摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：The pathogens of most infectious diseases invade the host through mucosal sites,and immunization with mucosal vaccines is the best means of combating these infectious *** delivery and nasal delivery are the most common methods of mucosal ***,the delivery process is inefficient,and mucosal vaccination is ineffective because the vaccine formulation is easily and rapidly removed and has difficulty in crossing the mucosal *** this paper,we investigated whether the mucosal immune response could be enhanced by ultrasound facilitation of nasal mucosal delivery of vaccine *** this purpose,we used manganese dioxide(MnO2)as the vaccine carrier/adjuvant,coated with chitosan oligosaccharide(COS)to enhance mucosal adsorption,and further physically adsorbed model antigen ovalbumin(OVA)to construct a nanoparticulate vaccine formulation MnO2@COS@*** treatment was found to promote antigen delivery and recruitment of dendritic cells(DCs)and macrophages as well as T-cell infiltration in nasal mucosal tissues through nasal mucosal immunization *** ultrasound assistance,MnO2@COS@OVA particles promoted the maturation of DCs in vitro and in vivo and promoted the production of effector memory T cells in vivo and cytokine secretion by splenocytes in *** particular,ultrasound treatment significantly increased the levels of secretory IgA antibodies in the nasal mucosa and genital tract mucosa of experimental *** addition,the experimental data showed that the MnO2@COS@OVA particles had good biocompatibility and caused no significant damage to the nasal mucosal and vital organ *** data suggest that ultrasound treatment can promote the induction of efficient immune responses to mucosal vaccines and provide new ideas for the opening and clinical translation of mucosal vaccines.

摘要：Fail-safe topology optimization is valuable for ensuring that optimized structures remain operable even under damaged *** selectively removing material stiffness in patches with a fixed shape,the complex phenomenon of local failure is modeled in fail-safe topology *** this work,we first conduct a comprehensive study to explore the impact of patch size,shape,and distribution on the robustness of fail-safe *** findings suggest that larger sizes and finer distribution of material patches can yield more robust fail-safe ***,a finer patch distribution can significantly increase computational costs,particularly for 3D *** keep computational efforts tractable,an efficient fail-safe topology optimization approach is established based on the framework of multi-resolution topology optimization(MTOP).Within the MTOP framework,the extended finite element method is introduced to establish a decoupling connection between the analysis mesh and the topology description *** examples demonstrate that the developed methodology is 2 times faster for 2D problems and over 25 times faster for 3D problems than traditional fail-safe topology optimization while maintaining similar levels of robustness.

摘要：Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in *** 3D tumor models share several important characteristics with their in vivo tumor ***,their applications in tumor modeling,drug screening,and precision-targeted treatment are ***,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor ***,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in *** the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor *** this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model *** multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.

摘要：Metabolites play important roles in numerous cell biology processes,such as cell proliferation,differentiation,stress response,and cell death[1].Recently,lactate and lactate-derived lysine residue lactylation(Kla)have emerged as newly discovered epigenetic modifications that play critical roles in various physiological and pathological *** the history of lactate research,we can categorize the studies into three mile stones(Fig.S1 online).