Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.

The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

Mussel-inspired electroactive, antibacterial and antioxidative composite membranes with incorporation of gold nanoparticles and antibacterial peptides for enhancing skin wound healing.

Large skin wounds are one of the most important health problems in the world. Skin wound repair and tissue regeneration are complex processes involving many physiological signals, and effective wound healing remains an enormous clinical challenge. Therefore, there is an urgent need for a strategy to rapidly kill bacteria, promote cell proliferation and accelerate wound healing. At present, electrical stimulation (ES) is often used in the clinical treatment of skin wounds and can simulate the endogenous biological current of the body and accelerate the repair process of skin wounds. However, a single ES strategy has difficulty covering the entire wound area, which may lead to unsatisfactory therapeutic effects. To overcome this deficiency, it is essential to develop a collaborative treatment strategy that combines ES with other treatments. In this study, gold nanoparticles and antibacterial peptides (Os) were loaded on the surface of poly(lactic-co-glycolic acid) (PLGA) material through the reducibility and adhesion of polydopamine (PDA) and improved the electrical activity, anti-inflammatory, antibacterial and biocompatibility properties of the polymer material. At the same time, this composite membrane material (Os/Au-PDA@PLGA) combined with ES was used in wound therapy to improve the wound healing rate. The results show that the new wound repair material has good biocompatibility and can effectively promote cell proliferation and migration. Through the combined application of gold nanoparticles and antibacterial peptides Os, the polymer materials have more efficient bactericidal and antioxidant effects. The antibacterial experiment results showed that gold nanoparticles could further enhance the antibacterial activity of antibacterial peptides. Furthermore, the Os/Au-PDA@PLGA composite membrane has good hydrophilicity and electrical activity, which can provide a more favorable cell microenvironment for wound healing. In vivo studies using a full-thickness skin defect model in rats showed that the Os/Au-PDA@PLGA composite membrane had a better therapeutic effect than the pure PLGA material. More importantly, the combination of the Os/Au-PDA@PLGA composite with ES significantly accelerated the rate of vascularization and collagen deposition and promoted wound healing compared with non-ES controls. Therefore, the combination of the Au/Os-PDA@PLGA composite membrane with ES may provide a new strategy for the effective treatment of skin wounds.

Bacterial protoplast-derived nanovesicles carrying CRISPR-Cas9 tools re-educate tumor-associated macrophages for enhanced cancer immunotherapy.

The CRISPR-Cas9 system offers substantial potential for cancer therapy by enabling precise manipulation of key genes involved in tumorigenesis and immune response. Despite its promise, the system faces critical challenges, including the preservation of cell viability post-editing and ensuring safe in vivo delivery. To address these issues, this study develops an in vivo CRISPR-Cas9 system targeting tumor-associated macrophages (TAMs). We employ bacterial protoplast-derived nanovesicles (NVs) modified with pH-responsive PEG-conjugated phospholipid derivatives and galactosamine-conjugated phospholipid derivatives tailored for TAM targeting. Utilizing plasmid-transformed E. coli protoplasts as production platforms, we successfully load NVs with two key components: a Cas9-sgRNA ribonucleoprotein targeting Pik3cg, a pivotal molecular switch of macrophage polarization, and bacterial CpG-rich DNA fragments, acting as potent TLR9 ligands. This NV-based, self-assembly approach shows promise for scalable clinical production. Our strategy remodels the tumor microenvironment by stabilizing an M1-like phenotype in TAMs, thus inhibiting tumor growth in female mice. This in vivo CRISPR-Cas9 technology opens avenues for cancer immunotherapy, overcoming challenges related to cell viability and safe, precise in vivo delivery.

Identification of potential key genes for colorectal cancer based on bioinformatics analysis.

This study aimed to explore key genes as potential biomarkers for colorectal cancer (CRC) diagnosis and prognosis in order to improve their clinical utility. To identify and screen candidate genes involved in CRC carcinogenesis and disease progression, we downloaded the microarray datasets GSE143939, GSE196006, and GSE200427 from the GEO database and applied the GEO2R tool to obtain differentially expressed genes (DEGs) between colorectal cancer tissue samples and normal tissue samples. Differentially expressed genes were analyzed using the DAVID online database for gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analyses. Protein-protein interaction network was constructed and related module analysis was performed using STRING and Cytoscape. In total, 241 DEGs were identified, including 127 downregulated and 114 upregulated genes. DEGs enriched functions and pathways included cellular response to chemical stimulus, extracellular region, carbonate dehydratase activity, cell division, spindle, and cell division. The abundant functions and pathways of DEGs included cellular response to chemical stimulus, extracellular region, carbonate dehydratase activity, cell division, spindle, cell adhesion molecule binding, Aldosterone-regulated sodium reabsorption, and Cell cycle-related processes. Fifteen key genes were identified, and bioprocess analyses showed that these genes were mainly enriched in cell cycle, cell division, mitotic spindle, and tubulin binding processes. It was found that CDK1, CEP55, MKI67, and TOP2A may be involved in CRC cancer invasion and recurrence. The pivotal genes identified in this study contribute to our understanding of the molecular and pathogenic mechanisms of CRC carcinogenesis and progression, and provide possible biomarkers for the diagnosis and treatment of CRC.

Enhancing Freshwater Production via Customizable and Highly Efficient Solar-Driven Seawater Desalination.

Solar-powered water generation is an appealing strategy for cost-effective and energy-sustainable seawater purification/desalination, where rational material selection and device design is crucial. Nevertheless, prevailing carbon-based photothermal materials in such systems still suffer from mediocre steam-to-water efficiency, failing to satisfy an adequate freshwater supply. Herein, we demonstrate a biomimetic corrugated evaporator (CE) affording carbon nanotube (CNT) encapsulated Fe nanocluster-decoration in the pursuit of high-efficiency seawater purification. The thus-customized CE demonstrates a maximum evaporation rate of 4.2 kg m-2 h-1 with a refraction angle of 60° and a water-lifting height of 5.5 cm, outperforming most state-of-the-art carbon-based counterparts. By employing a tailored architectural design and optimized condensing volume, the steam-to-water efficiency increases from 65.8 to 88.2% as the volume enlarges from 0.8 to 5.3 L, further harvesting a peak value of 91% under negative pressure. Light intensity simulation and experimental mechanistic investigation disclose the dual property-performance relationships between evaporator microstructure and evaporation rate, as well as between condensing device volume and steam-to-water efficiency. The universality of the theoretical guidance of this work will offer insight into the development of solar-driven evaporator construction toward simultaneous seawater desalination and clean water generation.

Prognostic modeling of overall survival and analysis of K-M survival curves in patients with primary colon cancer: A SEER-based study.

This study aimed to establish a validated prognostic survival column line chart by analyzing data from patients with colon cancer (CC) in the SEER database. The nomogram proposed in this study was based on the retrospective data of patients diagnosed with CC in the SEER database from 1975 to 2015. Randomly divided into training and validation sets, the nomogram was constructed using the Cox model, and the discriminatory power of the nomogram and its predictive accuracy were determined using the consistency index and associated calibration curves. In a multifactorial analysis of the main cohort, the independent factors for survival were age, sex, race, tumor stage, and tumor grade, all of which were included in the nomogram and were prognostic factors for patients with CC (P < .05). The calibration curve of the survival probability showed good agreement between the prediction of the nomogram and the actual observation. The validation calibration curve showed good correlation and agreement between predicted and observed values. Multifactorial analysis showed that the factors affecting the prognosis of patients with CC included age, sex, race, tumor-node-metastasis stage, and tumor pathological stage. The nomogram prediction model proposed in this study has high accuracy and can provide more accurate prognostic prediction and relevant reference values for assessing the postoperative survival of CC patients and guiding clinical decision-making.

Experimental Evaluation of the Properties of Recycled Aggregate Pavement Brick with a Composite Shaped Phase Change Material.

Brick waste makes up a significant part of the solid waste that is generated from building demolition globally. The disposal of this waste consumes land, causes environmental pollution, and is a waste of resources. In order to use this construction waste and increase its functionality, two types of stable-shape PEG-400/SiO2 composite shaped PCM and Tet/SiO2 composite shaped PCM were studied and added to recycled aggregate pavement bricks, and two new types of composite shaped PCM recycled aggregate pavement bricks were created. SEM, DSC, TGA, and other test methods found the two PCMs to be successfully adsorbed by SiO2, and the setting effect of PEG-400/SiO2 was found to be better than that of Tet/SiO2. The physicochemical properties of both composite shaped PCMs remained stable within the TGA test temperature range. The prepared PCM was added to the recycled aggregate pavement brick. A comprehensive analysis of the properties of the composite shaped PCM recycled orthopedic pavement brick found the compressive strength and flexural strength of Tet/SiO2 PCM recycled aggregate pavement brick to be significantly higher than those of PEG-400/SiO2 PCM recycled aggregate pavement brick. With a recycled aggregate content of 60% and a compound shaped PCM content of 5%, the 28-day strength of the recycled aggregate pavement brick was found to be higher than that of the recycled aggregate pavement brick with a recycled aggregate content of 70% and a compound shaped PCM content of 10%. This study provides reference for the optimization and upgrading of the thermal storage performance of composite shaped PCM in practical applications, and is of great significance for promoting thermal energy storage development and expanding its application range.

The key role of persistent free radicals on the surface of hydrochar and pyrocarbon in the removal of heavy metal-organic combined pollutants.

We show that persistent free radicals (PFRs) on the surface of biochar can produce hydroxyl radicals (•OH) by catalyzing H2O2 to facilitate the removal of the combined pollutant BPA-Cr(VI). Microstructure characterization showed that the structures of pyrocarbon and hydrochar were significantly different when prepared at different temperatures. As the preparation temperature and preparation time for biochar increased, the concentration of PFRs first increased and then decreased. When biochar, PFRs, and H2O2 were present in the same solution, the single pollutants BPA and Cr(VI) as well as the combined pollutant BPA-Cr(VI) could be removed effectively, with removal rates greater than 90%. However, when PFRs, BPA, H2O2, and Cr(VI) were present in the same solution, Cr(VI) competed with H2O2 for electrons and promoted the removal of BPA. The results of this study could be applied to sludge recycling and be used to develop approaches to catalytically degrade combined pollutants.

Implication for adsorption and degradation of dyes by humic acid: Light driven of environmentally persistent free radicals to activate reactive oxygen species.

Humic acid (HA) was applied as the biosorbent for the adsorption and degradation of dyes in the presence of environmentally persistent free radicals (EPFRs). Scanning Electron Microscope (SEM) analysis showed that the microstructure of the HA surface and the thermal stability was analyzed by thermogravimetric analysis (TGA). Following irradiation, semiquinone EPFRs (g-factor > 2.0045) were generated on the HA surface. Both O2 and the addition of H2O2 were able to promote the generation of hydroxyl and superoxide radicals for the degradation of dye in aqueous solution. Furthermore, adsorption was observed to remove large amounts of the dyes, while the instantaneous free radical degradation process reduced the dyes to the lower concentration. In addition, a linear relationship was observed between the consumption of EPFRs and dye degradation rates. In ternary systems, HA conformed to Langmuir (476.19-1250.12 mg/L) and pseudo-second-order kinetic models. This work offers new insights into HA-EPFRs and their potential applications.