Strengthening biopolymer adhesives through ureolysis-induced calcium carbonate precipitation.

Common adhesives for nonstructural applications are manufactured using petrochemicals and synthetic solvents. These adhesives are associated with environmental and health concerns because of their release of volatile organic compounds (VOCs). Biopolymer adhesives are an attractive alternative because of lower VOC emissions, but their strength is often insufficient.

Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.

The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.

Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach.

Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ-dehydrogenase (ReM2)-catalyzed Δ-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring.

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis.

Computational Analyses of Alkaloids as Green Corrosion Inhibitors on Fe(110).

One of the successful techniques developed for the inhibition of metal corrosion is the utilization of phytochemicals from plant extracts as corrosion inhibitors. Theoretical studies are utilized to predict how organic components behave on metal surfaces and can pave the way for the development and synthesis of innovative, efficient corrosion inhibitors. However, atomic-level insights into the inhibition mechanisms of these green components are still needed.

The History of Studies on Oxetane Ring Formation in Paclitaxel Biosynthesis.

There is no doubt that breakthroughs in the enzyme-mediated formation of the oxetane ring in paclitaxel biosynthesis constitute significant milestones in the biosynthesis of complex natural products. In this review, we summarize the understanding of the biosynthesis of the oxetane ring of paclitaxel from different viewpoints. Generally, it covers five aspects, (1) a different understanding of the mechanistic formation of the oxetane ring on the basis of sound chemical reasoning, (2) a reasonable speculation of the biosynthetic pathways and suitable surrogate substrates for oxetane ring formation based on the natural and chemical logical analysis, (3) Taxus genome-enabled enzymes identification, (4) the discovery of different enzymes that mediate oxetane ring formation, and (5) a mechanistic investigation involving the use of isotopic labelling experiments and quantum chemical calculations.

Ph3P-I2-mediated Syntheses of C-12 Carboxamide Indoloquinazolines and 2-Aminosubstituted-indol-3-ones from Isatins and Amines.

The Ph3P-I2-mediated reactions between isatins and amines were extensively investigated leading to the discovery of highly selective and divergent routes toward the synthesis of two distinct classes of indole-based frameworks. Through a strategic design of the reaction paths, we overcome potential side reactions to achieve convenient and straightforward one-pot methods to access either indoloquinazolines with C-12 carboxamide or 2-aminosubstituted indol-3-ones using the same reagent system. Mechanistic studies reveal the role of Ph3P-I2 in governing product selectivity, providing an efficient route to novel fused-indolone derivatives with promising applications in drug discovery and medicinal chemistry.

Helical Quintulene: Synthesis, Chirality, and Supramolecular Assembly.

Quintulene is a quintuply symmetrical cycloarene with a positively curved molecular geometry. First described by Staab and Sauer in 1984, its successful synthesis was not achieved until 2020. Due to the challenges posed by its positive curvature, structural extensions of quintulene have been studied rarely.

A ratiometric fluorescent probe for sensitively tracking peroxynitrite during drug-induced hepatotoxicity.

As one of the essential components of reactive oxygen species (ROS), peroxynitrite (ONOO-) plays an indispensable role in redox homeostasis and signal transduction processes, and its deviant levels are associated with numerous clinical diseases. Therefore, accurate and rapid detection of intracellular ONOO- levels is crucial for revealing its role in physiological and pathological processes. Herein, we constructed a ratiometric fluorescent probe to detect ONOO- levels in biological systems.

Activation of Primary C-H Bonds in Oxidative Cyclizations of Tambjamines Catalyzed by Rieske Oxygenases TamC and TamC.

Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591).

Essential oil composition, antidiabetic, cytotoxicity, antimicrobial, antioxidant activity, and molecular modeling analysis of secondary metabolites from .

, known as "Dhumuugaa" in Afan Oromo and "Sensel" or "Smiza" in Amharic, is traditionally used to treat ailments such as scabies, fever, asthma, diarrhea, malaria, and more. This study explored the chemical composition and biological activity of its extracts and isolated compounds. The essential oils were extracted using the hydrodistillation method, and their chemical composition was evaluated using GC-MS.

Localized Nanopore Fabrication in Silicon Nitride Membranes by Femtosecond Laser Exposure and Subsequent Controlled Breakdown.

Controlled breakdown has emerged as an effective method for fabricating solid-state nanopores in thin suspended dielectric membranes for various biomolecular sensing applications. On an unpatterned membrane, the site of nanopore formation by controlled breakdown is random. Nanopore formation on a specific site on the membrane has previously been realized using local thinning of the membrane by lithographic processes or laser-assisted photothermal etching under immersion in an aqueous salt solution.

Interplay between Two Structure Types in the Incommensurately Modulated ATaSe Compounds (A = Rb, Cs).

Incommensurately modulated crystals are a rare class of materials that are notoriously difficult to characterize properly. We have synthesized two new incommensurately modulated compounds, RbTaSe and CsTaSe, based on the MQ (M = Nb, Ta; Q = S, Se) unit using high-temperature solid-state synthesis. Using superspace crystallography in combination with second harmonic generation measurements, we confirmed both materials to be noncentrosymmetric, falling into the superspace group 1(αβγ)0, while the basic cell suggests 2/.

Contribution of Coal Tar Sources to Polycyclic Aromatic Compounds and Associated Ecological Risk in Lake Ontario Sediments: Inference from a Novel Marker.

Coal tar-related products as a source of polycyclic aromatic compounds (PACs) are particularly concerning due to high PAC concentrations and inadequate source management. Benzo[b]carbazole, a benzocarbazole isomer exclusively found in coal tar-derived products, acts as an ideal marker to distinguish coal tar sources from others, enabling more robust quantification of coal tar contributions to PACs. To evaluate the historical and recent contributions of coal tar-related sources to the levels of PACs in Lake Ontario and associated ecological risk, we analyzed 31 PACs and 3 BCBz isomers in surface sediments and a sediment core.

Enhancing Electron Donor-Acceptor Complex Photoactivation with a Stable Perylene Diimide Metal-Organic Framework.

Electron donor-acceptor complexes are commonly employed to facilitate photoinduced radical-mediated organic reactions. However, achieving these photochemical processes with catalytic amounts of donors or acceptors can be challenging, especially when aiming to reduce catalyst loadings. Herein, we have unveiled a framework-based heterogenization approach that significantly enhances the photoredox activity of perylene diimide species in radical addition reactions with alkyl silicates by promoting faster and more efficient electron donor-acceptor complex formation.

Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma.

Background: Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance.

EndoVIA for quantifying A-to-I editing and mapping the subcellular localization of edited transcripts.

Adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a prevalent post-transcriptional modification that is vital for numerous biological functions. Given that this modification impacts global gene expression, RNA localization, and innate cellular immunity, dysregulation of A-to-I editing has unsurprisingly been linked to a variety of cancers and other diseases. However, our current understanding of the underpinning mechanisms that connect dysregulated A-to-I editing and disease processes remains limited.

A probe-based capture enrichment method for detection of A-to-I editing in low abundance transcripts.

Exactly two decades ago, the ability to use high-throughput RNA sequencing technology to identify sites of editing by ADARs was employed for the first time. Since that time, RNA sequencing has become a standard tool for researchers studying RNA biology and led to the discovery of RNA editing sites present in a multitude of organisms, across tissue types, and in disease. However, transcriptome-wide sequencing is not without limitations.

Structural analysis of human ADAR2-RNA complexes by X-ray crystallography.

Adenosine deaminases acting on RNAs (ADARs) are a class of RNA editing enzymes found in metazoa that catalyze the hydrolytic deamination of adenosine to inosine in duplexed RNA. Inosine is a nucleotide that can base pair with cytidine, therefore, inosine is interpreted by cellular processes as guanosine. ADARs are functionally important in RNA recoding events, RNA structure modulation, innate immunity, and can be harnessed for therapeutically-driven base editing to treat genetic disorders.

En masse evaluation of RNA guides (EMERGe) for ADARs.

Adenosine Deaminases Acting on RNA (ADARs) convert adenosine to inosine in duplex RNA, and through the delivery of guide RNAs, can be directed to edit specific adenosine sites. As ADARs are endogenously expressed in humans, their editing capacities hold therapeutic potential and allow us to target disease-relevant sequences in RNA through the rationale design of guide RNAs. However, current design principles are not suitable for difficult-to-edit target sites, posing challenges to unlocking the full therapeutic potential of this approach.

The multifaceted roles of retinoids in eye development, vision, and retinal degenerative diseases.

Vitamin A (all-trans-retinol; at-Rol) and its derivatives, known as retinoids, have been adopted by vertebrates to serve as visual chromophores and signaling molecules, particularly in the eye/retina. Few tissues rely on retinoids as heavily as the retina, and the study of genetically modified mouse models with deficiencies in specific retinoid-metabolizing proteins has allowed us to gain insight into the unique or redundant roles of these proteins in at-Rol uptake and storage, or their downstream roles in retinal development and function. These processes occur during embryogenesis and continue throughout life.

Safety of interleukin inhibitors in patients with plaque psoriasis and history of neoplasms: a multicenter retrospective study - IL PSO (Italian landscape psoriasis).

Interleukin (IL) inhibitors are increasingly used in the management of moderate-to-severe plaque psoriasis. However, their use in patients with a history of cancer is debated. We conducted a multicenter retrospective study across nine Italian Dermatology Units to assess the real-world effectiveness and safety of IL inhibitors (IL-23, IL-17, IL-12/23) in 136 oncological patients with moderate-to-severe plaque psoriasis.

Low progesterone levels and their role in the co-existence of polycystic ovary syndrome and rheumatoid arthritis: a comprehensive analysis among Iraqi patient.

Polycystic ovarian syndrome (PCOS) is a low-grade and chronic inflammation defined by irregular hormonal status that primarily triggers females in their reproductive age. Multi cysts are a primary manifestation of PCOS; a high level of androgen production characterizes the condition via ovaries. Rheumatoid arthritis (RA) is a chronic, systemic, and symmetrical inflammatory autoimmune disease that affects 1-2% of adults.

Integrative multi-omics analysis of autism spectrum disorder reveals unique microbial macromolecules interactions.

Introduction: Gut microbiota alterations have been implicated in Autism Spectrum Disorder (ASD), yet the mechanisms linking these changes to ASD pathophysiology remain unclear.

Objectives: This study utilized a multi-omics approach to uncover mechanisms linking gut microbiota to ASD by examining microbial diversity, bacterial metaproteins, associated metabolic pathways and host proteome.

Methods: The gut microbiota of 30 children with severe ASD and 30 healthy controls was analyzed.