Enhanced antitumor effects of follicle-stimulating hormone receptor-mediated hexokinase-2 depletion on ovarian cancer mediated by a shift in glucose metabolism.

BACKGROUND: Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity. RESULTS: HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH ß 33-53 or retro-inverso FSH ß 33-53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway. CONCLUSIONS: These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.

Supercritical CO2 Foaming of Radiation Cross-Linked Isotactic Polypropylene in the Presence of TAIC.

Since the maximum foaming temperature window is only about 4 °C for supercritical CO2 (scCO2) foaming of pristine polypropylene, it is important to raise the melt strength of polypropylene in order to more easily achieve scCO2 foaming. In this work, radiation cross-linked isotactic polypropylene, assisted by the addition of a polyfunctional monomer (triallylisocyanurate, TAIC), was employed in the scCO2 foaming process in order to understand the benefits of radiation cross-linking. Due to significantly enhanced melt strength and the decreased degree of crystallinity caused by cross-linking, the scCO2 foaming behavior of polypropylene was dramatically changed. The cell size distribution, cell diameter, cell density, volume expansion ratio, and foaming rate of radiation-cross-linked polypropylene under different foaming conditions were analyzed and compared. It was found that radiation cross-linking favors the foamability and formation of well-defined cell structures. The optimal absorbed dose with the addition of 2 wt % TAIC was 30 kGy. Additionally, the foaming temperature window was expanded to about 8 °C, making the handling of scCO2 foaming of isotactic polypropylene much easier.

Efficient removal of perrhenate/pertechnetate by a pyridinium-based porous polymer.

The extraction of 99TcO4- from radioactive effluents is extremely crucial for the purposes of nuclear disposal and environmental remediation. Herein, utilizing a facile and low-cost synthesis method, we report a pyridinium-based cationic polymer network, CPP-Cl, with impressive adsorption performance and ultrafast adsorption kinetics towards ReO4-. The structure featuring highly density of charged pyridinium units was synthesized, making it an effective adsorbent for capturing ReO4-. The material showed fast ReO4- adsorption kinetics reaching adsorption equilibrium within 30 s, an excellent capture capability of 1069.7 mg/g, and exceptional separation efficiency of 94.3% for removing 1000 ppm ReO4-. Furthermore, it possessed excellent reusability in multiple sorption/desorption trials and good uptake capacity within a widely ranging pH values. It is noteworthy that the extraction efficiency of CPP-Cl for ReO4- from simulated nuclear waste can be up to 94.2%. The favorable performance of the material in multiple tests revealed that CPP-Cl has tremendous potential as a high-efficiency sorbent for capturing 99TcO4-/ReO4- in complex nuclear associated environmental systems.

Polystyrene microplastics alleviate adverse effects of benzo[a]pyrene on tissues and cells of the marine mussel, Mytilus galloprovincialis.

As two major ubiquitous pollutants, microplastics (MPs) and polycyclic aromatic hydrocarbons (PAHs) coexist in the marine environment. However, the role of MPs in altering the toxicity of PAHs to marine organisms is poorly understood. We therefore investigated the accumulation and toxicity of benzo[a]pyrene (B[a]P, 0.4 nM), in the marine mussel Mytilus galloprovincialis over a 4-day of exposure with or without the presence of 10 µm polystyrene microplastics (PS MPs) (10 particles/mL). The presence of PS MPs significantly decreased B[a]P accumulation in soft tissues of M. galloprovincialis by approximately 6.7%. Single exposure of PS MPs or B[a]P decreased the mean epithelial thickness (MET) of digestive tubules and enhanced reactive oxygen species (ROS) levels in haemolymph, while upon co-exposure the adverse impacts were alleviated. Real-time q-PCR results showed that most selected genes involved in stress response (FKBP, HSP90), immune (MyD88a, NF-κB) and detoxification (CYP4Y1) were induced for both single exposure and co-exposure. The co-presence of PS MPs down-regulated the mRNA expression of NF-κB in gills compared with of B[a]P alone. The uptake and toxicity reductions of B[a]P might result from the decrease of its bioavailable concentrations caused by the adsorption of B[a]P by PS MPs and the strong affinity of B[a]P to PS MPs. Adverse outcomes for the co-existence of marine emerging pollutants under long-term conditions remain to be further validated.

Polyethyleneimine Functionalized Mesoporous Magnetic Nanoparticles with Enhanced Antibacterial and Antibiofilm Activity in an Alternating Magnetic Field.

Despite a lot of research on the antibacterial effect of Fe3O4 nanoparticles, their interactions with biofilm matrix have not been well understood. The surface charge of nanoparticles mainly determines their ability to adhere on the biofilm. In this work, negatively charged Fe3O4 nanoparticles were synthesized via a trisodium citrate-assisted solvothermal method and then the surfaces were functionalized using polyethyleneimine (PEI) to obtain positively charged Fe3O4 nanoparticles. The antibacterial and antibiofilm activities of both negatively and positively charged Fe3O4 nanoparticles in an alternating magnetic field were then systematically investigated. The positively charged Fe3O4 nanoparticles showed a strong self-adsorbed attachment ability to the planktonic and sessile cells, resulting in a better antibacterial activity and enhanced biofilm eradication performance compared to the conventional Fe3O4 nanoparticles with negative charges. Fe3O4@PEI nanoparticles produced physical stress and thermal damage in response to an alternating magnetic field, inducing the accumulation of intracellular reactive oxygen species into live bacterial cells, bacterial membrane damage, and biofilm dispersion. Utilizing an alternating magnetic field along with positively charged nanoparticles leads to a synergistic antibacterial approach to improve the antibiofilm performance of magnetic nanoparticles.

Accelerated biocorrosion of stainless steel in marine water via extracellular electron transfer encoding gene phzH of Pseudomonas aeruginosa.

Microbiologically influenced corrosion (MIC) constantly occurs in water/wastewater systems, especially in marine water. MIC contributes to billions of dollars in damage to marine industry each year, yet the physiological mechanisms behind this process remain poorly understood. Pseudomonas aeruginosa is a representative marine electro-active bacterium, which has been confirmed to cause severe MIC on carbon steel through extracellular electron transfer (EET). However, little is known about how P. aeruginosa causes corrosion on stainless steel. In this study, the corrosivity of wild-type strain, phzH knockout, phzH complemented, and phzH overexpression P. aeruginosa mutants were evaluated to explore the underlying MIC mechanism. We found the accelerated MIC on 2205 duplex stainless steel (DSS) was due to the secretion of phenazine-1-carboxamide (PCN), which was regulated by the phzH gene. Surface analysis, Mott-Schottky test and H2O2 measurement results showed that PCN damaged the passive film by forming H2O2 to oxidize chromium oxide to soluble hexavalent chromium, leading to more severe pitting corrosion. The normalized corrosion rate per cell followed the same order as the general corrosion rate obtained under each experimental condition, eliminating the influence of the total amount of sessile cells on corrosion. These findings provide new insight and are meaningful for the investigation of MIC mechanisms on stainless steel. The understanding of MIC can improve the sustainability and resilience of infrastructure, leading to huge environmental and economic benefits.

In-situ mineralized robust polysiloxane-Ag@ZnO on cotton for enhanced photocatalytic and antibacterial activities.

A bifunctional interfacial layer was introduced onto the surface of cotton fabric which not only enhanced the interfacial bonding between Ag@ZnO and organic substrates but also improved the photocatalytic performance simultaneously. In detail, a modified cotton fabric (denoted as Cot-g-Si/Ag@ZnO) was fabricated through radiation-induced graft polymerization of γ-methacryloxypropyl trimethoxysilane and followed the in-situ formation of ZnO and loading of Ag nanoparticles simultaneously. Owing to ZnOSi between the graft chains and Ag@ZnO photocatalyst, the charge carrier concentration increased and Ag was prevented from oxidizing through the partial separation from ZnO, leading to enhanced near-field amplitudes of the localized surface plasmon resonance. Cot-g-Si/Ag@ZnO also exhibited excellent photocorrosion resistance, photostability and laundering durability. Its photocatalytic activity was fully maintained after several photodegradation cycles; moreover, after laundering durability test, the photocatalytic activity was improved compared with the newly prepared one. Credible mechanism for the photocatalytic activity of Cot-g-Si/Ag@ZnO under sunlight irradiation is proposed.

The uptake and elimination of polystyrene microplastics by the brine shrimp, Artemia parthenogenetica, and its impact on its feeding behavior and intestinal histology.

Microplastics are a ubiquitous contaminant of marine ecosystems that have received considerable global attention. The effects of microplastic ingestion on some marine biota have been evaluated, but the uptake, elimination, and histopathological impacts of microplastics remain under-investigated especially for zooplankton larvae. Here, we show that 10 µm polystyrene microspheres can be ingested and egested by Artemia parthenogenetica larvae, which impact their health. The results indicate that A. parthenogenetica larvae have a varying capacity to consume 10 µm polystyrene microspheres that is dependent on microplastic exposure concentrations, exposure times, and the availability of food. The lowest level of microplastics that was ingested by A. parthenogenetica was 0.15 particles/individual when exposed to 10 particles/mL and 0.05 particles/individual when exposed to 1 particle/mL over 24 h and 14 d, respectively. A. parthenogenetica larvae were able to egest feces with microplastics within 3 h of ingestion. However, ingested microplastics persisted in individuals for up to 14 days. Furthermore, microalgal feeding was significantly reduced by 27.2% in the presence of 102 particles/mL microplastics over 24 h. Histological analyses indicated that a greater abundance of lipid droplets was present among epithelia after 24 h of exposure at a concentration of 10 particles/mL. Moreover, intestinal epithelia were deformed and disorderedly arranged after 14 d of exposure. Overall, these results indicate that marine microplastic pollution could pose a threat to A. parthenogenetica health, especially that of larvae. Consequently, further research is required to evaluate the potential physiological and histopathological effects of microplastics for other marine invertebrate species.

Effects of ingested polystyrene microplastics on brine shrimp, Artemia parthenogenetica.

Microplastics are a contaminant of emerging concern which enter the marine environment from a variety of sources. The ingestion and toxic effects of microplastics on marine life, especially for filter feeders, are a cause of concern in view of their ubiquitous nature and their similar size as food sources. To assess the toxic effects of microspheres ingested by brine shrimp larvae, we exposed Artemia parthenogenetica to 10 µm polystyrene microspheres at different concentrations. These concentrations were approximate to the extrapolated marine aquatic environmentally relevant concentrations. The lowest polystyrene concentrations at which ingestion was visualized in A. parthenogenetica were 12 ±â€¯0.57 particles/mL (6.7 ±â€¯0.32 µg/L) and 1.1 ±â€¯0.16 particles/mL (0.61 ±â€¯0.088 µg/L), respectively. There were no significant impacts on the survival, growth or development in A. parthenogenetica occurring over the 14-d exposure across a range of polystyrene nominal concentrations (1-1000 particles/mL or 0.55-550 µg/L). However, abnormal ultrastructures of intestinal epithelial cells were observed upon exposure to polystyrene microspheres, including fewer and disordered microvilli, an increased number of mitochondrion and the appearance of autophagosome. These phenomena could affect nutrition absorption and energy metabolism. Although no major acute or chronic toxicity effects on A. parthenogenetica were observed over 24-h or 14-d exposures, this study provides evidence that the ingestion of polystyrene microplastics at extrapolated environmentally relevant concentrations can be visualized through a microscope to be causing a series of responses in intestinal epithelial cells.

Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy.

BACKGROUND: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. METHODS: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation. RESULTS: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively. CONCLUSIONS: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy.

A novel composite porous coating approach for bioactive titanium-based orthopedic implants.

Surface modification of titanium-based implants is considered a highly effective solution to enhance osseointegration. This study describes a novel Ti/hydroxyapatite (HA) composite porous coating produced using a cold spraying technique. Experimental results indicate desirable open-cell structure with 50-150 µm pore size and 60-65% macroporosity. In particular, the reinforced HA particles are exposed to the surface of the coating resulting in enhanced mineralization ability in simulated body fluid. None of the coatings displayed a cytotoxic response in SaOS-2 cells cultured in vitro for up to 48 h. The bond strength between the porous coating and the Ti substrate was found to be 20 MPa. These properties are comparative to or better than products currently on the market and thus this novel coating has potential use in orthopedics.