The LRP1-SHP2 pathway regulates TRPV1 sensitivity in the peripheral nervous system: Insights from amyloid beta 1-42 modulation.

Introduction: Mature adults often exhibit higher pain thresholds than younger individuals. However, this phenomenon is poorly understood, especially with regards to peripheral nervous system signaling.

Objectives: We investigated the involvement of amyloid beta (Aβ) in regulating heat pain sensitivity within the dorsal root ganglion (DRG) during adult maturation.

MDTR: a knowledge-guided interpretable representation for quantifying liver toxicity at transcriptomic level.

Introduction: Drug-induced liver injury (DILI) has been investigated at the patient level. Analysis of gene perturbation at the cellular level can help better characterize biological mechanisms of hepatotoxicity. Despite accumulating drug-induced transcriptome data such as LINCS, analyzing such transcriptome data upon drug treatment is a challenging task because the perturbation of expression is dose and time dependent.

Gut Microbiome Signature in Predisease Phase of Inflammatory Bowel Disease: Prediction to Pathogenesis to Prevention.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome.

Unraveling metabolic signatures in SARS-CoV-2 variant infections using multiomics analysis.

Introduction: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, notably delta and omicron, has significantly accelerated the global pandemic, worsening conditions worldwide. However, there is a lack of research concerning the molecular mechanisms related to immune responses and metabolism induced by these variants.

Methods: Here, metabolomics combined with transcriptomics was performed to elucidate the immunometabolic changes in the lung of hamsters infected with delta and omicron variants.

Deubiquitinase inhibitor bAP-15 suppresses renal epithelial to mesenchymal transition via inhibition of p300 stability.

Renal fibrosis is an irreversible disease that is common in patients with chronic kidney disease. Elevated levels of the histone acetyltransferase p300 have been reported in various fibrotic diseases, including renal fibrosis, suggesting that p300 may be a promising therapeutic target. To investigate the specific deubiquitinase (DUB) involved in the regulation of p300 protein stability in renal epithelial cells, we tested 13 DUB inhibitors using a kidney tubular epithelial cell line.

Predictive model for abdominal liposuction volume in patients with obesity using machine learning in a longitudinal multi-center study in Korea.

This study aimed to develop and validate a machine learning (ML)-based model for predicting liposuction volumes in patients with obesity. This study used longitudinal cohort data from 2018 to 2023 from five nationwide centers affiliated with 365MC Liposuction Hospital, the largest liposuction hospitals in Korea. Fifteen variables related to patient profiles were integrated and applied to various ML algorithms, including random forest, support vector, XGBoost, decision tree, and AdaBoost regressors.

Real-time volumetric imaging of cells and molecules in deep tissues with Takoyaki ultrasound.

Acoustic contrast agents and reporter genes play a critical role in allowing ultrasound to visualize blood flow, map molecules and track cellular function in opaque living organisms. However, existing ultrasound methods to image acoustic contrast agents predominantly focus on 2D planar imaging, while the biological phenomena of interest unfurl in three dimensions. Here, we introduce a method for efficient, dynamic imaging of contrast agents and reporter genes in 3D using multiplexed matrix array transducers.

DGDRP: drug-specific gene selection for drug response prediction via re-ranking through propagating and learning biological network.

Drug response prediction, especially in terms of cell viability prediction, is a well-studied research problem with significant implications for personalized medicine. It enables the identification of the most effective drugs based on individual genetic profiles, aids in selecting potential drug candidates, and helps identify biomarkers that predict drug efficacy and toxicity.A deeper investigation on drug response prediction reveals that drugs exert their effects by targeting specific proteins, which in turn perturb related genes in cascading ways.

Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD.

Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile.

Background: Primary sclerosing cholangitis associated with inflammatory bowel disease (IBD-PSC) carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid (BA) profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC is scarce. We aimed to assess the differences in gut microbiome composition as well as in the BA profile and BA-related microbial functions between IBD-PSC and IBD-only.

Enhancing the Evaluation System of Training Hospitals for Neurosurgical Residency Training and Education in South Korea : Striving for Balanced Participation and Differentiation.

The Korean Neurosurgical Society, with its 62 years of history, has witnessed substantial growth in the field of neurosurgery, producing over 3400 neurosurgeons, establishing 12 divisions and nine regional branches, and advancing in clinical management, diagnostic methods and academic research. Despite these developments, the regulations governing neurosurgical training and evaluation methods for training hospitals have remained largely unchanged, necessitating comprehensive revisions in response to evolving medical environments. To provide balanced participation opportunities for neurosurgery residents, the Korean Neurosurgical Society formed the Training Status Investigation Standard Change Task Force (TF team) under the Training Education Committee.

Degassing 4--Butylpyridine in the Spiro-MeOTAD Film Improves the Thermal Stability of Perovskite Solar Cells.

The organic molecular 2,2',7,7'-tetrakis(4,4'-dimethoxy-3-methyldiphenylamino)-9,9'-spirobifluorene (Spiro-MeOTAD) is known as a typical hole transport material in the development of an all-solid-state perovskite solar cell (PSC). Spiro-MeOTAD requires additives of lithium bifurflimide (LiTFSI) and 4--butylpyridine (tBP) to increase the conductivity and solubility for enhancing the photovoltaic performance of PSCs. However, those additives have an adverse effect on the thermal stability.

Generation of an induced pluripotent stem cell line from a patient with arrhythmogenic right ventricular cardiomyopathy harboring a TMEM43 splice-site variant.

Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy that is predominantly inherited and characterized by cardiac arrhythmias and structural abnormalities. TMEM43 (transmembrane protein 43) is one of the well-known genetic culprits behind ACM. In this study, we successfully generated an induced pluripotent stem cell (iPSC) line, YCMi010-A, derived from a male patient diagnosed with ACM.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/β-catenin signal pathway.

Aims: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored.

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations.

Discovery of N-(1-(2-hydroxyethyl)quinolin-2-one)-N'-(1-phenyl-1H-pyrazol-5-yl)methyl) urea as Mode-Selective TRPV1 antagonist.

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity.

Quantitative Analysis of the Effect of Stereotactic Radiosurgery for Postoperative Residual Cervical Dumbbell Tumors: A Multicenter Retrospective Cohort Study.

Objective: Stereotactic radiosurgery (SRS) has been performed for spinal tumors. However, the quantitative effect of SRS on postoperative residual cervical dumbbell tumors remains unknown. This study aimed to quantitatively evaluate the efficacy of SRS for treating postoperative residual cervical dumbbell tumors.