The results reveal that the inward particle flux increases with the bias voltage of the endplate.It is also found that the profile of radial electric field(Er)shear is flattened by the increased bias voltage.Radial velocity fluctuations affect the inward particle more than density fluctuations,and the frequency of the dominant mode driving inward particle flux increases with the biased voltage applied to the endplate.The experimental results in the PPT device provide a method to actively control the inward particle flux using a biased endplate and enrich the understanding of the relationship between E_(r)×B shear and turbulence transport.展开更多
Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-der...Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.展开更多
Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process re...Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process remain unclear.Long noncoding RNAs(lnc RNAs)are a newly identified class of functional RNAs that regulate cellular processes,such as gene expression and translation regulation.Recently,lnc RNAs have been reported to be involved in osteogenesis and bone formation.However,as the most abundant noncoding RNAs in vivo,the potential regulatory role of lnc RNAs in osteoclast formation and bone resorption urgently needs to be clarified.We recently found that the lnc RNA Nron(long noncoding RNA repressor of the nuclear factor of activated T cells)is highly expressed in osteoclast precursors.Nron is downregulated during osteoclastogenesis and bone ageing.To further determine whether Nron regulates osteoclast activity during orthodontic treatment,osteoclastic Nron transgenic(Nron c TG)and osteoclastic knockout(Nron CKO)mouse models were generated.When Nron was overexpressed,the orthodontic tooth movement rate was reduced.In addition,the number of osteoclasts decreased,and the activity of osteoclasts was inhibited.Mechanistically,Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation.In contrast,by deleting Nron specifically in osteoclasts,tooth movement speed increased in Nron CKO mice.These results indicate that lnc RNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.展开更多
Tooth number abnormality is one of the most common dental developmental diseases,which includes both tooth agenesis and supernumerary teeth.Tooth development is regulated by numerous developmental signals,such as the ...Tooth number abnormality is one of the most common dental developmental diseases,which includes both tooth agenesis and supernumerary teeth.Tooth development is regulated by numerous developmental signals,such as the well-known Wnt,BMP,FGF,Shh and Eda pathways,which mediate the ongoing complex interactions between epithelium and mesenchyme.Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number;however,the underlying mechanisms remain elusive.In this review,we summarized the major process of tooth development,the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality.In addition,potential treatment approaches for tooth number abnormality based on developmental biology are also discussed.This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.展开更多
Fault diagnosis is an important measure to ensure the safety of production, and all kinds of fault diagnosis methods are of importance in actual production process. However, the complexity and uncertainty of productio...Fault diagnosis is an important measure to ensure the safety of production, and all kinds of fault diagnosis methods are of importance in actual production process. However, the complexity and uncertainty of production process often lead to the changes of data distribution and the emergence of new fault classes, and the number of the new fault classes is unpredictable. The reconstruction of the fault diagnosis model and the identification of new fault classes have become core issues under the circumstances. This paper presents a fault diagnosis method based on model transfer learning and the main contributions of the paper are as follows: 1) An incremental model transfer fault diagnosis method is proposed to reconstruct the new process diagnosis model. 2) Breaking the limit of existing method that the new process can only have one more class of faults than the old process, this method can identify M faults more in the new process with the thought of incremental learning. 3) The method offers a solution to a series of problems caused by the increase of fault classes. Experiments based on Tennessee-Eastman process and ore grinding classification process demonstrate the effectiveness and the feasibility of the method.展开更多
Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscle...Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.展开更多
In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing ...In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing self-healing,however,the mechanism is unclear.Using this type of fracture mouse model,we discovered the activation of Hedgehog(Hh)signaling in the injured growth plate,which could activate chondrocytes in growth plate and promote cartilage repair.展开更多
Helicon wave plasma sources have the well-known advantages of high efficiency and high plasma density, with broad applications in many areas. The crucial mechanism lies with mode transitions, which has been an outstan...Helicon wave plasma sources have the well-known advantages of high efficiency and high plasma density, with broad applications in many areas. The crucial mechanism lies with mode transitions, which has been an outstanding issue for years. We have built a fluid simulation model and further developed the Peking University Helicon Discharge code. The mode transitions, also known as density jumps, of a single-loop antenna discharge are reproduced in simulations for the first time. It is found that large-amplitude standing helicon waves(SHWs) are responsible for the mode transitions, similar to those of a resonant cavity for laser generation.This paper intends to give a complete and quantitative SHW resonance theory to explain the relationship of the mode transitions and the SHWs. The SHW resonance theory reasonably explains several key questions in helicon plasmas, such as mode transition and efficient power absorption, and helps to improve future plasma generation methods.展开更多
Background Sharply increased beef consumption is propelling the genetic improvement projects of beef cattle in China.Three-dimensional genome structure is confirmed to be an important layer of transcription regulation...Background Sharply increased beef consumption is propelling the genetic improvement projects of beef cattle in China.Three-dimensional genome structure is confirmed to be an important layer of transcription regulation.Although genome-wide interaction data of several livestock species have already been produced,the genome structure states and its regulatory rules in cattle muscle are still limited.Results Here we present the first 3D genome data in Longissimus dorsi muscle of fetal and adult cattle(Bos taurus).We showed that compartments,topologically associating domains(TADs),and loop undergo re-organization and the structure dynamics were consistent with transcriptomic divergence during muscle development.Furthermore,we annotated cis-regulatory elements in cattle genome during myogenesis and demonstrated the enrichments of promoter and enhancer in selection sweeps.We further validated the regulatory function of one HMGA2 intronic enhancer near a strong sweep region on primary bovine myoblast proliferation.Conclusions Our data provide key insights of the regulatory function of high order chromatin structure and cattle myogenic biology,which will benefit the progress of genetic improvement of beef cattle.展开更多
Sodium metal battery(SMB)technology is one of the most promising candidates for next-generation rechargeable energy storage systems due to its high theoretical capacity and economical costeffectiveness.Unfortunately,i...Sodium metal battery(SMB)technology is one of the most promising candidates for next-generation rechargeable energy storage systems due to its high theoretical capacity and economical costeffectiveness.Unfortunately,its practical implementation is hindered by several challenges including short life-span and fast capacity decay,which is closely related to the uncontrollable generation of the sodium dendrites.Herein,a nitrogen and oxygen co-doped three-dimensional carbon cloth with hollow tubular fiber units was constructed as the host material for Na plating(Na@CC)to tackle these challenges.The obtained composite electrode can effectively reduce the nucleation overpotential of Na,guide the homogeneous Na^(+)flux,increase the kinetics of Na electrodeposition,lower the effective current density and eventually suppress the formation of electrochemically inactive Na dendrites.As a result,batteries built with the Na@CC composites exhibited stable long-term cycling stability.To gain an in-depth and comprehensive understanding of such phenomena,non-destructive and three-dimensional synchrotron X-ray tomography was employed to investigate the cycled batteries.Moreover,the COMSOL Multiphysics simulation was further employed to reveal the Na electrodeposition mechanisms.The current work not only showcases the feasibility of currently proposed sodiophilic 3 D Na@CC composite electrode but also provides fundamental insights into the underlying working mechanisms that govern its outstanding electrochemical performance.展开更多
The waves in a magnetic null could play important roles during 3D magnetic reconnection.Some preliminary clues in this paper show that the ion Bernstein wave(IBW)may be closely related to transport process in magnetic...The waves in a magnetic null could play important roles during 3D magnetic reconnection.Some preliminary clues in this paper show that the ion Bernstein wave(IBW)may be closely related to transport process in magnetic null region.The magnetic null configuration experiment reported here is set up in a linear helicon plasma device,Peking University plasma test device(PPT).The wave modes with frequencies between the first and third harmonics of local ion cyclotron frequency(w_(ci))are observed in the separatrix of magnetic null,which are identified as the IBW based on the dispersion relation.Further analysis shows that IBW could drive substantial particle flux across the magnetic separatrix.The theoretical radial particle flux driven by IBW and the measured parallel flow in PPT device are almost on the same order,which shows that IBW may play an important role during 3D reconnection process.展开更多
Xiangjiaba hydropowcr station is one of the complicated geological conditions of its dam foundation, parameters of rock masses are very important issues. To cascade power stations on the Jinsha River, China. Due to th...Xiangjiaba hydropowcr station is one of the complicated geological conditions of its dam foundation, parameters of rock masses are very important issues. To cascade power stations on the Jinsha River, China. Due to the evaluating the rock mass quality and determining the mechanical address these issues, several groups of rock borehole shear tests (RBSTs) were conducted on the black mudstone in the dam foundation of Xiangjiaba hydropower station in the second construction phase. Forty three groups of shear strengths of black mudstone samples were obtained from RBSTs, and the shear strength parameters (c and f) were calculated using the least squares method. In addition, the limitations and merits of RBST employed in the Xiangjiaba hydropower station were discussed. Test results indicate that the shear strength parameters obtained from RBST have a good correlation with the results from sotmd wave test in borehole. It is believed that RBST has a good adaptability and applicability in geotechnical engineering.展开更多
The soaring demand for electrical energy storage technologies stimulated by advanced portable devices, prospering electric vehicles, and large-scale grid storage applications have triggered explosive research on Li me...The soaring demand for electrical energy storage technologies stimulated by advanced portable devices, prospering electric vehicles, and large-scale grid storage applications have triggered explosive research on Li metal battery (LMB), which has been widely acknowledged as the most promising energy storage technology of the future that can break the energy-density bottleneck of the state-of-art lithium-ion battery (LIB) technology [1,2].展开更多
Propellant gas flow has an important impact on the ionization and acceleration process of Hall effect thrusters (HETs). In this paper, a particle-in-cell numerical method is used to study the effect of the anode tem...Propellant gas flow has an important impact on the ionization and acceleration process of Hall effect thrusters (HETs). In this paper, a particle-in-cell numerical method is used to study the effect of the anode temperature, i.e., the flow speed of the propellant gas, on the discharge characteristics of a HET. The simulation results show that, no matter the magnitude of the discharge voltage, the calculated variation trends of performance parameters with the anode temperature are in good agreement with the experimental ones presented in the literature. Further mechanism analysis indicates that the magnitude of the electron temperature is responsible for the two opposing variation laws found under different discharge voltages. When the discharge voltage is low, the electron temperature is low, and so is the intensity of the propellant ionization; the variation of the thruster performance with the anode temperature is thereby determined by the variation of the neutral density that affects the propellant utilization efficiency. When the discharge voltage is high, the electron temperature is large enough to guarantee a high degree of the propellant utilization no matter the magnitude of the anode temperature. The change of the thruster performance with the anode temperature is thus dominated by the change of the electron temperature and consequently the electron-neutral collisions as well as the electron cross-field mobility that affect the current utilization efficiency.展开更多
Double tearing modes(DTMs),induced by double current sheet configurations or two neighboring rational surfaces with the same safety factor in tokamaks,are widely observed in solar,space,and fusion plasmas.In this pape...Double tearing modes(DTMs),induced by double current sheet configurations or two neighboring rational surfaces with the same safety factor in tokamaks,are widely observed in solar,space,and fusion plasmas.In this paper,the evolution of DTMs without a guide field is investigated numerically using a hybrid model(electron fluid+ion PIC).The overall evolution processes of DTMs are qualitatively consistent with previous works using other models.The particle dynamics during the evolution of DTMs is analyzed in detail.Behaviors of ions and electrons present different characteristics around the reconnection region which gives rise to Hall effects producing the out-of-plane quadrupole magnetic field.In the explosive reconnection process with interactions between two DTMs islands,the asymmetric drive and the thin current layer feature lead to the emergence of secondary magnetic islands which develop with the late evolution of the DTMs.展开更多
Combining with empirical method, laboratory test and numerical simulation, a comprehensive system was presented to determine the mechanical parameters of jointed rock masses. The system has the following four function...Combining with empirical method, laboratory test and numerical simulation, a comprehensive system was presented to determine the mechanical parameters of jointed rock masses. The system has the following four functions: (1) Based on the field investigation of joints, the system can consider rock mass structures, by using network simulation technology. (2) Rock samples are conducted by numerical simulation with the input engineering mechanical parameters of rocks and joints obtained from laboratory tests. (3) The whole stress-strain curve of jointed rock masses under certain normal stress can be plotted from numerical simulation, and then the shear strength parameters of jointed rock masses can be obtained from the whole stress-strain curves under different normal stresses. (4) The statistical values of mechanical parameters of jointed rock masses can be determined according to numerical simulation. Based on the statistical values, combining with engineering experiences and geological investigations, the comprehensive mechanical parameters of jointed rock masses can be achieved finally. Several cases are presented to prove the engineering feasibility and suitability of this system.展开更多
基金supported by National Natural Science Foundation of China(No.11975038)the National Key Research and Development Program of China(No.2022YFA1604600)。
文摘The acceleration of electrons near three-dimensional(3D)magnetic nulls is crucial to the energy conversion mechanism in the 3D magnetic reconnection process.To explore electron acceleration in a 3D magnetic null topology,we constructed a pair of 3D magnetic nulls in the PKU Plasma Test(PPT)device and observed acceleration of electrons near magnetic nulls.This study measured the plasma floating potential and ion density profiles around the 3D magnetic null.The potential wells near nulls may be related to the energy variations of electrons,so we measured the electron distribution functions(EDFs)at different spatial positions.The axial variation of EDF shows that the electrons deviate from the Maxwell distribution near magnetic nulls.With scanning probes that can directionally measure and theoretically analyze based on curve fitting,the variations of EDFs are linked to the changes of plasma potential under 3D magnetic null topology.The kinetic energy of electrons accelerated by the electric field is 6 eV(v_(e)~7v_(Alfvén-e))and the scale of the region where accelerating electrons exist is in the order of serval electron skin depths.
基金Project supported by the National Key Research and Development Program of China(Grant No.2018YFE0303105)the Fundamental Research Funds for the Central Universities(Grant No.2022FRFK060021)the National MCF Energy Research and Development Program(Grant No.2019YFE03080300).
文摘The HIT-PSI is a linear plasma device built for physically simulating the high heat flux environment of future reactor divertors to test/develop advanced target plate materials.In this study,the geometry-modified SOLPS-ITER program is employed to examine the effects of the magnetic field strength and neutral pressure in the device on the heat flux experienced by the target plate of the HIT-PSI device.The findings of the numerical simulation indicate a positive correlation between the magnetic field strength and the heat flux density.Conversely,there is a negative correlation observed between the heat flux density and the neutral pressure.When the magnetic field strength at the axis exceeds 1 tesla and the neutral pressure falls below 10 Pa,the HIT-PSI has the capability to attain a heat flux of 10 MW·m-2 at the target plate.The simulation results offer a valuable point of reference for subsequent experiments at HIT-PSI.
基金supported by the State Commission of Development and Reform of ChinaNational Natural Science Foundation of China(Nos.42261134533,11261140326,11405038)。
文摘The Space Plasma Environment Research Facility(SPERF)for ground simulation of the space plasma environment is a key component of the Space Environment Simulation Research Infrastructure(SESRI),a major national science and technology infrastructure for fundamental research.It is designed to investigate outstanding issues in the space plasma environment,such as energetic particle acceleration,transport,and interaction with electromagnetic waves,as well as magnetic reconnection processes,in magnetospheric plasmas.The Tail-Research EXperiment(TREX)is part of the SPERF for laboratory studies of space physics relevant to magnetic reconnection,dipolarization and hydromagnetic wave excitation in the magnetotail.SPERFTREX is designed to carry out three types of experiments:the tail plasmoid for magnetic reconnection,dipolarization front formation,and magnetohydrodynamic waves excited by highspeed plasma jets.In this paper,the scientific goals and three scenarios of SPERF-TREX for typical processes in space plasmas are presented,and experimental plans for SPERF-TREX are also reviewed,together with the plasma sources applied to generate the plasma with the desired parameters and various magnetic configurations.
基金supported by the National MCF Energy R&D Program of China(No.2018YFE0303100)National Natural Science Foundation of China(No.11975038)。
文摘The inward particle transport is associated with the formation of peaked density profiles,which contributes to improve the fusion rate and the realization of steady-state discharge.The active control of inward particle transport is considered as one of the most critical issues of magnetic confinement fusion.Recently,it is realized preliminarily by adding a biased endplate in the Peking University Plasma Test(PPT)device.The results reveal that the inward particle flux increases with the bias voltage of the endplate.It is also found that the profile of radial electric field(Er)shear is flattened by the increased bias voltage.Radial velocity fluctuations affect the inward particle more than density fluctuations,and the frequency of the dominant mode driving inward particle flux increases with the biased voltage applied to the endplate.The experimental results in the PPT device provide a method to actively control the inward particle flux using a biased endplate and enrich the understanding of the relationship between E_(r)×B shear and turbulence transport.
基金supported by Quzhou City Jiang District Life Oasis Public Welfare Service Center,Health and Health Development Promotion Project(Oncology Research Special Project,no:BJHA-CRP-027).
文摘Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.
基金supported by grants from the National Natural Science Foundation Projects of China(81822012,81771043)National Science and Technology Major Project of China(2016YFC1102705)+1 种基金Special Fund of Chinese Central University for Basic Scientific Research(20173386)Training Program of Shanghai Municipal Health System for Excellent Talents(2017BR009)。
文摘Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process remain unclear.Long noncoding RNAs(lnc RNAs)are a newly identified class of functional RNAs that regulate cellular processes,such as gene expression and translation regulation.Recently,lnc RNAs have been reported to be involved in osteogenesis and bone formation.However,as the most abundant noncoding RNAs in vivo,the potential regulatory role of lnc RNAs in osteoclast formation and bone resorption urgently needs to be clarified.We recently found that the lnc RNA Nron(long noncoding RNA repressor of the nuclear factor of activated T cells)is highly expressed in osteoclast precursors.Nron is downregulated during osteoclastogenesis and bone ageing.To further determine whether Nron regulates osteoclast activity during orthodontic treatment,osteoclastic Nron transgenic(Nron c TG)and osteoclastic knockout(Nron CKO)mouse models were generated.When Nron was overexpressed,the orthodontic tooth movement rate was reduced.In addition,the number of osteoclasts decreased,and the activity of osteoclasts was inhibited.Mechanistically,Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation.In contrast,by deleting Nron specifically in osteoclasts,tooth movement speed increased in Nron CKO mice.These results indicate that lnc RNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
基金supported by grants from the National Key R&D Program of China(2022YFA1103201)Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)+2 种基金Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(201409006400)National Natural Science Foundation of China(82270963,82061130222)awarded to Y.S.National Natural Science Foundation Projects of China(92049201)awarded to X.W.
文摘Tooth number abnormality is one of the most common dental developmental diseases,which includes both tooth agenesis and supernumerary teeth.Tooth development is regulated by numerous developmental signals,such as the well-known Wnt,BMP,FGF,Shh and Eda pathways,which mediate the ongoing complex interactions between epithelium and mesenchyme.Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number;however,the underlying mechanisms remain elusive.In this review,we summarized the major process of tooth development,the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality.In addition,potential treatment approaches for tooth number abnormality based on developmental biology are also discussed.This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
文摘Fault diagnosis is an important measure to ensure the safety of production, and all kinds of fault diagnosis methods are of importance in actual production process. However, the complexity and uncertainty of production process often lead to the changes of data distribution and the emergence of new fault classes, and the number of the new fault classes is unpredictable. The reconstruction of the fault diagnosis model and the identification of new fault classes have become core issues under the circumstances. This paper presents a fault diagnosis method based on model transfer learning and the main contributions of the paper are as follows: 1) An incremental model transfer fault diagnosis method is proposed to reconstruct the new process diagnosis model. 2) Breaking the limit of existing method that the new process can only have one more class of faults than the old process, this method can identify M faults more in the new process with the thought of incremental learning. 3) The method offers a solution to a series of problems caused by the increase of fault classes. Experiments based on Tennessee-Eastman process and ore grinding classification process demonstrate the effectiveness and the feasibility of the method.
基金supported by the National Natural Science Foundation of China (No.31772574)the Program of National Beef Cattle and Yak Industrial Technology System (CARS-37)the scholarship from the China Scholarship Council (CSC),China。
文摘Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrade mRNA transcripts.Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically btamiR-365-3 p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3 p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of btamiR-365-3 p significantly reduced the expression levels of cyclin D1(CCND1), cyclin dependent kinase 2(CDK2) and proliferating cell nuclear antigen(PCNA) but stimulated the expression levels of muscle differentiation markers, i.e.,MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3 p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3 p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3 p resulted in the opposite consequences. Finally, we identified that activin A receptor type I(ACVR1) could be a direct target of bta-miR-365-3 p. It was demonstrated that bta-miR-365-3 p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays.Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level.Conclusion: Collectively, these data suggested that bta-miR-365-3 p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.
基金supported by grants from the National Key R&D Program of China(2022YFA1103200)National Natural Science Foundation Projects of China(81822012,82061130222,81771043,92049201,82001070)+1 种基金Shanghai Academic Leader of Science and Technology Innovation Action Plan(20XD1424000)the Shanghai Experimental Animal Research Project of Science and Technology Innovation Action Plan(8191101676,201409006400)。
文摘In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing self-healing,however,the mechanism is unclear.Using this type of fracture mouse model,we discovered the activation of Hedgehog(Hh)signaling in the injured growth plate,which could activate chondrocytes in growth plate and promote cartilage repair.
基金supported by the National Key R&D Program of China(No.2017YFE0301201)National Natural Science Foundation of China(No.11975038)the funding support from the State Key Laboratory of Nuclear Physics and Technology,Peking University(No.NPT2021ZZ03)。
文摘Helicon wave plasma sources have the well-known advantages of high efficiency and high plasma density, with broad applications in many areas. The crucial mechanism lies with mode transitions, which has been an outstanding issue for years. We have built a fluid simulation model and further developed the Peking University Helicon Discharge code. The mode transitions, also known as density jumps, of a single-loop antenna discharge are reproduced in simulations for the first time. It is found that large-amplitude standing helicon waves(SHWs) are responsible for the mode transitions, similar to those of a resonant cavity for laser generation.This paper intends to give a complete and quantitative SHW resonance theory to explain the relationship of the mode transitions and the SHWs. The SHW resonance theory reasonably explains several key questions in helicon plasmas, such as mode transition and efficient power absorption, and helps to improve future plasma generation methods.
基金supported by the National Natural Science Foundation of China[Grant No.31972558]the Agricultural Improved Seed Project of Shandong Province[Grant No.2020LZGC014-03]。
文摘Background Sharply increased beef consumption is propelling the genetic improvement projects of beef cattle in China.Three-dimensional genome structure is confirmed to be an important layer of transcription regulation.Although genome-wide interaction data of several livestock species have already been produced,the genome structure states and its regulatory rules in cattle muscle are still limited.Results Here we present the first 3D genome data in Longissimus dorsi muscle of fetal and adult cattle(Bos taurus).We showed that compartments,topologically associating domains(TADs),and loop undergo re-organization and the structure dynamics were consistent with transcriptomic divergence during muscle development.Furthermore,we annotated cis-regulatory elements in cattle genome during myogenesis and demonstrated the enrichments of promoter and enhancer in selection sweeps.We further validated the regulatory function of one HMGA2 intronic enhancer near a strong sweep region on primary bovine myoblast proliferation.Conclusions Our data provide key insights of the regulatory function of high order chromatin structure and cattle myogenic biology,which will benefit the progress of genetic improvement of beef cattle.
基金sponsored by the National Natural Science Foundation of China(U1904216)the QIBEBT I201922,Dalian National Laboratory for Clean Energy(DNL),CAS。
文摘Sodium metal battery(SMB)technology is one of the most promising candidates for next-generation rechargeable energy storage systems due to its high theoretical capacity and economical costeffectiveness.Unfortunately,its practical implementation is hindered by several challenges including short life-span and fast capacity decay,which is closely related to the uncontrollable generation of the sodium dendrites.Herein,a nitrogen and oxygen co-doped three-dimensional carbon cloth with hollow tubular fiber units was constructed as the host material for Na plating(Na@CC)to tackle these challenges.The obtained composite electrode can effectively reduce the nucleation overpotential of Na,guide the homogeneous Na^(+)flux,increase the kinetics of Na electrodeposition,lower the effective current density and eventually suppress the formation of electrochemically inactive Na dendrites.As a result,batteries built with the Na@CC composites exhibited stable long-term cycling stability.To gain an in-depth and comprehensive understanding of such phenomena,non-destructive and three-dimensional synchrotron X-ray tomography was employed to investigate the cycled batteries.Moreover,the COMSOL Multiphysics simulation was further employed to reveal the Na electrodeposition mechanisms.The current work not only showcases the feasibility of currently proposed sodiophilic 3 D Na@CC composite electrode but also provides fundamental insights into the underlying working mechanisms that govern its outstanding electrochemical performance.
基金supported by National Natural Science Foundation of China(No.11975038)the National MCF Energy R&D Program of China(Nos.2017YFE0300601 and 2018YFE0311400).
文摘The waves in a magnetic null could play important roles during 3D magnetic reconnection.Some preliminary clues in this paper show that the ion Bernstein wave(IBW)may be closely related to transport process in magnetic null region.The magnetic null configuration experiment reported here is set up in a linear helicon plasma device,Peking University plasma test device(PPT).The wave modes with frequencies between the first and third harmonics of local ion cyclotron frequency(w_(ci))are observed in the separatrix of magnetic null,which are identified as the IBW based on the dispersion relation.Further analysis shows that IBW could drive substantial particle flux across the magnetic separatrix.The theoretical radial particle flux driven by IBW and the measured parallel flow in PPT device are almost on the same order,which shows that IBW may play an important role during 3D reconnection process.
基金Supported by the National Basic Research Program of China(973 Program)(2011CB013502)the Youth Special Foundation of IWHR(YJ1106)
文摘Xiangjiaba hydropowcr station is one of the complicated geological conditions of its dam foundation, parameters of rock masses are very important issues. To cascade power stations on the Jinsha River, China. Due to the evaluating the rock mass quality and determining the mechanical address these issues, several groups of rock borehole shear tests (RBSTs) were conducted on the black mudstone in the dam foundation of Xiangjiaba hydropower station in the second construction phase. Forty three groups of shear strengths of black mudstone samples were obtained from RBSTs, and the shear strength parameters (c and f) were calculated using the least squares method. In addition, the limitations and merits of RBST employed in the Xiangjiaba hydropower station were discussed. Test results indicate that the shear strength parameters obtained from RBST have a good correlation with the results from sotmd wave test in borehole. It is believed that RBST has a good adaptability and applicability in geotechnical engineering.
基金supported by QIBEBT I201922, Dalian National Laboratory For Clean Energy (DNL), CASNational Natural Science Foundation of China (U1904216)。
文摘The soaring demand for electrical energy storage technologies stimulated by advanced portable devices, prospering electric vehicles, and large-scale grid storage applications have triggered explosive research on Li metal battery (LMB), which has been widely acknowledged as the most promising energy storage technology of the future that can break the energy-density bottleneck of the state-of-art lithium-ion battery (LIB) technology [1,2].
基金funded by National Natural Science Foundation of China(Nos.51507040,51736003 and 51777045)the Research Program(No.JSZL2016203C006)the Fundamental Research Funds for the Central Universities(No.HIT.NSRIF.2015079)
文摘Propellant gas flow has an important impact on the ionization and acceleration process of Hall effect thrusters (HETs). In this paper, a particle-in-cell numerical method is used to study the effect of the anode temperature, i.e., the flow speed of the propellant gas, on the discharge characteristics of a HET. The simulation results show that, no matter the magnitude of the discharge voltage, the calculated variation trends of performance parameters with the anode temperature are in good agreement with the experimental ones presented in the literature. Further mechanism analysis indicates that the magnitude of the electron temperature is responsible for the two opposing variation laws found under different discharge voltages. When the discharge voltage is low, the electron temperature is low, and so is the intensity of the propellant ionization; the variation of the thruster performance with the anode temperature is thereby determined by the variation of the neutral density that affects the propellant utilization efficiency. When the discharge voltage is high, the electron temperature is large enough to guarantee a high degree of the propellant utilization no matter the magnitude of the anode temperature. The change of the thruster performance with the anode temperature is thus dominated by the change of the electron temperature and consequently the electron-neutral collisions as well as the electron cross-field mobility that affect the current utilization efficiency.
基金supported by National Natural Science Foundation of China(Nos.11705039,11975087,and 42011530086)the China Postdoctoral Science Foundation(No.2018M631918)the Heilongjiang Postdoctoral Foundation(No.184744)。
文摘Double tearing modes(DTMs),induced by double current sheet configurations or two neighboring rational surfaces with the same safety factor in tokamaks,are widely observed in solar,space,and fusion plasmas.In this paper,the evolution of DTMs without a guide field is investigated numerically using a hybrid model(electron fluid+ion PIC).The overall evolution processes of DTMs are qualitatively consistent with previous works using other models.The particle dynamics during the evolution of DTMs is analyzed in detail.Behaviors of ions and electrons present different characteristics around the reconnection region which gives rise to Hall effects producing the out-of-plane quadrupole magnetic field.In the explosive reconnection process with interactions between two DTMs islands,the asymmetric drive and the thin current layer feature lead to the emergence of secondary magnetic islands which develop with the late evolution of the DTMs.
基金Supported by the National Basic Research Program of China (973 Program) (2011CB013502)the National Natural Science Foundation of China (51179210)
文摘Combining with empirical method, laboratory test and numerical simulation, a comprehensive system was presented to determine the mechanical parameters of jointed rock masses. The system has the following four functions: (1) Based on the field investigation of joints, the system can consider rock mass structures, by using network simulation technology. (2) Rock samples are conducted by numerical simulation with the input engineering mechanical parameters of rocks and joints obtained from laboratory tests. (3) The whole stress-strain curve of jointed rock masses under certain normal stress can be plotted from numerical simulation, and then the shear strength parameters of jointed rock masses can be obtained from the whole stress-strain curves under different normal stresses. (4) The statistical values of mechanical parameters of jointed rock masses can be determined according to numerical simulation. Based on the statistical values, combining with engineering experiences and geological investigations, the comprehensive mechanical parameters of jointed rock masses can be achieved finally. Several cases are presented to prove the engineering feasibility and suitability of this system.