During the breeding season, lymphocytes assemble into ellipse-shaped clusters in the uropygial gland of the jungle crow Corvus macrorhynchos.

Background: Recent studies indicate that the uropygial gland produces intraspecific chemosensory cues. The jungle crow Corvus macrorhynchos, which is a type of passerine, exhibits extreme morphological variation in the gonadal gland during the breeding season. Because the uropygial gland of the jungle crow sometimes exhibits morphological changes during the breeding season, we attempted to clarify the morphological changes in the uropygial gland of the jungle crow according to development and season.

Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.

DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation.

A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite.

Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide -methyltransferase (NNMT).

A case of treatment-resistant advanced gastric cancer with FGFR2 gene alteration successfully treated with pemigatinib.

Comprehensive genome profiling (CGP) is expected to widen the scope of cancer drug options by identifying the genes involved in carcinogenesis. However, a few patients can access recommended treatments following CGP. Herein, we report a case in which pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, was used as last-line therapy to treat a patient with advanced gastric cancer exhibiting FGFR2 genomic alterations, as determined by CGP testing.

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition.

Effects of systemic inflammation on the network oscillation in the anterior cingulate cortex and cognitive behavior.

Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 μg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance.

Extracting interpretable features for pathologists using weakly supervised learning to predict p16 expression in oropharyngeal cancer.

One drawback of existing artificial intelligence (AI)-based histopathological prediction models is the lack of interpretability. The objective of this study is to extract p16-positive oropharyngeal squamous cell carcinoma (OPSCC) features in a form that can be interpreted by pathologists using AI model. We constructed a model for predicting p16 expression using a dataset of whole-slide images from 114 OPSCC biopsy cases.

Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma.

Nicotinamide phosphoribosyltransferase (NAMPT) plays a major role in NAD biosynthesis in many cancers and is an attractive potential cancer target. However, factors dictating therapeutic efficacy of NAMPT inhibitors (NAMPTi) are unclear. We report that neuroendocrine phenotypes predict lung and prostate carcinoma vulnerability to NAMPTi, and that NAMPTi therapy against those cancers is enhanced by dietary modification.

In Situ Observation of Bubbles and the Effect of Ultrasonic Vibration on Bubble Behavior in EDM.

Accumulation and concentration of debris in deep hole electrical discharge machining (EDM) significantly hinder its machining efficiency and accuracy. It is believed that the movement of bubbles associated with the discharge gap flow field play a pivotal role in debris removal and influence the discharge conditions. Ultrasonic vibration (USV) of the electrode is thought to be an effective method for improving EDM-generated bubbles and debris exclusion.

Induction of open-form bile canaliculus formation by hepatocytes for evaluation of biliary drug excretion.

Biliary excretion is a major drug elimination pathway that affects their efficacy and safety. The currently available in vitro sandwich-cultured hepatocyte method is cumbersome because drugs accumulate in the closed bile canalicular lumen formed between hepatocytes and their amounts cannot be mealsured directly. This study proposes a hepatocyte culture model for the rapid evaluation of drug biliary excretion using permeation assays.

Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line.

Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line.

MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells.

Unlabelled: Glioma stem cells (GSC) promote the malignancy of glioblastoma (GBM), the most lethal brain tumor. ERK5 belongs to the MAPK family. Here, we demonstrated that MAPK kinase 5 (MEK5)-ERK5-STAT3 pathway plays an essential role in maintaining GSC stemness and tumorigenicity by integrating genetic and pharmacologic manipulation and RNA sequencing analysis of clinical specimens.

Therapeutic advantage of targeting lysosomal membrane integrity supported by lysophagy in malignant glioma.

Lysosomes function as the digestive system of a cell and are involved in macromolecular recycling, vesicle trafficking, metabolic reprogramming, and progrowth signaling. Although quality control of lysosome biogenesis is thought to be a potential target for cancer therapy, practical strategies have not been established. Here, we show that lysosomal membrane integrity supported by lysophagy, a selective autophagy for damaged lysosomes, is a promising therapeutic target for glioblastoma (GBM).

Mutational effects of chronic gamma radiation throughout the life cycle of Arabidopsis thaliana: Insight into radiosensitivity in the reproductive stage.

Organisms living on Earth have always been exposed to natural sources of ionizing radiation, but following recent nuclear disasters, these background levels have often increased regionally due to the addition of man-made sources of radiation. To assess the mutational effects of ubiquitously present radiation on plants, we performed a whole-genome resequencing analysis of mutations induced by chronic irradiation throughout the life cycle of Arabidopsis thaliana grown under controlled conditions. We obtained resequencing data from 36 second generation post-mutagenesis (M) progeny derived from 12 first generation (M) lines grown under gamma-irradiation conditions, ranging from 0.

Intracellular metabolic adaptation of intraepithelial CD4CD8αα T lymphocytes.

Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4CD8ααTCRβ T cells (double positive, DP) originated from CD4CD8αTCRβ T cells (single positive, SP) increase with aging. However, the metabolic requirements and the metabolic-related genes in IEL development remain unclear.

The Role of Nutrients in Maintaining Hematopoietic Stem Cells and Healthy Hematopoiesis for Life.

Nutrients are converted by the body to smaller molecules, which are utilized for both anabolic and catabolic metabolic reactions. Cooperative regulation of these processes is critical for life-sustaining activities. In this review, we focus on how the regulation of nutrient-driven metabolism maintains healthy hematopoietic stem cells (HSCs).

SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-β receptor stability.

Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, the most malignant form of glioma. The implication and underlying mechanisms of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on the GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr (SMURF2) activates its E3 ubiquitin ligase activity.

Leveraging Longitudinal Lifelog Data Using Survival Models for Predicting Risk of Relapse among Patients with Depression in Remission.

Managing depression relapse is a challenge given factors such as inconsistent follow-up and cumbersome psychological distress evaluation methods which leaves patients with a high risk of relapse to leave their symptoms untreated. In an attempt to bridge this gap, we proposed an approach on the use of personal longitudinal lifelog activity data gathered from individual smartphones of patients in remission and maintenance therapy (N=87) to predict their risk of depression relapse. Through the use of survival models, we modeled the activity data as covariates to predict survival curves to determine if patients are at risk of relapse.

Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma.

Aim: To investigate the therapeutic effect of lenvatinib (LEN) in liver disease etiology, especially nonviral hepatocellular carcinoma (HCC).

Methods And Results: Sixty-seven patients with unresectable advanced HCC (u-HCC) treated with LEN and consisting of 26 hepatitis C virus (HCV), 19 hepatitis B virus (HBV), 11 alcohol, and 11 nonalcoholic steatohepatitis (NASH) cases were retrospectively recruited. Univariate and multivariate Cox proportional hazard models were used to determine predictive factors for survival.

Genetic variation of the relict maple Acer miyabei: uncovering its history of disjunct occurrence and the role of mountain refugia in shaping genetic diversity.

Premise: Relict species provide valuable insights into the origin and formation of extant vegetation. Here, we aimed to elucidate the genetic structure and diversity of a riparian relic, Acer miyabei, in Japan. Once widely distributed, it now occurs in three isolated regions.