Ferroptosis is an iron‐dependent, lipid peroxide‐driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple‐negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin‐loaded exosomes labeled with folate (FA) to form FA‐vectorized exosomes loaded with erastin (erastin@FA‐exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti–tumor effect in vitro of erastin@FA‐exo were determined. Erastin@FA‐exo could increase the uptake efficiency of erastin into MDA‐MB‐231 cells; compared with erastin@exo and free erastin, erastin@FA‐exo has a better inhibitory effect on the proliferation and migration of MDA‐MB‐231 cells. Furthermore, erastin@FA‐exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA‐exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome‐based erastin preparations provide an innovative and powerful delivery platform for anti–cancer therapy.

Although ferroptosis has been recognized as a novel antitumoral treatment, high expression of nuclear factor erythroid 2-related factor 2 (NRF2) has been reported to be an antioxidant transcript factor that protects malignant cells from ferroptosis. Previous findings indicated that metallothionein 1D pseudogene (MT1DP), a long noncoding RNA (lncRNA), functioned to aggravate oxidative stress by repressing antioxidation. Here we aimed at assessing whether MT1DP could regulate erastin-induced ferroptosis on non-small cell lung cancer (NSCLC) and elucidating the mechanism. We found that ectopic expression of MT1DP sensitized A549 and H1299 cells to erastin-induced ferroptosis through downregulation of NRF2; in addition, ectopic MT1DP upregulated malondialdehyde (MDA) and reactive oxygen species (ROS) levels, increased intracellular ferrous iron concentration, and reduced glutathione (GSH) levels in cancer cells exposed to erastin, whereas downregulation of MT1DP showed the opposite effect. RNA pulldown assay and dual-luciferase reporter assay confirmed that MT1DP modulated the expression of NRF2 via stabilizing miR-365a-3p. As low solubility of erastin limits its efficient application, we further prepared folate (FA)-modified liposome (FA-LP) nanoparticles for targeted co-delivery of erastin and MT1DP to enhance the bioavailability and the efficiency of the drug/gene combination. Erastin/MT1DP@FA-LPs (E/M@FA-LPs) sensitized erastin-induced ferroptosis with decreased cellular GSH levels and elevated lipid ROS. In vivo analysis showed that E/M@FA-LPs had a favorable therapeutic effect on lung cancer xenografts. In short, our findings identify a novel strategy to elevate erastin-induced ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis.

Growing evidence confirms that ferroptosis plays an important role in tumor growth inhibition. However, some non‐small‐cell lung cancer (NSCLC) cell lines are less sensitive to erastin‐induced ferroptotic cell death. Elucidating the mechanism of resistance of cancer cells to erastin‐induced ferroptosis and increasing the sensitivity of cancer cells to erastin need to be addressed. In our experiment, erastin and acetaminophen (APAP) cotreatment inhibited NSCLC cell viability and promoted ferroptosis and apoptosis, accompanied with attenuation of glutathione and ectopic increases in lipid peroxides. Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde. As a downstream gene of Nrf2, heme oxygenase‐1 expression decreased significantly with the cotreatment of erastin and APAP, which could be rescued by BM. In vivo experiment showed that the combination of erastin and APAP had a synergic therapeutic effect on xenograft of lung cancer. In short, the present study develops a new effective treatment for NSCLC by synergizing erastin and APAP to induce ferroptosis.

The nitrifying bacteria community can be enriched by an alternating operation mode.

This paper explores the role of gender gap in the actuarial research community with advanced data science tools. The web scraping tools were employed to create a database of publications that encompasses six major actuarial journals. This database includes the article names, authors' names, publication year, volume, and the number of citations for the time period 2005-2018. The advanced tools built as part of the R software were used to perform gender classification based on the author's name. Further, we developed a social network analysis by gender in order to analyze the collaborative structure and other forms of interaction within the actuarial research community. A Poisson mixture model was used to identify major clusters with respect to the frequency of citations by gender across the six journals. The analysis showed that women's publishing and citation networks are more isolated and have fewer ties than male networks. The paper contributes to the broader literature on the "Matthew effect" in academia. We hope that our study will improve understanding of the gender gap within the actuarial research community and initiate a discussion that will lead to developing strategies for a more diverse, inclusive, and equitable community.

Introduction: Diabetes is a growing epidemic worldwide and requires effective clinical therapies. In recent years, β-cell transplantation has emerged as a promising treatment for diabetes, and an encapsulation approach has been proposed to ameliorate this treatment.Methods: Microfluidic technology had been used to generate microcapsules using a porous sodium alginate shell and a core containing β cells. The microcapsules were transplanted into diabetic mice and the therapeutic effect was measured.Results: Porous hydrogel shell allows exchange of small molecules of nutrients while protecting beta cells from immune rejection, while the core ensures high activity of the encapsulated cells. The glucose control effect of the microcapsules were more durable and better than conventional methods.Discussion: We believe that this system, which is composed of biocompatible porous hydrogel shell and enables highly activity of encapsulated β cells, can enhance therapeutic efficacy and has promising clinical applications.

Under the influences of global environmental change, the water cycle exhibits a characteristic “natural-social” duality. The theoretical framework of this dualistic water cycle model has become relatively mature and the frameworks for the natural and social water cycles of the process description are now relatively clear. Although many studies in this field focus on further improvement of the model, it is difficult to apply it to the multi-scenario regulation of water resources. To address this gap, based on the comprehensive integrated platform, this paper uses visual knowledge map technology and component technology to visualize the theoretical framework of the dualistic water cycle, and establishes a framework system for the visualization of the dualistic water cycle process. Three different water resource regulation scenarios were established in the system and example applications of water resources regulation using the system were realized. The simulation results of the system show that the system intends to assist the business function of water resources regulation, and it is able to set up a number of dynamic scenarios that can be controlled by users and assist the application of regional water resources regulation. The system’s regulatory process is visual, trustworthy, and operational, and it realizes the simulation application of water resources regulation under the framework of the dualistic water cycle.