In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity.

Antifungal peptides (AFPs) are emerging as promising candidates for advanced antifungal therapies because of their broad-spectrum efficacy and reduced resistance development. In silico design of AFPs, however, remains challenging, due to the lack of an efficient and well-validated quantitative assessment of antifungal activity. This study introduced an AFP design approach that leverages an innovative quantitative metric, named the antifungal index (AFI), through a three-step process, i.e., segmentation, single-point mutation, and global multipoint optimization. An exhaustive search of 100 putative AFP sequences indicated that random modifications without guidance only have a 5.97-20.24% chance of enhancing antifungal activity. Analysis of the search results revealed that (1) N-terminus truncation is more effective in enhancing antifungal activity than the modifications at the C-terminus or both ends, (2) introducing the amino acids within the 10-60% sequence region that enhance aromaticity and hydrophobicity are more effective in increasing antifungal efficacy, and (3) incorporating alanine, cysteine, and phenylalanine during multiple point mutations has a synergistic effect on enhancing antifungal activity. Subsequently, 28 designed peptides were synthesized and tested against four typical fungal strains. The success rate for developing promising AFPs, with a minimal inhibitory concentration of ≤5.00 µM, was an impressive 82.14%. The predictive and design tool is accessible at https://antifungipept.chemoinfolab.com.

0.36BiScO3-0.64PbTiO3/Epoxy 1-3-2 High-Temperature Composite Ultrasonic Transducer for Non-destructive Testing Applications.

The development of high-temperature nondestructive testing (NDT) requires ultrasonic transducers with good temperature resistance and high sensitivity for improved detection efficiency. Piezoelectric composite can improve the performance of transducers because of its high electromechanical coupling coefficient and adjustable acoustic impedance. In this study, 1-3-2 composites and 1-3-2 high-temperature composite ultrasonic transducers (HTCUTs) based on 0.36BiScO3-0.64PbTiO3 (BSPT), which are preferred piezoelectric materials at 200°C-300°C, and high-temperature epoxy with a center frequency of 6 MHz were designed and fabricated. From 25°C to 250°C, 1-3-2 composites show a higher electromechanical coupling coefficient kt especially at high temperatures (~0.53 at 25°C, and ~0.64 at 250°C) than monolithic BSPT (~0.5). The signal of the pulse-echo response of 1-3-2 HTCUTs is distinguishable up to 250 °C and remains stable (Vpp~500 mV) below 150°C, exhibiting higher sensitivity (improved by 7 dB) than that of monolithic BSPT high-temperature ultrasonic transducers (HTUTs). Bandwidth has been greatly enhanced especially at high temperatures (~103250°C) compared with that of monolithic BSPT HTUTs(~30250°C). To verify the excellent performance, B-mode scanning imaging measurement of a stepped steel block and defect location detection of a steel block were performed, showing the potential for high-temperature NDT applications.

Benzothiazole-Propanamide Linker Pyrrolidine (Morpholine) as Monoamine Oxidase-B and Butyrylcholinesterase Inhibitors.

According to the fusion technique create effective multi-target-directed ligands, in this study, we designed and synthesized a series of benzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl) or 3-(morph- olino-1-yl)propanamide derivatives, and evaluated their inhibitory potency against MAOs, AChE, BuChE by in vitro enzyme effect assays. Based on activity results, we found that derivatives N-(5-methylbenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 c) and N-(6-bromobenzo[d]thiazol-2-yl)-3-(pyrrolidin-1-yl)propanamide (2 h) showed good inhibitory potency against BuChE with IC50 values of 15.12 µM and 12.33 µM, respectively. Besides, 2 c and 2 h also exhibited selective MAO-B inhibitory effects with inhibition rates of 60.10 % and 66.30 % at 100 µM, respectively. In contrast, all designed derivatives were poor active against AChE and MAO-A at a concentration of 100 µM. The toxicity analysis in vitro by MTT and AO/EB fluorescence staining confirmed that 2 c and 2 h were nontoxic up to 100 µM. Molecular modeling studies showed that 2 c and 2 h could bind to the active site of BuChE. This research paves the way for further study aimed at designing MAO-B and BuChE inhibitors for the treatment of neurodegenerative disorders.

Gold-Catalyzed Anti-Markovnikov Oxidation of Au-Allenylidene to Generate Alkylidene Ketene.

It remains a long-standing challenge to directly convert alkynes to carboxylic derivatives. Herein, a unexpectedly anti-Markovnikov oxidation of a unique Au-allenylidene pathway instead of a traditional α-oxo gold carbene routine is disclosed for in situ formation and transformation of highly unsaturated alkylidene ketenes, which are subsequently trapped by broad nucleophiles such as alcohols, phenols, water, amines, and sulfoximines to easily access α,ß-unsaturated drugs and natural product derivatives by a multicomponent reaction. Based on this scenario, polyacrylate and polyacrylamide are efficiently afforded by corresponding multicomponent polymerization.

Metal-free polyporphyrin based photocatalysts for the functionalization of C(sp3)-H bonds in water.

The development of metal-free and water-compatible photocatalysts for visible light-induced environmentally friendly transformation in water is highly desirable. Herein, two types of polyporphyrin based heterogeneous photocatalysts with different water-solubility in water, namely, an insoluble polymer and a water-dispersible nanoparticle, were disclosed. Both of them exhibited excellent photocatalytic activity in visible-light induced functionalization of C(sp3)-H bonds on a wide range of substrates in water. The reusable and recyclable photocatalysts provided a green and sustainable approach for photocatalysis in water.

Copper-Catalyzed One-Step Formation of Four C-N Bonds toward Polyfunctionalized Triazoles via Multicomponent Reaction.

A novel four-component reaction of alkynes, amines, azides, and 2H-azirines has been developed for the first time by the efficient formation of four C-N bonds in one step under mild conditions, rapidly preparing polyfunctionalized triazoles with molecular diversity involving three different intermediates of copper-acetylide, copper-allenylidene, and copper-vinyl nitrene. Propargylic ester is disclosed as a "three-in-one" building block possessing triplicate cycloaddition and nucleophilic and electrophilic properties, which could enable such a four-component transformation by high yields, broad substrate scope, and functionalization.

Nb and Mn Co-Modified Na0.5Bi4.5Ti4O15 Bismuth-Layered Ceramics for High-Frequency Transducer Applications.

Lead-free environmentally friendly piezoelectrical materials with enhanced piezoelectric properties are of great significance for high-resolution ultrasound imaging applications. In this paper, Na0.5Bi4.5Ti3.86Mn0.06Nb0.08O15+y (NBT-Nb-Mn) bismuth-layer-structured ceramics were prepared by solid-phase synthesis. The crystallographic structure, micromorphology, and piezoelectrical and electromechanical properties of NBT-Nb-Mn ceramics were examined, showing their enhanced piezoelectricity (d33 = 33 pC/N) and relatively high electromechanical coupling coefficient (kt = 0.4). The purpose of this article is to describe the development of single element ultrasonic transducers based on these piezoelectric ceramics. The as-prepared high-frequency tightly focused transducer (ƒ-number = 1.13) had an electromechanical coupling coefficient of 0.48. The center frequency was determined to be 37.4 MHz and the -6 dB bandwidth to be 47.2%. According to the B-mode imaging experiment of 25 µm tungsten wires, lateral resolution of the transducer was calculated as 56 µm. Additionally, the experimental results were highly correlated to the results simulated by COMSOL software. By scanning a coin, the imaging effect of the transducer was further evaluated, demonstrating the application advantages of the prepared transducer in the field of high-sensitivity ultrasound imaging.

An Optimized Miniaturized Ultrasound Transducer for Transcranial Neuromodulation.

Transcranial ultrasound stimulation (TUS) is a young neuromodulation technology, which uses ultrasound to achieve non-invasive stimulation or inhibition of deep intracranial brain regions, with the advantages of non-invasive, deep penetration, and high resolution. It is widely considered to be one of the most promising techniques for probing brain function and treating brain diseases. In preclinical studies, developing miniaturized transducers to facilitate neuromodulation in freely moving small animals is critical for understanding the mechanism and exploring potential applications. In this article, a miniaturized transducer with a half-concave structure is proposed. Based on the finite element simulation models established by PZFlex software, several ultrasound transducers with different concave curvatures were designed and analyzed. Based on the simulation results, half-concave focused ultrasonic transducers with curvature radii of 5 mm and 7.5 mm were fabricated. Additionally, the emission acoustic fields of the ultrasonic transducers with different structures were characterized at their thickness resonance frequencies of 1 MHz using a multifunctional ultrasonic test platform built in the laboratory. To verify the practical ability for neuromodulation, different ultrasound transducers were used to induce muscle activity in mice. As a result, the stimulation success rates were (32 ± 10)%, (65 ± 8)%, and (84 ± 7)%, respectively, by using flat, #7, and #5 transducers, which shows the simulation and experimental results have a good agreement and that the miniaturized half-concave transducer could effectively converge the acoustic energy and achieve precise and effective ultrasonic neuromodulation.

Copper-catalyzed Z-selective synthesis of acrylamides and polyacrylamides via alkylidene ketenimines.

It remains very important to discover and study new fundamental intermediates consisting of carbon and nitrogen as the abundant elements of organic molecules. The unique alkylidene ketenimine could be formed in situ under mild conditions by an unexpected copper-catalyzed three-component reaction of alkyne, azide and water involving a successive cycloaddition, N2 extrusion and carbene-assisted rearrangement. Only Z-α,ß-unsaturated amides instead of E-α,ß-unsaturated amides or triazoles were acquired from alkylidene ketenimines with excellent selectivities and stereospecificities. In addition, a series of "approximate" alternating copolymers (poly (triazole-alt-Z-acrylamides)) with high Mns and yields were efficiently afforded by multicomponent polymerization through a very simple operation basing on this multicomponent reaction.

Single-Beam Acoustic Tweezer Prepared by Lead-Free KNN-Based Textured Ceramics.

Acoustic tweezers for microparticle non-contact manipulation have attracted attention in the biomedical engineering field. The key components of acoustic tweezers are piezoelectric materials, which convert electrical energy to mechanical energy. The most widely used piezoelectric materials are lead-based materials. Because of the requirement of environmental protection, lead-free piezoelectric materials have been widely researched in past years. In our previous work, textured lead-free (K, Na)NbO3 (KNN)-based piezoelectric ceramics with high piezoelectric performance were prepared. In addition, the acoustic impedance of the KNN-based ceramics is lower than that of lead-based materials. The low acoustic impedance could improve the transmission efficiency of the mechanical energy between acoustic tweezers and water. In this work, acoustic tweezers were prepared to fill the gap between lead-free piezoelectric materials research and applications. The tweezers achieved 13 MHz center frequency and 89% -6 dB bandwidth. The -6 dB lateral and axial resolution of the tweezers were 195 µm and 114 µm, respectively. Furthermore, the map of acoustic pressure measurement and acoustic radiation calculation for the tweezers supported the trapping behavior for 100 µm diameter polystyrene microspheres. Moreover, the trapping and manipulation of the microspheres was achieved. These results suggest that the KNN-based acoustic tweezers have a great potential for further applications.

High-Frequency 0.36BiScO3-0.64PbTiO3 Ultrasonic Transducer for High-Temperature Imaging Application.

( 1- x )BiScO3- x PbTiO3 (BS-PT) ceramics have excellent piezoelectricity and high Curie temperature at its morphotropic phase boundary (MPB) ( x = 0.64 ), so it is a promising piezoelectric material for fabricating high-temperature ultrasonic transducer (HTUT). Electric properties of 0.36BS-0.64PT ceramics were characterized at different temperatures, and an HTUT with the center frequency of about 15 MHz was designed by PiezoCAD based on the measuring results. The prepared HTUT was tested in a silicone oil bath at different temperatures systematically. The test results show that the HTUT can maintain a stable electrical resonance until 290 °C and get a clear echo response until 250 °C with slight changes of the center frequency. Then, a stepped metal block submerged in silicone oil was imaged by the HTUT until 250 °C. Velocity of silicone oil and axial resolution of the HTUT at different temperatures was calculated. The results verify the capability of 0.36BS-0.64PT-based HTUT for high-temperature ultrasonic imaging applications.

Evaluation of water quality and its driving forces in the Shaying River Basin with the grey relational analysis based on combination weighting.

The water quality of the Shaying River Basin and even the entire Huai River Basin has been widely concerned. Based on the water quality data acquired in flood and non-flood seasons from 2012 to 2016, the Shaying River Basin was selected as the research object. First, the principal component analysis method was used to identify the main pollution indices. Then, grey relational analysis combined with an analytic hierarchy process and entropy weight method was used to evaluate the water quality of the upper, middle, and lower reaches of the Shaying River Basin, while the single factor evaluation method was used for comparative analysis. Finally, the driving forces of water quality were analyzed and discussed from natural and human aspects. The results show that the main pollutants in the Shaying River Basin are total nitrogen, total phosphorus, and ammonium nitrogen. While the basin is seriously polluted by nitrogen and phosphorus, the spatial and temporal distribution of the pollution varies, although the overall trend toward improving water quality conditions is significant. The midstream region had the poorest water quality, which fluctuated between Classes III and V. The downstream region had generally good water quality, which could be ranked as Class III most of the time. And the upstream region had the best water quality with well-developed ecological conditions; all the water samples were ranked as Class I or II. The water quality improves significantly during the flood season when compared with that in the non-flood season. Seasonal climate variation, non-point source pollution emissions, the release of water from sluices and dams, and water resource management activities are the main reasons for the variations in water quality across the Shaying River Basin.

Preparation, Structure, and Electrical Properties of Cobalt-Modified Bi(Sc3/4In1/4)O3-PbTiO3-Pb(Mg1/3Nb2/3)O3 High-Temperature Piezoelectric Ceramics.

Cobalt-modified 0.40Bi(Sc3/4In1/4)O3-0.58PbTiO3-0.02Pb(Mg1/3Nb2/3)O3 ceramics (abbreviated as BSI-PT-PMN-xCo) were produced by conventional two-step solid-state processing. The phase structure, micro structure morphology, and electrical properties of BSI-PT-PMN-xCo were systematically studied. The introduction of Co ions exerted a significant influence on the structure and electrical properties. The experiment results demonstrated that Co ions entered the B-sites of the lattice, resulting in slight lattice distortion and a smaller lattice constant. The average grain size increased from ~1.94 µm to ~2.68 µm with the increasing Co content. The optimized comprehensive electrical properties were obtained with proper Co-modified content 0.2 wt.%. The Curie temperature (Tc) was 412 °C, the piezoelectric constant (d33) was 370 pC/N, the remnant polarization (Pr) was 29.2 µC/cm2, the relatively dielectric constant (εr) was 1450, the planar electromechanical coupling coefficient (kp) was 46.5, and the dielectric loss (tanδ) was 0.051. Together with the enhanced DC resistivity of 109 Ω cm under 300 °C and good thermal stability, BSI-PT-PMN-0.2Co ceramic is a promising candidate material for high-temperature piezoelectric applications.

Evolvable Acoustic Field Generated by a Transducer with 3D-Printed Fresnel Lens.

Evolvable acoustic fields are considered an effective method for solving technical problems related to fields such as biological imaging, particle manipulation, drug therapy and intervention. However, because of technical difficulties and the limited technology available for realizing flexible adjustments of sound fields, few studies have reported on this aspect in recent years. Herein, we propose a novel solution, using a Fresnel lens-focused ultrasonic transducer for generating excited-signal-dependent acoustic pressure patterns. Finite element analysis (FEA) is used to predict the performance of a transducer with a Fresnel lens. The Fresnel lens is printed using 3D additive manufacturing. Normalized intensity maps of the acoustic pressure fields are characterized from the Fresnel lens-focused transducer under various numbers of excited-signal cycles. The results demonstrate that under different cycle excitations, a temporal evolution acoustic intensity can be generated and regulated by an ultrasound transducer with a 3D Fresnel lens. This acoustical pattern control method is not only simple to realize but also has considerable application prospects.

Lead-Free KNN-Based Textured Ceramics for High-Frequency Ultrasonic Transducer Application.

Environment-friendly lead-free piezoelectric materials with excellent piezoelectric properties are needed for high-frequency ultrasonic transducer applications. Recently, lead-free 0.915(K0.45Na0.5Li0.05)NbO3-0.075BaZrO 3-0.01(Bi0.5Na0.5)TiO3 (KNLN-BZ-BNT) textured piezo- electric ceramics have high piezoelectric response, superior thermal stability, and excellent fatigue resistance, which are promising for devices applications. In this work, the KNLN-BZ-BNT textured ceramics were prepared by the tape-casting method. Microstructural morphology, phase transition, and electrical properties of KNLN-BZ-BNT textured ceramics were investigated. High-frequency needle-type ultrasonic transducers were designed and fabricated with these textured ceramics. The tightly focused transducers have a center frequency higher than 80 MHz and a -6-dB fractional bandwidth of 52%. Such transducers were built for an f -number close to 1, and the desired focal depth was achieved by press-focusing technology associated with a set of customer design fixture. Its lateral resolution was better than [Formula: see text] by scanning a 15- [Formula: see text] tungsten wire target. These promising results demonstrate that the lead-free KNLN-BZ-BNT textured ceramic is a good candidate for high-frequency ultrasonic transducer applications.

Interfacial redox processes in memristive devices based on valence change and electrochemical metallization.

Memristive devices based on electrochemical processes are promising candidates for next-generation memory and neuromorphic applications. The redox processes happening at the interfaces are crucial steps for the ionization as well as generation of counter charges, and are thus indispensable for successful resistive switching, but their detailed mechanism has not been fully clarified. Here, we study the interfacial redox reactions in the forming process of memristive devices based on valence change and electrochemical metallization, using high-resolution electron microscopy and electrostatic force microscopy observations. We show direct evidence for the anodic oxidation of oxygen ions and cathodic reduction of moisture in HfO2- and Ta2O5-based valence change cells, which could take place in different horizontal locations. We further found that the anodic reactions always led to more pronounced structural damage to the electrode, indicating the possibility of additional cathodic reactions without producing gaseous products. When an active electrode is present, oxidation of metal atoms takes place at the anodic interface instead. Further investigations on electrochemical metallization cells have identified Cu ionization and moisture reduction as the anodic and cathodic reactions, respectively, and formation of Cu nuclei at the cathodic interface was directly observed. These findings with microscopic evidence could facilitate future development of memristive devices.

High-speed true random number generation based on paired memristors for security electronics.

True random number generator (TRNG) is a critical component in hardware security that is increasingly important in the era of mobile computing and internet of things. Here we demonstrate a TRNG using intrinsic variation of memristors as a natural source of entropy that is otherwise undesirable in most applications. The random bits were produced by cyclically switching a pair of tantalum oxide based memristors and comparing their resistance values in the off state, taking advantage of the more pronounced resistance variation compared with that in the on state. Using an alternating read scheme in the designed TRNG circuit, the unbiasedness of the random numbers was significantly improved, and the bitstream passed standard randomness tests. The Pt/TaO x /Ta memristors fabricated in this work have fast programming/erasing speeds of ∼30 ns, suggesting a high random number throughput. The approach proposed here thus holds great promise for physically-implemented random number generation.