Ultra-slow-light and dynamically quantitative optical storage modulation via quasi-BICs.

We achieve dynamically tunable dual quasi-bound states in the continuum (quasi-BICs) by implementing them in a silicon-graphene multilayer composite structure and utilize the quasi-BIC modes to achieve ultra-large group delays (velocity of light slows down 105 times), showing 2-3 orders of magnitude higher than the group delays of previous electromagnetically induced transparency modes. The double-layer graphene holds great tuning capability and leads to the dramatically reduced group delay from 1929.82 to 1.58 ps with only 100 meV. In addition, the log-linear variation rule of group delay with Fermi level (Ef) in the range of 0-10 meV is analyzed in detail, and the double-logarithmic function relationship between the group delay and quality factor (Q-factor) is theoretically verified. Finally, the quantitative modulation of the optical storage is further realized in this basis. Our research provides ideas for the reform and upgrading of slow optical devices.

A novel insulin delivery system by ß cells encapsulated in microcapsules.

Introduction: Diabetes is a growing epidemic worldwide and requires effective clinical therapies. In recent years, ß-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 ß 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 ß cells, can enhance therapeutic efficacy and has promising clinical applications.

MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells.

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.

Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer.

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.

Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells.

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.

[Efficient and Stable Operation of Shortcut Nitrification by Entrapping Ammonia Oxidizing Bacteria].

In order to improve the efficiency of shortcut nitrification by entrapping ammonia oxidizing bacteria, the technique of ammonia oxidizing bacteria(AOB) enrichment culture was studied. The continuous operation method was used to inhibit the growth of nitrite-oxidizing bacteria(NOB) by free ammonia, at the same time, the NOB was gradually washed out of the system through the technology of sludge discharge. Polyvinyl alcohol(PVA) was used as the embedding material to immobilize the ammonia oxidizing bacteria after enrichment culture. The embedding rate of the reactor was 8%. The ammonia oxidation rate was increased by improving ammonia nitrogen loading in the continuous operation mode. The results showed that the ammonia oxidation rate(NH4+-N/VSS)was as high as 2.028 g·(g·d)-1 and the nitrite nitrogen accumulation rate was stabilized at more than 90%. High-throughput sequencing analysis was conducted on the bacterial community composition before and after enrichment culture, and the experimental result indicated that the culture diversity of raw sludge was larger. Nitrosomonas and Nitrospirae, which have nitrification function, accounted for 0.24% and 2.7%, respectively. The diversity of the activated sludge decreased significantly after the enrichment culture, Nitrosomonas(18%) became the dominant bacteria whereas Nitrospira occupied only 0.02%. After he embedding of ammonia oxidizing bacteria, the shortcut nitrification was realized rapidly. Finally, the shortcut nitrification rate reached 50 mg·(L·h)-1and the nitrite nitrogen accumulation was above 90%.