Mesoporous sodium four-coordinate aluminosilicate nanoparticles modulate dendritic cell pyroptosis and activate innate and adaptive immunity

Pyroptosis is a programmed cell death widely studied in cancer cells for tumour inhibition, but rarely in dendritic cell (DC) activation for vaccine development. Here, we report the synthesis of sodium stabilized mesoporous aluminosilicate nanoparticles as DC pyroptosis modulators and antigen carriers. By surface modification of sodium-stabilized four-coordinate aluminium species on dendritic mesoporous silica nanoparticles, the resultant Na-^IVAl-DMSN significantly activated DC through caspase-1 dependent pyroptosis via pH responsive intracellular ion exchange. The released proinflammatory cellular contents further mediated DC hyperactivation with prolonged cytokine release. In vivo studies showed that Na-^IVAl-DMSN induced enhanced cellular immunity mediated by natural killer (NK) cells, cytotoxic T cells, and memory T cells as well as humoral immune response. Our results provide a new principle for the design of next-generation nanoadjuvants for vaccine applications.

Na-^IVAl-DMSN acts as both antigen carriers and modulators to “hyperactivate” dendritic cells (DCs) via potassium (K⁺) efflux dependent pyroptosis, eventually leading to enhanced adaptive and innate immunity.     

Dynamic synovial fibroblasts are modulated by NBCn1 as a potential target in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive fibroblast-like synoviocytes (FLSs) and pannus formation. Various therapeutic strategies have been developed against inflammatory cytokines in RA in recent decades. Based on the migratory features of FLSs, we examined whether modulation of the migratory module attenuates RA severity. In this study, inflamed synovial fluid-stimulated FLSs exhibited enhanced migration and migratory apparatus expression, and sodium bicarbonate cotransporter n1 (NBCn1) was identified in primary cultured RA-FLSs for the first time. The NBC inhibitor S0859 attenuated the migration of FLSs induced with synovial fluid from patients with RA or with TNF-α stimulation. Inhibition of NBCs with S0859 in a collagen-induced arthritis (CIA) mouse model reduced joint swelling and destruction without blood, hepatic, or renal toxicity. Primary FLSs isolated from the CIA-induced mouse model also showed reduced migration in the presence of S0859. Our results suggest that inflammatory mediators in synovial fluid, including TNF-α, recruit NBCn1 to the plasma membrane of FLSs to provide dynamic properties and that modulation of NBCn1 could be developed into a therapeutic strategy for RA.Subject terms: Chemotaxis, Bone, Ion channel signalling, Rheumatoid arthritis, Drug development     

CeO_2和Y_2Ba_1Cu_1O_(5-δ)共同掺杂对Y_1Ba_2Cu_3O_(7-δ)的超导电性及其晶格结构的影响

采用固相反应法成功制备出一批Y123与Y211的摩尔比为1∶0.47的混合物,并在此混合物的基础上掺入CeO2,掺入的比例x分别为0.5wt%、1.0wt%、2.0wt%、3.0wt%、4.0wt%。采用了X-射线衍射仪对样品的晶格结构进行了分析,测量结果表明:x=1.0wt%时掺杂效果最好,同时也充分说明Y123的晶格结构与其超导电性之间存在着一种内在的必然关联。并通过对其测试临界转变温度以及转变宽度,测量结果也充分验证了上述结论。     

Diels–Alder dimerization of Morita–Baylis–Hillman acetates catalyzed by organocatalysts

DABCO-catalyzed dimerization of Morita–Baylis–Hillman acetates to synthesize a series of 3-alkyl-4-(E)-alkenyl-cyclohex-1-ene-1,4-dicarbonyl compounds in excellent yields with modest to excellent diastereoselectivity is reported. A plausible reaction mechanism is also proposed on the basis of previous literature and preliminary investigation the asymmetric version of the reaction.     

钙钛矿结构中的简谐子软模

利用复合空间型方法,在自由边界条件下解出了钙钛矿结构有限尺寸晶体的简谐振动方程.计算结果给出了收敛的简谐子谱分布,并发现了许多简谐子软模.用这些软模花样说明了钛酸钡晶体冷却时发生具有a畴和c畴结构的铁电相变.理论表明铁电相变过程涉及屏蔽电荷的激发及其在界面的缓慢扩散,以最后得出各个电畴内部的均匀自发极化 关键词： 晶格动力学 简谐子 软模 钛酸钡