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Rationale: Insufficient penetration and accumulation of theranostic payloads in solid tumors greatly challenge the clinical translation of cancer nanomedicines. To address this challenge, we synthesized natural melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets with good biocompatibility and self-assembling ability. Methods: We used an opto-acoustic synergistic irradiation (OASI) method that was effective at lower energy levels than ultrasound- or laser-only irradiation to safely vaporize the nanodroplets and to cavitate the generated microbubbles for mechanically enhancing intratumoral delivery. The delivered melanin and doxorubicin inside the tumors mediated secondary chemo-photothermal therapy under laser irradiation to fully kill cancer cells. Results: In vivo animal experiments demonstrated direct mechanical disruption of tumor structures (H&E staining), enhanced intratumoral penetration of melanin (photoacoustic imaging), and efficient intratumoral accumulation of doxorubicin (fluorescent imaging). Anti-tumor experiments demonstrated that the nanodroplets combined with OASI treatment and subsequent laser irradiation could efficiently eliminate melanoma tumors. Conclusion: Melanin-cored and doxorubicin-loaded perfluoropentane nanodroplets hold great promise for translational sono-chemo-photothermal cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Phase-change nanodroplets (PCNDs), which are liquid perfluorocarbon nanoparticles, have garnered much attention as ultrasound-responsive nanomedicines. The vaporization phenomenon has been employed to treat tumors mechanically. However, the ultrasound pressure applied to induce vaporization must be low to avoid damage to nontarget tissues., Aims: Here, we report that the pressure threshold for vaporization to induce cytotoxicity can be significantly reduced by selective intracellular delivery of PCNDs into targeted tumors., Methods and Results: In vitro experiments revealed that selective intracellular delivery of PCNDs induced PCND aggregation specifically inside the targeted cells. This close-packed configuration decreased the pressure threshold for vaporization to induce cytotoxicity. Moreover, following ultrasound exposure, significant decrease was observed in the viability of cells that incorporated PCNDs (35%) but not in the viability of cells that did not incorporate PCNDs (88%)., Conclusions: Intracellular delivery of PCNDs reduced ultrasound pressure applied for vaporization to induce cytotoxicity. Confocal laser scanning microscopy and flow cytometry revealed that prolonged PCND-cell incubation increased PCND uptake and aggregation. This aggregation effect might have contributed to the cytotoxicity threshold reduction effect., (© 2019 Wiley Periodicals, Inc.)

This study investigated the mechanical bioeffects exerted by acoustic droplet vaporization (ADV) under different experimental conditions using vessel phantoms with a 200-μm inner diameter but different stiffness for imitating the microvasculature in various tumors. High-speed microscopy, passive cavitation detection, and ultrasound attenuation measurement were conducted to determine the morphological characteristics of vascular damage and clarify the mechanisms by which the damage was initiated and developed. The results show that phantom erosion was initiated under successive ultrasound exposure (2 MHz, 3 cycles) at above 8-MPa peak negative pressures (PNPs) when ADV occurred with inertial cavitation (IC), producing lesions whose morphological characteristics were dependent on the amount of vaporized droplets. Slight injury occurred at droplet concentrations below (2.6±0.2)×10(6) droplets/mL, forming shallow and rugged surfaces on both sides of the vessel walls. Increasing the droplet concentration to up to (2.6±0.2)×10(7) droplets/mL gradually suppressed the damage on the distal wall, and turned the rugged surface on the proximal wall into tunnels rapidly elongating in the direction opposite to ultrasound propagation. Increasing the PNP did not increase the maximum tunnel depth after the ADV efficiency reached a plateau (about 71.6±2.7% at 10 MPa). Increasing the pulse duration effectively increased the maximum tunnel depth to more than 10 times the diameter of the vessel even though there was no marked enhancement in IC dose. It can be inferred that substantial bubble generation in single ADV events may simultaneously distort the acoustic pressure distribution. The backward ultrasound reinforcement and forward ultrasound shielding relative to the direction of wave propagation augment the propensity of backward erosion. The results of the present work provide information that is valuable for the prevention or utilization of ADV-mediated mechanical bioeffects in clinical applications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present work, we report a quantitative understanding on how to generate hydroxyl radicals from NO(2) and H(2)O in the troposphere upon photoexcitation at 410 nm by using multiconfigurational perturbation theory and density functional theory. The conical intersections dominate the nonadiabatic relaxation processes after NO(2) irradiated at approximately 410 nm in the troposphere and further control the generation of OH radical by means of hydrogen abstraction. In agreement with two-component fluorescence observed by laser techniques, there are two different photophysical relaxation channels along decreasing and increasing O-N-O angle of NO(2). In the former case, the conical intersection between B(2)B(1) and A(2)B(2) (CI ((2)B(2)/(2)B(1)) first funnels NO(2) out of the Franck-Condon region of B(2)B(1) and relaxes to the A(2)B(2) surface. Following the primary relaxation, the conical intersection between A(2)B(2) and X(2)A(1) (CI((2)B(2)/(2)A(1))) drives NO(2) to decay into highly vibrationally excited X(2)A(1) state that is more than 20,000 cm(-1) above zeroth-order |n(1),n(2),n(3) = 0 vibrational level. In the latter case, increasing the O-N-O angle leads NO(2) to relax to a minimum of B(2)B(1) with a linear O-N-O arrangement. This minimum point is also funnel region between B(2)B(1) and X(2)A(1) (CI((2)B(1)/(2)A(1))) and leads NO(2) to relax into a highly vibrationally excited X(2)A(1) state. The high energetic level of vibrationally excited state has enough energy to overcome the barrier of hydrogen abstraction (40-50 kcal/mol) from water vapor, producing OH ((2)Pi(3/2)) radicals. The collision between NO(2) and H(2)O molecules not only is a precondition of hydrogen abstraction but induces the faster internal conversion (CIIC) via conical intersections. The faster internal conversion favors more energy transfer from electronically excited states into highly vibrationally excited X(2)A(1) states. The collision (i.e., the heat motion of molecules) functions as the trigger and accelerator in the generation of OH radicals from NO(2) and H(2)O in the troposphere.

Sensory and chemical consequences of treating goat milk using an UV fluid processor were assessed. Milk was exposed to UV for a cumulative exposure time of 18 s and targeted UV dose of 15.8 +/- 1.6 mJ/cm2. A triangle test revealed differences between the odor of raw milk and UV irradiated milk. Oxidation and hydrolytic rancidity was measured by thiobarbituric acid reactive substances and acid degree values (ADV). As UV dose increased, there was an increase in thiobarbituric acid reactive substance values and ADV of the milk samples. A separate set of samples were processed using the fluid processor but with no UV exposure to see if lipase activity and agitation from pumping contributed to the differences in odor. The ADV increased at the same rate as samples exposed to UV; however, sensory studies indicated that the increase of free fatty acids was not enough to cause detectable differences in the odor of milk. Solid phase microextraction and gas chromatography were utilized for the analysis of volatile compounds as a result of UV exposure. There was an increase in the concentration of pentanal, hexanal, and heptanal (relative to raw goat milk) after as little as 1.3 mJ/cm2 UV dose. Ultraviolet irradiation at the wavelength 254 nm produced changes in the sensory and chemical properties of fluid goat milk.

In the past two decades, a great deal of attention has been paid to the environmental fate of mercury (Hg), and this is exemplified by the growing number of international conferences devoted uniquely to Hg cycling and its impacts on ecosystem functions and life. This interest in the biogeochemistry of Hg has resulted in a significant improvement of our understanding of its impact on the environment and human health. However, both past and current research, have been primarily oriented toward the study of direct impact of anthropogenic activities on Hg cycling. Besides a few indirect effects such as the increase in Hg methylation observed in acid-rain impacted aquatic systems or the reported enhanced Hg bioaccumulation in newly flooded water reservoirs; changes in Hg transformations/fluxes that may be related to global change have received little attention. A case in point is the depletion of stratospheric ozone and the resulting increase in solar UV-radiation reaching the Earth. This review and critical discussion suggest that increasing UV-B radiation at earth's surface could have a significant and complex impact on Hg cycling including effects on Hg volatilization (photo-reduction), solubilization (photo-oxidation), methyl-Hg demethylation, and Hg methylation. Therefore, this paper is written to provoke discussions, and more importantly, to stimulate research on potential impacts of incoming solar UV-radiation on global Hg fluxes and any toxicity aspects of Hg that may become exacerbated by UV-radiation.

The formation of marine aerosols and cloud condensation nuclei--from which marine clouds originate--depends ultimately on the availability of new, nanometre-scale particles in the marine boundary layer. Because marine aerosols and clouds scatter incoming radiation and contribute a cooling effect to the Earth's radiation budget, new particle production is important in climate regulation. It has been suggested that sulphuric acid derived from the oxidation of dimethyl sulphide is responsible for the production of marine aerosols and cloud condensation nuclei. It was accordingly proposed that algae producing dimethyl sulphide play a role in climate regulation, but this has been difficult to prove and, consequently, the processes controlling marine particle formation remains largely undetermined. Here, using smog chamber experiments under coastal atmospheric conditions, we demonstrate that new particles can form from condensable iodine-containing vapours, which are the photolysis products of biogenic iodocarbons emitted from marine algae. Moreover, we illustrate, using aerosol formation models, that concentrations of condensable iodine-containing vapours over the open ocean are sufficient to influence marine particle formation. We suggest therefore that marine iodocarbon emissions have a potentially significant effect on global radiative forcing.

Aims: Thermal injury of subendocardial tissue leads to a release of electrolytes and free radicals from the intracellular site creating a change in electrochemical potential (eP) between the distal and the proximal catheter tip electrodes. The aim of the study was to verify the detection of ablation-induced release of electrolytes and free radicals and to assess the suitability of control-line energy delivery at ablation by measuring eP., Methods and Results: In vitro tests under constant flow conditions were performed in a 101 bath of physiological saline solution or bovine blood. Endomyocardial preparations of fresh bovine hearts were used. Closed-loop temperature-controlled, irrigated and closed-loop eP-controlled ablations were performed. In vivo animal investigations were performed in six anaesthetized and ventilated pigs. The existence of the eP was established in the tank model and was confirmed in animal investigations. High correlations were found between eP and catheter tip temperature (r=0.87) and between maximum eP and induced lesion size (r=0.85). Also a high correlation (r=0.85, P<0.001) was found between eP and lesion volume., Conclusions: Control of energy delivery during RF ablation by the measurement of eP is feasible. In comparison with temperature controlled RF ablation, ablation guided by eP-measurement revealed a superior correlation with induced lesion size. Especially during cooled radiofrequency catheter ablation eP is the only parameter for control of energy delivery.

An ambient air study was conducted in the city of Florence, Italy, in the summer 1996. Tropospheric ozone was continuously monitored with automatic analyzers in three stations, two located in the urban area and one in the hilly surroundings (Settignano). A biomonitoring campaign based on the tobacco cv. Bel-W3 plants was performed in the same area. The highest values were constantly recorded in the Settignano station. The highest 1-hour mean recorded was 197 nl/l; the accumulated exposure over a threshold of 40 nl/l (AOT40) was well above the critical levels standards for protection of the vegetation. A consistent temporal variation was observed and July proved to be the month with the highest ozone levels. Cumulative frequency distribution of ozone maximum daily concentrations exhibited a good fitting to log-normality. No 'week-end' effect was observed. Biomonitoring data were in good agreement with chemico-physical ones.

A study was performed to investigate whether measurements of the evaporation rate from the skin of newborn infants by the gradient method are affected by the presence of non-ionizing radiation from phototherapy equipment or a radiant heater. The evaporation rate was measured experimentally with the measuring sensors either exposed to or protected from non-ionizing radiation. Either blue light (phototherapy) or infrared light (radiant heater) was used; in the former case the evaporation rate was measured from a beaker of water covered with a semipermeable membrane, and in the latter case from the hand of an adult subject, aluminium foil or with the measuring probe in the air. No adverse effect on the determinations of the evaporation rate was found in the presence of blue light. Infrared radiation caused an error of 0.8 g/m2h when the radiant heater was set at its highest effect level or when the ambient humidity was high. At low and moderate levels the observed evaporation rate was not affected. It is concluded that when clinical measurements are made from the skin of newborn infants nursed under a radiant heater, the evaporation rate can appropriately be determined by the gradient method.