Warm dense plasmas are crucial for high-energy-density physics and inertial confinement fusion research.Experiments involving laser-irradiated copper(Cu)foil were performed at the Shenguang-II facility.A highly orient...Warm dense plasmas are crucial for high-energy-density physics and inertial confinement fusion research.Experiments involving laser-irradiated copper(Cu)foil were performed at the Shenguang-II facility.A highly oriented pyrolytic graphite crystal spectrometer measured the time-integrated spectral distribution of Cu under varying laser intensities.Using the two-dimensional radiation-hydrodynamics code FLASH and the spectral analysis code FLYCHK,we simulated the temporal evolution of plasma density and temperature distributions,as well as the emission intensities of spectral lines at different temperatures and densities.The simulation results revealed that the two-electron satellite lines(J)and the resonance line(W)emissions of Cu originate predominantly from the radiation region near the critical density surface,with a density range from approximately 0.5 nc to 1.0 nc,and radiate primarily during the laser irradiation period.By analyzing the J/W intensity ratio of the measured spectral lines,we estimated the electron temperatures near the critical-density surface under different laser intensities.展开更多
The large manipulator outside the space cabin is a multi-degree of freedom actuator for space operations.In order to realize the automatic control and flexible operation of the space manipulator,a novel spoke structur...The large manipulator outside the space cabin is a multi-degree of freedom actuator for space operations.In order to realize the automatic control and flexible operation of the space manipulator,a novel spoke structure piezoelectric six-dimensional force/torque sensor with redundancy ability,high stiffness and good decoupling performance is innovatively proposed.Based on the deformation coordination relationship,the redundancy measurement mechanism is revealed.The mathematical models of the sensor with and without branch fault are established respectively.The finite element model is established to verify the feasibility of structure and redundancy measuring principle of the sensor.Depending on the theoretical analysis and simulation analysis,the prototype of the sensor is developed.Static and dynamic calibration experiments are carried out.The actual output voltage signal of the six-dimensional force/torque sensor is collected to establish the equation between the standard input applied load and the actual output voltage signal.Based on ant colony optimized BP algorithm,performance indexes of the sensor with and without branch fault are analyzed respectively.The experimental results show that the spoke piezoelectric sixdimensional force/torque sensor with the eight-point support structure has good accuracy and reliability.Meanwhile,it has strong decoupling characteristic that can effectively shield the coupling between dimensions.The nonlinear errors and maximum interference errors of decoupled data with and without branch faults are less than 1% and 2%,respectively.The natural frequency of the sixdimensional force sensor can reach 2856.45 Hz and has good dynamic characteristics.The research content lays a theoretical and experimental foundation for the design,development and application of the new six-dimensional force/torque sensors with redundancy.Meanwhile,it will significantly improve the research level in this field,and provide a strong guarantee for the smooth implementation of force feedback control of the space station manipulator project.展开更多
Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on su...Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.展开更多
We developed a monochromatic crystal backlight imaging system for the double-cone ignition(DCI) scheme, employing a spherically bent quartz crystal. This system was used to measure the spatial distribution and tempora...We developed a monochromatic crystal backlight imaging system for the double-cone ignition(DCI) scheme, employing a spherically bent quartz crystal. This system was used to measure the spatial distribution and temporal evolution of the head-on colliding plasma from the two compressing cones in the DCI experiments. The influence of laser parameters on the x-ray backlighter intensity and spatial resolution of the imaging system was investigated. The imaging system had a spatial resolution of 10 μm when employing a CCD detector. Experiments demonstrated that the system can obtain time-resolved radiographic images with high quality, enabling the precise measurement of the shape, size, and density distribution of the plasma.展开更多
Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed th...Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC<sub>50</sub> values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.展开更多
Adventitious root(AR)formation is critical for the efficient propagation of elite horticultural and forestry crops.Despite decades of research,the cellular processes and molecular mechanisms underlying AR induction in...Adventitious root(AR)formation is critical for the efficient propagation of elite horticultural and forestry crops.Despite decades of research,the cellular processes and molecular mechanisms underlying AR induction in woody plants remain obscure.We examined the details of AR formation in apple(Malus domestica)M.9 rootstock,the most widely used dwarf rootstock for intensive production,and investigated the role of polar auxin transport in postembryonic organogenesis.AR formation begins with a series of founder cell divisions and elongation of the interfascicular cambium adjacent to vascular tissues.This process is associated with a relatively high indole acetic acid(IAA)content and hydrolysis of starch grains.Exogenous auxin treatment promoted this cell division,as well as the proliferation and reorganization of the endoplasmic reticulum and Golgi membrane.In contrast,treatment with the auxin transport inhibitor N-1-naphthylphthalamic acid(NPA)inhibited cell division in the basal region of the cuttings and resulted in abnormal cell divisions during the early stage of AR formation.In addition,PIN-FORMED(PIN)transcripts were differentially expressed throughout the whole AR development process.We also detected upregulation of MdPIN8 and MdPIN10 during induction;upregulation of MdPIN4,MdPIN5,and MdPIN8 during extension;and upregulation of all MdPINs during AR initiation.This research provides an improved understanding of the cellular and molecular underpinnings of the AR process in woody plants.展开更多
Background: Individualized corneal refractive surgery requires an understanding of the basis of higher-order aberrations before surgery. To investigate the characteristics and distribution of anterior surface wavefron...Background: Individualized corneal refractive surgery requires an understanding of the basis of higher-order aberrations before surgery. To investigate the characteristics and distribution of anterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods: A total of 121 myopic patients (121 eyes, 18 - 45 years old) who underwent corneal refractive surgery were recruited from January to May 2016 at Affiliated Hospital, Yanbian University. Patients were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -0.25 to -10.00 D. The corneal anterior aberrations (total higher-order aberration;spherical aberration;Coma;Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results: The root-mean-square (RMS) of the third to sixth order aberrations of the corneal anterior wavefront aberrations at a 6 mm analysis diameter showed a decreasing trend in patients suitable for the corneal refractive surgery, and the RMS of the third order aberrations accounted for 62.92% of the total HOAs. The coma ratio (coma/total cornea higher-order aberrations) was increased with the increasing diopters, while the spherical aberration ratio (spherical aberration/total cornea higher-order aberrations) was not changed. In addition, the spherical aberration was 0.203 ± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19 ± 0.03 (range: -0.58 to 0.31). There were significant differences in the coma aberrations of preoperative corneal anterior surface (3, 1) between the low, middle and high myopia groups (P = 0.013). The spherical equivalent was positively correlated with the corneal coma of the anterior corneal surfaces (R =?-0.241, P = 0.009), and the Q value was positively correlated with the total higher-order aberrations (R = 0.326, P Conclusions: Individual wavefront aberrations on the anterior surfaces of the cornea are comparatively different, and the Zernike coefficients are related to the degree of myopia. Spherical aberrations are the most overriding aberrations of the cornea.展开更多
The spherical crystal imaging system,noted for its high energy spectral resolution(monochromaticity)and spatial resolution,is extensively applied in high energy density physics and inertial confinement fusion research...The spherical crystal imaging system,noted for its high energy spectral resolution(monochromaticity)and spatial resolution,is extensively applied in high energy density physics and inertial confinement fusion research.This system supports studies on fast electron transport,hydrodynamic instabilities,and implosion dynamics.The x-ray source,produced through laser-plasma interaction,emits a limited number of photons within short time scales,resulting in predominantly photon-starved images.Through ray-tracing simulations,we investigated the impact of varying crystal dimensions on the performance of a spherical crystal self-emission imager.We observed that increasing the crystal dimension leads to higher imaging efficiency but at the expense of monochromaticity,causing broader spectral acceptance and reduced spatial resolution.Furthermore,we presented a theoretical model to estimate the spatial resolution of the imaging system within a specific energy spectrum range,detailing the expressions for the effective size of the crystal.The spatial resolution derived from the model closely matches the numerical simulations.展开更多
The acute onset of the vision loss by optic never injury following orbital wall reconstruction, has been reported in 0.5% - 5.0% of the cases. Visual impairment can be recovered within an early period after injury. De...The acute onset of the vision loss by optic never injury following orbital wall reconstruction, has been reported in 0.5% - 5.0% of the cases. Visual impairment can be recovered within an early period after injury. Delayed visual recovery from optic nerve injury during a procedure of orbital wall reconstruction has not been reported. We report a case of delayed recovery from optic nerve injury which occurred following orbital wall reconstruction. A 78-year-old man underwent orbital wall reconstruction for medial wall fracture and resulting enophthalmos in the right eye, one week after a traffic accident. Immediate after surgery, postoperative visual acuity in the right eye decreased to light perception, and relative afferent pupillary defect (RAPD) was detected. In spite of mega-dose steroid treatment, the visual acuity did not improve. However, 8 months after surgery, visual acuity began to recover to 0.1, and the degree of RAPD decreased. Twelve months after surgery, visual acuity in the right eye was 0.4, and pupillary light reflex was normal. Our report suggests that patients with optic neuropathy by surgery or trauma require long-term follow-up, regardless of early response to mega-dose steroid treatment.展开更多
Grouting defects are an inherent challenge in construction practices,exerting a considerable impact on the operational structural integrity of connections.This investigation employed the impact-echo technique for the ...Grouting defects are an inherent challenge in construction practices,exerting a considerable impact on the operational structural integrity of connections.This investigation employed the impact-echo technique for the detection of grouting anomalies within connections,enhancing its precision through the integration of wavelet packet energy principles for damage identification purposes.A series of grouting completeness assessments were meticulously conducted,taking into account variables such as the divergent material properties of the sleeves and the configuration of adjacent reinforcement.The findings revealed that:(i)the energy distribution for the highstrength concrete cohort predominantly occupied the frequency bands 42,44,45,and 47,whereas for other groups,it was concentrated within the 37 to 40 frequency band;(ii)the delineation of empty sleeves was effectively discernible by examining the wavelet packet energy ratios across the spectrum of frequencies,albeit distinguishing between sleeves with 50%and full grouting density proved challenging;and(iii)the wavelet packet energy analysis yielded variable detection outcomes contingent on the material attributes of the sleeves,demonstrating heightened sensitivity when applied to ultrahigh-performance concrete matrices and GFRP-reinforced steel bars.展开更多
CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against mobile genetic elements(MGEs)through uptake of invader-derived spacers.De novo adaptation samples spacers from both invaders and hosts,whe...CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against mobile genetic elements(MGEs)through uptake of invader-derived spacers.De novo adaptation samples spacers from both invaders and hosts,whereas primed adaptation shows higher specificity to sample spacers from invaders in many model systems as well as in the subtype I-F system of Zymomonas mobilis.Self-derived spacers will lead to CRISPR self-interference.However,our in vivo study demonstrated that this species used the microhomology-mediated end joining(MMEJ)pathway to efficiently repair subtype I-F CRISPR-Cas system-mediated DNA breaks guided by the self-targeting spacers.MMEJ repair of DNA breaks requires direct microhomologous sequences flanking the protospacers and leads to DNA deletions covering the protospacers.Importantly,CRISPR-mediated genomic DNA breaks failed to be repaired via MMEJ pathway in presence of higher copies of short homologous DNA.Moreover,CRISPR-cleaved exogenous plasmid DNA was failed to be repaired through MMEJ pathway,probably due to the inhibition of MMEJ by the presence of higher copies of the plasmid DNA in Z.mobilis.Our results infer that MMEJ pathway discriminates DNA damages between in the host chromosome versus mobile genetic element(MGE)DNA,and maintains genome stability post CRISPR immunity in Z.mobilis.展开更多
Inertial fusion energy （IFE） has been considered a promising, nearly inexhaustible source of sustainable carbon-free power for the world＇s energy future. It has long been recognized that the control of hydrodynamic...Inertial fusion energy （IFE） has been considered a promising, nearly inexhaustible source of sustainable carbon-free power for the world＇s energy future. It has long been recognized that the control of hydrodynamic instabilities is of critical importance for ignition and high-gain in the inertial-confinement fusion （ICF） hot-spot ignition scheme. In this mini-review, we summarize the progress of theoretical and simulation research of hydrodynamic instabilities in the ICF central hot-spot implosion in our group over the past decade. In order to obtain sufficient understanding of the growth of hydrodynamic instabilities in ICF, we first decompose the problem into different stages according to the implosion physics processes. The decomposed essential physics pro- cesses that are associated with ICF implosions, such as Rayleigh-Taylor instability （RTI）, Richtmyer-Meshkov instability （RMI）, Kelvin-Helmholtz instability （KHI）, convergent geometry effects, as well as perturbation feed-through are reviewed. Analyti- cal models in planar, cylindrical, and spherical geometries have been established to study different physical aspects, including density-gradient, interface-coupling, geometry, and convergent effects. The influence of ablation in the presence of preheating on the RTI has been extensively studied by numerical simulations. The KHI considering the ablation effect has been discussed in detail for the first time. A series of single-mode ablative RTI experiments has been performed on the Shenguang-II laser facility. The theoretical and simulation research provides us the physical insights of linear and weakly nonlinear growths, and nonlinear evolutions of the hydrodynamic instabilities in ICF implosions, which has directly supported the research of ICF ignition target design. The ICF hot-spot ignition implosion design that uses several controlling features, based on our current understanding of hydrodynamic instabilities, to address shell implosion stability, has been briefly described, several of which are novel.展开更多
Gene editing technology involves the modification of a specific target gene to obtain a new function or phenotype.Recent advances in clustered regularly interspaced short palindromic repeats(CRISPR)-Cas-mediated techn...Gene editing technology involves the modification of a specific target gene to obtain a new function or phenotype.Recent advances in clustered regularly interspaced short palindromic repeats(CRISPR)-Cas-mediated technolo-gies have provided an efficient tool for genetic engineering of cells and organisms.Here,we review the three emerging gene editing tools(ZFNs,TALENs,and CRISPR-Cas)and briefly introduce the principle,classification,and mechanisms of the CRISPR-Cas systems.Strategies for gene editing based on endogenous and exogenous CRISPR-Cas systems,as well as the novel base editor(BE),prime editor(PE),and CRISPR-associated transposase(CAST)technologies,are described in detail.In addition,we summarize recent developments in the application of CRISPR-based gene editing tools for industrial microorganism and probiotics modifications.Finally,the potential challenges and future perspectives of CRISPR-based gene editing tools are discussed.展开更多
Archaea represents the third domain of life, with the information-processing machineries more closely resembling those of eukaryotes than the machineries of the bacterial counterparts but sharing metabolic pathways wi...Archaea represents the third domain of life, with the information-processing machineries more closely resembling those of eukaryotes than the machineries of the bacterial counterparts but sharing metabolic pathways with organisms of Bacteria, the sister prokaryotic phylum. Archaeal organisms also possess unique features as revealed by genomics and genome comparisons and by biochemical characterization of prominent enzymes. Nevertheless, diverse genetic tools are required for in vivo experiments to verify these interesting discoveries. Considerable efforts have been devoted to the development of genetic tools for archaea ever since their discovery, and great progress has been made in the creation of archaeal genetic tools in the past decade. Versatile genetic toolboxes are now available for several archaeal models, among which Sulfolobus microorganisms are the only genus representing Crenarchaeota because all the remaining genera are from Euryarchaeota. Nevertheless, genetic tools developed for Sulfolobus are probably the most versatile among all archaeal models, and these include viral and plasmid shuttle vectors, conventional and novel genetic manipulation methods, CRISPR-based gene deletion and mutagenesis, and gene silencing, among which CRISPR tools have been reported only for Sulfolobus thus far. In this review, we summarize recent developments in all these useful genetic tools and discuss their possible application to research into archaeal biology by means of Sulfolobus models.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the global pandemic coronavirus disease 2019(COVID-19),has proven itself to be a highly virulent respiratory pathogen with...Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the global pandemic coronavirus disease 2019(COVID-19),has proven itself to be a highly virulent respiratory pathogen with an unpredictable evolutionary capacity,posing a persistent threat to mankind.At the time of this manuscript’s publication.展开更多
Coronavirus-related diseases pose a significant challenge to the global health system.Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks,the traditional“one bug,one drug”paradigm ...Coronavirus-related diseases pose a significant challenge to the global health system.Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks,the traditional“one bug,one drug”paradigm struggles to address the growing number of emerging crises.Therefore,there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity.Here,we provide evidence that ATV006,an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase(RdRp),has broad antiviral activity against human and animal coronaviruses.Using mouse hepatitis virus(MHV)and human coronavirus NL63(HCoV-NL63)as a model,we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo.Remarkably,ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection.Due to its oral bioavailability and potency against multiple coronaviruses,ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.展开更多
Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing ...Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing tools are not available for this species.In this study,we developed an efficient genome editing tool for T.thermophilus HB27 based on its endogenous type IB,I-C,and III-A/B CRISPR-Cas systems.First,we systematically characterized the DNA interference capabilities of the different types of the native CRISPR-Cas systems in T.thermophilus HB27.We found that genomic manipulations such as gene deletion,mutation,and in situ tagging could be easily implemented by a series of genome-editing plasmids carrying an artificial self-targeting mini-CRISPR and a donor DNA responsible for the recombinant recovery.We also compared the genome editing efficiency of different CRISPR-Cas systems and the editing plasmids with donor DNAs of different lengths.Additionally,we developed a reporter gene system for T.thermophilus based on a heat-stableβ-galactosidase gene TTP0042,and constructed an engineered strain with a high production capacity of superoxide dismutases by genome modification.展开更多
Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targ...Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.Methods:We constructed an iASPP-derived peptide,called A8,that was derived from the C-terminus of iASPP.Here,we transfected A8 into two wildtype(WT)p53 cell lines,U2OS and A549,and then determined the number of apoptotic cells.The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation(IP),Dual-Luciferase reporter assays,and chromatin IP assays.Real-time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis-related factors.Results:Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines.Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters.Moreover,A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.Conclusions:These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.展开更多
A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up t...A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up to 97%yield)and excellent enantioselectivities(up to 97%ee).Moreover,the reaction worked well on a gram scale,indicating that our protocol has potential applications in the synthesis of chiral ligands and organocatalysts.展开更多
基金Project supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDA25051000,XDA25010100,XDA25010300,XDA25030100,and XDA25030200)。
文摘Warm dense plasmas are crucial for high-energy-density physics and inertial confinement fusion research.Experiments involving laser-irradiated copper(Cu)foil were performed at the Shenguang-II facility.A highly oriented pyrolytic graphite crystal spectrometer measured the time-integrated spectral distribution of Cu under varying laser intensities.Using the two-dimensional radiation-hydrodynamics code FLASH and the spectral analysis code FLYCHK,we simulated the temporal evolution of plasma density and temperature distributions,as well as the emission intensities of spectral lines at different temperatures and densities.The simulation results revealed that the two-electron satellite lines(J)and the resonance line(W)emissions of Cu originate predominantly from the radiation region near the critical density surface,with a density range from approximately 0.5 nc to 1.0 nc,and radiate primarily during the laser irradiation period.By analyzing the J/W intensity ratio of the measured spectral lines,we estimated the electron temperatures near the critical-density surface under different laser intensities.
基金supported by the National Natural Science Foundation of China(No.51875250)a Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program,China(No.2019KJB018)a Project of the“20 Regulations for New Universities”Funding Program of Jinan,China(No.202228116)。
文摘The large manipulator outside the space cabin is a multi-degree of freedom actuator for space operations.In order to realize the automatic control and flexible operation of the space manipulator,a novel spoke structure piezoelectric six-dimensional force/torque sensor with redundancy ability,high stiffness and good decoupling performance is innovatively proposed.Based on the deformation coordination relationship,the redundancy measurement mechanism is revealed.The mathematical models of the sensor with and without branch fault are established respectively.The finite element model is established to verify the feasibility of structure and redundancy measuring principle of the sensor.Depending on the theoretical analysis and simulation analysis,the prototype of the sensor is developed.Static and dynamic calibration experiments are carried out.The actual output voltage signal of the six-dimensional force/torque sensor is collected to establish the equation between the standard input applied load and the actual output voltage signal.Based on ant colony optimized BP algorithm,performance indexes of the sensor with and without branch fault are analyzed respectively.The experimental results show that the spoke piezoelectric sixdimensional force/torque sensor with the eight-point support structure has good accuracy and reliability.Meanwhile,it has strong decoupling characteristic that can effectively shield the coupling between dimensions.The nonlinear errors and maximum interference errors of decoupled data with and without branch faults are less than 1% and 2%,respectively.The natural frequency of the sixdimensional force sensor can reach 2856.45 Hz and has good dynamic characteristics.The research content lays a theoretical and experimental foundation for the design,development and application of the new six-dimensional force/torque sensors with redundancy.Meanwhile,it will significantly improve the research level in this field,and provide a strong guarantee for the smooth implementation of force feedback control of the space station manipulator project.
基金the Key Discipline of Zhejang Province in Public Health and Preventative Medicine(First Class,Category A)at the Hangzhou Medical College,China.
文摘Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.
基金Project supported by the staff of the Shenguang-Ⅱ upgrade Laser facilityThis study was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDA25010100,XDA25010300,XDA25030100,XDA25030200,and XDA25051000)+2 种基金the National Natural Science Foundation of China(Grant Nos.11827807 and 12105359)the Open Foundation of Key Laboratory of High Power Laser and Physics of Chinese Academy of Sciences(Grant No.SGKF202105)the Chinese Academy of Sciences Youth Interdisciplinary Team(Grant No.JCTD-2022-05).
文摘We developed a monochromatic crystal backlight imaging system for the double-cone ignition(DCI) scheme, employing a spherically bent quartz crystal. This system was used to measure the spatial distribution and temporal evolution of the head-on colliding plasma from the two compressing cones in the DCI experiments. The influence of laser parameters on the x-ray backlighter intensity and spatial resolution of the imaging system was investigated. The imaging system had a spatial resolution of 10 μm when employing a CCD detector. Experiments demonstrated that the system can obtain time-resolved radiographic images with high quality, enabling the precise measurement of the shape, size, and density distribution of the plasma.
文摘Virus nucleoprotein (NP) is an emerging target for drug development for Influenza. We designed benzamide derivatives as new inhibitors of NP that demonstrate good potency in blocking influenza A. Screening revealed that compound 39 was the most potent molecule in the series, exhibiting IC<sub>50</sub> values of 0.46 and 0.27 μM in blocking the replication of H3N2 (A/HK/8/68) and (A/WSN/33) influenza A viral strains. The observed inhibition of viral replication correlated well with cytopathic protection. Furthermore, based on computational analysis and fluorescence microscopy, it was determined that compound 39 inhibited nuclear accumulation by targeting influenza A viral nucleoproteins. Finally, the rodent pharmacokinetic profile of compound 32 displayed half-life of greater than 4 hours and bioavailability greater than 20%, suggesting this class of molecules had drug-like properties.
基金supported by the National Natural Science Foundation of China(Grant no.31601738).
文摘Adventitious root(AR)formation is critical for the efficient propagation of elite horticultural and forestry crops.Despite decades of research,the cellular processes and molecular mechanisms underlying AR induction in woody plants remain obscure.We examined the details of AR formation in apple(Malus domestica)M.9 rootstock,the most widely used dwarf rootstock for intensive production,and investigated the role of polar auxin transport in postembryonic organogenesis.AR formation begins with a series of founder cell divisions and elongation of the interfascicular cambium adjacent to vascular tissues.This process is associated with a relatively high indole acetic acid(IAA)content and hydrolysis of starch grains.Exogenous auxin treatment promoted this cell division,as well as the proliferation and reorganization of the endoplasmic reticulum and Golgi membrane.In contrast,treatment with the auxin transport inhibitor N-1-naphthylphthalamic acid(NPA)inhibited cell division in the basal region of the cuttings and resulted in abnormal cell divisions during the early stage of AR formation.In addition,PIN-FORMED(PIN)transcripts were differentially expressed throughout the whole AR development process.We also detected upregulation of MdPIN8 and MdPIN10 during induction;upregulation of MdPIN4,MdPIN5,and MdPIN8 during extension;and upregulation of all MdPINs during AR initiation.This research provides an improved understanding of the cellular and molecular underpinnings of the AR process in woody plants.
文摘Background: Individualized corneal refractive surgery requires an understanding of the basis of higher-order aberrations before surgery. To investigate the characteristics and distribution of anterior surface wavefront aberrations in patients suitable for corneal refractive surgery. Methods: A total of 121 myopic patients (121 eyes, 18 - 45 years old) who underwent corneal refractive surgery were recruited from January to May 2016 at Affiliated Hospital, Yanbian University. Patients were randomly selected by the Pentacam anterior segment analysis system with a spherical equivalent (SE) of -0.25 to -10.00 D. The corneal anterior aberrations (total higher-order aberration;spherical aberration;Coma;Trefoil) and Q and K values were detected, and a correlation analysis of the relevant parameters was carried out. Results: The root-mean-square (RMS) of the third to sixth order aberrations of the corneal anterior wavefront aberrations at a 6 mm analysis diameter showed a decreasing trend in patients suitable for the corneal refractive surgery, and the RMS of the third order aberrations accounted for 62.92% of the total HOAs. The coma ratio (coma/total cornea higher-order aberrations) was increased with the increasing diopters, while the spherical aberration ratio (spherical aberration/total cornea higher-order aberrations) was not changed. In addition, the spherical aberration was 0.203 ± 0.082 μm (range: 0.061 to 0.503 μm), and the Q30 was -0.19 ± 0.03 (range: -0.58 to 0.31). There were significant differences in the coma aberrations of preoperative corneal anterior surface (3, 1) between the low, middle and high myopia groups (P = 0.013). The spherical equivalent was positively correlated with the corneal coma of the anterior corneal surfaces (R =?-0.241, P = 0.009), and the Q value was positively correlated with the total higher-order aberrations (R = 0.326, P Conclusions: Individual wavefront aberrations on the anterior surfaces of the cornea are comparatively different, and the Zernike coefficients are related to the degree of myopia. Spherical aberrations are the most overriding aberrations of the cornea.
基金Project supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDA25051000,XDA25010100,XDA25010300,XDA25030100,and XDA25030200)。
文摘The spherical crystal imaging system,noted for its high energy spectral resolution(monochromaticity)and spatial resolution,is extensively applied in high energy density physics and inertial confinement fusion research.This system supports studies on fast electron transport,hydrodynamic instabilities,and implosion dynamics.The x-ray source,produced through laser-plasma interaction,emits a limited number of photons within short time scales,resulting in predominantly photon-starved images.Through ray-tracing simulations,we investigated the impact of varying crystal dimensions on the performance of a spherical crystal self-emission imager.We observed that increasing the crystal dimension leads to higher imaging efficiency but at the expense of monochromaticity,causing broader spectral acceptance and reduced spatial resolution.Furthermore,we presented a theoretical model to estimate the spatial resolution of the imaging system within a specific energy spectrum range,detailing the expressions for the effective size of the crystal.The spatial resolution derived from the model closely matches the numerical simulations.
文摘The acute onset of the vision loss by optic never injury following orbital wall reconstruction, has been reported in 0.5% - 5.0% of the cases. Visual impairment can be recovered within an early period after injury. Delayed visual recovery from optic nerve injury during a procedure of orbital wall reconstruction has not been reported. We report a case of delayed recovery from optic nerve injury which occurred following orbital wall reconstruction. A 78-year-old man underwent orbital wall reconstruction for medial wall fracture and resulting enophthalmos in the right eye, one week after a traffic accident. Immediate after surgery, postoperative visual acuity in the right eye decreased to light perception, and relative afferent pupillary defect (RAPD) was detected. In spite of mega-dose steroid treatment, the visual acuity did not improve. However, 8 months after surgery, visual acuity began to recover to 0.1, and the degree of RAPD decreased. Twelve months after surgery, visual acuity in the right eye was 0.4, and pupillary light reflex was normal. Our report suggests that patients with optic neuropathy by surgery or trauma require long-term follow-up, regardless of early response to mega-dose steroid treatment.
基金supported by financial support from the National Natural Science Foundation of China(U1904177)the Excellent Youth Natural Science Foundation of Henan Province of China(212300410079)+2 种基金the Subproject of the Key Project of the National Development and Reform Commission of China(202203001)the Project of Young Key Teachers in Henan Province of China(2019GGJS01)Horizontal Research Projects(20230352A).
文摘Grouting defects are an inherent challenge in construction practices,exerting a considerable impact on the operational structural integrity of connections.This investigation employed the impact-echo technique for the detection of grouting anomalies within connections,enhancing its precision through the integration of wavelet packet energy principles for damage identification purposes.A series of grouting completeness assessments were meticulously conducted,taking into account variables such as the divergent material properties of the sleeves and the configuration of adjacent reinforcement.The findings revealed that:(i)the energy distribution for the highstrength concrete cohort predominantly occupied the frequency bands 42,44,45,and 47,whereas for other groups,it was concentrated within the 37 to 40 frequency band;(ii)the delineation of empty sleeves was effectively discernible by examining the wavelet packet energy ratios across the spectrum of frequencies,albeit distinguishing between sleeves with 50%and full grouting density proved challenging;and(iii)the wavelet packet energy analysis yielded variable detection outcomes contingent on the material attributes of the sleeves,demonstrating heightened sensitivity when applied to ultrahigh-performance concrete matrices and GFRP-reinforced steel bars.
基金supported by the National Natural Science Foundation of China(31671291 to N.P.,31570055 to M.H.,and 31900400 to T.L.)the Fundamental Research Funds for the Central Universities(2662019PY028 to N.P.)National Natural Science Foundation of China(31900400)。
文摘CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against mobile genetic elements(MGEs)through uptake of invader-derived spacers.De novo adaptation samples spacers from both invaders and hosts,whereas primed adaptation shows higher specificity to sample spacers from invaders in many model systems as well as in the subtype I-F system of Zymomonas mobilis.Self-derived spacers will lead to CRISPR self-interference.However,our in vivo study demonstrated that this species used the microhomology-mediated end joining(MMEJ)pathway to efficiently repair subtype I-F CRISPR-Cas system-mediated DNA breaks guided by the self-targeting spacers.MMEJ repair of DNA breaks requires direct microhomologous sequences flanking the protospacers and leads to DNA deletions covering the protospacers.Importantly,CRISPR-mediated genomic DNA breaks failed to be repaired via MMEJ pathway in presence of higher copies of short homologous DNA.Moreover,CRISPR-cleaved exogenous plasmid DNA was failed to be repaired through MMEJ pathway,probably due to the inhibition of MMEJ by the presence of higher copies of the plasmid DNA in Z.mobilis.Our results infer that MMEJ pathway discriminates DNA damages between in the host chromosome versus mobile genetic element(MGE)DNA,and maintains genome stability post CRISPR immunity in Z.mobilis.
基金supported by the National Natural Science Foundation of China(Grant Nos.11275031,11675026,11475032,11475034,11575033,and 11274026)the Foundation of President of Chinese Academy of Engineering Physics(Grant No.2014-1-040)the National Basic Research Program of China(Grant No.2013CB834100)
文摘Inertial fusion energy （IFE） has been considered a promising, nearly inexhaustible source of sustainable carbon-free power for the world＇s energy future. It has long been recognized that the control of hydrodynamic instabilities is of critical importance for ignition and high-gain in the inertial-confinement fusion （ICF） hot-spot ignition scheme. In this mini-review, we summarize the progress of theoretical and simulation research of hydrodynamic instabilities in the ICF central hot-spot implosion in our group over the past decade. In order to obtain sufficient understanding of the growth of hydrodynamic instabilities in ICF, we first decompose the problem into different stages according to the implosion physics processes. The decomposed essential physics pro- cesses that are associated with ICF implosions, such as Rayleigh-Taylor instability （RTI）, Richtmyer-Meshkov instability （RMI）, Kelvin-Helmholtz instability （KHI）, convergent geometry effects, as well as perturbation feed-through are reviewed. Analyti- cal models in planar, cylindrical, and spherical geometries have been established to study different physical aspects, including density-gradient, interface-coupling, geometry, and convergent effects. The influence of ablation in the presence of preheating on the RTI has been extensively studied by numerical simulations. The KHI considering the ablation effect has been discussed in detail for the first time. A series of single-mode ablative RTI experiments has been performed on the Shenguang-II laser facility. The theoretical and simulation research provides us the physical insights of linear and weakly nonlinear growths, and nonlinear evolutions of the hydrodynamic instabilities in ICF implosions, which has directly supported the research of ICF ignition target design. The ICF hot-spot ignition implosion design that uses several controlling features, based on our current understanding of hydrodynamic instabilities, to address shell implosion stability, has been briefly described, several of which are novel.
基金supported by National Natural Science Foundation of China(32170096)Fundamental Research Funds for the Central Universities(2662022SKPY001).
文摘Gene editing technology involves the modification of a specific target gene to obtain a new function or phenotype.Recent advances in clustered regularly interspaced short palindromic repeats(CRISPR)-Cas-mediated technolo-gies have provided an efficient tool for genetic engineering of cells and organisms.Here,we review the three emerging gene editing tools(ZFNs,TALENs,and CRISPR-Cas)and briefly introduce the principle,classification,and mechanisms of the CRISPR-Cas systems.Strategies for gene editing based on endogenous and exogenous CRISPR-Cas systems,as well as the novel base editor(BE),prime editor(PE),and CRISPR-associated transposase(CAST)technologies,are described in detail.In addition,we summarize recent developments in the application of CRISPR-based gene editing tools for industrial microorganism and probiotics modifications.Finally,the potential challenges and future perspectives of CRISPR-based gene editing tools are discussed.
基金supported by the Danish Council of Independent Research (DFF-0602-02196, DFF-4181-00274, DFF-1323-00330)the Fundamental Research Funds for the Central Universities (2662015PX199)
文摘Archaea represents the third domain of life, with the information-processing machineries more closely resembling those of eukaryotes than the machineries of the bacterial counterparts but sharing metabolic pathways with organisms of Bacteria, the sister prokaryotic phylum. Archaeal organisms also possess unique features as revealed by genomics and genome comparisons and by biochemical characterization of prominent enzymes. Nevertheless, diverse genetic tools are required for in vivo experiments to verify these interesting discoveries. Considerable efforts have been devoted to the development of genetic tools for archaea ever since their discovery, and great progress has been made in the creation of archaeal genetic tools in the past decade. Versatile genetic toolboxes are now available for several archaeal models, among which Sulfolobus microorganisms are the only genus representing Crenarchaeota because all the remaining genera are from Euryarchaeota. Nevertheless, genetic tools developed for Sulfolobus are probably the most versatile among all archaeal models, and these include viral and plasmid shuttle vectors, conventional and novel genetic manipulation methods, CRISPR-based gene deletion and mutagenesis, and gene silencing, among which CRISPR tools have been reported only for Sulfolobus thus far. In this review, we summarize recent developments in all these useful genetic tools and discuss their possible application to research into archaeal biology by means of Sulfolobus models.
基金This work was supported by Shenzhen Science and Technology Program(JSGG20200225150431472,JSGG20210901145403012&KQTD20180411143323605)Guangdong Basic and Applied Basic Research Foundation(Grant#2020A1515110361)+3 种基金National Key Research and Development Program of China(#2021YFC0865100)Key-Area Research and Development Program of Guangdong Province(2021B1111110001)National Natural Science Foundation of China(grant#32041002,#82150206)D.G.is also supported by Guangdong Zhujiang Talents Program(#2016LJ06Y540)and National Ten-thousand Talents Program.The authors thank Lu Zhang,Ruyan Liao,Yongxia Shi and Jun Dai from Guangzhou Customs District Technology Center for the help in in vivo efficacy experiment.We also thank the other project participants,including Guanguan Li,Shuo Li and Xinjun Liu from Medi-X Pingshan,Southern University of Science and Technology for the support in preclinical study.
文摘Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of the global pandemic coronavirus disease 2019(COVID-19),has proven itself to be a highly virulent respiratory pathogen with an unpredictable evolutionary capacity,posing a persistent threat to mankind.At the time of this manuscript’s publication.
基金supported by the National Natural Science Foundation of China(No.82394461 and 32200108)the major project of Guangzhou National Laboratory(Grant No.GZNL2023A01008,China)Shenzhen Science and Technology Program(No.JSGG20210901145403012 and JSGG20200225150431472,China).
文摘Coronavirus-related diseases pose a significant challenge to the global health system.Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks,the traditional“one bug,one drug”paradigm struggles to address the growing number of emerging crises.Therefore,there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity.Here,we provide evidence that ATV006,an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase(RdRp),has broad antiviral activity against human and animal coronaviruses.Using mouse hepatitis virus(MHV)and human coronavirus NL63(HCoV-NL63)as a model,we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo.Remarkably,ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection.Due to its oral bioavailability and potency against multiple coronaviruses,ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.
基金the National Natural Science Foundation of China(32170096)the Fundamental Research Funds for the Central Universities(2662022S KPY001)Cooperation Fund of Huazhong Agricultural University-Agricultural Genomics Institute at Shenzhen(CAAS)(SZYJY2021002).
文摘Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products,abundant thermophilic enzymes,and promising fermentation capacities.However,efficient and versatile genome editing tools are not available for this species.In this study,we developed an efficient genome editing tool for T.thermophilus HB27 based on its endogenous type IB,I-C,and III-A/B CRISPR-Cas systems.First,we systematically characterized the DNA interference capabilities of the different types of the native CRISPR-Cas systems in T.thermophilus HB27.We found that genomic manipulations such as gene deletion,mutation,and in situ tagging could be easily implemented by a series of genome-editing plasmids carrying an artificial self-targeting mini-CRISPR and a donor DNA responsible for the recombinant recovery.We also compared the genome editing efficiency of different CRISPR-Cas systems and the editing plasmids with donor DNAs of different lengths.Additionally,we developed a reporter gene system for T.thermophilus based on a heat-stableβ-galactosidase gene TTP0042,and constructed an engineered strain with a high production capacity of superoxide dismutases by genome modification.
基金National Natural Science Foundation of China,Grant/Award Number:81602710。
文摘Background:Inhibitor of apoptosis-stimulating protein of p53(iASPP)is an evolutionarily conserved p53 inhibitor.Mechanistically,iASPP can accelerate tumorigenesis by inhibiting the transactivation function of p53.Targeting the interaction between iASPP and p53 may be a potential therapy for restoring the activity of p53 in tumors.Methods:We constructed an iASPP-derived peptide,called A8,that was derived from the C-terminus of iASPP.Here,we transfected A8 into two wildtype(WT)p53 cell lines,U2OS and A549,and then determined the number of apoptotic cells.The mechanism by which A8 affected apoptosis was further examined by immunoprecipitation(IP),Dual-Luciferase reporter assays,and chromatin IP assays.Real-time polymerase chain reaction and western blots were also used to examine the expression levels of apoptosis-related factors.Results:Our data demonstrate that A8 can increase apoptosis rates in WT p53 cell lines.Functional analysis suggested that A8 restored the transcriptional function and DNA binding activities of p53 toward the Bax and PUMA gene promoters.Moreover,A8 reduced cell proliferation and inhibited tumor growth in xenograft nude mice.Conclusions:These data provide a new approach for restoring the tumor suppressor function of p53 in cancer cells that express WT p53 and therefore may serve as a novel cancer treatment strategy.
基金the National Natural Science Foundation of China(No.21901107)Shenzhen Bay Laboratory(No.SZBL2019062801006)+5 种基金Shenzhen Science and Technology Innovation Committee(No.KQTD20150717103157174)Key-Area Research and Development Program of Guangdong Province(No.2020B010188001)Stable Support Plan Program of Shenzhen Science and Technology Innovation Committee(No.20200925161222002)Innovative Team of Universities in Guangdong Province(No.2020KCXTD016).G.Q.Chen gratefully acknowledges the National Natural Science Foundation of China(Nos.21901107 and 22171129)the Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020055)the Shenzhen Science and Technology Innovation Committee(No.JCYJ20210324104202007)for financial support.B.Ma is indebted to the financial support from the National Natural Science Foundation of China(No.22001113)B.Ma is the National Natural Science Foundation of China(No.22001113).
文摘A highly efficient and enantioselective method for the asymmetric reductive amination ofβ-keto phosphine de-rivatives was disclosed,and the correspondingβ-amino phosphine oxides could be obtained in high yields(up to 97%yield)and excellent enantioselectivities(up to 97%ee).Moreover,the reaction worked well on a gram scale,indicating that our protocol has potential applications in the synthesis of chiral ligands and organocatalysts.
