Synthesis of a fluorophilic magnetic microporous organic network for selective enrichment of fipronil and ethiprole in milk and egg samples.

Considering the widespreadly use, large consumption, and serious environmental and health threats of phenylpyrazole insecticides (PPIs), development of a selective and sensitive method for accurate detection of their residuals in food samples is of great significance and challenging. Herein, depending on the hydrophobic and F-containing characteristics of PPIs, a novel fluorinated magnetic microporous organic network (FMMON) was designed and prepared for efficient and selective magnetic solid-phase extraction (MSPE) of two typical PPIs (fipronil and ethiprole) from milk and egg samples before the HPLC-UV determination. FMMON owned large specific surface area, multiple interaction sites, excellent magnetic separation performance and stability and exhibited good extraction and selectivity for fipronil and ethiprole through the specific F-F, hydrogen bonding, hydrophobic, and π-π interactions.

An Injectable Oil-Based Depot Formulation of -Acyloxymethyl Prodrug of Ropivacaine for Long-Acting Local Analgesia: Formulation Development and In Vitro/In Vivo Evaluation.

The development of novel long-acting injectables for local anesthetics is necessary to effectively manage the acute postoperative pain. The aim of this study was to prepare an injectable oil-based formulation of ropivacaine (ROP) prodrug (ropivacaine stearoxil, ROP-ST) and to investigate the pharmacokinetics and pharmacodynamics after injectable administration. A novel -acyloxymethyl prodrug of ROP, i.

Investigating the Effect and Potential Mechanism of Rhamnetin 3--α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro.

: Rhamnetin 3--α-rhamnoside (ARR) is a major flavonoid of the herb Franch. & Sav., which has been used for treating liver diseases in China.

Silybin Cocrystals with Improved Solubility and Bioavailability.

Silymarin, an extract from milk thistle, is widely recognized for its therapeutic potential in treating liver disorders. However, its clinical utility is limited by the poor solubility and low bioavailability of its key active ingredient, Silybin. In this study, we sought to address this issue through the development of a novel cocrystal of Silyin.

Pharmacodynamic Mechanisms of Cicadae Periostracum in Parkinson's Disease: A Metabolomics-Based Study.

Cicadae Periostracum (CP) is a traditional Chinese animal-derived medicine with the potential to treat Parkinson's disease (PD). This study aims to explore the pharmacodynamic mechanisms of CP against PD-based on metabolomics technology and provide a theoretical basis for developing new anti-PD medicine. First, MPP-induced SH-SY5Y cells were used to evaluate the anti-PD activity of CP.

A Novel Nitrite Reductase from for Efficient Degradation of Nitrite.

Nitrite reductases play a crucial role in the nitrogen cycle, demonstrating significant potential for applications in the food industry and environmental remediation, particularly for nitrite degradation and detection. In this study, we identified a novel nitrite reductase (NiR) from a newly isolated denitrifying bacterium, YD01. We constructed a heterologous expression system using BL21/pET28a-Nir, which exhibited remarkable nitrite reductase enzyme activity of 29 U/mL in the culture broth, substantially higher than that reported for other strains.

Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma.

: Hepatocellular carcinoma (HCC) remains a significant global health concern, primarily due to the limited efficacy of targeted therapies, which are often compromised by drug resistance and adverse side effects. : In this study, we utilized a Tandem Mass Tag (TMT)-based quantitative proteomic approach to analyze global protein expression and serine/threonine/tyrosine (S/T/Y) phosphorylation modifications in HepG2 cells following treatment with three clinically relevant hepatocellular carcinoma-targeted agents: apatinib, regorafenib, and lenvatinib. : Utilizing KEGG pathway enrichment analysis, biological process enrichment analysis, and protein interaction network analysis, we elucidated the common and specific metabolic pathways, biological processes, and protein interaction regulatory networks influenced by three liver cancer therapeutics.

Structure-Antioxidant Activity Relationship of Polysaccharides Isolated by Microwave/Ultrasonic-Assisted Extraction from .

To investigate the structure-antioxidant activity relationship, polysaccharides were extracted using ultrasonic (U-PFPS) and microwave/ultrasonic-assisted methods (MU-PFPS). Compared to U-PFPS with a molecular weight of 1.566 × 10 kDa, MU-PFPS exhibited a lower molecular weight of 89.

Identification of Oligosaccharide Isomers Using Electrostatically Asymmetric OmpF Nanopore.

Glycans, unlike uniformly charged DNA and compositionally diverse peptides, are typically uncharged and exhibit rich stereoisomeric diversity in the glycosidic bonds between two monosaccharide units. This heterogeneity of charge and the structural complexity present significant challenges for accurate analysis. Herein, we developed a novel single-molecule oligosaccharide sensor, OmpF nanopore.

Roles of NLRC4 inflammasome in neurological disorders: Mechanisms, implications, and therapeutic potential.

The nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 4 (NLRC4) inflammasome, a vital component of the innate immune system, is known for defending against bacterial infections. However, recent insights have revealed its significant impact on neurological disorders. This comprehensive review discussed the mechanisms underlying the activation and regulation of the NLRC4 inflammasome, highlighting the complexity of its response to cellular stress and damage signals.

Assembly and architecture of endogenous NMDA receptors in adult cerebral cortex and hippocampus.

The cerebral cortex and hippocampus are crucial brain regions for learning and memory, which depend on activity-induced synaptic plasticity involving N-methyl-ᴅ-aspartate receptors (NMDARs). However, subunit assembly and molecular architecture of endogenous NMDARs (eNMDARs) in the brain remain elusive. Using conformation- and subunit-dependent antibodies, we purified eNMDARs from adult rat cerebral cortex and hippocampus.

Development of novel epoxyketone macrocyclic peptidyl proteasome inhibitors through OPA-mediated one-step cyclization of unprotected peptides.

Cyclization is a pivotal strategy for enhancing the drug-like characteristics of polypeptides. To develop potent and metabolically stable proteasome inhibitors, we generated a macrocyclic peptide skeleton using a straightforward and efficient cyclization strategy. Subsequent stability assessments confirmed the practicality of this approach.

Mutant KRAS and CK2 Cooperatively Stimulate SLC16A3 Activity to Drive Intrahepatic Cholangiocarcinoma Progression.

Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy affecting the liver and biliary system. Enhanced understanding of the pathogenic mechanisms underlying iCCA tumorigenesis and the discovery of appropriate therapeutic targets are imperative to improve patient outcomes. Here, we investigated the functions and regulations of solute carrier family 16 member 3 (SLC16A3), which has been reported to be a biomarker of poor prognosis in iCCA.

Uncommon Diterpenoids with Diverse Frameworks from the South China Sea Sponge and Their Anti-inflammatory Activities.

Uncommon diterpenoids with diverse frameworks, including one unexpected iodinated oxa-6/6/6/6-tetracyclic diterpene () and its monobrominated 6/6/6-tricyclic analogue () and one novel isodolastane-type diterpene featuring an unusual aromatic 5/7/6-tricyclic ring system () as well as a related known dolastane-type diterpenoid (), were isolated from the South China Sea sponge . Their structures, including absolute configurations, were established by extensive spectroscopic data analysis, X-ray diffraction analysis, and quantum mechanical-nuclear magnetic resonance and time-dependent density functional theory/electronic circular dichroism calculations. A plausible biosynthetic pathway of new compounds - was proposed.

Secondary Metabolites from the Mangrove Ecosystem-Derived Fungi spp.: Chemical Diversity and Biological Activity.

Mangrove ecosystems have attracted widespread attention because of their high salinity, muddy or sandy soil, and low pH, as well as being partly anoxic and periodically soaked by tides. Mangrove plants, soil, or sediment-derived fungi, especially the species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This paper reviews the structural diversity and biological activity of secondary metabolites isolated from mangrove ecosystem-derived species over the past 5 years (January 2020-October 2024), and 417 natural products (including 170 new compounds, among which 32 new compounds were separated under the guidance of molecular networking and the OSMAC approach) are described.

Software-aided efficient identification of the components of compound formulae and their metabolites in rats by UHPLC/IM-QTOF-MS and an in-house high-definition MS library: Sishen formula as a case.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges. Conventional strategies always exhibit the insufficiencies in overall coverage, analytical efficiency, and degree of automation, and the results highly rely on the personal knowledge and experience. The goal of this work was to establish a software-aided approach, by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) and in-house high-definition MS library, to enhance the identification of prototypes and metabolites of the compound formulae , taking Sishen formula (SSF) as a template.

Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR axis.

Dysfunctional cholesterol metabolism is highly prevalent in patients with hyperuricemia. Both uric acid and cholesterol are independent risk factors for atherosclerosis, contributing to an increased incidence of cardiovascular disease in hyperuricemia. Investigating the pathological mechanisms underlying cholesterol metabolism dysfunction in hyperuricemia is essential.

Clarification of the biosynthetic gene cluster involved in the antifungal prodrug echinocandin B and its robust production in engineered Aspergillus pachycristatus.

Echinocandin antifungals exhibit high efficacy against drug-resistant strains due to their unique mechanism of action. The production of their semi-synthetic precursors relies solely on microbial metabolism, leading to elevated production costs. Anidulafungin, an excellent echinocandin drug, is derived from echinocandin B (ECB), which is industrially produced by Aspergillus pachycristatus.

Butyrolactone I blocks the transition of acute kidney injury to chronic kidney disease in mice by targeting JAK1.

Chronic kidney disease (CKD) is a disease that affects more than 850 million people. Acute kidney injury (AKI) is a common cause of CKD, and blocking the AKI-CKD transition shows promising therapeutic potential. Herein, we found that butyrolactone I (BLI), a natural product, exerts significant nephroprotective effects, including maintenance of kidney function, inhibition of inflammatory response, and prevention of fibrosis, in both folic acid- and ureteral obstruction-induced AKI-CKD transition mouse models.

Intestinal rearrangement of biliopancreatic limbs, alimentary limbs, and common limbs in obese type 2 diabetic mice after duodenal jejunal bypass surgery.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice.

Structure-Based Rational Design and Evaluation of BET-Aurora Kinase Dual-Inhibitors for Treatment of Cancers.

Simultaneous inhibition of the bromodomain and extra-terminal domain and Aurora kinases is a promising anticancer therapeutic strategy. Based on our previous study on BET-kinase dual inhibitors, we employed the molecular docking approach to design novel dual BET-Aurora kinase A inhibitors. Through several rounds of optimization and with the guidance of the solved cocrystal structure of BRD4 bound to inhibitor , we finally obtained a series of highly potent dual BET-Aurora kinase A inhibitors.

Mechanism of HJ11 Decoction in the Treatment of Atherosclerosis Based on Network Pharmacology and Experimental Validation.

Background: HJ11 (HJ11 decoction), which is based on the traditional prescription Si-Miao-Yong-An decoction, has exerted a remarkable effect on atherosclerosis (AS). Nevertheless, the main components and underlying mechanisms of HJ11 for treating AS remain unclear.

Aim Of The Study: This study was designed to elucidate the mechanism of HJ11 in the treatment of AS through network pharmacology and in vivo experimental validation.

Engineered extracellular vesicles loaded in boronated cyclodextrin framework for pulmonary delivery.

Extracellular vesicles (EVs) are promising therapeutic carriers for their ideal nano-size and intrinsic biocompatibility, while rapid clearance and limited targeting ability are the major setbacks of EVs. With minimal absorption into the systemic circulation, inhalation for pulmonary disease therapy minimizes off-target toxicity to other organs and offers a safe and effective treatment for respiratory disorders. Herein, a nano-grid carrier made of boronated cyclodextrin framework (BCF) was prepared for pH/HO responsive release of EVs.

Multiple Enzymes Expressed by the Gut Microbiota Can Transform Typhaneoside and Are Associated with Improving Hyperlipidemia.

The mechanism of multiple enzymes mediated drug metabolism in gut microbiota is still unclear. This study explores multiple enzyme interaction process of typhactyloside (TYP) with gut microbiota and its lipid-lowering pharmacological activity. TYP, with bioavailability of only 2.