Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet

Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.     

Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors.     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

A Soft,Fast and Versatile Electrohydraulic Gripper with Capacitive Object Size Detection

Soft robotic grippers achieve increased versatility and reduced complexity through intelligence embodied in their flexible and conformal structures. The most widely used soft grippers are pneumatically driven; they are simple and effective but require bulky air compressors that limit their application space and external sensors or computationally expensive vision systems for pick verification. In this study, a multi-material architecture for self-sensing electrohydraulic bending actuators is presented that enables a new class of highly versatile and reconfigurable soft grippers that are electrically driven and feature capacitive pick verification and object size detection. These electrohydraulic grippers are fast (step input results in finger closure in 50 ms), draw low power (6.5 mW per finger to hold grasp), and can pick a wide variety of objects with simple binary electrical control. Integrated high-voltage driving electronics are presented that greatly increase the application space of the grippers and make them readily compatible with commercially available robotic arms.     

Untersuchungen zum Abbau von Maillard-Reaktionsprodukten durch amylolytische Enzyme

The enzymatic degradation of thermal treated α-glucans with amylolytic enzymes depends on the reaction environment (T, pH, moisture), the degree of polymerisation (DP) and the branch of the substrates as well as on the presence of amino compounds. The chemical changes of the α-glucans due to thermolysis at 180 °C are characterized by means of the amount of reducing substances and the amount of maltooligosaccharides (HPLC). In general the enzymatic degradability of the thermal treated α-glucans is decreased with increasing time of thermolysis, temperature and moisture content. The enzyme activity with the thermal treated α-glucans is diminished in the same way. The addition of amino compounds reduces the enzymatic degradability only at the beginning of the reaction. With increasing time of thermolysis the thermolysates without glycine addition are hardly degradated. As reason for these differences in the enzymatic degradation transglycosylation and non-enzymatic browning reactions (caramalisation/ Maillard-reaction) are assumed.     

System performance analysis of cooperative multihop relaying network applying approximation to dual‐hop relaying network

In this paper, the closed‐form expressions for outage probability, channel capacity, and average symbol error probability are derived for amplify‐and‐forward multihop relay network. Based on approximation of multihop relay by dual‐hop relay systems, the analytical expressions are obtained for the case when maximal ratio combining technique is employed at each relay while destination node uses selection combining technique. The impact of system and channel parameters on the system performances is investigated, and numerical results are graphically presented. The derived analytical expressions are verified by numerical simulation.     

0.8 μW 12-bit SAR ADC sensors interface for RFID applications

The design and first measuring results of an ultra-low power 12 bit successive-approximation ADC for autonomous multi-sensor systems are presented. The comparator and the DAC are optmised for low power consumption. The power consumption is 0.52 μW from a 1.2 V supply with a sample clock of 3.125 kHz and 0.85 μW at 6.25 kHz. This gives 136 pJ per conversion or 66 fJ per conversion step. As per authors’ knowledge, 66 fJ per conversion step is the best reported so far.The ADC was realised in the NXP CMOS 0.14 μm technology; the area was 0.35 mm². Only four metal layers were used in order to allow 3D integration of the sensors.     

In situ Characterization of SiO2 Nanoparticle Biointeractions Using BrightSilica

By adding a gold core to silica nanoparticles (BrightSilica), silica‐like nanoparticles are generated that, unlike unmodified silica nanoparticles, provide three types of complementary information to investigate the silica nano‐biointeraction inside eukaryotic cells in situ. Firstly, organic molecules in proximity of and penetrating into the silica shell in live cells are monitored by surface‐enhanced Raman scattering (SERS). The SERS data show interaction of the hybrid silica particles with tyrosine, cysteine and phenylalanine side chains of adsorbed proteins. Composition of the biomolecular corona of BrightSilica nanoparticles differs in fibroblast and macrophage cells. Secondly, quantification of the BrightSilica nanoparticles using laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) micromapping indicates a different interaction of silica nanoparticles compared to gold nanoparticles under the same experimental conditions. Thirdly, the metal cores allow the investigation of particle distribution and interaction in the cellular ultrastructure by cryo nanoscale X‐ray tomography (cryo‐XT). In 3D reconstructions the assumption is confirmed that BrightSilica nanoparticles enter cells by an endocytotic mechanism. The high SERS intensities are explained by the beneficial plasmonic properties due to agglomeration of BrightSilica. The results have implications for the development of multi‐modal qualitative and quantitative characterization in comparative nanotoxicology and bionanotechnology.     

Speed up of Video Enhancement based on Human Perception

This paper presents SUVEHP (speed up of video enhancement based on human perception), a human perception-based model oriented to reduce the computational time of digital video restoration. In particular, two specific hypothesis tests able to classify degraded frame regions are proposed. Classification is performed in agreement with regions visual significance in order to enable or inhibit motion compensated enhancement. The level of the proposed hypothesis tests is theoretically assessed. Moreover, extensive experimental results on video sequences affected by additive Gaussian noise show that SUVEHP speeds up some standard motion compensated denoisers up to 60%, preserving or even slightly increasing both the objective and subjective visual quality of the restored sequences.