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.     

Improved Stretchable and Sensitive Fe Nanowire-Based Strain Sensor by Optimizing Areal Density of Nanowire Network

Flexible strain sensors, when considering high sensitivity and a large strain range, have become a key requirement for current robotic applications. However, it is still a thorny issue to take both factors into consideration at the same time. Here, we report a sandwich-structured strain sensor based on Fe nanowires (Fe NWs) that has a high GF (37–53) while taking into account a large strain range (15–57.5%), low hysteresis (2.45%), stability, and low cost with an areal density of Fe NWs of 4.4 mg/cm². Additionally, the relationship between the contact point of the conductive network, the output resistance, and the areal density of the sensing unit is analyzed. Microscopically, the contact points of the conductive network directly affect the sensor output resistance distribution, thereby affecting the gauge factor (GF) of the sensor. Macroscopically, the areal density and the output resistivity of the strain sensor have the opposite percolation theory, which affects its linearity performance. At the same time, there is a positive correlation between the areal density and the contact point: when the stretching amount is constant, it theoretically shows that the areal density affects the GF. When the areal density reaches this percolation threshold range, the sensing performance is the best. This will lay the foundation for rapid applications in wearable robots.     

基于LCVR调谐的全偏振多谱段成像系统

提出一种新型全偏振多谱段成像系统,将液晶相位可变延迟器LCVR应用于全偏振成像技术,在可见-近红外波段上可快速实现光的全偏振态的精确调制.系统由光学镜头、LCVR、偏振片、滤波片和CCD探测器组成.文章首先介绍了系统结构、工作原理和光学设计,并提出了适合本系统的偏振定标方法,建立了偏振定标系统,实现了利用较小面积的偏振...     

The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice

Here, we explored the possible interaction between duloxetine and SEP-363856 (SEP-856) in depression-related reactions. The results showed that oral administration of duloxetine showed powerful antidepressant-like effects in both the forced swimming test (FST) and the suspension tail test (TST). SEP-856 orally administered alone also exerted an antidepressant-like effect in FST and TST, especially at doses of 0.3, 1, and 10 mg/kg. In addition, duloxetine (15 mg/kg) and SEP-856 (15 mg/kg) both showed antidepressant-like effects in the sucrose preference test (SPT). Most importantly, in the above experiments, compared with duloxetine alone, the simultaneous use of duloxetine and SEP-856 caused a more significant antidepressant-like effect. It is worth noting that doses of drug combination in FST and TST did not change the motor activities of mice in the open-field test (OFT). Thus, duloxetine and SEP-856 seem to play a synergistic role in regulating depression-related behaviors and might be beneficial for refractory depression.     

Enhancement of feasibility of macroscopic quantum superposition state with the quantum Rabi-Stark model

We propose an efficient scheme to generate a macroscopical quantum superposition state with a cavity optomechanical system, which is composed of a quantum Rabi-Stark model coupling to a mechanical oscillator. In a low-energy subspace of the Rabi-Stark model, the dressed states and then the effective Hamiltonian of the system are given. Due to the coupling of the mechanical oscillator and the atom-cavity system, if the initial state of the atom-cavity system is one of the dressed states, the mechanical oscillator will evolve into a corresponding coherent state. Thus, if the initial state of the atom-cavity system is a superposition of two dressed states, a coherent state superposition of the mechanical oscillator can be generated. The quantum coherence and their distinguishable properties of the two coherent states are exhibited by Wigner distribution. We show that the Stark term can enhance significantly the feasibility and quantum coherence of the generated macroscopic quantum superposition state of the oscillator.     

原子系统中偶极-偶极相互作用对量子存储支撑熵不确定度的调控研究

本文研究了Markovian过程和non-Markovian过程两种情况下,原子系统中偶极-偶极(D-D)相互作用和失谐量对两原子系统量子存储支撑(QMA)熵不确定度的调控作用.与Markovian过程相比,在non-Markovian过程中,由于库环境的记忆效应使得具有D-D相互作用的两原子系统QMA熵不确定度的演化行为呈现出振荡上升现象,且熵不确定度的上升趋势得到减缓,从而抑制了由系统量子噪声引起的退相干效应.此外,D-D相互作用对两原子系统QMA熵不确定度具有显著的调控能力,且D-D相互作用比失谐量的调控能力更强.     

Coherent beam combination of adaptive fiber laser array with tilt-tip and phase-locking control

We present an experimental study on tilt-tip(TT) and phase-locking(PL) control in a coherent beam combination(CBC) system of adaptive fiber laser array.The TT control is performed using the adaptive fiber-optics collimator(AFOC),and the PL control is realized by the phase modulator(PM).Cascaded and simultaneous controls of TT and PL using stochastic parallel gradient descent(SPGD) algorithm are investigated in this paper.Two-fiber-laser-,four-fiber-laser-,and six-fiber-laser-arrays are employed to study the TT and PL control.In the cascaded control system,only one high-speed CMOS camera is used to collect beam data and a computer is used as the controller.In a simultaneous control system one high-speed CMOS camera and one photonic detector(PD) are employed,and a computer and a control circuit based on field programmable gate array(FPGA) are used as the controllers.Experimental results reveal that both cascaded and simultaneous controls of TT using AFOC and PL using PM in fiber laser array are feasible and effective.Cascaded control is more effective in static control situation and simultaneous control can be applied to the dynamic control system directly.The control signals of simultaneous PL and TT disturb each other obviously and TT and PL control may compete with each other,so the control effect is limited.     

偶氮侧基聚合物光致异构动力学研究

本文对偶氮侧基聚合物相位共轭光时间特性进行了研究,得到了相位共扼光产生机制─光致异构过程的时间常数.在相位共轭光上升阶段,其时间常数在0.4～0.5s之间,在相让共轭光的衰减过程,衰减满足双指数关系,分段拟合得到较好的结果,且得到快过程的时间常数为0.27s,慢过程的时间常数为0.78s.     

激光单分子探测技术的研究

文中介绍利用激光激发分子荧光的方法探测液体中单个染料分子的新技术，以及作者自行设计和研制的激光单分子探测谱仪。通过探测“光子爆发”，把单个染料分子的荧光同很强的背景杂散光区别开来。进一步用８２ＭＨｚ高重复频率的锁模激光器和时间门符合技术，成功地消除了Ｒａｍａｎ散射光。目前该谱仪达到的检测限为灵敏区内仅有～７个Ｒ６Ｇ分子。     

The Synthesis and Biological Activities of [5-(4-Substituted Phenylsulfinyl/Sulfonyl)-1,3-Dimethyl-1H-Pyrazol-4-Yl]-Arylmethanones

Abstract

A novel series of pyrazole derivatives containing substituted phenylsulfinyl/sulfonyl group have been synthesized via the oxidation of intermediate pyrazole sulfoether with H₂O₂ in acetic acid. The novel compounds were characterized by melting point, ¹H NMR, FT-IR, MS, and elemental analysis or HRMS. The biological activity results showed that most of the title compounds exhibit significant fungicidal activities against Alternaria solani Sorauer, Phytophthora capsici, and Corynespora cassiicola.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]