Optimizing drug-like properties of selective butyrylcholinesterase inhibitors for cognitive improvement: Enhancing aqueous solubility by disrupting molecular plane.

Most recently, worldwide interest in butyrylcholinesterase (BChE) as a potential target for treating Alzheimer's disease (AD) has increased. In this study, the previously obtained selective BChE inhibitors with benzimidazole-oxadiazole scaffold were further structurally modified to increase their aqueous solubility and pharmacokinetic (PK) characteristics. S16-1029 showed improved solubility (3280 µM, upgraded by 14 times) and PK parameters, including plasma exposure (AUC0-inf = 1729.95 ng/mL*h, upgraded by 2.6 times) and oral bioavailability (Fpo = 48.18%, upgraded by 2 times). S16-1029 also displayed weak or no inhibition against Cytochrome P450 (CYP450) and human ether a-go-go related gene (hERG) potassium channel. In vivo experiments on tissue distribution revealed that S16-1029 could cross the blood-brain barrier (BBB) and reach the central nervous system (CNS). In vivo cognitive improvement efficacy and good in vitro target inhibitory activity (eqBChE IC50 = 11.35 ± 4.84 nM, hBChE IC50 = 48.1 ± 11.4 nM) were also assured. The neuroprotective effects against several AD pathology characteristics allowed S16-1029 to successfully protect the CNS of progressed AD patients. According to the findings of this study, altering molecular planarity might be a viable strategy for improving the drug-like property of CNS-treating drugs.

Conformal Noble Metal High-Entropy Alloy Nanofilms by Atomic Layer Deposition for an Enhanced Hydrogen Evolution Reaction.

The current synthesis methods of high-entropy alloy (HEA) thin-film coatings face huge challenges in facile preparation, precise thickness control, conformal integration, and affordability. These challenges are more specific and noteworthy for noble metal-based HEA thin films where the conventional sputtering methods encounter thickness control and high-cost issues (high-purity noble metal targets required). Herein, for the first time, we report a facile and controllable synthesis process of quinary HEA coatings consisting of noble metals (Rh, Ru, Pt, Pd, and Ir), by sequential atomic layer deposition (ALD) coupled with electrical Joule heating for post-alloying. Furthermore, the resulting quinary HEA thin film with a thickness of ∼50 nm and an atomic ratio of 20:15:21:18:27 shows promising potential as a platform for catalysis, exhibiting enhanced electrocatalytic hydrogen evolution reaction (HER) performances with lower overpotentials (e.g., from 85 to 58 mV in 0.5 M H2SO4) and higher stability (by retaining more than 92% of the initial current after 20 h with a current density of 10 mA/cm2 in 0.5 M H2SO4) than other noble metal-based structure counterparts in this work. The enhanced material properties and device performances are attributed to the efficient electron transfer of HEA with the increased number of active sites. This work not only presents RhRuPtPdIr HEA thin films as promising HER catalysts but also sheds light on controllable fabrication of conformal HEA-coated complex structures toward a broad range of applications.

Noble metal alloy thin films by atomic layer deposition and rapid Joule heating.

Metal alloys are usually fabricated by melting constituent metals together or sintering metal alloy particles made by high energy ball milling (mechanical alloying). All these methods only allow for bulk alloys to be formed. This manuscript details a new method of fabricating Rhodium-Iridium (Rh-Ir) metal alloy films using atomic layer deposition (ALD) and rapid Joule heating induced alloying that gives functional thin film alloys, enabling conformal thin films with high aspect ratios on 3D nanostructured substrate. In this work, ALD was used to deposit Rh thin film on an Al2O3 substrate, followed by an Ir overlayer on top of the Rh film. The multilayered structure was then alloyed/sintered using rapid Joule heating. We can precisely control the thickness of the resultant alloy films down to the atomic scale. The Rh-Ir alloy thin films were characterized using scanning and transmission electron microscopy (SEM/TEM) and energy dispersive spectroscopy (EDS) to study their microstructural characteristics which showed the morphology difference before and after rapid Joule heating and confirmed the interdiffusion between Rh and Ir during rapid Joule heating. The diffraction peak shift was observed by Grazing-incidence X-ray diffraction (GIXRD) indicating the formation of Rh-Ir thin film alloys after rapid Joule heating. X-ray photoelectron spectroscopy (XPS) was also carried out and implied the formation of Rh-Ir alloy. Molecular dynamics simulation experiments of Rh-Ir alloys using Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) were performed to elucidate the alloying mechanism during the rapid heating process, corroborating the experimental results.

Ordered Mesoporous Alumina with Tunable Morphologies and Pore Sizes for CO2 Capture and Dye Separation.

We describe a versatile and scalable strategy toward long-range and periodically ordered mesoporous alumina (Al2O3) structures by evaporation-induced self-assembly of a structure-directing ABA triblock copolymer (F127) mixed with aluminum tri-sec-butoxide-derived sol additive. We found that the separate preparation of the alkoxide sol-gel reaction before mixing with the block copolymer enabled access to a relatively unexplored parameter space of copolymer-to-additive composition, acid-to-metal molar ratio, and solvent, yielding ordered mesophases of two-dimensional (2D) lamellar, hexagonal cylinder, and 3D cage-like cubic lattices, as well as multiscale hierarchical ordered structures from spinodal decomposition-induced macro- and mesophase separation. Thermal annealing in air at 900 °C yielded well-ordered mesoporous crystalline γ-Al2O3 structures and hierarchically porous γ-Al2O3 with 3D interconnected macroscale and ordered mesoscale pore networks. The ordered Al2O3 structures exhibited tunable pore sizes in three different length scales, <2 nm (micropore), 2-11 nm (mesopore), and 1-5 µm (macropore), as well as high surface areas and pore volumes of up to 305 m2/g and 0.33 cm3/g, respectively. Moreover, the resultant mesoporous Al2O3 demonstrated enhanced adsorption capacities of carbon dioxide and Congo red dye. Such hierarchically ordered mesoporous Al2O3 are well-suited for green environmental solutions and urban sustainability applications, for example, high-temperature solid adsorbents and catalyst supports for carbon dioxide sequestration, fuel cells, and wastewater separation treatments.

Changing Treatment May Affect the Predictive Ability of European Treatment Outcome Study Scoring for the Prognosis of Patients with Chronic Myeloid Leukemia.

OBJECTIVE: Previous studies compared the predictive ability of the European Treatment Outcome Study (EUTOS), Sokal, and Hasford scoring systems and demonstrated inconsistent findings with unknown reasons. This study was conducted to determine a useful scoring system to predict the prognosis of patients with chronic myeloid leukemia (CML) and identify the probable factors that affect the scoring. MATERIALS AND METHODS: This is a retrospective cohort study. The predictive ability of EUTOS and the factors that affect scoring were analyzed in 234 Chinese chronic-phase CML patients treated with frontline imatinib, including a few patients temporarily administered hydroxyurea for cytoreduction before imatinib. Patients were stratified into different risk groups according to each scoring system to assess the treatment outcomes and the predictive ability of EUTOS scores between patients who received imatinib during the entire follow-up period and patients who received altered treatment because of intolerance, progression, and treatment failure. RESULTS: Sixty-one (26.0%) patients received altered treatments during the follow-up. In the EUTOS low- and high-risk groups, the 5-year overall survival was 94.6% and 84.7% (p=0.011), 5-year event-free survival was 92.6% and 77.6% (p=0.001), and 5-year progression-free survival (PFS) was 95.3% and 82.4% (p=0.001), respectively. The predictive ability of EUTOS was better than that of the Sokal and Hasford scores (p=0.256, p=0.062, p=0.073) without statistical significance. All three scoring systems were valid in predicting early optimal response. Kaplan-Meier analysis showed a high association between overall PFS and the EUTOS scores in the standard-dose imatinib group (p<0.001). CONCLUSION: This study suggests that the EUTOS scoring system could predict the outcome of chronic-phase CML patients treated with standard-dose imatinib. Altered treatment is a crucial factor that affects the prognostic impact of EUTOS scoring. Achieving complete cytogenetic response at 18 months is an essential factor in predicting the prognosis of patients with CML.

Micro-fabrication and monitoring of three-dimensional microstructures based on laser-induced thermoplastic formation.

This article reports a novel laser-induced micro-fabrication method and its monitoring system for three-dimensional (3D) microstructures. The mechanism of the method is that a small zone of thermoplastic material melted by laser heating grows in liquid surrounding environment, solidifying into a convex microstructure, such as micro-dot or micro-pillar. A laser diode (808 nm) with maximum power output of 130 mW is used as power source, and a kind of paraffin mixed with stearic acid and paint serves as the thermoplastic material for 3D microstructure formation experiments. A light microscope system consisting of a charge-coupled device (CCD) and a computer is utilized to realize real-time observation of the micro-fabricating process. The distribution of local temperature rise on material surface created by laser irradiation is simulated. The effects of liquid environment on microstructure formation have been theoretically analyzed and experimentally studied. Experiments are further carried out to investigate the relationship between laser spot and fabricated microstructures. The results indicate that the widths of micro-dots or micro-pillars are mostly determined by the size of focal spot, and their heights increase with the enlargement of laser power density. With this method, a micro-dot array of Chinese characters meaning "China" has been successfully fabricated through computer programming. This method has the advantages of implementing direct, mask-less, real-time and inexpensive 3D microstructure fabrication. Therefore, it would be widely applied in the fields of micro/nano-technology for practical fabrication of different kinds of 3D microstructures.

[Measurement of fruit maturity based on laser-induced photoluminescence spectrum].

Grounding on the concepts of biophotonics measurement, the authors first used a red semiconductor laser (655 nm) to irradiate fruits. Compared with other kinds of illuminating sources, the red semiconductor laser is less expensive and takes little space. The laser-induced photoluminescence spectrums could be detected by coupling fibre-optics probe when the fruits are illuminated by laser. And the spectrum has a distinct peak of relative intensity around the 685 nm wavelength that varies with the degree of fruit maturity. Sugar content measurement was used to prove the laser-induced photoluminescence measurement. The authors tested the sugar content of the fruit specimens, and found that the relative peak value of the fruits' laser-induced photoluminescence spectrum decreases with the increase in their sugar content. The authors used partial least-squares (PLS) regression to perform an analysis of the relationship between the laser-induced photoluminescence intensity and the sugar content, fitting a curve of the two parameters. The correlation coefficient r of the fitted value and the actual value is 98.92% for red-inside plum and 97.31% for nectarine. So the authors could generalize that there is an approximate linear relationship between the peak value of laser-induced photoluminescence intensity and the sugar content of fruits, and we could use the maturity measurement based on this concept to decide the fruit ripeness. The authors designed the analytic program for this laser-induced photoluminescence spectrum measurement system, which mainly realizes two functions: generating the standard ripe spectrum of a certain kind of fruit from a quantity of their spectra, and, according to this standard spectrum, determining the maturity degree of an unknown spectrum, and at the same time, displaying the unknown laser-induced photoluminescence spectrum. Incorporating this analytic program with the optical spectrometer, it becomes conceivable to test the fruit maturity very conveniently and quickly. The measurement system of fruit maturity based on laser-induced photoluminescence spectrum has also been used to test various fruits. This measurement is nondestructive and inexpensive, and does not require complicated equipment, a feature of great importance in real-time measurement of fruit maturity.