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.     

气相生长氮化铝单晶的新方法

通过在钨坩埚盖开小孔的方法改变氮化铝结晶衬底上的温度场分布,在开孔处形成局部低温区;由于孔的几何尺寸的限制和氮化铝晶体生长的各向异性,开孔处的氮化铝晶体单晶化;随后,开孔处的单晶起籽晶的作用,逐渐长成较大尺寸、较高质量的氮化铝单晶.目前用该方法已经制备出直径大于2mm的氮化铝单晶体.     

Electrochemical Immunoassay for Tumor Marker CA19-9 Detection Based on Self-Assembled Monolayer

A CA19-9 electrochemical immunosensor was constructed using a hybrid self-assembled membrane modified with a gold electrode and applied to detect real samples. Hybrid self-assembled membranes were selected for electrode modification and used to detect antigens. First, the pretreated working electrodes were placed in a 3-mercaptopropionic acid (MPA)/β-mercaptoethanol (ME) mixture for 24 h for self-assembly. The electrodes were then placed in an EDC/NHS mixture for 1 h. Layer modification was performed by stepwise dropwise addition of CA19-9 antibody, BSA, and antigen. Differential pulse voltammetry was used to characterize this immunosensor preparation process. The assembled electrochemical immunosensor enables linear detection in the concentration range of 0.05–500 U/mL of CA19-9, and the detection limit was calculated as 0.01 U/mL. The results of the specificity measurement test showed that the signal change of the interfering substance was much lower than the response value of the detected antigen, indicating that the sensor has good specificity and strong anti-interference ability. The repeatability test results showed that the relative standard deviations were less than 5%, showing good accuracy and precision. The CA19-9 electrochemical immunosensor was used for the actual sample detection, and the experimental results of the standard serum addition method showed that the RSD values of the test concentrations were all less than 10%. The recoveries were 102.4–115.0%, indicating that the assay has high precision, good accuracy, and high potential application value.     

Precise electro-reduction of alkyl halides for radical defluorinative alkylation

Reported here is a precise electro-reduction strategy for radical defluorinative alkylation towards the synthesis of gem-difluoroalkenes from α-trifluoromethylstyrenes. According to the redox-potential difference of the radical precursors, direct or indirect electrolysis is respectively adopted to realize the precise reduction. An easy-to-handle, catalyst-and metal-free condition is developed for the reduction of alkyl radical precursors that are generally easier to be reduced than α-trifluorome...     

Palladium-catalyzed hydrosilylation of ynones to access silicon-stereogenic silylenones by stereospecific aromatic interaction-assisted Si–H activation

Hydrosilylation is one of the most important reactions in synthetic chemistry and ranks as a fundamental method to access organosilicon compounds in industrial and academic processes. However, the enantioselective construction of chiral-at-silicon compounds via catalytic asymmetric hydrosilylation remained limited and difficult. Here we report a highly enantioselective hydrosilylation of ynones, a type of carbonyl-activated alkynes, using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand. The stereospecific hydrosilylation of ynones affords a series of silicon-stereogenic silylenones with up to 94% yield, 20:1 regioselectivity and 98:2 enantioselectivity. The density functional theory(DFT) calculations were conducted to elucidate the reaction mechanism and origin of high degree of stereoselectivity, in which the powerful potential of aromatic interaction in this reaction is highlighted by the multiple C–H-π interaction and aromatic cavity-oriented enantioselectivitydetermining step during desymmetric functionalization of Si–H bond.     

Optical properties of two-dimensional perovskites

The optical properties of two-dimensional (2D) perovskites recently receive numerous research focus thanks to the strong quantum and dielectric confinement effects. In addition to the strong excitonic effect at room temperature, 2D perovskites also have appealing features that their optical properties can be flexibly tuned by alternating organic or inorganic layers. Particularly, 2D chiral perovskites and 2D perovskites based heterostructures are emerging as new platforms to extend their functionalities. To optimize performance of 2D perovskites-based optoelectronic devices, it is critical to understand the fundamentals and explore the strategies to engineer their optical properties. This review begins with an introduction to the excitons and self-trapped excitons of 2D perovskites. Subsequently, inorganic/organic layer effects on optical properties and 2D perovskites based heterostructures are discussed. We also discussed the nonlinear optical properties of 2D perovskite. We are looking forward to that this review can stimulate more efforts to understand and optimize the optical properties of 2D perovskites.     

A Simple Hydrothermal Method for the Growth of ZnO Crystals

ZnO microstructures have been grown from zinc chloride (ZnCl₂) and ammonia solution at 100 °C for 1 – 24 hours. X‐ray diffraction, scanning electron microscope and field‐emission scanning microscope were utilized to investigate the structural properties and morphology of the ZnO crystals. Structural investigations show that phase‐pure hexagonal structure ZnO has been successfully synthesized, and the hexagonal structure ZnO can be achieved in solutions with an appropriate range of concentrations. Under our experimental conditions, several different morphologies of ZnO structures were obtained, including flower‐like and bar flower‐like. The relationship between the morphology and experimental conditions are discussed.     

Monoterpenoid Indole Alkaloids with Promoting Neurite Growth from Tabernaemontana divaricata

Main observation and conclusion Phytochemical investigations on Tabernaemontana divaricata led to the isolation of seven undescribed monoterpenoid indole alka-l...     

Combining Metabolic Alkyne Labeling and Click Chemistry for Secretome Analysis of Serum-Containing Conditioned Medium

Main observation and conclusion Bioorthogonal click chemistry has emerged as a powerful tool for the specific modification of proteins in complex mixtures.Metab...