Pyroptosis is a newly discovered inflammatory form of programmed cell death, which promotes systemic immune response in cancer immunotherapy. GSDMD is one of the key molecules executing pyroptosis, while therapeutical delivery of GSDMD to tumor cells is of great challenge. In this study, an extracellular vesicles‐based GSDMD‐N mRNA delivery system (namely EVTx) is developed for enhanced cancer immunotherapy, with GSDMD‐N mRNA encapsulated inside, Ce6 (Chlorin e6 (Ce6), a hydrophilic sensitizer) incorporated into extracellular vesicular membrane, and HER2 antibody displayed onto the surface. Briefly, GSDMD‐N mRNA is translationally repressed in donor cells by optimized puromycin, ensuring the cell viability and facilitating the mRNA encapsulation into extracellular vesicles. When targeted and delivered into HER2+ breast cancer cells by the engineered extracellular vesicles, the translational repression is unleashed in the recipient cells as the puromycin is diluted and additionally inactivated by sonodynamic treatment as the extracellular vesicles are armed with Ce6, allowing GSDMD‐N translation and pyroptosis induction. In addition, sonodynamic treatment also induces cell death in the recipient cells. In the SKBR3‐ and HER2 transfected 4T1‐ inoculated breast tumor mouse models, the engineered EVTx efficiently induces a powerful tumor immune response and suppressed tumor growth, providing a nanoplatform for cancer immunotherapy.

BACKGROUND: Arterial stiffness (AS) was associated with heart failure (HF) in previous studies based on specific populations with small samples and the effects of age and blood pressure on AS were not taken into account. Whether AS was independently associated with new-onset HF in community dwellers has not been fully investigated to date. METHODS: Individuals who participated in health evaluations and underwent synchronized brachial-ankle pulse wave velocity (baPWV) screening in 2010 to 2019 were included. They were free of HF and atrial fibrillation at baseline. The participants were allocated to 3 groups according to their baPWV values. Normal AS was defined as baPWV <1400 cm/s, borderline AS was defined as 1400≤baPWV<1800 cm/s, and elevated AS was defined as baPWV ≥1800 cm/s. Cox proportional hazard regression was used to calculate hazard ratios with 95% CIs of new-onset HF across different AS groups. RESULTS: A total of 40 064 participants were enrolled with a mean age of 48.81±12.67 years. During a mean 5.53 years of follow-up, 411 participants developed HF. Compared with the normal AS group, the hazard ratio (95% CI) for incident HF was 1.97 (1.36–2.86) for the borderline AS group and 2.24 (1.49–3.38) for the elevated AS group in the multivariable-adjusted model. For each 1 SD (359 cm/s) increase in baPWV, the hazard ratio (95% CI) for new-onset HF was 1.10 (1.02–1.20). CONCLUSIONS: AS was positively associated with a higher risk of new-onset HF independently of traditional risk factors, with a dose-responsive effect.

The roles of long non-coding RNA (lncRNAs) in ischemic stroke (IS) have been widely illustrated. Here, we focused on the function and mechanism of lncRNA SNHG7 in IS. Methods: Middle cerebral artery occlusion (MCAO) was used for inducing mice to establish IS models in vivo. Oxygen and glucose deprivation/reoxygenation (OGD/R) was used for treating PC12 cells to establish IS models in vitro. Relative expression of SNHG7 and miR-9 was determined by qRT-PCR. The neuronal injury was assessed by measuring relative activity of ROS, malondialdehyde (MDA) level and cell viability. Cell viability was determined by MTT assay. Dual-luciferase reporter (DLR) assay was employed to test the target of SNHG7 or miR-9. Western blot was used to determine the protein expression of SIRT1. Apoptosis rate was measured by flow cytometry. Results: SNHG7 was down-regulated and miR-9 was up-regulated by MCAO treatment in brain tissues of mice and by OGD/R treatment in PC12 cells. Overexpression of SNHG7 or suppression of miR-9 decreased the relative activity of ROS and the MDA level as well as enhancing cell viability, and SNHG7 reduced apoptosis rate in OGD/R-induced PC12 cells (IS cells). MiR-9 was targeted by SNHG7 and SIRT1 was targeted by miR-9. The protein expression of SIRT1 was reduced by OGD/R treatment in PC12 cells. The suppressive effects of SNHG7 on the relative activity of ROS, the MDA level and apoptosis rate as well as the promotion effect of SNHG7 on cell viability were reversed by miR-9 mimics or sh-SIRT1 in IS cells. Conclusion: LncRNA SNHG7 alleviated OGD/R-induced neuronal injury by mediating miR-9/SIRT1 axis in vitro.

The optimization of rolling schedule is the main content of tandem cold rolling which will affect the quality of products directly. A rolling schedule with the objectives of minimum energy consumption, relative power margin and slippage preventing is established. First, in order to make the rolling schedule more accurate in the calculation process, a mathematical model combines with deep neural network is proposed to calculate the rolling force. Second, a multi-objective particle swarm optimizer with dynamic opposition-based learning is proposed to optimize the rolling schedule. It has a new particle learning strategy to update the moving position of particles. Moreover, opposition-based learning is proposed to make the particles jump out of local optima. Finally, the experiments are carried out based on the field data. Simulation results demonstrate that the accuracy of the rolling force is greatly improved. The proposed algorithm has a promising performance on both diversity and convergence. At the same time, the optimized rolling schedule can well balance the rolling power and prevent slipping between five stands comparing with the original rolling schedule. INDEX TERMS Multi-objective optimization, tandem cold rolling, deep neural network, rolling force, rolling schedule.