Effect of oxide interactions on chromium speciation transformation during simulated municipal solid waste incineration.

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al2O3) and the effects of four oxides (SiO2, Al2O3, Fe2O3, and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al2O3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al2O3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO2 was better for the reduction of Na2CrO4 and K2CrO4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO4 decomposed above 700°C to form MgCr2O4, and the reaction between MgCrO4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl3, it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO2, Al2O3, and Fe2O3, which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment.

Optimizing Conjugation Chemistry, Antibody Conjugation Site, and Surface Density in Antibody-Nanogel Conjugates (ANCs) for Cell-Specific Drug Delivery.

Targeted delivery of therapeutics using antibody-nanogel conjugates (ANCs) with a high drug-to-antibody ratio has the potential to overcome some of the inherent limitations of antibody-drug conjugates (ADCs). ANC platforms with simple preparation methods and precise tunability to evaluate structure-activity relationships will greatly contribute to translating this promise into clinical reality. In this work, using trastuzumab as a model antibody, we demonstrate a block copolymer-based ANC platform that allows highly efficient antibody conjugation and formulation. In addition to showcasing the advantages of using an inverse electron-demand Diels-Alder (iEDDA)-based antibody conjugation, we evaluate the influence of antibody surface density and conjugation site on the nanogels upon the targeting capability of ANCs. We show that compared to traditional strain-promoted alkyne-azide cycloadditions, the preparation of ANCs using iEDDA provides significantly higher efficiency, which results in a shortened reaction time, simplified purification process, and enhanced targeting toward cancer cells. We also find that a site-specific disulfide-rebridging method in antibodies offers similar targeting abilities as the more indiscriminate lysine-based conjugation method. The more efficient bioconjugation using iEDDA allows us to optimize the avidity by fine-tuning the surface density of antibodies on the nanogel. Finally, with trastuzumab-mertansine (DM1) antibody-drug combination, our ANC demonstrates superior activities in vitro compared to the corresponding ADC, further highlighting the potential of ANCs in future clinical translation.

Site-Specific Antibody Conjugation Using Modified Bisected N-Glycans: Method Development and Potential toward Tunable Effector Function.

Antibody-drug conjugates (ADCs) have garnered worldwide attention for disease treatment, as they possess high target specificity, a long half-life, and outstanding potency to kill or modulate the functions of targets. FDA approval of multiple ADCs for cancer therapy has generated a strong desire for novel conjugation strategies with high biocompatibility and controllable bioproperties. Herein, we present a bisecting glycan-bridged conjugation strategy that enables site-specific conjugation without the need for the oligosaccharide synthesis and genetic engineering of antibodies. Application of this method is demonstrated by conjugation of anti-HER2 human and mouse IgGs with a cytotoxic drug, monomethyl auristatin E. The glycan bridge showed outstanding stability, and the resulting ADCs eliminated HER2-expressing cancer cells effectively. Moreover, our strategy preserves the feasibility of glycan structure remodeling to fine-tune the immunogenicity and pharmacokinetic properties of ADCs through glycoengineering.

Targeted Drug Delivery Using a Plug-to-Direct Antibody-Nanogel Conjugate.

Targeted drug delivery using antibody-drug conjugates has attracted great attention due to its enhanced therapeutic efficacy compared to traditional chemotherapy. However, the development has been limited due to a low drug-to-antibody ratio and laborious linker-payload optimization. Herein, we present a simple and efficient strategy to combine the favorable features of polymeric nanocarriers with antibodies to generate an antibody-nanogel conjugate (ANC) platform for targeted delivery of cytotoxic agents. Our nanogels stably encapsulate several chemotherapeutic agents with a wide range of mechanisms of action and solubility. We showcase the targetability of ANCs and their selective killing of cancer cells over-expressing disease-relevant antigens such as human epidermal growth factor receptor 2, epidermal growth factor receptor, and tumor-specific mucin 1, which cover a broad range of breast cancer cell types while maintaining low to no toxicity to non-targeted cells. Overall, our system represents a versatile approach that could impact next-generation nanomedicine in antibody-targeted therapeutics.

Multiplexed Analysis of the Cellular Uptake of Polymeric Nanocarriers.

Polymeric nanocarriers (PNCs) are versatile drug delivery vehicles capable of delivering a variety of therapeutics. Quantitatively monitoring their uptake in biological systems is essential for realizing their potential as next-generation delivery systems; however, existing quantification strategies are limited due to the challenges of detecting polymeric materials in complex biological samples. Here, we describe a metal-coded mass tagging approach that enables the multiplexed quantification of the PNC uptake in cells using mass spectrometry (MS). In this approach, PNCs are conjugated with ligands that bind strongly to lanthanide ions, allowing the PNCs to be sensitively quantitated by inductively coupled plasma-MS. The metal-coded tags have little effect on the properties or toxicity of the PNCs, making them biocompatible. We demonstrate that the conjugation of different metals to the PNCs enables the multiplexed analysis of cellular uptake of multiple distinct PNCs at the same time. This multiplexing capability should improve the design and optimization of PNCs by minimizing biological variability and reducing analysis time, effort, and cost.

Influence of Polymer Structure and Architecture on Drug Loading and Redox-Triggered Release.

Disulfide cross-linked nanoassemblies have attracted considerable attention as a drug delivery vehicle due to their responsiveness to the natural redox gradient in biology. Fundamentally understanding the factors that influence the drug loading capacity, encapsulation stability, and precise control of the liberation of encapsulated cargo would be profoundly beneficial to redox-responsive materials. Reported herein are block copolymer (BCP)-based self-cross-linked nanogels, which exhibit high drug loading capacity, high encapsulation stability, and controllable release kinetics. BCP nanogels show considerably higher loading capacity and better encapsulation stability than the random copolymer nanogels at micromolar glutathione concentrations. By partially substituting thiol-reactive pyridyl disulfide into the unreactive benzyl or butyl group, we observed opposite effects on the cross-linking process of BCP nanogels. We further studied the redox-responsive cytotoxicity of our drug-encapsulated nanogels in various cancer cell lines.

Evaluating Endosomal Escape of Caspase-3-Containing Nanomaterials Using Split GFP.

The ability for biologics to access intracellular targets hinges on the translocation of active, unmodified proteins. This is often achieved using nanoscale formulations, which enter cells through endocytosis. This uptake mechanism often limits the therapeutic potential of the biologics, as the propensity of the nanocarrier to escape the endosome becomes the key determinant. To appropriately evaluate and compare competing delivery systems of disparate compositions, it is therefore critical to assess endosomal escape efficiencies. Unfortunately, quantitative tools to assess endosomal escape are lacking, and standard approaches often lead to an erroneous interpretation of cytosolic localization. In this study we use a split-complementation endosomal escape (SEE) assay to evaluate levels of cytosolic caspase-3 following delivery by polymer nanogels and mesoporous silica nanoparticles. In particular, we use SEE as a means to enable the systematic investigation of the effect of polymer composition, polymer architecture (random vs block), hydrophobicity, and surface functionality. Although polymer structure had little influence on endosomal escape, nanogel functionalization with cationic and pH-sensitive peptides significantly enhanced endosomal escape levels and, further, significantly increased the amount of nanogel per endosome. This work serves as a guide for developing an optimal caspase-3 delivery system, as this caspase-3 variant can be easily substituted for a therapeutic caspase-3 cargo in any system that results in cytosolic accumulation and cargo release. In addition, these data provide a framework that can be readily applied to a wide variety of protein cargos to assess the independent contributions of both uptake and endosomal escape of a wide range of protein delivery vehicles.

Mitochondrial genome of the yellow catfish Pelteobagrus fulvidraco and insights into Bagridae phylogenetics.

The mitochondrial genome (mitogenome) can provide important information for understanding phylogenetic analysis and molecular evolution. Herein, we amplified the complete mitogenome sequence of Pelteobagrus fulvidraco. The mitogenome was 16,526 bp in length and included 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes and a non-coding control region (D-loop). Both the organization and location of genes in the mitogenome were consistent with those from Siluriformes fishes previously published in GenBank. The phylogenetic relationships based on Bayesian inference (BI) and Maximum likelihood (ML) methods showed that P. fulvidraco has close relationships with Pelteobagrus eupogon and Tachysurus intermedius, suggesting that P. fulvidraco belongs to Tachysurus. This study provides evidence that Tachysurus, Pseudobagrus and Leiocassis do not form monophyly, but that these three genera form a monophyletic group. Our results provide reference for further phylogenetic research of the Bagridae species.

Cellular AND Gates: Synergistic Recognition to Boost Selective Uptake of Polymeric Nanoassemblies.

The development of nanoparticle-based biomedical applications has been hampered due to undesired off-target effects. Herein, we outline a cellular AND gate to enhance uptake selectivity, in which a nanoassembly-cell interaction is turned on, only in the concurrent presence of two different protein functions, an enzymatic reaction (alkaline phosphatase, ALP) and a ligand-protein (carbonic anhydrase IX, CA IX) binding event. Selective uptake of nanoassemblies was observed in cells that overexpress both of these proteins (unicellular AND gate). Interestingly, selective uptake can also be achieved in CA IX overexpressed cells, when cocultured with ALP overexpressed cells, where the nanoassembly presumably acts as a mediator for cell-cell communication (bicellular AND gate). This logic-gated cellular uptake could find use in applications such as tumor imaging or theranostics.

Electron Localization-Triggered Proton Pumping Toward Cu Single Atoms for Electrochemical CO2 Methanation of Unprecedented Selectivity.

Slow multi-proton coupled electron transfer kinetics and unexpected desorption of intermediates severely hinder the selectivity of CO2 methanation. In this work, a one-stone-two-bird strategy of pumping protons and improving adsorption configuration/capability enabled by electron localization is developed to be highly efficient for CH4 electrosynthesis over Cu single atoms anchored on bismuth vacancies of BiVO4 (Bi1-xVO4─Cu), with superior kinetic isotope effect and high CH4 Faraday efficiency (92%), far outperforming state-of-the-art electrocatalysts for CO2 methanation. Control experiments and theoretical calculations reveal that the bismuth vacancies (VBi) not only act as active sites for H2O dissociation but also induce electron transfer toward Cu single-atom sites. The VBi-induced electron localization pumps *H from VBi sites to Cu single atoms, significantly promoting the generation and stabilization of the pivotal intermediate (*CHO) for highly selective CH4 electrosynthesis. The metal vacancies as new initiators show enormous potential in the proton transfer-involved hydrogenative conversion processes.

Phenylalanine-mediated changes in the soil bacterial community promote nitrogen cycling and plant growth.

Soil amino acids (AAs) are the most active components of soil N, which can be mineralized or absorbed by bacteria as N and C sources. We hypothesized that exogenous AAs could regulate the bacterial community and affect soil N cycling, and the effect sizes could vary depending on individual AAs. Here, we applied feather (keratin)-based compost rich in AAs to Poncirus trifoliata (L.) to evaluate the regulation of bacterial community by AAs; furthermore, we applied six individual AAs to test their effects. The compost significantly increased soil hydrolysable AA content, ammonia monooxygenase gene abundance, and plant growth and changed bacterial community structure. Redundancy analysis revealed that the effects of AAs on the bacterial community composition were greater than those of soil chemical properties, and phenylalanine (Phe) was the most effective among thirteen individual AAs. When applied individually, Phe caused the greatest increase in N cycling-related enzyme activity and plant growth and most significantly altered the bacterial community structure among the six exogenous AAs. Notably, Phe significantly increased the relative abundances of Burkholderia-Caballeronia-Paraburkholderia, Azospirillum, Cupriavidus, and Achromobacter, whose abundances were significantly positively correlated with plant biomass, and significantly reduced the relative abundances of Arachidicoccus, Pseudopedobacter, Sphingobacterium, and Paenibacillus, whose abundances were significantly negatively correlated with plant biomass. We demonstrate that soil AAs strongly shape the bacterial community. Particularly, Phe enhances N cycling and plant growth by increasing the potentially beneficial bacterial taxa and inhibiting the potentially harmful bacterial taxa, which needs further validation.

Identification of the molecular characteristics associated with microsatellite status of colorectal cancer patients for the clinical application of immunotherapy.

Background: Mismatch repair-proficient (pMMR) microsatellite stability (MSS) in colorectal cancer (CRC) indicates an unfavorable therapeutic response to immunotherapy with immune checkpoint inhibitors (ICIs). However, the molecular characteristics of CRC patients with pMMR MSS remain largely unknown. Methods: Heterogeneities between mismatch repair-deficient (dMMR) microsatellite instability (MSI) and pMMR MSS CRC patients were investigated at the single-cell level. Next, an MSS-related risk score was constructed by single-sample gene set enrichment analysis (ssGSEA). The differences in immune and functional characteristics between the high- and low-score groups were systematically analyzed. Results: Based on the single-cell RNA (scRNA) atlas, an MSS-specific cancer cell subpopulation was identified. By taking the intersection of the significant differentially expressed genes (DEGs) between different cancer cell subtypes of the single-cell training and validation cohorts, 29 MSS-specific cancer cell marker genes were screened out for the construction of the MSS-related risk score. This risk score signature could efficiently separate pMMR MSS CRC patients into two subtypes with significantly different immune characteristics. The interactions among the different cell types were stronger in the MSS group than in the MSI group, especially for the outgoing signals of the cancer cells. In addition, functional differences between the high- and low-score groups were preliminarily investigated. Conclusion: In this study, we constructed an effective risk model to classify pMMR MSS CRC patients into two completely different groups based on the specific genes identified by single-cell analysis to identify potential CRC patients sensitive to immunotherapy and screen effective synergistic targets.

Conferring liver selectivity to a thyromimetic using a novel nanoparticle increases therapeutic efficacy in a diet-induced obesity animal model.

Optimization of metabolic regulation is a promising solution for many pathologies, including obesity, dyslipidemia, type 2 diabetes, and inflammatory liver disease. Synthetic thyroid hormone mimics-based regulation of metabolic balance in the liver showed promise but was hampered by the low biocompatibility and harmful effects on the extrahepatic axis. In this work, we show that specifically directing the thyromimetic to the liver utilizing a nanogel-based carrier substantially increased therapeutic efficacy in a diet-induced obesity mouse model, evidenced by the near-complete reversal of body weight gain, liver weight and inflammation, and cholesterol levels with no alteration in the thyroxine (T4) / thyroid stimulating hormone (TSH) axis. Mechanistically, the drug acts by binding to thyroid hormone receptor ß (TRß), a ligand-inducible transcription factor that interacts with thyroid hormone response elements and modulates target gene expression. The reverse cholesterol transport (RCT) pathway is specifically implicated in the observed therapeutic effect. Overall, the study demonstrates a unique approach to restoring metabolic regulation impacting obesity and related metabolic dysfunctions.

Effect of Strain Rate Sensitivity on Fracture of Laminated Rings under Dynamic Compressive Loading.

The effects of cladding layers of rate-sensitive materials on the ductility and fracture strain of compressed rings are numerically investigated by using the finite element method (FEM) and employing the Johnson-Cook (J-C) model. The results show that ductility is governed by the behavior of the material that is located at the ring outer wall regardless of the volume fraction of the core and clad materials. However, as the number of layers increases, this influence becomes less noticeable. Moreover, as barreling increases at the outer wall and decreases at the inner wall, fracture strain increases. Furthermore, the effects of ring shape factor and bonding type of clad and core materials are numerically evaluated. The numerical results show that less force per unit volume is required to fracture narrower rings and that using a noise diffusion pattern at the interface of the materials is more suitable to simulate crack propagation in the compressed rings and functionally graded materials (FGMs). Additionally, delamination has a direct relation to layer thickness and can occur even in the presence of perfect bonding conditions owing to differences among the material and fracture parameters of laminated layers.

Portulaca oleracea extract reduces gut microbiota imbalance and inhibits colorectal cancer progression via inactivation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: Portulaca oleracea is a known medicinal plant with antioxidant, anti-inflammatory, and anticancer activities, and it may also function an important role in colorectal cancer (CRC). PURPOSE: We probed into study the critical function of Portulaca oleracea extract (POE) in CRC and the related downstream factors. METHODS: Azoxymethane (AOM) and dextransodiumsulfate (DSS) were used to induce mouse models of CRC, which were then administered different doses of POE to evaluate the therapeutic effects of POE on CRC. Diversity, abundance, and function of gut microbiota were analyzed. Moreover, the potential molecular targets of POE inhibiting CRC development were determined. Expression of c-Myc and cyclin D1 as well as CRC cell proliferation and apoptosis was detected. RESULTS: POE treatment inhibited AOM/DSS-induced CRC development in mice and ameliorated gut microbial imbalance. Bioinformatic analysis revealed marked differences in the gut microbiota between CRC samples and normal samples and that 20 differential microbiota may be involved in CRC development through the Wnt signaling pathway. Additionally, c-Myc and cyclin D1 were identified to be the key downstream target genes of the Wnt/ß-catenin signaling pathway. In vitro data revealed that POE played a suppressive role in the proliferation of CRC cells by reducing the expression of c-Myc and cyclin D1 and inactivating the Wnt/ß-catenin signaling pathway. CONCLUSION: This study underlines that POE reduces gut microbiota imbalance and inhibits CRC development and progression via inactivation of the Wnt/ß-catenin signaling pathway and downregulation of c-Myc and cyclin D1 expression, which is expected to be a potential biomarker for CRC.

Numerical Study on the Effect of Pre-Strain on Detwinning in Rolled Mg Alloy AZ31.

The deformation behavior of rolled Mg alloy AZ31, previously compressed along the rolling direction (RD), was numerically investigated under reverse tension. The EVPSC-TDT model was employed to study the effect of pre-strain on detwinning for 3%, 6% and 9% pre-compressed materials along the RD. A new criterion was proposed to control the exhaustion of detwinning under reverse tension. Numerical results show good agreement with the corresponding experimental data. It was demonstrated that the proposed criteria can capture the key features associated with detwinning in pre-compressed materials. Regardless of the amount of pre-compression, detwinning is activated under reverse tension, leading to low yield stress and a typical s-shaped flow curve. The inflection point reflects the exhaustion of detwinning, which is delayed when increasing the amount of pre-compression.

Increasing Necking Strain through Corrugation: Identifying Composite Systems That Can Benefit from Corrugated Geometry.

Under some circumstances, composites with a corrugated reinforcement geometry show larger necking strains compared to traditional straight reinforced composites. In this work, finite element modeling studies were performed for linearly hardening materials, examining the effect of material parameters on the stress-strain response of both corrugation and straight-reinforced composites. These studies showed that improvements in necking strain depend on the ability of the corrugation to unbend and to provide a boost in work hardening at the right time. It was found that there is a range of matrix yield strengths and hardening rates for which a corrugated geometry will improve the necking strain and also a lower threshold of reinforcement yield strength below which no improvement in necking strain is possible. In addition, benefit maps and surfaces were generated that show which regions of property space benefit through corrugation and the corresponding improvement in necking strain that can be achieved.

Bi3TaO7 film: a promising photoelectrode for photoelectrochemical water splitting.

Most of the transition metal bismuth salts have excellent visible absorption range and carrier transport properties due to their unique structure capable of orbits and s-p bonds. As one of the transition metal bismuth salts, Bi3TaO7 is firstly directly prepared on fluorine-doped SnO2 transparent conductive glass (FTO) as a photoanode for photoelectrochemical (PEC) water oxidation via a simple hydrothermal method using a special precursor solution. The growth mechanism of the Bi3TaO7 film is investigated in detail. Besides, the Bi3TaO7 photoanode exhibits a wide visible light response range with an optical band gap of 2.88 eV, which is useful for its PEC properties. Bi3TaO7 achieves an excellent PEC performance by tuning the calcination temperature, producing a photocurrent density of 23.0 µA cm-2 at 1.23 V vs. RHE and showing excellent stability that decays by only 2% after illumination for 6000 s. The above results indicate that Bi3TaO7 has broad application prospects in the field of PEC water oxidation.

Investigation of the In-Plane Mechanical Anisotropy of Magnesium Alloy AZ31B-O by VPSC⁻TDT Crystal Plasticity Model.

The in-plane mechanical anisotropy of magnesium alloy sheet, which significantly influences the design of the parts produced by Mg alloy sheets, is of great importance regarding its wide application. Though the stress-strain response and texture evolution have been intensively investigated, and the anisotropy of Mg alloy can be significantly substantiated by its R-value, which reveals the lateral response of a material other than the primary response. As a consequence, the conjunction of viscoplastic self-consistent model and twinning and detwinning scheme (VPSC-TDT) is employed to investigate the in-plane anisotropy of magnesium alloy AZ31B-O sheet. The loading cases include both tension and compression along different paths with respect to the processing direction of the sheet. It is revealed that the stress-strain relation, texture evolution, R-value, and involved deformation mechanisms are all loading path-dependent. The unique R-values of Mg alloys are interpreted with the aid of modeling behaviors of Mg single crystals. The results agree well with the corresponding experiments. It is found that the hexagonal close-packed (HCP) crystallographic structure, deformation twinning, and initial basal texture are responsible for the characteristic behavior of Mg alloys.

Study on the Pressure Bearing Capability of Folded Multi-Port Flat Tube.

The pressure bearing capability of a folded multi-port flat tube (MPFT), which has the advantage of retaining the corrosion property of corrosion resistant materials, was investigated in this study with both a burst pressure test and finite element simulation. Results show that the folded tube's failure is mainly caused by the breaking of the inner ribs. Instead of detecting inner pressure, the bulging ratio, which is supposed to be small under service pressure, rises rapidly before failure. Therefore, it is suggested to use bulging ratio to visibly determine the working status of folded MPFTs. Based on FE simulations, the pressure bearing capability of the folded MPFT was improved by optimizing the relevant folding parameters. In addition, the influence of in-plane bending was also investigated. It is found that the folded MPFTs can still retain most of the pressure bearing capability after in-plane bending.