Selective Synthesis of Cyclopeptides with a 2-Oxindole or 3a-Hydroxy-hexahydropyrrolo-[2,3-]indole Structure by Cytochrome P450 Enzymes.

The structural groups of 2-oxindole and tricyclic 3a-hydroxy-hexahydropyrrolo-[2,3-]indole (HO-HPI) are important pharmacophores. Chemical synthesis of complex alkaloids containing a 2-oxindole or HO-HPI moiety, especially the latter one, has been a long-standing challenge. Herein, we characterized the P450 enzyme AfnD, and its homologue proteins, HmtT, ClpD, KtzM, and LtzR, as cyclopeptide 2-oxindole and HO-HPI monooxygenases (cpOPMOs) that could introduce a 2-oxindole or HO-HPI moiety into the tryptophan-containing cyclopeptides in a pH-dependent manner.

The Hoverfly Attracting Property of a Methyl Salicylate-Containing ()-β-Farnesene Analog (3e) and Potential Mechanism by Mediating the EcorOBP15 and EcorOR3.

Using natural enemies provides a sustainable method to control major agricultural pests. Hoverflies are significant natural enemies of aphids and efficient pollinators. Herbivore-induced plant volatiles (HIPVs), including ()-β-farnesene (EBF) and methyl salicylate (MeSA), are key olfactory cues mediating hoverflies behavior.

Hydrolysis, Ligand Exchange, and Redox Properties of Vanadium Compounds: Implications of Solution Transformation on Biological, Therapeutic, and Environmental Applications.

Vanadium is a transition metal with important industrial, technological, biological, and biomedical applications widespread in the environment and in living beings. The different reactions that vanadium compounds (VCs) undergo in the presence of proteins, nucleic acids, lipids and metabolites under mild physiological conditions are reviewed. In the environment vanadium is present naturally or through anthropogenic sources, the latter having an environmental impact caused by the dispersion of VCs in the atmosphere and aquifers.

Unusual Phospholipids from Linked to Depression.

A multifactorial association study detected a probable causal connection between the prevalence of in the gut microbiome and the incidence of major depressive disorder (MDD) in the human host. A bioassay-guided fractionation approach identified bacterially produced metabolites that induced pro-inflammatory immune responses. The metabolites are unusual phospholipids that resemble conventional cardiolipins, in which diethanolamine (DEA) replaces the central glycerol.

Inhibition of EphB4 Receptor Signaling by Ephrin-B2-Competitive and Non-Competitive DARPins Prevents Angiogenesis.

The receptor tyrosine kinase EphB4 is involved in tumor angiogenesis, proliferation, and metastasis. Designed ankyrin repeat proteins (DARPins) binding to the EphB4 extracellular domain were identified from a combinatorial library using phage display. Surface plasmon resonance (SPR) allowed us to distinguish between DARPins that either compete with the EphB4 ligand ephrin-B2 for binding to a common site or target a different epitope.

Quaternary Ammonium Compounds: A New Driver and Hidden Threat for Prevalence in Hospital Wastewater and Human Feces.

The emergence of mobile colistin resistance gene has attracted global attention. The prevalence of -positive (MCRPEC) in humans largely decreased following the ban of colistin as an animal growth promoter in China. However, the prevalence of MCRPEC in the hospital environment and the relationship between disinfectants and remain unclear.

Identification of Key Amino Acids in the A Domains of Polymyxin Synthetase Responsible for 2,4-Diaminobutyric Acid Adenylation in NBRC3020 Strain.

Developing novel nonribosomal peptides (NRPs) requires a comprehensive understanding of the enzymes involved in their biosynthesis, particularly the substrate amino acid recognition mechanisms in the adenylation (A) domain. This study focused on the A domain responsible for adenylating l-2,4-diaminobutyric acid (l-Dab) within the synthetase of polymyxin, an NRP produced by NBRC3020. To date, investigations into recombinant proteins that selectively adenylate l-Dab─exploring substrate specificity and enzymatic activity parameters─have been limited to reports on A domains found in enzymes synthesizing l-Dab homopolymers (pldA from USE31 and pddA from NBRC15115), which remain exceedingly rare.

Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.

The nascent field of targeted protein degradation (TPD) could revolutionize biomedicine due to the ability of degrader molecules to selectively modulate disease-relevant proteins. A key limitation to the broad application of TPD is its dependence on small-molecule ligands to target proteins of interest. This leaves unstructured proteins or those lacking defined cavities for small-molecule binding out of the scope of many TPD technologies.

Gold-Modified Covalent Organic Frameworks-Assisted Laser Desorption/Ionization Mass Spectrometry for Analysis of Metabolites Induced by Triclosan Exposure.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) holds great promise for the rapid and sensitive detection of biomolecules, but its precise detection of small molecule metabolites is hindered by severe background interference from the organic matrix in the low molecular weight range. To address this issue, nanomaterials have commonly been utilized as substrates in LDI-MS. Among them, covalent organic frameworks (COFs), known for their unique optical absorption and structural properties, have garnered significant attention.

Two-Dimensional Tantalum Carbo-Selenide for Hydrogen Evolution.

Herein, we report the synthesis of two-dimensional TaSeC (2D-TaSeC) nanosheets using electrochemical lithiation in multilayer TaSeC followed by sonication in deionized water. Multilayer TaSeC was obtained via solid-state synthesis of FeTaSeC followed by chemical etching of Fe. 2D-TaSeC exhibited promising electrocatalytic activity for the hydrogen evolution reaction from water compared to multilayer TaSeC and 2D-TaSe.

Regulation of Bone Remodeling by Metal-Phenolic Networks for the Treatment of Systemic Osteoporosis.

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal-phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts.

PEDOT/Polypyrrole Core-Sheath Fibers for Use as Conducting Polymer Artificial Muscles.

Electropolymerized polypyrrole (PPy) is considered as one of the promising polymers for use in ionic-electroactive or conducting polymer (CP) actuators. Its electromechanical properties surpass those of other prominent CPs such as poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT/PSS) or polyaniline. However, freestanding and linear contracting actuator fibers made solely of electropolymerized PPy are not available yet.

Detection of STAT4 in Multiple Sclerosis patients by polymerase chain reaction and flowcytometry.

Multiple sclerosis (MS) is a disease of the central nervous system, characterized by progressive demyelination and inflammation. MS is characterized by immune system attacks on the myelin sheath surrounding nerve fibers. Genome-wide association studies revealed a polymorphism in the signal transducer and activator of transcription 4 (STAT4) gene that increases risk for MS.

Factors Associated With Cocaine Use at 17 and 20 Years Old: A Longitudinal Analysis of a Nationally Representative Cohort.

Purpose: Despite growing concerns about trends in cocaine use, there is a shortage of longitudinal research that prospectively examines risk and protective factors associated with cocaine initiation and use in general youth populations. This study addresses this gap.

Methods: Growing Up in Ireland is a nationally representative cohort.

Damage activates EXG1 and RLP44 to suppress vascular differentiation during regeneration in Arabidopsis.

Plants possess remarkable regenerative abilities to form de novo vasculature after damage and in response to pathogens that invade and withdraw nutrients. To look for common factors that affect vascular formation upon stress, we searched for Arabidopsis thaliana genes differentially expressed upon Agrobacterium infection, nematode infection and plant grafting. One such gene was cell wall related and highly induced by all three stresses and was named ENHANCED XYLEM AND GRAFTING1 (EXG1) since mutations in it promoted ectopic xylem formation in Vascular cell Induction culture System Using Arabidopsis Leaves (VISUAL) and enhanced graft formation.

Pitfalls in performing genome-wide association studies on ratio traits.

Genome-wide association studies (GWAS) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator.

Postoperative pancreatic fistula risk assessment using digital pathology based analyses at the parenchymal resection margin of the pancreas - Results from the randomized multicenter RECOPANC trial.

Background: In pancreatic surgery Postoperative pancreatic fistula (POPF) represents the most dreaded complication, for which pancreatic texture is acknowledged as one of the strongest predictors. No consensual objective reference has been defined to evaluate the pancreas composition. The presented study aimed to mine histology data of the pancreatic tissue composition with AI assist and correlate it with clinic-pathological parameters derived from the RECOPANC study.

Strengthening serological studies: the need for greater geographical diversity, biobanking, and data-accessibility.

Serological studies uniquely strengthen infectious disease surveillance, expanding prevalence estimates to encompass asymptomatic infections, and revealing the otherwise inapparent landscape of immunity, including who is and is not susceptible to infection. They are thus a powerful complement to often incomplete epidemiological and public health measures (administrative measures of vaccination coverage, incidence estimates, etc.).

Urinary biomarkers of preeclampsia: An update.

Preeclampsia (PE), a pregnancy-related syndrome, has motivated extensive research to understand its pathophysiology and develop early diagnostic methods. 'Omic' technologies, focusing on genes, mRNA, proteins, and metabolites, have revolutionized biological system studies. Urine emerges as an ideal non-invasive specimen for omics analysis, offering accessibility, easy collection, and stability, making it valuable for identifying biomarkers.

Multiomics in cancer biomarker discovery and cancer subtyping.

The advent of multiomics has ushered in a new era of cancer research characterized by integrated genomic, transcriptomic and proteomic analysis to unravel the complexities of cancer biology and facilitate the discovery of novel biomarkers. This chapter provides a comprehensive overview of the concept of multiomics, detailing the significant advances in the underlying technologies and their contributions to our understanding of cancer. It delves into the evolution of genomics and transcriptomics, breakthroughs in proteomics, and overarching progress in multiomic methodologies, highlighting their collective impact on cancer biomarker discovery.

Ion mobility spectrometry and ion mobility-mass spectrometry in clinical chemistry.

Advancements in clinical chemistry have major implications in terms of public health, prompting many clinicians to seek out chemical information to aid in diagnoses and treatments. While mass spectrometry (MS) and hyphenated-MS techniques such as LC-MS or tandem MS/MS have long been the analytical methods of choice for many clinical applications, these methods routinely demonstrate difficulty in differentiating between isomeric forms in complex matrices. Consequently, ion mobility spectrometry (IM), which differentiates molecules on the basis of size, shape, and charge, has demonstrated unique advantages in the broad application of stand-alone IM and hyphenated IM instruments towards clinical challenges.

In vitro photodynamic therapy of Candida albicans, the cause of vulvovaginal candidiasis, is enhanced by Bacillus and Enterococcus probiotics.

Background: Candida albicans is the primary cause of vulvovaginal candidiasis, a worldwide health concern for women. The use of supplemental methods, such as antimicrobial photodynamic therapy (aPDT) and probiotics, was promoted by the ineffectiveness of the existing antifungal drugs.

Methods: This study examines the combined effects of probiotics (Bacillus and Enterococcus isolated from the fermented pickles) and PDT (using red laser (655 nm, 18 J/cm) as a light source and methylene blue dye (30 mg/mL) as a photosensitizer) on the in vitro virulence activity of C.

Synthesis, biological evaluation and molecular docking studies of flavonol-3-O-β-D-glycoside as a potential inhibitor of SARS-CoV-2 main protease (3CLpro) in drug development for COVID-19.

The COVID-19 pandemic began in March 2020 and has affected many countries and infected over a million people. It has had a serious impact on people's physical and mental health, daily life and the global economy. Today, many drugs show limited efficacy in the treatment of COVID-19 and studies to develop effective drugs continue.