Novel tertiary diarylethylamines as functionally selective agonists of the kappa opioid receptor.

Novel kappa opioid receptor (KOR) agonists that preferentially activate G-protein signaling versus β-arrestin-2 recruitment are described. Starting from a literature-reported phenol-containing diphenethylamine KOR agonist, structure-activity relationship (SAR) studies revealed replacement of the phenol with various non-hydroxylated bicyclic heteroaromatics led to tertiary diarylethylamines which retained KOR agonist activity and improved metabolic stability in human liver microsomes. Further optimizations produced compound 39, a potent activator of G-protein signaling (GTPγS EC = 14 nM, 83 % E) that did not elicit a β-arrestin-2 recruitment functional response (E < 10 %).

Floating BiOBr/TiC aerogel spheres for efficient degradation of quinolone antibiotics: Rapid oxygen transfer via triphase interface and effective charges separation by internal electric field.

The limited transport of oxygen at the solid-liquid interface and the poor charge separation efficiency of single catalyst significantly impedes the generation of reactive oxygen species (ROS), thereby weakening the application potential of photocatalytic technology in water pollution control. Herein, a hollow porous photocatalytic aerogel sphere (calcium alginate/cellulose nanofibers (CA/CNF)) loaded BiOBr/TiC, combining a favourable mass transfer structure with effective catalytic centers was firstly presented. The floatability and hollow pore structure facilitated rapid O transfer via a triphase interface, thereby promoting the generation of ROS.

CA-SQBG: Cross-attention guided Siamese quantum BiGRU for drug-drug interaction extraction.

Accurate and efficient drug-drug interaction extraction (DDIE) from the medical corpus is essential for pharmacovigilance, drug therapy and drug development. To solve the problems of unbalance dataset and lack of accurate manual annotations in DDIE, a cross-attention guided Siamese quantum BiGRU (CA-SQBG) is constructed to improve feature representation learning ability for DDIE. It mainly consists of two quantum BiGRUs (QBiGRUs) and a cross-attention, where two QBiGRUs are Siamese implemented in a variational quantum environment to learn the contextual semantic feature representation of drug pairs, cross-attention is employed to learn mutual information from the Siamese QBiGRUs, which in turn allows the two modules to extract DDI more collaboratively.

24-Epibrassinolide treatment alleviates frost damage of apple flower via regulating proline, ROS, and energy metabolism.

Frost damage to apple flowers significantly affects both the quality and yield of apples, potentially leading to substantial economic losses. This study investigates the application of the environmentally friendly plant hormone 24-epibrassinolide (EBR) on apple flowers to assess its effects under frost stress conditions. The findings indicate that exogenous EBR treatment maintained favorable flower morphology, mitigated pistil browning, and reduced ion leakage.

Inducing resistance of postharvest fruits and vegetables through acibenzolar-S-methyl application: A review of implications and mechanisms.

Significant losses of vegetables and fruits occur at multiple stages, including harvest, sorting, storage, and transportation, primarily due to mechanical damage, pathogen invasion, and the natural process of senescence. To mitigate postharvest decay and maintain superior quality of produce, conventional techniques such as low temperature storage and synthetic fungicide treatment are widely employed. Acibenzolar-S-methyl (ASM), an effective plant resistance inducers, has demonstrated its efficacy in protecting against a diverse range of fungal and bacterial pathogens.

Targeting extracellular matrix components to attenuate microglia neuroinflammation: A study of fibulin-2 and CSPGs in a model of multiple sclerosis.

The extracellular matrix (ECM) plays an important role in the central nervous system (CNS), shaping tissue structure and functions as well as contributing to the pathology of chronic diseases such as multiple sclerosis (MS). ECM components, including fibulin-2 (FBLN2) and chondroitin sulfate proteoglycans (CSPGs), may impact neuroinflammation and remyelination. We investigated the capacity of FBLN2 to modulate immune responses and evaluated its interaction with CSPGs in experimental autoimmune encephalomyelitis (EAE), a common model for MS.

Callistephus A from Callistephus chinensis Nees alleviates concanavalin A-induced immunological liver injury in mice by inhibiting the activation of JAK/STAT1 and MAPK signaling pathways.

Callistephus chinensis Nees is an herbaceous plant in the Asteraceae family that has various traditional effects, especially in preventing liver disease. Callistephus A (CA) is a sesquiterpene compound with a rare 6/7 ring skeleton, which has been isolated only from the Callistephus chinensis Nees, but whether CA protects the liver is unknown. Immunological liver injury (ILI) is a common liver disease mediated by the immune system.

Development of a comprehensive food glycomic database and its application: Associations between dietary carbohydrates and insulin resistance.

Carbohydrates are an integral part of a healthy diet. The molecular compositions of carbohydrates encompass a very broad range of unique structures with many being ill-defined. This vast structural complexity is distilled into vague categories such as total carbohydrates, sugars, starches, and soluble/insoluble fibers.

Metagenomic insight into the diffusion signal factor mediated social traits of anammox consortia after starvation.

Biomass starvation is common in biological wastewater treatment. As a social trait of microbial community, how quorum sensing (QS) regulated bacterial trade-off through interactions after starvation remains unclear. This study deciphered the mechanism of anaerobic ammonium oxidation (anammox) consortia in response to starvation, including reducing extracellular electron transfer (EET), adenosine 5'-triphosphate (ATP) content and amino acid metabolism.

Nitrogen removal from multi-electrolyte saline wastewater via mainstream anammox in warm climate conditions.

High salts concentrations in wastewater hinder its biological treatment. Recent research has investigated the inhibitory effect of salinity on the anammox process, mainly focusing on NaCl. Thus, the inhibition caused by multi-electrolytes salinity on freshwater anammox bacteria remains unclear.

Trends, characteristics, and outcomes of pregnancy in women with attention-deficit hyperactivity disorder: A nationwide analysis.

Objective: To assess clinical and obstetric characteristics associated with pregnant patients with a diagnosis of attention-deficit hyperactivity disorder (ADHD).

Methods: This serial cross-sectional study queried the Agency of Healthcare Research and Quality's Healthcare Cost and Utilization Project National Inpatient Sample. The study population was 16,759,786 hospital deliveries from 2016 to 2020.

Protocol for the generation of HLF+ HOXA+ human hematopoietic progenitor cells from pluripotent stem cells.

Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.

Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single-particle cryo-EM.

One of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interactions, HIV-2 CA assembly remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we report high-resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6.

Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.

Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).

Conceptualizing a load and volume autoregulation integrated velocity model to minimize neuromuscular fatigue and maximize neuromuscular adaptations in resistance training.

Resistance training (RT) load and volume are considered crucial variables to appropriately prescribe and manage for eliciting the targeted acute responses (i.e., minimizing neuromuscular fatigue) and chronic adaptations (i.

Integrated metabolomic and transcriptomic strategies to reveal adaptive mechanisms in barley plant during germination stage under waterlogging stress.

Barley (Hordeum vulgare L.) is an important cereal crop used in animal feed, beer brewing, and food production. Waterlogging stress is one of the prominent abiotic stresses that has a significant impact on the yield and quality of barley.

Assessment of geochemistry and irrigation suitability of the River Ganga, Varanasi, India: PCA reduction for water quality index and health risk evaluation.

Surface water chemistry of the River Ganga at Varanasi was analyzed at 10 locations over 3 years (2019-2021) across pre-monsoon, monsoon, and post-monsoon seasons. The study aimed to assess water parameters using principal component analysis (PCA), calculate the water quality index (WQI), determine processes governing water chemistry, evaluate irrigation suitability, and estimate non-carcinogenic health risks. The physical parameters measured included pH (8.

How low should we go? Outcomes of ECMO in neonates with low gestational age or birth weight.

Purpose: Initial recommendations for ECMO had relative contraindications for low birth weight (BW) or low gestational age (GA) babies. However, more recent literature has demonstrated improved and acceptable outcomes of ECMO in smaller neonates. The purpose of this study was to understand both utilization and survival in patients with lower GA and BW.

ISCT MSC committee statement on the US FDA approval of allogenic bone-marrow mesenchymal stromal cells.

The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.

Comparing the Palmar Radiocarpal Artery Vascularized Bone Graft with Alternatives for Unstable Scaphoid Nonunions: A Retrospective Analysis.

Purpose: We compared the radiographic union and magnitude of humpback deformity correction when using different vascularized bone grafts (VBGs) and nonvascularized bone grafts (NVBGs) in the treatment of unstable scaphoid nonunions (USNUs).

Methods: This was a retrospective radiographic review of 93 patients with an USNU treated between 2013 and 2022 at a single center by a single surgeon. Inclusion criteria included skeletally mature patients with radiographic evidence of an USNU resulting from failure of either nonsurgical or operative treatment.

Otherwise, inoperable. The role of ECMO in thoracic surgery - focus on the mediastinum.

The use of extracorporeal membrane oxygenation (ECMO) in surgery is expanding as the medical community started adopting it, with good results, for procedures with high risk of respiratory and hemodynamic instability. This technique provided the possibility to reduce the number of patients previously considered inoperable because of these limitations. Thymic epithelial tumors (TETs) are rare neoplastic mediastinal lesions, with a reported incidence of 0.

Correlations between spinopelvic parameters and health-related quality of life in degenerative lumbar scoliosis patients before and after long -level fusion surgery.

Background: For degenerative lumbar scoliosis (DLS), prior studies mainly focused on the preoperative relationship between spinopelvic parameters and health-related quality of life (HRQoL), lacking an exhaustive evaluation of the postoperative situation. Therefore, the postoperative parameters most closely bonded with clinical outcomes has not yet been well-defined in DLS patients. The objective of this study was to comprehensively assess the correlation between radiographic parameters and HRQoL before and after surgery, and to identified the most valuable spinopelvic parameters for postoperative curative effect.