The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.

Thrombus formed in blood vessel is a progressive process, which would lead to life-threatening thrombotic diseases such as ischemic stroke. Unlike other diseases, the recognition of thrombus is usually in the late stage where blood vessels are largely blocked. So acute thrombotic diseases have a narrow therapeutic window, and remain leading causes of morbidity and mortality, whereas current thrombolysis therapy has limited therapeutic effects and bleeding complications. Thrombolytic agents in unwanted sites would cause hemorrhage due to the activation of plasminogen. Moreover, untargeted thrombolysis therapy require large amounts of thrombolytic agents, which in return would enhance hemorrhage risk. To improve the efficiency while minimizing the adverse effects of traditional thrombolysis therapy, novel drug delivery systems have been investigated. Various targeting strategies including ultrasound and magnetic field directed targeting, and specific binding, have been designed to deliver thrombolytic drugs to the thrombotic sites. These strategies demonstrate promising results in reducing bleeding risk as well as allowing less dosage of thrombolytic drugs with lowered clot lysis time. In this review, we discuss recent progress on targeted delivery of thrombolytics, and summarize treatment advantages and shortcomings, potentially helping to further promote the development of targeted thrombolysis.

Over the last decade, researchers have paid more and more attention to the natural compound curcumin for its potential application in anticancer therapy. However, the application of curcumin has been limited owing to its rapid metabolism in the body. HO‐3867, a stable curcumin analog, shows potent antitumor activities against various tumor cells. Yet, information on HO‐3867’s impact on non‐small‐cell lung cancer (NSCLC) cells is lacking. Herein, we evaluated the cytotoxicity of HO‐3867 in NSCLC cells. We discovered that HO‐3867 suppressed the viability of NSCLC cells containing wild‐type p53. In NSCLC cells, HO‐3867 promotes both apoptosis and ferroptosis, the latter of which is a newly discovered mode of cell death. Mechanically, HO‐3867‐induced apoptosis relied on the inhibition of Mcl‐1 and Bcl‐2 and the upregulation of Bax. Moreover, NSCLC cells undergo ferroptosis when treated with HO‐3867 via activating the p53‐DMT1 axis and suppressing GPX4. Additionally, HO‐3867 caused an accumulation of reactive oxygen species (ROS) in NSCLC in a way that was dependent on the presence of iron. Our findings point to the possibility that HO‐3867 might be employed as a therapeutic agent for treating NSCLC.

The purpose of this paper is to establish a transition strategy for tilt-rotor vertical takeoff and landing (VTOL) unmanned aerial vehicles (UAVs) based on an optimal design method. Firstly, The flyable transition corridor was calculated based on both the UAV’s dynamic equations and its aerodynamic and dynamic characteristics. The dynamic equations of the UAV were organized into state equation forms. The initial and final value constraints of the control and state variables in the transition process were recorded, as were the constraints of the transition process. The transition strategy design problem was transformed into an optimal control problem with constraints, while the Gauss pseudospectral method (GPM) was employed to transform and solve the problem. In addition, performance indicators were designed based on the transition quality requirements for transition time, attitude stability, and control continuity. Sensitivity was analyzed according to different index terms with different dimensions and effects. Finally, the rationality of the transition strategy designed in this paper was verified according to different simulation scenarios.

One direction in optimizing wind farm production is reducing wake interactions from upstream turbines. This can be done by optimizing turbine layout as well as optimizing turbine yaw and pitch angles. In particular, wake steering by optimizing yaw angles of wind turbines in farms has received significant attention in recent years. One of the challenges in yaw optimization is developing fast optimization algorithms which can find good solutions in real-time. In this work, we developed a random search algorithm to optimize yaw angles. Optimization was performed on a layout of 39 turbines in a 2 km by 2 km domain. Algorithm specific parameters were tuned for highest solution quality and lowest computational cost. Testing showed that this algorithm can find near-optimal (<1% of best known solutions) solutions consistently over multiple runs, and that quality solutions can be found under 200 iterations. Empirical results show that as wind farm density increases, the potential for yaw optimization increases significantly, and that quality solutions are likely to be plentiful and not unique.