In Pursuit of Lead Innovation: Pharmaceutically Important and Distinct Amide-Free Succinate Dehydrogenase Inhibitors.

Though succinate dehydrogenase inhibitors (SDHIs) are quite successful in the modern agrochemical industry, the Fungicide Resistance Action Committee has classified the resistance risk as "medium to high". Structural analysis reveals that these antifungal chemotypes are highly conserved with amides as a consistent feature. This chemical factor may be a potential factor for the ever-increasing resistance risk.

Siccanin-related drimane meroterpenoids: biological activities and synthesis.

Covering: 1962 to 2023Drimane (hydro)quinones biosynthetically arise from the combination of drimane-type terpenoids with phenols or equivalents. Since the isolation of siccanin in 1962 (structure identified in 1967), over 200 natural drimane (hydro)quinones have been reported. They are widespread with remarkably diverse architectures and biological functions, which are achieved by varying either the drimane subunit, hydroquinone segment, or the fusion types of drimane and hydroquinone segment both of them.

Degradation-Risk-Inspired Optimization of the Antifungal Oxazolinyl Aniline Lead by a Fusion of Triazole with Nicotinamide.

The discovery of readily available and easily modifiable new models is a crucial and practical solution for agrochemical innovation. Antifungal function-oriented fusion of triazole with the prevalidated lead ()- affords a novel framework with a broad and enhanced antifungal spectrum. Characterized by the easy accessibility and adjustability of [1,2,4]triazolo[4,3-]pyridine, modular fine-tuning provided a set of unprecedented leads (e.

Modular Synthesis and Antimicrobial Investigation of Mycoleptodiscin A and Simplified Indolosesquiterpenoids.

The structure-activity relationship of the unusual indolosesquiterpenoid mycoleptodiscin A is unknown due to natural scarcity and inefficient synthesis. A modular approach leveraging Larock indole synthesis has been established to access mycoleptodiscin A and a divergent collection of drimenyl indoles. It features the utilization of an inexpensive (+)-sclareolide, modularity, purification-economy, and scalability, which facilitates the first biological evaluation of mycoleptodiscin A and related precursors.

Multidimensional Optimization of -LE001 for New Leads with Enhanced Antifungal Profiles.

Scaffold hopping and structural fine-tuning are important strategies for agrochemical innovation. Multidimensional optimization of the prevalidated antifungal lead was conducted via the design, synthesis, and bioevaluation of 53 new compounds differing in either scaffold or substituent. The antifungal structure-activity relationship (SAR) revealed that a number of amides containing 2-(2-oxazolinyl) aniline (NHPhOx) or 2-(2-thiazolinyl) aniline (NHPhthiOx) demonstrated a more promising antifungal effect than both and the positive control boscalid.

Eudistomins Y-Inspired Design and Divergent Optimization of Heteroaryl Ketones for New Antifungal Leads.

The discovery of structurally distinct leads is imperative in modern agrochemical science. Inspired by eudistomins Y and the framework-related pharmaceuticals, aryl heteroaryl ketone was drawn as a common model intriguing the design and divergent synthesis of 14 kinds of heteroaryl ketones aligned with their oxime derivatives. Antifungal function-oriented phenotypical screen protruded benzothiazolyl-phenyl oxime as a promising model, and the concomitant modification led to benzothiazolyl oxime (EC = 5.

Facile Synthesis and First Antifungal Exploration of Tetracyclic Meroterpenoids: (+)-Aureol, (-)-Pelorol, and Its Analogs.

As an important bioactive molecular backbone, drimane meroterpenoids have drawn a great deal of attention from both pharmacologists and chemists. Inspired by the prevalidated success of conformational restriction in the discovery of novel pharmaceutical leads, two distinct tetracyclic drimane meroterpenoids, (-)-pelorol and (+)-aureol, were synthesized from the inexpensive starting material (-)-sclareol through 10 and 8 steps with 5.6% and 5.

Design and Discovery of α-Oximido-arylacetamides as Novel Antifungal Leads.

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the -aminophenyloxazoline () scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead .

Research on Optical Fiber Ring Resonator Q Value and Coupling Efficiency Optimization.

The coupling efficiency of the fiber ring resonator has an important influence on the scale factor of the resonant fiber gyroscope. In order to improve the scale factor of the gyroscope, the coupling efficiency of the fiber ring resonator and its influential factors on the scale factor of the gyroscope are analyzed and tested. The results show that the coupling efficiency is affected by both the splitting ratio of the coupler and the loss in the cavity.

Antifungal Function Oriented Scaffold Hopping for the Discovery of Oxazolyl-oxazoline as a Novel Model against .

Discovery of novel structural models is extremely important in agrochemical innovation. Scaffold hopping was conducted, and 16 kinds of novel models were synthesized and biologically evaluated. Oxazolyl-oxazoline showed a promising potential against with EC value of 18.

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation.

Chromatography-Free Synthesis of βCarboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of βCarbolines as Promising Antifungal and Antibacterial Candidates.

Agrochemical science prioritizes the discovery and effective synthesis of innovative and promising lead compounds. Herein, we developed an efficient column chromatography-free synthesis for βcarboline 1-hydrazides via a mild CuBr-catalyzed oxidation and investigated the antifungal and antibacterial activities and mechanisms for these compounds. In our study, compounds (EC = 0.

Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.

Drimane meroterpenoids have drawn increasing attention in the discovery of novel pharmaceutical leads owing to their structural diversity and bioactivity variation, but further development is significantly impeded by the lack of an efficient modular route of preparation. A nickel-catalyzed decarboxylative cross-coupling paradigm has been established to expeditiously access a constellation of drimane meroterpenoids. The redox-active drimane precursor is a bench-stable coupling partner and is easily available from the inexpensive feedstock sclareol.

The application of a novel hydrodynamic cavitation device to debride intra-articular monosodium urate crystals.

Introduction: Efficient and complete debridement of intra-articular deposits of monosodium urate crystals is rarely achieved by existing arthroscopic tools such as shavers or radiofrequency ablation, while cavitation technology represents a prospective solution for the non-invasive clearance of adhesions at intra-articular interfaces.

Methods: Simulation modeling was conducted to identify the optimal parameters for the device, including nozzle diameters and jet pressures. Gouty arthritis model was established in twelve rats that were equally and randomly allocated into a cavitation debridement group or a curette debridement group.

Radial Extracorporeal Shock Wave Therapy Enhances Graft Maturation at 2-Year Follow-up After ACL Reconstruction: A Randomized Controlled Trial.

Background: Graft maturation is an important prognostic factor for hamstring autograft anterior cruciate ligament reconstruction (ACLR). It remains unclear whether extracorporeal shock wave therapy (ESWT) can promote graft healing after ACLR.

Purpose: To evaluate the therapeutic and graft maturation effects of ESWT in hamstring autograft ACLR.

Asymmetric Synthesis of Sakuranetin-Relevant Flavanones for the Identification of New Chiral Antifungal Leads.

Discovery and efficient synthesis of new promising leads have a central role in agrochemical science. Reported herein is the sakuranetin-directed synergistic exploration of an asymmetric synthesis and an antifungal evaluation of chiral flavanones. A new palladium catalytic system with CarOx-type ligands was successfully identified for the highly enantioselective addition of arylboronic acids to chromones.

Palladium Catalyzed Enantioselective Hayashi-Miyaura Reaction for Pharmaceutically Important 4-Aryl-3,4-dihydrocoumarins.

The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins was successfully established, providing a straightforward asymmetric approach to achieving pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology features easily accessible and bench-stable ligands, a wide substrate scope, mild conditions, and accommodation of electron-withdrawing arylboronic acids.

Facile and divergent optimization of chromazonarol enabled the identification of simplified drimane meroterpenoids as novel pharmaceutical leads.

The diversity of drimane hydroquinones was significantly expanded by the facile construction of (+)-chromazonarol relevant natural products, isomers, and analogues for the discovery of new pharmaceutical leads. The structure-activity relationship of (+)-chromazonarol relevant (non)-natural products was delineated via the synergistic interaction of the programmable synthesis and bioactivity-guided screening. The first divergent derivatization of (+)-chromazonarol demonstrated that the phenolic hydroxyl group is one inviolable requirement for antifungal effect.

Deactivation of the dorsal anterior cingulate cortex indicated low postoperative sports levels in presurgical patients with chronic ankle instability.

Background: Injury-related fear contributed to disability in chronic ankle instability (CAI), while there still lacked exploration on the appraisal processes of the injury-related stimuli. This study aimed to compare the neural activities of the appraisal processes of sprain-related stimuli between presurgical chronic ankle instability patients and healthy controls through functional magnetic resonance imaging (fMRI) and evaluate its relationships with the clinical outcomes of orthopedic surgeries.

Methods: Eighteen presurgical CAI patients and fourteen healthy controls were recruited and underwent an fMRI session with visual stimulation of movies that showing typical ankle sprains accidents or control videos and the corresponding fear ratings.

Lateral ankle instability-induced neuroplasticity in brain grey matter: A voxel-based morphometry MRI study.

Objectives: The deficits in sensory pathways caused by peripheral edema, pain, and inflammation of the damaged ligaments may induce maladaptive changes within the central nervous system. The purpose of this study was to determine whether patients with lateral ankle instability (LAI) exhibit morphological differences of brain grey matter when compared with healthy controls, and then assess the relationships between the observed differences and the characteristics of patients.

Design: Cross-sectional.

Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model.

Introduction: Animal models are valid for research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is the most common method, while stable MSU deposition enveloped by inflammatory cells was rarely reported.

Objective: To develop a modified gouty arthritis rat model characterized by intra-articular MSU deposition and continuous joint pain with a minimally invasive method.

Outcomes of arthroscopic bone graft transplantation for Hepple stage V osteochondral lesions of the talus.

Background: Based on MRI imaging findings, osteochondral lesions of the talus (OLT) can be classified into five stages, in which stage V represents OLT with subchondral cyst formation. The aim of this study was to evaluate the outcomes of patients undergoing arthroscopic transplantation of calcaneus bone graft for Hepple stage V OLT.

Methods: This retrospective study included 24 patients with Hepple stage V OLT (15 men and 9 women), with an average age of 39.

Discovery and preliminary mechanism of 1-carbamoyl β-carbolines as new antifungal candidates.

Natural β-carboline alkaloids are ideal models for the discovery of pharmaceutically important entities. Various 1-substituted β-carbolines were synthesized from commercially inexpensive tryptophan and demonstrated significant in vitro antifungal activity against G. graminis.

Determinants of the Fiscal Support of Governments in Response to the COVID-19 Pandemic.

Fiscal support measures have different implications for public finances in the near term and beyond the COVID-19 pandemic. For this purpose, this paper examines the determinants of governments' fiscal support in response to the COVID-19 pandemic. The empirical analysis is based on the cross-sectional data estimations from 129 developed and developing countries.

Modular Synthesis of Drimane Meroterpenoids Leveraging Decarboxylative Borylation and Suzuki Coupling.

Drimane meroterpenoids have attracted an increasing amount of attention in the discovery of therapeutically important probes, while the laggard synthetic accessibility is a conspicuous challenge. A new paradigm merging decarboxylative borylation and Suzuki coupling was developed as a powerful platform. Key features include the mild conditions, good chemoselectivity, operational facility, scalability, and easy availability of the coupling partners.