Repurposing of intestinal defensins as multi-target,dual-function amyloid inhibitors via cross-seeding

Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases, including Alzheimer''s disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). While significant efforts have been made to develop different prevention strategies and preclinical hits for these diseases, conventional design strategies of amyloid inhibitors are mostly limited to either a single prevention mechanism (amyloid cascade vs. microbial infection) or a single amyloid protein (Aβ, hIAPP, or hCT), which has prevented the launch of any successful drug on the market. Here, we propose and demonstrate a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins, human α-defensin 6 (HD-6) and human β-defensin 1 (HBD-1), as multiple-target, dual-function, amyloid inhibitors. Both HD-6 and HBD-1 can cross-seed with three amyloid peptides, Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC), to prevent their aggregation towards amyloid fibrils from monomers and oligomers, rescue SH-SY5Y and RIN-m5F cells from amyloid-induced cytotoxicity, and retain their original antimicrobial activity against four common bacterial strains at sub-stoichiometric concentrations. Such sequence-independent anti-amyloid and anti-bacterial functions of intestinal defensins mainly stem from their cross-interactions with amyloid proteins through amyloid-like mimicry of β-sheet associations. In a broader view, this work provides a new out-of-the-box thinking to search and repurpose a huge source of antimicrobial peptides as amyloid inhibitors, allowing the blocking of the two interlinked pathological pathways and bidirectional communication between the central nervous system and intestines via the gut–brain axis associated with neurodegenerative diseases.

Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases. Here, we proposed a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins as multiple-target, dual-function amyloid inhibitors.     

Dielectric Properties Investigation of Metal–Insulator–Metal (MIM) Capacitors

This study presents the construction and dielectric properties investigation of atomic-layer-deposition Al₂O₃/TiO₂/HfO₂ dielectric-film-based metal–insulator–metal (MIM) capacitors. The influence of the dielectric layer material and thickness on the performance of MIM capacitors are also systematically investigated. The morphology and surface roughness of dielectric films for different materials and thicknesses are analyzed via atomic force microscopy (AFM). Among them, the 25 nm Al₂O₃-based dielectric capacitor exhibits superior comprehensive electrical performance, including a high capacitance density of 7.89 fF·µm⁻², desirable breakdown voltage and leakage current of about 12 V and 1.4 × 10⁻¹⁰ A·cm⁻², and quadratic voltage coefficient of 303.6 ppm·V⁻². Simultaneously, the fabricated capacitor indicates desirable stability in terms of frequency and bias voltage (at 1 MHz), with the corresponding slight capacitance density variation of about 0.52 fF·µm⁻² and 0.25 fF·µm⁻². Furthermore, the mechanism of the variation in capacitance density and leakage current might be attributed to the Poole–Frenkel emission and charge-trapping effect of the high-k materials. All these results indicate potential applications in integrated passive devices.     

Co-Catalyzed Asymmetric Intramolecular [3+2] Cycloaddition of Yne-Alkylidenecyclopropanes and its Reaction Mechanism

Developing new transition metal-catalyzed asymmetric cycloadditions for the synthesis of five-membered carbocycles (FMCs) is a research frontier in reaction development due to the ubiquitous presence of chiral FMCs in various functional molecules. Reported here is our discovery of a highly enantioselective intramolecular [3+2] cycloaddition of yne-alkylidenecyclopropanes (yne-ACPs) to bicyclo[3.3.0]octadiene and bicyclo[4.3.0]nonadiene molecules using a cheap Co catalyst and commercially available chiral ligand (S)-Xyl-BINAP. This reaction avoids the use of precious Pd and Rh catalysts, which are usually the choices for [3+2] reactions with ACPs. The enantiomeric excess in the present reaction can be up to 92 %. Cationic cobalt(I) species was suggested by experiments as the catalytic species. DFT calculations showed that this [3+2] reaction starts with oxidative cyclometallation of alkyne and ACP, followed by ring opening of the cyclopropyl (CP) group and reductive elimination to form the cycloadduct. This mechanism is different from previous [3+2] reactions of ACPs, which usually start from CP cleavage, not from oxidative cyclization.     

A class of azocarbazole-based carboxylates: High-efficiency ionic unimolecular photobase generators for thiol-epoxy click polymerization under blue light

Two new unimolecular azocarbazole-based visible photobase generators (Ac-C-Base) with different strong bases such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 1,1,3,3-tetramethylguanidine (TMG) as the potential active species were prepared. Their structures were confirmed by ¹H NMR, ¹³C NMR, and HR-MS. According to the photolysis and EPR results, Ac-C-Base could generate free radicals and strong bases simultaneously through the photodecarboxylation mechanism under 455 nm LED irradiation. Thus they can effectively catalyze the thiol-epoxy polymerization without post exposure baking under light exposure. In addition, the Ac-C-TBD containing a stronger base shows a faster polymerization rate and higher epoxy conversion.     

One-step construction of MoO_2 uniform nanoparticles on graphene with enhanced lithium storage

Transition-metal oxides are considered to be a promising anode material for lithium-ion batteries(LIBs)due to their high capacities,low cost,and ease of synthesis.Herein,a hybrid nanosheet composed of uniform MoO_2 nanoparticles(NPs) homogeneously immobilized on the reduced graphene oxide nanosheets(MoO_2 NP@rGO) is first synthesized by a self-templating and subsequent calcination treatment.The unique two-dimensional hybridnanosheets provides several merits.rGO can be used as a favorable support for the loading of electrochemically active MoO_2 NPs.Meanwhile,MoO_2 NPs can effectively prevent the stacking of the rGO.The effective combination of MoO_2 NPs and rGO nanosheets furnish additional electrochemically interfacial active sites for extra lithium ion sto rage.Noticeably,the as-fabricated hybrid nanosheets deliver a reversible capacity of 641 mAh/g after 350 cycles at a current density of 1000 mA/g with a good rate capability.The greatly enhanced lithium storage properties of MoO_2 NP@rGO indicate the importance of elaborate construction of novel hybrid hierarchical structures.     

METHANE REFORMING WITH CARBON DIOXIDE TO PRODUCE SYNGAS?a?aCATALYST REGENERATION

The regeneration conditions of the deactivated catalyst 18wt%NiO/a-A12O3 used in methane reforming with carbon dioxide were studied by using a fix-bed flow reactor and TPR technique. When the deactivated catalyst was reduced at 1 123 K in a conventional regeneration process, the activity increased a little, but was still much lower than that of the fresh catalyst. When the deactivated catalyst was reduced, then treated in site With an activity-rejuvenating agent of 5-10 vo1% C (aqueous hydrogen peroxide solution) and reduced again at 1123K, the activity was renewed to approach that of the fresh one.     

NiO/γ-Al2O3催化剂中NiO与γ-Al2O3间的相互作用

利用溶胶－凝胶法制备了不同含量的 ＮｉＯ／γ－Ａｌ_２Ｏ_３催化剂,通过ＸＲＤ,ＸＰＳ和 ＴＰＲ等技术考察了制备方法、ＮｉＯ含量和焙烧温度对催化剂结构和Ｎｉ存在状态的影响,发现溶胶－凝胶法制备的催化剂活性组分ＮｉＯ与担体γ－Ａｌ_２Ｏ_３间具有强相互作用．详细地讨论了Ｎｉ物种的还原状态与以“Ｎｉ~０”为活性中心的催化反应的活性之间的关系．溶胶－凝胶法制备的催化剂经高温焙烧后,Ｎｉ以一种类尖晶石结构的固溶体形式存在,这种固溶体态尖晶石可能会抑制Ｎｉ的烧结和流失,提高催化剂的稳定性．     

染料结合2μm无孔硅胶亲和填料的制备与应用

在２μｍ无孔硅胶表面键合３ 氨丙基 三乙氧基硅烷（ＡＰＳ）,并与三嗪染料活性蓝Ｆ３ＧＡ（ＣｉｂａｃｒｏｎＢｌｕｅＦ３ＧＡ,ＣＢ）反应,制得亲和色谱填料,并采用扫描电镜、元素分析、ｐＨ稳定性测试对此填料进行鉴定与表征。该填料具有良好的色谱性能,且对生物大分子有一定的亲和选择性,改变ｐＨ值及离子强度对溶菌酶的结合量有明显影响,可用于分离卵清蛋白（Ｏｖａｌ）和溶菌酶（Ｌｙｓ）,且对α ,β ,γ 球蛋白有不同的亲和作用,并可从鸡蛋清中制备少量溶菌酶。     

毛细管气相色谱法同时测定水产品中的多氯联苯和有机氯农药残留量

建立了毛细管气相色谱法同时测定水产品中多氯联苯和有机氯农药的方法，用高氯酸与冰乙酸的混合溶液消化样品，以石油醚提取，浓硫酸净化后，用毛细管气相色谱法测定，方法的回收法为88％－110％，相对标准偏差为8％－19％（n=6)，检出限为0．08－0．60ug/kg，方法简便，快速，结果准确。