Discovery and SAR study of highly selective and potent 1,2,4-oxadiazole-based S1PR1 agonists.

Sphingosine-1-phosphate receptor 1 (S1PR1) is a validated therapeutic target for immune-mediated diseases such as multiple sclerosis and ulcerative colitis, owing to its critical role in regulating of lymphocyte migration. However, the clinical utility of current S1PR1 agonists is often limited by cardiovascular adverse effects, particularly dose-dependent bradycardia. Enhancing receptor subtype selectivity represents a promising strategy to mitigate these risks.

Interactions of extracellular polymeric substances with ferrihydrite and subsequent 17α-ethinylestradiol photodegradation: Impact of Fe(III)-EPS complexes formation.

Microbial-derived extracellular polymeric substances (EPS) and iron minerals are ubiquitous in aquatic environments, and they can influence the fate of organic micropollutants such as 17α-ethinylestradiol (EE2). However, the interactions between EPS and iron minerals, and their influence on EE2 photodegradation, are seldom addressed in the literature. This study explored the effects of EPS derived from different aerobic or anaerobic microbials on the reductive dissolution of ferrihydrite (Fhy) and subsequent EE2 photodegradation, with emphasis on the impact of Fe-EPS complexes formation.

Synergy in the transformation of Bisphenol A by anaerobic microorganisms and manganese dioxide: The bridging role of extracellular polymeric substances.

In aquatic environments, bisphenol A (BPA) can undergo natural attenuation through microbial activity and manganese oxide-mediated processes. They commonly coexist, and that suggests the need to consider potential synergies between biotic and abiotic processes in BPA attenuation. This study explored BPA transformation in the coexistence of anaerobic microorganisms and β-MnO, with emphasis on the role of extracellular polymeric substances (EPS) commonly present in dissolved organic matter.

Clinical and pathological features of 209 cases of pilomatricoma in children: a retrospective study.

Background: Pilomatricoma, albeit benign, may have a potential impact on children's appearance and health. Clinical practice has revealed variations in the clinical manifestations, anatomical locations, and sizes of pilomatricoma among different pediatric patients. However, few studies have comprehensively summarized the correlations between these features and treatment efficacy, which is crucial for enhancing clinicians' understanding and diagnostic accuracy of the disease.

Target-aware 3D molecular generation based on guided equivariant diffusion.

Recent molecular generation models for structure-based drug design (SBDD) often produce unrealistic 3D molecules due to the neglect of structural feasibility and drug-like properties. In this paper, we introduce DiffGui, a target-conditioned E(3)-equivariant diffusion model that integrates bond diffusion and property guidance, to address the above challenges. The combination of atom diffusion and bond diffusion guarantees the concurrent generation of both atoms and bonds by explicitly modeling their interdependencies.

Recent advances in Cu-based heterostructures and their Li-CO battery application.

Lithium carbon dioxide (Li-CO) batteries have recently attracted extensive attention since they offer a great approach to simultaneously realize CO capture and conversion. However, the sluggish kinetics and complex reaction mechanism at the cathodic side significantly hinder the improvement in the performance of Li-CO batteries. Therefore, highly-efficient electrocatalysts are required to solve the problems encountered in Li-CO batteries.

Exploring a Quantitative Formula for the Total Surgical Amount in Patients With Type III Acute Acquired Concomitant Esotropia.

Purpose: To establish a dose-response reference for surgical planning in type III acute acquired concomitant esotropia (AACE).

Methods: This study included consecutive patients who underwent unilateral or bilateral medial rectus recession for type III AACE or common forms of esotropia correction from January 2019 to August 2023. All patients with a minimum follow-up of 3 months were analyzed.

Fungal spore inactivation in drinking water by UV: Kinetics and mechanistic insights with transcriptomic and metabolomic analyses.

Fungal spores in drinking water distribution systems can resist chlor(am)ination and cause odor issues and health risks, posing a significant threat to drinking water safety. Conventional low-pressure mercury lamps emitting at 254 nm (UV) exhibit limited effectiveness against fungal spores. Far-ultraviolet light at 222 nm (UV) has emerged as a promising approach for efficient fungal spore inactivation.

Comparison of Artificial Intelligence and Traditional Methods in Preoperative Planning for Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

Although the application of artificial intelligence in orthopedics is becoming increasingly widespread, and initial progress has been made particularly in total hip arthroplasty (THA), its use in preoperative planning remains in the exploratory stage. Most existing studies are small-scale observational studies with inconsistent results, making it difficult to establish a unified clinical consensus. Therefore, our study aims to explore the latest research developments and potential unique advantages of artificial intelligence in preoperative planning for THA.

Design and synthesis of Betti base derivatives as EGFR inhibitors.

EGFR serves as a critical oncogenic driver in NSCLC pathogenesis. While multiple generations of EGFR TKIs have been clinically approved, their efficacy is frequently limited by rapid drug resistance. Several EGFR allosteric inhibitors targeting a site adjacent to the ATP-binding site have been reported.

Reasonable Design of Near-Infrared Boron Dipyrromethene with Cationic Pyridinium for Super-Resolution Imaging of Dynamic Voltages of Mitochondria in Living Cells.

Mitochondrial membrane potential (ΔΨ) is a critical regulator of cellular homeostasis and an established biomarker in mitochondrial dysfunction. While super-resolution fluorescence imaging reveals intrinsic links between mitochondrial ultrastructure and function, prolonged monitoring of the dynamic ΔΨ remains constrained by the scarcity of photostable voltage-sensitive probes. Here, we designed and synthesized three water-soluble near-infrared boron dipyrromethene (BODIPY) probes ().

Alpha-ketoglutarate protects against myocardial infarction via FTO-mediated anti-inflammatory macrophage activation.

Ischemic heart disease lacks optimal therapies targeting post-infarction inflammation and remodeling. The role of TCA cycle metabolites in modulating macrophage-driven cardiac inflammation remains unclear. This study hypothesized that AKG supplementation attenuates cardiac dysfunction by regulating macrophage activation via TCA cycle replenishment and FTO-dependent epigenetic mechanisms.

Ultra-fast SOP rotation tracking and its enabled feedforward adaptive equalization based on superimposed chirp pilot.

We propose to track state of polarization (SOP) rotation by utilizing chirp pilots processed through fractional Fourier transform (FrFT). Superimposed on dual-polarization data signal, the chirp pilots with different FrFT rotation orders can converge to fractional energy peaks and then be distinguished by combining FrFT with MIMO structure. Consequently, SOP rotation resulting in energy distribution can be estimated by leveraging aggregated peaks in the matched fraction domain.

A p-n CuGaS/g-CN heterojunction in S-scheme with escalated charge transport and photothermal effect for solar-driven hydrogen evolution.

The construction of built-in electric field (BIEF) in heterojunction is an effective strategy to enhance solar-driven hydrogen (H) production by minimizing charge carrier recombination and improving transport kinetics. Herein, p-type ternary sulfide CuGaS (CGS) and n-type g-CN nanosheets (CN) are integrated to construct a p-n heterojunction through a simple co-precipitation method for photocatalytic hydrogen evolution reaction (HER). In situ X-ray photoelectron spectroscopy (in situ XPS), in situ electron paramagnetic resonance (EPR) and density functional theory (DFT) calculations revealed that differences in Fermi levels and carrier concentrations between CGS and CN induce charge migration following an S-scheme mechanism, which aligned well with the intrinsic p-n junction field.

Regulation mechanisms of biochar-derived endogenous substances on heavy metal mobility in the soil-crop system: A critical review.

The utilization of biochar (BC) for the remediation of heavy metals (HMs) in contaminated soils has attracted considerable global interest. This review synthesizes advancements in the formation, composition, and fraction distribution of endogenous substances in BC, as well as their roles in regulating both cationic and anionic HMs in soils over the past decade (up to 2025). The physicochemical and structural properties of BC are determined by feedstock selection and pyrolysis temperature, which regulate the composition, concentration, and fractionation of its constituents.

Palmatine inhibits colorectal cancer proliferation and metastasis by regulating miR-363-3p/AURKA axis.

Colorectal cancer, a prevalent digestive system malignancy, is characterized by a high incidence, low early detection rate, limited surgical resection opportunities, and high mortality. Palmatine (PAL), an active ingredient primarily found in Coptidis Rhizoma, exhibits diverse pharmacological effects, including antibacterial, anti-inflammatory, and anti-tumor properties. While PAL has been shown to effectively curb the progression of colorectal cancer, the underlying mechanisms have yet to be fully elucidated.

Predictive model for feeding intolerance in neonates with hypoxic ischemic encephalopathy during therapeutic hypothermia.

To construct a nomogram for feeding intolerance (FI) during therapeutic hypothermia (TH) in neonates with hypoxic-ischemic encephalopathy (HIE). 179 neonates with HIE were recruited between March 2017 and July 2023 and clinical data subjected to least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis. A predictive model was constructed and verified by receiver operating characteristic (ROC) curve analysis, calibration plots and decision curve analysis (DCA).

Quantitative analysis of PBAT microplastics and their degradation products in soil by mass spectrometry.

Global production of biodegradable plastics is increasing, but the degradation behavior of microplastics derived from these items in soil is still scarcely reported. In this study, a method for quantifying soil poly(butylene adipate-co-terephthalate) (PBAT) microplastics was developed, and their degradation behavior in three different soils was investigated. PBAT was quantified by analyzing the content of the monomer terephthalic acid (TPA) released during thermally assisted alkali hydrolysis, using liquid chromatography-mass spectrometry (LC-MS).

Oral microbiota-regulating and inflammation-targeted polymersome-hydrogels for RNAi therapy of ulcerative colitis.

The treatment of ulcerative colitis is harassed by its intricate pathogenesis and the harsh gastrointestinal environment. Herein, oral microbiota-regulating and inflammation-targeted polymersome-hydrogels are developed by incorporating gallic acid and tumor necrosis factor α-specific siRNA-encapsulated polymersomes (GA-siTNFα-PS) into self-healable and eatable hydrogels (SHE-Gel) formed from thiolated sodium alginate and dopamine-modified oxidized inulin (DA-OIn) for oral RNAi therapy of ulcerative colitis. SHE-Gel is stable in stomach, resides in the intestine, and degrades in the colon by colon-specific inulinase.

Sex-based differences in mitochondrial activity and cellular calcium signaling in isolated mice cardiomyocytes intervened by doxorubicin.

Doxorubicin (DOX) is widely used in cancer therapy, but its cardiac toxicity remains a significant challenge. Sex plays a role in DOX-induced cardiotoxicity, with females exhibiting less sensitivity. However, the precise molecular mechanisms underlying this difference are not fully understood.

Design of pyrrolo[2,3-]pyrimidine-endoperoxide hybrids as first-in-class dual degraders of cyclin D1/3 and CDK4/6 with potent antiproliferative effects.

The hyperactive Cyclin D-CDK4/6 heterodimer is a key cell cycle regulator in breast cancer, and CDK4/6 inhibitors featuring pyridine/pyrrolo[2,3-]pyrimidine scaffolds are clinically used treatments. In addition, numerous studies have reported the antitumor activity of endoperoxide compounds. In this study, we designed and synthesized a series of novel endoperoxide-pyridine/pyrrolo[2,3-]pyrimidine derivatives.

Map geographic information road extraction method based on generative adversarial network and U-Net.

In today's rapidly developing remote sensing technology, accurately extracting geographic information from maps is crucial for many key areas such as urban planning, environmental monitoring, and traffic management. However, due to the complexity and variability of remote sensing images, effectively extracting road information from multi-scale geographic images remains a technical challenge. Therefore, the study innovatively proposes a fusion model for panchromatic and multi-spectral images and a fusion map geographic information extraction model from the perspectives of image fusion and road segmentation.

Response of mercury methylation to algal bloom decomposition or elevated CO in surface sediments from the East China Sea.

Methylmercury (MeHg), a neurotoxin bioaccumulated in aquatic food webs, poses risks to ecosystems and human health, with marine products mainly contributing to global human MeHg exposure. The East China Sea (ECS), influenced by anthropogenic Hg inputs and environmental changes like algal boom and elevated CO, is critical for understanding MeHg dynamics. This study investigated how algal decomposition and elevated CO (1000 ppm) affect Hg methylation in the ECS sediments.

Bacterial infection in weaned piglets promotes diarrhea by inducing the NLRP3 inflammasome-pyroptosis pathway.

Bacterial infections in weaned piglets are a major cause of diarrhea and even death. However, the mechanism by which bacterial infections in weaned piglets lead to diarrhea remains unclear. The NLRP3 inflammasome and pyroptosis are considered key factors in mucosal immune damage.

Prenatal fentanyl exposure affects social dominance and myelination patterns in the adult mouse brain.

Fentanyl use has reached epidemic proportions, and more adults are administering the drug illicitly. Despite its high use rates, very little is known of the long-term effects following prenatal fentanyl exposure. Using an oral model of lower-dose prenatal fentanyl administration in mice, we found that fentanyl-exposed offspring developed similarly to their saline-exposed counterparts.