Comprehensive multi-omics analysis elucidates colchicine-induced toxicity mechanisms and unveils the therapeutic potential of MLN4924 and kinase inhibitors.

Colchicine is a widely prescribed anti-inflammatory drug for the treatment of gout, familial Mediterranean fever and pericarditis, but its narrow therapeutic window presents a significant risk of severe toxicity. Despite its clinical relevance, the molecular mechanisms underlying colchicine's pharmacological effects and associated toxicity and explored potential therapeutic interventions to mitigate its adverse effects. We showed the colchicine's impact on cellular morphology in human umbilical vein endothelial cells (HUVEC) and HeLa cells including cell rounding and detachment following 24 h of exposure that revealed pronounced cytotoxic effects.

Regulating copper homeostasis of tumor cells to promote cuproptosis for enhancing breast cancer immunotherapy.

Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on CuS (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects.

Mycobacterium tuberculosis short mutant H37Rv-S with reduced growth adaptability is more readily recognized by the host immune system.

Mycobacterium tuberculosis (Mtb) is the bacterium responsible for causing Tuberculosis (TB) and understanding its mechanisms of virulence, persistence, and pathogenesis is a global research priority. Attenuated strains of Mtb are valuable tools for investigating the genes and proteins involved in these processes. In this study, we identified an Mtb mutant, H37Rv-S, which exhibits a shorter mycelium, smoother colony, slower growth, and reduced antibiotics resistance compared to the wild-type strain H37Rv.

Immunostimulatory activity of sea buckthorn polysaccharides via TLR2/4-mediated MAPK and NF-κB signaling pathways in vitro and in vivo.

SP0.1-1, derived from Sea buckthorn (Hippophae rhamnoides L.), has been discovered to exhibit unique antioxidant activity.

The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma.

Background: Osteosarcoma, as the most common primary malignant bone tumor, has become one of the main causes of cancer-related deaths in adolescents and children. This study thus proposes new biomarkers for OS based on whole-transcriptome re-analysis and experimental confirmation.

Methods: We find two circRNA dataset related to OS, from tissue and cell perspectives respectively, from the GEO database.

[Alpha-bisabolol reverses ABCB1-mediated multidrug resistance in tumor and its mechanisms].

Objective To investigate whether alpha-bisabolol can effectively reverse ATP binding cassette subfamily B member 1 (ABCB1)-mediated multidrug resistance (MDR) in tumors and to explore the underlying mechanisms. Methods The network pharmacology was utilized to analyze the active components of Agrimonia Eupatoria, predict target genes, and perform GO and KEGG pathway analysis. Molecular docking and thermal stability assays were conducted to examine the interaction between alpha-bisabolol and ABCB1.

Insights from the international workshop on "Adapting agriculture to climate change and air pollution".

An international workshop on "Adapting Agriculture to Climate Change and Air Pollution" took place at Nanjing University of Information Science and Technology, Nanjing, China, during 23-27 October, 2023. Experts working in various multi-disciplinary areas of agroecosystem and environmental research gathered for academic communication and discussions. Two discussion groups focused on "agriculture under air pollution and climate change: current challenges and priorities for the future" and "adapting agriculture to air pollution and climate change: current status and next steps.

Mechanistic Modeling of Pollutant Mass Redistribution (Sorption/Desorption) in Heterogeneous Systems Explaining Unexpected Slow Kinetics.

Redistribution of pollutants between different solid phases occurs frequently in field and laboratory settings. Examples include the input of urban particles carrying pollutants into soils or rivers with suspended particles or passive sampling. Since multiple mass transfer mechanisms are involved and natural particles typically are very heterogeneous, modeling of sorption/desorption kinetics is challenging.

Exploring Ion Transmission Mechanisms in Clay-Based 2D Nanofluidics for Osmotic Energy Conversion.

Clay-based 2D nanofluidics present a promising avenue for osmotic energy harvesting due to their low cost and straightforward large-scale preparation. However, a comprehensive understanding of ion transport mechanisms, and horizontal and vertical transmission, remains incomplete. By employing a multiscale approach in combination of first-principles calculations and molecular dynamics simulations, the issue of how transmission directions impact on the clay-based 2D nanofluidics on osmotic energy conversion is addressed.

Horizontal transfer of plasmid-like extrachromosomal circular DNAs across graft junctions in Solanaceae.

The transfer of genetic material between stocks and scions of grafted plants has been extensively studied; however, the nature and frequency of the transferred material remain elusive. Here, we report a grafting system involving woody goji as the stock and herbaceous tomato as the scion, which was developed using in vitro and in vivo approaches; the results confirmed horizontal transfer of multiple nuclear DNA fragments from donor goji cells to recipient tomato cells. Tomato tissues containing goji donor DNA fragments at or near the grafting junctions had a perennial-biased anatomical structure, from which roots or shoots were regenerated.

Pan-immune-inflammation value as a novel prognostic biomarker for digestive system cancers: a meta-analysis.

Background: Digestive system cancers pose a significant global health challenge with high incidence and mortality rates. Inflammation is a key factor in cancer progression, necessitating reliable prognostic indicators. The pan-immune-inflammation value (PIV), as a new biomarker of immune-inflammatory response, has emerged as a potential prognostic biomarker for cancers.

Health impacts of takeaway management zones around schools in six different local authorities across England: a public health modelling study using PRIMEtime.

Background: In England, the number of takeaway food outlets ('takeaways') has been increasing for over two decades. Takeaway management zones around schools are an effective way to restrict the growth of new takeaways but their impacts on population health have not been estimated.

Methods: To model the impact of takeaway management zones on health, we used estimates of change in and exposure to takeaways (across home, work, and commuting buffers) based on a previous evaluation suggesting that 50% of new outlets were prevented from opening because of management zones.

DAPNet: multi-view graph contrastive network incorporating disease clinical and molecular associations for disease progression prediction.

Background: Timely and accurate prediction of disease progress is crucial for facilitating early intervention and treatment for various chronic diseases. However, due to the complicated and longitudinal nature of disease progression, the capacity and completeness of clinical data required for training deep learning models remains a significant challenge. This study aims to explore a new method that reduces data dependency and achieves predictive performance comparable to existing research.

Superior proton conductivity of amino acid-modified UiO-66-(COOH) embedded in chitosan: Mechanistic insights into the acid-base interactions.

We focus on optimizing acid-base interactions and hydrogen bonding networks to achieve enhanced proton conductivity under low relative humidity (RH) and high temperature. By functionalizing UiO-66-(COOH) with glutamic acid (Glu) and lysine (Lys), we generate Glu-UiO-66-(COOH) and Lys-UiO-66-(COOH). These modified materials are subsequently incorporated into chitosan (CS) to produce the composites Glu-UiO-66-(COOH)@CS and Lys-UiO-66-(COOH)@CS.

Preparation of hydrophobic and lipophilic carboxymethyl cellulose composite aerogel using ferrous ion/ persulfate and its directed oxidation for oil-water emulsion separation.

In particular, efficient oxidative demulsification is an effective method for oil-water separation. However, the inactivation of free radicals owing to the rapid release of transition metals is the main factor that reduces the effectiveness. In this study, a hydrophobic and lipophilic CP/SiO@Fe composite aerogel was prepared using carboxymethyl cellulose as substrate, polyvinyl alcohol as reinforcement, and SiO nanoparticles as hydrophobic modifier.

Preparation of soybean isolate protein/xanthan gum/agar-Lycium ruthenicum anthocyanins intelligent indicator films and its application in mutton preservation.

The preparation of intelligent indicator films containing anthocyanins and their utilization for real-time monitoring of meat freshness represents a prominent research topic of food packaging. In this study, anthocyanins (ALR) were extracted from Lycium ruthenicum (LR) using solvent extraction. Subsequently, these anthocyanins were incorporated into films composed of soybean isolate protein (SPI), xanthan gum (XG) and agar, resulting in SPI/XG/Agar-ALR pH-responsive intelligent indicator films.

Nondigestible stachyose binds membranous HSP90β on small intestinal epithelium to regulate the exosomal miRNAs: A new function and mechanism.

Oligosaccharides are conventionally recognized as "passersby" in the small intestine. However, our research has reframed this understanding by uncovering a new function of oligosaccharide stachyose, which binds hydrophobic residues of membranous HSP90β on small intestinal epithelial cells, thus reprograming the exosomal miRNA profile. CRISPR-Cas9-mediated HSP90β knockout abolished the accumulation of stachyose on cell membrane and its regulatory effects on these miRNAs.

β-catenin disruption decreases macrophage exosomal α-SNAP and impedes Treg differentiation in acute liver injury.

Hepatic macrophages and regulatory T cells (Tregs) play an important role in the maintenance of liver immune homeostasis, but the mechanism by which hepatic macrophages regulate Tregs in acute liver injury remains largely unknown. Here, we found that the hepatic Treg proportion and β-catenin expression in hepatic macrophages were associated with acetaminophen (APAP) and D-galactosamine (D-GalN)/ lipopolysaccharide (LPS)-induced acute liver injury. Interestingly, β-catenin was markedly upregulated only in infiltrating macrophages, but not in resident Kupffer cells.

Electron Transfer Mediator Modulates Type II Porphyrin-Based Metal-Organic Framework Photosensitizers for Type I Photodynamic Therapy.

Photodynamic therapy (PDT), a minimally invasive and effective local treatment, heavily depends on photosensitizer (PS) performance and oxygen availability. Despite the use of PS-based metal-organic frameworks (MOFs) to address the solubility and aggregation issues of PSs, the inherent hypoxic intolerance of mainstream Type II PDT remains challenging. Herein, we report an electron transfer strategy for the fabrication of hypoxia-tolerant Type I MOFs by encapsulating thymoquinone (TQ) into existing Type II MOFs.

Characteristics of a CCL21-gene modified dendritic cell vaccine utilized for a clinical trial in non-small cell lung cancer.

The treatment of non-small cell lung cancer has made major strides with the use of immune checkpoint inhibitors, but there remains a significant need for therapies that can overcome immunotherapy resistance. Dendritic cell (DC) vaccines have been proposed as a therapy that can potentially enhance the antitumor immune response. We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab.