Metabolic profiling of 5- Methoxy-N,N-diallyltryptamine in human liver microsomes and zebrafish using LC-Orbitrap MS.

The metabolic profiles of tryptamine-derived new psychoactive substance 5-Methoxy-N, N-diallyltryptamine (5-MeO-DALT) were investigated using both zebrafish and human liver microsome models. The ultra-high performance liquid chromatography Q Exactive Quadrupole-Orbitrap high resolution mass spectrometer (UPLC-Q-Orbitrap-HRMS) was employed to analyze the intoxicated zebrafish samples, as well as human liver microsomes samples. The mass spectrometric data were analyzed by a software of Compound Discoverer with a database of potential metabolites.

Expert consensus on clinical genome sequencing interpretation and reporting.

Genome sequencing (GS) refers to a technology that comprehensively and systematically detects the DNA sequences of an individual's nuclear and mitochondrial genomes. It aims to identify genetic variants and investigate their roles in human health and disease progression. As an emerging diagnostic tool, GS offers significant support for clinical diagnosis due to its high throughput, accuracy, and comprehensiveness.

Clinical validation of RNA sequencing for Mendelian disorder diagnostics.

Despite rapid advancements in clinical sequencing, over half of diagnostic evaluations still lack definitive results. RNA sequencing (RNA-seq) has shown promise in research settings for bridging this gap by providing essential functional data for accurate interpretation of diagnostic sequencing results. However, despite advanced research pipelines, clinical translation of diagnostic RNA-seq has not yet been realized.

[Predictive Value of Platelet Parameters for Arterial Complications in Patients with Myeloproliferative Neoplasms].

Objective: To analyze the occurrence of arterial events and platelet parameters in patients with polycythemia vera (PV) and essential thrombocythemia (ET), and to explore the characteristics of platelet parameters in patients with PV and ET and their relationship with arterial complications.

Methods: The clinical and laboratory data of newly diagnosed PV and ET patients who visited the Department of Hematology, Beijing Anzhen Hospital, Capital Medical University from August 2017 to August 2022 were retrospectively analyzed.

Results: 86 MPN patients (46 males and 40 females) were enrolled, including 44 PV patients and 42 ET patients, with an median age of 61(23-83) years.

Toxicological Assessment of Ketamine in Juvenile Zebrafish ().

This study investigates the toxic effects of ketamine on juvenile zebrafish, driven by increasing concerns over ketamine's prevalence and its potential neurotoxic effects that may disrupt behavior and metabolism. Employing a high-throughput behavior tracking system, the research analyzed the locomotor activity of 6-day post-fertilization (6 dpf) zebrafish exposed to various concentrations of ketamine. The integration of behavioral analysis with metabolic profiling was a notable innovation, as it establishes a comprehensive understanding of ketamine's effects on both acute behavioral inhibition and metabolic responses.

FuSViz-visualization and interpretation of structural variation using cancer genomics and transcriptomics data.

Structural variation (SV) is a frequent category of genetic alterations important for understanding cancer genome evolution and revealing key cancer driver events. With the development of high-throughput sequencing technologies, the ability to detect SVs of various sizes and types has improved, at both the DNA and RNA levels. However, SV calls are still prone to a considerable fraction of false positives, which necessitates visual inspection and manual curation as part of the quality control process.

Genome sequencing enhances the diagnostic yield and expands the genetic landscape of male breast cancer.

Purpose: To understand the broader genetic landscape of male breast cancer (MBC), focusing on the utility of genome sequencing (GS) beyond (HGNC: 1100, 1101) variants.

Methods: Twenty-four patients with MBC underwent a multistep genetic analysis. Initial screening targeted variants followed by GS to identify pathogenic/likely pathogenic germline variants through a 3-tiered classification.

The Utility of Ultra-Deep RNA sequencing in Mendelian Disorder Diagnostics.

Clinical RNA-seq has become an essential tool for resolving variants of uncertain significance (VUS), particularly those affecting gene expression and splicing. However, most reference data and diagnostic protocols employ relatively modest sequencing depths (∼50-150 million reads), which may fail to capture low-abundance transcripts and rare splicing events critical for accurate diagnoses. We evaluated the diagnostic and translational utility of ultra-high-depth (up to ∼one billion unique reads) RNA-seq in four clinically accessible tissues (blood, fibroblast, LCL, and iPSC) using Ultima sequencing platform.

Identification of In Vivo and In Vitro Metabolites of Fentanyl Using UHPLC-Q-Orbitrap-HRMS.

A comparative analysis of the metabolites and metabolic pathways of fentanyl was conducted in liver microsomes and zebrafish models utilizing ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A total of 21 metabolites were identified across both liver microsomes and zebrafish models. These included 9 phase I metabolites, such as N-dealkylated, N-oxidated and hydroxylated products, and 12 phase II metabolites, including glucuronidated, methylated, and sulfated products, as well as a series of products derived from conjugation with glutathione.

TET1 participates in oxaliplatin-induced neuropathic pain by regulating microRNA-30b/Nav1.6.

Chemotherapy-induced neuropathic pain poses significant clinical challenges and severely impacts patient quality of life. Sodium ion channels are crucial in regulating neuronal excitability and pain. Our research indicates that the microRNA-30b (miR-30b) in rat dorsal root ganglia (DRG) contributes to chemotherapy-induced neuropathic pain by regulating the Nav1.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is a crucial transcriptional regulator of cartilage development and homeostasis. Dysregulation of is associated with a wide spectrum of skeletal disorders, including campomelic dysplasia, acampomelic campomelic dysplasia, and scoliosis. Yet how variants contribute to the spectrum of axial skeletal disorders is not well understood.

Numerical Simulation of Fluid Shear Stress Distribution in Microcracks of Trabecular Bone.

Bone is one of the hardest tissues in the human body, but it can undergo microcracks under long-term and periodic mechanical loads. The Newton iterative method was used to calculate the steady state, and the effects of different inlet and outlet pressures, trabecular gap width and height, and microcrack's depth and width on the fluid shear stress (FSS) were studied, and the gradient of FSS inside the microcrack was analyzed. The results show that the pressure difference and trabecular gap heigh are positively correlated with the FSS (the linear correlation coefficients were 0.

Preliminary study assessing the long-term surgical outcomes of TBX6-associated congenital scoliosis (TACS) patients using the propensity score matching method: exploring the clinical implications of genetic discoveries in congenital scoliosis.

Background: Compound inheritance of TBX6 accounts for approximately 10% of sporadic congenital scoliosis (CS) cases. Such cases are called TBX6-associated congenital scoliosis (TACS). TACS has been reported to have certain common clinical phenotypes.

Planar cell polarity zebrafish models of congenital scoliosis reveal underlying defects in notochord morphogenesis.

Congenital scoliosis (CS) is a type of vertebral malformation for which the etiology remains elusive. The notochord is pivotal for vertebrae development, but its role in CS is still understudied. Here, we generated a zebrafish knockout of ptk7a, a planar cell polarity (PCP) gene that is essential for convergence and extension (C&E) of the notochord, and detected congenital scoliosis-like vertebral malformations (CVMs).

Identification of novel M2 macrophage-related molecule ATP6V1E1 and its biological role in hepatocellular carcinoma based on machine learning algorithms.

Hepatocellular carcinoma (HCC) remains the most prevalent form of primary liver cancer, characterized by late detection and suboptimal response to current therapies. The tumour microenvironment, especially the role of M2 macrophages, is pivotal in the progression and prognosis of HCC. We applied the machine learning algorithm-CIBERSORT, to quantify cellular compositions within the HCC TME, focusing on M2 macrophages.

Exploring the multifaceted role of key lncRNA in glioma: From genetic expression to clinical implications and immunotherapy potential.

Background: Long non-coding RNAs (lncRNAs) are implicated in a variety of regulatory functions within tumors, yet their specific roles in glioma remain underexplored.

Methods: We extracted glioma patient data from The Cancer Genome Atlas and UCSC Xena database for analysis using R, focusing on genomic characterization, biological enrichment, immune evaluation, and the development of a predictive model employing machine learning techniques. Additionally, we conducted cell culture and proliferation assays.

Pathophysiological impacts of 5-MeO-MiPT on zebrafish (Danio rerio) via the Gα-PLC signaling pathway.

Novel Psychoactive Substances (NPS) derived from tryptamines has been detected in aquatic environments, leading to environmental toxicology concerns. However, the specific toxicological mechanism, underlying these NPS, remains unclear. In our previous work, we used 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) as the representative drug for NPS, and found that, 5-MeO-MiPT led to obvious behavioral inhibition and oxidative stress responses in zebrafishes model.

Prediction of Bone Remodeling in Rat Caudal Vertebrae Based on Fluid-Solid Coupling Simulation.

Some previous researches have demonstrated that appropriate mechanical stimulation can enhance bone formation. However, most studies have employed the strain energy density (SED) method for predicting bone remodeling, with only a few considering the potential impact of wall fluid shear stress (FSS) on this process. To bridge this gap, the current study compared the prediction of bone formation and resorption via SED and wall FSS by using fluid-solid coupling numerical simulation.

Explainable El Niño predictability from climate mode interactions.

The El Niño-Southern Oscillation (ENSO) provides most of the global seasonal climate forecast skill, yet, quantifying the sources of skilful predictions is a long-standing challenge. Different sources of predictability affect ENSO evolution, leading to distinct global effects. Artificial intelligence forecasts offer promising advancements but linking their skill to specific physical processes is not yet possible, limiting our understanding of the dynamics underpinning the advancements.

Exudates of Microcystis aeruginosa on oxidative stress and inflammatory responses in gills of Sinocyclocheilus grahami.

Early cyanobacterial blooms studies observed that exposure to blue-green algae led to fish gills impairment. The objective of this work was to evaluate the toxic mechanisms of exudates of Microcystis aeruginosa (MaE) on fish gills. In this study, the toxic mechanism of MaE (2×10 cells/mL) and one of its main components phytosphingosine (PHS) with two concentrations 2.

Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression.

Experimental and Thermal Stress Field Numerical Simulation Study on Laser Metal Deposition of Ti-48Al-2Cr-2Nb Alloy.

The experimental and numerical simulation analysis of a TiAl alloy by laser metal deposition technology is presented in this paper. The research examines the macroscopic morphology, microstructure, and mechanical properties of samples as laser power varies. It also delves into how the temperature field and residual stress evolve under different laser powers.