A novel importance scores based variable selection approach and validation using a MIR and NIR dataset.

Variable selection is important in spectral analysis for improving interpretation quality and accuracy. This study introduces a novel variable selection process, named "VMHBSC", which consists of six steps, with each letter representing one step. To demonstrate its process and advantages, two datasets were employed, a mid-infrared spectral (MIR) dataset (234 × 7468, sample number × variables) of Chenpi samples (a traditional Chinese medicinal material derived from the dried peel of mature tangerines) and a near-infrared spectral (NIR) dataset (16000 × 256) for modeling competition.

Discovery of a Selective and Orally Bioavailable RET Degrader with Effectiveness in Various Mutations.

The rearranged during transfection (RET) mutation such as the G810C mutation has significantly restricted the clinical application of selective RET inhibitors in the treatment of RET-driven cancers. This study designed and evaluated RET proteolysis targeting chimeras (PROTACs) based on selpercatinib (LOXO-292), identifying as a potent and selective RET PROTAC. effectively inhibited the proliferation of BaF3 cells with various RET mutations, showing IC values of 2.

Characterization and genomic analysis of Abortusequi phage, vB_SalP_LDDK01, and its biocontrol application in donkey meat.

Abortusequi ( Abortusequi) is the primary cause of abortions in equine animals, and can cause serious foodborne illness. Thus, effective biocontrol strategies are needed to decontaminate and control the emergence of foodborne diseases. In recent years, phages have been used as a new strategy for modulating foodborne pathogens and food safety.

Base-Controlled Synthesis of Heteroatom-Embedded 9-Membered Cycloalkynes and 6-Membered Sultams through Copper-Catalyzed Cyclization.

A facile copper-catalyzed, base-controlled cyclization reaction has been developed for the synthesis of 9-membered cycloalkyne and 6-membered heterocycle sultams under mild conditions. This protocol utilizes a copper-catalyzed intramolecular A (alkyne-aldehyde-amine) coupling reaction to efficiently synthesize 9-membered cycloalkyne sultams in yields up to 90%. Alternatively, by substituting NaHCO with DBU, the protocol achieves selective deprotection of the -propargyl group, thereby facilitating the formation of 6-membered heterocyclic sultams, also in high yields.

Oral Delivery of 5-Demethylnobiletin by Media-Milled Black Rice Particle-Stabilized Pickering Emulsion Alleviates Colitis in Mice: Synergistic Effects of Carrier and Loaded Bioactive.

Traditional colitis treatment strategies have issues such as side effects and poor lesion targeting. In this study, a milled black rice particle-stabilized Pickering emulsion (BR-5-DMN) has been developed as a delivery vehicle for 5-demethylnobiletin (5-DMN) to treat colitis. The alleviating effects of three 5-DMN delivery systems: BR-5-DMN, Tween 80 emulsion for upper gastrointestinal delivery, and soybean oil with most 5-DMN entering the colon were compared.

Pregnancy and Nursing Management for Embryo-Transferred and Genetically Modified Rabbits.

With the advancement of scientific research, the demand for gene-edited rabbit models is increasing. However, there are limited pregnancy and feeding management systems for gene-edited rabbits, leading to low survival rates among gene-edited rabbits prepared by many inexperienced researchers. Therefore, proper guidance is essential.

Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.

Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.

Cysteine Leukotriene Receptor Antagonist-Montelukast-Treatment Improves Experimental Abdominal Aortic Aneurysms in Mice.

Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear. Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE).

Novel Cinnamic Acid Derivatives Containing Naproxen as NLRP3 Inhibitors: Synthesis and Evaluation of Their Biological Activity.

Long-term use of naproxen can lead to serious side effects. Inspired by the biological activity of cinnamic acid, a series of cinnamic acid derivatives containing naproxen were designed and synthesized, and their anti-inflammatory activities and mechanisms were explored in vitro. Our results indicated that all of naproxen derivatives showed more significant inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production and had a lower degree of cytotoxicity than that of naproxen.

Effects of Caffeic Acid Phenethyl Ester on Embryonic Development Through Regulation of Mitochondria and Endoplasmic Reticulum.

Caffeic acid phenethyl ester (CAPE) is one of the main active components of the natural medicine propolis, which has antioxidant, anti-tumor, and immunomodulatory activities. This study aimed to analyze the effects and underlying mechanisms of CAPE added to the medium of in vitro cultures on the developmental competence, mitochondria, and endoplasmic reticulum of porcine embryos. The results demonstrated that 1 nM of CAPE significantly improved the quality of porcine embryos, increased the rate of blastocyst formation, and enhanced the proliferation ability.

The isolation, bioactivity, and synthesis of natural products from with anti-HIV activities.

Natural products isolated from have attracted considerable attention from the chemical community due to their unique structures and promising anti-HIV activities. Recent progresses in the isolation and bioactivity studies for these natural molecules were summarized comprehensively. From the 23 previously uncharacterized compounds isolated from the plant , litseaverticillol B demonstrated the most potent anti-HIV activity , with IC ranging from 2 to 3 μg/mL.

Cytotoxicity of natural and synthetic cannabinoids and their synergistic antiproliferative effects with cisplatin in human ovarian cancer cells.

Introduction: Cannabinoids are reported to suppress the growth of ovarian cancer cells, but it is unclear whether structural modifications can improve their cytotoxic effects.

Methods: Herein, an investigation into the antiproliferative effects of natural cannabinoids on human ovarian cancer Caov-3 cells identified cannabidiol (CBD) as the most promising cannabinoid. Furthermore, chemical modifications of CBD yielded a group of derivatives with enhanced cytotoxicity in Caov-3 cells.

An activatable "AIE + ESIPT" fluorescent probe for dual-imaging of lipid droplets and hydrogen peroxide in drug-induced liver injury model.

Background: Drug-induced liver injury (DILI) is one of the most common liver diseases. The crucial role of lipid droplets (LDs) and hydrogen peroxide (HO), two important biomarkers in the pathophysiology of DILI, has spurred considerable efforts to accurately visualize HO and LDs for elucidating their functions in the progression of DILI. However, construction of a single fluorescent probe that is able to simultaneously image HO and LDs dynamics remains to be a challenging task.

Interfacial subregions of SARS-CoV-2 spike RBD to hACE2 affect intermolecular affinity by their distinct roles played in association and dissociation kinetics.

SARS-CoV-2's rapid global transmission depends on spike RBD's strong affinity to hACE2. In the context of binding hot spots well defined, the work investigated how interfacial subregions of SARS-CoV-2 spike RBD to hACE2 affect intermolecular affinity and their potential distinct roles involved in association and dissociation kinetics due to their local structural characteristics. Three spatially consecutive subregions of SARS-CoV-2 RBD were structurally partitioned across RBD's receptor binding motif (RBM).

Ischemic Stroke Induces ROS Accumulation, Maladaptive Mitophagy, and Neuronal Apoptosis in Minipigs.

Reactive oxygen species (ROS)-induced adaptive/maladaptive mitophagy plays an essential role in the pathophysiology of acute ischemic stroke (AIS). However, most studies have been conducted using rodent models, which limits their clinical application. In this study, we aimed to develop porcine models of permanent stroke and observe the pathophysiological alterations caused by acute ischemic stroke, focusing on ROS-induced mitophagy.

Stereocontrolled Synthesis of Cyclobutylamines Enabled by Lewis Acid-Catalyzed (3 + 2 + 2) Cycloaddition/Ring-Opening Strategy of Bicyclo[1.1.0]butanes with Triazinanes.

Herein, we develop a modular and efficient "cycloaddition/ring-opening" strategy of bicyclo[1.1.0]butanes (BCBs) with triazinanes to provide a series of -diastereoselective cyclobutylamines via 2,4-diazabicyclo[4.

Trends and challenges in organoid modeling and expansion with pluripotent stem cells and somatic tissue.

The increasing demand for disease modeling, preclinical drug testing, and long waiting lists for alternative organ substitutes has posed significant challenges to current limitations in organoid technology. Consequently, organoid technology has emerged as a cutting-edge tool capable of accurately recapitulating the complexity of actual organs in physiology and functionality. To bridge the gaps between basic research and pharmaceutical as well as clinical applications, efforts have been made to develop organoids from tissue-derived stem cells or pluripotent stem cells.

Bisphenol A impairs oocyte maturation by dysfunction of cumulus cells.

Bisphenol A (BPA) is a well-known environmental endocrine disruptor that has detrimental effects on reproduction. This study aimed to investigate whether BPA exposure could disrupt the function of cumulus cells and influence oocyte maturation and development. Porcine oocytes at the germinal vesicle stage were exposed to BPA for 44 h.

In vitro and in vivo evaluation of novel ursolic acid derivatives as potential antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA).

The misuse and abuse of antibiotics have led to the increase of drug resistance and the emergence of multi-drug resistant bacteria. Therefore, it is an urgent need to develop novel antimicrobial agents to address this problem. Natural products (NPs) could provide an effective strategy for the discovery of drug due to their wide range of source and biological activities.

Methyl Paraben Affects Porcine Oocyte Maturation Through Mitochondrial Dysfunction.

Parabens are widely used in various industries, which are including chemical, pharmaceutical, food, cosmetic, and plastic processing industries. Among these, methyl paraben (MP) serves as an antimicrobial preservative in processed foods, pharmaceuticals, and cosmetics, and it is particularly detected in baby care products. Studies indicate that MP functions as an endocrine-disrupting compound with estrogenic properties, negatively affecting mitochondrial bioenergetics and antioxidant activity in testicular germ cells.

Discovery of novel KSP-targeting PROTACs with potent antitumor effects in vitro and in vivo.

Kinesin spindle protein (KSP) plays a crucial role during mitosis, making it an attractive target for cancer treatment. Herein, we report the design, synthesis, and evaluation of the first series of KSP degraders by using the utilization of the proteolysis-targeting chimera (PROTAC) technology. Compound 21 was identified as a potent KSP degrader with a DC (concentration causing 50 % of protein degradation) value of 114.