Lanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis.

Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism.

Comprehensive assessment of rice bran dietary fiber on gut microbiota composition and metabolism during in vitro fermentation.

Rice bran, a by-product of rice processing, is rich in various nutrients. As one of the main components of rice bran, dietary fiber has a variety of potential health benefits, especially its probiotic effects on gut health. This study involved the preparation and characterization of soluble rice bran dietary fibers (RB-SDF) and insoluble rice bran dietary fibers (RB-IDF), followed by an investigation into their gastrointestinal probiotic impact and principal metabolites.

Discovery of new fungal jumonji H3K27 demethylase inhibitors for the treatment of Cryptococcus neoformans and Candida auris infections.

Invasive fungal infections have become a serious public health problem. To tackle the challenges of limited efficacy in antifungal therapy and severe drug resistance, antifungal drugs with new mechanisms of action are urgently needed. Our previous study identified JIB-04 to be an inhibitor of fungal histone demethylase (HDM).

Fortification of yogurt with mulberry leaf extract: Effects on physicochemical, antioxidant, microbiological and sensory properties during 21-days of storage.

Mulberry leaves are medicinal and edible, with many physiological functions. To improve the potential function of yogurt, the effects of mulberry leaf extract (MLE) incorporation on the fermentation kinetics, physicochemical, antioxidant properties, and sensory parameters of yogurt were evaluated. The results showed that 0.

Producing Freestanding Single-Crystal BaTiO Films through Full-Solution Deposition.

Strontium aluminate, with suitable lattice parameters and environmentally friendly water solubility, has been strongly sought for use as a sacrificial layer in the preparation of freestanding perovskite oxide thin films in recent years. However, due to this material's inherent water solubility, the methods used for the preparation of epitaxial films have mainly been limited to high-vacuum techniques, which greatly limits these films' development. In this study, we prepared freestanding single-crystal perovskite oxide thin films on strontium aluminate using a simple, easy-to-develop, and low-cost chemical full-solution deposition technique.

MLKL-USP7-UBA52 signaling is indispensable for autophagy in brain through maintaining ubiquitin homeostasis.

Individuals with genetic elimination of (mixed lineage kinase domain like pseudokinase) exhibit an increased susceptibility to neurodegenerative diseases like Alzheimer disease (AD). However, the mechanism is not yet fully understood. Here, we observed significant compromise in macroautophagy/autophagy in the brains of knockout (KO) mice, as evidenced by the downregulation of BECN1/Beclin1 and ULK1 (unc-51 like autophagy activating kinase 1).

Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress-induced anxiety-like behavior.

JOURNAL/nrgr/04.03/01300535-202506000-00024/figure1/v/2024-08-05T133530Z/r/image-tiff The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions. Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress.

Production of γ-aminobutyric acid-enriched sourdough bread using an isolated strain JC30.

A γ-aminobutyric acid (GABA)-producing strain JC30 was isolated from traditional kimchi, which was identified as by 16S rDNA sequencing. . JC30 was highly tolerant to acid, bile salt, and high temperatures.

Colossal Ferroelectric Photovoltaic Effect in Inequivalent Double-Perovskite BiFeMnO Thin Films.

Double perovskite films have been extensively studied for ferroelectric order, ferromagnetic order, and photovoltaic effects. The customized ion combinations and ordered ionic arrangements provide unique opportunities for bandgap engineering. Here, a synergistic strategy to induce chemical strain and charge compensation through inequivalent element substitution is proposed.

Clinical study on improving the function of female bladder in controlling urine by acupuncture Zhibian (BL54) under ultrasound guidance.

Objective: To observe the effect of acupuncture Zhibian (BL54) on the function of the bladder in controlling urine in women under ultrasound.

Method: 74 healthy subjects were randomly divided into deep acupuncture group of 37 cases and shallow acupuncture group of 37 cases. Under the guidance of ultrasound, the two groups of subjects were acupunctured at bilateral BL54.

Astrocyte-mediated regulation of BLA neurons alleviates risk-assessment deficits in DISC1-N mice.

Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood.

Discovery of New Tricyclic Oxime Sampangine Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcosis and Candidiasis.

() and () are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound showed excellent inhibitory activity against (MIC = 0.

Efficacy of Warm Acupuncture Therapy Combined with Kegel Exercise on Postpartum Pelvic Floor Dysfunction in Women.

Introduction And Hypothesis: The objective was to observe the clinical efficacy of warm acupuncture combined with Kegel exercise in treating postpartum pelvic floor dysfunction in women.

Methods: A total of 70 primiparous women with postpartum pelvic floor muscle (PFM) injury were randomly divided into a combination group (n = 35, receiving warm acupuncture at Zhibian (BL54) acupoint and Kegel exercise) and a sham control group (n = 35, receiving sham warm acupuncture and Kegel exercise). Both groups were treated three times a week for 4 consecutive weeks.

Divergent Selection in Low Recombination Regions Shapes the Genomic Islands in Two Incipient Shorebird Species.

Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such as divergent selection and local recombination rate variation, can influence the formation of these genomic islands. Examination of the genomic landscapes of species pairs that are still in the early stages of speciation provides an insight into this conundrum.

Polygonum cuspidatum Sieb. et Zucc. Extracts improve sepsis-associated acute kidney injury by inhibiting NF-κB-mediated inflammation and pyroptosis.

Ethnopharmacological Relevance: Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) is a herbaceous perennial plant in the Polygonaceae family that produces biofunctional stilbenes and quinones.

Discovery of Pyrazolone Carbothioamide Derivatives as Inhibitors of the Pdr1-KIX Interaction for Combinational Treatment of Azole-Resistant Candidiasis.

has emerged as an important opportunistic pathogen of invasive candidiasis due to increasing drug resistance. Targeting Pdr1-KIX interactions with small molecules represents a potential strategy for treating drug-resistant candidiasis. However, effective Pdr1-KIX inhibitors are rather limited, hindering the validation of target druggability.

Controlling antifungal activity with light: Optical regulation of fungal ergosterol biosynthetic pathway with photo-responsive CYP51 inhibitors.

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition.

Anion-induced robust ferroelectricity in sulfurized pseudo-rhombohedral epitaxial BiFeO thin films polarization rotation.

Polarization rotation caused by various strains, such as substrate and/or chemical strain, is essential to control the electronic structure and properties of ferroelectric materials. This study proposes anion-induced polarization rotation with chemical strain, which effectively improves ferroelectricity. A method for the sulfurization of BiFeO thin films by introducing sulfur anions is presented.

Discovery of a new chemical scaffold for the treatment of superbug infections.

has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound showed potent and efficacy against infection.

Discovery of BRD4-HDAC Dual Inhibitors with Improved Fungal Selectivity and Potent Synergistic Antifungal Activity against Fluconazole-Resistant .

Over the past several decades, invasive fungal infections, especially candidiasis, have caused dramatic morbidity and mortality due to ineffective antifungal drugs and severe drug resistance. Herein, new BRD4-histone deacetylase (HDAC) inhibitors were designed to restore the susceptibility of () to fluconazole (FLC). Interestingly, several compounds showed excellent selectivity against fungal HDACs.

Target- and prodrug-based design for fungal diseases and cancer-associated fungal infections.

Invasive fungal infections (IFIs) are emerging as a serious threat to public health and are associated with high incidence and mortality. IFIs also represent a frequent complication in patients with cancer who are undergoing chemotherapy. However, effective and safe antifungal agents remain limited, and the development of severe drug resistance further undermines the efficacy of antifungal therapy.

MicroRNA-128 suppresses tau phosphorylation and reduces amyloid-beta accumulation by inhibiting the expression of GSK3β, APPBP2, and mTOR in Alzheimer's disease.

Introduction And Aims: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aβ) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aβ pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD.

Sugar Beverage Habitation Relieves Chronic Stress-Induced Anxiety-like Behavior but Elicits Compulsive Eating Phenotype via vLS Neurons.

Chronically stressed individuals are reported to overconsume tasty, palatable foods like sucrose to blunt the psychological and physiological impacts of stress. Negative consequences of high-sugar intake on feeding behavior include increased metabolic disease burdens like obesity. However, the neural basis underlying long-term high-sugar intake-induced overeating during stress is not fully understood.