Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1-benzo[]imidazole () exhibited optimal antifungal activity against (), affording an excellent half-maximal effective concentration (EC) of 0.

Engineering Phenothiazine-Based Functional Mimics of Host Defense Peptides as New Agrochemical Candidates: Design, Synthesis, and Antibacterial Evaluation.

In the protracted "arms race" between host and plant pathogenic bacteria, host organisms have evolved powerful weapons known as host defense peptides (HDPs). However, natural HDPs are not suitable for large-scale applications; therefore, researchers have chosen to develop bespoke small-molecule functional mimics. Phenothiazine derivatives were developed as functional HDPs mimics, owing to their broad biological activity and high lipophilicity.

Identification of natural Rutaecarpine as a potent tobacco mosaic virus (TMV) helicase candidate for managing intractable plant viral diseases.

Background: Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost-effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double-stranded RNA unwinding.

Novel mandelic acid derivatives suppress virulence of Ralstonia solanacearum via type III secretion system.

Background: Bacterial wilt induced by Ralstonia solanacearum is regarded as one of the most devastating diseases. However, excessive and repeated use of the same bactericides has resulted in development of bacterial resistance. Targeting bacterial virulence factors, such as type III secretion system (T3SS), without inhibiting bacterial growth is a possible assay to discover new antimicrobial agents.

Effectiveness and Safety of Bu Shen Kai Qiao Fang in the Treatment of Alzheimer's Disease: Study Protocol for a Multicenter, Prospective, Real-World Clinical Trial.

Background: Alzheimer's disease (AD) is a common degenerative disease of the nervous system with serious impact on quality of life of patients and their families. With an aging population, AD has become a major public health problem in China and worldwide. However, the physiological and pathological mechanisms of AD have not been fully elucidated, and there is a lack of effective prevention and clinical treatment methods.

Novel spiro[chromanone-2,4'-piperidine]-4-one derivatives as potential inhibitors of fatty acid synthesis in pathogens: Design, synthesis, and biological evaluation.

Bacterial survival depends on membrane lipid homeostasis that enables to regulate lipid composition to adapt and optimize their growth in diverse environments. Therefore, the development of inhibitors that interfere with the bacterial fatty acid synthesis process is considered to be a promising tactic. In this study, 58 novel spirochromanone derivatives were prepared and their structure-activity relationship (SAR) was investigated.

Discovery of Epipodophyllotoxin-Derived B as Promising FtsZ Inhibitor for Controlling Bacterial Cell Division: Structure-Based Virtual Screening, Synthesis, and SAR Study.

The emergence of phytopathogenic bacteria resistant to antibacterial agents has rendered previously manageable plant diseases intractable, highlighting the need for safe and environmentally responsible agrochemicals. Inhibition of bacterial cell division by targeting bacterial cell division protein FtsZ has been proposed as a promising strategy for developing novel antibacterial agents. We previously identified 4'-demethylepipodophyllotoxin (DMEP), a naturally occurring substance isolated from the barberry species , as a novel chemical scaffold for the development of inhibitors of FtsZ from the rice blight pathogen pv.

[Mechanism of emodin in relieving neuropathic pain by regulating serum metabolism].

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery.

A Hypopituitarism Patient with Bickerstaff's Brainstem Encephalitis Overlapped by Guillain-Barré Syndrome: A Case Report.

We present a rare case of Bickerstaff's brainstem encephalitis (BBE) overlapped with Guillain-Barré syndrome (GBS), which might be triggered by the patient's hypopituitarism condition. A 36-year-old woman with a history of hypopituitarism presented with a headache on the first day. Gradually, diplopia, ataxia, dysarthria, dysphagia, hypoesthesia, limb weakness, hypersomnolence, and respiratory muscle paralysis were developed in less than ten days.

An enriched environment delays the progression from mild cognitive impairment to Alzheimer's disease in senescence-accelerated mouse prone 8 mice.

A previous study demonstrated that middle-aged (5-6 months of age) senescence-accelerated mouse prone 8 (SAMP8) mice can be used as animal models of mild cognitive impairment (MCI). An enriched environment (EE) can mitigate cognitive decline and decrease the pathological changes associated with various neurodegenerative diseases. In the present study, the learning-memory abilities of SAMP8 mice during the MCI phase (5 months of age) was evaluated and neuropathological changes in the hippocampus were examined after the mice were exposed to an EE for 60 days.

Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain.

The aim of this study was to explore the relationships among gut microbiota disturbances and serum and spinal cord metabolic disorders in neuropathic pain. 16S rDNA amplicon sequencing and serum and spinal cord metabolomics were used to identify alterations in the microbiota and metabolite profiles in the sham rats and the chronic constriction injury (CCI) model rats. Correlations between the abundances of gut microbiota components at the genus level, the levels of serum metabolites, and pain-related behavioural parameters were analysed.

Antibacterial Functions and Proposed Modes of Action of Novel 1,2,3,4-Tetrahydro-β-carboline Derivatives that Possess an Attractive 1,3-Diaminopropan-2-ol Pattern against Rice Bacterial Blight, Kiwifruit Bacterial Canker, and Citrus Bacterial Canker.

In recent years, naturally occurring tetrahydro-β-carboline (THC) alkaloids and their derivatives have been of biological interest. However, few studies and developments have reported the use of such structures in managing plant bacterial diseases. Herein, an array of novel THC derivatives containing an attractive 1,3-diaminopropan-2-ol pattern were prepared to evaluate the antiphytopathogen activity and and explore innovative antibacterial frameworks.

Synthesis and Docking Study of -(Cinnamoyl)-'-(substituted)acryloyl Hydrazide Derivatives Containing Pyridinium Moieties as a Novel Class of Filamentous Temperature-Sensitive Protein Z Inhibitors against the Intractable pv. Infections in Rice.

pv. () is an offensive phytopathogen that can invade a wide range of plant hosts to develop bacterial diseases, including the well-known rice bacterial leaf blight. However, few agrochemicals have been identified to effectively prevent and eliminate -induced diseases.

Curcumin-Cu(II) Ensemble-Based Fluorescence "Turn-On" Mode Sensing the Plant Defensive Hormone Salicylic Acid and .

Salicylic acid (SA), a crucial, plant-derived signal molecule, is capable of launching global transcriptional reprogramming to assist plants in obtaining the systemic acquired resistance (SAR) mechanism. Thus, the accurate detection of SA will not only significantly contribute to the understanding of the plant SAR but also contribute to crop protection and to the security of the agricultural production and food supply. However, detection of SA using fluorescent probes is a great challenge for scientists, because SA analogues can significantly interfere with the detection results.

Synthesis of novel 18β-glycyrrhetinic piperazine amides displaying significant in vitro and in vivo antibacterial activities against intractable plant bacterial diseases.

Background: The limited amount of agrochemicals targeting plant bacterial diseases has motivated us to study innovative antibacterial surrogates with fresh modes of action. Notably, fabrication of violent apoptosis inducers to control the reproduction of pathogenic bacteria should be a feasible way to control plant bacterial diseases. To achieve this aim, we constructed a series of novel 18β-glycyrrhetinic piperazine amides based on the natural bioactive ingredient 18β-glycyrrhetinic acid to evaluate the in vitro and in vivo antibacterial activity and induced apoptosis behaviors on tested pathogens.

Novel piperazine-tailored ursolic acid hybrids as significant antibacterial agents targeting phytopathogens Xanthomonas oryzae pv. oryzae and X. axonopodis pv. citri probably directed by activation of apoptosis.

Background: Induced apoptosis is an effective technique that can reprogram cellular physiological and pathological processes to eradicate undesirable cells using their innate systems. Inspired by this, numerous apoptosis inducers have been developed to treat animal diseases, especially in the anticancer field. However, few studies have reported on the development of inductive agents that attack plant pathogens by activation of apoptosis.

Target Discovery in through an Activity-Based Protein Profiling Technique Based on Bioactive Oxadiazole Sulfones.

is an extremely destructive and rebellious phytopathogen that can cause bacterial wilt diseases in more than 200 plant species. To explore and discover the potential targets in for the purpose of developing new agrochemicals targeting this infection, here, we exploited a typical activity-based protein profiling technique for target discovery in based on an activity-based probe derived from bioactive oxadiazole sulfones. A total of 65 specific targets were identified with high confidence through a quantitative chemical proteomic approach.

Design, Synthesis, Antibacterial Evaluation, and Induced Apoptotic Behaviors of Epimeric and Chiral 18β-Glycyrrhetinic Acid Ester Derivatives with an Isopropanolamine Bridge against Phytopathogens.

Because only a handful of agrochemicals can manage bacterial infections, the discovery and development of innovative, inexpensive, and high-efficiency antibacterial agents targeting these infections are challenging. Herein, a series of novel epimeric and chiral 18β-glycyrrhetinic acid (GA) ester derivatives with various tertiary amine pendants were designed, synthesized, and screened for pharmacological activity. Results showed that some of the title compounds were conferred with significantly enhanced antibacterial activity toward phytopathogens pv (, -, and , EC values within 3.

Synthesis of Thiazolium-Labeled 1,3,4-Oxadiazole Thioethers as Prospective Antimicrobials: In Vitro and in Vivo Bioactivity and Mechanism of Action.

In this study, a type of thiazolium-labeled 1,3,4-oxadiazole thioether bridged by diverse alkyl chain lengths was constructed. The antimicrobial activity of the fabricated thioether toward plant pathogenic bacteria and fungi was then screened. Antibacterial evaluation indicated that title compounds possess specific characteristics that enable them to severely attack three phytopathogens, namely, , , and with minimal EC values of 0.

Pinellia Total Alkaloids Modulate the GABAergic System in Hippocampal Formation on Pilocarpine-Induced Epileptic Rats.

Objective: To investigate the neuromodulatory effect of pinellia total alkaloids (PTA) on the gamma-aminobutyric acidergic (GABAergic) system in epileptic rats, and preliminarily evaluate the anti-epileptic effect of PTA.

Methods: Ninety-one male Sprague-Dawley rats were randomized to a control group (n=17) or an epileptic group (n=74) using computer-generated random numbers. Status epilepticus (SE) was induced with pilocarpine in the epileptic group.

Rational Optimization and Action Mechanism of Novel Imidazole (or Imidazolium)-Labeled 1,3,4-Oxadiazole Thioethers as Promising Antibacterial Agents against Plant Bacterial Diseases.

The emergence and widespread occurrence of plant bacterial diseases that cause global production constraints have become major challenges to agriculture worldwide. To promote the discovery and development of new bactericides, imidazole-labeled 1,3,4-oxadiazole thioethers were first fabricated by integrating the crucially bioactive scaffolds of the imidazole motif and 1,3,4-oxadiazole skeleton in a single molecular architecture. Subsequently, a superior antibacterial compound A was gradually discovered possessing excellent competence against plant pathogens Xanthomonas oryzae pv oryzae and Xanthomonas axonopodis pv citri with EC values of 0.

Protective effects of curcumin on acrolein-induced neurotoxicity in HT22 mouse hippocampal cells.

Background: Aging is one of the most important inevitable risk factors of Alzheimer disease (AD). Oxidative stress plays a critical role in the process of aging. Curcumin has been proposed to improve neural damage, especially neurodegenerative injury, through its antioxidant and anti-inflammatory properties.