An Activatable Phototheranostic Nanoplatform for Tumor Specific NIR-II Fluorescence Imaging and Synergistic NIR-II Photothermal-Chemodynamic Therapy.

The phototheranostics in the second near-infrared window (NIR-II) have proven to be promising for the precise cancer theranostics. However, the non-responsive and "always on" imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR-II phototheranostic nanoplatform (Ag2 S-Fe(III)-DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self-assembly of Ag2 S QDs (NIR-II fluorescence probe) and ultra-small semiconductor polymer dots (DBZ Pdots, NIR-II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in "off" state, due to the FRET between Ag2 S QDs and DBZ Pdots. However, the NIR-II fluorescence signal of AFD NPs can be rapidly "turn on" by the overexpressed GSH in tumor tissues, achieving a superior tumor-to-normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR-II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR-II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti-tumor therapeutic effect. The work provides a promising strategy for the development of TME activated NIR-II phototheranostic nanoprobes.

Abundance, characteristics, and removal of microplastics in the Cihu Lake-wetland microcosm system.

Sewage treatment plants (STPs) are significant routes through which microplastics (MPs) are released into the aquatic environment. Constructed wetland is an effective facility for deep treatment of tailwater. At present, research on the removal of MPs in the tailwater of STPs by multi-stage constructed wetlands is limited. This work investigated and analyzed the removal characteristics of MPs in the tailwater treatment system of Cihu wetland park in Huangshi, Hubei Province of China. The abundance/removal of MPs in the Cihu Lake-wetland microcosm system was investigated. The results showed that the multi-stage constructed wetlands achieved a total removal rate of 94.7% for MPs with 2.2 particles/L MPs in the effluent. The removal rates of MPs reached 89 and 37.5%, respectively, in the (horizontal/vertical) subsurface flow constructed wetland and surface flow constructed wetland. The abundance of MPs in receiving water of Cihu Lake substantially decreased due to the dilution of wetland effluents. This study partially bridged the knowledge gap hypothesis on the treatment of MPs in tailwater by multi-stage constructed wetlands.

Green Bank and Effelsberg Radio Telescope Searches for Axion Dark Matter Conversion in Neutron Star Magnetospheres.

Axion dark matter (DM) may convert to radio-frequency electromagnetic radiation in the strong magnetic fields around neutron stars. The radio signature of such a process would be an ultranarrow spectral peak at a frequency determined by the mass of the axion particle. We analyze data we collected from the Robert C. Byrd Green Bank Telescope in the L band and the Effelsberg 100-m Telescope in the L band and S band from a number of sources expected to produce bright signals of axion-photon conversion, including the Galactic center of the Milky Way and the nearby isolated neutron stars RX J0720.4-3125 and RX J0806.4-4123. We find no evidence for axion DM and are able to set constraints on the existence of axion DM in the highly motivated mass range between ∼5 and 11 µeV with the strongest constraints to date on axions in the ∼10-11 µeV range.

Radio Signals from Axion Dark Matter Conversion in Neutron Star Magnetospheres.

We show that axion dark matter may be detectable through narrow radio lines emitted from neutron stars. Neutron star magnetospheres host both a strong magnetic field and a plasma frequency that increases towards the neutron star surface. As the axions pass through the magnetosphere, they can resonantly convert into radio photons when the plasma frequency matches the axion mass. We solve the axion-photon mixing equations, including a full treatment of the magnetized plasma, to obtain the conversion probability. We discuss possible neutron star targets and how they may probe the QCD-axion parameter space in the mass range of ∼0.2-40 µeV.

Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery.

BACKGROUND: Unfractionated heparin (UFH) is widely used as a reversible anti-coagulant in cardiopulmonary bypass (CPB). However, the pharmacokinetic characteristics of UFH in CPB surgeries remain unknown because of the lack of means to directly determine plasma UFH concentrations. The aim of this study was to establish a pharmacokinetic model to predict plasma UFH concentrations at the end of CPB for optimal neutralization with protamine sulfate. METHODS: Forty-one patients undergoing CPB during cardiac surgery were enrolled in this observational clinical study of UFH pharmacokinetics. Patients received intravenous injections of UFH, and plasma anti-FIIa activity was measured with commercial anti-FIIa assay kits. A population pharmacokinetic model was established by using nonlinear mixed-effects modeling (NONMEM) software and validated by visual predictive check and Bootstrap analyses. Estimated parameters in the final model were used to simulate additional protamine administration after cardiac surgery in order to eliminate heparin rebound. Plans for postoperative protamine intravenous injections and infusions were quantitatively compared and evaluated during the simulation. RESULTS: A two-compartment pharmacokinetic model with first-order elimination provided the best fit. Subsequent simulation of postoperative protamine administration suggested that a lower-dose protamine infusion over 24 h may provide better elimination and prevent heparin rebound than bolus injection and other infusion regimens that have higher infusion rates and shorter duration. CONCLUSION: A two-compartment model accurately reflects the pharmacokinetics of UFH in Chinese patients during CPB and can be used to explain postoperative heparin rebound after protamine neutralization. Simulations suggest a 24-h protamine infusion is more effective for heparin rebound prevention than a 6-h protamine infusion.

BNAS: Efficient Neural Architecture Search Using Broad Scalable Architecture.

Efficient neural architecture search (ENAS) achieves novel efficiency for learning architecture with high-performance via parameter sharing and reinforcement learning (RL). In the phase of architecture search, ENAS employs deep scalable architecture as search space whose training process consumes most of the search cost. Moreover, time-consuming model training is proportional to the depth of deep scalable architecture. Through experiments using ENAS on CIFAR-10, we find that layer reduction of scalable architecture is an effective way to accelerate the search process of ENAS but suffers from a prohibitive performance drop in the phase of architecture estimation. In this article, we propose a broad neural architecture search (BNAS) where we elaborately design broad scalable architecture dubbed broad convolutional neural network (BCNN) to solve the above issue. On the one hand, the proposed broad scalable architecture has fast training speed due to its shallow topology. Moreover, we also adopt RL and parameter sharing used in ENAS as the optimization strategy of BNAS. Hence, the proposed approach can achieve higher search efficiency. On the other hand, the broad scalable architecture extracts multi-scale features and enhancement representations, and feeds them into global average pooling (GAP) layer to yield more reasonable and comprehensive representations. Therefore, the performance of broad scalable architecture can be promised. In particular, we also develop two variants for BNAS that modify the topology of BCNN. In order to verify the effectiveness of BNAS, several experiments are performed and experimental results show that 1) BNAS delivers 0.19 days which is 2.37× less expensive than ENAS who ranks the best in RL-based NAS approaches; 2) compared with small-size (0.5 million parameters) and medium-size (1.1 million parameters) models, the architecture learned by BNAS obtains state-of-the-art performance (3.58% and 3.24% test error) on CIFAR-10; and 3) the learned architecture achieves 25.3% top-1 error on ImageNet just using 3.9 million parameters.

NIR-II fluorescence imaging guided tumor-specific NIR-II photothermal therapy enhanced by starvation mediated thermal sensitization strategy.

Photothermal therapy (PTT) is hampered by limited light penetration depth and cell thermoresistance induced by over-expressed heat shock proteins (HSPs). Herein, we proposed a tumor-specific enhanced NIR-II PTT through the starvation mediated thermal sensitization strategy. A semiconducting polymer with superior NIR-II fluorescence imaging (FI) performance and NIR-II PTT efficacy was synthesized and encapsulated into folate modified liposomes, together with a glycolysis inhibitor, 2-deoxy-d-glucose (2DG). Upon specifically targeting folate receptors and guidance of NIR-II FI, spatiotemporal 2DG release could be achieved by the trigger of NIR-II photothermal effect. The released 2DG could not only deplete the energy supply of tumor cells by inhibiting tumor anaerobic glycolysis, but also decrease the ATP levels and hamper the production of HSPs, ultimately enhancing the tumor thermal sensitivity toward PTT. Owing to the sensitization effect of 2DG, tumor cells with overexpressed folate receptors could be significantly damaged by NIR-II PTT with an enhanced therapeutic efficiency. The work provided a promising strategy for specific starvation/NIR-II PTT synergistic therapy towards tumors.

Pumping O2 with no N2: An Overview of Hollow Fiber Membrane Oxygenators with Integrated Arterial Filters.

The advancement of cardiac surgery benefits from the continual technological progress of cardiopulmonary bypass (CPB). Every improvement in the CPB technology requires further clinical and laboratory tests to prove its safety and effectiveness before it can be widely used in clinical practice. In order to reduce the priming volume and eliminate a separate arterial filter in the CPB circuit, several manufacturers developed novel hollow-fiber membrane oxygenators with integrated arterial filters (IAF). Clinical and experimental studies demonstrated that an oxygenator with IAF could reduce total priming volume, blood donor exposure and gaseous microemboli delivery to the patient. It can be easily set up and managed, simplifying the CPB circuit without sacrificing safety. An oxygenator with IAF is expected to be more beneficial to the patients with low body weight and when using a minimized extracorporeal circulation system. The aim of this review manuscript was to discuss briefly the concept of integration, the current oxygenators with IAF, and the in-vitro / in-vivo performance of the oxygenators with IAF.

Tumor Microenvironment-Responsive Fe(III)-Porphyrin Nanotheranostics for Tumor Imaging and Targeted Chemodynamic-Photodynamic Therapy.

The development of effective and safe tumor nanotheranostics remains a research imperative. Herein, tumor microenvironment (TME)-responsive Fe(III)-porphyrin (TCPP) coordination nanoparticles (FT@HA NPs) were prepared using a simple one-pot method followed by modification with hyaluronic acid (HA). FT@HA NPs specifically accumulated in CD44 receptor-overexpressed tumor tissues through the targeting property of HA and upon endocytosis by tumor cells. After cell internalization, intracellular acidic microenvironments and high levels of glutathione (GSH) triggered the rapid decomposition of FT@HA NPs to release free TCPP molecules and Fe(III) ions. The released Fe(III) ions could trigger GSH depletion and Fenton reaction, activating chemodynamic therapy (CDT). Meanwhile, the fluorescence and photodynamic effects of the TCPP could be also activated, achieving controlled reactive oxygen species (ROS) generation and avoiding side effects on normal tissues. Moreover, the rapid consumption of GSH further enhanced the efficacy of CDT and photodynamic therapy (PDT). The in vivo experiments further demonstrated that the antitumor effect of these nanotheranostics was significantly enhanced and that their toxicity and side effects against normal tissues were effectively suppressed. The FT@HA NPs can be applied for activated tumor combination therapy under the guidance of dual-mode imaging including fluorescence imaging and magnetic resonance imaging, providing an effective strategy for the design and preparation of TME-responsive multifunctional nanotheranostics for precise tumor imaging and combination therapy.

Beneficial effect of preventative intra-aortic balloon pumping in high-risk patients undergoing first-time coronary artery bypass grafting-a single center experience.

Although intra-aortic balloon pumping (IABP) has been used widely as a routine cardiac assist device for perioperative support in coronary artery bypass grafting (CABG), the optimal timing for high-risk patients undergoing first-time CABG using IABP is unknown. The purpose of this investigation is to compare preoperative and preventative IABP insertion with intraoperative or postoperative obligatory IABP insertion in high-risk patients undergoing first-time CABG. We reviewed our IABP patients' database from 2002 to 2007; there were 311 CABG patients who received IABP treatment perioperatively. Of 311 cases, 41 high-risk patients who had first-time on-pump or off-pump CABG (presenting with three or more of the following criteria: left ventricular ejection fraction less than 0.45, unstable angina, CABG combined with aneurysmectomy, or left main stenosis greater than 70%) entered the study. We compared perioperatively the clinical results of 20 patients who underwent preoperative IABP placement (Group 1) with 21 patients who had obligatory IABP placement intraoperatively or postoperatively during CABG (Group 2). There were no differences in preoperative risk factors, except left ventricular aneurysm resection, between the two groups. There were no differences in indications for high-risk patients between the two groups. The mean number of grafts was similar. There were no significant differences in the need for inotropes, or in cerebrovascular, gastrointestinal, renal, and infective complications postoperatively. There were no IABP-related complications in either group. Major adverse cardiac event (severe hypotension and/or shock, myocardial infarction, and severe hemodynamic instability) was higher in Group 2 (14 [66.4%] vs. 1 [5%], P < 0.0001) during surgery. The time of IABP pumping in Group 1 was shorter than in Group 2 (72.5 +/- 28.9 h vs. 97.5 +/- 47.7 h, P < 0.05). The duration of ventilation and intensive care unit stay in Group 1 was significantly shorter than in Group 2, respectively (22.0 +/- 1.6 h vs. 39.6 +/- 2.1 h, P < 0.01 and 58.0 +/- 1.5 h vs. 98.5 +/- 1.9 h, P < 0.005). There were no differences in mortality between the two groups (n = 1 in Group 1 and n = 3 in Group 2). Preoperative and preventative insertion of IABP can be performed safely in selected high-risk patients undergoing CABG, with results comparable to those in patients who received obligatory IABP intraoperatively and postoperatively. Therefore, earlier IABP support as part of surgical strategy may help to improve the outcome in high-risk first-time CABG patients.

Multifunctional Theranostic Liposomes Loaded with a Hypoxia-Activated Prodrug for Cascade-Activated Tumor Selective Combination Therapy.

Photodynamic therapy (PDT) is becoming a promising therapeutic regimen but is limited by the hypoxic microenvironment in solid tumors and the undesirable post-treatment phototoxicity side effects on normal tissues. To overcome these restrictions and enhance the antitumor therapeutic effect, near-infrared (NIR) light-activated, cancer cell-specific, hypoxia prodrug-loaded chlorin e6 liposomes were developed for tumor selective combination therapy guided by multimodal imaging. The photothermal agent indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ) were coencapsulated into the liposomes, followed by modification with cRGD and conjugation with GdIII to form ICG/TPZ@Ce6-GdIII theranostic liposomes (ITC-GdIII TLs). In the ITC-GdIII TLs, both the fluorescence and photodynamic effect of Ce6 were quenched by ICG via fluorescence resonance energy transfer. The ITC-GdIII TLs can effectively reach the tumor site through the enhanced permeability and retention effect as well as the cRGD-mediated active targeting ability. The fluorescence and photodynamic effect of Ce6 can be activated by the photothermal effect of ICG under NIR light. Upon subsequent irradiation with a 660 nm laser, the released Ce6 could kill cancer cells by generating cytotoxic singlet oxygen. Furthermore, the PDT process would induce hypoxia, which in turn activated the antitumor activity of the codelivered hypoxia-activated prodrug TPZ for a combination antitumor effect. The TLs could be utilized for multimodal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided cascade-activated tumor inhibition with optimized therapeutic efficiency and minimized side effects, holding great potential for constructing intelligent nanotheranostics.

Endogenous oxygen generating multifunctional theranostic nanoplatform for enhanced photodynamic-photothermal therapy and multimodal imaging.

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), has been considered as a noninvasive option for cancer therapy. However, insufficient penetration depth, tumor hypoxia, and a single treatment method severely limit the effectiveness of treatment. Methods: In this study, a multifunctional theranostic nanoplatform has been fabricated based on Au/Ag-MnO2 hollow nanospheres (AAM HNSs). The Au/Ag alloy HNSs were first synthesized by galvanic replacement reaction and then the MnO2 nanoparticles were deposited on the Au/Ag alloy HNSs by the reaction between Ag and permanganate (KMnO4), finally obtained the AAM HNSs. Then, SH-PEG was modified on the surface of AAM HNSs by the interaction of sulfhydryl and Au/Ag alloy, which improved the dispersibility and biocompatibility of the HNS. Next, the PDT photosensitizer Ce6 was loaded into AAM HNSs, benefiting from the hollow interior of the structure, and the AAM-Ce6 HNSs were obtained. Results: The AAM HNSs exhibit broad absorption at the near infrared (NIR) biological window and remarkable photothermal conversion ability in the NIR-II window. The MnO2 nanoparticles can catalyze endogenous H2O2 to generate O2 and enhance the therapeutic effect of PDT on tumor tissue. Simultaneously, MnO2 nanoparticles intelligently respond to the tumor microenvironment and degrade to release massive Mn2+ ions, which introduce magnetic resonance imaging (MRI) properties. When AAM-Ce6 HNSs are loaded with Ce6, the AAM-Ce6 HNSs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging, FL/PAI/MRI) guided combination tumor phototherapy (PTT/PDT). Conclusion: This multifunctional nanoplatform shows synergistic therapeutic efficacy better than any single therapy by achieving multimodal imaging guided cancer combination phototherapy, which are promising for the diagnosis and treatment of cancer.

[Study on the oxidation of solutions of aniline and phenol on Ti/SnO2-Sb2O5 electrode by UV-Vis spectroscopy and HPLC].

The electrocatalytic oxidation and degradation of phenol and aniline were studied at Ti/SnO2-Sb2O5 electrode by UV-Vis spectroscopy and high performance liquid chromatography (HPLC). It is shown that hydroquinone, benzoquinone and maleic acid are the same intermediates and products during oxidation of both aniline and phenol. This indicates that the oxidation of the two compounds probably has the same degradation routes. The electropolymerization of anilines results in different oxidation and degradation course of aniline and phenol.