Discovery of Chemicals to Either Clear or Indicate Amyloid Aggregates by Targeting Memory‐Impairing Anti‐Parallel Aβ Dimers

Amyloid‐β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. Herein parallel and anti‐parallel variants of Aβ(1–40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti‐parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA‐approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aβ interactions with dimer‐specific molecules.     

常温直接沉淀法制备ZnO纳米棒

在常温下, 以PEG-400(聚乙二醇400)为表面活性剂, 采用直接沉淀法合成了ZnO纳米棒. 产物用XRD, TEM, SAED和 HRTEM等进行了表征. 结果表明, 所得ZnO为一维的纳米棒, 属于六方纤维矿的单晶结构. ZnO纳米棒的直径在20~40 nm之间, 长度在300~800 nm范围. (0001)面为ZnO纳米棒的生长方向. 讨论了ZnO相的生成和ZnO纳米棒的形成机理以及PEG-400在其形成过程中的作用.     

Dynamic role of the correlation effect revealed in the exceptionally slow autodetachment rates of the vibrational Feshbach resonances in the dipole-bound state

Real-time autodetachment dynamics of the loosely bound excess electron from the vibrational Feshbach resonances of the dipole-bound states (DBS) of 4-bromophonoxide (4-BrPhO⁻) and 4-chlorophenoxide (4-ClPhO⁻) anions have been thoroughly investigated. The state-specific autodetachment rate measurements obtained by the picosecond time-resolved pump-probe method on the cryogenically cooled anions exhibit an exceptionally long lifetime (τ) of ∼823 ± 156 ps for the 11′¹ vibrational mode of the 4-BrPhO⁻ DBS. Strong mode-dependency in the wide dynamic range has also been found, giving τ ∼ 5.3 ps for the 10′¹ mode, for instance. Though it is nontrivial to get the state-specific rates for the 4-ClPhO⁻ DBS, the average autodetachment lifetime of the 19′¹20′¹/11′¹ mode has been estimated to be ∼548 ± 108 ps. Observation of these exceptionally slow autodetachment rates of vibrational Feshbach resonances strongly indicates that the correlation effect may play a significant role in the DBS photodetachment dynamics. Fermi''s golden rule has been invoked so that the correlation effect is taken into account in the form of the interaction between the charge and the induced dipole where the latter is given by the polarizable counterparts of the electron-rich halogenated compound and the diffuse non-valence electron. This report suggests that one may measure, from the real-time autodetachment dynamics, the extent of the correlation effect contribution to the stabilization and/or dynamics of the excess non-valence electron among many different types of long-range interactions of the DBS.

Exceptionally slow autodetachment dynamics of the vibrational Feshbach resonances found in the dipole-bound state of 4-bromophonoxide (4-BrPhO⁻) or 4-chlorophenoxide (4-ClPhO⁻) anions reveals the associated dynamic role of the correlation effect.     

Simplified global fault accommodation control design of uncertain nonlinear systems with unknown time-varying powers

This paper addresses the problem of global robust fault accommodation tracking for a class of uncertain nonlinear systems with unknown powers and actuator faults. It is assumed that the powers of the concerned system are unknown time-varying functions, all system nonlinearities are unknown, and unknown actuator faults depend on the time-varying power of a control input. A fault accommodation state-feedback controller is explicitly constructed based on the nonlinear error transformation technique using time-varying performance functions. Global tracking with the preselected performance bounds is established in the presence of unknown time-varying powers and unexpected actuator faults. Different from the previous results dealing with the problem of unknown time-varying powers, the proposed tracking strategy does not require the knowledge of the bounds of the time-varying powers and the nonlinear bounding functions of system nonlinearities. An underactuated mechanical system is simulated to validate the effectiveness of the proposed theoretical approach.     

Event-triggered output-feedback tracking of a class of nonlinear systems with unknown time delays

A single function approximation (SFA) approach for event-triggered output-feedback tracker design is presented for uncertain nonlinear time-delay systems in lower-triangular form. Contrary to the existing event-triggered output-feedback control methods dependent on multiple function approximators in the presence of lower-triangular nonlinearities, the proposed SFA approach provides the following advantages: (i) the simple observer structure independent of function approximators; (ii) one event-triggering condition based on only a tracking error; and (iii) the simple control scheme using one function approximator. Thus, the structural simplicity is allowed for implementing the observer and the event-triggering law in the sensor part and the adaptive tracker in the control part. Under the proposed SFA-based event-triggered control scheme, it is shown that the boundedness of closed-loop signals and the existence of a minimum inter-event time are guaranteed regardless of unknown time-delay nonlinearities and unmeasurable state variables.

     

Expression patterns of antioxidant proteins in brains of patients with sporadic Creutzfeldt-Jacob disease

Using two-dimensional gel electrophoresis (2-DE) and Western blot analysis, we were able to identify and quantify six antioxidant proteins, peroxiredoxin (Prx) I, Prx II, Prx III, 1-Cys Prx, putative peroxisomal antioxidant enzyme (PLP), and mitochondrial Mn superoxide dismutase (Mn-SOD) in two individual brain regions, cerebellum and frontal cortex of patients with sporadic Creutzfeldt-Jacob (sCJD). Among six antioxidant proteins, 1-Cys Prx showed significant increase (P > 0.05) in sCJD frontal cortex whereas Prx I was decreased (P > 0.01). In cerebellum, levels of all antioxidant proteins studied were comparable to those of controls. Our findings provide evidence for the link between aberrant expression of antioxidant proteins, 1-Cys Prx and Prx I and CJD neuropathogenesis and we discuss the neuropathological meaning of these dysregulated antioxidant proteins in sCJD brain.     

Spirometallodendrimers: terpyridine-based intramacromolecular cyclization upon complexation

The first examples of metallodendritic spiranes have been obtained via incorporation of single terpyridine units within each dendritic quadrant.