Lipid-Polymer Nanoparticles Mediate Compartmentalized Delivery of Cas9 and sgRNA for Glioblastoma Vasculature and Immune Reprogramming.

Hypervascularized glioblastoma is naturally sensitive to anti-angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid-polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep-2 decoration for blood-brain barrier (BBB) penetration. The lipid-polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge-elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin-6 (IL-6) and interleukin-10 (IL-10) reduction to develop anti-glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy.

Modified zero-valent iron nanoparticles enhanced remediation of PCBs-contaminated soil.

The high toxicity and persistence of polychlorinated biphenyls (PCBs) in the environment require effective remediation of PCBs-contaminated soil. This study used polylactic acid (PLA) and polyethylene glycol 4000 (PEG-4000) to modify zero-valent iron nanoparticles (nZVI) and conducted characterization analysis. It was found that when the addition amount of PLA was 2 %, the dispersion of modified nZVI was better. The initial pH and water to soil ratio were subjected to single factor experiments and fitted using RSM response surface methodology. The optimal reaction conditions were obtained as follows: the addition amount was 84 g·kg-1, the initial pH was 5.41, and the optimal removal rate was 74 % when the ratio of water to soil was 1.8:1. PLA and PEG-4000 were biodegradable substances that played crucial roles in enhancing the effectiveness of nZVI for PCBs-contaminated soil. By encapsulating nZVI with PLA, we significantly reduced its oxidation when exposed to air. Additionally, the inclusion of PEG-4000 helped prevent the particles from clumping together. The synergistic effect of them increased the effective reaction of nZVI and PCBs and ultimately leading to more efficient remediation. This study offered a new pathway for the efficient green remediation of PCBs-contaminated soil.

Efficient removal of Hg0 from cement kiln flue gas using CexFeyOz composite catalyst.

In this study, a kind of CexFeyOz composite with oxygen vacancy structure and strong oxygen storage capacity was prepared by coprecipitation method. Under the condition of no HCl of flue gas, the Hg0 in the flue gas of cement kiln was efficiently and economically removed by using 6-8% oxygen. The results showed that the optimum preparation conditions of the catalyst were Ce-Fe molar ratio of 1-11 and calcination temperature of 550 °C. In addition, the reaction temperature, space velocity, the concentration of O2, SO2, and NO had significant effects on the removal efficiency of Hg0 at different rates. More precisely, at the reaction temperature of 350 °C, low airspeed, high concentration of O2, and low concentration of SO2 and NO, the efficiency reached the highest value. According to XPS results, the elemental valence of the CexFeyOz composite changed after the reaction. The redox pairs of Ce3+-Ce4+ and Fe3+-Fe2+ had the ability to transfer electrons, which enabled more oxygen adsorbed on the catalyst surface to be converted into O2-, leading to the improvement of the oxidation efficiency of Hg0.

Modulation of Tumor Immune Microenvironment and Prognostic Value of Ferroptosis-Related Genes, and Candidate Target Drugs in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor, among which IDH1-wild type GBM has a poor prognosis. Recent studies have shown that ferroptosis-related genes (FRGs) are correlated with the development and progression of cancer. In GBM, the role of FRGs associated with IDH1 status as biological indicators and therapeutic targets remains to be clarified. Ten of FRGs (STEAP3, HSPB1, MAP1LC3A, SOCS1, LOX, CAPG, CP, GDF15, CDKN1A, and CD44) associated with IDH1 status in GBM were identified as key genes through screening by survival analysis and Random Forest using The Cancer Genome Atlas (TCGA) datasets, and the protein expressions of key genes were verified. Transwell and qPCR results showed that ferroptosis promoted the migration of glioblastoma cells and affected the expression of key genes. Our study established the ferroptosis-related prognostic model for GBM patients based on ten key genes by a different modeling method from previous study, the GSVA algorithm. Further, we took the methods of functional enrichment analysis, clinical characteristics, immune cell infiltration, immunomodulator, ESTIMATE and single nucleotide variant (SNV) analysis to study the molecular mechanisms of prognostic model and key genes. The results showed that ten key genes were strongly associated with immune-related factors and were significantly involved in the p53 signaling pathway, senescence and autophagy in cancer, and in the negative regulation of protein kinase activity. Moreover, potential therapeutic drugs were identified by Virtual Screening and Molecular Docking. Our study indicated that the novel ferrotosis-related prognostic model for GBM patients and key genes possessed the prognostic and therapeutic values.

Immunotherapeutic Value of MAP1LC3C and Its Candidate FDA-Approved Drugs Identified by Pan-Cancer Analysis, Virtual Screening and Sensitivity Analysis.

Background: The autophagy pathway within the tumour microenvironment can be regulated to inhibit or promote tumour development. In the fight against tumour growth, immunotherapy induces an anti-tumour immune response, whereas autophagy modulates this immune response. A key protein in the autophagy pathway, microtubule-associated protein 1 light chain 3 (MAP1LC3), has recently become a hotspot for tumour research. As a relatively novel member, the function of MAP1LC3C in tumours still need to be investigated. Therefore, the goal of this study was to look into the possible link between MAP1LC3C and immunotherapy for 33 kinds of human malignancies by using pan-cancer analysis. Methods: High-throughput sequencing data from The Cancer Genome Atlas, Genotype-Tissue Expression Project and Cancer Cell Line Encyclopedia databases, combined with clinical data, were used to analyze the expression of MAP1LC3C in 33 types of cancer, as well as patient prognosis and neoplasm staging. Activity scores were calculated using ssGSEA to assess the MAP1LC3C activity in pan-cancer. Associations between MAP1LC3C and the tumour microenvironment, including immune cell infiltration and immunomodulators, were analyzed. Moreover, tumour tissue ImmuneScores and StromalScores were analyzed using the ESTIMATE algorithm. Additionally, associations between MAP1LC3C and tumour mutational burden/microsatellite instability, were investigated. Finally, based on the expression and structure of MAP1LC3C, the United States Food and Drug Administration (FDA)-approved drugs, were screened by virtual screening, molecular docking and NCI-60 drug sensitivity analysis. Results: Our study found that MAP1LC3C was differentially expressed in tumour and normal tissues in 23 of 33 human cancer types, among which MAP1LC3C had prognostic effects in 12 cancer types, and MAP1LC3C expression was significantly correlated with tumour stage in four cancer types. In addition, MAP1LC3C activity in 14 cancer types was consistent with changes in transcription levels. Moreover, MAP1LC3C strongly correlated with immune infiltration, immune modulators and immune markers. Finally, a number of FDA-approved drugs were identified via virtual screening and drug sensitivity analysis. Conclusion: Our study investigated the prognostic and immunotherapeutic value of MAP1LC3C in 33 types of cancer, and several FDA-approved drugs were identified to be highly related to MAP1LC3C and can be potential cancer therapeutic candidates.

Preparation of graphene-based catalysts and combined DBD reactor for VOC degradation.

The objective of this study was to compare the transformation of by-products between single dielectric barrier discharge (SDBD) and double dielectric barrier discharge (DDBD), to optimize the preparation of graphene-based catalysts and apply them in combination with DBD for volatile organic compound degradation. We compared the degradation performance of SDBD and DDBD, prepared, and characterized graphene-based catalysts. SEM, BET, XRD, and FTIR analyses showed that the morphologies and internal structures of the three catalysts were the best when 0.25 mL of [BMIM]PF6 was added. When MnOx/rGO, FeOx/rGO, and TiOx/rGO were used in combination with DDBD, the degradation rates of benzene were found to be 83.5%, 77.2%, and 63.8%, respectively, whereas the O3 transformation rates were 60%, 79%, and 40%, respectively. Moreover, the NO2 transformation rates were 70%, 55%, and 42.5%, respectively, whereas the NO transformation rates were 69%, 39%, and 33.5%, respectively. The CO2 selectivity was 62%, 51%, and 49%, respectively. MnOx/rGO exhibited superior performance in the degradation of benzene series, NO transformation, NO2 transformation, CO2 selectivity, and energy efficiency. On the other hand, FeOx/rGO exhibited superior performance for O3 transformation. Based upon the XPS analysis, it was found that Mn3O4 and Fe3O4 played a leading role in promoting the degradation of benzene series and the transformation of by-products.

Distribution and genetic diversity of microbial populations in the pilot-scale biofilter for simultaneous removal of ammonia, iron and manganese from real groundwater.

A pilot-scale biofilter treating real groundwater was developed in this study, which showed that ammonia, iron and manganese were mainly removed at 0.4, 0.4 and 0.8 m of the filter bed, respectively, and the corresponding removal efficiencies were 90.82%, 95.48% and 95.90% in steady phase, respectively. The variation of microbial populations in the biofilter during start-up process was also investigated using high-throughput pyrosequencing (HTP). Results indicated that the main functional microbes for ammonia, iron and manganese removal were Nitrosomonas, Crenothrix and Crenothrix, respectively, which was mainly distributed at 0.8, 0, and 0.8 m of the filter bed with a corresponding abundance of 8.7%, 28.12% and 11.33% in steady phase, respectively. Kinds of other bacteria which may be related to methane, hydrogen sulfide and organic matter removal, were also found. In addition, small part of archaea was also detected, such as Candidatus Nitrososphaera, which plays a role in nitritation.

Adsorption intrinsic kinetics and isotherms of lead ions on steel slag.

Batch experiments were carried out to investigate the kinetics of adsorption of lead ions by steel slag on the basis of the external diffusion, intra-particle diffusion and adsorption reaction model (pseudo-first-order, pseudo-second-order). The results showed that the controlling step for the adsorption kinetics changed with the varying experimental parameters. When the particle size of steel slag was larger than 120 mesh, intra-particle diffusion of Pb(2+) was the controlling step, and when the initial concentration of Pb(2+) was less than 150 m gL(-1) or the shaking rate was lower than 150 rpm, external diffusion of Pb(2+) was promoted. Contrary to the former experimental conditions the adsorption reaction was the controlling step, and the adsorption followed second-order kinetics, with an adsorption rate constant of 13.26 g mg(-1)min(-1). The adsorption isotherm of Pb(2+) with steel slag followed the Langmuir model, with a correlation coefficient of 0.99.

Kinetic models for the adsorption of lead ions by steel slag.

Batch experiments were carried out to investigate the kinetics of adsorption of lead ions by steel slag on the basis of the external diffusion, intraparticle diffusion and adsorption reaction model (pseudo-first-order, pseudo-second-order). The results showed that the controlling step for the adsorption kinetics changed with experimental parameters varied. When the particle size of steel slag was larger than 120 mesh, intraparticle diffusion of Pb(2+) was the controlling step; when the initial concentration of Pb(2+) was less than 150 mg L(-1) or the shaking rate was lower than 150 rpm, external diffusion of Pb(2+) was promoted. Contrary to the former experimental conditions, the adsorption reaction was the controlling step, and the adsorption followed second-order kinetics, with an adsorption rate constant of 13.26 g mg(-1) min(- 1). The adsorption isotherm of Pb(2+) with steel slag followed the Langmuir model, with a correlation coefficient of 0.99.