S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.

Background: Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH.

Activation of protein kinase C decreases equilibrative nucleobase transporter 1-mediated substrate uptake via phosphorylation of threonine 231.

Protein kinase C (PKC) signalling has been shown to be dysregulated in various cancers including acute lymphoblastic leukemia (ALL). We have previously determined that changes in the expression levels of SLC43A3-encoded equilibrative nucleobase transporter 1 (ENBT1) can significantly alter 6-mercaptopurine (6-MP) toxicity in ALL cells. 6-MP is a common drug used in ALL chemotherapy.

Structural and functional analysis of the Nipah virus polymerase complex.

Nipah virus (NiV) is a bat-borne, zoonotic RNA virus that is highly pathogenic in humans. The NiV polymerase, which mediates viral genome replication and mRNA transcription, is a promising drug target. We determined the cryoelectron microscopy (cryo-EM) structure of the NiV polymerase complex, comprising the large protein (L) and phosphoprotein (P), and performed structural, biophysical, and in-depth functional analyses of the NiV polymerase.

Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer's disease.

In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies.

Diversity and Evolution of the Mobilome Associated with Antibiotic Resistance Genes in .

is an important cause of pyogenic infections, bacteremia, and chronic maxillary sinusitis. Mobile genetic elements (MGEs) play a key role in lateral gene transfer, resulting in broad transfer of antibiotic resistance genes (ARGs). However, studies on ARG-associated MGEs in are still rare.

MOF@Ag/AAB/Au@Ag composite matrix full-dimensional divergence effect-based SERS paper sensor for rapid carbaryl quantification.

Carbaryl is a broad-spectrum carbamate fungicide that may pose a threat to ecosystems and human health. To prevent and control the harm caused by excessive application of carbaryl, a full-dimensional divergence effect SERS sensor has been constructed. Biodegradable paper chips were used as sensor substrates.

Engineering of Silkworm Tyrosyl-tRNA Synthetase Variants to Create Halogenated Silk Fiber with Improved Thermal Stability.

Silk fiber, produced by the silkworm , is a protein fiber with an excellent mechanical strength and broad biocompatibility. Multiple approaches, including genetic and chemical methods, must be combined to tailor silk fiber properties for wide applications, such as textiles and biomaterials. Genetic code expansion (GCE) is an alternative method to alter proteins' chemical and physical properties by incorporating synthetic amino acids into their primary structures.

From phenotypic to molecular diagnosis: Insights from a clinical immunology service focused on inborn errors of immunity in Colombia.

Introduction: Inborn errors of immunity include a broad spectrum of genetic diseases, in which a specific gene mutation might alter the entire emphasis and approach for an individual patient.

Objective: To conduct a comprehensive analysis of the correlation between phenotypic and molecular diagnoses in patients with confirmed inborn errors of immunity at a tertiary hospital in Cali, Colombia.

Materials And Methods: We conducted a retrospective study in which we sequentially evaluated all available institutional medical records with a diagnosis of inborn errors of immunity.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition.

Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF Syndrome and reveals broad immune cell defects.

Introduction: STAT3 orchestrates crucial immune responses through its pleiotropic functions as a transcription factor. Patients with germline monoallelic dominant negative or hypermorphic STAT3 variants, who present with immunodeficiency and/or immune dysregulation, have revealed the importance of balanced STAT3 signaling in lymphocyte differentiation and function, and immune homeostasis. Here, we report a novel missense variant of unknown significance in the DNA binding domain of STAT3 in a patient who experienced hypogammaglobulinemia, lymphadenopathy, hepatosplenomegaly, immune thrombocytopenia, eczema and enteropathy over a 35-year period.

Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.

Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.

Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).

Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.

The PurR family transcriptional regulator promotes butenyl-spinosyn production in Saccharopolyspora pogona.

Butenyl-spinosyn, derived from Saccharopolyspora pogona, is a broad-spectrum and effective bioinsecticide. However, the regulatory mechanism affecting butenyl-spinosyn synthesis has not been fully elucidated, which hindered the improvement of production. Here, a high-production strain S.

The gendered nature of leader behaviors: Navigating stereotype threat from conservation of resources and gender role perspectives.

Previous research has highlighted the benefits followers gain from their leaders' initiating structure and consideration. Adopting a leader-centric perspective, we propose that leaders' gender influences the impact of these behaviors for leaders themselves. Drawing from conservation of resources and gender role theories, we explain why gender-role-inconsistent leader behaviors (behaviors that go against gender stereotypes, such as initiating structure for women and consideration for men) is detrimental, while engaging in gender-role-consistent leader behaviors (such as initiating structure for men and consideration for women) is beneficial.

Regioselective Access to Substituted Benzothiophenes/furans through Electrochemical Selenium-Promoted Skeletal Rearrangement.

An electrochemical strategy for the regioselective construction of seleno-benzothiophenes/furans is reported through electrochemical selenocyclization, followed by Wagner-Meerwein rearrangement. This electro-oxidative tandem process operates under metal-free and external chemical oxidant-free conditions. Advantageously, unprotected homopropargyl alcohols were found to be compatible under the reaction conditions, releasing water and dihydrogen as the biproduct.

MOMENT registry: Patients with advanced non-small-cell lung cancer harboring exon 14 skipping treated with systemic therapy.

exon 14 ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with ex14 skipping NSCLC receiving conventional therapies.

χ-sepnet: Deep Neural Network for Magnetic Susceptibility Source Separation.

Magnetic susceptibility source separation (χ-separation), an advanced quantitative susceptibility mapping (QSM) method, enables the separate estimation of paramagnetic and diamagnetic susceptibility source distributions in the brain. Similar to QSM, it requires solving the ill-conditioned problem of dipole inversion, suffering from so-called streaking artifacts. Additionally, the method utilizes reversible transverse relaxation ( ) to complement frequency shift information for estimating susceptibility source concentrations, requiring time-consuming data acquisition for (e.

Molecular evidence for the role of the ovipositor of the fall armyworm: Where to lay or not to lay?

Oviposition behavior in insects has received considerable attention, but studies have mainly focused on the antennae, neglecting the role of the ovipositor. In this study, we investigated the functional characteristics of the ovipositor in oviposition site selection by the fall armyworm (FAW) Spodoptera frugiperda, a destructive invasive pest of maize and other cereals. In oviposition choice assays females exhibited significant repellency to isothiocyanate (ITC), volatiles specific to non-preferred cruciferous plants.

Radical Brook rearrangement: past, present, and future.

The Brook rearrangement has emerged as one of the most pivotal transformations in organic chemistry, with broad applications spanning organic synthesis, drug design, and materials science. Since its discovery in the 1950s, the anion-mediated Brook rearrangement has been extensively studied, laying the groundwork for the development of numerous innovative reactions. In contrast, the radical Brook rearrangement has garnered comparatively less attention, primarily due to the challenges associated with the controlled generation of alkoxyl radicals under mild conditions.

Current methods for detecting and assessing HIV-1 antibody resistance.

Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies.

Targeted detection of sequence variants in cell-free DNA from cerebrospinal fluid in pediatric central nervous system tumors.

The emergence of liquid biopsy technologies holds great promise in the cancer setting, including in pediatric central nervous system (CNS) tumors. In contrast to broad lower-depth sequencing, commonly referred to as low pass whole genome sequencing (WGS), targeted platforms with a higher depth of coverage have also been established. Here, we review targeted liquid biopsy techniques with applicability to pediatric CNS tumors.

Comparative thoracic radiography in healthy and tuberculosis-positive sun bears ().

Early and accurate diagnosis of pulmonary tuberculosis (TB) is key to effective outbreak management, and in humans thoracic radiography is used extensively for screening purposes. In wildlife TB radiography is a relatively accessible diagnostic tool, particularly in under-resourced settings, however its use is limited by body size. Sun bears are susceptible to human-associated TB, and their small body size makes thoracic radiography feasible.

Liquid chromatography-tandem mass spectrometry for the quantification of ripretinib and its metabolites DP-5439 in human plasma.

Background: Ripretinib, a broad-spectrum tyrosine kinase inhibitor, has been approved for the treatment of advanced gastrointestinal stromal tumors in adult patients. Clinical studies have shown that higher exposure of ripretinib correlates with improved efficacy, highlighting the potential clinical significance of therapeutic drug monitoring. In this study, a simple and stable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was attempted to be established and validated for pharmacokinetic studies of ripretinib and its metabolite DP-5439 and therapeutic drug monitoring in human plasma.

Protective effects of small RNAs encapsulated in -derived exosomes against non-alcoholic fatty liver disease.

Introduction: , a traditional medicinal plant, is renowned for its therapeutic properties, including the promotion of anti-inflammatory and bile secretion. Notably, it has demonstrated efficacy in the treatment of jaundice. This study aimed to evaluate the potential of -derived exosomes (ACDEs) as a novel therapeutic approach in non-alcoholic fatty liver disease (NAFLD).

Viral niche-partitioning: comparative genomics of giant viruses across environmental gradients in a high Arctic freshwater-saltwater lake.

Giant viruses (GVs; ) impact the biology and ecology of a wide range of eukaryotic hosts, with implications for global biogeochemical cycles. Here, we investigated GV niche separation in highly stratified Lake A at the northern coast of Ellesmere Island, Nunavut, Canada. This lake is composed of a layer of ice-covered freshwater that overlies saltwater derived from the ancient Arctic Ocean, and it therefore provides a broad gradient of environmental conditions and ecological habitats, each with a distinct protist community and rich assemblages of associated GVs.

Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.

Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.