Melanoma,a common malignant skin tumor,faces challenges with multidrug resistance and high recurrence rates.Combining photodynamic therapy(PDT)and immunotherapy offers a promising personalized treatment approach.Howev...Melanoma,a common malignant skin tumor,faces challenges with multidrug resistance and high recurrence rates.Combining photodynamic therapy(PDT)and immunotherapy offers a promising personalized treatment approach.However,poor water solubility and significant side effects of photosensitizers and immune checkpoint inhibitors(ICIs)limit their application.Enhancing delivery efficiency while reducing adverse effects is crucial.Herein,we formulate BM@HSSC nanoparticles(NPs),which consist of a reduction-responsive hyaluronic acid(HA)backbone modified with photosensitizer chlorin e6(Ce6)and loaded with the programmed cell death-ligand 1(PD-L1)inhibitor BMS-1.This system synergistically integrates PDT,immunogenic cell death(ICD),and immunotherapy for melanoma treatment.BM@HSSC NPs target and accumulate at the tumor site via the CD44 receptor.The disulfide bonds(-S-S-)in the NPs react with high glutathione(GSH)concentrations in tumor cells,rapidly releasing Ce6 and BMS-1.Under 660 nm laser irradiation,BM@HSSC NPs generate cytotoxic reactive oxygen species(ROS),inducing cell apoptosis and triggering ICD via PDT damage-associated molecular patterns(DAMPs)and tumor-associated antigens(TAAs)released from ICD promote dendritic cell(DC)maturation,enhancing antigen presentation and activating cytotoxic T lymphocytes(CTLs).Meanwhile,BMS-1 blocks the programmed cell death-1(PD-1)/PD-L1 pathway,countering the immunosuppressive tumor microenvironment(iTME)and inhibiting tumor cell immune escape.This strategy amplifies antitumor immune responses by enhancing immunogenicity and synergizing with ICIs,resulting in robust antitumor efficacy.展开更多
The cohesive solids in liquid flows are featured by the dynamic growth and breakage of agglomerates, and the difficulties in the development, design and optimization of these systems are related to this significant fe...The cohesive solids in liquid flows are featured by the dynamic growth and breakage of agglomerates, and the difficulties in the development, design and optimization of these systems are related to this significant feature.In this paper, discrete particle method is used to simulate a solid–liquid flow system including millions of cohesive particles, the growth rate and breakage rate of agglomerates are then systematically investigated. It was found that the most probable size of the agglomerates is determined by the balance of growth and breakage of the agglomerates the cross point of the lines of growth rate and breakage rate as a function of the particle numbers in an agglomerate, marks the most stable agglomerate size. The finding here provides a feasible way to quantify the dynamic behaviors of growth and breakage of agglomerates, and therefore offers the possibility of quantifying the effects of agglomerates on the hydrodynamics of fluid flows with cohesive particles.展开更多
The selection of an optimized restoration building block(RBB)scheme among all available schemes is one of the most important factors impacting the power system restoration process after a complete or partial blackout....The selection of an optimized restoration building block(RBB)scheme among all available schemes is one of the most important factors impacting the power system restoration process after a complete or partial blackout.This paper presents a data envelopment analysis(DEA)model used as an empirical method to assess the RBB schemes.An N-level evaluation scale cloud system is built based on cloud theory to transform qualitative I/O indices of DEA model into quantitative values.Through joint utilization of the CCR(Charnes,Cooper and Rhodes)model and the LJK(Li,Jahanshahloo and Khodabakhshi)model,the established Joint-DEA model makes the newly proposed Cloud-DEA method a more feasible and robust method in assessment of RBB schemes.展开更多
基金supported by the National Natural Sciences Foundation of China(Grant Nos.:31971308 and 81960769)Science and Technology Plan Project of Shihezi University,China(Grant No.:2023AB047)+2 种基金National S&T Major Project,China(Grant No.:2019ZX09301-147)Luzhou Science and Technology Plan,China(Grant No.:2018CDLZ-10)Sichuan Science and Technology Program,China(Grant No.:2021YFS0081).
文摘Melanoma,a common malignant skin tumor,faces challenges with multidrug resistance and high recurrence rates.Combining photodynamic therapy(PDT)and immunotherapy offers a promising personalized treatment approach.However,poor water solubility and significant side effects of photosensitizers and immune checkpoint inhibitors(ICIs)limit their application.Enhancing delivery efficiency while reducing adverse effects is crucial.Herein,we formulate BM@HSSC nanoparticles(NPs),which consist of a reduction-responsive hyaluronic acid(HA)backbone modified with photosensitizer chlorin e6(Ce6)and loaded with the programmed cell death-ligand 1(PD-L1)inhibitor BMS-1.This system synergistically integrates PDT,immunogenic cell death(ICD),and immunotherapy for melanoma treatment.BM@HSSC NPs target and accumulate at the tumor site via the CD44 receptor.The disulfide bonds(-S-S-)in the NPs react with high glutathione(GSH)concentrations in tumor cells,rapidly releasing Ce6 and BMS-1.Under 660 nm laser irradiation,BM@HSSC NPs generate cytotoxic reactive oxygen species(ROS),inducing cell apoptosis and triggering ICD via PDT damage-associated molecular patterns(DAMPs)and tumor-associated antigens(TAAs)released from ICD promote dendritic cell(DC)maturation,enhancing antigen presentation and activating cytotoxic T lymphocytes(CTLs).Meanwhile,BMS-1 blocks the programmed cell death-1(PD-1)/PD-L1 pathway,countering the immunosuppressive tumor microenvironment(iTME)and inhibiting tumor cell immune escape.This strategy amplifies antitumor immune responses by enhancing immunogenicity and synergizing with ICIs,resulting in robust antitumor efficacy.
基金Supported by TOTAL(DS-2885)the National Natural Science Foundation of China(91434201,21422608)the “Strategic Priority Research Program” of the Chinese Academy of Sciences(XDA07080000)
文摘The cohesive solids in liquid flows are featured by the dynamic growth and breakage of agglomerates, and the difficulties in the development, design and optimization of these systems are related to this significant feature.In this paper, discrete particle method is used to simulate a solid–liquid flow system including millions of cohesive particles, the growth rate and breakage rate of agglomerates are then systematically investigated. It was found that the most probable size of the agglomerates is determined by the balance of growth and breakage of the agglomerates the cross point of the lines of growth rate and breakage rate as a function of the particle numbers in an agglomerate, marks the most stable agglomerate size. The finding here provides a feasible way to quantify the dynamic behaviors of growth and breakage of agglomerates, and therefore offers the possibility of quantifying the effects of agglomerates on the hydrodynamics of fluid flows with cohesive particles.
基金supported by the National Natural Science Foundation of China under Grant 51377103the Participation in Research Program for undergraduate students of Shanghai Jiao Tong University under Grant T030PRP26041.
文摘The selection of an optimized restoration building block(RBB)scheme among all available schemes is one of the most important factors impacting the power system restoration process after a complete or partial blackout.This paper presents a data envelopment analysis(DEA)model used as an empirical method to assess the RBB schemes.An N-level evaluation scale cloud system is built based on cloud theory to transform qualitative I/O indices of DEA model into quantitative values.Through joint utilization of the CCR(Charnes,Cooper and Rhodes)model and the LJK(Li,Jahanshahloo and Khodabakhshi)model,the established Joint-DEA model makes the newly proposed Cloud-DEA method a more feasible and robust method in assessment of RBB schemes.
