Size-dependent desolvation of hydrophobic nanoparticles in aqueous osmolytes.

The salting effect of osmolytes on the hydrophobic association and solvation of proteins has been extensively studied over several decades. However, the effect of the solute size and the underlying mechanisms are poorly documented. In this study, the effects of urea and trimethylamine--oxide (TMAO) on the pairwise interactions of hydrophobic carbon nanoparticles (NPs) with different sizes have been studied using molecular dynamics simulations.

Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH by targeting cystathionine γ-lyase.

The transcription factor Forkhead box protein O1 (FoxO1) is a well-established regulator of glucose and lipid metabolism, yet its role in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis remains debated. This study investigates hepatocyte-specific FoxO1 mechanisms driving hepatic inflammation in MASH. Using hepatocyte-specific FoxO1-knockout (KO) mice fed a methionine-choline-deficient diet and LPS-treated FoxO1-KO cells, we demonstrated that FoxO1 depletion exacerbates hepatic inflammation, ballooning degeneration, and upregulates TNF-α, CXCL8, and CXCL2 in vivo and in vitro.

The antibody-drug conjugate SHR-A1904 for targeting CLDN18.2 in advanced gastric or gastroesophageal junction cancer: a phase 1 trial.

Claudin-18 isoform 2 (CLDN18.2), a tight junction protein expressed in non-malignant gastric epithelium and exposed on tumor cell surface during malignant transformation, is a promising therapeutic target for gastric and gastroesophageal junction (G/GEJ) cancers. SHR-A1904 is an antibody-drug conjugate comprising CLDN18.

Investigation of the Defect Cu Centers in the Paddle Wheel MOF: Defective Structures, EPR Spectra, and HO Adsorption.

Due to the different Cu centers, the [CuCu(HO)LCl] MOF has been widely studied using electron paramagnetic resonance (EPR) spectra, particularly regarding its capacity for gas molecule adsorption. In the present work, based on the occupation sites of Cu in [CuCu(HO)LCl], three corresponding fragments, dimer [CuO]-[CuO] (C), defective [CuO] (C), and [CuN] (C), are established to investigate the two different EPR signals (S and S) and the local environment of Cu. By applying the order perturbation formulas of the spin-Hamiltonian parameters, C and C can be excluded because of the EPR silence of the antiferromagnetically coupled Cu pair at low (7 K) temperatures and the silent signal of Cu.

Antiallergic drugs drive the alteration of microbial community and antibiotic resistome in surface waters: A metagenomic perspective.

Antiallergic drugs (AADs) are emerging contaminants of global concern due to their environmental persistence and potential ecological impacts. This study investigated the effects of seven AADs (chlorpheniramine, diphenhydramine, cetirizine, loratadine, desloratadine, sodium cromoglicate and calcium gluconate) at environmentally relevant concentrations on antibiotic resistome and bacterial community structures in water using microcosm experiments and metagenomic sequencing. The results showed that AADs increased the abundance of antibiotic-resistant bacteria (ARB) by 1.

Deciphering the Physical Binding Mechanism of Enzyme-Photosensitizer Facilitates Catalysis-Augmented Photodynamic Therapy.

Enzyme-photosensitizer (PS) conjugates hold great promise for clinical treatment of cancer and infectious diseases via catalysis-augmented photodynamic therapy (PDT). Compared to covalent coupling, physical binding utilizing noncovalent interactions provides a simple and nondestructive strategy to combine PS with enzymes. However, the mechanism of enzyme-PS physical combination remains largely unknown, and physically bonded enzyme-PS conjugates are rarely reported.

Environmental Charge-Mediated Nanopiezocatalysis for Sonodynamic Therapy.

Piezocatalysis garners growing attention in sonodynamic therapy (SDT). However, its mechanism remains controversial due to the prominent but conflicting theories of energy band and piezoelectric effect. The former just focuses on the role of carriers, while the latter emphasizes only the contribution of screening charges.

A New Supercritical Phase and Fast Transport of Water in Two-Dimensions.

Water structure and dynamics in confinement systems differ significantly from those in the bulk phase. Here, we report a new supercritical (SC) phase of water found in a 0.65 nm Au nanoslit.

A cation-gating mechanism for enhanced CO2/N2 separation by porous nanostructure supported ionic liquid membrane.

2D porous material supported ionic liquid membranes (SILMs) have demonstrated great potential for CO2 separation and purification, outperforming the original porous material. However, the working mechanism behind their enhanced CO2 selectivity remains unclear. In this study, we have conducted molecular dynamics simulation to investigate the CO2/N2 separation performance and the underlying mechanism of SILMs taking 2D rhombic N-graphdiyne (r-N-GDY) with intrinsic high thermal stability and porous structure covered with 1-butyl-3-methylimidazolium tetrafluoroborate as the representative SILM model.

Functional characterization of an epsilon glutathione S-transferase (SfGSTe9) associated with insecticide detoxification in Spodoptera frugiperda.

The fall armyworm, Spodoptera frugiperda (J. E. Smith) is a notorious insect pest of poaceae and causes severe economic damage to major cereal crop.

Antihistamine drug loratadine at environmentally relevant concentrations promotes conjugative transfer of antibiotic resistance genes: Coeffect of oxidative stress and ion transport.

Due to the widespread use of loratadine (LOR) as an antihistamine, it is widely distributed in the environment as an emerging contaminant. However, its impact on the dissemination of antibiotic resistance genes (ARGs) remains unclear. This study investigated the effect of LOR on the conjugative transfer of ARGs and elucidated the potential mechanisms through transcriptome analysis.

Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury.

Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries.

Evaluations of the Perturbation Resistance of the Deep-Learning-Based Ligand Conformation Optimization Algorithm.

In recent years, the deep learning (DL) technique has rapidly developed and shown great success in scoring the protein-ligand binding affinities. The protein-ligand conformation optimization based on DL-derived scoring functions holds broad application prospects, for instance, drug design and enzyme engineering. In this study, we evaluated the robustness of a DL-based ligand conformation optimization protocol (DeepRMSD+Vina) for optimizing structures with input perturbations by examining the predicted ligand binding poses and scoring.

Characteristics of heterotrophic endophytic bacteria in four kinds of edible raw vegetables: species distribution, antibiotic resistance, and related genes.

This study aimed to explore antibiotic resistance characteristics and species of heterotrophic endophytic bacteria (HEB) in four kinds of edible raw vegetables, including radishes, lettuces, onions, and tomatoes. A total of 144 HEB were isolated and tested for resistance to sulfamethoxazole (SMZ), tetracycline (TET), cefotaxime (CTX), and ciprofloxacin (CIP), and their species were identified by 16S rRNA gene sequencing. Antibiotic resistance genes (ARGs) and class I integron in antibiotic-resistant isolates were analyzed by polymerase chain reaction.

RNAi targeting Na and CPR via leaf delivery reduces adult emergence and increases the susceptibility to λ-cyholthin in Tuta absoluta (Meyrick).

The tomato leafminer, Tuta absoluta (Meyrick), one of the most economically destructive pests of tomato, causes severe yields losses of tomato production globally. Rapid evolution of insecticide resistance requires the development of alternative control strategy for this pest. RNA interference (RNAi) represents a promising, innovative control strategy against key agricultural insect pests, which has recently been licensed for Colorado Potato Beetle control.

Inhibition of FoxO1 ameliorates hepatic steatosis and hepatitis in nonalcoholic steatohepatitis mice through regulation of gut microbiota.

Objective: We aimed to investigate the role of forkhead box O1 (FoxO1) inhibitor AS1842856 (AS) in nonalcoholic steatohepatitis (NASH) mice and the potential mechanisms.

Methods: Mice were given methionine-choline-sufficient (MCS), or methionine- and choline-deficient (MCD) diet for 5 weeks, along with AS (60 mg/kg) or vehicle gavage treatment (0.2 mL/day).

Fully Flexible Molecular Alignment Enables Accurate Ligand Structure Modeling.

Accurate protein-ligand binding poses are the prerequisites of structure-based binding affinity prediction and provide the structural basis for in-depth lead optimization in small molecule drug design. However, it is challenging to provide reasonable predictions of binding poses for different molecules due to the complexity and diversity of the chemical space of small molecules. Similarity-based molecular alignment techniques can effectively narrow the search range, as structurally similar molecules are likely to have similar binding modes, with higher similarity usually correlated to higher success rates.

Metagenomic insights into effects of carbon/nitrogen ratio on microbial community and antibiotic resistance in moving bed biofilm reactor.

This study investigated the effects of carbon/nitrogen (C/N) ratio on microbial community in moving bed biofilm reactor (MBBR) using metagenomic analysis, and the dynamic changes of relevant antibiotic resistance genes (ARGs) were also analyzed. The results showed that under low C/N ratio, MBBR exhibited average removal rates of 98.41 % for ammonia nitrogen and 75.

Graphene Quantum Dots Nanoantibiotic-Sensitized TiO Heterojunctions for Sonodynamic-Nanocatalytic Therapy of Multidrug-Resistant Bacterial Infections.

The exploration of sonodynamic therapy (SDT) as a possible replacement for antibiotics by creating reactive oxygen species (ROS) is suggested as a non-drug-resistant theranostic method. However, the low-efficiency ROS generation and complex tumor microenvironment which can deplete ROS and promote tumor growth will cause the compromised antibacterial efficacy of SDT. Herein, through an oxygen vacancy engineering strategy, TiO microspheres with an abundance of Ti are synthesized using a straightforward reductant co-assembly approach.

Organic-Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme.

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods.

Effects of clarithromycin exposure on the growth of Microcystis aeruginosa and the production of algal dissolved organic matter.

Antibiotics are commonly found in the aquatic environment, which can affect microbial community compositions and activities, and even have potential adverse impacts on human and ecosystem health. The current understanding of the effects of antibiotics on microalgae growth and algal dissolved organic matter (DOM) remains indistinct. To understand the toxic effects of antibiotics on the microalgae, Microcystis aeruginosa was exposed to clarithromycin (CLA) in this study.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.