Neuropeptide Y neurons mediate opioid-induced itch by disinhibiting GRP-GRPR microcircuits in the spinal cord.

Itch is a common side effect of opioid analgesics. The specific neurons mediating opioid-induced itch are still debated, and the mechanistic neuronal circuits remain elusive. Here, we show that the μ-opioid receptors (MOR) on neuropeptide Y (NPY) inhibitory interneurons mediate opioid-induced itch at the spinal cord level in mice.

Concurrent nonalcoholic fatty liver disease may decrease liver fibrosis severity in patients with primary biliary cholangitis.

Background: The purpose of this study was to evaluate how nonalcoholic fatty liver disease (NAFLD) impacts the progression and prognosis of primary biliary cholangitis (PBC).

Methods: This retrospective study enrolled patients diagnosed with PBC. NAFLD patients were identified according to the 2023 American Association for the Study of Liver Diseases guidelines.

Elucidating the Biosynthetic Pathway and Mechanisms of Retrochalcones.

Chalcone is a privileged natural product skeleton for drug discovery, and retrochalcone represents a group of nonclassical chalcones with a distinctive oxygen substitution pattern. Echinatin, a hepatoprotective agent, is a retrochalcone derived from . Despite their initial discovery half a century ago, the biosynthetic mechanisms of retrochalcones have remained elusive.

Non-invasive longitudinal monitoring of vascularization in tissue-engineered grafts by ultrasound localization microscopy.

Tissue engineering is a rapidly advancing field aimed at regenerating damaged tissues by combining cells, biomaterials, and bioactive molecules. Adequate vascularization is a critical determinant of successful tissue regeneration, as it supports both the regenerative process and the maintenance of physiological functions in the newly formed tissue. Traditional methods for evaluating vascularization, such as histological and immunohistochemical techniques, are inherently invasive and limited to endpoint analysis.

Agxt2l-mediated glycerophospholipid metabolism in trophocytes explains Apis mellifera queen's higher oviposition over A. cerana.

Apis mellifera and Apis cerana are two important honey bee species widely kept and studied. But their queens differ greatly in egg-laying capacity. To determine the mechanisms of this difference, we compare gene expression, chromatin accessibility and spatial localization of differential genes in the ovaries of the two species in virgin queens and laying queens using ATAC-seq, RNA-Seq, homologous gene alignment and spatial transcriptome.

The recurrence and multi-organ involvement of giant penile plexiform neurofibroma in an adult with neurofibromatosis type 1: a case report.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with malignant potential, affecting various anatomical regions, predominantly the head and neck. Urogenital involvement is relatively uncommon. In particular, penile neurofibromatosis is exceedingly rare, with fewer than 20 cases documented globally.

Effects of auditory rhythmic adaptation on lower limb joint mechanics during single-leg drop landings in individuals with functional ankle instability.

Objective: This study investigates the effects of auditory rhythmic adaptation on lower limb joint mechanics in individuals with Functional Ankle Instability (FAI) during drop landings, aiming to explore potential rehabilitation strategies.

Methods: Twenty male FAI individuals performed single-leg drop landings under four rhythmic conditions (no rhythm, 60, 120, 180 bpm) after auditory rhythmic adaptation. Joint mechanics data were collected, and analyzed using two-way repeated measures ANOVA to examine the main effects and interaction effects of rhythm and limb condition.

Non-targeted and Targeted Metabolomics Techniques Reveal Striatal Metabolome Characteristics in the Ketamine-Induced Conditioned Place Preference Mice Model.

Ketamine is a synthesized anesthetic drug that was used extensively as a surgical anesthetic in the 1960s. Currently, ketamine is being investigated extensively for its potential as a treatment for depression. However, the addictive nature of ketamine has become an issue that cannot be ignored at this stage.

Maternal exposure to norfloxacin induces impairment of cardiac development in zebrafish offspring.

Fluoroquinolone antibiotics (FQs) play a crucial role in human and animal medicine, but their increasing use and high persistence have posed serious threats to ecosystems and public health. FQs have been found to be associated with heart developmental defects. However, the intergenerational effects of FQs on fish cardiac development remain poorly understood.

Endothelial cells expressing CPE and vWF are involved in the Immunopathogenesis of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an immune-mediated, non-suppurative cholestatic liver disease. Liver sinusoidal endothelial cells (LSECs) play a pivotal role in maintaining hepatic immune tolerance. Emerging research indicates that under certain stimuli, LSECs can transition from a tolerogenic to an immunogenic role.

Safety and Immunogenicity of a Canine Distemper DNA Vaccine Formulated with Lipid Nanoparticles in Dogs, Foxes, and Raccoon Dogs.

Background: canine distemper (CD) is a highly contagious and fatal disease caused by canine distemper virus (CDV), posing a significant threat to carnivores. New CDV strain circulation and multi-species infection may lead to the potential dilemma of safety concern and insufficient efficacy of the commercial modified live vaccines. Safe and effective vaccines for canine and wildlife prevention of CD need to be continuously updated and developed.

Light field-controlled PHz currents in intrinsic metals.

Oriented electric currents in metals are routinely driven by applying an external electric potential. Although the response of electrons to the external electric fields occurs within attoseconds, conventional electronics do not use this speed potential. Ultrashort laser pulses with controlled shapes of electric fields that switch direction at petahertz frequencies open perspectives for driving currents in metals.

Whole-genome resequencing reveals genetic evolution of honeybees (Apis cerana) in high-altitude and overwintering adaptation.

Over time, populations of Apis cerana across diverse geographical regions have undergone distinct phenotypic adaptations in response to varied climates, arising from prolonged natural evolutionary processes. Understanding the molecular genetic underpinnings and the implications of climate change on the adaptive evolution of A. cerana is crucial for its conservation amidst environmental shifts.

Bridging inflammation and venous thrombosis: the NLRP3 inflammasome connection.

NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome is a critical regulator of inflammatory responses in the body and is closely associated with the inflammatory processes of various diseases. In recent years, research has increasingly focused on the role of the NLRP3 inflammasome in venous thromboembolism (VTE). Venous thromboembolism is a common and potentially fatal vascular disease with a complex pathophysiology involving multiple cellular and molecular pathways.

Targeting toll-like receptors: unveiling potential therapeutic strategies for deep vein thrombosis.

Deep vein thrombosis (DVT) is a complex multifactorial vascular disease characterized by abnormal blood stasis and coagulation within the deep veins, primarily occurring in the lower limbs. This pathological condition not only causes local circulatory disruption but also has the potential to trigger life-threatening pulmonary embolism through thrombus detachment, thus posing a major threat to human health. Toll - like receptors (TLRs), essential components of the innate immune system, have been increasingly acknowledged as crucial determinants in the pathogenesis of DVT.

Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production.

Heterologous expression of polyketide synthase (PKS) genes in Escherichia coli has enabled the production of various valuable natural and synthetic products. However, the limited availability of malonyl-CoA (M-CoA) in E. coli remains a substantial impediment to high-titer polyketide production.

Deciphering the role of reactive oxygen species in idiopathic asthenozoospermia.

Asthenozoospermia is a severe condition characterized by abnormal sperm motility, contributing to 50% of male infertility cases. Idiopathic asthenozoospermia refers to a form of this condition with no identifiable causes through routine clinical examinations, potentially linked to apoptosis and oxidative stress induced by excessive reactive oxygen species (ROS). At low concentrations, ROS positively influence physiological processes, including sperm mature and motility.

Insights into the Mechanisms of Sugar Acceptor Selectivity of Plant Flavonoid Apiosyltransferases.

Flavonoid apiosides are widely distributed in cereals, fruits, vegetables, and medicinal herbs and play critical roles in human health. Their facile and efficient synthesis has been a hot but challenging topic in the fields of both organic chemistry and biosynthesis. However, very few apiosyltransferases (ApiGTs) have been reported thus far.

Unraveling the Causal Association Between Circulating Copper Levels and Erectile Dysfunction: A Comprehensive Analysis via Bidirectional Two Sample Mendelian Randomization Study.

Erectile dysfunction (ED) is a prevalent condition severely impacting men's quality of life. While micronutrient balance is critical for sexual health, observational studies on micronutrient and ED remain inconclusive. The objective of this study was to evaluate the causal role of circulating levels of copper and other micronutrients in ED risk by Mendelian randomization (MR).

Multi-Agent-Network-Based Idea Generator for Zinc-Ion Battery Electrolyte Discovery: A Case Study on Zinc Tetrafluoroborate Hydrate-Based Deep Eutectic Electrolytes.

Aqueous deep eutectic electrolytes (DEEs) offer great potential for low-cost zinc-ion batteries but often have limited performance. Discovering new electrolytes is therefore crucial, yet time-consuming and resource-intensive. In response, this work presents a Large Language Model (LLM)-based multi-agent network that proposes DEE compositions for zinc-ion batteries.

Elucidation of the biosynthetic pathway of hydroxysafflor yellow A.

Hydroxysafflor yellow A (HSYA) is a clinical investigational new drug for the treatment of acute ischemic stroke. It has a unique quinochalcone di-C-glycoside structure and is exclusively found in the flowers of safflower (Carthamus tinctorius). To date, little is known about the biosynthesis of HSYA.

Physiologically based pharmacokinetic modeling of tapentadol in children to support pediatric dose selection.

Tapentadol, an effective opioid analgesic, is indicated for the treatment of pain that cannot be managed with non-opioid medications. This study employed a physiologically based pharmacokinetic (PBPK) model to characterize the disposition of tapentadol in children across different age groups and to refine pediatric dosing strategies. Initially, an adult PBPK model was developed using the 'middle-out' strategy, which was then adjusted by scaling anatomical and physiological parameters to apply it to pediatric populations.

Structural insights into the human system yL amino acid transporter complex.

System yL facilitates the sodium-independent transport of cationic and sodium-dependent transport of neutral amino acids via heteromeric amino acid transporters. System yL consists of either SLC7A6 (yLAT2) or SLC7A7 (yLAT1) and 4F2hc (SLC3A2). The yLAT2-4F2hc complex mediates the exchange of -lysine (Lys), -arginine (Arg), -leucine (Leu), and -glutamine (Gln) and is important for the glutamate-glutamine cycle and ammonia clearance.

MRI-based machine learning reveals proteasome subunit PSMB8-mediated malignant glioma phenotypes through activating TGFBR1/2-SMAD2/3 axis.

Gliomas are the most prevalent and aggressive neoplasms of the central nervous system, representing a major challenge for effective treatment and patient prognosis. This study identifies the proteasome subunit beta type-8 (PSMB8/LMP7) as a promising prognostic biomarker for glioma. Using a multiparametric radiomic model derived from preoperative magnetic resonance imaging (MRI), we accurately predicted PSMB8 expression levels.

Molecular and Structural Characterization of a Chalcone di--Methyltransferase RdCMT from and Its Application in De Novo Biosynthesis of Farrerol in .

Methylation plays a crucial role in drug design and optimization. While numerous methyltransferases have been characterized from plants, -methyltransferases, particularly those targeting phenolic skeletons, are rare. In this study, we identified a novel di--methyltransferase RdCMT from the medicinal plant .