The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process th...The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process that leads to a significant deterioration of non-uniformity when scaling up to larger areas.Since the performance of gaseous detectors is highly dependent on the choice of working gas,optimizing the gas mixture offers a promising solution to improve the uniformity performance.This paper addresses these challenges through a combined approach of simulation based on Garfield++and experimental studies.The simulation investigates the properties of different mixing fractions of gas mixtures and their impact on detector performance,including gain uniformity and time resolution.To verify the simulation results,experimental tests were conducted using a multi-channel PICOSEC MM prototype with different gas mixtures.The experimental results are consistent with the findings of the simulation,indicating that a higher concentration of neon significantly improves the detector’s gain uniformity.Furthermore,the influence of gas mixtures on time resolution was explored as a critical performance indicator.The study presented in this paper offers valuable insights for improving uniformity in large-area PICOSEC MM detectors and optimizing overall performance.展开更多
Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy...Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).展开更多
The development of narrow-bandgap polymer donors with complementary absorption and matched energy levels for perylene diimides(PDI)-based nonfullerene acceptors(NFAs)has received little attention.The high-lying highes...The development of narrow-bandgap polymer donors with complementary absorption and matched energy levels for perylene diimides(PDI)-based nonfullerene acceptors(NFAs)has received little attention.The high-lying highest occupied molecular orbital(HOMO)level and low degree of crystallinity of the star donor polymer PCE10 limit its application in PDI-based Organic solar cells(OSCs).In this study,two benzo[1,2-b:4,5-b′]difuran(BDF)-based narrow-bandgap polymer donors,PBDF and PBDFCl,were synthesized to improve the photovoltaic performance of PDI-based OSCs.The smaller BDF moiety with higher electronegativity endows the resulting polymers with stronger aggregation and lower HOMO energy levels.The power conversion efficiency(PCE)value of the PBDF:Ph(PDI)3-based OSCs was 7.24%,which is much higher than that of PCE10-based OSCs(6.09%).Further chlorination of the conjugated side chain elevated the PCE to 8.84%,which is 1.4 times higher than that of PCE10-based OSCs.These results demonstrate the significant contribution of designing novel narrow-bandgap polymer donors to boost the PCE of PDI-based OSCs and highlight the importance of matching the aggregation behaviors of polymeric donor materials with that of NFAs.展开更多
A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has...A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.展开更多
Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for study...Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.展开更多
We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multipl...We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multiple parton interactions and gluon contributions is studied and found to be a possible source of the splitting of the particle yields as a function of p_T with respect to the multiplicity. No obvious particle species dependence of the splitting is observed.The multiplicity dependence of the ratios Kˉ/πˉ, K^+/π^+,/πˉ, p/π^+, and K_s^0 at mid-rapidity in p+ p collisions is found to follow a tendency similar to that in Au t Au collisions at (s_(NN))^(1/2) = 200 GeV at the Relativistic Heavy Ion Collider, indicating similar underlying initial production mechanisms despite the differences in the initial colliding systems.展开更多
Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, wh...Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.展开更多
Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely unde...Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.展开更多
In the paper,we discuss the development of the multigap resistive plate chamber time-of-fight(TOF)technology and the production of the solenoidal tracker at RHIC(STAR)TOF detector in China at the beginning of the twen...In the paper,we discuss the development of the multigap resistive plate chamber time-of-fight(TOF)technology and the production of the solenoidal tracker at RHIC(STAR)TOF detector in China at the beginning of the twenty-frst century.Subsequently,recent experimental results from the frst beam energy scan program(BES-I)at the Relativistic Heavy Ion Collider(RHIC)pertaining to measurements of collectivity,chirality,criticality,global polarization,strangeness,heavy favor,dilepton and light nuclei productions are reviewed.展开更多
We present a comprehensive study on the individual sources of an inclusive photon production during high-energy hadronic collisions.The cross section and invariant yields of inclusive photons are obtained as a functio...We present a comprehensive study on the individual sources of an inclusive photon production during high-energy hadronic collisions.The cross section and invariant yields of inclusive photons are obtained as a function of pT at mid-rapidity(|y|<0.5)in p+p and Au+Au collisions at√SNN=200GeVrespectively.These results provide crucial inputs to separate measurements of open bottom and charm hadron yield suppression in heavyion collisions,which are used to test the mass hierarchy of the parton energy loss in the quark gluon plasma created during these collisions.The procedure developed in this study can also be applied to other measurements of electrons from an open heavy-flavor hadron decay,such as the collective flow in the RHIC beam energy scan program.展开更多
Since its first application to induce mutations in mammalian cells （Cong et al., 2013： Mall et al., 2013）, CRISPR/Cas9 has rapidly become a routine technique to perform genome editing in a variety of biological sys...Since its first application to induce mutations in mammalian cells （Cong et al., 2013： Mall et al., 2013）, CRISPR/Cas9 has rapidly become a routine technique to perform genome editing in a variety of biological systems due to its facile, robust, and multiplexable fea- tures （Hwang et al, 2013; Wang et al., 2013; Guo et al., 2014; Liu, 2017）.展开更多
The mudstone,gray tuffite and carbonaceous shale in the Upper Carboniferous Batamayineishan Formation(Bashan Formation)are essential source rocks for the volcanic reservoir in eastern Junggar,northwestern China.The ke...The mudstone,gray tuffite and carbonaceous shale in the Upper Carboniferous Batamayineishan Formation(Bashan Formation)are essential source rocks for the volcanic reservoir in eastern Junggar,northwestern China.The kerogen components,vitrinite reflectance,Rock-Eval pyrolysis,lipid biomarkers and isotope compositions were measured to understand the provenance and depositional environment of Bashan Formation under the background of volcanic activities.There were 10 and 4 periods of volcanic eruptions identified in the wells CS and DZ,respectively.The source rocks developed in the late or intermittent phase of volcanic activity.The original island arcs of the Early Carboniferous evolved into the Wucaiwan sag and the Dishuiquan sag in the Bashan Formation.The Wucaiwan sag inherited the restricted,closed residual sea,which had a slightly anoxic and hypersaline environment.The Dishuiquan sag was generally an oxidizing lacustrine environment,influenced by a marine transgression that may have occurred at the end of the DZ_(Ⅲ)period during the Late Carboniferous.Although the total organic matter decreased due to the volcanic eruption,ash could cause an increase of aquatic organisms,coinciding with increases in salinity and reducibility in the Dishuiquan sag.展开更多
Efficient photosensitizers are crucial for the success of photodynamic therapy(PDT).Herein,we reported two[3+2+1]coordinated organometallic Iridium(III)complexes(labeled as Ir-C1 and Ir-C4).Ir-C1/C4 can generate both ...Efficient photosensitizers are crucial for the success of photodynamic therapy(PDT).Herein,we reported two[3+2+1]coordinated organometallic Iridium(III)complexes(labeled as Ir-C1 and Ir-C4).Ir-C1/C4 can generate both type I and type II reactive oxygen species(ROS).In vitro experiments,Ir-C1/C4 show low biotoxicity and high phototoxicity of half-maximal inhibitory concentration values of 14 nM and 33 nM on rectal cancer cell line HCT116,respectively.Western blot analysis revealed that the Ir-C1/C4 activated ferroptosis,apoptosis,and inhibiting autophagy simultaneously.Proteomics analysis demonstrated that the photosensitizers destroyed the endoplasmic reticulum(ER),blocking the signal transmission and material transfer between the ER and other tissues of the cell,especially the ER to Golgi vesicle-mediated transport.Ir-C1/C4 can achieve better antitumor performance than commercial photosensitizer Chlorin e6 and the ferroptosis activator RSL3 at lower concentrations.The low biotoxicity and high phototoxicity make them ideal candidates for PDT.The findings provide new insights into the design of photosensitizers for metal complexes and have significant implications for the development of PDT and related drugs.展开更多
Humanoid robot joints require real-time torque detection to provide accurate force feedback informa-tion for the control system.To meet the measurement requirements and realize the miniaturization of the sensor,a torq...Humanoid robot joints require real-time torque detection to provide accurate force feedback informa-tion for the control system.To meet the measurement requirements and realize the miniaturization of the sensor,a torque sensor based on the magnetoelastic effect is developed,utilizing planar spiral coils as detection probes.In this work,a planar spiral coil mutual inductance calculation model is established to solve the mutual inductance coefficient,and the mechanical structure and circuit design of the sensor are completed.Finally,a torque loading platform is built to perform calibration experiments,and the hysteresis model is improved to compensate for the hysteresis phenomenon.The calibration results indicate that the sensor shows excellent loaded nonlinearity of 3.08%F.S.,unloaded nonlinearity of 2.71% F.S.,loaded repeatability of 2.48% F.S.,unloaded repeatability of 1.89% F.S.and hysteresis of 1.9% F.S.,at a compact probe size of 13.8×9.9×1.8 mm.展开更多
Gene expression must be precisely regulated in cells and functional nucleic acids are the most widely utilized tools for gene manipulation.Photocontrol of how these nucleic acid tools work in the cellular environment ...Gene expression must be precisely regulated in cells and functional nucleic acids are the most widely utilized tools for gene manipulation.Photocontrol of how these nucleic acid tools work in the cellular environment can precisely manipulate gene expression through a non-invasive way.Here we report a methodology on multiplex photocontrol of functional nucleic acids to achieve totally temporal and orthogonal regulation of gene expression in living cells.We select two functional nucleic acid systems as examples,DNAzyme and CRISPR/Cas9,and demonstrate the power of light control for precise gene manipulation by rational design of chemically modified oligonucleotides through introduction of two photocleavable linkers.Unlike the previous modulation of functional nucleic acids by simply activating or deactivating,we successfully achieve versatile controlling patterns using light as the governing factor.This design represents a generalized pathway towards the photo-controllable functional nucleic acids,which greatly enriches the toolbox for optogenetic studies.展开更多
Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and p...Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.展开更多
Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The pres...Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.展开更多
One of the main purposes of heavy-ion collisions over a wide range of beam energy is to study the bulk properties of strong interaction matter and understand the Quantum Chromo Dy- namics （QCD） phase diagram, which ...One of the main purposes of heavy-ion collisions over a wide range of beam energy is to study the bulk properties of strong interaction matter and understand the Quantum Chromo Dy- namics （QCD） phase diagram, which carries wealth of infor- mation of the phase transition and the possibly existing criti- cal point of the strongly interacting system [1]. Such system exists as hadron gases at lower temperature and low baryon density. By increasing the temperature or density, the bound- ary of the hadrons disappears and the confined quarks move freely in the whole system.展开更多
Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is unclear.This study aimed to evaluate the efficacy and safety of rasagili...Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is unclear.This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD.Methods:A 26-weeks,randomized,double-blind,placebo-controlled study has been performed at 15 sites in China and enrolled outpatients(≥35 years old)with idiopathic PD without a history of using any dopaminergic drugs.Participants were randomized 1:1 to receive rasagiline 1 mg once daily or placebo.The primary endpoint was the change of the Unified Parkinson’s Disease Rating Scale(UPDRS)total score from baseline to 26 weeks treatment.Secondary endpoints included changes in UPDRS subscale scores from part Ⅰ to Ⅲ.Health status was assessed with the PD Questionnaire(PDQ)-39 and EuroQol-Five-Dimension(EQ-5D)questionnaire.Safety profile was collected until 30 weeks after randomization.Results:A total of 130 patients(n=65/group)were recruited,and 127(rasagiline,n=64;placebo,n=63)were included in the full analysis set.Baseline characteristics were comparable between the two groups.The decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group(−3.18±0.95 vs.−0.18±0.98,P=0.025),and the mean UPDRS part I non-motor symptoms score(−0.54±0.15 vs.-0.08±0.15,P=0.003)were significantly decreased in the rasagiline group compared with placebo treated patients.An improvement trend was observed in the active treatment group for the subscales evaluation with parts Ⅱ and Ⅲ,while the difference to placebo was not statistically significant.Life quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated patients.The overall incidence of treatment-emergent adverse events(AEs)was slightly lower in the rasagiline group(41.5%)than in the placebo group(46.2%).Conclusions:Rasagiline is effective,safe,and well tolerated as monotherapy for the treatment of Chinese PD patients.展开更多
基金supported by the National Natural Science Foundation of China(12125505).
文摘The PICOSEC Micromegas(MM)is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure.It features a two-stage amplification process that leads to a significant deterioration of non-uniformity when scaling up to larger areas.Since the performance of gaseous detectors is highly dependent on the choice of working gas,optimizing the gas mixture offers a promising solution to improve the uniformity performance.This paper addresses these challenges through a combined approach of simulation based on Garfield++and experimental studies.The simulation investigates the properties of different mixing fractions of gas mixtures and their impact on detector performance,including gain uniformity and time resolution.To verify the simulation results,experimental tests were conducted using a multi-channel PICOSEC MM prototype with different gas mixtures.The experimental results are consistent with the findings of the simulation,indicating that a higher concentration of neon significantly improves the detector’s gain uniformity.Furthermore,the influence of gas mixtures on time resolution was explored as a critical performance indicator.The study presented in this paper offers valuable insights for improving uniformity in large-area PICOSEC MM detectors and optimizing overall performance.
基金supported by the National Key Research and Development Program of China(No.2022YFA1602200)the National Natural Science Foundation of China(Nos.12341501 and 12405174)the Hefei Comprehensive National Science Center for the strong support on the STCF key technology research project.
文摘Electron-positron colliders operating in the GeV center-of-mass range,or tau-charm energy region,have been proved to enable competitive frontier research due to several unique features.With the progress of high-energy physics in the last two decades,a new-generation Tau-Charm factory,called the Super Tau-Charm Facility(STCF),has been actively promoted by the particle physics community in China.STCF has the potential to address fundamental questions such as the essence of color confinement and the matter-antimatter asymmetry within the next decades.The main design goals of the STCF are a center-of-mass energy ranging from 2 to 7 GeV and a luminosity surpassing 5×10^(34)cm^(−2)s^(−1)that is optimized at a center-of-mass energy of 4 GeV,which is approximately 50 times that of the currently operating Tau-Charm factory-BEPCII.The STCF accelerator has two main parts:a double-ring collider with a crab-waist collision scheme and an injector that provides top-up injections for both electron and positron beams.As a typical third-generation electron-positron circular collider,the STCF accelerator faces many challenges in both accelerator physics and technology.In this paper,the conceptual design of the STCF accelerator complex is presented,including the ongoing efforts and plans for technological research and develop-ment,as well as the required infrastructure.The STCF project aims to secure support from the Chinese central government for its construction during the 15th Five-Year Plan(2026-2030).
基金supported by the National Natural Science Foundation of China(Nos.52273195 and 51973169)Young Top-notch Talent Cultivation Program of Hubei Province,Natural Science Foundation of Hubei Province(No.2022CFB097)。
文摘The development of narrow-bandgap polymer donors with complementary absorption and matched energy levels for perylene diimides(PDI)-based nonfullerene acceptors(NFAs)has received little attention.The high-lying highest occupied molecular orbital(HOMO)level and low degree of crystallinity of the star donor polymer PCE10 limit its application in PDI-based Organic solar cells(OSCs).In this study,two benzo[1,2-b:4,5-b′]difuran(BDF)-based narrow-bandgap polymer donors,PBDF and PBDFCl,were synthesized to improve the photovoltaic performance of PDI-based OSCs.The smaller BDF moiety with higher electronegativity endows the resulting polymers with stronger aggregation and lower HOMO energy levels.The power conversion efficiency(PCE)value of the PBDF:Ph(PDI)3-based OSCs was 7.24%,which is much higher than that of PCE10-based OSCs(6.09%).Further chlorination of the conjugated side chain elevated the PCE to 8.84%,which is 1.4 times higher than that of PCE10-based OSCs.These results demonstrate the significant contribution of designing novel narrow-bandgap polymer donors to boost the PCE of PDI-based OSCs and highlight the importance of matching the aggregation behaviors of polymeric donor materials with that of NFAs.
基金supported by National Natural Science Foundation of China (31670170 and 31270209)by Ministry monomer, GAG facilitates Aβ fibrilization by pulling PrPC monomer to oligomerize
文摘A plethora of evidence suggests that protein misfolding and aggregation are underlying mechanisms of various neurodegenerative diseases,such as prion diseases and Alzheimer's disease(AD).Like prion diseases,AD has been considered as an infectious disease in the past decades as it shows strain specificity and transmission potential.Although it remains elusive how protein aggregation leads to AD,it is becoming clear that cellular prion protein(PrP^c)plays an important role in AD pathogenesis.Here,we briefly reviewed AD pathogenesis and focused on recent progresses how PrP^c contributed to AD development.In addition,we proposed a potential mechanism to explain why infectious agents,such as viruses,conduce AD pathogenesis.Microbe infections cause AD deposition and upregulation of PrP^c,which lead to high affinity binding between AD oligomers and PrP^c.The interaction between PrP^c and AP oligomers in turn activates the Fyn signaling cascade,resulting in neuron death in the central nervous system(CNS).Thus,silencing PrP^c expression may turn out be an effective treatment for PrP^c dependent AD.
基金partially supported by the National Natural Science Foundation of China(81202110,81120108019,U1132605 and 81325016)
文摘Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.
基金supported by the Major State Basic Research Development Program in China(No.2014CB845400)the National Natural Science Foundation of China(No.11375184)+2 种基金the Youth Innovation Promotion Association Fund of CAS(No.CX2030040079)the Ministry of Science and Technology(Mo ST)of China(No.2016YFE0104800)the Science and Technological Fund of Anhui Province for Outstanding Youth(No.1808085J02)
文摘We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multiple parton interactions and gluon contributions is studied and found to be a possible source of the splitting of the particle yields as a function of p_T with respect to the multiplicity. No obvious particle species dependence of the splitting is observed.The multiplicity dependence of the ratios Kˉ/πˉ, K^+/π^+,/πˉ, p/π^+, and K_s^0 at mid-rapidity in p+ p collisions is found to follow a tendency similar to that in Au t Au collisions at (s_(NN))^(1/2) = 200 GeV at the Relativistic Heavy Ion Collider, indicating similar underlying initial production mechanisms despite the differences in the initial colliding systems.
基金supported by the grants from the National Science Foundation of China (No. 31271556)Association Francaise contre les Myopathies (AFM)the Agence Nationale de la Recherche (ANR-09-BLAN-0262-03) in France
文摘Myosin XVIIIA, or MYO18A, is a unique PDZ domain-containing unconventional myosin and is evolutionarily conserved from Drosophila to vertebrates. Although there is evidence indicating its expression in the somites, whether it regulates muscle function re- mains unclear. We show that the two zebrafish myo18a genes （myo18aa and myo18ab） are predominantly expressed at somite borders during early developmental stages. Knockdown of these genes or overexpression of the MYO18A PDZ domain disrupts myofiber integrity, induces myofiber lesions, and compromises the localization of dystrophin, ^-dystroglycan （^-DG） and laminin at the myotome boundaries. Cell transplantation experiments indicate that myo18a morphant myoblasts fail to form elongated myofibers in the myotomes of wild-type embryos, which can be rescued by the full-length MYO18A protein. These results suggest that MYO18A likely functions in the adhesion process that maintains the stable attachment of myofibers to ECM （extracellular matrix） and muscle integrity during early development.
基金supported by grants from the National Science Foundation of China (31670170 & 81560442)from MOST (2018YFA0507201)from the Natural Science Foundation of Guangdong Province (2017ZC0236)。
文摘Tumor Necrosis Factor α(TNFα) is best known as a mediator of inflammation and immunity, and also plays important roles in tumor biology. However, the role of TNFα in tumor biology is complex and not completely understood. In a human melanoma cell line, M2, and a lung carcinoma cell line, A549, TNFα up-regulates prion protein(PrP) level, and promotes tumor cell migration in a PrP dependent manner. Silencing PRNP abrogates TNFα induced tumor cell migration;this phenotype is reversed when PRNP is re-introduced. Treatment with TNFα activates nuclear factor kappa B(NF-κB)signaling, which then mitigates autophagy by reducing the expression of Forkhead Box P3(FOXP3). Down regulation of FOXP3 reduces the transcription of synaptosome associated protein 29(SNAP29), which is essential in the fusion of autophagosome and lysosome creating autolysosome. FOXP3 being a bona fide transcription factor for SNAP29 is confirmed in a promoter binding assay. Accordingly, silencing SNAP29 in these cell lines also up-regulates PrP, and promotes tumor cell migration without TNFα treatment. But, when SNAP29 or FOXP3 is silenced in these cells, they are no longer respond to TNFα. Thus, a reduction in autophagy is the underlying mechanism by which expression of PrP is up-regulated,and tumor cell migration is enhanced upon TNFα treatment. Disrupting the TNFα-NF-κB-FOXP3-SNAP29 signaling axis may provide a therapeutic approach to mitigate tumor cell migration.
基金National Key Research and Development Program of China(No.2022YFA1604900)National Natural Science Foundation of China(No.12025501)Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB34000000)。
文摘In the paper,we discuss the development of the multigap resistive plate chamber time-of-fight(TOF)technology and the production of the solenoidal tracker at RHIC(STAR)TOF detector in China at the beginning of the twenty-frst century.Subsequently,recent experimental results from the frst beam energy scan program(BES-I)at the Relativistic Heavy Ion Collider(RHIC)pertaining to measurements of collectivity,chirality,criticality,global polarization,strangeness,heavy favor,dilepton and light nuclei productions are reviewed.
基金This work was supported by National Key Research and Development Program of China(Nos.2018YFE0205200,2018YFE0104700,and 2020YFE0202002)National Natural Science Foundation of China(No.11890712)+2 种基金Natural Science Foundation of Anhui Province(No.1808085J02)Fundamental Research Funds for the Central Universities(No.WK2030000013)the Project funded by the China Postdoctoral Science Foundation(No.2019M652177).
文摘We present a comprehensive study on the individual sources of an inclusive photon production during high-energy hadronic collisions.The cross section and invariant yields of inclusive photons are obtained as a function of pT at mid-rapidity(|y|<0.5)in p+p and Au+Au collisions at√SNN=200GeVrespectively.These results provide crucial inputs to separate measurements of open bottom and charm hadron yield suppression in heavyion collisions,which are used to test the mass hierarchy of the parton energy loss in the quark gluon plasma created during these collisions.The procedure developed in this study can also be applied to other measurements of electrons from an open heavy-flavor hadron decay,such as the collective flow in the RHIC beam energy scan program.
基金supported by the grants from the National Natural Science Foundation of China (No.31101038 to M.Shao,31471360 and 31671509 to D.-L.Shi)Shandong Provincial Natural Science Foundation (ZR2017BC068 to M.Shao)
文摘Since its first application to induce mutations in mammalian cells （Cong et al., 2013： Mall et al., 2013）, CRISPR/Cas9 has rapidly become a routine technique to perform genome editing in a variety of biological systems due to its facile, robust, and multiplexable fea- tures （Hwang et al, 2013; Wang et al., 2013; Guo et al., 2014; Liu, 2017）.
基金financially supported by the National Natural Science Foundation of China(Nos.41503048,41872145)the Key Laboratory Project of Gansu Province(No.1309RTSA041)。
文摘The mudstone,gray tuffite and carbonaceous shale in the Upper Carboniferous Batamayineishan Formation(Bashan Formation)are essential source rocks for the volcanic reservoir in eastern Junggar,northwestern China.The kerogen components,vitrinite reflectance,Rock-Eval pyrolysis,lipid biomarkers and isotope compositions were measured to understand the provenance and depositional environment of Bashan Formation under the background of volcanic activities.There were 10 and 4 periods of volcanic eruptions identified in the wells CS and DZ,respectively.The source rocks developed in the late or intermittent phase of volcanic activity.The original island arcs of the Early Carboniferous evolved into the Wucaiwan sag and the Dishuiquan sag in the Bashan Formation.The Wucaiwan sag inherited the restricted,closed residual sea,which had a slightly anoxic and hypersaline environment.The Dishuiquan sag was generally an oxidizing lacustrine environment,influenced by a marine transgression that may have occurred at the end of the DZ_(Ⅲ)period during the Late Carboniferous.Although the total organic matter decreased due to the volcanic eruption,ash could cause an increase of aquatic organisms,coinciding with increases in salinity and reducibility in the Dishuiquan sag.
基金supported by the National Natural Science Foundation of China grant(52273197,52303382)the Shenzhen Key Laboratory of Functional 383 Aggregate Materials(ZDSYS 20211021111400001)+2 种基金the Science,Technology,and 384 Innovation Commission of Shenzhen Municipality(JCYJ 2021324134613038,JCYJ 20220530143805012,KQTD 20210811090142053,GJHZ 20210705141810031)the Innovation and Technology Commission(ITC-CNERC14SC01 and ITCPD/17-9)YXLH-AIE2022.
文摘Efficient photosensitizers are crucial for the success of photodynamic therapy(PDT).Herein,we reported two[3+2+1]coordinated organometallic Iridium(III)complexes(labeled as Ir-C1 and Ir-C4).Ir-C1/C4 can generate both type I and type II reactive oxygen species(ROS).In vitro experiments,Ir-C1/C4 show low biotoxicity and high phototoxicity of half-maximal inhibitory concentration values of 14 nM and 33 nM on rectal cancer cell line HCT116,respectively.Western blot analysis revealed that the Ir-C1/C4 activated ferroptosis,apoptosis,and inhibiting autophagy simultaneously.Proteomics analysis demonstrated that the photosensitizers destroyed the endoplasmic reticulum(ER),blocking the signal transmission and material transfer between the ER and other tissues of the cell,especially the ER to Golgi vesicle-mediated transport.Ir-C1/C4 can achieve better antitumor performance than commercial photosensitizer Chlorin e6 and the ferroptosis activator RSL3 at lower concentrations.The low biotoxicity and high phototoxicity make them ideal candidates for PDT.The findings provide new insights into the design of photosensitizers for metal complexes and have significant implications for the development of PDT and related drugs.
基金supported in part by Guangxi Science and Technology Program,China(2024AB12006)the Open Fund of Innovation Center for Control Actuators,China(ICCA18-202405)China Huaneng Group.,Ltd.Headquarters Technology Project(HNKJ24-HF15).
文摘Humanoid robot joints require real-time torque detection to provide accurate force feedback informa-tion for the control system.To meet the measurement requirements and realize the miniaturization of the sensor,a torque sensor based on the magnetoelastic effect is developed,utilizing planar spiral coils as detection probes.In this work,a planar spiral coil mutual inductance calculation model is established to solve the mutual inductance coefficient,and the mechanical structure and circuit design of the sensor are completed.Finally,a torque loading platform is built to perform calibration experiments,and the hysteresis model is improved to compensate for the hysteresis phenomenon.The calibration results indicate that the sensor shows excellent loaded nonlinearity of 3.08%F.S.,unloaded nonlinearity of 2.71% F.S.,loaded repeatability of 2.48% F.S.,unloaded repeatability of 1.89% F.S.and hysteresis of 1.9% F.S.,at a compact probe size of 13.8×9.9×1.8 mm.
基金supported by the National Natural Science Foundation of China(22222706,22307107,22477144)the National Key R&D Program of China(2020YFA0211200)the Guangdong Basic Research Center of Excellence(GBRCE)for Functional Molecular Engineering and the Guangdong Basic and Applied Basic Research Foundation(2024B1515040028)。
文摘Gene expression must be precisely regulated in cells and functional nucleic acids are the most widely utilized tools for gene manipulation.Photocontrol of how these nucleic acid tools work in the cellular environment can precisely manipulate gene expression through a non-invasive way.Here we report a methodology on multiplex photocontrol of functional nucleic acids to achieve totally temporal and orthogonal regulation of gene expression in living cells.We select two functional nucleic acid systems as examples,DNAzyme and CRISPR/Cas9,and demonstrate the power of light control for precise gene manipulation by rational design of chemically modified oligonucleotides through introduction of two photocleavable linkers.Unlike the previous modulation of functional nucleic acids by simply activating or deactivating,we successfully achieve versatile controlling patterns using light as the governing factor.This design represents a generalized pathway towards the photo-controllable functional nucleic acids,which greatly enriches the toolbox for optogenetic studies.
基金This work was supported by the National Key Basic Research Program of China[grant numbers G1999054008,2006cb500706,2011CB504104]the National Natural Science Foundation of China[grant number 81430022]the Shanghai Science and Technology Fund[grant number 10411954500].
文摘Background:Parkinson’s disease(PD)is a chronic,progressive and debilitating disease,which affects over 2.5 million people in China.PD is characterized clinically by resting tremor,muscular rigidity,bradykinesia and postural instability.As the disease progresses,additional complications can arise such as non-motor and neurobehavioral symptoms.Pharmacological treatment and surgical intervention for PD have been implemented in China.Until 10 years ago,there was lack of standardization for the management of PD in different regions and among different physicians,leading to different treatment levels in different regions and different physicians.Since then,the Chinese Parkinson’s Disease and Movement Disorder Society have published three versions of guidelines for the management of PD in China,in 2006,2009 and 2014,respectively.Correspondingly,the overall level of treatment for PD in China improved.Objectives:To update the treatment guidelines based on current foreign and domestic practice guidelines and clinical evidence,and to improve the treatment options available to physicians in the management of PD.Summary:A variety of treatment recommendations in the treatment guidelines have been proposed,including physical activity and disease-modifying medication,which should be initiated at the early-stage of the disease.The principles of dosage titration should be followed to avoid acute adverse reactions to the drugs,to achieve a satisfactory clinical effect with a low dose and to reduce the incidence of long-term motor complications.Moreover,different treatment strategies should be considered at different stages of the disease.Importantly,treatment guidelines and personalized treatments should be valued equally.A set of treatment recommendations has been developed to assist physicians to improve and optimize clinical outcomes for patients with PD in China.
基金by Novartis China.This work was also supported by grants from the National Program of Basic Research(2011CB504104)of ChinaNational“Twelfth Five-Year”Plan for Science&Technology Support(2012BAI10B03).
文摘Objective:Chronic levodopa(L-dopa)treatment in Parkinson’s disease(PD)is often associated with the development of motor complications,but the corresponding epidemiological data is rare in Chinese PD patients.The present survey was to investigate the prevalence rate of wearing-off(WO)and dyskinesia among the patients with PD in China.Methods:From May 2012 to October 2012,a 3-step registry survey for wearing off(WO)and dyskinesia patients with PD receiving levodopa therapy was performed simultaneously at 28 movement disorders clinics in China.Results:There were 1,558 PD patients fulfilling the inclusion criteria.Among them,1,051 had at least one positive response of 9-item wearing off questionnaire(WOQ-9),724 and 160 patients were finally diagnosed with WO and dyskinesia by movement disorders specialists,respectively.The overall prevalence rates of WO and dyskinesia were 46.5%(95%CI 44.0%-48.9%)and 10.3%(95%CI 8.8%-11.8%),respectively.The mean score of WOQ-9 for those with WO was 3.8(SD=1.8),with movement slowness being the most common motor symptoms and pain/aching being the most common non-motor symptoms.Better improvement of motor symptoms(n=354,87.8%)and long-term disease control and drug selection(n=288,71.5%)were the two most frequently considered factors when movement disorders specialists adjusted therapeutic strategies for patients with WO.Conclusions:This survey provided the first multi-center epidemiological data of motor complications among PD patients on L-dopa therapy from China's Mainland.WO prevalence rate among Chinese PD patients was in line with,while dyskinesia prevalence rate was lower than previous reports from other Countries.
基金supported by National Program on Key Basic Research Project(Grant No.2015CB856903)National Natural Science Foundation of China(Grant No.U1332207)
文摘One of the main purposes of heavy-ion collisions over a wide range of beam energy is to study the bulk properties of strong interaction matter and understand the Quantum Chromo Dy- namics （QCD） phase diagram, which carries wealth of infor- mation of the phase transition and the possibly existing criti- cal point of the strongly interacting system [1]. Such system exists as hadron gases at lower temperature and low baryon density. By increasing the temperature or density, the bound- ary of the hadrons disappears and the confined quarks move freely in the whole system.
文摘Background:Rasagiline is a monoamine oxidase-B inhibitor used for Parkinson’s disease(PD)treatment,but its effectiveness on Chinese patients is unclear.This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD.Methods:A 26-weeks,randomized,double-blind,placebo-controlled study has been performed at 15 sites in China and enrolled outpatients(≥35 years old)with idiopathic PD without a history of using any dopaminergic drugs.Participants were randomized 1:1 to receive rasagiline 1 mg once daily or placebo.The primary endpoint was the change of the Unified Parkinson’s Disease Rating Scale(UPDRS)total score from baseline to 26 weeks treatment.Secondary endpoints included changes in UPDRS subscale scores from part Ⅰ to Ⅲ.Health status was assessed with the PD Questionnaire(PDQ)-39 and EuroQol-Five-Dimension(EQ-5D)questionnaire.Safety profile was collected until 30 weeks after randomization.Results:A total of 130 patients(n=65/group)were recruited,and 127(rasagiline,n=64;placebo,n=63)were included in the full analysis set.Baseline characteristics were comparable between the two groups.The decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group(−3.18±0.95 vs.−0.18±0.98,P=0.025),and the mean UPDRS part I non-motor symptoms score(−0.54±0.15 vs.-0.08±0.15,P=0.003)were significantly decreased in the rasagiline group compared with placebo treated patients.An improvement trend was observed in the active treatment group for the subscales evaluation with parts Ⅱ and Ⅲ,while the difference to placebo was not statistically significant.Life quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated patients.The overall incidence of treatment-emergent adverse events(AEs)was slightly lower in the rasagiline group(41.5%)than in the placebo group(46.2%).Conclusions:Rasagiline is effective,safe,and well tolerated as monotherapy for the treatment of Chinese PD patients.
