Development of single-action,two-step clinching system using finite element analysis

Traditional manufacturing processes for bending and combining the upper and lower heat insulation plates for a car catalytic converter need two kinds of bending dies. This study was carried out to develop a single-action, two-step clinching system for clinching heat insulation plates. To design the operating mechanism for this clinching system, finite element analysis was used to estimate the bending load needed and to predict the bent shape of the heat insulation plate. Then a recovery and cushioning system was designed for the bending die. It is expected that this new process will improve the manufacturing quality of heat insulation plates and will reduce manufacturing cost. And a higher value-added technique for mold and pressing systems was introduced.

大型路堑边坡在加固期的稳定性分析

通过现场监测和数值模拟对某大型路堑边坡在加固作用下的稳定性进行了研究。通过六个加固期的施工,最终形成了边坡上部的锚杆抗滑桩、边坡下部的抗滑桩和土钉的加固体系。通过在边坡上布设了监测系统对支护结构效果进行监测,研究了边坡在各个加固阶段的稳定性变化。监测结果表明,在加固过程中,边坡的安全系数、抗滑桩的挠曲变形和弯曲应力变化较为明显。其中变化最明显的是土钉墙加固阶段。实际测量的桩顶位移比计算的要小,分析认为,这是由于受到边坡上部分的锚固作用和边坡下部分的混凝土覆盖层的约束作用造成的。随着加固体系的逐步完善,边坡的安全系数也逐渐增大,并且满足干湿条件下的规定值。

M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy.Lipid nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 pandemic.This study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid tumor.The dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication.Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth inhibition.These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

Graphene foam/hydrogel scaffolds for regeneration of peripheral nerve using ADSCs in a diabetic mouse model

The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.

Electrically controlled mRNA delivery using a polypyrrolegraphene oxide hybrid film to promote osteogenic differentiation of human mesenchymal stem cells

Direct messenger ribonucleic acid(mRNA)delivery to target cells or tissues has revolutionized the field of biotechnology.However,the applicability of regenerative medicine is limited by the technical difficulties of various mRNA-loaded nanocarriers.Herein,we report a new conductive hybrid film that could guide osteogenic differentiation of human adipose-derived mesenchymal stem cells(hADMSCs)via electrically controlled mRNA delivery.To find optimal electrical conductivity and mRNAloading capacity,the polypyrrole-graphene oxide(PPy-GO)hybrid film was electropolymerized on indium tin oxide substrates.We found that the fluorescein sodium salt,a molecule partially mimicking the physical and chemical properties of mRNAs,can be effectively absorbed and released by electrical stimulation(ES).The hADMSCs cultivated on the PPy-GO hybrid film loaded with pre-osteogenic mRNAs showed the highest osteogenic differentiation under electrical stimulation.This platform can load various types of RNAs thus highly promising as a new nucleic acid delivery tool for the development of stem cell-based therapeutics.