Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environmen...Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.展开更多
This paper presents a new method .linear programming method. to calculate the proportion of the cement raw material. Its advanlages are as following : good practicability, convenience for analysis, and being easy for ...This paper presents a new method .linear programming method. to calculate the proportion of the cement raw material. Its advanlages are as following : good practicability, convenience for analysis, and being easy for controlling. The mathematical model given in the paper is apt to be realized on computer.展开更多
UML Class diagram generation from textual requirements is an important task in object-oriented design and programing course.This study proposes a method for automatically generating class diagrams from Chinese textual...UML Class diagram generation from textual requirements is an important task in object-oriented design and programing course.This study proposes a method for automatically generating class diagrams from Chinese textual requirements on the basis of Natural Language Processing(NLP)and mapping rules for sentence pattern matching.First,classes are identified through entity recognition rules and candidate class pruning rules using NLP from requirements.Second,class attributes and relationships between classes are extracted using mapping rules for sentence pattern matching on the basis of NLP.Third,we developed an assistant tool integrated into a precision micro classroom system for automatic generation of class diagram,to effectively assist the teaching of object-oriented design and programing course.Results are evaluated with precision,accuracy and recall from eight requirements of object-oriented design and programing course using truth values created by teachers.Our research should benefit beginners of object-oriented design and programing course,who may be students or software developers.It helps them to create correct domain models represented in the UML class diagram.展开更多
In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon-Mann-Whitney （WMW） test is among the most popular h...In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon-Mann-Whitney （WMW） test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calcu- late the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we pre- sented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molec- ular biomarkers for lung carcinoma and chronic obstructive pulmonary disease （COPD）. We foundthat approximated P values were generally higher than the exact solution provided by EDISON- WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http：// www.ccb.uni-saarland.de/software/wtest/.展开更多
Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understoo...Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.展开更多
Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive...During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.展开更多
Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various dise...Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.展开更多
Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis...Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.展开更多
Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal deg...Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.展开更多
A trust region algorithm is proposed for solving bilevel programming problems where the lower level programming problem is a strongly convex programming problem with linear constraints. This algorithm is based on a tr...A trust region algorithm is proposed for solving bilevel programming problems where the lower level programming problem is a strongly convex programming problem with linear constraints. This algorithm is based on a trust region algorithm for nonsmooth unconstrained optimization problems, and its global convergence is also proved.展开更多
The Internet of Things emphasizes the concept of objects connected with each other, which includes all kinds of wireless sensor networks. An important issue is to reduce the energy consumption in the sensor networks s...The Internet of Things emphasizes the concept of objects connected with each other, which includes all kinds of wireless sensor networks. An important issue is to reduce the energy consumption in the sensor networks since sensor nodes always have energy constraints. Deployment of thousands of wireless sensors in an appropriate pattern will simultaneously satisfy the application requirements and reduce the sensor network energy consumption. This article deployed a number of sensor nodes to record temperature data. The data was then used to predict the temperatures of some of the sensor node using linear programming. The predictions were able to reduce the node sampling rate and to optimize the node deployment to reduce the sensor energy consumption. This method can compensate for the temporarily disabled nodes. The main objective is to design the objective function and determine the constraint condition for the linear programming. The result based on real experiments shows that this method successfully predicts the values of unknown sensor nodes and optimizes the node deployment. The sensor network energy consumption is also reduced by the optimized node deployment.展开更多
Engineering optimization problems can be always classified into two main categories including the linear programming(LP)and nonlinear programming(NLP)problems.Each programming problem further involves the unconstraine...Engineering optimization problems can be always classified into two main categories including the linear programming(LP)and nonlinear programming(NLP)problems.Each programming problem further involves the unconstrained conditions and constrained conditions for design variables of the optimized system.This paper will focus on the issue about the design problem of NLP with the constrained conditions.The employed method for such NLP problems is a variant of particle swarm optimization(PSO),named improved particle swarm optimization(IPSO).The developed IPSO is to modify the velocity updating formula of the algorithm to enhance the search ability for given optimization problems.In this work,many different kinds of physical engineering optimization problems are examined and solved via the proposed IPSO algorithm.Simulation results compared with various optimization methods reported in the literature will show the effectiveness and feasibility for solving NLP problems with the constrained conditions.展开更多
In a recent study published in Nature,Zhang et al.employed an innovative approach by reprogramming and engineering yeast strain for combined biosynthesis of vindoline and catharanthine,followed by an additional in vit...In a recent study published in Nature,Zhang et al.employed an innovative approach by reprogramming and engineering yeast strain for combined biosynthesis of vindoline and catharanthine,followed by an additional in vitro chemical step for the successful synthesis of the anti-cancer vinblastine.Development and utilization of plant resources have played indispensable roles in the treatment of human diseases,which had been an amazing focus of biomedical research for decades.Monoterpene indole alkaloids(MIAs),the plant secondary metabolites that mainly exist in Gentianales,had been a popular family of the medicinal drug research because of their remarkable structural diversities and biological activities.展开更多
The concept of the spacecraft Reachable Domain(RD)has garnered significant scholarly attention due to its crucial role in space situational awareness and on-orbit service applications.While the existing research has l...The concept of the spacecraft Reachable Domain(RD)has garnered significant scholarly attention due to its crucial role in space situational awareness and on-orbit service applications.While the existing research has largely focused on single-impulse RD analysis,the challenge of Multi-Impulse RD(MIRD)remains a key area of interest.This study introduces a methodology for the precise calculation of spacecraft MIRD.The reachability constraints specific to MIRD are first formulated through coordinate transformations.Two restricted maneuvering strategies are examined.The derivation of two extremum conditions allows for determining the accessible orientation range and the nodes encompassing the MIRD.Subsequently,four nonlinear programming models are developed to address two types of MIRD by skillfully relaxing constraints using scale factors.Numerical results validate the robustness and effectiveness of the proposed approach,showing substantial agreement with Monte Carlo simulations and confirming its applicability to spacecraft on various elliptical orbits.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
Generating dynamically feasible trajectory for fixed-wing Unmanned Aerial Vehicles(UAVs)in dense obstacle environments remains computationally intractable.This paper proposes a Safe Flight Corridor constrained Sequent...Generating dynamically feasible trajectory for fixed-wing Unmanned Aerial Vehicles(UAVs)in dense obstacle environments remains computationally intractable.This paper proposes a Safe Flight Corridor constrained Sequential Convex Programming(SFC-SCP)to improve the computation efficiency and reliability of trajectory generation.SFC-SCP combines the front-end convex polyhedron SFC construction and back-end SCP-based trajectory optimization.A Sparse A^(*)Search(SAS)driven SFC construction method is designed to efficiently generate polyhedron SFC according to the geometric relation among obstacles and collision-free waypoints.Via transforming the nonconvex obstacle-avoidance constraints to linear inequality constraints,SFC can mitigate infeasibility of trajectory planning and reduce computation complexity.Then,SCP casts the nonlinear trajectory optimization subject to SFC into convex programming subproblems to decrease the problem complexity.In addition,a convex optimizer based on interior point method is customized,where the search direction is calculated via successive elimination to further improve efficiency.Simulation experiments on dense obstacle scenarios show that SFC-SCP can generate dynamically feasible safe trajectory rapidly.Comparative studies with state-of-the-art SCP-based methods demonstrate the efficiency and reliability merits of SFC-SCP.Besides,the customized convex optimizer outperforms off-the-shelf optimizers in terms of computation time.展开更多
Deep-time Earth research plays a pivotal role in deciphering the rates,patterns,and mechanisms of Earth's evolutionary processes throughout geological history,providing essential scientific foundations for climate...Deep-time Earth research plays a pivotal role in deciphering the rates,patterns,and mechanisms of Earth's evolutionary processes throughout geological history,providing essential scientific foundations for climate prediction,natural resource exploration,and sustainable planetary stewardship.To advance Deep-time Earth research in the era of big data and artificial intelligence,the International Union of Geological Sciences initiated the“Deeptime Digital Earth International Big Science Program”(DDE)in 2019.At the core of this ambitious program lies the development of geoscience knowledge graphs,serving as a transformative knowledge infrastructure that enables the integration,sharing,mining,and analysis of heterogeneous geoscience big data.The DDE knowledge graph initiative has made significant strides in three critical dimensions:(1)establishing a unified knowledge structure across geoscience disciplines that ensures consistent representation of geological entities and their interrelationships through standardized ontologies and semantic frameworks;(2)developing a robust and scalable software infrastructure capable of supporting both expert-driven and machine-assisted knowledge engineering for large-scale graph construction and management;(3)implementing a comprehensive three-tiered architecture encompassing basic,discipline-specific,and application-oriented knowledge graphs,spanning approximately 20 geoscience disciplines.Through its open knowledge framework and international collaborative network,this initiative has fostered multinational research collaborations,establishing a robust foundation for next-generation geoscience research while propelling the discipline toward FAIR(Findable,Accessible,Interoperable,Reusable)data practices in deep-time Earth systems research.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.展开更多
BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression i...BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.展开更多
基金supported by the National Council of Science and Technology in Mexico(CONACYT)708452 CONACYT to LMM855559 CONACYT to GCC+1 种基金573686 CONACYT to RMRPAICYT 2021 to ACM。
文摘Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.
文摘This paper presents a new method .linear programming method. to calculate the proportion of the cement raw material. Its advanlages are as following : good practicability, convenience for analysis, and being easy for controlling. The mathematical model given in the paper is apt to be realized on computer.
基金This work is supported by the Collaborative education project of QST Innovation Technology Group Co.,Ltd and the Ministry of Education of PRC(NO.201801243022).
文摘UML Class diagram generation from textual requirements is an important task in object-oriented design and programing course.This study proposes a method for automatically generating class diagrams from Chinese textual requirements on the basis of Natural Language Processing(NLP)and mapping rules for sentence pattern matching.First,classes are identified through entity recognition rules and candidate class pruning rules using NLP from requirements.Second,class attributes and relationships between classes are extracted using mapping rules for sentence pattern matching on the basis of NLP.Third,we developed an assistant tool integrated into a precision micro classroom system for automatic generation of class diagram,to effectively assist the teaching of object-oriented design and programing course.Results are evaluated with precision,accuracy and recall from eight requirements of object-oriented design and programing course using truth values created by teachers.Our research should benefit beginners of object-oriented design and programing course,who may be students or software developers.It helps them to create correct domain models represented in the UML class diagram.
文摘In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon-Mann-Whitney （WMW） test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calcu- late the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we pre- sented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molec- ular biomarkers for lung carcinoma and chronic obstructive pulmonary disease （COPD）. We foundthat approximated P values were generally higher than the exact solution provided by EDISON- WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http：// www.ccb.uni-saarland.de/software/wtest/.
文摘Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
基金supported by the National Natural Sci‐ence Foundation of China(Grant No.62306325)。
文摘During the use of robotics in applications such as antiterrorism or combat,a motion-constrained pursuer vehicle,such as a Dubins unmanned surface vehicle(USV),must get close enough(within a prescribed zero or positive distance)to a moving target as quickly as possible,resulting in the extended minimum-time intercept problem(EMTIP).Existing research has primarily focused on the zero-distance intercept problem,MTIP,establishing the necessary or sufficient conditions for MTIP optimality,and utilizing analytic algorithms,such as root-finding algorithms,to calculate the optimal solutions.However,these approaches depend heavily on the properties of the analytic algorithm,making them inapplicable when problem settings change,such as in the case of a positive effective range or complicated target motions outside uniform rectilinear motion.In this study,an approach employing a high-accuracy and quality-guaranteed mixed-integer piecewise-linear program(QG-PWL)is proposed for the EMTIP.This program can accommodate different effective interception ranges and complicated target motions(variable velocity or complicated trajectories).The high accuracy and quality guarantees of QG-PWL originate from elegant strategies such as piecewise linearization and other developed operation strategies.The approximate error in the intercept path length is proved to be bounded to h^(2)/(4√2),where h is the piecewise length.
基金supported by the Natural Science Foundation of Chongqing,No.CSTB2023NSCQ-mSX0561(to WL).
文摘Effective treatment methods for stroke,a common cerebrovascular disease with a high mortality rate,are still being sought.Exosome therapy,a form of acellular therapy,has demonstrated promising efficacy in various diseases in animal models;however,there is currently insufficient evidence to guide the clinical application of exosome in patients with stroke.This article reviews the progress of exosome applications in stroke treatment.It aims to elucidate the significant potential value of exosomes in stroke therapy and provide a reference for their clinical translation.At present,many studies on exosome-based therapies for stroke are actively underway.Regarding preclinical research,exosomes,as bioactive substances with diverse sources,currently favor stem cells as their origin.Due to their high plasticity,exosomes can be effectively modified through various physical,chemical,and genetic engineering methods to enhance their efficacy.In animal models of stroke,exosome therapy can reduce neuroinflammatory responses,alleviate oxidative stress damage,and inhibit programmed cell death.Additionally,exosomes can promote angiogenesis,repair and regenerate damaged white matter fiber bundles,and facilitate the migration and differentiation of neural stem cells,aiding the repair process.We also summarize new directions for the application of exosomes,specifically the exosome intervention through the ventricular-meningeal lymphatic system.The review findings suggest that the treatment paradigm for stroke is poised for transformation.
基金supported by the Spanish Ministerio de Ciencia e Innovación/Agencia Española de Investigación(PID2021-124096OB-I00)(to JLV)JGR was granted by Demensfonden,The Royal Physiografic Society of Lund,Neurofonden,The Greta och Johan Kocks stiftelser,and Bertil och Ebon Norlins stiftelse.
文摘Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.
基金supported by the National Natural Science Foundation of China,Nos.82171076(to XS)and U22A20311(to XS),82101168(to TL)Shanghai Science and technology Innovation Action Plan,No.23Y11901300(to JS)+1 种基金Science and Technology Commission of Shanghai Municipality,No.21ZR1451500(to TL)Shanghai Pujiang Program,No.22PJ1412200(to BY)。
文摘Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss.Ferroptosis has been demonstrated to be associated with retinal degenerative diseases.However,the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored.Bioinformatics and biochemical analyses in this study revealed xC^(–),solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model.This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway,through which cystine depletion,iron ion accumulation,and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment.We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo.Conversely,solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H_(2)O_(2)-induced ferroptosis of 661W cells.These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.
文摘A trust region algorithm is proposed for solving bilevel programming problems where the lower level programming problem is a strongly convex programming problem with linear constraints. This algorithm is based on a trust region algorithm for nonsmooth unconstrained optimization problems, and its global convergence is also proved.
基金supported in part by the National High-Tech Research and Development (863) Program of China(No. 2011AA010101)the National Natural Science Foundation of China (Nos. 61103197 and 61073009)+2 种基金the Science and Technology Key Project of Jilin Province(No. 2011ZDGG007)the Youth Foundation of Jilin Province of China (No. 201101035)the Fundamental Research Funds for the Central Universities of China(No. 200903179)
文摘The Internet of Things emphasizes the concept of objects connected with each other, which includes all kinds of wireless sensor networks. An important issue is to reduce the energy consumption in the sensor networks since sensor nodes always have energy constraints. Deployment of thousands of wireless sensors in an appropriate pattern will simultaneously satisfy the application requirements and reduce the sensor network energy consumption. This article deployed a number of sensor nodes to record temperature data. The data was then used to predict the temperatures of some of the sensor node using linear programming. The predictions were able to reduce the node sampling rate and to optimize the node deployment to reduce the sensor energy consumption. This method can compensate for the temporarily disabled nodes. The main objective is to design the objective function and determine the constraint condition for the linear programming. The result based on real experiments shows that this method successfully predicts the values of unknown sensor nodes and optimizes the node deployment. The sensor network energy consumption is also reduced by the optimized node deployment.
基金This work was partially supported by the Ministry of Science and Technology of Taiwan Under Grant No.MOST 108-2221-E-366-003.
文摘Engineering optimization problems can be always classified into two main categories including the linear programming(LP)and nonlinear programming(NLP)problems.Each programming problem further involves the unconstrained conditions and constrained conditions for design variables of the optimized system.This paper will focus on the issue about the design problem of NLP with the constrained conditions.The employed method for such NLP problems is a variant of particle swarm optimization(PSO),named improved particle swarm optimization(IPSO).The developed IPSO is to modify the velocity updating formula of the algorithm to enhance the search ability for given optimization problems.In this work,many different kinds of physical engineering optimization problems are examined and solved via the proposed IPSO algorithm.Simulation results compared with various optimization methods reported in the literature will show the effectiveness and feasibility for solving NLP problems with the constrained conditions.
文摘In a recent study published in Nature,Zhang et al.employed an innovative approach by reprogramming and engineering yeast strain for combined biosynthesis of vindoline and catharanthine,followed by an additional in vitro chemical step for the successful synthesis of the anti-cancer vinblastine.Development and utilization of plant resources have played indispensable roles in the treatment of human diseases,which had been an amazing focus of biomedical research for decades.Monoterpene indole alkaloids(MIAs),the plant secondary metabolites that mainly exist in Gentianales,had been a popular family of the medicinal drug research because of their remarkable structural diversities and biological activities.
基金supported by the National Natural Science Foundation of China(Nos.12372052,12125207)the Young Elite Scientists Sponsorship Program,China(No.2021JCJQ-QT-047)+1 种基金the Natural Science Foundation of Hunan Province,China(No.2023JJ20047)the Technology Innovation Team of Manned Space Engineering,China。
文摘The concept of the spacecraft Reachable Domain(RD)has garnered significant scholarly attention due to its crucial role in space situational awareness and on-orbit service applications.While the existing research has largely focused on single-impulse RD analysis,the challenge of Multi-Impulse RD(MIRD)remains a key area of interest.This study introduces a methodology for the precise calculation of spacecraft MIRD.The reachability constraints specific to MIRD are first formulated through coordinate transformations.Two restricted maneuvering strategies are examined.The derivation of two extremum conditions allows for determining the accessible orientation range and the nodes encompassing the MIRD.Subsequently,four nonlinear programming models are developed to address two types of MIRD by skillfully relaxing constraints using scale factors.Numerical results validate the robustness and effectiveness of the proposed approach,showing substantial agreement with Monte Carlo simulations and confirming its applicability to spacecraft on various elliptical orbits.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
基金supported by the National Natural Science Foundation of China(No.62203256)。
文摘Generating dynamically feasible trajectory for fixed-wing Unmanned Aerial Vehicles(UAVs)in dense obstacle environments remains computationally intractable.This paper proposes a Safe Flight Corridor constrained Sequential Convex Programming(SFC-SCP)to improve the computation efficiency and reliability of trajectory generation.SFC-SCP combines the front-end convex polyhedron SFC construction and back-end SCP-based trajectory optimization.A Sparse A^(*)Search(SAS)driven SFC construction method is designed to efficiently generate polyhedron SFC according to the geometric relation among obstacles and collision-free waypoints.Via transforming the nonconvex obstacle-avoidance constraints to linear inequality constraints,SFC can mitigate infeasibility of trajectory planning and reduce computation complexity.Then,SCP casts the nonlinear trajectory optimization subject to SFC into convex programming subproblems to decrease the problem complexity.In addition,a convex optimizer based on interior point method is customized,where the search direction is calculated via successive elimination to further improve efficiency.Simulation experiments on dense obstacle scenarios show that SFC-SCP can generate dynamically feasible safe trajectory rapidly.Comparative studies with state-of-the-art SCP-based methods demonstrate the efficiency and reliability merits of SFC-SCP.Besides,the customized convex optimizer outperforms off-the-shelf optimizers in terms of computation time.
基金Strategic Priority Research Program of the Chinese Academy of Sciences,No.XDB0740000National Key Research and Development Program of China,No.2022YFB3904200,No.2022YFF0711601+1 种基金Key Project of Innovation LREIS,No.PI009National Natural Science Foundation of China,No.42471503。
文摘Deep-time Earth research plays a pivotal role in deciphering the rates,patterns,and mechanisms of Earth's evolutionary processes throughout geological history,providing essential scientific foundations for climate prediction,natural resource exploration,and sustainable planetary stewardship.To advance Deep-time Earth research in the era of big data and artificial intelligence,the International Union of Geological Sciences initiated the“Deeptime Digital Earth International Big Science Program”(DDE)in 2019.At the core of this ambitious program lies the development of geoscience knowledge graphs,serving as a transformative knowledge infrastructure that enables the integration,sharing,mining,and analysis of heterogeneous geoscience big data.The DDE knowledge graph initiative has made significant strides in three critical dimensions:(1)establishing a unified knowledge structure across geoscience disciplines that ensures consistent representation of geological entities and their interrelationships through standardized ontologies and semantic frameworks;(2)developing a robust and scalable software infrastructure capable of supporting both expert-driven and machine-assisted knowledge engineering for large-scale graph construction and management;(3)implementing a comprehensive three-tiered architecture encompassing basic,discipline-specific,and application-oriented knowledge graphs,spanning approximately 20 geoscience disciplines.Through its open knowledge framework and international collaborative network,this initiative has fostered multinational research collaborations,establishing a robust foundation for next-generation geoscience research while propelling the discipline toward FAIR(Findable,Accessible,Interoperable,Reusable)data practices in deep-time Earth systems research.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I^(2)=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC.
