A hybrid simulator with novel bicone-wire grid antenna.

The simulator is an indispensable device for the study of high-altitude electromagnetic pulse (HEMP) effects. In order to improve the quality of the electric field waveforms of the HEMP simulator, we carried out simulation and experimental studies for the biconical-wire grid antenna. A new bicone-wire grid antenna HEMP simulator was designed by using skeletonized cones instead of solid cones, which can substantially improve the mobility of the simulator. The effects of different aspect ratios and different cone structures of the simulator on the waveform and distribution characteristics of the electric field were analyzed. The accuracy of the simulation results was verified by testing the bicone-wire grid antenna simulator with the new structure. The results obtained are as follows: First, the simulator can provide a HEMP environment compliant with the International Electrotechnical Commission (IEC) standard in an area of 5 × 6 × 2 m3. Second, the simulator possesses optimal waveform quality and working space among simulators with different aspect ratios. Finally, the influence of using skeletonized cones instead of solid cones on the simulator's electric field waveforms is negligible, and the mobility of the new simulator is significantly improved compared to the original simulator.

ß-Galactosidase-Activatable Fluorescent and Photoacoustic Imaging of Tumor Senescence.

ß-Galactosidase (ß-gal) is the gold standard marker of cellular senescence, which is linked with various age-related diseases. Therefore, it is essential to develop more excellent probes that can real-time monitor ß-gal activity in cellular senescence in vivo. Fluorescent/photoacoustic (FL/PA) dual-modal imaging possesses excellent sensitivity and spatial resolution. To our knowledge, there has been no tumor-targeted FL/PA probe to image cellular senescence by monitoring the activity of ß-gal in vivo. Therefore, we developed a tumor-targeted FL/PA probe (Gal-HCy-Biotin) for ß-gal-activatable imaging of tumor senescence. Gal-HCy without tumor-targeted biotin is used as a control probe. Gal-HCy-Biotin is superior to Gal-HCy due to the higher kinetic parameter of Gal-HCy-Biotin than Gal-HCy in vitro. Moreover, biotin could help Gal-HCy-Biotin enter and accumulate in tumor cells with higher FL/PA signal. In detail, Gal-HCy-Biotin or Gal-HCy could image senescent tumor cells with 4.6-fold or 3.5-fold FL enhancement and 4.1-fold or 3.3-fold PA enhancement. Gal-HCy-Biotin or Gal-HCy could image tumor senescence with 2.9-fold or 1.7-fold FL enhancement and 3.8-fold or 1.3-fold PA enhancement. We envision that Gal-HCy-Biotin will be applied for FL/PA imaging of tumor senescence in clinic.

Caspase-3-Responsive Fluorescent/Photoacoustic Imaging of Tumor Apoptosis.

Caspase-3 is an essential executor in apoptosis, and its activation has been regarded as a biomarker of cell apoptosis. The development of Caspase-3-responsive multimodal probes is a promising research prospect. Fluorescent/photoacoustic (FL/PA) imaging has attracted considerable attention due to the high sensitivity of FL as well as the high spatial resolution and penetration depth of PA. To our knowledge, there has been no tumor-targeted FL/PA probe to monitor the activity of Caspase-3 in vivo. Therefore, we developed a tumor-targeted FL/PA probe (Bio-DEVD-HCy) for Caspase-3-responsive imaging of tumor apoptosis. Ac-DEVD-HCy without tumor-targeted biotin is used as a control probe. In vitro experiments indicated that Bio-DEVD-HCy is superior to Ac-DEVD-HCy because of the higher kinetic parameter of Bio-DEVD-HCy in comparison to Ac-DEVD-HCy. Cell and tumor imaging results suggested that Bio-DEVD-HCy could enter and accumulate in tumor cells with higher FL/PA signal with the help of tumor-targeted biotin. In detail, Bio-DEVD-HCy or Ac-DEVD-HCy could image apoptotic tumor cells with 4.3-fold or 3.5-fold FL enhancement and 3.4-fold or 1.5-fold PA enhancement. Bio-DEVD-HCy or Ac-DEVD-HCy could image tumor apoptosis with 2.5-fold or 1.6-fold FL enhancement and 4.1-fold or 1.9-fold PA enhancement. We envision that Bio-DEVD-HCy will be applied for FL/PA imaging of tumor apoptosis in clinical settings.

Intracellular Formation of Hemicyanine Nanoparticle Enhances Tumor-Targeting Photoacoustic Imaging and Photothermal Therapy.

Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumors. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye make it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, Probe-1 is developed to enhance PAI and PTT of liver tumors due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displays a 4.6-fold higher PAI signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 shows extended retention time (10 vs 6 h) and 2.1-fold higher PAI signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increase 18 °C (Tmax : 55 °C) with a 3.3-fold decreased volume while that in Group Probe-2 mildly increase 9.8 °C (Tmax : 46.8 °C) with a 4.3-fold increased volume. It is envisioned that this smart self-assembly strategy can be easily adjusted for PAI and PTT of more tumors.

Sequential self-assembly and disassembly of curcumin hydrogel effectively alleviates inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract with unclear etiology and insufficient therapeutic efficacy. The development of specific, effective and safe IBD treatment drugs is of great clinical significance. Curcumin (Cur) is a good candidate to prevent and manage inflammatory diseases (such as IBD) due to its antioxidant and anti-inflammatory effects with safety profile. However, its poor aqueous solubility and instability under physiological conditions greatly limit its therapeutic efficacy. Herein, we exploited a Cur precursor Cur-FFEYp to locally deliver and slowly release Cur at inflamed regions for treatment of IBD by a sequential self-assembly and disassembly strategy. The much higher catalytic efficiency of alkaline phosphatase (ALP) than esterase towards Cur-FFEYp validated the sequential ALP-induced self-assembly with the formation of Cur hydrogel and esterase-guided disassembly with the slow release of Cur. In cell and animal experiments, Cur-FFEYp can effectively enhance the anti-inflammatory effect of Cur on inflammatory macrophages and significantly alleviate two types of IBD. We envision that by using other biomarkers to conduct the sequential self-assembly and disassembly processes and replacing other drugs, our smart strategy could be easily adjusted for the treatment of more diseases or cancers.

Older Wheelchair Users Recommend Age-Friendly Design Improvements to a Wheelchair Maintenance App: Mixed Methods Development Study.

BACKGROUND: Wheelchair part failures have doubled over the past decade. Preventative wheelchair maintenance reduces wheelchair failures and prevents user consequences. We are developing a smartphone app called WheelTrak, which alerts users when maintenance is required, to encourage maintenance practices and compliance. OBJECTIVE: This mixed methods study aimed to develop a wheelchair maintenance app using broad stakeholder advice and investigate older adults' interaction experience with the app and their perceived barriers to and facilitators of maintenance. METHODS: Interviews were conducted with stakeholders, including mobility device users, to generate needs statements and app specifications. The app was designed in 2 stages. Stage 1 involved the development of the app according to the specifications and evaluation of the app interface by lead users. Stage 2 included the revision of the app screens and manual functionality testing. Usability testing and semistructured interviews were conducted with older wheelchair and scooter users. The System Usability Scale was used to measure app usability. RESULTS: Interviews with power and manual wheelchair users (37/57, 65%), wheelchair service providers (15/57, 26%), manufacturers (2/57, 4%), seating and mobility researchers (1/57, 2%), and insurance plan providers (2/57, 4%) informed the needs and specifications of the app technology. The 2-stage development process delivered a fully functional app that met the design specifications. In total, 12 older adults (mean age 74.2, SD 9.1 years; n=10, 83% women; and n=2, 17% men) participated in the usability testing study. Of the 12 participants, 9 (75%) agreed to use WheelTrak for preventative maintenance. WheelTrak scored an average System Usability Scale score of 60.25 (SD 16). Four overarching themes were identified: WheelTrak app improvements, barriers to maintenance, consequences related to mobility device failure, and smart technology use and acceptance. Older adults preferred the simplicity, readability, personalization, and availability of educational resources in the app. Barriers to maintenance pertained to health issues and lack of maintenance knowledge among older adults. Facilitators of maintenance included notification for maintenance, app connectivity with the service provider, reporting of device failure, and the presence of a caregiver for maintenance. CONCLUSIONS: This study highlighted age-friendly design improvements to the app, making it easy to be used and adopted by older wheelchair users. The WheelTrak app has close to average system usability. Additional usability testing will be conducted following app revision in the future.