Carvedilol induces pyroptosis through NLRP3-caspase1-ASC inflammasome by nuclear migration of NF-κB in prostate cancer models.

BACKGROUND: Pyroptosis is an inflammatory type of programmed cell death, and could overcome the drug-resistance induced by anti-apoptotic effect of cancers. Carvedilol (CVL), a ß-adrenergic receptors antagonist, has shown anti-inflammatory response and anti-cancer effect. The aim of this study is to investigate whether pyroptosis can be activated by CVL in prostate cancer (PCa). METHODS AND RESULTS: Datasets were used to analyze the expressions of pyroptosis-related proteins. Intracellular morphological change, cell viability, LDH and Il-1ß release by cells,, and Hoechst/PI staining were used to detect the occurrence of pyroptosis. Realtime-PCR, western blot, immunofluorescence, and immunohistochemistry (IHC) were used to investigate the expressions of pyroptosis-related proteins. Datasets analyze showed the expressions of NLRP3, Caspase 1, ASC and GSDMD were all decreased in PCa comparing with normal tissues, but without prognostic significance. CVL treatment weakened the viabilities of PCa cells. Cell morphology changing, cytoplasmic vacuole formation, membrane integrity loss, LDH and IL-1ß release and PI positive cells increasing were observed. NLRP3, Caspase 1, ASC, GSDMD and N-GSDMD expressions were elevated after CVL treatment, accompanied by a tendency of NF-κB transferring into nucleus. In vivo, CVL inhibited the growth of subcutaneous transplanted tumor. IHC showed CVL increased the expressions of NLRP3, ASC, and GSDMD, and decreased the expression of Ki-67 in transplanted tumor tissues. CONCLUSION: This study demonstrated that CVL could induce pyroptosis in PCa cells through NLRP3-caspase1-ASC inflammasome by promoting nuclear translocation of NF-κB, which would lay a foundation for the application of adrenergic receptor antagonist in PCa.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Liquid metal integrated PU/CNT fibrous membrane for human health monitoring.

Wearable flexible sensors are widely used in several applications such as physiological monitoring, electronic skin, and telemedicine. Typically, flexible sensors that are made of elastomeric thin-films lack sufficient permeability, which leads to skin inflammation, and more importantly, affects signal detection and consequently, reduces the sensitivity of the sensor. In this study, we designed a flexible nanofibrous membrane with a high air permeability (6.10 mm/s), which could be effectively used to monitor human motion signals and physiological signals. More specifically, a flexible membrane with a point (liquid metal nanoparticles)-line (carbon nanotubes)-plane (liquid metal thin-film) multiscale conductive structure was fabricated by combining liquid metal (LM) and carbon nanotubes (CNTs) with a polyurethane (PU) nanofibrous membrane. Interestingly, the excellent conductivity and fluidity of the liquid metal enhanced the sensitivity and stability of the membrane. More precisely, the gauge factor (GF) values of the membrane is 3.0 at 50% strain and 14.0 at 400% strain, which corresponds to a high strain sensitivity within the whole range of deformation. Additionally, the proposed membrane has good mechanical properties with an elongation at a break of 490% and a tensile strength of 12 MPa. Furthermore, the flexible membrane exhibits good biocompatibility and can efficiently monitor human health signals, thereby indicating potential for application in the field of wearable electronic devices.

Small-diameter PCL/PU vascular graft modified with heparin-aspirin compound for preventing the occurrence of acute thrombosis.

The occurrence of acute thrombosis, directly related to platelet aggregation and coagulant system, is a considerable reason for the failure of small-diameter vascular grafts. Heparin is commonly used as a functional molecule for graft modification due to the strong anticoagulant effect. Unfortunately, heparin cannot directly resist the adhesion and aggregation of platelets. Therefore, we have prepared a heparin-aspirin compound by coupling heparin with aspirin, an antiplatelet drug, and covalently grafted it onto the surface of polycaprolactone/polyurethane composite tube. In this way, the graft not only showed a dual function of both anticoagulation and antiplatelet, but also effectively avoided the rapid drug release and excessive toxicity to other organs caused by simple blending the medicine with material matrix. The compound retained the original function of heparin, showing good hydrophilicity and biocompatibility, which could promote the adhesion and proliferation of endothelial cells (ECs) and facilitate the process of tissue regeneration. What's more, the compound showed more effective than heparin in reducing platelet activation and preventing thrombosis. The graft modified by this compound maintained completely unobstructed for one month of implantation, while severe obstruction or stenosis occurred in PCL/PU and PCL/PU-Hep lumen at the first week, verifying the effect of the compound on preventing acute thrombosis. In general, this study proposed a designing method for small-diameter vascular graft which could prevent acute thrombosis and promote intimal construction.

Impacts of physical-chemical property of polyethylene on depolymerization and biodegradation in yellow and dark mealworms with high purity microplastics.

Yellow and dark mealworms (Tenebrio molitor and Tenebrio obscurus) biodegrade commercial polyethylene (PE) materials at a high rate. We examined the impact of physical and chemical properties on biodegradation using high purity microplastics (MPs). These included high-density polyethylene (HDPE), low-density polyethylene (LDPE), and linear low-density polyethylene (LLDPE), all with different weight average molecular weights (Mw) and different crystallinity degrees in T. molitor and T. obscurus larvae. The biodegradation extent in the two mealworms was similar but strongly depended on the polymer type in sequence, since LDPE > LLDPE> HDPE (with respective Mw of 222.5, 110.5 and 182 kDa). When LDPE MPs with Mw of 0.84, 6.4 and 106.8 kDa and HDPE with Mw of 52, 105 and 132.7 kDa were tested, the PE MPs with lower Mw showed a greater extent of depolymerization. The results of dominance analysis indicated that less branching structure and higher crystallinity degree negatively impacted depolymerization and biodegradation. Py-GC/MS analysis confirmed the breaking of the macromolecule backbone as well as the formation of oxidized functional groups after all the tested PE materials passed through the mealworm intestine. The results demonstrated that molecular weight, PE type, branching, and crystallinity degree significantly affect the biodegradation capability of PE by the mealworms, and possibly by other biological systems as well.

Novel coagulation waste-based Fe-containing carbonaceous catalyst as peroxymonosulfate activator for pollutants degradation: Role of ROS and electron transfer pathway.

A facile one-step pyrolysis method was employed to prepare an iron containing carbonaceous catalyst using coagulation waste (CW) from paper mill. The catalyst (noted as PMCW) was used to activate peroxymonosulfate (PMS) for decomposition of Reactive Red 2 (RR2). The degradation mechanism was analyzed by reactive oxygen species (ROS) scavenging experiments, electron spin resonance spectroscopy, electrochemical measurements, selective deactivation of the functional groups on the catalyst surface, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. Results showed that, besides ROS (•OH, SO4•- and 1O2), electron transfer pathways induced by -OH functional groups and the π-π* system are involved in the degradation mechanism of RR2. Concerning different decomposition pathways, seven intermediates were identified, and three important steps, including attack on the azo group, cleaving the N9-C10 bond, and opening the naphthalene ring, were deduced via application and analysis of quadrupole time-of-flight liquid chromatography/mass spectrometry (QTOF LC/MS) and density functional theory (DFT) calculations based on Fukui indices and electrostatic potential (ESP) distributions. This work not only provides a novel facile recycling strategy of industrial waste from paper manufacturing to good carbonaceous catalysts but also deepens the understanding of the mechanisms of PMS activation with carbonaceous materials.

A biomimetic orthogonal-bilayer tubular scaffold for the co-culture of endothelial cells and smooth muscle cells.

In blood vessels, endothelial cells (ECs) grow along the direction of blood flow, while smooth muscle cells (SMCs) grow circumferentially along the vessel wall. To mimic this structure, a polycaprolactone (PCL) tubular scaffold with orthogonally oriented bilayer nanofibers was prepared via electrospinning and winding. ECs were cultured on the inner layer of the scaffold with axial nanofibers and SMCs were cultured on the outer layer of the scaffold with circumferential nanofibers. Fluorescence images of the F-actin distribution of ECs and SMCs indicated that cells adhered, stretched, and proliferated in an oriented manner on the scaffold. Moreover, layers of ECs and SMCs formed on the scaffold after one month of incubation. The expression levels of platelet-endothelial cell adhesion molecule 1 (PECAM-1) and a contractile SMC phenotype marker in the EC/SMC co-culture system were much higher than those in individual culture systems, thus demonstrating that the proposed biomimetic scaffold promoted the intercellular junction of ECs and preserved the contractile phenotype of SMCs.

Cell adhesion, ammonia removal and granulation of autotrophic nitrifying sludge facilitated by N-acyl-homoserine lactones.

In this study, six N-acyl-homoserine lactone (AHL) molecules (C6-HSL, C8-HSL, C10-HSL, 3-oxo-C6-HSL, 3-oxo-C8-HSL and 3-oxo-C10-HSL) were each dosed into a bioreactor and seeded using autotrophic nitrifying sludge (ANS). The effects of the AHLs on cell adhesion, nitrification and sludge granulation were investigated. The results indicated that the efficiencies of cell adhesion and ammonia removal both had a close correlation with the side chain length and ß position substituent group of the AHLs. The best-performing AHL in terms of accelerating bacterial attached-growth was 3-oxo-C6-HSL, whereas C6-HSL outperformed the others in terms of the ammonia degradation rate. The addition of 3-oxo-C6-HSL or C6-HSL increased the biomass growth rate, microbial activity, extracellular proteins and nitrifying bacteria, which can accelerate the formation of nitrifying granules. Consequently, selecting AHL molecules that could improve bacteria in attached-growth mode and nitrification efficiency simultaneously will most likely facilitate the rapid granulation of nitrifying sludge.