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Epithelial-mesenchymal transition (EMT) plays an irreplaceable role in the development of silicosis. However, molecular mechanisms of EMT induced by silica exposure still remain to be addressed. Herein, metabolic profiles of human alveolar type II epithelial cells (A549 cells) exposed directly to silica were characterized using non-targeted metabolomic approaches. A total of 84 differential metabolites (DMs) were identified in silica-treated A549 cells undergoing EMT, which were mainly enriched in metabolisms of amino acids (e.g., glutamate, alanine, aspartate), purine metabolism, glycolysis, etc. The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica. Remarkably, glutamine catabolism was significantly promoted in the silica-treated A549 cells, and the levels of related metabolites (e.g., succinate) and enzymes (e.g., α-ketoglutarate (α-KG) dehydrogenase) were substantially up-regulated, with a preference to α-KG pathway. Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail (zinc finger transcription factor). Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.

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Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

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Silica nanoparticles are increasingly considered for drug delivery applications. These applications require an understanding of their biocompatibility, including their interactions with the immune system. However, systematic studies for silica nanoparticle immunological safety profiles are lacking. To fill this gap, we conducted an in vitro study investigating various aspects of silica nanoparticles' interactions with blood and immune cells. Four types of silica nanoparticles with variations in size and porosity were studied. These included nonporous Stöber silica nanoparticles with average diameters of approximately 50 and 100 nm (SNP50 and SNP100), mesoporous silica nanoparticles of approximately 100 nm (Meso100), and hollow mesoporous silica nanoparticles of approximately 100 nm (HMSNP100) in diameter, respectively. The hematological compatibility was assessed using hemolysis, complement activation, platelet aggregation, and plasma coagulation assays. The effects of nanoparticles on immune cell function were studied using in vitro phagocytosis, chemotaxis, natural killer cell cytotoxicity, leukocyte proliferation, human lymphocyte activation, colony-forming unit granulocyte-macrophage, and leukocyte procoagulant activity assays. The in vitro findings suggest that at high concentrations, corresponding to the in vivo human dose of 40 mg/kg, silica nanoparticles demonstrated an array of immunotoxic effects that depended on their physicochemical properties. However, all types of silica nanoparticles studied were not immunotoxic at concentrations corresponding to lower doses (≤ 8 mg/kg) comparable to that of nanocarriers in other nanomedicines currently used in the clinic. These findings are promising for using silica nanoparticles for the systemic delivery of bioactive and imaging agents.

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Mallomonas thrive primarily in freshwaters and dominate plankton communities, especially in oligotrophic waters. The cells have a siliceous cell covering of regularly arranged scales. Despite their ecological importance, the intricate structure and evolutionary significance of their silica scales are still unexplored. We investigated the nanopatterns on the scales and hypothesized that they may play a role in UV shielding. UVA and UVB exposure experiments were performed with 20 Mallomonas species, categorized into four groups based on the nanopattern of the scales (plain-scaled, meshed, striated, and papilliferous group); a fifth group consisted of the species that have extremely thick, robust scales regardless of the nanopattern. We revealed that thick scales were associated with enhanced UVB resistance, suggesting a protective role. No significant differences in UVA response were observed among the groups, except for the meshed group, which showed lower resistance, likely due to the less regular pattern on the shield. In conclusion, the scale case, composed of sufficiently silicified scales, provides effective UV protection in freshwater environments, regardless of the particular nanopattern. In increased UVB radiation, the thickness of the scales plays role. Contrary to expectations, cell size and phylogeny do not strongly predict UV resistance. The study highlights the diverse UV responses of Mallomonas, but further studies are needed to understand the role of scales/nanopatterns in the ecological adaptations of the species.

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Thiol-functionalized mesoporous silica and materials potentially dedicated to diverse applications of composite materials, metal colloids, and metal catalysts, etc. Here, we developed a new synthesis route for 3-methacryloxypropyl trimethoxy silane (MPTMS) functionalized mesoporous silica (KIT-6), achieving a 71.5% enhancement in thiol functionalization on KIT-6 surfaces. Characterization using XRD, TEM, BET, FTIR, Raman, 29Si NMR, XPS, and ICP-OES revealed structural and morphological features. XRD, TEM, and BET confirmed the three-dimensional structural stabilization of mesoporous silica with ~4 nm pore diameter and a surface area of 1451 m2 g-1. FTIR, Raman, and 29Si NMR studies established the mechanism of thiol functionalization, the formation of a new wormhole chain structural framework (WCSF), and stabilization through hydrogen bonding within the mesopores. The 29Si NMR spectra showed characteristic peaks (T3, T2, Q4, Q3) indicating self-condensed functionalized thiols with siloxane networks. XPS analysis validated enhanced thiol functionalization, indicating a structurally homogeneous WCSF suitable for mercury adsorption. ICP-OES measured a mercury adsorption capacity of 3199.6 mg g-1 for KIT-6, with an Hg2+/S ratio of 1.8, corroborated by molecular structure and mechanism analysis. This innovative thiol functionalization approach enhances the efficacy of applications such as extracting Hg2+ from contaminated sources.

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Crystalline silica has emerged as a prominent occupational toxicant over extended periods, leading to the development of lung disease and cancer. The objective of this investigation is to establish a benchmark dose (BMD) for crystalline silica micro and nanoparticles based on the dehydrogenase activity of the A549 lung-cell line. The impact of exposure to crystalline silica micro-particles (C-SiO2 MPs) and crystalline silica nanoparticles (C-SiO2 NPs) on A549 epithelial lung cells was examined for durations of 24 and 72 h to evaluate cell viability using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The determination of dose-response and BMD was carried out through the BMD software v 3.2. The findings reveal a dose-dependent relationship between cell viability and both C-SiO2 MPs and -NPs. The BMDL values for 24 h treatment of C-SiO2 MPs and -NPs were determined to be 2.26 and 0.97 µg/ml, respectively, based on exponential models. Correspondingly, these values were found to be 1.17 and 0.85 µg/ml for the 72 h treatment. This investigation underscores the significance of particle size as a contributing factor in assessing occupational health risks. Moreover, the utilization of BMDL can facilitate the determination of more precise values for occupational exposures by considering various parameters associated with particle presence.

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The emergence of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) has become a global health challenge due to the overuse of antibiotics. Natural substances including enzymes and essential oils have shown great potential as alternative treatment options. However, the combinational use of these natural agents remains challenging due to the denaturation of enzymes upon direct contact with oil. In this study, we report the design of a Pickering emulsion containing two natural antibacterial agents, lysozyme and tea tree oil, stabilized by fractal silica nanoparticles. In this design, the enzyme activity is kept and the volatility problem of tea tree oil is mitigated. Due to synergistic bacterial cell wall digestion and membrane disruption functions, potent bactericidal efficacy in vitro against drug-resistant bacteria is achieved. The therapeutic potential is further demonstrated in a wound healing model with drug-resistant bacteria infection, better than a synthetic antibiotic, Ampicillin. This study opens new avenues for the development of natural product-based antimicrobial treatments with promising application potential.

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BACKGROUND: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. OBJECTIVE: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. METHODS: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. RESULTS: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. CONCLUSIONS: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.

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Environmental disasters are extreme environmental processes such as earthquakes, volcanic eruptions, landslides, tsunamis, floods, cyclones, storms, wildfires and droughts that are the consequences of the climate crisis due to human intervention in the environment. Their effects on human health have alarmed the global scientific community. Among them, autoimmune diseases, a heterogeneous group of disorders, have increased dramatically in many parts of the world, likely as a result of changes in our exposure to environmental factors. However, only a limited number of studies have attempted to discover and analyze the complex association between environmental disasters and autoimmune diseases. This narrative review has therefore tried to fill this gap. First of all, the activation pathways of autoimmunity after environmental disasters have been analyzed. It has also been shown that wildfires, earthquakes, desert dust storms and volcanic eruptions may damage human health and induce autoimmune responses to inhaled PM2.5, mainly through oxidative stress pathways, increased pro-inflammatory cytokines and epithelial barrier damage. In addition, it has been shown that heat stress, in addition to increasing pro-inflammatory cytokines, may also disrupt the intestinal barrier, thereby increasing its permeability to toxins and pathogens or inducing epigenetic changes. In addition, toxic volcanic elements may accelerate the progressive destruction of myelin, which may potentially trigger multiple sclerosis. The complex and diverse mechanisms by which vector-borne, water-, food-, and rodent-borne diseases that often follow environmental diseases may also trigger autoimmune responses have also been described. In addition, the association between post-disaster stress and the onset or worsening of autoimmune disease has been demonstrated. Given all of the above, the rapid restoration of post-disaster health services to mitigate the flare-up of autoimmune conditions is critical.

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Acid-leached gangue residue is produced after the gangue extraction of metal ions; the main component is silicon, which can be used to extract silica. To ascertain the kinetics and mechanism of silica extraction from acid-leached coal gangue residue, this study explored the effects of the NaOH concentration, solid-to-liquid ratio, reaction temperature, and reaction time on the extraction process. The optimized conditions, determined through this investigation, involved a NaOH concentration of 4 mol/L, a reaction time of 4 h, a solid-to-liquid ratio of 1:4, and a reaction temperature of 180 °C, yielding a SiO2 extraction ratio of 90.16%. Additionally, the leaching kinetics of silica in a NaOH solution were examined using three kinetic equations from the "unreacted shrinking core model". The results revealed that the control type of the leaching process was the "mixing control", and the apparent activation energy was determined to be 52.36 kJ/mol.

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This study presents test results and deep discussion regarding measurements of the fracture toughness of new concrete composites based on ternary blended cements (TCs). A composition of the most commonly used mineral additive (i.e., fly ash (FA)) in combination with nano-silica (NS) has been proposed as a partial replacement of the ordinary Portland cement (OPC) binder. The novelty of this article is related to the fact that ordinary concretes with FA + NS additives are most often used in construction practice, and there is a decided lack of fracture toughness test results concerning these materials. Therefore, in order to fill this gap in the literature, an extensive evaluation of the fracture mechanic parameters of TC was carried out. Four series of concretes were created, one of which was the reference concrete (REF), and the remaining three were TCs. The effect of a constant content of 5% NS and various FA contents, such as 0, 15%, and 25% wt., as a partial replacement of cement was studied. The parameters of the linear and nonlinear fracture mechanics were analyzed in this study (i.e., the critical stress intensity factor (KIcS), critical crack tip opening displacement (CTODc), and critical unit work of failure (JIc)). In addition, the main mechanical parameters (i.e., the compressive strength (fcm) and splitting tensile strength (fctm)) were evaluated. Based on the studies, it was found that the addition of 5% NS without FA increased the strength and fracture parameters of the concrete by approximately 20%. On the other hand, supplementing the composition of the binder with 5% NS in combination with the 15% FA additive caused an increase in all mechanical parameters by approximately another 20%. However, an increase in the FA content in the concrete mix of another 10% caused a smaller increase in all analyzed factors (i.e., by approximately 10%) compared with a composite with the addition of the NS modifier only. In addition, from an ecological point of view, by utilizing fine waste FA particles combined with extremely fine particles of NS to produce ordinary concretes, the demand for OPC can be reduced, thereby lowering CO2 emissions. Hence, the findings of this research hold practical importance for the future application of such materials in the development of green concretes.

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As an integrable micro-optical device, micro lens arrays (MLAs) have significant applications in modern optical imaging, new energy technology, and advanced displays. In order to reduce the impact of laser modification on wet etching, we propose a technique of femtosecond laser penetration-induced modification-assisted wet etching (FLIPM-WE), which avoids the influence of previous modification layers on subsequent laser pulses and effectively improves the controllability of lens array preparation. We conducted a detailed study on the effects of the laser single pulse energy, pulse number, and hydrofluoric acid etching duration on the morphology of micro lenses and obtained the optimal process parameters. Ultimately, two types of fused silica micro lens arrays with different focal lengths but the same numerical aperture (NA = 0.458) were fabricated using the FLPIM-WE technology. Both arrays exhibited excellent geometric consistency and surface quality (Ra~30 nm). Moreover, they achieved clear imaging at various magnifications with an adjustment range of 1.3×~3.0×. This provides potential technical support for special micro-optical systems.

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Silica fume (SF) is an essential component in ultra-high-performance concrete (UHPC) to compact the matrix, but the nucleus effect also causes rapid hydration, which results in high heat release and large shrinkage. In this paper, the carboxylic agents, including polyacrylic acid and polycarboxylate superplasticizer, were used to surface modify SF to adjust the activity to mitigate hydration at an early time and to promote continuous hydration for a long period. The surface and dispersion properties of modified SF (MSF), as well as the strength and pore structure of UHPC, were studied, and the stability of the modification was also investigated. The results demonstrated that, after treatment, the carboxylic groups were grafted on the SF surface, the dispersion of SF was improved due to the increased negative pentanal of the particle surface and the steric hindrance effect, the early hydration was delayed about 3-5 h, and the hydration heat release was also mitigated. The compressive strength of UHPC with MSF reached a maximum of 138.7 MPa at 3 days, which decreased about 3.7% more than the plain group, while flexural strength varied insignificantly. More pores and cracks were observed in the matrix with MSF, and the hydration degree was promoted with MSF addition. The grafted group on SF fell off under an alkali environment after 1 h.

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Layered Ti3C2Tx MXene has been successfully intercalated and exfoliated with the simultaneous generation of a 3D silica network by treating its cationic surfactant intercalation compound (MXene-CTAB) with an alkoxysilane (TMOS), resulting in a MXene-silica nanoarchitecture, which has high porosity and specific surface area, together with the intrinsic properties of MXene (e.g., photothermal response). The ability of these innovative MXene silica materials to induce thermal activation reactions of previously adsorbed compounds is demonstrated here using NIR laser irradiation. For this purpose, the pinacol rearrangement reaction has been selected as a first model example, testing the effectiveness of NIR laser-assisted photothermal irradiation in these processes. This work shows that Ti3C2Tx-based nanoarchitectures open new avenues for applications that rely on the combined properties inherent to their integrated nanocomponents, which could be extended to the broader MXene family.

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The dual nature of asphalt binder necessitates improvements to mitigate rutting and fatigue since it performs as an elastic material under the regime of rapid loading or cold temperatures and as a viscous fluid at elevated temperatures. The present investigation assesses the effectiveness of Nano Alumina (NA), Nano Silica (NS), and Nano Titanium Dioxide (NT) at weight percentages of 0, 2, 4, 6, and 8% in asphalt cement to enhance both asphalt binder and mixture performance. Binder evaluations include tests for consistency, thermal susceptibility, aging, and workability, while mixture assessments focus on Marshall properties, moisture susceptibility, resilient modulus, permanent deformation, and fatigue characteristics. NS notably improves binder viscosity by about 138% and reduces penetration by approximately 40.8% at 8% nanomaterial (NM) content, significantly boosting hardness and consistency. NS also enhances Marshall stability and decreases air voids, increasing the mix's durability. For moisture resistance, NS at 8% NM content elevates the Tensile Strength Ratio (TSR) to 91.0%, substantially surpassing the 80% standard. Similarly, NA and NT also show improved TSR values at 8% NM content, with 88.0% and 84.1%, respectively. Additionally, NS, NA, and NT reduce permanent deformation by 82%, 69%, and 64% at 10,000 cycles at 8% NM content, illustrating their effectiveness in mitigating pavement distress. Notably, while higher NM content generally results in better performance across most tests, the optimal NM content for fatigue resistance is 4% for NS and 6% for both NA and NT, reflecting their peak performance against various types of pavement distresses. These results highlight the significant advantages of nanoparticles in improving asphalt's mechanical properties, workability, stability, and durability. The study recommends further field validation to confirm these laboratory findings and ensure that enhancements translate into tangible improvements in real-world pavement performance and longevity.

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Embedding quantum dots into porous matrices is a very beneficial approach for generating hybrid nanostructures with unique properties. In this contribution we explore strategies to dope nanoporous SiO2 thin films made by atomic layer deposition and selective wet chemical etching with precise control over pore size with CdSe quantum dots. Two distinct strategies were employed for quantum dot deposition: in situ growth of CdSe nanocrystals within the porous matrix via successive ionic layer adsorption reaction, and infiltration of pre-synthesized quantum dots. To address the impact of pore size, layers with 10 nm and 30 nm maximum pore diameter were used as the matrix. Our results show that though small pores are potentially accessible for the in situ approach, this strategy lacks controllability over the nanocrystal quality and size distribution. To dope layers with high-quality quantum dots with well-defined size distribution and optical properties, infiltration of preformed quantum dots is much more promising. It was observed that due to higher pore volume, 30 nm porous silica shows higher loading after treatment than the 10 nm porous silica matrix. This can be related to a better accessibility of the pores with higher pore size. The amount of infiltrated quantum dots can be influenced via drop-casting of additional solvents on a pre-drop-casted porous matrix as well as via varying the soaking time of a porous matrix in a quantum dot solution. Luminescent quantum dots deposited via this strategy keep their luminescent properties, and the resulting thin films with immobilized quantum dots are suited for integration into optoelectronic devices.

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The use of heterogeneous catalysts to increase the development of green chemistry is a rapidly growing area of research to save industry money. In this paper, mesoporous SiO2-Al2O3 mixed oxide supports with various Si/Al ratios were prepared using two different sol-gel routes: hydrolytic sol-gel (HSG) and non-hydrolytic sol-gel (NHSG). The HSG route was investigated in both acidic and basic media, while the NHSG was explored in the presence of ethanol and diisopropyl ether as oxygen donors. The resulting SiO2-Al2O3 mixed oxide supports were characterized using EDX, N2 physisorption, powder XRD, 29Si, 27Al MAS-NMR and NH3-TPD. The mesoporous SiO2-Al2O3 supports prepared by NHSG seemed to be more regularly distributed and also more acidic. Consequently, a simple one-step NHSG (ether and alcohol routes) was selected to prepare mesoporous and acidic SiO2-Al2O3-NiO mixed oxide catalysts, which were then evaluated in ethylene oligomerization. The samples prepared by the NHSG ether route showed better activity than those prepared by the NHSG alcohol route in the oligomerization of ethylene at 150 °C.

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Multi drug resistance (MDR) in breast carcinoma still poses a significant impairment to successful chemotherapy. As the arsenal of anticancer agents increases with improved preclinical methods, the growth of therapeutic drug combinations is now unprecedented. The malignancies addressed by mono drugs often fail to limit cancer progression, resulting in resistant cancer, thereby offering combinatorial therapies a terrific edge over monodrug regimes. However, the selection of drug combinations required enough preliminary evidence for their synergistic effect. The fundamental mechanisms of MDR to chemotherapeutics are associated with the overexpression of membrane efflux pumps, alternations in drug targets, and increased drug metabolism. Unfortunately, it is very difficult for drugs to overcome resistance produced on their own or by another different drug action. In this context, herein, we report a simple delivery system for coencapsulation and intracellular codelivery of dual-drug thymoquinone (TQ) and doxorubicin (DOX) to resensitize DOX-resistant MDA MB231 cell line (231 R). The 231 R cell line developed in our lab showed an enhanced expression of the ATP-binding cassette (ABC) transporters P-gp1/MDR-1 and a declined miR-298 expression. The present delivery system is based on amine-functionalized mesoporous silica nanoparticles (MSNs), in which the side chain amine functional group was used to react with the carbonyl group of TQ, which acts as a pro-drug system (TQ-MSN) to release TQ and DOX simultaneously. DOX was encapsulated later into the above TQ-MSN by a simple diffusion method. The drugs containing MSNs were further coated with a hyaluronic acid-conjugated PEG-PLGA polymer (HA@TQ-DOX-MSN). This simple nanostrategy interferes with the MDR-1/miR-298 cross-talk, thereby allowing a significant reduction in drug efflux from the cell and highlighting a promising nanotechnology-based combinatorial delivery approach in managing breast cancer chemoresistance.

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This study aimed to recover high-purity silica from hematite tailings (HTs) using superconducting high-gradient magnetic separation (S-HGMS) technology. This process involved converting silica into a silicone-rich concentrate and subsequently employing a fluorine-free mixed acid to leach the silicon-rich concentrate to remove impurities and achieve refinement and purification. The optimization of the S-HGMS process was conducted using the "Box-Behnken Design" method, resulting in the following optimal conditions: a pulp concentration of 50 g/L, a magnetic velocity ratio of 0.076 T s/m, and a pulp velocity of 500 mL/min. These conditions yielded a silica grade range of 61.905% in the HTs to 91.818% in the silicon-rich concentrate, with corresponding recovery rates of 53.031%. Under the optimized leaching process, this resulted in an increase in the silica content from 91.818% in the silicon-rich concentrate to 99.938% in high-purity silica. Additionally, by analyzing the production process of 1 kg of high-purity silica from HTs using the process LCA method, environmental hotspots were identified, and corresponding solutions were proposed. This approach is vital for efficient utilization of HTs as a resource. This process has low energy consumption and is environmentally friendly, enabling the reduction of hematite tailings. It has a wide range of applications and offers substantial economic benefits, rendering it a promising candidate for industrial applications.

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The nasty urine microenvironment (UME) impedes neourethral regeneration by inhibiting angiogenesis and inducing an excessive inflammatory response. Cellular adaptation to hypoxia improves regeneration in numerous tissues. In this study, heterogeneous porous hypoxia-mimicking scaffolds were fabricated for urethral reconstruction via promoting angiogenesis and modulating the inflammatory response based on sustained release of dimethyloxalylglycine (DMOG) to promote HIF-1α stabilization. Such scaffolds exhibit a two-layered structure: a dense layer composed of electrospun poly (l-lactic acid) (PLLA) nanofibrous mats and a loose layer composed of a porous gelatin matrix incorporated with DMOG-loaded mesoporous silica nanoparticles (DMSNs) and coated with poly(glycerol sebacate) (PGS). The modification of PGS could significantly increase rupture elongation, making the composite scaffolds more suitable for urethral tissue regeneration. Additionally, sustained release of DMOG from the scaffold facilitates proliferation, migration, tube formation, and angiogenetic gene expression in human umbilical vein endothelial cells (HUVECs), as well as stimulates M2 macrophage polarization and its regulation of HUVECs migration and smooth muscle cell (SMCs) contractile phenotype. These effects were downstream of the stabilization of HIF-1α in HUVECs and macrophages under hypoxia-mimicking conditions. Furthermore, the scaffold achieved better urethral reconstruction in a rabbit urethral stricture model, including an unobstructed urethra with a larger urethral diameter, increased regeneration of urothelial cells, SMCs, and neovascularization. Our results indicate that heterogeneous porous hypoxia-mimicking scaffolds could promote urethral reconstruction via facilitating angiogenesis and modulating inflammatory response.