The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycle...The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.展开更多
Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overf...Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overfishing.To analyze the genetic variations of A.fangsiao caused by the fluctuation of resources,the population genetic structure of nine sampling locations collected from the Bohai Sea to the South China Sea were investigated,using mtDNA COI fragments and microsatellite DNA.The results of F-statistics,AMOVA,STRUCTURE and PCA analyses showed three phylogeographic clades(Clades A,B and C),revealing limited genetic exchange between north and south populations.These clades diverged in 2.23(Clades A and B)and 3.67(Clades A,B and C)million years ago,during the dramatic environmental fluctuations,such as sea level and temperature changes,have exerted great influence on the survival distribution pattern of global organisms.Our results for low genetic connectivity among A.fangsiao populations provide insights into the development of management strategies,that is,to manage this species as separate management unit.展开更多
In cyberspace security,the privacy in location-based services(LBSs) becomes more critical. In previous solutions,a trusted third party(TTP) was usually employed to provide disturbance or obfuscation,but it may become ...In cyberspace security,the privacy in location-based services(LBSs) becomes more critical. In previous solutions,a trusted third party(TTP) was usually employed to provide disturbance or obfuscation,but it may become the single point of failure or service bottleneck. In order to cope with this drawback,we focus on another important class,establishing anonymous group through short-range communication to achieve k-anonymity with collaborative users. Along with the analysis of existing algorithms,we found users in the group must share the same maximum anonymity degree,and they could not ease the process of preservation in a lower one. To cope with this problem,we proposed a random-QBE algorithm to put up with personalized anonymity in user collaboration algorithms,and this algorithm could preserve both query privacy and location privacy. Then we studied the attacks from passive and active adversaries and used entropy to measure user's privacy level. Finally,experimental evaluations further verify its effectiveness and efficiency.展开更多
Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using world...Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.展开更多
Overuse of fungicides and fertilizers has resulted in copper(Cu)contamination of soils and toxic levels of Cu in apple fruits.To breed Cu-resistant apple(Malus domestica)cultivars,the underlying molecular mechanisms a...Overuse of fungicides and fertilizers has resulted in copper(Cu)contamination of soils and toxic levels of Cu in apple fruits.To breed Cu-resistant apple(Malus domestica)cultivars,the underlying molecular mechanisms and key genes involved in Cu resistance must be identified.Here,we show that MdWRKY11 increases Cu tolerance by directly promoting the transcription of MdHMA5.MdHMA5 is a Cu transporter that may function in the storage of excess Cu in root cell walls and stems for Cu tolerance in apple.The transcription factor MdWRKY11 is highly induced by excess Cu.MdWRKY11 overexpression in transgenic apple enhanced Cu tolerance and decreased Cu accumulation.Apple calli transformed with an MdWRKY11-RNAi construct exhibited the opposite phenotype.Both an in vivo chromatin immunoprecipitation assay and an in vitro electrophoretic mobility shift assay indicated that MdWRKY11 binds to the promoter of MdHMA5.Furthermore,MdWRKY11 promoted MdHMA5 expression in transgenic apple plants,as revealed by quantitative PCR.Moreover,inhibition of MdWRKY11 expression by RNA interference led to a significant decrease in MdHMA5 transcription.Thus,MdWRKY11 directly regulates MdHMA5 transcription.Our work resulted in the identification of a novel MdWRKY11-MdHMA5 pathway that mediates Cu resistance in apple.展开更多
The skin is the largest organ of the human body,and its aging is visible to the naked eye.The aging rate of men and women is slightly different.This study compared the protein expression of skin samples on the curved ...The skin is the largest organ of the human body,and its aging is visible to the naked eye.The aging rate of men and women is slightly different.This study compared the protein expression of skin samples on the curved forearms of 11 healthy women and 9 healthy men.Quantitative proteomics analysis found that the expression of epidermal proteins in men and women of the same age group was different.Compared with female skin,in male skin,20 proteins were upregulated,and 7 proteins were downregulated.These data suggest that men and women have differences in the speed of skin aging.For the first time in this experiment,a non-invasive mass spectrometer was used to detect 27 different-related epidermal proteins between men and women.Compared with women,among the 20 epidermal proteins upregulated in men,their functions can be classified into antioxidants,epidermal lipid metabolism,signal transduction,membrane transport,and cell biological processes;the 7 downregulated proteins are involved in a variety of biological processes and inflammatory reactions.Our experiments have discovered epidermal proteins related to the differences between men and women,enriching the library of epidermal differential proteins between men and women and enriching the mechanism of skin aging between men and women from the perspective of epidermal differential proteins.展开更多
Iron(Fe)is an essential micronutrient for plants.Fe deficiency,resulting from poor availability induced by its insolubility in most soils,severely affects the growth and yield of apple(Malus domestica Borkh.).Except f...Iron(Fe)is an essential micronutrient for plants.Fe deficiency,resulting from poor availability induced by its insolubility in most soils,severely affects the growth and yield of apple(Malus domestica Borkh.).Except for the application of an Fe nutrition agent,there is a lack of efficient and environmently-friendly ways to relieve plants from Fe deficiency in a modern orchard.Here,we observed that melatonin(MT),as an efficient reactive oxygen species(ROS)scavenger,could alleviate the chlorosis of leaves in apple under Fe deficiency,following increased Fe content,decreased chlorophyll degradation and stable photosynthetic rate.Exogenous melatonin induced the synthesis of endogenous melatonin and improved the activities of antioxidant enzymes,which decreased the oxidative damage induced by Fe deficiency through properly scavenging O_(2)•−and H_(2)O_(2).In addition,exogenous melatonin promoted the expression of its synthetase genes,but decreased their protein level,inferring post-transcriptional regulation.In brief,melatonin improved the tolerance to Fe deficiency through ROS migration and chloroplast protection in apple.This work uncovered the role of melatonin on Fe deficiency tolerance and also provided a potential way to relieve plants from Fe deficiency stress for apple production.展开更多
Exergy analysis is a unified approach to evaluating the quantity and quality of energy in integrated energy systems(IESs).However,exergy analysis models have been relatively underexplored for IES operation in energy t...Exergy analysis is a unified approach to evaluating the quantity and quality of energy in integrated energy systems(IESs).However,exergy analysis models have been relatively underexplored for IES operation in energy transmission networks.This study addresses this gap by developing an input-benefit exergy model and an exergy loss calculation model for each link within heat-and-electricity-based IESs(HE-IESs),encompassing the transmission networks.Then,an exergy-based unified optimal operation model for HE-IESs is introduced by minimizing the total exergy loss of the system.In addition,the effect of load rate on the energy efficiency of energy conversion equipment is considered.By applying piecewise linearization to the non-convex terms in the objective function and the equality constraints,the proposed optimization model is accurately and efficiently analyzed as a mixed-integer second-order cone pro-gramming problem.The case study results demonstrate that the proposed model reduces equipment-related ex-ergy loss,with approximately 3.2 times the heat net-work-related exergy loss.Moreover,the average deviation gaps of the overall system's exergy loss and equipment's output exergy power between the proposed and the existing models reach 12.94%and 27.83%,respectively.The maximum relative error of the solution results with the proposed linearization method remains below 1.2%,satisfying the requirements of practical application.展开更多
Quick-start generation units are critical devices and flexible resources to ensure a high penetration level of renewable energy in power systems.By considering the wind uncertainty and both binary and continuous decis...Quick-start generation units are critical devices and flexible resources to ensure a high penetration level of renewable energy in power systems.By considering the wind uncertainty and both binary and continuous decisions of quickstart generation units within the intraday dispatch,we develop a Wasserstein-metric-based distributionally robust optimization model for the day-ahead network-constrained unit commitment(NCUC)problem with mixed-integer recourse.We propose two feasible frameworks for solving the optimization problem.One approximates the continuous support of random wind power with a finite number of events,and the other leverages the extremal distributions instead.Both solution frameworks rely on the classic nested column-and-constraint generation(C&CG)method.It is shown that due to the sparsity of L_(1)-norm Wasserstein metric,the continuous support of wind power generation could be represented by a discrete one with a small number of events,and the rendered extremal distributions are sparse as well.With this reduction,the distributionally robust NCUC model with complicated mixed-integer recourse problems can be efficiently handled by both solution frameworks.Numerical studies are carried out,demonstrating that the model considering quick-start generation units ensures unit commitment(UC)schedules to be more robust and cost-effective,and the distributionally robust optimization method captures the wind uncertainty well in terms of out-of-sample tests.展开更多
Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(...Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.展开更多
Tuberculosis remains the worldwide infectious disease. To identify the therapeutic potential of M. vaccae in treating tuberculosis,M. vaccae was injected into Mycobacterium tuberculosis(M. tuberculosis) infected mice....Tuberculosis remains the worldwide infectious disease. To identify the therapeutic potential of M. vaccae in treating tuberculosis,M. vaccae was injected into Mycobacterium tuberculosis(M. tuberculosis) infected mice. The optimal dose of M. vaccae(22.5 μg/mouse) treated mice showed lower pathological change index,spleen weight index,lung weight index and vital M. tuberculosis count than those of the untreated group. Treatment with M. vaccae enhanced the percentages of CD3+ and CD4+ T cells,IFN-γ+CD4+ T cells,innate immune cells including NK cells,NK1.1+ T cells and γδ T cells,and reduced the percentage of IL-4+CD4+ T cells. Therefore,M. vaccae could protect the mice from M. tuberculosis infection and improved mouse innate and adaptive cell-mediated immunity,suggesting that M. vaccae is a potential immunotherapeutic agent in pulmonary tuberculosis.展开更多
Psoriasis (Ps)is an inflammatory skin disease caused by genetic and environmental factors.Previous studies on DNA methylation (DNAm)found genetic markers that are closely associated with Ps,and evidence has shown that...Psoriasis (Ps)is an inflammatory skin disease caused by genetic and environmental factors.Previous studies on DNA methylation (DNAm)found genetic markers that are closely associated with Ps,and evidence has shown that DNAm mediates genetic risk in Ps.In this study,Consensus Clustering was used to analyze DNAm data,and 114Ps patients were divided into three subclassifications.Investigation of the clinical characteristics and copy number variations (CNVs)of DEFB4,IL22,and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI)score.The proportion of late-onset (≥40 years)Ps patients was significantly higher in type I than in types H and III (P =0.035).Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P =0.086).The CNVs of DEFB4and LCE3C showed no significant differences but the CNV oflL22significantly differed among the three subelassifications (P =0.044).This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population.These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.展开更多
A power system unit commitment(UC)problem considering uncertainties of renewable energy sources is investigated in this paper,through a distributionally robust optimization approach.We assume that the first and second...A power system unit commitment(UC)problem considering uncertainties of renewable energy sources is investigated in this paper,through a distributionally robust optimization approach.We assume that the first and second order moments of stochastic parameters can be inferred from historical data,and then employed to model the set of probability distributions.The resulting problem is a two-stage distributionally robust unit commitment with second order moment constraints,and it can be recast as a mixed-integer semidefinite programming(MI-SDP)with finite constraints.The solution algorithm of the problem comprises solving a series of relaxed MI-SDPs and a subroutine of feasibility checking and vertex generation.Based on the verification of strong duality of the semidefinite programming(SDP)problems,we propose a cutting plane algorithm for solving the MI-SDPs;we also introduce an SDP relaxation for the feasibility checking problem,which is an intractable biconvex optimization.Experimental results on the IEEE 6-bus system are presented,showing that without any tuning of parameters,the real-time operation cost of distributionally robust UC method outperforms those of deterministic UC and two-stage robust UC methods in general,and our method also enjoys higher reliability of dispatch operation.展开更多
Integrated photonics provides a route to both miniaturization of quantum key distribution(QKD)devices and enhancing their performance.A key element for achieving discrete-variable QKD is a singlephoton detector.It is ...Integrated photonics provides a route to both miniaturization of quantum key distribution(QKD)devices and enhancing their performance.A key element for achieving discrete-variable QKD is a singlephoton detector.It is highly desirable to integrate detectors onto a photonic chip to enable the realization of practical and scalable quantum networks.We realize a heterogeneously integrated,superconducting silicon-photonic chip.Harnessing the unique high-speed feature of our optical waveguide-integrated superconducting detector,we perform the first optimal Bell-state measurement(BSM)of time-bin encoded qubits generated from two independent lasers.The optimal BSM enables an increased key rate of measurement-device-independent QKD(MDI-QKD),which is immune to all attacks against the detection system and hence provides the basis for a QKD network with untrusted relays.Together with the timemultiplexed technique,we have enhanced the sifted key rate by almost one order of magnitude.With a 125-MHz clock rate,we obtain a secure key rate of 6.166 kbps over 24.0 dB loss,which is comparable to the state-of-the-art MDI-QKD experimental results with a GHz clock rate.Combined with integrated QKD transmitters,a scalable,chip-based,and cost-effective QKD network should become realizable in the near future.展开更多
Radiation-tolerant materials are widely desired in nuclear reactors. High-entropy alloys(HEAs) exhibiting superior mechanical performance and swelling tolerance are being considered as next-generation nuclear structur...Radiation-tolerant materials are widely desired in nuclear reactors. High-entropy alloys(HEAs) exhibiting superior mechanical performance and swelling tolerance are being considered as next-generation nuclear structural materials. However, an understanding of HEAs irradiation tolerance at an atomic scale is still lacking. In this study, the atomic scale irradiation response of AlCoCrFeNi_(2.1), composed of face-centered cubic(FCC) phase and B2 phase, has been systematically investigated at 298 and 723 K. The bubble volume ratio of the B2 phase is much larger than that of the FCC phase under the same irradiation conditions, and hence, the FCC phase has superior swelling tolerance than the B2 phase. Also, order-disorder transformation occurred in both L12and B2 phases. The different irradiation responses between the FCC and B2 phases, depend firstly on composition and secondly on crystal structure. The higher compositional complexity and complicated atomic-level lattice environment of the FCC phase contribute to better radiation performance than B2 phase. The results pave a way for exploring radiation-tolerant structural high-entropy alloys.展开更多
Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determ...Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determine whether the variants of COL11A1 are associated with adult and children height,we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was chr1_103380393 with P value of 4.8 * 10^(-7). Chr1_103380393 also showed nominal significance in the validation stage(P = 1.21 * 10^(-6)). Combined analysis of 16,738 samples strengthened the original association of chr1_103380393 with adult height(P_(combined)= 3.1 * 10^(-8)), with an increased height of 0.292sd(standard deviation) per G allele(95% CI:0.19-0.40). There was no evidence(P = 0.843) showing that chr1_103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258.This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.展开更多
Transmission electron microscopy(TEM)and atom probe tomography(APT)techniques were used to investigate the nanoscale orderedα_(2)(Ti_(3)Al)precipitates in Ti–Al binary alloys.Ti–6Al and Ti–8Al binary alloys were s...Transmission electron microscopy(TEM)and atom probe tomography(APT)techniques were used to investigate the nanoscale orderedα_(2)(Ti_(3)Al)precipitates in Ti–Al binary alloys.Ti–6Al and Ti–8Al binary alloys were solution treated and aged to obtain Widmanstatten microstructure and promoteα_(2)precipitates.The TEM results displayed strong short-range ordering ofα_(2)precipitates in Ti–8Al alloy,while no evidence of the superlattice reflections ofα_(2)in Ti–6Al alloy.The results acquired from APT showed theα_(2)clusters and atoms distribution at the interface between the matrix andα_(2)precipitates.The size and morphology ofα_(2)particles in Ti–8Al alloy,respectively,obtained by TEM and APT are closely consistent.Meanwhile,the APT results displayed tiny size clusters in Ti–6Al alloy,which supposed to give evidence of the initial ordering process ofα_(2)precipitates in the absence of correlative results from TEM.展开更多
基金The authors are grateful for support from the National Social Science Fund of China(21AJL015).
文摘The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.
基金The National Natural Science Foundation of China under contract Nos 32170536 and 31672257。
文摘Amphioctopus fangsiao(Cephalopoda:Octopodidae)is an important commercial species in the coastal waters of China.In recent years,however,the resource of A.fangsiao have declined because of habitat destruction and overfishing.To analyze the genetic variations of A.fangsiao caused by the fluctuation of resources,the population genetic structure of nine sampling locations collected from the Bohai Sea to the South China Sea were investigated,using mtDNA COI fragments and microsatellite DNA.The results of F-statistics,AMOVA,STRUCTURE and PCA analyses showed three phylogeographic clades(Clades A,B and C),revealing limited genetic exchange between north and south populations.These clades diverged in 2.23(Clades A and B)and 3.67(Clades A,B and C)million years ago,during the dramatic environmental fluctuations,such as sea level and temperature changes,have exerted great influence on the survival distribution pattern of global organisms.Our results for low genetic connectivity among A.fangsiao populations provide insights into the development of management strategies,that is,to manage this species as separate management unit.
基金supported by the National Natural Science Foundation of China (Grant No.61472097)the Specialized Research Fund for the Doctoral Program of Higher Education(Grant No.20132304110017)+1 种基金the Natural Science Foundation of Heilongjiang Province of China (Grant No.F2015022)the Fujian Provincial Key Laboratory of Network Security and Cryptology Research Fund (Fujian Normal University) (No.15003)
文摘In cyberspace security,the privacy in location-based services(LBSs) becomes more critical. In previous solutions,a trusted third party(TTP) was usually employed to provide disturbance or obfuscation,but it may become the single point of failure or service bottleneck. In order to cope with this drawback,we focus on another important class,establishing anonymous group through short-range communication to achieve k-anonymity with collaborative users. Along with the analysis of existing algorithms,we found users in the group must share the same maximum anonymity degree,and they could not ease the process of preservation in a lower one. To cope with this problem,we proposed a random-QBE algorithm to put up with personalized anonymity in user collaboration algorithms,and this algorithm could preserve both query privacy and location privacy. Then we studied the attacks from passive and active adversaries and used entropy to measure user's privacy level. Finally,experimental evaluations further verify its effectiveness and efficiency.
基金supported by grants from the National Key R&D Program of China(Grant No.2019YFA0508502)the CAMS Innovation Fund for Medical Sciences(Grant No.2019-I2M-5-073)the National Natural Science Foundation of China(Grant Nos.81788101,81972679,and 81821001)。
文摘Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers.
基金supported by the National Key Research and Development Program of China(SQ2018YFD100303 and 2019YFD1000104)National Natural Science Fund(No.31772279)the Construction of Beijing science and technology innovation and service capacity in top subjects(CEFFPXM2019_014207_000032).
文摘Overuse of fungicides and fertilizers has resulted in copper(Cu)contamination of soils and toxic levels of Cu in apple fruits.To breed Cu-resistant apple(Malus domestica)cultivars,the underlying molecular mechanisms and key genes involved in Cu resistance must be identified.Here,we show that MdWRKY11 increases Cu tolerance by directly promoting the transcription of MdHMA5.MdHMA5 is a Cu transporter that may function in the storage of excess Cu in root cell walls and stems for Cu tolerance in apple.The transcription factor MdWRKY11 is highly induced by excess Cu.MdWRKY11 overexpression in transgenic apple enhanced Cu tolerance and decreased Cu accumulation.Apple calli transformed with an MdWRKY11-RNAi construct exhibited the opposite phenotype.Both an in vivo chromatin immunoprecipitation assay and an in vitro electrophoretic mobility shift assay indicated that MdWRKY11 binds to the promoter of MdHMA5.Furthermore,MdWRKY11 promoted MdHMA5 expression in transgenic apple plants,as revealed by quantitative PCR.Moreover,inhibition of MdWRKY11 expression by RNA interference led to a significant decrease in MdHMA5 transcription.Thus,MdWRKY11 directly regulates MdHMA5 transcription.Our work resulted in the identification of a novel MdWRKY11-MdHMA5 pathway that mediates Cu resistance in apple.
基金the Science and Technology Action Plan for Prevention and Treatment of Major Diseases sponsored by the National Health and Family Planning Commission of the People’s Republic of China(Grant No.2017ZX-01E-002)Anhui Institute of Translational Medicine(ZHYX2020A005).
文摘The skin is the largest organ of the human body,and its aging is visible to the naked eye.The aging rate of men and women is slightly different.This study compared the protein expression of skin samples on the curved forearms of 11 healthy women and 9 healthy men.Quantitative proteomics analysis found that the expression of epidermal proteins in men and women of the same age group was different.Compared with female skin,in male skin,20 proteins were upregulated,and 7 proteins were downregulated.These data suggest that men and women have differences in the speed of skin aging.For the first time in this experiment,a non-invasive mass spectrometer was used to detect 27 different-related epidermal proteins between men and women.Compared with women,among the 20 epidermal proteins upregulated in men,their functions can be classified into antioxidants,epidermal lipid metabolism,signal transduction,membrane transport,and cell biological processes;the 7 downregulated proteins are involved in a variety of biological processes and inflammatory reactions.Our experiments have discovered epidermal proteins related to the differences between men and women,enriching the library of epidermal differential proteins between men and women and enriching the mechanism of skin aging between men and women from the perspective of epidermal differential proteins.
基金supported by the National Key Research&Development Program of China(Project No.2019YFD1000104 and 2018YFD1000303)the National Natural Science Foundation of China(No.31772279)the Construction of Beijing Science and Technology Innovation and Service Capacity in Top Subjects(CEFF-PXM2019_014207_000032).
文摘Iron(Fe)is an essential micronutrient for plants.Fe deficiency,resulting from poor availability induced by its insolubility in most soils,severely affects the growth and yield of apple(Malus domestica Borkh.).Except for the application of an Fe nutrition agent,there is a lack of efficient and environmently-friendly ways to relieve plants from Fe deficiency in a modern orchard.Here,we observed that melatonin(MT),as an efficient reactive oxygen species(ROS)scavenger,could alleviate the chlorosis of leaves in apple under Fe deficiency,following increased Fe content,decreased chlorophyll degradation and stable photosynthetic rate.Exogenous melatonin induced the synthesis of endogenous melatonin and improved the activities of antioxidant enzymes,which decreased the oxidative damage induced by Fe deficiency through properly scavenging O_(2)•−and H_(2)O_(2).In addition,exogenous melatonin promoted the expression of its synthetase genes,but decreased their protein level,inferring post-transcriptional regulation.In brief,melatonin improved the tolerance to Fe deficiency through ROS migration and chloroplast protection in apple.This work uncovered the role of melatonin on Fe deficiency tolerance and also provided a potential way to relieve plants from Fe deficiency stress for apple production.
基金supported by the National Natural Science Foundation of China(No.51937005).
文摘Exergy analysis is a unified approach to evaluating the quantity and quality of energy in integrated energy systems(IESs).However,exergy analysis models have been relatively underexplored for IES operation in energy transmission networks.This study addresses this gap by developing an input-benefit exergy model and an exergy loss calculation model for each link within heat-and-electricity-based IESs(HE-IESs),encompassing the transmission networks.Then,an exergy-based unified optimal operation model for HE-IESs is introduced by minimizing the total exergy loss of the system.In addition,the effect of load rate on the energy efficiency of energy conversion equipment is considered.By applying piecewise linearization to the non-convex terms in the objective function and the equality constraints,the proposed optimization model is accurately and efficiently analyzed as a mixed-integer second-order cone pro-gramming problem.The case study results demonstrate that the proposed model reduces equipment-related ex-ergy loss,with approximately 3.2 times the heat net-work-related exergy loss.Moreover,the average deviation gaps of the overall system's exergy loss and equipment's output exergy power between the proposed and the existing models reach 12.94%and 27.83%,respectively.The maximum relative error of the solution results with the proposed linearization method remains below 1.2%,satisfying the requirements of practical application.
基金supported by the Guangdong R&D Program in Key Areas (No.2021B0101230004)supported in part by the U.S.National Science Foundation (No.CMMI-1635472)supported by the Key Program of National Natural Science Foundation of China (No.51937005)。
文摘Quick-start generation units are critical devices and flexible resources to ensure a high penetration level of renewable energy in power systems.By considering the wind uncertainty and both binary and continuous decisions of quickstart generation units within the intraday dispatch,we develop a Wasserstein-metric-based distributionally robust optimization model for the day-ahead network-constrained unit commitment(NCUC)problem with mixed-integer recourse.We propose two feasible frameworks for solving the optimization problem.One approximates the continuous support of random wind power with a finite number of events,and the other leverages the extremal distributions instead.Both solution frameworks rely on the classic nested column-and-constraint generation(C&CG)method.It is shown that due to the sparsity of L_(1)-norm Wasserstein metric,the continuous support of wind power generation could be represented by a discrete one with a small number of events,and the rendered extremal distributions are sparse as well.With this reduction,the distributionally robust NCUC model with complicated mixed-integer recourse problems can be efficiently handled by both solution frameworks.Numerical studies are carried out,demonstrating that the model considering quick-start generation units ensures unit commitment(UC)schedules to be more robust and cost-effective,and the distributionally robust optimization method captures the wind uncertainty well in terms of out-of-sample tests.
基金supported by the National Key R&D Program of China (2019YFA0508502/3 and 2021YFC2300604)the Natural Science Foundation of China (Reference numbers 82388201, 82241216, and 32270963)+1 种基金the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220008)the Anhui Key Research and Development Plan (Reference number 2023z04020011)。
文摘Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.
文摘Tuberculosis remains the worldwide infectious disease. To identify the therapeutic potential of M. vaccae in treating tuberculosis,M. vaccae was injected into Mycobacterium tuberculosis(M. tuberculosis) infected mice. The optimal dose of M. vaccae(22.5 μg/mouse) treated mice showed lower pathological change index,spleen weight index,lung weight index and vital M. tuberculosis count than those of the untreated group. Treatment with M. vaccae enhanced the percentages of CD3+ and CD4+ T cells,IFN-γ+CD4+ T cells,innate immune cells including NK cells,NK1.1+ T cells and γδ T cells,and reduced the percentage of IL-4+CD4+ T cells. Therefore,M. vaccae could protect the mice from M. tuberculosis infection and improved mouse innate and adaptive cell-mediated immunity,suggesting that M. vaccae is a potential immunotherapeutic agent in pulmonary tuberculosis.
基金Acknowledgements This work was supported by grants from National Natural Science Foundation of China （#30671901 #30628014）, National 863 Science Program by Ministry of Science and Technology of China （#2007AA021010, 2007AA021109）, National 973 Basic Science Project by Ministry of Science ＆ Technology of China （#2010CB911901）.
基金mainly supported by the National Natural Science Foundation of China (No.81502713)Grants for Scientific Research of BSKY (No.XJ201634)Anhui Medical University,and Key Program of Outstanding Talents of Anhui Province (No.gxyqZD2017028).
文摘Psoriasis (Ps)is an inflammatory skin disease caused by genetic and environmental factors.Previous studies on DNA methylation (DNAm)found genetic markers that are closely associated with Ps,and evidence has shown that DNAm mediates genetic risk in Ps.In this study,Consensus Clustering was used to analyze DNAm data,and 114Ps patients were divided into three subclassifications.Investigation of the clinical characteristics and copy number variations (CNVs)of DEFB4,IL22,and LCE3C in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI)score.The proportion of late-onset (≥40 years)Ps patients was significantly higher in type I than in types H and III (P =0.035).Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients (P =0.086).The CNVs of DEFB4and LCE3C showed no significant differences but the CNV oflL22significantly differed among the three subelassifications (P =0.044).This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population.These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.
基金This work was supported by the National Natural Science Foundation of China(51937005)the National Key Research and Development Program of China(2016YFB0900100).
文摘A power system unit commitment(UC)problem considering uncertainties of renewable energy sources is investigated in this paper,through a distributionally robust optimization approach.We assume that the first and second order moments of stochastic parameters can be inferred from historical data,and then employed to model the set of probability distributions.The resulting problem is a two-stage distributionally robust unit commitment with second order moment constraints,and it can be recast as a mixed-integer semidefinite programming(MI-SDP)with finite constraints.The solution algorithm of the problem comprises solving a series of relaxed MI-SDPs and a subroutine of feasibility checking and vertex generation.Based on the verification of strong duality of the semidefinite programming(SDP)problems,we propose a cutting plane algorithm for solving the MI-SDPs;we also introduce an SDP relaxation for the feasibility checking problem,which is an intractable biconvex optimization.Experimental results on the IEEE 6-bus system are presented,showing that without any tuning of parameters,the real-time operation cost of distributionally robust UC method outperforms those of deterministic UC and two-stage robust UC methods in general,and our method also enjoys higher reliability of dispatch operation.
基金supported by the National Key Research and Development Program of China(Nos.2017YFA0303704,2019YFA0308700,and 2017YFA0304002)the National Natural Science Foundation of China(Nos.11690032,11321063,and 12033002)+2 种基金the NSFC-BRICS(No.61961146001)the Leading-Edge Technology Program of Jiangsu Natural Science Foundation(No.BK20192001)the Fundamental Research Funds for the Central Universities.
文摘Integrated photonics provides a route to both miniaturization of quantum key distribution(QKD)devices and enhancing their performance.A key element for achieving discrete-variable QKD is a singlephoton detector.It is highly desirable to integrate detectors onto a photonic chip to enable the realization of practical and scalable quantum networks.We realize a heterogeneously integrated,superconducting silicon-photonic chip.Harnessing the unique high-speed feature of our optical waveguide-integrated superconducting detector,we perform the first optimal Bell-state measurement(BSM)of time-bin encoded qubits generated from two independent lasers.The optimal BSM enables an increased key rate of measurement-device-independent QKD(MDI-QKD),which is immune to all attacks against the detection system and hence provides the basis for a QKD network with untrusted relays.Together with the timemultiplexed technique,we have enhanced the sifted key rate by almost one order of magnitude.With a 125-MHz clock rate,we obtain a secure key rate of 6.166 kbps over 24.0 dB loss,which is comparable to the state-of-the-art MDI-QKD experimental results with a GHz clock rate.Combined with integrated QKD transmitters,a scalable,chip-based,and cost-effective QKD network should become realizable in the near future.
基金supported by financial support from the National Natural Science Foundation of China(Nos.51771201 and 52071124)the Key Project of Natural Science Foundation of Tianjin(No.20JCZDJC00440)+1 种基金the National Key Research and Development Program(No.2018YFB0703402)the Open Research Fund from the State Key Laboratory of Rolling and Automation,Northeastern University(No.2020RALKFKT002)。
文摘Radiation-tolerant materials are widely desired in nuclear reactors. High-entropy alloys(HEAs) exhibiting superior mechanical performance and swelling tolerance are being considered as next-generation nuclear structural materials. However, an understanding of HEAs irradiation tolerance at an atomic scale is still lacking. In this study, the atomic scale irradiation response of AlCoCrFeNi_(2.1), composed of face-centered cubic(FCC) phase and B2 phase, has been systematically investigated at 298 and 723 K. The bubble volume ratio of the B2 phase is much larger than that of the FCC phase under the same irradiation conditions, and hence, the FCC phase has superior swelling tolerance than the B2 phase. Also, order-disorder transformation occurred in both L12and B2 phases. The different irradiation responses between the FCC and B2 phases, depend firstly on composition and secondly on crystal structure. The higher compositional complexity and complicated atomic-level lattice environment of the FCC phase contribute to better radiation performance than B2 phase. The results pave a way for exploring radiation-tolerant structural high-entropy alloys.
基金supported by the grant from the Youth National Science Foundation of China (No.31100908)
文摘Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determine whether the variants of COL11A1 are associated with adult and children height,we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was chr1_103380393 with P value of 4.8 * 10^(-7). Chr1_103380393 also showed nominal significance in the validation stage(P = 1.21 * 10^(-6)). Combined analysis of 16,738 samples strengthened the original association of chr1_103380393 with adult height(P_(combined)= 3.1 * 10^(-8)), with an increased height of 0.292sd(standard deviation) per G allele(95% CI:0.19-0.40). There was no evidence(P = 0.843) showing that chr1_103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258.This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.
基金financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA22010101)the Natural Key Research and Development Program of China(Nos.2016YFC0304201 and 2016YFC0304206)+1 种基金the Natural Science Foundation of China(No.51871225)the Youth Innovation Promotion Association CAS and Liaoning Revitalization Talents Program(No.XLYC1907005)。
文摘Transmission electron microscopy(TEM)and atom probe tomography(APT)techniques were used to investigate the nanoscale orderedα_(2)(Ti_(3)Al)precipitates in Ti–Al binary alloys.Ti–6Al and Ti–8Al binary alloys were solution treated and aged to obtain Widmanstatten microstructure and promoteα_(2)precipitates.The TEM results displayed strong short-range ordering ofα_(2)precipitates in Ti–8Al alloy,while no evidence of the superlattice reflections ofα_(2)in Ti–6Al alloy.The results acquired from APT showed theα_(2)clusters and atoms distribution at the interface between the matrix andα_(2)precipitates.The size and morphology ofα_(2)particles in Ti–8Al alloy,respectively,obtained by TEM and APT are closely consistent.Meanwhile,the APT results displayed tiny size clusters in Ti–6Al alloy,which supposed to give evidence of the initial ordering process ofα_(2)precipitates in the absence of correlative results from TEM.
