Green Synthesis of Silymarin–Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis

Background: Silymarin (SIL) has long been utilized to treat a variety of liver illnesses, but due to its poor water solubility and low membrane permeability, it has a low oral bioavailability, limiting its therapeutic potential. Aim: Design and evaluate hepatic-targeted delivery of safe biocompatible formulated SIL-loaded chitosan nanoparticles (SCNPs) to enhance SIL’s anti-fibrotic effectiveness in rats with CCl₄-induced liver fibrosis. Methods: The SCNPs and chitosan nanoparticles (CNPs) were prepared by ionotropic gelation technique and are characterized by physicochemical parameters such as particle size, morphology, zeta potential, and in vitro release studies. The therapeutic efficacy of successfully formulated SCNPs and CNPs were subjected to in vivo evaluation studies. Rats were daily administered SIL, SCNPs, and CNPs orally for 30 days. Results: The in vivo study revealed that the synthesized SCNPs demonstrated a significant antifibrotic therapeutic action against CCl₄-induced hepatic injury in rats when compared to treated groups of SIL and CNPs. SCNP-treated rats had a healthy body weight, with normal values for liver weight and liver index, as well as significant improvements in liver functions, inflammatory indicators, antioxidant pathway activation, and lipid peroxidation reduction. The antifibrotic activities of SCNPs were mediated by suppressing the expression of the main fibrosis mediators TGFβR1, COL3A1, and TGFβR2 by boosting the hepatic expression of protective miRNAs; miR-22, miR-29c, and miR-219a, respectively. The anti-fibrotic effects of SCNPs were supported by histopathology and immunohistochemistry (IHC) study. Conclusions: According to the above results, SCNPs might be the best suitable carrier to target liver cells in the treatment of liver fibrosis.     

Peer to peer trade in HTM5 meta model for agent oriented cloud robotic systems

Cloud computing is a methodology and not a technology. Adaptation of cloud computing services for robotic applications is relatively straightforward while adaptation of underlying ideas will require a new design attitude. Cloud computing is a cost-effective and dynamic business model. Currently cloud robotics is understood as a client server methodology which enables robots utilize resources and services placed at centralized servers. These cloud servers treat robots as any other client computer offering them platform, infrastructure, process or algorithm as a service. HTM5 is an OMG MDA based multi-view meta-model for agent oriented development of cloud robotic systems. HTM5 encourages design of peer-to-peer service ecosystems based on an open registry and matchmaking mechanism. In peer-to-peer cloud robotics, a robot can trade its hardware, software and functional resources as a service to other robots in the ecosystem. The peer-to-peer trade in such systems may be driven by contracts and relationships between its member agents. This article discusses trade-view model of HTM5 methodology and its use in developing a cloud robotic ecosystem that implements peer-to-peer, contract based economy. The article also presents a case study with experiments that implement distributed artificial intelligence and peer-to-peer service oriented trade on simulated and real robot colonies.     

Estimation of SPIO Nanoparticles Uptakes by Macrophages Using Transmission Electron Microscopy

Due to their interesting size-dependent magnetic characteristics and relative biocompatibility, magnetic superparamagnetic iron oxide (SPIO) nanoparticles have been widely exploited as probes for cell and subcellular structure identification, as well as medication and gene delivery. A thorough understanding of the mechanics of the interaction between nanoparticles and macrophages is vital in managing dynamic processes in nanomedicine. In this study, the interaction behavior and uptake of SPIO nanoparticles by M1- and M2-type macrophages were investigated. Mice monocytes were differentiated into M1 and M2 macrophages, and the uptake of SPIO nanoparticles was studied using a TEM microscope. A high resolution image of 1 nm resolution, an image processing technique, was developed to extract the SPIO-NPs from tomographic TEM microscopic images. Lysosomes appear to be the zones of high concentrations of SPIO inside macrophages. Lysosomes were first selected in each image, and then segmentation by the Otsu thresholding method was used to extract the SPIO-NPs. The Otsu threshold method is a global thresholding technique used to automatically differentiate SPIOs from the background. The SPIO-NPs appear in red colors, and the other pixels in the image are considered background. Then, an estimation of the SPIO-NP uptakes by lysosomes is produced. Higher uptake of all-sized nanoparticles was observed in M1- and M2-type macrophages. An accurate estimation of the number of SPIO-NPs was obtained. This result will help in controlling targeted drug delivery and assessing the safety impact of the use of SPIO-NPs in nanomedicine for humans.     

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9^-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.     

In Vitro Rescue of the Bile Acid Transport Function of ABCB11 Variants by CFTR Potentiators

ABCB11 is responsible for biliary bile acid secretion at the canalicular membrane of hepatocytes. Variations in the ABCB11 gene cause a spectrum of rare liver diseases. The most severe form is progressive familial intrahepatic cholestasis type 2 (PFIC2). Current medical treatments have limited efficacy. Here, we report the in vitro study of Abcb11 missense variants identified in PFIC2 patients and their functional rescue using cystic fibrosis transmembrane conductance regulator potentiators. Three ABCB11 disease-causing variations identified in PFIC2 patients (i.e., A257V, T463I and G562D) were reproduced in a plasmid encoding an Abcb11-green fluorescent protein. After transfection, the expression and localization of the variants were studied in HepG2 cells. Taurocholate transport activity and the effect of potentiators were studied in Madin–Darby canine kidney (MDCK) clones coexpressing Abcb11 and the sodium taurocholate cotransporting polypeptide (Ntcp/Slc10A1). As predicted using three-dimensional structure analysis, the three variants were expressed at the canalicular membrane but showed a defective function. Ivacaftor, GLP1837, SBC040 and SBC219 potentiators increased the bile acid transport of A257V and T463I and to a lesser extent, of G562D Abcb11 missense variants. In addition, a synergic effect was observed when ivacaftor was combined with SBC040 or SBC219. Such potentiators could represent new pharmacological approaches for improving the condition of patients with ABCB11 deficiency due to missense variations affecting the function of the transporter.     

Adsorption of U(Ⅵ) from acid solution on a low-cost sorbent:equilibrium,kinetic, and thermodynamic assessments

In this paper, waste clay was cured with ethyl acetate to obtain treated clay(TC), which was modified with gallic acid to obtain a low-cost sorbent that was characterized by EDX, SEM, and FTIR analysis. Uranium(Ⅵ) adsorption was achieved using the batch adsorption method on the TC and gallic acid-modified treated clay(GMTC). The maximum uptakes of U(Ⅵ) on TC and GMTC were 37.2 and 193.0 mg/g, respectively.The U(Ⅵ) adsorption kinetics on the TC and GMTC sorbents were well-fitted by the pseudo-second-order mechanism, and the adsorption equilibrium followed the Langmuir model. The optimum parameters were applied to El Sela leach solution for uranium recovery.     

Review of carbon dioxide (CO2) based heating and cooling technologies: Past,present, and future outlook

Refrigerants bearing high global warming potential (GWP) and ozone depletion potential (ODP) were outlawed or facing time-beared permission under the Montreal (1987), Kyoto (1997) protocols, F-Gas law (2015), Paris Accord (2016), and recent Kigali Amendment to Montreal Protocol (2019). In order to modify followed by the paradigm shift of existing heating and cooling systems, American Society of Heating, Refrigeration, and Air-Conditioning Engineers (ASHRAE) envisaged natural and synthetic refrigerants (Synrefs) are under investigation globally. Carbon dioxide (CO₂) is a popular natural refrigerant (Natref) replacing Synrefs used in commercial heating, ventilation, air conditioning, and refrigeration (HVAC&R) systems globally. A rampant rise is observed in markets of Asia (Japan and China), North America (the United States and Canada), the Australian continent, and Africa (South Africa) by reaching 20 000 CO₂-stores around the globe. The European markets are leading the utilization of CO₂ in the heat pump, and refrigeration, CO₂ based markets estimate 14% of the total food retail stores (400 m²). Japan is the second leading market of CO₂ heat pump and refrigeration with more than 10 200 CO₂ condensing units. CO₂ transcritical systems have a share of more than 10% in only European market (large stores); however, their share is less than 10% of total stores in other major markets of the world. New pump and compressor-driven transcritical CO₂ systems integrate ejectors, condensers, and booster systems to reduce energy consumptions, enhance efficiency, efficacy, and coefficient of performance. This article reports a critical review of the CO₂ based heating, cooling, and refrigeration system and presents updated literature along with barriers and challenges on commercial use of Natref-based heating and cooling applications worldwide.     

Synthesis of PVA/PVP based hydrogel for biomedical applications: a review

The composition and synthesis of hydrogel were developed by using Polyvinyl alcohol (PVA) and Polyvinylpyrrolidone (PVP). Polyvinyl alcohol (PVA) and Polyvinylpyrrolidone (PVP) based hydrogels are the most popular water-soluble, biodegradable, biocompatible, non-carcinogenic, and extremely low cytotoxicity synthetic polymers due to their good biocompatibility have been used in numerous biomedical applications, such as implants, artificial organs, drug delivery devices, and wound dressings. In this review paper, details of synthetic of hydrogel formulations with PVA and PVP for biomedical applications.     

Membrane-hydration-state detection in proton exchange membrane fuel cells using improved ambient-condition-based dynamic model

Proton-exchange-membrane fuel cells (PEMFCs) are a popular source of alternative energy because of their operational reliability and compactness. This paper presents an improved model to represent the semi-empirical voltage of PEMFCs to overcome the limitations of existing models. The proposed model considers variations in ambient conditions, such as the ambient temperature and relative humidity, to obtain the accurate output voltage that corresponds to variations in dynamic and static loads. The proposed model was developed by conducting several experiments on the Horizon PEMFC system under normal, humid, and dry ambient conditions. Subsequently, the model parameters corresponding to each case were optimised using the quantum lightning search algorithm (QLSA). Parameters demonstrating significant variations with ambient conditions were finally represented as a function of the ambient temperature and relative humidity via statistical regression analysis. The voltage obtained using the modified model was verified by conducting experiments on both the Horizon and NEXA PEMFC systems by varying the ambient temperature and relative humidity with root mean square error (RMSE) less than 0.5. As observed, the results we obtained using the modified model closely approximated those obtained using PEMFCs under various operating conditions, and in both cases, the PEMFC voltage was observed to vary with the ambient and load conditions. The inherent advantages of the proposed PEMFC model include its ability to determine the membrane-water content and water pressure inside PEMFCs. The membrane-water content provides clear indications regarding the occurrence of drying and flooding faults. Under normal conditions, this membrane water content ranges from 11 to 7 for both the Horizon and NEXA PEMFC system. The simulation results suggested using the threshold membrane-water-content level as a possible indicator of fault occurrence under extreme ambient conditions. The limits of the said threshold were observed to be useful for fault diagnosis within PEMFC systems.     

Fog Computing for Big Data Analytics in IoT Aided Smart Grid Networks

Wireless Personal Communications - The recent integration of Internet of Things and Cloud Computing (CC) technologies into a Smart Grid (SG) revolutionizes its operation. The scalable and unlimited...