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
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 hu- man height. To d...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 hu- man height. To determine whether the variants of COL11A 1 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 chrl 103380393 with P value of 4.8 × 10-7. Chrl_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 chrl 103380393 with adult height （Pcombinea - 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 chrl 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
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 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
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
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
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
Objective： To investigate the expressions of heparanase （Hpa） and basic fibroblast growth factor （bFGF） in oral squamous-cell carcinoma （OSCC）, and to evaluate the relationship between the expressions and tumor...Objective： To investigate the expressions of heparanase （Hpa） and basic fibroblast growth factor （bFGF） in oral squamous-cell carcinoma （OSCC）, and to evaluate the relationship between the expressions and tumor angiogenesis and progression. Methods： The expressions of Hpa mRNA and bFGF mRNA of OSCC were examined using in situ hybridization. The microvascular density （MVD） was assessed through immunohistochemistry staining. Results： The expressions of Hpa mRNA and bFGF mRNA were associated with tumor MVD and lymph node metastasis. Concomitant expression of Hpa mRNA and bFGF mRNA was associated with higher tumor MVD as compared with expression of either factor alone. Conclusion： Hpa and bFGF might contribute to the angiogenesis and lymph node metastasis in OSCC and they cooperate in promoting vascularization.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
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
AI-driven interior design generation offers promising applications.However,current AI-based diffusion models struggle to generate indoor layouts in pixel-level alignment with the indoor structure.This study proposes a...AI-driven interior design generation offers promising applications.However,current AI-based diffusion models struggle to generate indoor layouts in pixel-level alignment with the indoor structure.This study proposes a new stable diffusion-based interior design workflow with an Interior Design Control Network(IDCN).IDCN ensures that the batchgenerated creative interior designs based on an input image of an unfurnished room match the indoor structure.Generating innovative designs and rendering images directly with the proposed method eliminates the tedious creative design and drawing work in traditional design practices.The results indicate that the proposed method with the new design approach achieves nearly real-time design generation and modiflcation and signiflcantly enhances design creativity and efflciency.Moreover,the proposed method can be generalized to other design generation tasks,thereby promoting the transformation toward intelligent design.展开更多
Allogeneic“off-the-shelf”chimeric antigen receptor(CAR)T-cell therapy offers numerous advantages over autologous approaches.However,two critical challenges are encountered:graft-versus-host disease(GVHD)and poor per...Allogeneic“off-the-shelf”chimeric antigen receptor(CAR)T-cell therapy offers numerous advantages over autologous approaches.However,two critical challenges are encountered:graft-versus-host disease(GVHD)and poor persistence due to both extrinsic(host immune rejection)and intrinsic(TCR deletion-mediated)mechanisms.To prevent GVHD and prevent host-mediated graft rejection,allogeneic CAR-T-cell strategies typically employ selective editing of surface receptors or ligands,including(1)reducing the risk of GVHD by gene editing with TCR deletion[1,2];(2)diminishing allogeneic immunogenicity by knocking out HLA andβ2 m,which can alleviate T-cell-mediated immune rejection but inadvertently activates NK cells[3];and(3)preventing NK-cell-dependent lysis by overexpressing NK-inhibitory ligands,such as the nonclassical HLA molecules HLA-E and HLA-G[4].Recently,Wu et al.introduced a novel strategy that targets signal peptide peptidase-like 3(SPPL3)in allogeneic CAR-T cells.This approach confers dual resistance to both allogeneic rejection(mediated by T/NK cells)and Fas-dependent activation-induced cell death(AICD).Importantly,endogenous TCR expression was preserved,thereby enhancing CAR-T-cell persistence without increasing the risk of GVHD.In a phase 1 clinical trial,SPPL3-null CAR-T cells exhibited both safety and promising efficacy in patients with B-cell hematologic malignancies[5].展开更多
Background and Objectives:The increasing prevalence of hyperuricemia in children is a global health concern.Plant dietary fiber may influence uric acid levels by improving gut health and lowering blood glucose and lip...Background and Objectives:The increasing prevalence of hyperuricemia in children is a global health concern.Plant dietary fiber may influence uric acid levels by improving gut health and lowering blood glucose and lipid levels.This study aims to examine the relationship between plant-based dietary fiber intake and hyperuricemia risk in Chinese children aged 6-17 years.Methods and Study Design:This study analyzed dietary fiber intake data from 11,423 children(aged 6-17 years)from the China Children and Lactating Women Nutrition and Health Surveillance(CCLWNHS)conducted between 2016 and 2019.Plant dietary fiber intake was assessed using a food frequency questionnaire.Logistic regression was performed,adjusting for age,sex,body mass index(BMI),smoking,alcohol consumption,physical activity,and energy intake.Restricted cubic splines(RCS)and receiver operating characteristic(ROC)curves were utilized to explore nonlinear relationships and identify cut-off values for dietary fiber intake.Results:Among the 11,423 children,1,730(15.1%)were diagnosed with hyperuricemia.The average daily fiber intake was 8.28±5.90g,with cereal fiber accounting for 56.1-57.8%.A significant negative correlation was found between cereal dietary fiber intake and hyperuricemia risk(p=0.0004).Stratified analysis indicated that overweight/obesity status modified this relationship.ROC curve analysis identified optimal intake cut-off values:8.35 g/day for boys and 11.1 g/day for girls.Conclusions:Processed and ultraprocessed foods still have a lower contribution to energy and nutrient intake in Jakarta than nonprocessed foods and processed ingredients.展开更多
The promotion of quantum network applications demands the scalable connection of quantum resources.It is preferable to set up multiple logical networks coexisting on a single physical network infrastructure to accommo...The promotion of quantum network applications demands the scalable connection of quantum resources.It is preferable to set up multiple logical networks coexisting on a single physical network infrastructure to accommodate a larger number of users.Here we present a quantum virtual network architecture that offers this level of scalability,without being constrained to a fixed physical-layer network relying solely on passive multiplexing components.The architecture can be understood as arising from the superposition of a fully connected entanglement distribution network and port-based virtual local area network,which group multiusers by access ports.In terms of hardware,we leverage a semiconductor chip with a high figure-of-merit modal overlap to directly generate high-quality polarization entanglement,and a streamlined polarization analysis module,which requires only one single-photon detector for each end user.We experimentally perform the BBM92 QKD protocol on the five-user quantum virtual network and demonstrate voice and image encryption on a campus area network.Our results may provide insights into the realization of large-scale quantum networks with integrated and cost-efficient photonic architecture.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 m...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. Cellular ＆ Molecular Immunology.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
HMBOX1 was a novel transcription factor possibly involving in function of pancreas and cytotoxicity of NK cells. For function determination, recombinant human HMBOX1 protein was obtained and purified, and the monoclon...HMBOX1 was a novel transcription factor possibly involving in function of pancreas and cytotoxicity of NK cells. For function determination, recombinant human HMBOX1 protein was obtained and purified, and the monoclonal antibodies against HMBOX1 were prepared. The full-length cDNA fragment encoding HMBOX1 was amplified from NK-92 cells and inserted into prokaryotic expression vector pET22b. The pET22b-HMBOX1-6his vector was then transformed into E. coli Rosetta （DE3） and induced by 1 mM IPTG for 4 h at 37℃. The fusion HMBOX1 protein was mainly expressed in inclusion bodies, which was purified and refolded using Ni^2＋-affinity chromatography. With the purified fusion HMBOX1 protein as antigen, monoclonal antibodies against HMBOX1 were generated, providing a potentially useful tool for further study in HMBOX1 functions. Using these anti-HMBOX1 mAbs, we identified that HMBOX1 is located in both cytoplasm and nucleus and could be detected in 10 human normal tissues, including cerebrum, pancreas, kidney and liver tissues. Moreover, the expression in hepatic carcinoma was significantly lower than that in adjacent tissues.展开更多
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 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 hu- man height. To determine whether the variants of COL11A 1 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 chrl 103380393 with P value of 4.8 × 10-7. Chrl_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 chrl 103380393 with adult height （Pcombinea - 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 chrl 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 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.
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.
文摘Objective： To investigate the expressions of heparanase （Hpa） and basic fibroblast growth factor （bFGF） in oral squamous-cell carcinoma （OSCC）, and to evaluate the relationship between the expressions and tumor angiogenesis and progression. Methods： The expressions of Hpa mRNA and bFGF mRNA of OSCC were examined using in situ hybridization. The microvascular density （MVD） was assessed through immunohistochemistry staining. Results： The expressions of Hpa mRNA and bFGF mRNA were associated with tumor MVD and lymph node metastasis. Concomitant expression of Hpa mRNA and bFGF mRNA was associated with higher tumor MVD as compared with expression of either factor alone. Conclusion： Hpa and bFGF might contribute to the angiogenesis and lymph node metastasis in OSCC and they cooperate in promoting vascularization.
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funded by the 2021 Nantong Science and Technology Plan Project“Research on the digital design of popularization of scientiflc knowledge”(Grant No.JCZ21074)。
文摘AI-driven interior design generation offers promising applications.However,current AI-based diffusion models struggle to generate indoor layouts in pixel-level alignment with the indoor structure.This study proposes a new stable diffusion-based interior design workflow with an Interior Design Control Network(IDCN).IDCN ensures that the batchgenerated creative interior designs based on an input image of an unfurnished room match the indoor structure.Generating innovative designs and rendering images directly with the proposed method eliminates the tedious creative design and drawing work in traditional design practices.The results indicate that the proposed method with the new design approach achieves nearly real-time design generation and modiflcation and signiflcantly enhances design creativity and efflciency.Moreover,the proposed method can be generalized to other design generation tasks,thereby promoting the transformation toward intelligent design.
文摘Allogeneic“off-the-shelf”chimeric antigen receptor(CAR)T-cell therapy offers numerous advantages over autologous approaches.However,two critical challenges are encountered:graft-versus-host disease(GVHD)and poor persistence due to both extrinsic(host immune rejection)and intrinsic(TCR deletion-mediated)mechanisms.To prevent GVHD and prevent host-mediated graft rejection,allogeneic CAR-T-cell strategies typically employ selective editing of surface receptors or ligands,including(1)reducing the risk of GVHD by gene editing with TCR deletion[1,2];(2)diminishing allogeneic immunogenicity by knocking out HLA andβ2 m,which can alleviate T-cell-mediated immune rejection but inadvertently activates NK cells[3];and(3)preventing NK-cell-dependent lysis by overexpressing NK-inhibitory ligands,such as the nonclassical HLA molecules HLA-E and HLA-G[4].Recently,Wu et al.introduced a novel strategy that targets signal peptide peptidase-like 3(SPPL3)in allogeneic CAR-T cells.This approach confers dual resistance to both allogeneic rejection(mediated by T/NK cells)and Fas-dependent activation-induced cell death(AICD).Importantly,endogenous TCR expression was preserved,thereby enhancing CAR-T-cell persistence without increasing the risk of GVHD.In a phase 1 clinical trial,SPPL3-null CAR-T cells exhibited both safety and promising efficacy in patients with B-cell hematologic malignancies[5].
基金funded by Qilu Health Outstanding Young Talents Project,Shandong Provincial Natural Science Foundation(ZR2023QH157)Chinese Medicine Science and Technology Project of Shandong Province(2020Q041,2020Q043)Shandong Medical and Health Science and Technology Development Project(202412021239).
文摘Background and Objectives:The increasing prevalence of hyperuricemia in children is a global health concern.Plant dietary fiber may influence uric acid levels by improving gut health and lowering blood glucose and lipid levels.This study aims to examine the relationship between plant-based dietary fiber intake and hyperuricemia risk in Chinese children aged 6-17 years.Methods and Study Design:This study analyzed dietary fiber intake data from 11,423 children(aged 6-17 years)from the China Children and Lactating Women Nutrition and Health Surveillance(CCLWNHS)conducted between 2016 and 2019.Plant dietary fiber intake was assessed using a food frequency questionnaire.Logistic regression was performed,adjusting for age,sex,body mass index(BMI),smoking,alcohol consumption,physical activity,and energy intake.Restricted cubic splines(RCS)and receiver operating characteristic(ROC)curves were utilized to explore nonlinear relationships and identify cut-off values for dietary fiber intake.Results:Among the 11,423 children,1,730(15.1%)were diagnosed with hyperuricemia.The average daily fiber intake was 8.28±5.90g,with cereal fiber accounting for 56.1-57.8%.A significant negative correlation was found between cereal dietary fiber intake and hyperuricemia risk(p=0.0004).Stratified analysis indicated that overweight/obesity status modified this relationship.ROC curve analysis identified optimal intake cut-off values:8.35 g/day for boys and 11.1 g/day for girls.Conclusions:Processed and ultraprocessed foods still have a lower contribution to energy and nutrient intake in Jakarta than nonprocessed foods and processed ingredients.
基金supported by the National Natural Science Foundation of China(Grant Nos.12274233,and 12274223)the Major Scientific Research Project of Anhui Province(Grant No.KJ2021ZD0005)+3 种基金the Scientific Research Planning Project of Anhui Province(Grant No.2022AH040020)the University Collaborative Innovation Project of Anhui Province(Grant No.GXXT-2021-091)the Program of Song Shan Laboratory(Included in the Management of Major Science and Technology Program of Henan Province)(Grant No.221100210800-02)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.SJCX23_0569)。
文摘The promotion of quantum network applications demands the scalable connection of quantum resources.It is preferable to set up multiple logical networks coexisting on a single physical network infrastructure to accommodate a larger number of users.Here we present a quantum virtual network architecture that offers this level of scalability,without being constrained to a fixed physical-layer network relying solely on passive multiplexing components.The architecture can be understood as arising from the superposition of a fully connected entanglement distribution network and port-based virtual local area network,which group multiusers by access ports.In terms of hardware,we leverage a semiconductor chip with a high figure-of-merit modal overlap to directly generate high-quality polarization entanglement,and a streamlined polarization analysis module,which requires only one single-photon detector for each end user.We experimentally perform the BBM92 QKD protocol on the five-user quantum virtual network and demonstrate voice and image encryption on a campus area network.Our results may provide insights into the realization of large-scale quantum networks with integrated and cost-efficient photonic architecture.
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. Cellular ＆ Molecular Immunology.
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）.
文摘HMBOX1 was a novel transcription factor possibly involving in function of pancreas and cytotoxicity of NK cells. For function determination, recombinant human HMBOX1 protein was obtained and purified, and the monoclonal antibodies against HMBOX1 were prepared. The full-length cDNA fragment encoding HMBOX1 was amplified from NK-92 cells and inserted into prokaryotic expression vector pET22b. The pET22b-HMBOX1-6his vector was then transformed into E. coli Rosetta （DE3） and induced by 1 mM IPTG for 4 h at 37℃. The fusion HMBOX1 protein was mainly expressed in inclusion bodies, which was purified and refolded using Ni^2＋-affinity chromatography. With the purified fusion HMBOX1 protein as antigen, monoclonal antibodies against HMBOX1 were generated, providing a potentially useful tool for further study in HMBOX1 functions. Using these anti-HMBOX1 mAbs, we identified that HMBOX1 is located in both cytoplasm and nucleus and could be detected in 10 human normal tissues, including cerebrum, pancreas, kidney and liver tissues. Moreover, the expression in hepatic carcinoma was significantly lower than that in adjacent tissues.
