Business process execution language(BPEL)is a most recognized standard workflow language.However,it is difficult to be used in the ubiquitous system computing environment because it is difficult to describe the contex...Business process execution language(BPEL)is a most recognized standard workflow language.However,it is difficult to be used in the ubiquitous system computing environment because it is difficult to describe the context information in the selection of the flow through the branch.To solve this problem,we propose a new BPEL workflow system with context-awareness by using aspect-oriented programming(AOP).This system is composed of a BPEL system module and a weaving module using AOP for context-aware.The BPEL system module generates a BPEL workflow program.And the weaving module converts a context-aware mark-up language(CAML)document to the aspect-oriented program that is applied to context-aware code without modification of the existing BPEL document.We also define a new document form that is called CAML,which provides a context-aware that is not available in BPEL.The system can generate a context-aware workflow program.It is developed in a way that inserts context information using AOP to provide context-aware services.展开更多
Aspect-oriented programs have received much attention from software testing researchers. Various testing techniques and approaches have been proposed to tackle issues and challenges when testing aspect-oriented progra...Aspect-oriented programs have received much attention from software testing researchers. Various testing techniques and approaches have been proposed to tackle issues and challenges when testing aspect-oriented programs including traditional mutation testing. In traditional mutation testing of aspect-oriented programs, mutants are generated by making small changes to the syntax of the aspect-oriented language. Recently, a new approach known as semantic mutation testing has been proposed. This approach mutates the semantics of the language in which the program is written. The mutants generated misunderstandings of the language which are different classes of faults. Aspect-oriented programming presents itself with different properties that can be further explored with respect to semantic mutation testing. This paper describes various possible scenarios that semantic mutation testing strategy might have particular value in testing aspect-oriented programs.展开更多
Business Process Exeention Language （BPEL） is being used in various applications as the standard of workflow. As the requirerments increase to describe application processes in BPEL, BPEL documentt is getting more C...Business Process Exeention Language （BPEL） is being used in various applications as the standard of workflow. As the requirerments increase to describe application processes in BPEL, BPEL documentt is getting more Complplicated. Therefore it is difficult to describe applications in BPEL with high reliability. In order to write highly reliable BPEL document, it is necessary to check if the document is working correctly in accordance with user＇s intention. But it is difficult to carry out the test since BPEL engine doesn＇t provide a profiling function. In this paper, we suggest a BPEL system with a real-time profiling function. The suggested system consists of an integrated development environment and a BPEL nunning environment. BPEL integrated development environment has a BPEL to Java（B2J） engine, which generates and executes a Java workflow program from a BPEL document, and a converter, which converts Java Weaving XML （JWX） documents to Aspect-oriented programs. The new functions are described in JWX, which is Extensive Markup Lan-guage （XML）-based document. Since aspect-oriented programming technique provides the way to modularize main and supplemental requirements, it guarantees the low degree of coupling between BPEL workflow program and new functions by weaving them. Our approach can be extended to add other functions to provide context-aware services.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
Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 str...Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.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
Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will tak...Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will take,in the next five years,to further support the global cause of women.One of the measures is:China will launch 1,000"small and beautiful"livelihood programs with Chinese assistance that take women and girls as priority beneficiaries.展开更多
Aspect-oriented modeling can uncover potential design faults,yet most existing work fails to achieve both separation and composition in a natural and succinct way.This study presents an aspect-oriented modeling and an...Aspect-oriented modeling can uncover potential design faults,yet most existing work fails to achieve both separation and composition in a natural and succinct way.This study presents an aspect-oriented modeling and analysis approach with hierarchical Coloured Petri Nets(HCPN).HCPN has sub-models and well-defined semantics combining a set of submodels.These two characteristics of HCPN are nicely integrated into aspect oriented modeling.Submodels are used to model aspects while the combination mechanism contributes to aspects weaving.Furthermore,the woven aspect oriented HCPN model can be simulated and analyzed by the CPN Tools.A systematic web application case study is conducted.The results show the system original properties are satisfied after weaving aspects and all design flaws are revealed.As such,the approach can support web application design and analysis in an aspect-oriented fashion concisely and effectively.展开更多
To solve the identification and comprehension problem of crosscutting concerns in existing legacy software system, a framework of aspect-oriented software reveme engineering is proposed. An approach on re-modularizing...To solve the identification and comprehension problem of crosscutting concerns in existing legacy software system, a framework of aspect-oriented software reveme engineering is proposed. An approach on re-modularizing traversal features of legacy system is presented based on various unified modeling language （UML） diagrams. While modeling crosscutting concerns in UML use case diagrams, the non-functional requirements that affect several use case modules can be enveloped into aspect modules with a stereotype mechanism. The recurring message transmission patterns can be re-modularized as aspects in UML sequence diagrams with UML collaborations. Standard UML activity diagram notations are extended and modified by node fusion and addition, which support the graphical composition operation between crosscutting behaviors and primary business roles of concurrent systems. Case study indicates that travernal features of software system can be extracted and re-modularized from various perspectives in aspect-oriented reverse engineering, which improves comprehensibility and maintainability of legacy systems.展开更多
In recent years, mobile devices have become widespread and refined, and they have offered increased convenience in human life. For these reasons, a variety of embedded systems have been designed. Therefore, improving ...In recent years, mobile devices have become widespread and refined, and they have offered increased convenience in human life. For these reasons, a variety of embedded systems have been designed. Therefore, improving methods for developing of embedded software systematically has become an important issue. Platform-based design is one example of an embedded-system design method that can reduce the design cost via improving a design’s abstraction level. However, platform-based design lacks precise definitions for platforms and design processes. This paper provides an approach that combines the aspects and platform-based design methods for developing embedded software. The approach is built on platform-based design methodology and uses the separating of concerns (SoC) concept to define the aspects and to reduce the crosscutting concerns in embedded system modeling. For aspect issues, we use the extended UML notation with aspects to describe both the static structure and the dynamic structure of the embedded system. We used an example of a digital photo frame system to demonstrate our approach.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
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
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
Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells c...Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.展开更多
BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both brea...BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.展开更多
基金Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,Science and Technology(No.2010-0025831)
文摘Business process execution language(BPEL)is a most recognized standard workflow language.However,it is difficult to be used in the ubiquitous system computing environment because it is difficult to describe the context information in the selection of the flow through the branch.To solve this problem,we propose a new BPEL workflow system with context-awareness by using aspect-oriented programming(AOP).This system is composed of a BPEL system module and a weaving module using AOP for context-aware.The BPEL system module generates a BPEL workflow program.And the weaving module converts a context-aware mark-up language(CAML)document to the aspect-oriented program that is applied to context-aware code without modification of the existing BPEL document.We also define a new document form that is called CAML,which provides a context-aware that is not available in BPEL.The system can generate a context-aware workflow program.It is developed in a way that inserts context information using AOP to provide context-aware services.
文摘Aspect-oriented programs have received much attention from software testing researchers. Various testing techniques and approaches have been proposed to tackle issues and challenges when testing aspect-oriented programs including traditional mutation testing. In traditional mutation testing of aspect-oriented programs, mutants are generated by making small changes to the syntax of the aspect-oriented language. Recently, a new approach known as semantic mutation testing has been proposed. This approach mutates the semantics of the language in which the program is written. The mutants generated misunderstandings of the language which are different classes of faults. Aspect-oriented programming presents itself with different properties that can be further explored with respect to semantic mutation testing. This paper describes various possible scenarios that semantic mutation testing strategy might have particular value in testing aspect-oriented programs.
基金supported by MKE(The Ministry of Knowledge Economy),Koreathe ITRC support program supervised by the NIPA(NIPA-2009-(C1090-0902-0007))
文摘Business Process Exeention Language （BPEL） is being used in various applications as the standard of workflow. As the requirerments increase to describe application processes in BPEL, BPEL documentt is getting more Complplicated. Therefore it is difficult to describe applications in BPEL with high reliability. In order to write highly reliable BPEL document, it is necessary to check if the document is working correctly in accordance with user＇s intention. But it is difficult to carry out the test since BPEL engine doesn＇t provide a profiling function. In this paper, we suggest a BPEL system with a real-time profiling function. The suggested system consists of an integrated development environment and a BPEL nunning environment. BPEL integrated development environment has a BPEL to Java（B2J） engine, which generates and executes a Java workflow program from a BPEL document, and a converter, which converts Java Weaving XML （JWX） documents to Aspect-oriented programs. The new functions are described in JWX, which is Extensive Markup Lan-guage （XML）-based document. Since aspect-oriented programming technique provides the way to modularize main and supplemental requirements, it guarantees the low degree of coupling between BPEL workflow program and new functions by weaving them. Our approach can be extended to add other functions to provide context-aware services.
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The National Natural Science Foundation of China[72174184]provided policy and financialsupport for this research.
文摘Objectives This study aimed to evaluate the effectiveness of the stepped self-care program on the self-care,self-efficacy,and quality of life of stroke survivors.Methods This quasi-experimental study allocated 110 stroke survivors from two neurology wards into an intervention group(n=55)who received the stepped self-care program and a control group(n=55)who received usual care from June to December 2023.The Self-Care of Stroke Inventory,Stroke Self-Efficacy Questionnaire,and the short version of the Stroke Specific Quality of Life Scale were administered at baseline(T0),immediately post-intervention(T_(1)),and at 1-month(T_(2))and 3-month(T_(3))follow-ups.Data were analyzed using repeated measures analyses of variance,and generalized estimating equations.Results A total of 48 participants in the intervention group and 50 participants in the control group completed the study.No statistically significant differences were observed at T0 in any of the measured indicators(all P>0.05).The study showed significant group,time,and group×time interaction effects across the assessed outcomes(all P<0.05).Follow-up between-group comparisons at T_(1),T_(2),and T_(3) indicated that the intervention group had significantly higher scores in self-care maintenance,self-care monitoring,self-care management,self-efficacy,and quality of life than the control group(all P<0.001).Conclusions The stepped self-care program significantly improved self-care behaviors,self-efficacy,and quality of life among stroke survivors.These findings support the broader implementation of this approach in post-discharge home self-care.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
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.
文摘Editor's Note In his keynote address at the opening ceremony of the Global Leaders'Meeting on Women,held in Beijing on October 13,2025,Chinese President Xi Jinping announced a series of measures China will take,in the next five years,to further support the global cause of women.One of the measures is:China will launch 1,000"small and beautiful"livelihood programs with Chinese assistance that take women and girls as priority beneficiaries.
基金supported by the NSF of China under grants No.61173048 and No.61300041Specialized Research Fund for the Doctoral Program of Higher Education under grant No.20130074110015+2 种基金the Fundamental Research Funds for the Central Universities under Grant No.WH1314038the Humanities and Social Science Research Planning Fund of the Education Ministry of China under grant No.15YJCZH201the Research Innovation Program of Shanghai Municipal Education Commission under grant No.14YZ134
文摘Aspect-oriented modeling can uncover potential design faults,yet most existing work fails to achieve both separation and composition in a natural and succinct way.This study presents an aspect-oriented modeling and analysis approach with hierarchical Coloured Petri Nets(HCPN).HCPN has sub-models and well-defined semantics combining a set of submodels.These two characteristics of HCPN are nicely integrated into aspect oriented modeling.Submodels are used to model aspects while the combination mechanism contributes to aspects weaving.Furthermore,the woven aspect oriented HCPN model can be simulated and analyzed by the CPN Tools.A systematic web application case study is conducted.The results show the system original properties are satisfied after weaving aspects and all design flaws are revealed.As such,the approach can support web application design and analysis in an aspect-oriented fashion concisely and effectively.
基金Project supported by National Natural Science Foundation of China (Grant No .60473063)
文摘To solve the identification and comprehension problem of crosscutting concerns in existing legacy software system, a framework of aspect-oriented software reveme engineering is proposed. An approach on re-modularizing traversal features of legacy system is presented based on various unified modeling language （UML） diagrams. While modeling crosscutting concerns in UML use case diagrams, the non-functional requirements that affect several use case modules can be enveloped into aspect modules with a stereotype mechanism. The recurring message transmission patterns can be re-modularized as aspects in UML sequence diagrams with UML collaborations. Standard UML activity diagram notations are extended and modified by node fusion and addition, which support the graphical composition operation between crosscutting behaviors and primary business roles of concurrent systems. Case study indicates that travernal features of software system can be extracted and re-modularized from various perspectives in aspect-oriented reverse engineering, which improves comprehensibility and maintainability of legacy systems.
文摘In recent years, mobile devices have become widespread and refined, and they have offered increased convenience in human life. For these reasons, a variety of embedded systems have been designed. Therefore, improving methods for developing of embedded software systematically has become an important issue. Platform-based design is one example of an embedded-system design method that can reduce the design cost via improving a design’s abstraction level. However, platform-based design lacks precise definitions for platforms and design processes. This paper provides an approach that combines the aspects and platform-based design methods for developing embedded software. The approach is built on platform-based design methodology and uses the separating of concerns (SoC) concept to define the aspects and to reduce the crosscutting concerns in embedded system modeling. For aspect issues, we use the extended UML notation with aspects to describe both the static structure and the dynamic structure of the embedded system. We used an example of a digital photo frame system to demonstrate our approach.
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 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.
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 Canada First Research Excellence Fund,Medicine by Design(to CMM)。
文摘Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative medicine.The brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be changed.An exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.
