Astrocyte-Specific Phenotyping of FAD as an Alzheimer's Disease Mouse Model.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, characterized by memory decline and behavioral changes. Its pathological features include senile plaques, neurofibrillary tangles, and reactive gliosis, comprising abnormal accumulations of β-amyloid peptide (Aβ) and hyperphosphorylated tau protein surrounded by reactive astrocytes and microglia. Recently, it has emerged that severe reactive astrocytes and MAOB-dependent production of GABA and HO are the real causes of learning and memory impairment and neurodegeneration.

Strengthening Effect Evaluation of Developed Stiff-Type Polyurea Sprayed on Masonry Beam Surface Under Static Loading in Experimental and Numerical Tests.

Recently, deteriorated masonry structures aged over 30 years have shown serious structural problems. Simple and rapid maintenance plans are urgently needed for aging masonry structures. Polyurea (PU) is an effective retrofitting material for aging structures due to its easy spray application.

Epigenetic control of Topoisomerase 1 activity presents a cancer vulnerability.

DNA transactions introduce torsional constraints that pose an inherent risk to genome integrity. While topoisomerase 1 (TOP1) activity is essential for removing DNA supercoiling, aberrant stabilization of TOP1:DNA cleavage complexes (TOP1ccs) can result in cytotoxic DNA lesions. What protects genomic hot spots of topological stress from aberrant TOP1 activity remains unknown.

Structural Modification and Characteristics of Lappaconitine Alkaloid for the Discovery of Bioactive Components by Hypervalent Iodine Reagent.

Lappaconitine, a diterpene alkaloid isolated from Nakai, exhibits a wide range of biological activities, making it a promising candidate for the development of novel derivatives with therapeutic potential. In our research, we executed a two-step transformation via oxidative cleavage of lappaconitine's vicinal diol using the hypervalent iodine reagent PhI(OAc), followed by strong alkaline hydrolysis. This approach yielded four new unanticipated compounds, whose structures were identified by spectroscopic methods and/or X-ray crystallography.

Prognostic value of lateral lymph node metastasis in pretreatment MRI for rectal cancer in patients undergoing neoadjuvant chemoradiation followed by surgical resection without lateral lymph node dissection: A systemic review and meta-analysis.

Purpose: To systematically review and meta-analyze the prognostic significance of lateral lymph node metastasis (LLNM) on pretreatment MRI in patients with rectal cancer who undergo neoadjuvant chemoradiation followed by curative surgical resection without lateral lymph node dissection (LLND).

Methods: We searched the MEDLINE and EMBASE databases until September 27, 2023, utilizing the following search terms: (rectal OR rectum OR colorectal) AND (lateral OR sidewall) AND (lymph OR node). The QUIPS tool was employed to evaluate methodological quality.

Prognostication of lung adenocarcinomas using CT-based deep learning of morphological and histopathological features: a retrospective dual-institutional study.

Objectives: To develop and validate CT-based deep learning (DL) models that learn morphological and histopathological features for lung adenocarcinoma prognostication, and to compare them with a previously developed DL discrete-time survival model.

Methods: DL models were trained to simultaneously predict five morphological and histopathological features using preoperative chest CT scans from patients with resected lung adenocarcinomas. The DL score was validated in temporal and external test sets, with freedom from recurrence (FFR) and overall survival (OS) as outcomes.

Deep learning-based iodine contrast-augmenting algorithm for low-contrast-dose liver CT to assess hypovascular hepatic metastasis.

Purpose: To investigate the image quality and diagnostic performance of low-contrast-dose liver CT using a deep learning-based iodine contrast-augmenting algorithm (DLICA) for hypovascular hepatic metastases.

Methods: This retrospective study included 128 patients who underwent contrast-enhanced dual-energy CT for hepatic metastasis surveillance between July 2019 and June 2022 using a 30% reduced iodine contrast dose in the portal phase. Three image types were reconstructed: 50-keV virtual monoenergetic images (50-keV VMI); linearly blended images simulating 120-kVp images (120-kVp); and post-processed 120-kVp images using DLICA (DLICA 120-kVp).

Unlocking the Potential of A-Site Ca-Doped LaCoFeO: A Redox-Stable Cathode Material Enabling High Current Density in Direct CO Electrolysis.

Massive carbon dioxide (CO) emission from recent human industrialization has affected the global ecosystem and raised great concern for environmental sustainability. The solid oxide electrolysis cell (SOEC) is a promising energy conversion device capable of efficiently converting CO into valuable chemicals using renewable energy sources. However, Sr-containing cathode materials face the challenge of Sr carbonation during CO electrolysis, which greatly affects the energy conversion efficiency and long-term stability.

Histone H3 Tail Modifications Alter Structure and Dynamics of the H1 C-Terminal Domain Within Nucleosomes.

The highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) undergoes extensive condensation upon binding to nucleosomes, and stabilizes nucleosomes and higher-order chromatin structures but its interactions in chromatin are not well defined. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits exchange between multiple defined FRET structures. Moreover, crosslinking studies indicate that the first 30 residues of the H1 CTD participate in relatively localized contacts with the first ∼25 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA.

Circadian control of cisplatin-DNA adduct repair and apoptosis in culture cells.

Cisplatin, a widely prescribed chemotherapeutic agent for treating solid tumors, induces DNA adducts and activates cellular defense mechanisms, including DNA repair, cell cycle checkpoint control, and apoptosis. Considering the circadian rhythmicity displayed by most chemotherapeutic agents and their varying therapeutic efficacy based on treatment timing, our study aimed to investigate whether the circadian clock system influences the DNA damage responses triggered by cisplatin in synchronized cells. We examined the DNA damage responses in circadian-synchronized wild-type mouse embryonic fibroblasts (WT-MEF; clock-proficient cells), cryptochrome1 and 2 double knock-out MEF (CRY; clock-deficient cells), and mouse hepatocarcinoma Hepa1c1c7 cells.

Spontaneous histone exchange between nucleosomes.

The nucleosome is the fundamental gene-packing unit in eukaryotes. Nucleosomes comprise ∼147 bp DNA wrapped around an octameric histone protein core composed of two H2A-H2B dimers and one (H3-H4) tetramer. The strong yet flexible DNA-histone interactions are the physical basis of the dynamic regulation of genes packaged in chromatin.

Methods to investigate nucleosome structure and dynamics with single-molecule FRET.

The nucleosome is the fundamental building block of chromatin. Changes taking place at the nucleosome level are the molecular basis of chromatin transactions with various enzymes and factors. These changes are directly and indirectly regulated by chromatin modifications such as DNA methylation and histone post-translational modifications including acetylation, methylation, and ubiquitylation.

Spontaneous Histone Exchange Between Nucleosomes.

The nucleosome is the fundamental gene-packing unit in eukaryotes. Nucleosomes comprise ∼147 bp DNA wrapped around an octameric histone protein core composed of two H2A-H2B dimers and one (H3-H4) tetramer. The strong yet flexible DNA-histone interactions are a physical basis of the dynamic regulation of genes packaged in chromatin.

Histone H3 tail modifications regulate structure and dynamics of the H1 C-terminal domain within nucleosomes.

Despite their importance, how linker histone H1s interact in chromatin and especially how the highly positively charged and intrinsically disordered H1 C-terminal domain (CTD) binds and stabilizes nucleosomes and higher-order chromatin structures remains unclear. Using single-molecule FRET we found that about half of the H1 CTDs in H1-nucleosome complexes exhibit well-defined FRET values indicative of distinct, static conformations, while the remainder of the population exhibits dynamically changing values, similar to that observed for H1 in the absence of nucleosomes. We also find that the first 30 residues of the CTD participate in relatively localized interactions with the first ∼20 bp of linker DNA, and that two separate regions in the CTD contribute to H1-dependent organization of linker DNA, consistent with some non-random CTD-linker DNA interactions.

Methods of Visualizing the Results of an Artificial-Intelligence-Based Computer-Aided Detection System for Chest Radiographs: Effect on the Diagnostic Performance of Radiologists.

It is unclear whether the visualization methods for artificial-intelligence-based computer-aided detection (AI-CAD) of chest radiographs influence the accuracy of readers' interpretation. We aimed to evaluate the accuracy of radiologists' interpretations of chest radiographs using different visualization methods for the same AI-CAD. Initial chest radiographs of patients with acute respiratory symptoms were retrospectively collected.

Deep Learning-Based Computer-Aided Detection System for Preoperative Chest Radiographs to Predict Postoperative Pneumonia.

Rationale And Objectives: The role of preoperative chest radiography (CR) for prediction of postoperative pneumonia remains uncertain. We aimed to develop and validate a prediction model for postoperative pneumonia incorporating findings of preoperative CRs evaluated by a deep learning-based computer-aided detection (DL-CAD) system MATERIALS AND METHODS: This retrospective study included consecutive patients who underwent surgery between January 2019 and March 2020 and divided into development (surgery in 2019) and validation (surgery between January and March 2020) cohorts. Preoperative CRs obtained within 1-month before surgery were analyzed with a commercialized DL-CAD that provided probability values for the presence of 10 different abnormalities in CRs.

Effects of Histone H2B Ubiquitylations and H3K79me on Transcription Elongation.

Post-translational modifications of histone proteins often mediate gene regulation by altering the global and local stability of the nucleosome, the basic gene-packing unit of eukaryotes. We employed semisynthetic approaches to introduce histone H2B ubiquitylations at K34 (H2BK34ub) and K120 (H2BK120ub) and H3K79 trimethylation (H3K79me3). With these modified histones, we investigated their effects on the kinetics of transcription elongation by RNA polymerase II (Pol II) using single-molecule FRET.

The Effects of Histone H2B ubiquitylations and H3K79me on Transcription Elongation.

Post-translational modifications of histone proteins often mediate gene regulation by altering the global and local stability of the nucleosome, the basic gene-packing unit of eukaryotes. We employed semi-synthetic approaches to introduce histone H2B ubiquitylations at K34 (H2BK34ub) and K120 (H2BK120ub) and H3 K79 trimethylation (H3K79me3). With these modified histones, we investigated their effects on the kinetics of transcription elongation by RNA Polymerase II (Pol II) using single-molecule FRET.

Blast resistance of RC tubular structure under internal ANFO explosion.

The degree of structural damage is significantly more severe when a blast occurs inside than outside of a structure. However, existing designs for RC structures such as reinforced concrete containment vessels (RCCV) do not include design features to protect the structure for internal blast. Therefore, the internal blast resistance capacity of RC structures is evaluated by performing internal blast tests on RC tubular structures.

The Effects of Histone H2B Ubiquitylations on the Nucleosome Structure and Internucleosomal Interactions.

Eukaryotic gene compaction takes place at multiple levels to package DNA to chromatin and chromosomes. Two of the most fundamental levels of DNA packaging are at the nucleosome and dinucleosome stacks. The nucleosome is the basic gene-packing unit and is composed of DNA wrapped around a histone core.

Acute frataxin knockdown in induced pluripotent stem cell-derived cardiomyocytes activates a type I interferon response.

Friedreich ataxia, the most common hereditary ataxia, is a neuro- and cardio-degenerative disorder caused, in most cases, by decreased expression of the mitochondrial protein frataxin. Cardiomyopathy is the leading cause of premature death. Frataxin functions in the biogenesis of iron-sulfur clusters, which are prosthetic groups that are found in proteins involved in many biological processes.

Machine-Learning-Based Clinical Biomarker Using Cell-Free DNA for Hepatocellular Carcinoma (HCC).

(1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC.