Cytoskeletal response of microvessel endothelial cells to an applied stress force at the submicrometer scale studied by atomic force microscopy

Cytoskeleton fibers form an intricate three-dimensional network to provide structure and function to microvessel endothelial cells. During accommodation to blood flowing, stress fiber bundles become more prominent and align with the direction of blood flow. This network either mechanically resists the applied shear stress (lateral force) or, if deformed, is dynamically remodeled back to a preferred architecture. However, the detailed response of these stress fiber bundles to applied lateral force at submicrometer scales are as yet poorly understood. In our in vitro study, the tip, topography probe in lateral force microscopy of atomic force microscopy, acted as a tool for exerting quantitative vertical and lateral force on the filaments of the cytoskeleton. Moreover, the authors developed a formula to calculate the value of lateral force exerted on every point of the filaments. The results show that cytoskeleton fibers of healthy tight junctions in rat cerebral microvessel endothelial cells formed a cross-type network, and were reinforced and elongated in the direction of scanning under lateral force of 15-42 nN. Under peroxidation (H(2)O(2) of 300 micromol/L), the cytoskeleton remodeled at intercellular junctions, and changed over the meshwork structures into a dense bundle, that redistributed the stress. Once mechanical forces were exerted on an area, the cells shrank and lost morphologic tight junctions. It would be useful in our understanding of certain pathological processes, such as cerebral ischemia/reperfusion injury, which maybe caused by biomechanical forces and which are overlooked in current disease models.     

Ethanol Oxidation via 12-Electron Pathway on Spiky Au@AuPd Nanoparticles Assisted by Near-Infrared Light

In this work, ethanol oxidation reaction (EOR) via 12-electron (C1-12e) pathway on spiky Au@AuPd nanoparticles (NPs) with ultrathin AuPd alloy shells is achieved in alkaline media with the assistance of the near-infrared (NIR) light. It is found that OH radicals can be produced from the OH_ads species adsorbed on the surfaces of Pd atoms led by surface plasmon resonance (SPR) effect of spiky Au@AuPd NPs under the irradiation of NIR light. Moreover, OH radicals play the key role for the achievement of EOR proceeded by the desirable C1-12e pathway because OH radicals can directly break the C–C bonds of ethanol. Accordingly, the electrocatalytic performance of spiky Au@AuPd NPs toward EOR under NIR light is greatly improved. For instance, their mass activity can be up to 33.2 A mg_pd⁻¹ in the 0.5 m KOH solution containing 0.5 m ethanol, which is about 158 times higher than that of commercial Pd/C catalysts (0.21 A mg_pd⁻¹) and is better than those of the state-of-the-art Pd-based catalysts reported in literature thus far, to the best of our knowledge. Moreover, their highest mass activity can be further improved to 118.3 A mg_pd⁻¹ in the 1.5 m KOH solution containing 1.25 m ethanol.     

Ratiometric Nanothermometer Based on a Radical Excimer for In Vivo Sensing (Small 32/2023)

Ratiometric fluorescent nanothermometers with near-infrared emission play an important role in in vivo sensing since they can be used as intracellular thermal sensing probes with high spatial resolution and high sensitivity, to investigate cellular functions of interest in diagnosis and therapy, where current approaches are not effective. Herein, the temperature-dependent fluorescence of organic nanoparticles is designed, synthesized, and studied based on the dual emission, generated by monomer and excimer species, of the tris(2,4,6-trichlorophenyl)methyl radical (TTM) doping organic nanoparticles (TTMd-ONPs), made of optically neutral tris(2,4,6-trichlorophenyl)methane (TTM-αH), acting as a matrix. The excimer emission intensity of TTMd-ONPs decreases with increasing temperatures whereas the monomer emission is almost independent and can be used as an internal reference. TTMd-ONPs show a great temperature sensitivity (3.4% K⁻¹ at 328 K) and a wide temperature response at ambient conditions with excellent reversibility and high colloidal stability. In addition, TTMd-ONPs are not cytotoxic and their ratiometric outputs are unaffected by changes in the environment. Individual TTMd-ONPs are able to sense temperature changes at the nano-microscale. In vivo thermometry experiments in Caenorhabditis elegans (C. elegans) worms show that TTMd-ONPs can locally monitor internal body temperature changes with spatio-temporal resolution and high sensitivity, offering multiple applications in the biological nanothermometry field.     

Platinum Nanoparticles to Enable Electrodynamic Therapy for Effective Cancer Treatment

Electrochemical therapy (EChT), by inserting electrodes directly into tumors to kill cancer cells under direct current (DC), is clinically used in several countries. In EChT, the drastic pH variation nearby the inserted electrodes is the main cause of tumor damage. However, its limited effective area and complex electrode configuration have hindered the clinical application of EChT in treating diverse tumor types. Herein, a conceptually new electric cancer treatment approach is presented through an electro‐driven catalytic reaction with platinum nanoparticles (PtNPs) under a square‐wave alternating current (AC). The electric current triggers a reaction between water molecules and chloride ions on the surface of the PtNPs, generating cytotoxic hydroxyl radicals. Such a mechanism, called electrodynamic therapy (EDT), enables effective killing of cancer cells within the whole electric field, in contrast to EChT, which is limited to areas nearby electrodes. Remarkable tumor destruction efficacy is further demonstrated in this in vivo EDT treatment with PtNPs. Therefore, this study presents a new type of cancer therapy strategy with a tumor‐killing mechanism different from existing methods, using nanoparticles with electrocatalytic functions. This EDT method appears to be minimally invasive, and is able to offer homogeneous killing effects to the entire tumor with a relatively large size.     

Magnetoelectric Radical Hydrocarbons

The molecular radicals, systems with unpaired electrons of open‐shell electronic structures, set the stage for a multidisciplinary science frontier relevant to the cooperative magnetic exchange interaction and magnetoelectric effect. Here ferroelectricity together with magnetic spin exchange coupling in molecular radical hydrocarbon solids is reported, representing a new class of magnetoelectrics. Electronic correlation through radical–radical interactions plays a decisive role in the coupling between magnetic and charge orders. A substantial photoconductance and visible‐light photovoltaic effect are found in radical hydrocarbons. The ability to simultaneously control and retrieve the changes in magnetic and electrical responses opens up a new breadth of applications, such as radical magnetoelectrics, magnets, and optoelectronics.     

The antioxidant capacity of complex mixtures by kinetic analysis of crocin bleaching inhibition

The capability of a compound or of a mixture of compounds to quench peroxyl radicals was measured by analyzing the kinetics of the competition of a parallel reaction where peroxyl radicals bleach the carotenoid crocin. This kinetic approach, originally described for the analysis of antioxidants reacting with hydroxyl radicals in water, was modified by both decreasing the polarity of the solvent, thus allowing the analysis of lipophilic compounds, and by substituting a source of peroxyl radicals for the hydroxyl radical generating system. Single compounds as well as complex mixtures were analyzed by kinetic data processing. Overall antioxidant capacity, relative to that of α-tocopherol or of its soluble analog Trolox C, was calculated. As examples of the use of this test, the antioxidant capacities of a crude rosemary extract, Maillard reaction products, and virgin olive oils were measured.     

Study on the influence factors of the photocatalysis degradation of Humic Acid

The effects of Humic Acid (HA) concentration,pH value and aeration on the photocatalysis degradation of HA by the silica gel supported TiO2 were studied.Moreover,the effect of aeration on the generation of hydroxyl radicals are investigated.The experimental results indicated that the hydroxyl radicals are generated during the photocatalysis process.The generation of hydroxyl radicals is increasing linearly with the reaction time,approximately.Moreover,the generation rate of hydroxyl under the condition of aeration is 1.57 times of that under the condition without aeration,which is the main influent factor on the reaction rate.Therefore,the reaction rate constant with and without aeration is 0.012 min-1 and 0.0063 min-1,respectively.The degradation rate decreases when the initial HA concentration increases,which is due to that more TiO2 active sites are occupied by HA when the HA concentration is higher.Moreover,HA can absorb large amount of photons,which can prevent those available photons to arrive at the activate TiO2 particles.The degradation rate decreases when increasing pH value,which is due to that the adsorption of HA on the TiO2 particles is weakened and not benefit for the degradation process of HA.     

Effect of time of restriction on the decrease in mitochondrial H2O2 production and oxidative DNA damage in the heart of food-restricted rats

In the present study, the question if medium-term (4 months) caloric restriction (40%) decreases mitochondrial H2O2 production and oxidative DNA damage was investigated. Caloric restriction (CR) is the only experimental manipulation that increases maximum life span. Previous long-term CR studies have showed that CR decreases the mitochondrial rate of free radical production in diverse tissues and species. Those studies agree with the idea that the superior longevity of the restricted animals can be partly due to their lower mitochondrial rate of free radical generation. However, caloric restriction effects strongly depend on implementation time. Previous studies have shown that the decrease induced by CR on oxygen radical generation and oxidative damage to mitochondrial DNA occurs after 1 year but not after 6 weeks of restriction. In the present investigation, mitochondrial H2O2 production did not change in medium-term (4 months) caloric restricted animals, and, in agreement with that, no differences were found in either mitochondrial or nuclear oxidative DNA damage between restricted and ad libitum-fed animals. These results confirm the importance of the time of CR implementation, and show that time longer than 4 months is needed to decrease the mitochondrial rate of free radical generation and the oxidative damage to mtDNA in the rat heart.     

Discovery of Aporphine Analogues as Potential Antiplatelet and Antioxidant Agents: Design,Synthesis, Structure–Activity Relationships,Biological Evaluations,and in silico Molecular Docking Studies

To explore the potential of aporphine alkaloids, a novel series of functionalized aporphine analogues with alkoxy (OCH₃, OC₂H₅, OC₃H₇) functional groups at C1/C2 of ring A and an acyl (COCH₃ and COPh) or phenylsulfonyl (SO₂Ph and SO₂C₆H₄‐3‐CH₃) functionality at the N6 position of ring B of the aporphine scaffold were synthesized and evaluated for their arachidonic acid (AA)‐induced antiplatelet aggregation inhibitory activity and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free‐radical‐scavenging antioxidant activity, with acetylsalicylic acid and ascorbic acid as standard references, respectively. The preliminary structure–activity relationship related to AA‐induced platelet aggregation inhibitory activity results showed that the aporphine analogues 1‐[1,2,9,10‐tetramethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone and 1‐[2‐(benzyloxy)‐1,9,10‐trimethoxy‐6a,7‐dihydro‐4H‐dibenzo[de,g]quinolin‐6(5H)‐yl]ethanone to be the best compounds of the series. Moreover, the DPPH free‐radical‐scavenging antioxidant activity results demonstrated that the aporphine analogues 1,2,9,10‐tetramethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2‐ethoxy‐1,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 1‐ethoxy‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, 2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐1‐propoxy‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline, and 1‐(benzyloxy)‐2,9,10‐trimethoxy‐6‐(methylsulfonyl)‐5,6,6a,7‐tetrahydro‐4H‐dibenzo[de,g]quinoline were the best compounds of the series. Moreover, in silico molecular docking simulation studies of the active analogues were also performed.