Research on methods to increase the flashover voltage of supporting insulators in Tesla transformers.

This paper presents three methods aimed at enhancing the flashover voltage of the supporting insulator in a Tesla transformer. These methods include optimizing the maximum electric field on the insulator surface, adjusting the overall structure of the insulator, and changing the surface structure of the insulator. Ten insulator samples with different structures were designed based on electric field simulation. Subsequent experiments were conducted to validate the effectiveness of these methods in improving flashover voltage. On this basis, the supporting insulator of the Tesla transformer was redesigned, leading to an increased output voltage. The results are summarized in the following. First, optimization of the shielding rings of the cathode and anode reduces the electric field at the triple junction, which significantly increases the flashover voltage. Second, extending the inclination starting position of insulators with the same inclination angle effectively reduces the surface electric field intensity and increases the flashover voltage. Third, increasing the inclination angle within a certain range while keeping the inclination starting position constant extends the creepage distance and enhances the flashover voltage. However, excessively large inclination angles may lead to a decrease in flashover voltage due to excessive normal electric field. Fourth, grooving on the insulator surface at appropriate locations can inhibit the development of the streamer and improve flashover voltage. Finally, the supporting insulator of the Tesla transformer was redesigned based on these results, elevating the output voltage from 750 kV to over 1 MV.

Photoactivated Gas-Generating Nanocontrast Agents for Long-Term Ultrasonic Imaging-Guided Combined Therapy of Tumors.

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.

Framework Nucleic Acids Combined with 3D Hybridization Chain Reaction Amplifiers for Monitoring Multiple Human Tear Cytokines.

Existing tear sensors are difficult to perform multiplexed assays due to the minute amounts of biomolecules in tears and the tiny volume of tears. Herein, the authors leverage DNA tetrahedral frameworks (DTFs) modified on the wireless portable electrodes to effectively capture 3D hybridization chain reaction (HCR) amplifiers for automatic and sensitive monitoring of multiple cytokines in human tears. The developed sensors allow the sensitive determination of various dry eye syndrome (DES)-associated cytokines in human tears with the limit of detection down to 0.1 pg mL-1, consuming as little as 3 mL of tear fluid. Double-blind testing of clinical DES samples using the developed sensor and commercial ELISA shows no significant difference between them. Compared with single-biomarker diagnosis, the diagnostic accuracy of this sensor based on multiple biomarkers has improved by ≈16%. The developed system offers the potential for tear sensors to enable personalized and accurate diagnosis of various ocular diseases.

Triboelectric-Responsive Drug Delivery Hydrogel for Accelerating Infected Wound Healing.

Electrotherapy is of great interest in the field of tissue repair as an effective, well-tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F-TENG) and a triboelectric-responsive drug delivery hydrogel (TR-DDH) for healing of bacterium-infected wounds. F-TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR-DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart-responsive drug delivery systems.

The effect of initial electrons generation approaches on nanosecond pulsed breakdown characteristics.

In this paper, the effects of initial electrons generation approaches on nanosecond pulsed breakdown characteristics are analyzed. Based on the numerical simulations with a 3D PIC-MCC model, the impacts of field-enhancement factor and initial electron concentration on nanosecond pulsed breakdown characteristics are investigated. Three types of switches are designed and subjected to testing under pulse voltages with rise times of 40, 70, and 120 ns, respectively. The results can be summarized as follows. First, the field-enhancement factor and initial electron concentration have significant influences on the development of the discharge channel. Second, the cathode-grooved self-triggered switch exhibits lower breakdown time delay jitter than the hemispherical self-breakdown switch at low pressure, while the differences in jitter between the two switches become negligible at high pressure. Third, the cathode-grooved self-triggered switch shows a lower breakdown time delay jitter compared to the pre-ionization self-triggered switch for pulse voltages with rise times of 40 and 70 ns. Conversely, this trend reverses for pulse voltage with a rise time of 120 ns. Finally, the breakdown time delay jitter for both the cathode-grooved self-triggered switch and the pre-ionization self-triggered switch has been reduced, and both switches are suitable for different operating requirements and conditions.

Camouflage Nanoparticles Enable in Situ Bioluminescence-Driven Optogenetic Therapy of Retinoblastoma.

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for in situ bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes. To conduct proof-of-concept research, this study employs a mouse model of retinoblastoma. In comparison to external blue light irradiation, the developed system enables an in situ bioluminescence-activated apoptotic pathway to inhibit tumor growth with greater therapeutic efficacy, resulting in a significant reduction in ocular tumor size. Furthermore, unlike external blue light irradiation, which causes retinal damage and corneal neovascularization, the camouflage nanoparticle-based optogenetic system maintains retinal structural integrity while avoiding corneal neovascularization.

Antisense Oligonucleotides Selectively Enter Human-Derived Antibiotic-Resistant Bacteria through Bacterial-Specific ATP-Binding Cassette Sugar Transporter.

Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic-resistant bacteria. Herein, bacteria-specific ATP-binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1-4)-glucosidically linked glucose polymers. Compared with their cell-penetrating peptide counterparts, which are non-specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic-acid-modified nanoparticles are selectively internalized into the human-derived multidrug-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic-resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

Fluorescence, ultrasonic and photoacoustic imaging for analysis and diagnosis of diseases.

Biomedical imaging technology, which allows us to peer deeply within living subjects and visually explore the delivery and distribution of agents in living things, is producing tremendous opportunities for the early diagnosis and precise therapy of diseases. In this feature article, based on reviewing the latest representative examples of progress together with our recent efforts in the bioimaging field, we intend to introduce three typical kinds of non-invasive imaging technologies, i.e., fluorescence, ultrasonic and photoacoustic imaging, in which optical and/or acoustic signals are employed for analyzing various diseases. In particular, fluorescence imaging possesses a series of outstanding advantages, such as high temporal resolution, as well as rapid and sensitive feedback. Hence, in the first section, we will introduce the latest studies on developing novel fluorescence imaging methods for imaging bacterial infections, cancer and lymph node metastasis in a long-term and real-time manner. However, the issues of imaging penetration depth induced by photon scattering and light attenuation of biological tissue limit their widespread in vivo imaging applications. Taking advantage of the excellect penetration depth of acoustic signals, ultrasonic imaging has been widely applied for determining the location, size and shape of organs, identifying normal and abnormal tissues, as well as confirming the edges of lesions in hospitals. Thus, in the second section, we will briefly summarize recent advances in ultrasonic imaging techniques for diagnosing diseases in deep tissues. Nevertheless, the absence of lesion targeting and dependency on a professional technician may lead to the possibility of false-positive diagnosis. By combining the merits of both optical and acoustic signals, newly-developed photoacoustic imaging, simultaneously featuring higher temporal and spatial resolution with good sensitivity, as well as deeper penetration depth, is discussed in the third secretion. In the final part, we further discuss the major challenges and prospects for developing imaging technology for accurate disease diagnosis. We believe that these non-invasive imaging technologies will introduce a new perspective for the precise diagnosis of various diseases in the future.

Targeted delivery of dexamethasone in acute pneumonia.

Pneumonia has contributed to significant mortality owing to the irreversible injury to the lungs and severe inflammation of the tissue. Dexamethasone (DEX) is regarded as an effective drug to relieve the level of pneumonia, while the adverse effect of which is non-negligible. Here, we developed a targeted delivery strategy based on platelet-derived extracellular vesicles (PEVs), which are naturally occurring nanoparticles released by platelets, for DEX delivery in acute pneumonia, aiming to reduce the side effects and improve the therapeutic efficacy. Our strategy may shed light on the problems in DEX-based acute pneumonia therapy clinically.