Acetaminophen (APAP), a classic nonsteroidal anti-inflammatory drug (NSAID), has attracted much attention due to the overdose-induced hepatotoxicity in the past several decades. ...N-Acetyl-p-benzoquinone imine (NAPQI), the P450-dependent metabolism of APAP, leads to GSH depletion, protein binding, mitochondrial oxidative stress, and eventually the liver injury. Herein, we develop a Fe-based metal-organic framework (MOF) to deliver and transform acetaminophen into toxic “chemo” drug through the cascade reaction for enhanced cancer therapy. In the acidic tumor microenvironment, the Fe-based MOF collapses and releases abundant Fe ions to generate hydroxyl radicals (•OH) via Fenton reaction, subsequently catalyzing nontoxic APAP into toxic NAPQI. Meanwhile, NAPQI depletes intracellular glutathione (GSH) rapidly, leading to alleviating the antioxidant ability of cancer cells and amplifying Fenton activity. The intracellular oxidative stress and the toxic metabolite of APAP can provide a synergistic effect on antitumor activity.
We develop a Fe-based metal-organic framework (MOF) to deliver and transform acetaminophen into toxic “chemo” drug through the cascade reaction for enhanced cancer therapy. The intracellular oxidative stress and the toxic metabolite of APAP can provide a synergistic effect on antitumor activity. Display omitted
The development of chemoimmunotherapy with reduced systemic toxicity using local formulations is an effective strategy for combating tumor recurrence. Herein, we reported a localized hydrogel system ...for antitumor chemoimmunotherapy, formed by doxorubicin (DXR)-loaded bovine serum albumin (BSA) nanoparticles self-cross-linked with natural polysaccharide chitosan (CS). The drug-loaded hydrogel (DXR-CBGel) with antiswelling performance and prolonged drug-release profile was combined with antiprogrammed cell death protein 1 (aPD-1) as an in situ vaccine for treating glioblastoma multiforme (GBM) lesions. The antiswelling hydrogel system shows excellent biosafety for volume-sensitive GBM lesions. Both the albumin-bound formulation and the in situ gelation design facilitate the local retention and sustained release of DXR to generate long-term chemoimmunotherapy with reduced systemic toxicity. The chemotherapy-induced immunogenic cell death of DXR with the assistance of immunotherapeutic CS can trigger tumor-specific immune responses, which are further amplified by an immune checkpoint blockade to effectively inhibit cancer recurrence. The strategy of combining albumin-bound drug formulation and biocompatible polymer-based hydrogel for localized chemoimmunotherapy shows great potential against postsurgery glioblastoma recurrence.
Abstract
Two‐dimensional (2D) membranes have demonstrated potential for molecular separation; however, their applicability for Li/Mg ion separation has been restricted by their negatively‐charged and ...easily‐swellable properties in water. Moreover, their practical application has been hindered by the challenge of producing significant quantities of single‐layer nanosheets. To overcome these challenges, we have developed a scalable method for synthesizing micro‐sized nitrate ZnAl layered double hydroxide (LDH) and subsequent exfoliating to yield monolayer nanosheets for the construction of 2D membranes. The sub‐nanometer channels of the LDH membrane is positively charged, which prevents the passage of magnesium ions. These channels also impede the flow of magnesium ions that are more difficult to dehydrate. As a result, the LDH membranes exhibit robust lithium–magnesium separation ability, with a separation ratio of 6 (Li/Mg). This work provides a method for producing high‐quality LDH nanosheets and validates the enormous potential of LDH membranes in the field of lithium–magnesium separation.
Abstract
Brain disease gene identification is critical for revealing the biological mechanism and developing drugs for brain diseases. To enhance the identification of brain disease genes, ...similarity-based computational methods, especially network-based methods, have been adopted for narrowing down the searching space. However, these network-based methods only use molecular networks, ignoring brain connectome data, which have been widely used in many brain-related studies. In our study, we propose a novel framework, named brainMI, for integrating brain connectome data and molecular-based gene association networks to predict brain disease genes. For the consistent representation of molecular-based network data and brain connectome data, brainMI first constructs a novel gene network, called brain functional connectivity (BFC)-based gene network, based on resting-state functional magnetic resonance imaging data and brain region-specific gene expression data. Then, a multiple network integration method is proposed to learn low-dimensional features of genes by integrating the BFC-based gene network and existing protein–protein interaction networks. Finally, these features are utilized to predict brain disease genes based on a support vector machine-based model. We evaluate brainMI on four brain diseases, including Alzheimer’s disease, Parkinson’s disease, major depressive disorder and autism. brainMI achieves of 0.761, 0.729, 0.728 and 0.744 using the BFC-based gene network alone and enhances the molecular network-based performance by 6.3% on average. In addition, the results show that brainMI achieves higher performance in predicting brain disease genes compared to the existing three state-of-the-art methods.
In this study, the enrichment sequencing batch biofilm reactor (SBBR) and conventional enrichment reactor (SBR) were established, and a new strategy was developed to achieve higher biomass yield and ...polyhydroxyalkanoate (PHA) production from food waste than those achieved through the conventional method. After the 10th day of an expanded cultivation period, the respective active biomass concentrations in SBR and SBBR were 5.16 and 13.92 g/L, indicating a significant improvement in the biomass yield of mixed microbial culture in the SBBR. The PHA accumulation test revealed that maximum PHA concentration in SBR and SBBR reached 6.60 and 12.70 g/L, respectively, after 80 days of enrichment, indicating that compared to SBR, the SBBR could more effectively improve the PHA accumulation capacity. Meganema, Thauera, and Paracoccus were the dominant PHA-accumulating bacteria in the SBR and SBBR. Additionally, the volumetric productivity of the SBBR was 3.22 g COD/L/d, twice that of the SBR. This study provides new strategies and insights for improving PHA production and reducing the costs of PHA production and reactor investment.
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In situ growth of dispersed active sites on substrates is a strategy for designing highly efficient catalysts for sulfate radical (SO4•−)-based advanced oxidation processes (SR-AOPs). Here, magnetic ...biochar composite (Fe3O4/BC) was fabricated as an activator to trigger PDS (peroxydisulfate) for norfloxacin (NOR) removal, achieving reliable NOR removal efficiency (>90%) within 10 min. Based on the synergistic effect between Fe3O4 and BC, the removal rate increases to 0.0265 L mg−1 min−1. Fe3O4/BC exhibited decent adaptability, stability, and recyclability toward affecting factors variation during PDS activation, attributed to the synergistic effect between Fe3O4 and BC. The electron transfer of magnetic Fe3O4 coupled with the adsorption and conduction function of carbon skeleton, which overcomes typical problems as crystal agglomeration, metal leaching, and catalysts recovery etc. The electron-rich Fe(II) sites promote the radical pathway by generating reactive oxygen species (ROS, •OH, SO4•− and O2•−), and radicals evolution contributing to the form of 1O2 in non-radical pathway. Under the effect of multipath in NOR degradation, HPLC-QTOF-MS spectroscopy and DFT calculation revealed the possible degradation pathway of NOR. In addition, according to toxicity prediction, the overall NOR contamination toxicity of NOR was effectively alleviated by Fe3O4/BC + PDS system. Overall, this study presents a promising composite in PDS activation and views the active species evolution in the NOR removal system, which is crucial for mechanism study in relevant research in the future.
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•Fe3O4 in collaboration with biochar promotinged the NOR removal to over 90% within 10 min.•The Fe3O4/BC + PDS system exhibited higher 80% NOR removal efficiency in lake water matrices.•High mineralization (>50%) with minimal leached Fe (<50 μg/L) was maintained after 6 cycles.•Multiple pathways (radical and non-radical pathways) participated in the NOR degradation in the Fe3O4/BC + PDS system.•Active species (SO4.•−, •OH, •O2−, and 1O2) evolution process have been systematic investigated.
In order to obtain more accurate precipitation data and better simulate the precipitation on the Tibetan Plateau, the simulation capability of 14 Coupled Model Intercomparison Project Phase 6 (CMIP6) ...models of historical precipitation (1982–2014) on the Qinghai-Tibetan Plateau was evaluated in this study. Results indicate that all models exhibit an overestimation of precipitation through the analysis of the Taylor index, temporal and spatial statistical parameters. To correct the overestimation, a fusion correction method combining the Backpropagation Neural Network Correction (BP) and Quantum Mapping (QM) correction, named BQ method, was proposed. With this method, the historical precipitation of each model was corrected in space and time, respectively. The correction results were then analyzed in time, space, and analysis of variance (ANOVA) with those corrected by the BP and QM methods, respectively. Finally, the fusion correction method results for each model were compared with the Climatic Research Unit (CRU) data for significance analysis to obtain the trends of precipitation increase and decrease for each model. The results show that the IPSL-CM6A-LR model is relatively good in simulating historical precipitation on the Qinghai-Tibetan Plateau (
R
=0.7, RSME=0.15) among the uncorrected data. In terms of time, the total precipitation corrected by the fusion method has the same interannual trend and the closest precipitation values to the CRU data; In terms of space, the annual average precipitation corrected by the fusion method has the smallest difference with the CRU data, and the total historical annual average precipitation is not significantly different from the CRU data, which is better than BP and QM. Therefore, the correction effect of the fusion method on the historical precipitation of each model is better than that of the QM and BP methods. The precipitation in the central and northeastern parts of the plateau shows a significant increasing trend. The correlation coefficients between monthly precipitation and site-detected precipitation for all models after BQ correction exceed 0.8.
This paper investigates the dynamic behavior of a rolling mill during variable gauge rolling. Considering that the variation of rolling process parameters and the movement of hydraulic cylinder are ...the remarkable features of the variable gauge rolling process, the dynamic rolling force model and the hydraulic cylinder dynamic model were established respectively, and the rolling mill dynamic model was established based on the structure-process coupling strategy. The Incremental Harmonic Balance Method (IHBM) is used to solve the amplitude–frequency characteristics of the rolling mill system, and the Runge–Kutta method is used to solve the vibration characteristics. The results indicate that as the piston of the hydraulic cylinder is displaced, the stiffness of hydraulic cylinder changes and exhibits nonlinear features. The nonlinear characteristics of the hydraulic cylinder affect the dynamic behavior of the rolling mill, which presents different dynamic behaviors when the piston is in different initial positions for variable gauge rolling. The results provide a theoretical reference for the analysis and control of rolling mill dynamic behavior during variable gauge rolling.
