Enzyme-Dynamic Extracellular Vesicles for Metalloimmunotherapy of Malignant Pleural Effusions.

Malignant pleural effusions (MPEs) are hard to treat, and their onset usually signals terminal cancer. Immunotherapies hold promise but must overcome the immunosuppressive MPE microenvironment. Herein, we treat MPEs via synergistically combining two emerging cancer therapy modalities: enzyme-dynamic therapy (EDT) and metalloimmunotherapy. To do so, a nanoplatform termed "A-R-SOME" was developed which comprises MPE-targeted M1 type extracellular vesicles (EVs) loaded with (1) a manganese-based superoxide dismutase (SOD) enzyme, (2) stimulator of interferon genes (STING) agonist diABZI-2, and (3) signal transducer and an activator of transcription 3 (STAT3) small interfering RNA. Endogenous reactive oxygen species within tumors induced immunogenic cell death by EDT, along with STING activation by both Mn and diABZI-2, and suppression of the STAT3 pathway. Systemically administered A-R-SOME alleviated the MPE immunosuppressive microenvironment, triggered antitumor systemic immunity, and long-term immune memory, leading to the complete eradication of MPE and pleural tumors with 100% survival rate in an aggressive murine model. A-R-SOME-induced immune effects were also observed in human patient-derived MPE, pointing toward the translation potential of A-R-SOME as an experimental malignancy treatment.

Exosomal lncRNA ROR1-AS1 from cancer-associated fibroblasts inhibits ferroptosis of lung cancer cells through the IGF2BP1/SLC7A11 signal axis.

BACKGROUND: Targeting ferroptosis is a potential strategy for cancer treatment. Activated cancer-associated fibroblasts (CAFs) can affect the progression of lung cancer through exosomes. This study investigated the mechanism by which exosomal lncRNA ROR1-AS1 derived from CAFs affects ferroptosis of lung cancer cells. METHODS: CAFs were identified by western blot and immunofluorescence. Exosomes derived from CAFs (CAF-exo) were analyzed by transmission electron microscope, nanoparticle tracking analysis and western blot. The expression levels of ROR1-AS1, IGF2BP1 and SLC7A11 in lung cancer were analyzed by bioinformatics analysis and detected by qPCR and western blot. The lung cancer cells were treated with Erastin and/or CAF-exo, then cell viability was detected by cell counting kit-8, and the ferroptosis-related indicators were detected by corresponding kits. The relationship between IGF2BP1 and ROR1-AS1 or SLC7A11 was determined by RNA pull down and RNA immunoprecipitation, and their effects on cell ferroptosis were confirmed by rescue experiments. Xenotransplantation experiment was used to determine the effect of CAF-exo on tumor growth and ferroptosis in vivo. Immunohistochemistry was used to identify the Ki-67 and 4-HNE expression. RESULTS: ROR1-AS1, IGF2BP1 and SLC7A11 were upregulated in lung cancer and indicated poor prognosis. LncRNA ROR1-AS1 increased the stability of SLC7A11 mRNA by interacting with IGF2BP1. Exosomal ROR1-AS1 from CAFs inhibited ferroptosis of lung cancer cells in vitro and in vivo. The effect of ROR1-AS1 overexpression or IGF2BP1 overexpression on ferroptosis of lung cancer cells was partially reversed by IGF2BP1 silencing or SLC7A11 inhibition. CONCLUSIONS: CAFs secrete exosomal ROR1-AS1 to promote the expression of SLC7A11 by interacting with IGF2BP1, thereby inhibiting ferroptosis of lung cancer cells.

Preparation of Waste-LDPE/SBS Composite High-Viscosity Modifier and Its Effect on the Rheological Properties and Microstructure of Asphalt.

To reduce the cost of high-viscosity modifier (HVM) and alleviate white pollution problems, we prepared the environment-friendly HVM (E-HVM) by using waste-low density polyethylene/styrene-butadiene-styrene (waste-LDPE/SBS) composite. The physical characteristics of the E-HVM modifier were first investigated. Additionally, the effects of E-HVM modifier dosage (8 wt% to 20 wt%) on the rheological properties and microstructure of asphalt were, respectively, researched by dynamic shear rheometer (DSR), bending beam rheometer (BBR), and fluorescence microscopy (FM). The results show that the E-HVM modifier has lower molecular weight, and its distribution is wider than that of the Tafpack-Super (TPS) modifier; thus, the E-HVM modifier had better compatibility with asphalt, which has also been proven by FM images. Due to these reasons, the E-HVM modifier improves the high-temperature performances of asphalt more effectively than the TPS modifier, which is shown by the higher dynamic viscosity (60 °C) and G* and the lower δ and Jnr(τ) Furthermore, compared to TPS modified asphalt, E-HVM modified asphalt also has a higher fatigue life at different strain levels (2.5% and 5.0%), but worse low-temperature performance. Following a comprehensive consideration of performances, the reasonable dosage range of E-HVM modifier is 12 wt% to 16 wt%.

Preparation of Mn2+ Doped Piperazine Phosphate as a Char-Forming Agent for Improving the Fire Safety of Polypropylene/Ammonium Polyphosphate Composites.

A piperazine phosphate doped with Mn2+ (HP-Mn), as a new char-forming agent for intumescent flame retardant systems (IFR), was designed and synthesized using 1-hydroxy ethylidene-1,1-diphosphonic acid, piperazine, and manganese acetate tetrahydrate as raw materials. The effect of HP-Mn and ammonium polyphosphate (APP) on the fire safety and thermal stability of polypropylene (PP) was investigated. The results showed that the combined incorporation of 25 wt.% APP/HP-Mn at a ratio of 1:1 endowed the flame retardant PP (PP6) composite with the limiting oxygen index (LOI) of 30.7% and UL-94 V-0 rating. In comparison with the pure PP, the peak heat release rate (PHRR), the total heat release (THR), and the smoke production rate (PSPR) of the PP6 were reduced by 74%, 30%, and 70%, respectively. SEM and Raman analysis of the char residues demonstrated that the Mn2+ displayed a catalytic cross-linking charring ability to form a continuous and compact carbon layer with a high degree of graphitization, which can effectively improve the flame retardancy of PP/APP composites. A possible flame-retardant mechanism was proposed to reveal the synergistic effect between APP and HP-Mn.

Effect of Rejuvenators on the Workability and Performances of Reclaimed Asphalt Mixtures.

The use of rejuvenators has enhanced the workability of asphalt mixtures containing the reclaimed asphalt pavement (RAP). This conclusion is based on the determination of viscosity of asphalt binders, while not validated from reclaimed asphalt mixtures. In this study, the effect of two rejuvenators (ordinary and emulsified rejuvenator) on the workability of reclaimed asphalt mixtures was evaluated by measuring the mixing torque and determining the air void content of reclaimed mixtures. In addition, their effects on the performances of reclaimed mixture were studied via the three indexes tests, rutting test and freeze-thaw splitting tests. The experimental results show that mixing torque and air void content of reclaimed mixtures with the emulsified rejuvenator is 4% and 6% lower than that with the ordinary rejuvenator, respectively. This indicates that improvement of the workability of reclaimed mixtures can be achieved by using an emulsified rejuvenator, but not by an ordinary rejuvenator. That is also the reason that at least 20% greater high-temperature stability is found for reclaimed mixtures by using the emulsified rejuvenator than using the ordinary rejuvenator. In addition, reclaimed mixtures with the emulsified rejuvenator show similar moisture susceptibility to that with the ordinary rejuvenator. This study provides a feasible method to assess the workability effect of rejuvenators on reclaimed mixtures directly and recommends the use of an emulsified rejuvenator to improve the workability and high-temperature stability of reclaimed mixtures.

Evaluation of Properties and Micro-Characteristics of Waste Polyurethane/Styrene-Butadiene-Styrene Composite Modified Asphalt.

In order to solve the problems caused by asphalt diseases and prolong the life cycle of asphalt pavement, many studies on the properties of modified asphalt have been conducted, especially polyurethane (PU) modified asphalt. This study is to replace part of the styrene-butadiene-styrene (SBS) modifier with waste polyurethane (WP), for preparing WP/SBS composite modified asphalt, as well as exploring its properties and microstructure. On this basis, this paper studied the basic performance of WP/SBS composite modified asphalt with a conventional performance test, to analyze the high- and low-temperature rheological properties, permanent deformation resistance and storage stability of WP/SBS composite modified asphalt by dynamic shear rheometer (DSR) and bending beam rheometer (BBR) tests. The microstructure of WP/SBS composite modified asphalt was also observed by fluorescence microscope (FM) and Fourier transform infrared spectroscopy (FTIR), as well as the reaction between WP and asphalt. According to the results of this study, WP can replace SBS as a modifier to prepare WP/SBS composite modified asphalt with good low-temperature resistance, whose high-temperature performance will be lower than that of SBS modified asphalt. After comprehensive consideration, 4% SBS content and 15% WPU content (4 S/15 W) are determined as the suitable types of WPU/SBS composite modified asphalt.

Using Silane Coupling Agent Coating on Acidic Aggregate Surfaces to Enhance the Adhesion between Asphalt and Aggregate: A Molecular Dynamics Simulation.

Acidic aggregates have the merits of high strength and good abrasion resistance capacity. However, its poor adhesion with asphalt binder constrains its application in pavement construction. Among these, the granite aggregate is the typical one. Therefore, this study modified granite aggregates' surface to improve their adhesion property with the asphalt binder. Specifically, the silane coupling agent (SCA) KH-560 was adopted to achieve the modification purpose. Subsequently, asphalt mixtures with modified and unmodified granite, basalt, and limestone were subjected to the boiling test, immersion test, and freeze-thaw splitting test to estimate the asphalt adhesion property. Moreover, a molecular dynamic simulation was employed to characterize the asphalt-aggregate interface from the molecular scale. The radius distribution function (RDF) and interaction energy were used as the primary indicators. The results showed that the SCA could efficiently improve the adhesion between asphalt and granite aggregates, comparable with the alkaline aggregates. In terms of the molecular scale, the incorporation of SCA could significantly increase the concentration distribution of asphalt molecules on the aggregate surface. Meanwhile, the interaction energy was correspondingly increased due to the considerable growth of non-bond interaction.

Anti-DKK1 antibody promotes bone fracture healing through activation of ß-catenin signaling.

In this study we investigated if Wnt/ß-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of ß-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in ß-catenin(Prx1ER) conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (µCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing process in CD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the ß-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through ß-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in ß-catenin(Prx1ER) conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.