Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.

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Detachment of droplets from solid surfaces is a basic and crucial process in practical applications such as heat transfer and digital microfluidics. In this study, electrowetting actuations with square pulse signals are employed to detach droplets from a hydrophobic surface. The threshold voltage for droplet detachment is obtained both experimentally and theoretically to find that it is almost constant for various droplet volumes ranging from 0.4 to 10 μL. It is also found that droplets can be detached more easily when the width of applied pulse is well-matched to the spreading time (i.e., the time to reach the maximum spread diameter). When the droplet is actuated by a double square pulse, the threshold voltage is reduced by ∼20% from that for a single square pulse actuation. Finally, by introducing an interdigitated electrode system, it is demonstrated that droplets can be detached from the solid bottom surface without using a top needle electrode.

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PurposeRetinal photocoagulation and nondamaging laser therapy are used for treatment of macular disorders, without understanding of the response mechanism and with no rationale for dosimetry. To establish a proper titration algorithm, we measured the range of tissue response and damage threshold. We then evaluated safety and efficacy of nondamaging retinal therapy (NRT) based on this algorithm for chronic central serous chorioretinopathy (CSCR) and macular telangiectasia (MacTel).MethodsRetinal response to laser treatment below damage threshold was assessed in pigmented rabbits by expression of the heat shock protein HSP70 and glial fibrillary acidic protein (GFAP). Energy was adjusted relative to visible titration using the Endpoint Management (EpM) algorithm. In clinical studies, 21 eyes with CSCR and 10 eyes with MacTel were treated at 30% EpM energy with high spot density (0.25-diameter spacing). Visual acuity, retinal and choroidal thickness, and subretinal fluid were monitored for 1 year.ResultsAt 25% EpM energy and higher, HSP70 was expressed acutely in RPE, and GFAP upregulation in Müller cells was observed at 1 month. Damage appeared starting at 40% setting. Subretinal fluid resolved completely in 81% and partially in 19% of the CSCR patients, and visual acuity improved by 12 ± 3 letters. Lacunae in the majority of MacTel patients decreased while preserving the retinal thickness, and vision improved by 10 letters.ConclusionsHeat shock protein expression in response to hyperthermia helps define the therapeutic window for NRT. Lack of tissue damage enables high-density treatment to boost clinical efficacy, therapy in the fovea, and retreatments to manage chronic diseases.

We have synthesized BaTiO3 nanowires (NWs) via a simple hydrothermal method at low temperature and developed a lead-free, flexible nanocomposite generator (NCG) device by a simple, low-cost, and scalable spin-coating method. The hydrothermally grown BaTiO3 NWs are mixed in a polymer matrix without a toxic dispersion enhancer to produce a piezoelectric nanocomposite (p-NC). During periodical and regular bending and unbending motions, the NCG device fabricated by utilizing a BaTiO3 NWs-polydimethylsiloxane (PDMS) composite successfully harvests the output voltage of ∼ 7.0 V and current signals of ∼ 360 nA, which are utilized to drive a liquid crystal display (LCD). We also characterized the instantaneous power (∼ 1.2 μW) of the NCG device by calculating the load voltage and current through the connected external resistance.

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A single crystal Pb(Mg1/3Nb2/3)O3‐Pb(Zr,Ti)O3 (PMN‐PZT) energy harvester is demonstrated by solid‐state crystal growth and an optimized delamination process. The flexible harvester generates an output voltage of 100 V and a current of 20 µA. The advanced reconfigurable rectifying circuit enhanced conversion efficiency of the PMN‐PZT harvester is compared to conventional rectifier. Finally, a self‐powered military boot is fabricated using the harvester as a demonstration of use in operating consumer electronics.