Leveraging high-throughput screening technologies in targeted mRNA delivery.

Messenger ribonucleic acid (mRNA) has emerged as a promising molecular preventive and therapeutic approach that opens new avenues for healthcare. Although the use of delivery systems, especially lipid nanoparticles (LNPs), greatly improves the efficiency and stability of mRNA, mRNA tends to accumulate in the liver and hardly penetrates physiological barriers to reach the target site after intravenous injection. Hence, the rational design of targeting strategies aimed at directing mRNA to specific tissues and cells remains an enormous challenge in mRNA therapy. High-throughput screening (HTS) is a cutting-edge targeted technique capable of synthesizing chemical compound libraries for the large-scale experiments to validate the efficiency of mRNA delivery system. In this review, we firstly provide an overview of conventional low-throughput targeting strategies. Then the latest advancements in HTS techniques for mRNA targeted delivery, encompassing optimizing structures of large-scale delivery vehicles and developing large-scale surface ligands, as well as the applications of HTS techniques in extrahepatic systemic diseases are comprehensively summarized. Moreover, we illustrate the selection of administration routes for targeted mRNA delivery. Finally, challenges in the field and potential solutions to tackle them are proposed, offering insights for future development toward mRNA targeted therapy.

Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment.

As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.

Antitumor activity of Koningic acid in thyroid cancer by inhibiting cellular glycolysis.

PURPOSE: Koningic acid (KA), a sesquiterpene lactone, has been identified as an antimicrobial agent. Recent studies have revealed KA's antitumor activities in colorectal cancer, leukemia, and lung cancer. However, its antitumor effect in thyroid cancer remains largely unknown. METHODS: The effects of KA on proliferation, colony formation, apoptosis in thyroid cancer cells were assessed by MTT assay and flow cytometry. After KA treatment, the glycolysis ability of thyroid cancer cells was detected by ECAR, and the glycolytic products and relative ATP levels were measured by ELISA. The underlying mechanisms of antineoplastic activity of KA in thyroid cancer were detected by Western blot. Finally, the antineoplastic activity in vivo was observed in Xenograft mouse models. RESULTS: KA inhibited the proliferation, colony formation, and increased cell apoptosis in thyroid cancer cell lines in a dose and time-dependent manner. We verified that the glycolysis ability, ATP production, and lactic acid level in thyroid cancer cells had experienced an extensive decrease after KA treatment. In addition, lactic acid, the metabolite of glycolysis, could weaken the effect of KA on its colony formation ability in C643 thyroid cancer cell line. Our data also showed that KA kills thyroid cancer cells by inhibiting the MAPK/ERK pathway and decreasing Bcl-2 level. By contrast with the control group, the growth of xenograft tumor was dramatically inhibited by KA without obvious drug side effects. CONCLUSION: Our data demonstrate that KA kills thyroid cancer cell lines by inhibiting their glycolysis ability, the MAPK/ERK pathway and the Bcl-2 level and suggest that KA has potential clinical value in thyroid cancer therapy.

Fabrication of Robust, Highly Conductive, and Elastic Hybrid Carbon Foam Platform for High-Performance Compressible Asymmetry Supercapacitors.

Highly conductive and elastic three-dimensional (3D) porous carbon materials are ideal platforms to fabricate electrodes for high-performance compressible supercapacitors. Herein, a robust, highly conductive, and elastic carbon foam (CF) hybrid material is reported, which is fabricated by integrating cellulose nanofiber/multiwalled carbon nanotube (CNF/MWCNT) aerogel sheets with a melamine sponge (MS), followed by carbonization. The carbonized CNF/MWCNT aerogel sheets contribute to the high conductivity and specific surface area of the CF, and the 3D network-like skeleton derived from the carbonization of the MS enhances the elasticity and stability of the CF. More importantly, the CF possesses good scalability, allowing the introduction of electroactive materials such as polypyrrole (PPy) and Fe3O4 to fabricate high-performance compressible PPy-CF and Fe3O4-CF electrodes. Moreover, an assembled PPy-CF//Fe3O4-CF device shows reversible charging-discharging at a voltage of 1.6 V and demonstrates a high specific capacitance (172.5 F/g) and an outstanding energy density (59.9 W h/kg). The device exhibits capacitance retention rates reaching 98.3% and stable energy storage characteristics even under different degrees of compressive deformation. This study offers a scalable strategy for fabricating high-performance compressible supercapacitors, thereby providing a new means of satisfying the energy storage needs of portable electronic devices that are prone to deformation.

Investigation of the Residual Mechanical and Porosity Properties of Cement Mortar under Axial Stress during Heating.

The preload load on concrete during heating is considered to cause a 'densification' of cement mortar which led to the increased compressive strength. In order to assess the influence of coupled load and heating effects on porosity characteristics of concrete, the porosity of mortar after mechanical and thermal loading was measured by X-ray computed tomography (X-ray CT). The preload at pre-stress ratios of 0, 0.2, 0.4, and 0.6 (ratio of stress applied to the specimen to its compressive strength at room temperature) were applied on mortar specimens during heating. The residual compressive strengths of the heated and stressed mortar specimens were tested after cooling to room temperature. Combined analyses of the residual compressive strength test results and porosity test results, it shows that the porosity of the specimens under the coupled stressing and heating conditions were slightly lower than that under the unstressed conditions; however, the conclusion that the increase of compressive strength of stressed mortar was caused by the 'densification' of cement paste was insufficient. The preload reduced the cracks in the mortar, especially the crack induced due to the thermal mismatch in aggregates and hardened cement paste (HCP), and this may account for the increased compressive strength of stressed mortar.

Monitoring Traffic Information with a Developed Acceleration Sensing Node.

In this paper, an acceleration sensing node for pavement vibration was developed to monitor traffic information, including vehicle speed, vehicle types, and traffic flow, where a hardware design with low energy consumption and node encapsulation could be accomplished. The service performance of the sensing node was evaluated, by methods including waterproof test, compression test, sensing performance analysis, and comparison test. The results demonstrate that the sensing node is low in energy consumption, high in strength, IPX8 waterproof, and high in sensitivity and resolution. These characteristics can be applied to practical road environments. Two sensing nodes were spaced apart in the direction of travelling. In the experiment, three types of vehicles passed by the monitoring points at several different speeds and values of d (the distance between the sensor and the nearest tire center line). Based on cross-correlation with kernel pre-smoothing, a calculation method was applied to process the raw data. New algorithms for traffic flow, speed, and axle length were proposed. Finally, the effects of vehicle speed, vehicle weight, and d value on acceleration amplitude were statistically evaluated. It was found that the acceleration sensing node can be used for traffic flow, vehicle speed, and other types of monitoring.

Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is a rare malignancy and has a very poor prognosis due to its aggressive behavior and resistance to treatment. No effective treatment modalities are currently available. Lenvatinib has shown encouraging results in the patients with radioiodine-refractory differentiated thyroid cancer (DTC); however, lenvatinib monotherapy has a relatively low efficacy against ATC. In this study, we assessed the antitumor effects of a combination of lenvatinib and microtubule inhibitor paclitaxel in ATC cells in vitro and in vivo. Our data showed that lenvatinib monotherapy was less effective than paclitaxel monotherapy in ATC cell lines and xenografts. The addition of lenvatinib to paclitaxel synergistically inhibited colony formation and tumor growth in nude mice, and induced G2/M phase cell cycle arrest and cell apoptosis as compared to lenvatinib or paclitaxel monotherapy. Taken together, this is the first study to suggest that lenvatinib/paclitaxel combination may be a promising candidate therapeutic strategy for ATC.

Electrically pumped random lasing with an onset voltage of sub-3 V from ZnO-based light-emitting devices featuring nanometer-thick MoO3 interlayers.

We have previously reported on electrically pumped random lasing (RL) with onset voltages at least 3.3 V from ZnO-based light-emitting devices with metal-insulator-semiconductor (MIS) structures in the form of Au/SiO2/ZnO. Here, by inserting an ∼5 nm thick MoO3 layer between SiO2 and ZnO films in the aforementioned MIS structured device, the RL onset voltage is decreased to only ∼2.6 V and, moreover, the output optical power is multiplied several times. Such improved RL performance is ascribed to the enhanced injection of holes into ZnO via the MoO3 interlayer that features a low-lying conductive band and therefore a large work function.