Mode of action analysis for mouse liver tumor formation by MGK-264 and human relevance.

MGK-264, an insecticidal synergist, has been shown to increase the incidence of liver tumors in male and female mice. As MGK-264 is not a genotoxic compound, a series of investigative studies were conducted to elucidate the mode of action (MoA) for liver tumor production by MGK-264. Male and female CD-1 mice were given diets containing MGK-264 at 400, 3000, and 6000 ppm for 7 and/or 14 days.

Prediction of human pharmacokinetics of procymidone and its major phase I and II metabolites using a PBPK model with enterohepatic circulation.

Physiologically based pharmacokinetic (PBPK) modeling is a valuable approach for addressing the scarcity of human toxicokinetic data, particularly in the risk assessment of agrochemicals. While numerous PBPK models have been developed to describe various pharmacokinetics processes, modeling the complex kinetics of enterohepatic circulation remains challenging. Procymidone, a widely used fungicide, undergoes initial metabolism to hydroxylated-procymidone, an active metabolite with antiandrogenic properties, followed by glucuronidation.

Short-term outcomes of modified Lapidus procedure using the InCore® Lapidus System for hallux valgus: Case series of four cases.

Introduction: Hallux valgus is a common foot deformity often associated with first tarsometatarsal (TMT) joint instability. The Lapidus procedure, involving first TMT joint arthrodesis, is a well-established surgical procedure for severe cases, but the issue lies in the method of fixation. The InCore® Lapidus System is a novel intramedullary fixation system for modified Lapidus procedure.

Mode of action analysis for rat thyroid gland follicular cell tumor formation by MGK-264 and human relevance.

MGK-264 (N-(2-ethylhexyl)-5-norborene-2.3-dicarboximide or N-octyl bicycloheptene dicarboximide), an insecticidal synergist, produced thyroid gland follicular cell (TFC) tumors in male Sprague-Dawley (SD) rats in a carcinogenicity study. The purpose of this study was to evaluate the possible mode of action (MoA) for TFC tumor induction by MGK-264 and its relevance to humans.

Ordered Graphane Nanoribbons Synthesized via High-Pressure Diels-Alder Polymerization of 2,2'-Bipyrazine.

Graphane shares the same two-dimensional honeycomb structure of graphene, but its saturated carbon skeleton gives rise to a bandgap and therefore provides more possibilities for the development of novel carbon-based semiconductors. However, the hydrogenation of graphene usually leads to disordered and incompletely hydrogenated graphane, and the precise synthesis of graphane with a specific configuration is still very challenging. Here, we synthesized a crystalline graphane nanoribbon (GANR) via pressure-induced polymerization of 2,2'-bipyrazine (BPZ).

Solid-State Alder-Ene Reaction of 1-Hexene under High Pressure.

The Alder-ene reaction is a chemical reaction between an alkene with an allylic hydrogen, and it provides an efficient method to construct the C-C bond. Traditionally, this reaction requires catalysts, high temperatures, or photocatalysis. In this study, we reported a high-pressure-induced solid-state Alder-ene reaction of 1-hexene at room temperature without a catalyst.

High Microsatellite but No Mitochondrial DNA Variation in an Invasive Japanese Mainland Population of the Parasitoid Wasp .

Invasive populations are predicted to have reduced genetic diversity due to bottleneck events. The parasitoid wasp was previously identified only in the subtropical area of the southern Japanese islands and Taiwan but was recently found in the temperate area of the Japanese mainland. The distribution of this species may have recently expanded northward due to factors such as climatic events and global warming.

High-Pressure Polymerization of Phenol toward Degree-4 Carbon Nanothread.

Saturated sp-carbon nanothreads (CNTh) have garnered significant interest due to their predicted high Young's modulus and thermal conductivity. While the incorporation of heteroatoms into the central ring has been shown to influence the formation of CNTh and yield chemically homogeneous products, the impact of pendant groups on the polymerization process remains underexplored. In this study, we investigate the pressure-induced polymerization of phenol, revealing two phase transitions occurring below 0.

Pressure-induced polymerization of 1,4-difluorobenzene towards fluorinated diamond nanothreads.

Pressure-induced polymerization (PIP) of aromatic molecules has emerged as an effective method for synthesizing various carbon-based materials. The selection of suitable functionalized molecular precursors is crucial for obtaining the desired structures and functions. In this work, 1,4-difluorobenzene (1,4-DFB) was selected as the building block for PIP.

Association of recent antibiotic exposure and coronary artery lesions in Kawasaki disease: nationwide study.

Objectives: To investigate the relationship between recent antibiotic exposure and the development of coronary artery lesions (CALs) during the clinical course of Kawasaki disease (KD).

Design: Data were obtained from the 25th nationwide epidemiological survey of KD conducted in Japan from 2017 to 2018. Baseline characteristics and clinical course were compared between Antibiotics (+) and Antibiotics (-) groups.

High-Pressure Behaviors of Hydrogen Bonds in Fluorine-Doped Brucite.

Brucite, Mg(OH) (3̅1, = 1), is a prototype material for studying hydrogen bonds in solid hydroxides. In this study, substitutional effects of fluorine (F) on the hydrogen-bonding geometries of hydrogenated and deuterated brucite were investigated under ambient conditions and at high pressure using combined experimental methods of neutron powder diffraction, Raman spectroscopy, and infrared (IR) spectroscopy. Under ambient conditions, neutron powder diffraction results showed that F substitution decreased the donor-acceptor distance and increased the hydroxyl covalent bond lengths of both hydrogenated and deuterated brucite, strengthening the hydrogen bond.

Exocrine gland-resident memory CD8 T cells use mechanosensing for tissue surveillance.

Tissue-resident CD8 T cells (T) continuously scan peptide-MHC (pMHC) complexes in their organ of residence to intercept microbial invaders. Recent data showed that T lodged in exocrine glands scan tissue in the absence of any chemoattractant or adhesion receptor signaling, thus bypassing the requirement for canonical migration-promoting factors. The signals eliciting this noncanonical motility and its relevance for organ surveillance have remained unknown.

A high-temperature and high-pressure cell for in situ visualization of reaction processes by neutron imaging.

This study developed a high-temperature and high-pressure (HTHP) cell for in situ neutron imaging of hydrothermal reactions. The cell's maximum temperature and pressure were 500 °C and 50 MPa, respectively, and its vessel for observing reactions comprised SUS316 stainless steel. Neutron transmission images were obtained to observe the behavior of sub- and supercritical water and the decomposition of two plastics (polypropylene and polyethylene) at HTHP.

Frequency of cytosine methylation in the adjacent regions of soybean retrotransposon depends on chromosomal location.

Mobilization of transposable elements (TEs) is suppressed by epigenetic mechanisms involving cytosine methylation. However, few studies have focused on clarifying relationships between epigenetic influences of TEs on the adjacent DNA regions and time after insertion of TEs into the genome and/or their chromosomal location. Here we addressed these issues using soybean retrotransposon .

Regulator of G-protein signaling 1 critically supports CD8 T cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member is one of the most up-regulated genes in tissue-resident memory (T) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking.

Novel approach for verification of a human PBPK modeling strategy using chimeric mice in the health risk assessment of epyrifenacil.

In the human risk assessment by physiologically based pharmacokinetic modeling (PBPK), verification of the modeling strategy and confirmation of the reliability of the output data are important when the clinical data are not available. A new herbicide, epyrifenacil, is metabolized to S-3100-CA in mammals and causes hepatotoxicity in mice. S-3100-CA is transferred to the liver by transporters and eliminated by biliary excretion and metabolism.

Three-dimensional Imaging Reveals Immune-driven Tumor-associated High Endothelial Venules as a Key Correlate of Tumor Rejection Following Depletion of Regulatory T Cells.

High endothelial venules (HEV) are specialized post capillary venules that recruit naïve T cells and B cells into secondary lymphoid organs (SLO) such as lymph nodes (LN). Expansion of HEV networks in SLOs occurs following immune activation to support development of an effective immune response. In this study, we used a carcinogen-induced model of fibrosarcoma to examine HEV remodeling after depletion of regulatory T cells (Treg).

A divergent RWP-RK transcription factor determines mating type in heterothallic Closterium.

The Closterium peracerosum-strigosum-littorale complex (Closterium, Zygnematophyceae) has an isogamous mating system. Members of the Zygnematophyceae are the closest relatives to extant land plants and are distantly related to chlorophytic models, for which a genetic basis of mating type (MT) determination has been reported. We thus investigated MT determination in Closterium.

Theoretical Validation of Skin Sensitization Assay "ADRA" Using the Products Formed by Nucleophilic Reagents and Chemicals.

Amino acid derivative reactivity assay (ADRA) is an assay for assessing the skin sensitization potential of chemicals by evaluating the reactivity of nucleophilic reagents that mimic skin proteins. -(2-(1-Naphthyl)acetyl)-l-cysteine (NAC) and α--(2-(1-naphthyl)acetyl)-l-lysine (NAL), used as nucleophilic reagents, are small-molecule derivatives of two different amino acids, each with a naphthalene ring attached. The rate of decrease in the amount of NAC or NAL in the reaction solution is evaluated in this assay as an indicator of the test substance's skin sensitization ability.

Current overview on the genetic basis of key genes involved in soybean domestication.

Modern crops were created through the domestication and genetic introgression of wild relatives and adaptive differentiation in new environments. Identifying the domestication-related genes and unveiling their molecular diversity provide clues for understanding how the domesticated variants were selected by ancient people, elucidating how and where these crops were domesticated. Molecular genetics and genomics have explored some domestication-related genes in soybean ().

Evaluation of the mode of action and human relevance of liver tumors in male mice treated with epyrifenacil.

Epyrifenacil (trademark name: Rapidicil®), a novel protoporphyrinogen oxidase (PPO)-inhibiting herbicide, induces hepatocellular adenomas and carcinomas in male CD-1 mice after 78 weeks treatment. The mode of action (MOA) of these mouse liver tumors and their relevance to humans was assessed based on the 2006 International Programme on Chemical Safety (IPCS) Human Relevance Framework. Epyrifenacil is not genotoxic and induced liver tumors via the postulated porphyria-mediated cytotoxicity MOA with the following key events: (#1) PPO inhibition; (#2) porphyrin accumulation; (#3) hepatocellular injury; with (#4) subsequent regenerative cell proliferation; and ultimately (#5) development of liver tumors.

Atomic distribution and local structure in-situ VII from in situ neutron diffraction.

Ice polymorphs show extraordinary structural diversity depending on pressure and temperature. The behavior of hydrogen-bond disorder not only is a key ingredient for their structural diversity but also controls their physical properties. However, it has been a challenge to determine the details of the disordered structure in ice polymorphs under pressure, because of the limited observable reciprocal space and inaccuracies related to high-pressure techniques.

Naïve Primary Mouse CD8 T Cells Retain Immune Responsiveness After Electroporation-Based CRISPR/Cas9 Genetic Engineering.

CRISPR/Cas9 technology has revolutionized genetic engineering of primary cells. Although its use is gaining momentum in studies on CD8 T cell biology, it remains elusive to what extent CRISPR/Cas9 affects function of CD8 T cells. Here, we optimized nucleofection-based CRISPR/Cas9 genetic engineering of naïve and -activated primary mouse CD8 T cells and tested their immune responses.

KRAS mutation in intrahepatic cholangiocarcinoma: Linkage with metastasis-free survival and reduced E-cadherin expression.

Background And Aims: Although KRAS mutations are the major driver of intrahepatic cholangiocarcinoma (ICC), their role remains unexplored. This study aimed to elucidate the prognostic effects, association with clinicopathologic characteristics and potent functions of KRAS mutations in ICC.

Methods: A hundred and seven resected stage I-III ICCs were analysed for KRAS mutation status and its link with clinicopathological features.