Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as th...Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as the training population data,using BSLMM,TWAS,and eQTL mapping to prescreen features according to |β_(b)|>0,top 1%of phenotypic variation explained(PVE),expression-associated single nucleotide polymorphisms(eSNPs),and egenes(false discovery rate(FDR)<0.01),where these loci were set as extra fixed effects(named GBLUP-Fix)and random effects(GFBLUP)to improve the prediction accuracy in the validation population,respectively.The results suggested that both GBLUP-Fix and GFBLUP models could improve the accuracy of longissimus dorsi muscle(LDM),water holding capacity(WHC),shear force(SF),and pH in Huaxi cattle on average from 2.14 to 8.69%,especially the improvement of GFBLUP-TWAS over GBLUP was 13.66%for SF.These methods also captured more genetic variance than GBLUP.Our study confirmed that multi-omics-assisted large-effects loci prescreening could improve the accuracyofgenomic prediction.展开更多
The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic ...The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.展开更多
Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are i...Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are increasingly considered new sources for GS.Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics.Results:We utilized the Cosine kernel to map genomic and transcriptomic data as n×n symmetric matrix(G matrix and T matrix),combined with the best linear unbiased prediction(BLUP)for GS.Here,we defined five kernel-based prediction models:genomic BLUP(GBLUP),transcriptome-BLUP(TBLUP),multi-omics BLUP(MBLUP,M=ratio×G+(1-ratio)×T),multi-omics single-step BLUP(mss BLUP),and weighted multi-omics single-step BLUP(wmss BLUP)to integrate transcribed individuals and genotyped resource population.The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that(1)MBLUP was far preferred to GBLUP(ratio=1.0),(2)the prediction accuracy of wmss BLUP and mss BLUP had 4.18%and 3.37%average improvement over GBLUP,(3)We also found the accuracy of wmss BLUP increased with the growing proportion of transcribed cattle in the whole resource population.Conclusions:We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy.Moreover,wmss BLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.展开更多
Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-lengt...Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene.The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy,in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7.In this study,we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer(ISS)sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length(FL)gene expression.It happens that there was a protospacer adjacent motif(PAM)at one end of the ISS sequence according to the design of sgRNA.The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells.Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction,in which deleting small fragments,inserting small amounts and mutation.Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8%(P<0.05).In the primary cultured chondrocytes of SMA mice,in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23%(P<0.05)and significantly improve SMN protein levels(P<0.05).CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases,but it is rarely reported in the treatment of SMA diseases.This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing,which can effectively promote the production of SMN2 FL gene expressions,in which there was an important clinical reference value.展开更多
Objective:The aim of our study was to explore the influence of interstitial brachytherapy with 125I seeds on Caspase-3 and Egr-1 expressions of Lewis lung carcinoma in C57BL mice.Methods:Model mice of C57BL were plant...Objective:The aim of our study was to explore the influence of interstitial brachytherapy with 125I seeds on Caspase-3 and Egr-1 expressions of Lewis lung carcinoma in C57BL mice.Methods:Model mice of C57BL were planted with Lewis lung cells (LLC) and divided into the treatment group (n=18) and the control group (n=17).In each mouse of the treatment group,two BT-125-1 Model 125I seeds with apparent activity of 9.25 MBq were implanted into the tumor;whereas in each mouse of the control group two dummy seeds were implanted.The mice survival rates of both groups were recorded after 21 days.The tumor weights and dimensions of survived mice were measured,and the tumor volume inhibition rate was calculated.T-test was performed to compare differences of tumor weights and volumes between these two groups.Routine pathological slides of tumor tissue were observed under light microscope.The expression of Caspase-3 was detected by immunohistochemical method and the expression of Egr-1 was detected by RT-PCR method.Results:The survival rates were 88.88% in the treatment group and 70.59% in the control group,the difference had no statistical significance (P > 0.05).The tumor volume inhibition rate was 71.12%.Pathological examination showed degeneration and necrosis of cancer cells at the site nearby the seed in the treated group,but the tumor cells alive were still presented nearby the seed in the control group.The expressions of Caspase-3 and Egr-1 in the treated group were higher than those in the control group (t=12.825,P < 0.01;t=7.039,P < 0.01;respectively).Conclusion:The interstitial brachytherapy with 125I seeds could significantly inhibit the growth of Lewis lung carcinoma of mice.The possible mechanism may be that 125I interstitial brachytherapy can enhance the expressions of Egr-1 and Caspase-3,which could induce tumor cellular apoptosis.展开更多
Energy issues in transportation systems have garnered increasing attention recently.This study proposes a systematic methodology for policy-makers to minimize energy consumption in multimodal intercity transportation ...Energy issues in transportation systems have garnered increasing attention recently.This study proposes a systematic methodology for policy-makers to minimize energy consumption in multimodal intercity transportation systems considering suppliers’operational constraints and travelers’mobility requirements.A bi-level optimization model is developed for this purpose and considers the air,rail,private auto,and transit modes.The upper-level model is a mixed integer nonlinear program aiming to minimize energy consumption subject to transportation suppliers’operational constraints and traffic demand distribution to paths resulting from the lower-level model.The lower-level model is a linear program seeking to maximize the trip utilities of travelers.The interactions between the multimodal transportation suppliers and intercity traffic demand are considered under the goal of minimizing system energy consumption.The proposed bi-level mixed integer model is relaxed and transformed into a mathematical program with complementarity constraints,and solved using a customized branch-and-bound algorithm.Numerical experiments,conducted using multimodal travel options between Lafayette,Indiana and Washington,D.C.reiterate that shifting traffic demand from private cars to the transit and rail modes significantly reduce energy consumption.Moreover,the proposed methodology provides tools to quantitatively analyze system energy consumption and traffic demand distribution among transportation modes under specific policy instruments.The results illustrate the need to systematically incorporate the interactions among traveler preferences,network structure,and supplier operational schemes to provide policy-makers insights for developing traffic demand shift mechanisms to minimize system energy consumption.Hence,the proposed methodology provide policy-makers the capability to analyze energy consumption in the transportation sector by a holistic approach.展开更多
The power and transportation systems are urban interdependent critical infrastructures(CIs).During the post-disaster restoration process,transportation mobility and power restoration process are interdependent,and the...The power and transportation systems are urban interdependent critical infrastructures(CIs).During the post-disaster restoration process,transportation mobility and power restoration process are interdependent,and their functionalities significantly affect the well-beings of other urban CIs.Therefore,to enhance the resilience of urban CIs,successful recovery strategies should promote CI function cooperatively and synergistically to distribute goods and services efficiently.This paper develops an integrative framework that addresses the challenges of enhancing the recovery efficiency of urban power and transportation systems in short-term recovery period.Specifically,the post-storm recovery process is considered as a scheduling problem with the constraints representingcrew dispatch,equipment and fuel limit.We propose a new framework for co-optimizing the recovery scheduling of power and transportation systems,respecting precedency requirement and network constraints.The advantages and benefits of co-optimized recovery scheduling are validated in a testing system.展开更多
The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to e...The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.展开更多
Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascula...Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy.High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development.Therefore,we explored how high-salt diets during pregnancy could affect the offspring.Methods:Rats were divided into three groups and fed with low,normal,and high salt diets.The offspring were separated into three groups after weaning based on dietary salt concentration.The blood pressure and urine protein content of both dams and offspring were measured.To evaluate cardiac function,we used Masson staining and immunodetection to confirm the fibrosis status.Finally,we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide(NO)/cGMP-dependent protein kinase I(PKGI)pathway and the angiotensin receptor.Results:High-salt diets increased blood pressure,and offspring previously exposed to high-salt environments were predisposed to hypertension.High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition(EMT).Under these conditions,the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor(AT1R)was upregulated,though the type-2 angiotensin II receptor(AT2R)had the opposite effect.Conclusion:High-salt diets induce high blood pressure and increase predisposition to hypertension in offspring.They are accompanied by cardiac fibrosis,which could be caused by the activation of NO/PKGI and upregulation of AT1R.展开更多
Organolead halide perovskite is a newly emerging low-cost,solution-processable material with a broadband absorption from the ultraviolet(UV)to visible(Vis)region,which has attracted a great deal of interest in high-pe...Organolead halide perovskite is a newly emerging low-cost,solution-processable material with a broadband absorption from the ultraviolet(UV)to visible(Vis)region,which has attracted a great deal of interest in high-performance optoelectronic devices.However,some practicable applications need a cover of UV–Vis–NIR region for photoelectric conversion,a task that remains a significant challenge for further extending the absorption toward the near-infrared radiation(NIR)region.Here,to the best of our knowledge,we prove for the first time an ultrasensitive flexible broadband photodetector based on porous organolead perovskitephthalocyanine heterostructure,which combines the synergetic properties of high UV–Vis absorbance of perovskite with enhanced NIR absorption for triclinic lead phthalocyanine.The photosensitivity of the as-prepared devices reaches up to 10^(4) at a low intensity of 10mWcm^(−2),which is among the largest values reported for broadband photodetectors.Significantly,performed at room temperature,the device achieves a pA scale dark current along with an ultrafast response speed of less than 0.6 ms for as-adopted full spectra.Our results provide an easy and promising route to develop low-cost,flexible and highly sensitive UV–Vis–NIR photodetectors.展开更多
Objective:To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta(PA).Methods:This case-control study included clinical data from singleton mother...Objective:To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta(PA).Methods:This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017.According to the intraoperative findings after delivery,the study population was divided into PA and non-PA groups.We compared the pregnancy outcomes between the two groups,used multivariate logistic regression to analyze the risk factors for placental accreta.Results:For this study we included 11,074 pregnant women with a history of cesarean section;and of these,869 cases were in the PA group and 10,205 cases were in the non-PA group.Compared with the non-PA group,the probability of postpartum hemorrhage(236/10,205,2.31%vs.283/869,32.57%),severe postpartum hemorrhage(89/10,205,0.87%vs.186/869,21.75%),diffuse intravascular coagulation(3/10,205,0.03%vs.4/869,0.46%),puerperal infection(33/10,205,0.32%vs.12/869,1.38%),intraoperative bladder injury(1/10,205,0.01%vs.16/869,1.84%),hysterectomy(130/10,205,1.27%vs.59/869,6.79%),and blood transfusion(328/10,205,3.21%vs.231/869,26.58%)was significantly increased in the PA group(P<0.05).At the same time,the neonatal birth weight 3250.00(2950.00–3520.00)g vs.2920.00(2530.00–3250.00)g),the probability of neonatal comorbidities(245/10,205,2.40%vs.61/869,7.02%),and the rate of neonatal intensive care unit admission(817/10,205,8.01%vs.210/869,24.17%)also increased significantly(P<0.05).Weight(odds ratio)(OR)=1.03,95%confidence interval(CI):1.01–1.05)),parity(OR=1.18,95%CI:1.03–1.34),number of miscarriages(OR=1.31,95%CI:1.17–1.47),number of previous cesarean sections(OR=2.57,95%CI:2.02–3.26),history of premature rupture of membrane(OR=1.61,95%CI:1.32–1.96),previous cesarean-section transverse incisions(OR=1.38,95%CI:1.12–1.69),history of placenta previa(OR=2.44,95%CI:1.50–3.96),and the combination of prenatal hemorrhage(OR=9.95,95%CI:8.42–11.75)and placenta previa(OR=91.74,95%CI:74.11–113.56)were all independent risk factors for PA.Conclusion:There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section,and this required close clinical attention.Weight before pregnancy,parity,number of miscarriages,number of previous cesarean sections,history of premature rupture of membranes,past transverse incisions in cesarean sections,a history of placenta previa,prenatal hemorrhage,and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section.These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.展开更多
Objective: To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.Methods: This was a 10-year single-center, retrospect...Objective: To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.Methods: This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18-55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR.Results: In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793)vs. 5.9% (1803/30,336),P < 0.05 and 3.5% (932/26,793)vs. 2.4% (745/30,336),P < 0.05, respectively). A female fetus was an independent risk factor for either PE or FGR (adjusted odds ratio: 1.169 or 1.563;95% confidence interval: 1.036-1.319 or 1.349-1.810, respectively). In twin pregnancies, the incidence of early-onset PE was greater in pregnancies with two females compared with two males or one male plus one female (4.6% (46/1003)vs. 4.1% (54/1305)vs. 2.4% (33/1391),P < 0.05). Female-female twins was an independent risk factor for PE (adjusted odds ratio: 1.367, 95% confidence interval: 1.011-1.849), especially early-onset PE.Conclusion: The female fetus was associated with PE in both singleton and twin pregnancies and was also a risk factor of FGR in singleton pregnancies.展开更多
Objective:This study aimed to investigate the immune response of a pregnant woman who recovered from the coronavirus disease 2019(COVID_(R)S)by using single-cell transcriptomic profiling of peripheral blood mononuclea...Objective:This study aimed to investigate the immune response of a pregnant woman who recovered from the coronavirus disease 2019(COVID_(R)S)by using single-cell transcriptomic profiling of peripheral blood mononuclear cells(PBMCs)and to analyze the properties of different immune cell subsets.Methods:PBMCs were collected from the COVID_(R)S patient at 28 weeks of gestation,before a cesarean section.The PBMCs were then analyzed using single-cell RNA sequencing.The transcriptional profiles of myeloid,T,and natural killer(NK)cell subsets were systematically analyzed and compared with those of healthy pregnant controls from a published single-cell RNA sequencing data set.Results:We identified major cell types such as T cells,B cells,NK cells,and myeloid cells in the PBMCs of our COVID_(R)S patient.The increase of myeloid and B cells and decrease of T cells and NK cells in the PBMCs in this patient were quite distinct compared with that in the control subjects.After reclustering and Augur analysis,we found that CD16 monocytes and mucosal-associated invariant T(MAIT)cells were mostly affected within different myeloid,T,and NK cell subtypes in our COVID_(R)S patient.The proportion of CD16 monocytes in the total myeloid population was increased,and the frequency of MAIT cells in the total T and NK cells was significantly decreased in the COVID-RS patient.We also observed significant enrichment of gene sets related to antigen processing and presentation,T-cell activation,T-cell differentiation,and tumor necrosis factor superfamily cytokine production in CD16 monocytes,and enrichment of gene sets related to antigen processing and presentation,response to type II interferon,and response to virus in MAIT cells.Conclusion:Our study provides a single-cell resolution atlas of the immune gene expression patterns in PBMCs from a COVID_(R)S patient.Our findings suggest that CD16-positive monocytes and MAIT cells likely play crucial roles in the maternal immune response against severe acute respiratory syndrome coronavirus 2 infection.These results contribute to a better understanding of the maternal immune response to severe acute respiratory syndrome coronavirus 2 infection and may have implications for the development of effective treatments and preventive strategies for the coronavirus disease 2019 in pregnant women.展开更多
基金This research was supported by the National Natural Science Foundations of China(31872975)the Science and Technology Project of Inner Mongolia Autonomous Region,China(2020GG0210)the Program of National Beef Cattle and Yak Industrial Technology System,China(CARS-37).
文摘Presently,integrating multi-omics information into a prediction model has become a ameliorate strategy for genomic selection to improve genomic prediction accuracy.Here,we set the genomic and transcriptomic data as the training population data,using BSLMM,TWAS,and eQTL mapping to prescreen features according to |β_(b)|>0,top 1%of phenotypic variation explained(PVE),expression-associated single nucleotide polymorphisms(eSNPs),and egenes(false discovery rate(FDR)<0.01),where these loci were set as extra fixed effects(named GBLUP-Fix)and random effects(GFBLUP)to improve the prediction accuracy in the validation population,respectively.The results suggested that both GBLUP-Fix and GFBLUP models could improve the accuracy of longissimus dorsi muscle(LDM),water holding capacity(WHC),shear force(SF),and pH in Huaxi cattle on average from 2.14 to 8.69%,especially the improvement of GFBLUP-TWAS over GBLUP was 13.66%for SF.These methods also captured more genetic variance than GBLUP.Our study confirmed that multi-omics-assisted large-effects loci prescreening could improve the accuracyofgenomic prediction.
基金Research and Development Program of China(2023YFD1400200)the Natural Science Foundation of Fujian Province,China(2022J01125)+2 种基金the Fujian Key Laboratory for Monitoring and Integrated Management of Crop Pests,China(MIMCP-202301)the Fujian Provincial Science and Technology Key Project,China(2022NZ030014)the National Natural Science Foundation of China(NSFC31871914).
文摘The conserved DNA damage repair complex,MMS21-SMC5/6(Methyl methane sulfonate 21-Structural maintenance of chromosomes 5/6),has been extensively studied in yeast,animals,and plants.However,its role in phytopathogenic fungi,particularly in the highly destructive rice blast fungus Magnaporthe oryzae,remains unknown.In this study,we functionally characterized the homologues of this complex,MoMMS21 and MoSMC5,in M.oryzae.We first demonstrated the importance of DNA damage repair in M.oryzae by showing that the DNA damage inducer phleomycin inhibited vegetative growth,infection-related development and pathogenicity in this fungus.Additionally,we discovered that MoMMS21 and MoSMC5 interacted in the nuclei,suggesting that they also function as a complex in M.oryzae.Gene deletion experiments revealed that both MoMMS21 and MoSMC5 are required for infection-related development and pathogenicity in M.oryzae,while only MoMMS21 deletion affected growth and sensitivity to phleomycin,indicating its specific involvement in DNA damage repair.Overall,our results provide insights into the roles of MoMMS21 and MoSMC5 in M.oryzae,highlighting their functions beyond DNA damage repair.
基金funds from the National Natural Science Foundations of China(32172693)the Program of National Beef Cattle and Yak Industrial Technology System(CARS-37)。
文摘Background:Genomic selection(GS)has revolutionized animal and plant breeding after the first implementation via early selection before measuring phenotypes.Besides genome,transcriptome and metabolome information are increasingly considered new sources for GS.Difficulties in building the model with multi-omics data for GS and the limit of specimen availability have both delayed the progress of investigating multi-omics.Results:We utilized the Cosine kernel to map genomic and transcriptomic data as n×n symmetric matrix(G matrix and T matrix),combined with the best linear unbiased prediction(BLUP)for GS.Here,we defined five kernel-based prediction models:genomic BLUP(GBLUP),transcriptome-BLUP(TBLUP),multi-omics BLUP(MBLUP,M=ratio×G+(1-ratio)×T),multi-omics single-step BLUP(mss BLUP),and weighted multi-omics single-step BLUP(wmss BLUP)to integrate transcribed individuals and genotyped resource population.The predictive accuracy evaluations in four traits of the Chinese Simmental beef cattle population showed that(1)MBLUP was far preferred to GBLUP(ratio=1.0),(2)the prediction accuracy of wmss BLUP and mss BLUP had 4.18%and 3.37%average improvement over GBLUP,(3)We also found the accuracy of wmss BLUP increased with the growing proportion of transcribed cattle in the whole resource population.Conclusions:We concluded that the inclusion of transcriptome data in GS had the potential to improve accuracy.Moreover,wmss BLUP is accepted to be a promising alternative for the present situation in which plenty of individuals are genotyped when fewer are transcribed.
基金Nantong Science and Technology Program,grant number(JC2018090)the Practice Innovation Training Program Projects for the Jiangsu College Students,grant number(201810304028z)the Scientific Innovation Research of College Graduates in Jiangsu Province,grant number(KYCX18-2415)。
文摘Spinal muscular atrophy(SMA)is an autosomal recessive hereditary neuromuscular disease.Exon 7 and 8 of survival of motor neuron 1(SMN1)gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene.The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy,in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7.In this study,we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer(ISS)sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length(FL)gene expression.It happens that there was a protospacer adjacent motif(PAM)at one end of the ISS sequence according to the design of sgRNA.The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells.Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction,in which deleting small fragments,inserting small amounts and mutation.Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8%(P<0.05).In the primary cultured chondrocytes of SMA mice,in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23%(P<0.05)and significantly improve SMN protein levels(P<0.05).CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases,but it is rarely reported in the treatment of SMA diseases.This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing,which can effectively promote the production of SMN2 FL gene expressions,in which there was an important clinical reference value.
文摘Objective:The aim of our study was to explore the influence of interstitial brachytherapy with 125I seeds on Caspase-3 and Egr-1 expressions of Lewis lung carcinoma in C57BL mice.Methods:Model mice of C57BL were planted with Lewis lung cells (LLC) and divided into the treatment group (n=18) and the control group (n=17).In each mouse of the treatment group,two BT-125-1 Model 125I seeds with apparent activity of 9.25 MBq were implanted into the tumor;whereas in each mouse of the control group two dummy seeds were implanted.The mice survival rates of both groups were recorded after 21 days.The tumor weights and dimensions of survived mice were measured,and the tumor volume inhibition rate was calculated.T-test was performed to compare differences of tumor weights and volumes between these two groups.Routine pathological slides of tumor tissue were observed under light microscope.The expression of Caspase-3 was detected by immunohistochemical method and the expression of Egr-1 was detected by RT-PCR method.Results:The survival rates were 88.88% in the treatment group and 70.59% in the control group,the difference had no statistical significance (P > 0.05).The tumor volume inhibition rate was 71.12%.Pathological examination showed degeneration and necrosis of cancer cells at the site nearby the seed in the treated group,but the tumor cells alive were still presented nearby the seed in the control group.The expressions of Caspase-3 and Egr-1 in the treated group were higher than those in the control group (t=12.825,P < 0.01;t=7.039,P < 0.01;respectively).Conclusion:The interstitial brachytherapy with 125I seeds could significantly inhibit the growth of Lewis lung carcinoma of mice.The possible mechanism may be that 125I interstitial brachytherapy can enhance the expressions of Egr-1 and Caspase-3,which could induce tumor cellular apoptosis.
基金funding provided by the U.S.Department of Transportation through the NEXTRANS Center,the USDOT Region 5 University Transportation Center.
文摘Energy issues in transportation systems have garnered increasing attention recently.This study proposes a systematic methodology for policy-makers to minimize energy consumption in multimodal intercity transportation systems considering suppliers’operational constraints and travelers’mobility requirements.A bi-level optimization model is developed for this purpose and considers the air,rail,private auto,and transit modes.The upper-level model is a mixed integer nonlinear program aiming to minimize energy consumption subject to transportation suppliers’operational constraints and traffic demand distribution to paths resulting from the lower-level model.The lower-level model is a linear program seeking to maximize the trip utilities of travelers.The interactions between the multimodal transportation suppliers and intercity traffic demand are considered under the goal of minimizing system energy consumption.The proposed bi-level mixed integer model is relaxed and transformed into a mathematical program with complementarity constraints,and solved using a customized branch-and-bound algorithm.Numerical experiments,conducted using multimodal travel options between Lafayette,Indiana and Washington,D.C.reiterate that shifting traffic demand from private cars to the transit and rail modes significantly reduce energy consumption.Moreover,the proposed methodology provides tools to quantitatively analyze system energy consumption and traffic demand distribution among transportation modes under specific policy instruments.The results illustrate the need to systematically incorporate the interactions among traveler preferences,network structure,and supplier operational schemes to provide policy-makers insights for developing traffic demand shift mechanisms to minimize system energy consumption.Hence,the proposed methodology provide policy-makers the capability to analyze energy consumption in the transportation sector by a holistic approach.
基金supported by the U.S.National Science Foundation Project(No.ECCS-171121)CARRER Award(No.CMMI-1554559)CSUFRD-IoT Award.
文摘The power and transportation systems are urban interdependent critical infrastructures(CIs).During the post-disaster restoration process,transportation mobility and power restoration process are interdependent,and their functionalities significantly affect the well-beings of other urban CIs.Therefore,to enhance the resilience of urban CIs,successful recovery strategies should promote CI function cooperatively and synergistically to distribute goods and services efficiently.This paper develops an integrative framework that addresses the challenges of enhancing the recovery efficiency of urban power and transportation systems in short-term recovery period.Specifically,the post-storm recovery process is considered as a scheduling problem with the constraints representingcrew dispatch,equipment and fuel limit.We propose a new framework for co-optimizing the recovery scheduling of power and transportation systems,respecting precedency requirement and network constraints.The advantages and benefits of co-optimized recovery scheduling are validated in a testing system.
基金supported by National Nature Science Foundation of China(30871083)Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine(BXJ201442)
文摘The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.
基金This work was supported by National Key R&D Program of China(No.2018YFC1002902)the National Natural Science Foundation(No.81830045,81671533 and 81571518)General program of Guangdong province Natural Science Foundation(No.2020A1515010273).
文摘Background:High salt-diets have become significant threats to human health,resulting in hypertension and cardiovascular diseases.Hypertensive disorders during pregnancy are complicated,since the maternal cardiovascular system undergoes extensive physiological changes during pregnancy.High-salt diets during pregnancy can disturb the intrauterine environment and negatively affect fetal development.Therefore,we explored how high-salt diets during pregnancy could affect the offspring.Methods:Rats were divided into three groups and fed with low,normal,and high salt diets.The offspring were separated into three groups after weaning based on dietary salt concentration.The blood pressure and urine protein content of both dams and offspring were measured.To evaluate cardiac function,we used Masson staining and immunodetection to confirm the fibrosis status.Finally,we extracted protein from cardiac tissue to test the expression levels of the Nitric Oxide(NO)/cGMP-dependent protein kinase I(PKGI)pathway and the angiotensin receptor.Results:High-salt diets increased blood pressure,and offspring previously exposed to high-salt environments were predisposed to hypertension.High-salt diets were also found to induce cardiac fibrosis and exacerbate fibrosis in offspring and alter the epithelial-mesenchymal transition(EMT).Under these conditions,the NO/PKGI pathway was activated in cardiac tissue and the type-1angiotensin II receptor(AT1R)was upregulated,though the type-2 angiotensin II receptor(AT2R)had the opposite effect.Conclusion:High-salt diets induce high blood pressure and increase predisposition to hypertension in offspring.They are accompanied by cardiac fibrosis,which could be caused by the activation of NO/PKGI and upregulation of AT1R.
基金the National Natural Science Foundation of China Grant No.10974074,61540076the Research Fund for the Doctoral Program of Higher Education of China Grant No.20110211110005the Research Project of Graduate Teacher of Gansu Province Grant No.2014B-079.
文摘Organolead halide perovskite is a newly emerging low-cost,solution-processable material with a broadband absorption from the ultraviolet(UV)to visible(Vis)region,which has attracted a great deal of interest in high-performance optoelectronic devices.However,some practicable applications need a cover of UV–Vis–NIR region for photoelectric conversion,a task that remains a significant challenge for further extending the absorption toward the near-infrared radiation(NIR)region.Here,to the best of our knowledge,we prove for the first time an ultrasensitive flexible broadband photodetector based on porous organolead perovskitephthalocyanine heterostructure,which combines the synergetic properties of high UV–Vis absorbance of perovskite with enhanced NIR absorption for triclinic lead phthalocyanine.The photosensitivity of the as-prepared devices reaches up to 10^(4) at a low intensity of 10mWcm^(−2),which is among the largest values reported for broadband photodetectors.Significantly,performed at room temperature,the device achieves a pA scale dark current along with an ultrafast response speed of less than 0.6 ms for as-adopted full spectra.Our results provide an easy and promising route to develop low-cost,flexible and highly sensitive UV–Vis–NIR photodetectors.
基金supported by grants from the National Key R&D Program of China(No.2016YFC1000405,2017YFC1001402,and 2018YFC10029002)the National Natural Science Foundation(No.81830045,81671533,and 82071652).
文摘Objective:To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta(PA).Methods:This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017.According to the intraoperative findings after delivery,the study population was divided into PA and non-PA groups.We compared the pregnancy outcomes between the two groups,used multivariate logistic regression to analyze the risk factors for placental accreta.Results:For this study we included 11,074 pregnant women with a history of cesarean section;and of these,869 cases were in the PA group and 10,205 cases were in the non-PA group.Compared with the non-PA group,the probability of postpartum hemorrhage(236/10,205,2.31%vs.283/869,32.57%),severe postpartum hemorrhage(89/10,205,0.87%vs.186/869,21.75%),diffuse intravascular coagulation(3/10,205,0.03%vs.4/869,0.46%),puerperal infection(33/10,205,0.32%vs.12/869,1.38%),intraoperative bladder injury(1/10,205,0.01%vs.16/869,1.84%),hysterectomy(130/10,205,1.27%vs.59/869,6.79%),and blood transfusion(328/10,205,3.21%vs.231/869,26.58%)was significantly increased in the PA group(P<0.05).At the same time,the neonatal birth weight 3250.00(2950.00–3520.00)g vs.2920.00(2530.00–3250.00)g),the probability of neonatal comorbidities(245/10,205,2.40%vs.61/869,7.02%),and the rate of neonatal intensive care unit admission(817/10,205,8.01%vs.210/869,24.17%)also increased significantly(P<0.05).Weight(odds ratio)(OR)=1.03,95%confidence interval(CI):1.01–1.05)),parity(OR=1.18,95%CI:1.03–1.34),number of miscarriages(OR=1.31,95%CI:1.17–1.47),number of previous cesarean sections(OR=2.57,95%CI:2.02–3.26),history of premature rupture of membrane(OR=1.61,95%CI:1.32–1.96),previous cesarean-section transverse incisions(OR=1.38,95%CI:1.12–1.69),history of placenta previa(OR=2.44,95%CI:1.50–3.96),and the combination of prenatal hemorrhage(OR=9.95,95%CI:8.42–11.75)and placenta previa(OR=91.74,95%CI:74.11–113.56)were all independent risk factors for PA.Conclusion:There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section,and this required close clinical attention.Weight before pregnancy,parity,number of miscarriages,number of previous cesarean sections,history of premature rupture of membranes,past transverse incisions in cesarean sections,a history of placenta previa,prenatal hemorrhage,and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section.These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.
基金National Key R&D Program of China(No. 2016YFC1000405, 2017YFC1001402, 2018YFC1004104, and 2018YFC10029002)National Natural Science Foundation(No. 81830045, 81671533, 81571518, and 81971415)General program of Guangdong province Natural Science Foundation(No. 2020A1515010273)。
文摘Objective: To investigate whether the fetal gender affects the incidence of pre-eclampsia (PE) and fetal growth restriction (FGR) in singleton and twin pregnancies.Methods: This was a 10-year single-center, retrospective, cohort study from January 2009 to January 2019. A total of 57,129 singleton and 3699 twin pregnancies aged between 18-55 years old were recruited at the Third Affiliated Hospital of Guangzhou Medical University, China. We used multivariable logistic regression to analyze the effect of fetal gender on the incidence of PE and FGR.Results: In singleton pregnancies, the incidence rates of PE and FGR with a female fetus were higher than those with a male fetus (6.4% (1713/26,793)vs. 5.9% (1803/30,336),P < 0.05 and 3.5% (932/26,793)vs. 2.4% (745/30,336),P < 0.05, respectively). A female fetus was an independent risk factor for either PE or FGR (adjusted odds ratio: 1.169 or 1.563;95% confidence interval: 1.036-1.319 or 1.349-1.810, respectively). In twin pregnancies, the incidence of early-onset PE was greater in pregnancies with two females compared with two males or one male plus one female (4.6% (46/1003)vs. 4.1% (54/1305)vs. 2.4% (33/1391),P < 0.05). Female-female twins was an independent risk factor for PE (adjusted odds ratio: 1.367, 95% confidence interval: 1.011-1.849), especially early-onset PE.Conclusion: The female fetus was associated with PE in both singleton and twin pregnancies and was also a risk factor of FGR in singleton pregnancies.
基金National Key R&D Program of China(no.2022YFC2704501,2022YFC2704503 and 2022YFC2704505)National Natural Science Foundation of China(no.81830045 and 82071652)+1 种基金Sino-German Center for Research Promotion’s Rapid Response Funding Call for Bilateral Collaborative Proposals Between China and Germany in COVID-19 Related Research(grant/award no.C-0032)General Program of Guangdong Province Natural Science Foundation(no.2021A1515011039 and 2020A1515010273)。
文摘Objective:This study aimed to investigate the immune response of a pregnant woman who recovered from the coronavirus disease 2019(COVID_(R)S)by using single-cell transcriptomic profiling of peripheral blood mononuclear cells(PBMCs)and to analyze the properties of different immune cell subsets.Methods:PBMCs were collected from the COVID_(R)S patient at 28 weeks of gestation,before a cesarean section.The PBMCs were then analyzed using single-cell RNA sequencing.The transcriptional profiles of myeloid,T,and natural killer(NK)cell subsets were systematically analyzed and compared with those of healthy pregnant controls from a published single-cell RNA sequencing data set.Results:We identified major cell types such as T cells,B cells,NK cells,and myeloid cells in the PBMCs of our COVID_(R)S patient.The increase of myeloid and B cells and decrease of T cells and NK cells in the PBMCs in this patient were quite distinct compared with that in the control subjects.After reclustering and Augur analysis,we found that CD16 monocytes and mucosal-associated invariant T(MAIT)cells were mostly affected within different myeloid,T,and NK cell subtypes in our COVID_(R)S patient.The proportion of CD16 monocytes in the total myeloid population was increased,and the frequency of MAIT cells in the total T and NK cells was significantly decreased in the COVID-RS patient.We also observed significant enrichment of gene sets related to antigen processing and presentation,T-cell activation,T-cell differentiation,and tumor necrosis factor superfamily cytokine production in CD16 monocytes,and enrichment of gene sets related to antigen processing and presentation,response to type II interferon,and response to virus in MAIT cells.Conclusion:Our study provides a single-cell resolution atlas of the immune gene expression patterns in PBMCs from a COVID_(R)S patient.Our findings suggest that CD16-positive monocytes and MAIT cells likely play crucial roles in the maternal immune response against severe acute respiratory syndrome coronavirus 2 infection.These results contribute to a better understanding of the maternal immune response to severe acute respiratory syndrome coronavirus 2 infection and may have implications for the development of effective treatments and preventive strategies for the coronavirus disease 2019 in pregnant women.
