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As one of the triazine herbicides with widespread usage in agriculture, metribuzin exerted nonnegligible hazardous effects on plants via excessive accumulation of reactive oxygen species and destruction of antioxidant enzymes, but the underlying harmful mechanism of metribuzin-induced oxidative damage to plants has never been exploited. Here, Arabidopsis thaliana glutathione reductase 2 (AtGR2) was employed as the biomarker to evaluate the adverse impacts of metribuzin on plants. The fluorescence intensity of AtGR2 was decreased based on the static quenching mechanism with the prediction of a single binding site toward metribuzin, and the complex formation was presumed to be mainly impelled by hydrogen bonding and van der Waals forces from the negative ΔH and ΔS. In addition, the loosened and unfolded skeleton of AtGR2 along with the increased hydrophilicity around the tryptophan residues were investigated. Besides, the glutathione reductase activity of AtGR2 was also destroyed due to structural and conformational changes. At last, the severe inhibiting growth of Arabidopsis seedling roots was discovered under metribuzin exposure. Hence, the evaluation of the molecular interaction mechanism of AtGR2 with metribuzin will establish valuable assessments of the toxic effects of metribuzin on plants.

To alleviate decision-making pressure on rail transit dispatchers in the emergency handling process, this work sorts out the scenario elements of rail transit emergency cases, establishes a scenario element system, and uses the information weight method to determine the weight of each scenario element. Based on the information of the key decision points, the complete process of emergencies is divided into various scenarios, and an emergency case representation model is constructed. The model establishes a database of historical emergency cases in rail transit, utilizes the scenarios as the search object to match the similarity of emergencies, and provides the decision-making support information to handle the current emergencies. Furthermore, the model constructed in this paper is subjected to an actual emergency case for analysis and calculation, which verify the validity and feasibility of the proposed model.

Dielectric capacitors are fundamental for electric power systems due to the fast charging/discharging rate and high-power density.[1,2] Recently, rapidly increased demands of miniaturization and integration continuously challenge energy storage density of dielectric capacitors, especially for that could be compatible with the complementary metal-oxide-semiconductor (CMOS) technology, for developing energy-autonomous systems and implantable/wearable electronics, where high-κ capacitors become increasingly desirable in the next-generation applications.[3-5] However, their recoverable energy storage densities (Urec) are low in emerging capacitive energy storage materials. Here, by structure evolution between fluorite HfO2 and perovskite hafnate who have similar metal sublattices, we create an amorphous hafnium-based oxide that exhibits a giant Urec of ~155 J/cm3 with an efficiency (η) of 87%, which is record-high in high-κ materials and state-of-the-art in dielectric energy storage. The improved energy density is owing to the strong structure disordering in both short and long ranges induced by oxygen instability in between the two energetically-favorable crystalline forms. As a result, the carrier avalanche is impeded and an ultrahigh breakdown strength (Eb) up to 12 MV/cm is achieved, which, accompanying with a large permittivity (εr), remarkably enhances the dielectric energy storage. Our study provides a new and widely applicable playground for designing high-performance dielectric energy storage with the strategy exploring the boundary among different categories of materials.

Zinc oxide nanoparticles (ZnO NPs) have been known as a therapeutic agent and drug delivery system for treating various diseases, including infectious diseases and cancer. However, due to the low biocompatibility, short in vivo half-life, and potential toxicity, the previous studies on ZnO NPs were mainly focused on their in vitro applications. The effective and safe ZnO NP-based systems which can be used for in vivo drug delivery have been rarely reported. In this study, we developed a novel dual-responsive hybrid ZnO NP (ZnO/DPPG/PEG-pp-PE) consisting of the ZnO NPs, phospholipid (DPPG), and enzyme-sensitive amphiphilic polymer (PEG-pp-PE), which could respond to both tumoral matrix metalloproteinase 2 (MMP2) and intracellular acidic pH, for tumor-targeted drug delivery and multidrug resistant (MDR) cancer treatment. The dual-responsive ZnO/DPPG/PEG-pp-PE could easily load the model drug, doxorubicin (DOX), and showed excellent physicochemical properties, stability, and MMP2 and pH dual sensitivity. The ZnO/DPPG/PEG-pp-PE/DOX showed the MMP2-dependent cellular uptake, enhanced cell penetration, and improved anticancer activity in the MDR cancer cells and their spheroids. In the MDR tumor-bearing mice, the ZnO/DPPG/PEG-pp-PE/DOX improved the biocompatibility, tumor targetability, and anticancer activity of DOX and ZnO without significant toxicity compared to the free DOX, ZnO/DOX, and nonsensitive ZnO NPs. The data suggested that the dual-sensitive ZnO-based nanomedicine could be a promising delivery system for targeted drug delivery and therapy against the MDR cancer.

Background Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD. Methods Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently. Results A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%. Conclusion The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite. Trial registration PROSPERO Nr: CRD42021286192

Background Interstitial lung diseases (ILDs) can be induced and even exacerbated by radiotherapy in thoracic cancer patients. The roles of immune responses underlying the development of these severe lung injuries are still obscure and need to be investigated. Methods A severe lung damage murine model was established by delivering 16 Gy X-rays to the chest of mice that had been pre-treated with bleomycin (BLM) and thus hold ILDs. Bioinformatic analyses were performed on the GEO datasets of radiation-induced lung injury (RILI) and BLM-induced pulmonary fibrosis (BIPF), and RNA-sequencing data of the severely damaged lung tissues. The screened differentially expressed genes (DEGs) were verified in lung epithelial cell lines by qRT-PCR assay. The injured lung tissue pathology was analyzed with H&E and Masson’s staining, and immunohistochemistry staining. The macrophage chemotaxis and activity promoted by the stressed epithelial cells were determined by using a cell co-culture system. The expressions of p21 in MLE-12 and Beas-2B cells were detected by qRT-PCR, western blot, and immunofluorescence. The concentration of CCL7 in cell supernatant was measured by ELISA assay. In some experiments, Beas-2B cells were transfected with p21-siRNA or CCL7-siRNA before irradiation and/or BLM treatment. Results After the treatment of irradiation and/or BLM, the inflammatory and immune responses, chemokine-mediated signaling pathways were steadily activated in the severely injured lung, and p21 was screened out by the bioinformatic analysis and further verified to be upregulated in both mouse and human lung epithelial cell lines. The expression of P21 was positively correlated with macrophage infiltration in the injured lung tissues. Co-culturing with stressed Beas-2B cells or its conditioned medium containing CCL7 protein, U937 macrophages were actively polarized to M1-phase and their migration ability was obviously increased along with the damage degree of Beas-2B cells. Furthermore, knockdown p21 reduced CCL7 expression in Beas-2B cells and then decreased the chemotaxis of co-cultured macrophages. Conclusions P21 promoted CCL7 release from the severely injured lung epithelial cell lines and contributed to the macrophage chemotaxis in vitro, which provides new insights for better understanding the inflammatory responses in lung injury.

The single echinoderm microtubule-associated protein-like 4 (EML4) gene and anaplastic lymphoma kinase (ALK) gene fusion is the most common variant of ALK rearrangements in non-small cell lung cancer (NSCLC). Herein, we firstly report that coexistence of a novel histone methyltransferase (SETD2)-ALK, EML4-ALK double-fusion is sensitive to alectinib as first-line therapy, and response to immunotherapy combined with chemotherapy after resistant. The patient responded to alectinib as a first-line therapy and achieved progression-free survival (PFS) for 26 months. After resistance, liquid biopsy showed that the reason of drug resistance was the disappearance of SETD2-ALK and EML4-ALK fusion variants. In addition, chemotherapy combined with immunotherapy subsequently achieved a survival benefit of more than 25 months. Therefore, alectinib may be a viable therapeutic option for NSCLC patients with double ALK fusion and immunotherapy combined with chemotherapy may be a viable therapeutic option when double ALK fusion loss may be the mechanism of alectinib resistance.

Aseisimic earth fissures are complex consequences of groundwater withdrawal and natural hydrogeologic conditions. This paper aims to improve the understanding of the mechanism of earth fissuring and investigate the relative importance of various factors to fissure activity, including bedrock geometry, piezometric depletion, compressibility and thickness of the exploited aquifer. For these purposes, a test case characterized by an impermeable and incompressible rock ridge in a subsiding basin is developed, where stress/displacement analyses and fissure state are predicted using an interface finite element model. Three different methods for global sensitivity analysis are used to quantify the extent of the fissure opening to the aforementioned factors. The conventional sampling based Sobol' sensitivity analysis is compared to two surrogate based methods, the general polynomial chaos expansion based Sobol' analysis and a feature importance evaluation of a gradient boosting decision tree model. Numerical results indicate that earth fissure is forming in response to tensile stress accumulation above the ridge associated to pore pressure depletion, inducing the fissure opening at land surface with further downward propagation. Sensitivity analysis highlights that the geometry of bedrock ridge is the most influential feature. Specifically, the fissure grows more when the ridge is steeper and closer to the land surface. Pore pressure depletion is a secondary feature and required to reach a certain threshold to activate the fissure. As for this specific application, the gradient boosting tree is the most suitable method for its better performance in capturing fissure characteristics.