Design, Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Quinoxaline-2-Oxyacetate Hydrazide.

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 µg/mL against G. zeae, EC50 = 1.01 µg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 µg/mL against A. alternata, EC50 = 0.20 µg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

Development of a large flow electro-hydrostatic actuator equipped with four magnetostrictive-actuated pumps.

With the advantages of high energy density, high accuracy, and fast response, smart material-driven electro-hydrostatic actuators (SMEHAs) have attracted significant attention in recent years. However, the low flow rate of SMEHAs constrains their application. One potential solution to enhance the flow rate is to increase the number of smart material-actuated pumps. In view of this, this paper proposes a new configuration of an electro-hydrostatic actuator equipped with four magnetostrictive-actuated pumps (FMEHA) to achieve a large flow rate. The mathematical model of the FMEHA is established to investigate the driving phase matching between pumps and the active flow distribution valve. The physical prototype of FMEHA is fabricated. Simulations and experiments are conducted to assess its performance under various driving parameters, including the number of pumps, driving phase, frequency, and amplitude. The optimal driving parameters for the FMEHA are determined based on the results obtained. Experimental findings demonstrate that with a driving phase of 340°, a frequency of 250 Hz, and an amplitude of 20 A, the FMEHA achieves a maximum flow rate of 6.2 l/min.

Preparation, Characterization, and Lubrication Performances of Water-Based Nanolubricant for Micro Rolling Strips.

Water-based nanolubricants are widely used in rolling processes due to their unique characteristics. As a common additive, nanoparticles could significantly improve the tribological properties of the lubricant. However, the effect of the physical properties of the particles on the anti-friction behavior is unclear. In this study, the effect of Fe3O4 nanoparticles as an additive for the prepared lubricant is studied. The tribological properties of Fe3O4 water-based nanolubricant are examined using a tribometer and a scratch meter. The absorption energy is calculated using the molecular dynamic simulation method, and the best parameters for the preparation of the nanolubricant are obtained. The developed nanolubricant is used in the rolling process. The results show that the processing quality of samples is promoted and the tribological properties of water-based lubricant can be significantly promoted by an Fe3O4 nanoparticle additive. An economical and environmentally friendly method is presented through which the water-based Fe3O4 nanolubricant can be prepared for the replacement of oil-based lubricant in cold rolling strips.

A Survey of Needle Steering Approaches in Minimally Invasive Surgery.

In virtue of a curved insertion path inside tissues, needle steering techniques have revealed the potential with the assistance of medical robots and images. The superiority of this technique has been preliminarily verified with several maneuvers: target realignment, obstacle circumvention, and multi-target access. However, the momentum of needle steering approaches in the past decade leads to an open question-"How to choose an applicable needle steering approach for a specific clinical application?" This survey discusses this question in terms of design choices and clinical considerations, respectively. In view of design choices, this survey proposes a hierarchical taxonomy of current needle steering approaches. Needle steering approaches of different manipulations and designs are classified to systematically review the design choices and their influences on clinical treatments. In view of clinical consideration, this survey discusses the steerability and acceptability of the current needle steering approaches. On this basis, the pros and cons of the current needle steering approaches are weighed and their suitable applications are summarized. At last, this survey concluded with an outlook of the needle steering techniques, including the potential clinical applications and future developments in mechanical design.

Novel 5-Sulfonyl-1,3,4-thiadiazole-Substituted Flavonoids as Potential Bactericides and Fungicides: Design, Synthesis, Three-Dimensional Quantitative Structure-Activity Relationship Studies.

Flavonoids, ubiquitous natural products, provide sources for drug discovery owing to their structural diversity, broad-spectrum pharmacological activity, and excellent environmental compatibility. To develop antibacterial and antifungal agents with novel mechanisms of action and innovative structures, a series of novel 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoids were designed and synthesized, and their biological activities against seven agriculturally common phytopathogenic microorganisms were evaluated. The results of the antimicrobial bioassay showed that most of the target compounds displayed excellent inhibitory effects against Xanthomonas oryzae, Rhizoctonia solani, and Colletotrichum orbiculare. Compounds 1, 3, 7, 9, 13, and 14 exhibited remarkable antibacterial activity against X. oryzae pv. oryzae with EC50 values below 10 µg/mL, which were superior to bismerthiazol (70.89 µg/mL). Compound 2 (EC50 = 0.41 µg/mL) displayed the most effective inhibitory potency against R. solani in vivo, comparable protective effects with the positive control carbendizam. Preliminary mechanistic studies indicated that compound 2 induced disordered entanglement of hyphae, shrinkage of hyphal surfaces, extravasation of cellular contents, and vacuole swelling and rupture, which disrupted normal hyphal growth. Subsequently, compounds 35-53 with good antifungal activity were designed and synthesized based on reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) models. Compound 49 showed high efficacy and superior antifungal activity against R. solani, with an EC50 value of 0.28 µg/mL and a half-maximal effective concentration of 0.46 µg/mL.

Discovery and Evaluation of Pyrazolo[3,4-d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor.

The identification and lead optimization of a series of pyrazolo[3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.