bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainty-Controlled Remaining Useful Life Prediction of Bearings with a New Data-Augmentation Strategy
Authors: Wang Ran , Yan Fucheng , Shi Ruyu , Yu Liang , Deng Yingjun
Published: November 2022

The remaining useful life (RUL) of bearings based on deep learning methods has been increasingly used. However, there are still two obstacles in deep learning RUL prediction: (1) the training process of the deep learning model requires enough data, but run-to-failure data are limited in the actual industry; (2) the mutual dependence between RUL predictions at different time instants are commonly ignored in existing RUL prediction methods. To overcome these problems, a RUL prediction method combining the data augmentation strategy and Wiener–LSTM network is proposed. First, the Sobol sampling strategy is implemented to augment run-to-failure data based on the degradation model. Then, the Wiener–LSTM model is developed for the RUL prediction of bearings. Different from the existing LSTM-based bearing RUL methods, the Wiener–LSTM model utilizes the Wiener process to represent the mutual dependence between the predicted RUL results at different time instants and embeds the Wiener process into the LSTM to control the uncertainty of the result. A joint optimization strategy is applied in the construction of the loss function. The efficacy and superiority of the proposed method are verified on a rolling bearing dataset obtained from the PRONOSTIA platform. Compared with the conventional bearing RUL prediction methods, the proposed method can effectively augment the bearing run-to-failure data and, thus, improve the prediction results. Meanwhile, fluctuations of the bearing RUL prediction result are significantly suppressed by the proposed method, and the prediction errors of the proposed method are much lower than other comparative methods.
Intelligent Position Control for Intelligent Pneumatic Actuator with Ball-Beam (IPABB) System
Authors: Muftah Mohamed Naji , Faudzi Ahmad Athif Mohd , Sahlan Shafishuhaza , Mohamaddan Shahrol
Published: November 2022

A pneumatic actuator system is considered extremely nonlinear, making accurate position control of this actuator difficult to obtain. In this article, a novel cascade fractional-order PID (CFOPID) controller for the intelligent pneumatic actuator (IPA) positioning system utilizing particle swarm optimization (PSO) is presented. The pneumatic system was modeled using the system identification (SI) technique. To demonstrate the effectiveness of the CFOPID controller, a comparison to the FOPID controller is performed based on the rise, settling, and peak times, peak overshoot, and integral of square error (ISE). From the results obtained, the proposed CFOPID controller provides superior control over the FOPID controller. For the application of the position controller, the proposed system incorporates an intelligent pneumatic actuated ball and beam (IPABB) system. The mathematical model of the system was developed and validated through a simulation utilizing a PID (outer loop) and CFOPID controller (inner loop). The suggested controller’s accuracy and robustness have been studied by a comparative examination of the results obtained utilizing the proposed and other prior controllers on the same system. The results indicate that the intelligent pneumatic actuator, when coupled with a CFOPID controller, is capable of controlling the positioning of the ball and beam system.
Marine Bacteria Associated with Colonization and Alteration of Plastic Polymers
Authors: Carrasco-Acosta Marina , Santos-Garcia Marta , Garcia-Jimenez Pilar
Published: November 2022

The aim of this work was molecular identification of bacteria associated with marine sand at the drift line, where most plastic debris is deposited, and evaluation of the alteration of plastic polymers by them. Bacterial communities growing on plastic polymer surfaces may differentially cause surface alteration through exopolysaccharide production. This alteration can be analyzed by changes in spectra regions of colonized polymers compared to uncolonized polymers using Fourier Transform Infrared Spectroscopy (FTIR). In this study, bacteria located in sand at the drift line above sea water, where microplastics are most abundant, were isolated and identified through 16S rRNA. Six of the identified species produced exopolysaccharides, namely Bacillus thuringiensis, B. cereus, Bacillus sp. Proteus penneri, Alcaligenes faecalis and Myroides gitamensis. These bacteria species were inoculated into plates, each containing two frequently reported types of polymers at the drift line. Specifically, the two types of plastic polymers used were polypropylene and polystyrene spheres in whole and mechanically crushed states. Differences in bacterial growth were reported as inferred from weight increase of polypropylene and polystyrene spheres after 1-year long culture. Results also showed that Alcaligenes faecalis, Bacillus cereus and Proteus penneri colonized polypropylene spheres and modified spectra regions of FTIR. It is concluded that bacteria located in sand can be considered plastic-altering bacteria as changes in FTIR-spectra of polymers can be related to bioalteration.
Application of Ozone Therapy in Paediatric Dentistry
Authors: D’Amario Maurizio , Di Carlo Mariachiara , Natale Salvatore Massimo , Memè Lucia , Marzo Giuseppe , Matarazzo Giorgio , Capogreco Mario
Published: November 2022

The therapeutic use of ozone has been suggested for a long time in general dentistry and paediatric dentistry for its antimicrobial, virucidal, disinfectant, and biocompatible properties. Ozone has also anti-inflammatory, analgesic, and immunostimulant properties, and it promotes tissue regeneration. Dental treatment in children is often complex and ozone could support the clinician to enhance the approach and prognosis with young patients, non-cooperant children, or special needs patients. The efficiency of ozone will certainly increase if studies continue to show positive outcomes in a growing number of dental paediatric conditions. This review explores the recent literature of ozone therapy in paediatric dentistry and suggests fields of application for future randomized controlled trials (RCTs).
Fiberglass as a Novel Building Material: A Life Cycle Assessment of a Pilot House
Authors: Bjånesøy Stavroula , Heinonen Jukka , Ögmundarson Ólafur , Árnadóttir Áróra , Marteinsson Björn
Published: November 2022

Alternative building materials have the potential to reduce environmental pressure from buildings, though the use of these materials should be guided by an understanding of the embodied environmental impacts. Extensive research on embodied greenhouse gas emissions from buildings has been conducted, but other impacts are less frequently reported. Furthermore, uncertainty is rarely reported in building LCA studies. This paper provides a piece for filling those gaps by comprehensively reporting the embodied environmental impacts of a fiberglass house within the LCA framework, modeled in the OpenLCA software using the Ecoinvent 3.7.1 inventory database. The ReCiPe 2016 impact assessment method is used to report a wide range of environmental impacts. The global warming potential is calculated to be 311 kgCO2 eq/m2. Additionally, a hotspot analysis is included to identify areas that should be the focus for improvement, as well as an uncertainty analysis based on Monte Carlo. The embodied emissions are given context by a scenario analysis over a 50-year use phase in three different grid conditions and with two different energy efficiency levels. Based on the results of this study, it is determined that fiberglass does not provide a viable alternative to conventional building materials if the purpose is to reduce embodied emissions from buildings.
Enhancement of Gain Coefficient of Li-Like Ion 3d-4f Soft X-ray Laser Oscillation by a Single Resonator
Authors: Namba Shinichi , Wang Jiahao , Ohiro Hikari , Zhang Jiawei , Kishimoto Maki , Yamasaki Kotaro , Hasegawa Noboru , Dinh Thanhhung , Ishino Masahiko , Higashiguchi Takeshi , Nishikino Masaharu
Published: November 2022

A recombination plasma soft X-ray laser that is associated with Li-like Aluminum ion Al10+ 3d-4f transition (wavelength: 15.47 nm) was investigated to increase the gain coefficient. By optimizing the time interval of the 16-pulse train, higher-density plasma with a low temperature could be generated, and thus, we obtained the gain coefficient of 9.84 cm−1 at the pump laser pulse energy which was as low as 3 J. To further enhance the X-ray laser output energy, the single resonator which was installed by using a Mo/Si multilayer mirror that has a high reflectivity of 0.45 at 15.5 nm, and the X-ray spectrum after the double pass in the lasing medium was measured. As a result, the output intensity was increased to be 1.5 times higher than t=when it was compared with those that were conducted with no X-ray mirror.
Process Development of Polyhydroxyalkanoates Production by Halophiles Valorising Food Waste
Authors: Wang Ke , Chen Chang , Zhang Ruihong
Published: November 2022

Polyhydroxyalkanoates (PHA) is an emerging biodegradable plastic family that can replace a broad spectrum of conventional thermoplastics and is promising in the sustainable process development and valorization of organic waste. This study established a novel production system of PHA from food waste through halophilic microbial fermentation with spent medium recycling. The essential processing parameters for batch cultivation of Haloferax mediterranei were optimized for food waste substrate (a 40 g/L loading and 2.5 vvm of aeration), which achieved a yield of 0.3 g PHA/g COD consumed. A batch bioreactor system was developed, which produced 7.0 ± 0.7 g/L cell dry mass and 4.5 ± 0.2 g/L PHA with a 20% dissolved oxygen (DO) level. A DO above 50% saturation resulted in faster cell growth and similar cell mass production but 25% less PHA production. The spent saline medium, treated with H2O2 and rotary evaporation, was successfully reused for four consecutive batches and provided consistent PHA concentrations and product qualities.
Integrated Bioinformatics-Based Subtractive Genomics Approach to Decipher the Therapeutic Drug Target and Its Possible Intervention against Brucellosis
Authors: Khan Kanwal , Alhar Munirah Sulaiman Othman , Abbas Muhammad Naseer , Abbas Syed Qamar , Kazi Mohsin , Khan Saeed Ahmad , Sadiq Abdul , Hassan Syed Shams ul , Bungau Simona , Jalal Khurshid
Published: November 2022

Brucella suis, one of the causative agents of brucellosis, is Gram-negative intracellular bacteria that may be found all over the globe and it is a significant facultative zoonotic pathogen found in livestock. It may adapt to a phagocytic environment, reproduce, and develop resistance to harmful environments inside host cells, which is a crucial part of the Brucella life cycle making it a worldwide menace. The molecular underpinnings of Brucella pathogenicity have been substantially elucidated due to comprehensive methods such as proteomics. Therefore, we aim to explore the complete Brucella suis proteome to prioritize the novel proteins as drug targets via subtractive proteo-genomics analysis, an effort to conjecture the existence of distinct pathways in the development of brucellosis. Consequently, 38 unique metabolic pathways having 503 proteins were observed while among these 503 proteins, the non-homologs (n = 421), essential (n = 350), drug-like (n = 114), virulence (n = 45), resistance (n = 42), and unique to pathogen proteins were retrieved from Brucella suis. The applied subsequent hierarchical shortlisting resulted in a protein, i.e., isocitrate lyase, that may act as potential drug target, which was finalized after the extensive literature survey. The interacting partners for these shortlisted drug targets were identified through the STRING database. Moreover, structure-based studies were also performed on isocitrate lyase to further analyze its function. For that purpose, ~18,000 ZINC compounds were screened to identify new potent drug candidates against isocitrate lyase for brucellosis. It resulted in the shortlisting of six compounds, i.e., ZINC95543764, ZINC02688148, ZINC20115475, ZINC04232055, ZINC04231816, and ZINC04259566 that potentially inhibit isocitrate lyase. However, the ADMET profiling showed that all compounds fulfill ADMET properties except for ZINC20115475 showing positive Ames activity; whereas, ZINC02688148, ZINC04259566, ZINC04232055, and ZINC04231816 showed hepatoxicity while all compounds were observed to have no skin sensitization. In light of these parameters, we recommend ZINC95543764 compound for further experimental studies. According to the present research, which uses subtractive genomics, proteins that might serve as therapeutic targets and potential lead options for eradicating brucellosis have been narrowed down.
A Flower Bud from the Lower Cretaceous of China
Authors: Chen Li-Jun , Wang Xin
Published: November 2022

Background: Although various angiosperms (including their flowers) have been reported from the Yixian Formation (Lower Cretaceous) of China, which is famous worldwide for its fossils of early angiosperms, no flower bud has hitherto been seen in the Early Cretaceous. Such a lack of examples hinders our understanding of the evolution of flowers. Methods: The specimen studied in the present paper was collected from an outcrop of the Yixian Formation (the Barremian-Aptian, Lower Cretaceous) of Dawangzhangzi in Lingyuan, Liaoning, China. The specimen was photographed using a Nikon D200 digital camera, its details were observed and photographed using a Nikon SMZ1500 stereomicroscope, and some of its details were observed using a Leo 1530 VP SEM. Results: We report a fossilized flower bud, Archaebuda lingyuanensis gen. et sp. nov, from the Yixian Formation of China. The debut of Archaebuda in the Yixian Formation provides first-hand material for debate on the early evolution of angiosperm flowers and underscores the great diversity of angiosperms in the Yixian Formation.
Computationally Designed Anti-LuxP DNA Aptamer Suppressed Flagellar Assembly- and Quorum Sensing-Related Gene Expression in Vibrio parahaemolyticus
Authors: Yusof Nur Afiqah Md , Razali Siti Aisyah , Mohd Padzil Azyyati , Lau Benjamin Yii Chung , Baharum Syarul Nataqain , Nor Muhammad Nor Azlan , Raston Nurul Hanun Ahmad , Chong Chou Min , Ikhsan Natrah Fatin Mohd , Situmorang Magdalena Lenny , Fei Low Chen
Published: November 2022

(1) Background: Quorum sensing (QS) is the chemical communication between bacteria that sense chemical signals in the bacterial population to control phenotypic changes through the regulation of gene expression. The inhibition of QS has various potential applications, particularly in the prevention of bacterial infection. QS can be inhibited by targeting the LuxP, a periplasmic receptor protein that is involved in the sensing of the QS signaling molecule known as the autoinducer 2 (AI-2). The sensing of AI-2 by LuxP transduces the chemical information through the inner membrane sensor kinase LuxQ protein and activates the QS cascade. (2) Methods: An in silico approach was applied to design DNA aptamers against LuxP in this study. A method combining molecular docking and molecular dynamics simulations was used to select the oligonucleotides that bind to LuxP, which were then further characterized using isothermal titration calorimetry. Subsequently, the bioactivity of the selected aptamer was examined through comparative transcriptome analysis. (3) Results: Two aptamer candidates were identified from the ITC, which have the lowest dissociation constants (Kd) of 0.2 and 0.5 micromolar. The aptamer with the lowest Kd demonstrated QS suppression and down-regulated the flagellar-assembly-related gene expression. (4) Conclusions: This study developed an in silico approach to design an aptamer that possesses anti-QS properties.
Modulation of Canine Melanocortin-3 and -4 Receptors by Melanocortin-2 Receptor Accessory Protein 1 and 2
Authors: Ji Ren-Lei , Jiang Shan-Shan , Tao Ya-Xiong
Published: November 2022

The neural melanocortin receptors (MCRs), melanocortin-3 and -4 receptors (MC3R and MC4R), have crucial roles in regulating energy homeostasis. The melanocortin-2 receptor accessory proteins (MRAPs, MRAP1 and MRAP2) have been shown to regulate neural MCRs in a species-specific manner. The potential effects of MRAP1 and MRAP2 on canine neural MCRs have not been investigated before. Herein, we cloned canine (c) MC3R and identified one canine MRAP2 splice variant, MRAP2b, with N-terminal extension of cMRAP2a. Canine MC3R showed higher maximal responses to five agonists than those of human MC3R. We further investigated the modulation of cMRAP1, cMRAP2a, and cMRAP2b, on cMC3R and cMC4R pharmacology. For the cMC3R, all MRAPs had no effect on trafficking; cMRAP1 significantly decreased Bmax whereas cMRAP2a and cMRAP2b significantly increased Bmax. Both MRAP1 and MRAP2a decreased Rmaxs in response to α-MSH and ACTH; MRAP2b only decreased α-MSH-stimulated cAMP generation. For the MC4R, MRAP1 and MRAP2a increased cell surface expression, and MRAP1 and MRAP2a increased Bmaxs. All MRAPs had increased affinities to α-MSH and ACTH. MRAP2a increased ACTH-induced cAMP levels, whereas MRAP2b decreased α-MSH- and ACTH-stimulated cAMP production. These findings may lead to a better understanding of the regulation of neural MCRs by MRAP1 and MRAP2s.
Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses
Authors: Rubekina Anna A. , Kamzeeva Polina N. , Alferova Vera A. , Shustova Elena Yu. , Kolpakova Ekaterina S. , Yakovchuk Elizaveta V. , Karpova Evgenia V. , Borodulina Maria O. , Belyaev Evgeny S. , Khrulev Alexei A. , Korshun Vladimir A. , Shirshin Evgeny A. , Kozlovskaya Liubov I. , Aralov Andrey V.
Published: November 2022

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.
Optical Study of Lysozyme Molecules in Aqueous Solutions after Exposure to Laser-Induced Breakdown
Authors: Sarimov Ruslan M. , Matveyeva Tatiana A. , Mozhaeva Vera A. , Kuleshova Aleksandra I. , Ignatova Anastasia A. , Simakin Alexander V.
Published: November 2022

The properties of a lysozyme solution under laser-induced breakdown were studied. An optical breakdown under laser action in protein solutions proceeds with high efficiency: the formation of plasma and acoustic oscillations is observed. The concentration of protein molecules has very little effect on the physicochemical characteristics of optical breakdown. After exposure to optical breakdown, changes were observed in the enzymatic activity of lysozyme, absorption and fluorescence spectra, viscosity, and the sizes of molecules and aggregates of lysozyme measured by dynamic light scattering. However, the refractive index of the solution and the Raman spectrum did not change. The appearance of a new fluorescence peak was observed upon excitation at 350 nm and emission at 434 nm at exposure for 30 min. Previously, a peak in this range was associated with the fluorescence of amyloid fibrils. However, neither the ThT assay nor the circular dichroism dispersion confirmed the formation of amyloid fibrils. Probably, under the influence of optical breakdown, a small part of the protein degraded, and a part changed its native state and aggregated, forming functional dimers or “native aggregates”.
Molecular Modeling of Allosteric Site of Isoform-Specific Inhibition of the Peroxisome Proliferator-Activated Receptor PPARγ
Authors: Almahmoud Suliman , Zhong Haizhen A.
Published: November 2022

The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor and controls a number of gene expressions. The ligand binding domain (LBD) of PPARγ is large and involves two binding sites: orthosteric and allosteric binding sites. Increased evidence has shown that PPARγ is an oncogene and thus the PPARγ antagonists have potential as anticancer agents. In this paper, we use Glide Dock approach to determine which binding site, orthosteric or allosteric, would be a preferred pocket for PPARγ antagonist binding, though antidiabetic drugs such as thiazolidinediones (TZDs) bind to the orthosteric site. The Glide Dock results show that the binding of PPARγ antagonists at the allosteric site yielded results that were much closer to the experimental data than at the orthosteric site. The PPARγ antagonists seem to selectively bind to residues Lys265, Ser342 and Arg288 at the allosteric binding site, whereas PPARγ agonists would selectively bind to residues Leu228, Phe363, and His449, though Phe282 and Lys367 may also play a role for agonist binding at the orthosteric binding pocket. This finding will provide new perspectives in the design and optimization of selective and potent PPARγ antagonists or agonists.
Interplay of Hydration and Protonation Dynamics in the K-Channel of Cytochrome c Oxidase
Authors: Gorriz Rene F. , Imhof Petra
Published: November 2022

Cytochrome c oxidase is a membrane protein of the respiratory chain that consumes protons and molecular oxygen to produce water and uses the resulting energy to pump protons across the membrane. Our molecular dynamics simulations with an excess proton located at different positions in one of the proton-conducting channels, the K-channel, show a clear dependence of the number of water molecules inside the channel on the proton position. A higher hydration level facilitates the formation of hydrogen-bonded chains along which proton transfer can occur. However, a sufficiently high hydration level for such proton transport is observed only when the excess proton is located above S365, i.e., the lower third of the channel. From the channel entrance up to this point, proton transport is via water molecules as proton carriers. These hydronium ions move with their surrounding water molecules, up to K362, filling and widening the channel. The conformation of K362 depends on its own protonation state and on the hydration level, suggesting its role to be proton transport from a hydronium ion at the height of K362 to the upper part of the channel via a conformational change. The protonation-dependent conformational dynamics of E101 at the bottom of the channel renders proton transfer via E101 unlikely. Instead, its role is rather that of an amplifier of H96’s proton affinity, suggesting H96 as the initial proton acceptor.
Impact of COVID-19 on Lung Disease in People with Cystic Fibrosis: A 6-Month Follow-Up Study on Respiratory Outcomes
Authors: Medino Paola , Alicandro Gianfranco , Rosazza Chiara , Ciciriello Fabiana , Gramegna Andrea , Biffi Arianna , Daccò Valeria , Lucidi Vincenzina , Cipolli Marco , Boraso Mariaserena , Nazzari Erica , Colombo Carla
Published: November 2022

Background: The impact of COVID-19 on respiratory outcomes in people with cystic fibrosis (pwCF) has not been clearly characterized. We evaluated changes in respiratory function indicators derived from spirometry and pulmonary exacerbation rates 6 months after SARS-CoV-2 infection. Methods: This multicentre prospective study was based on pwCF enrolled between October, 2020 and June, 2021 in the DECO COVID-19 project. PwCF complaining of COVID-like symptoms were tested with real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. Mean changes in respiratory function indicators and time to first episode of pulmonary exacerbation were compared between RT-PCR-positive and RT-PCR-negative patients. Regression models were used to adjust for baseline percent predicted forced expiratory volume in one second (ppFEV1) values, number of comorbidities, and initiation of CFTR modulator therapy during the follow-up. Results: We enrolled 26 pwCF with RT-PCR-confirmed infection and 42 with a RT-PCR-negative test. After 6 months of follow-up, mean ppFEV1 changes were not significantly different between groups (+0.3% in positive vs. +0.2% in negative patients, p = 0.19). The 6-month cumulative probabilities of a first episode of pulmonary exacerbation were: 0.575 among RT-PCR-negative patients and 0.538 among those with a positive test (adjusted hazard ratio: 0.88, 95% CI: 0.44–1.75). Conclusions: COVID-19 did not appear to negatively affect respiratory outcomes of pwCF at 6 months from infection.
Chondrogenic Potential of Human Umbilical Cord Mesenchymal Stem Cells Cultured with Exosome-Depleted Fetal Bovine Serum in an Osteoarthritis Mouse Model
Authors: Chang Yu-Hsun , Wu Kun-Chi , Ding Dah-Ching
Published: November 2022

Osteoarthritis (OA) is characterized by the loss of articular cartilage and is also an age-related disease. Recently, stem cell therapy for cartilage repair has emerged. The stem cells need to be cultured with a fetal bovine serum (FBS)-supplemented medium. The effect of FBS-containing exosomes on the differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) is unknown. The morphology, proliferation, surface marker expressions, and trilineage differentiation ability of two groups of HUCMSCs, cultured with conventional (FBS) and exosome-depleted FBS (Exo(-)FBS), were evaluated. In a mouse OA model after two groups of HUCMSCs transplantation, the rotarod activity, histology, and immunohistochemistry (type II collagen, aggrecan, IL-1β, and MMP13) of the cartilage were evaluated. The Exo(-)FBS-cultured HUCMSCs, like FBS-cultured HUCMSCs, displayed classic MSC characteristics, including spindle-shaped morphology, surface marker expression (positive for CD44, CD73, CD90, CD105, and HLA-ABC and negative for CD34, CD45, and HLA-DR), and trilineage differentiation (chondrogenesis, osteogenesis, and adipogenesis). The Exo(-)FBS-cultured HUCMSCs proliferated significantly slower than those of the FBS-cultured HUCMSCs (p < 0.01). The trilineage gene expression of PPAR-γ, FABP4, APAL, type II collagen, aggrecan, and SOX9 was significantly increased in the Exo(-)FBS-cultured HUCMSCs than in the FBS-cultured HUCMSCs and undifferentiated controls. The Exo(-)FBS- and FBS-cultured HUCMSCs-transplanted mice showed a better rotarod activity than in the control OA mice (n = 3 in each group). A significant histological improvement in hyaline cartilage destruction after the transplantation of both types of FBS-cultured HUCMSCs was noted when compared with the OA knees. The Exo(-)FBS-cultured HUCMSCs-transplanted knees showed a higher International Cartilage Repair Society histological score (p < 0.05), staining intensity of type II collagen (p < 0.01), and aggrecan (p < 0.01) than in the control knees. Moreover, both types of the FBS-cultured HUCMSCs-transplanted knees significantly decreased the expression of MMP13 and IL-1β compared to that in the OA knees (p < 0.01). The Exo(-)FBS-cultured HUCMSCs harbor chondrogenic potential and attenuated cartilage destruction in a mouse OA model. Our study provides a basis for future clinical trials using Exo(-)FBS-cultured stem cells to treat OA.
Immunoglobulin Y Specific for SARS-CoV-2 Spike Protein Subunits Effectively Neutralizes SARS-CoV-2 Infectivity and Ameliorates Disease Manifestations In Vivo
Authors: Yeh Chia-Tsui , Lee Chia-Ying , Ho Yi-Jung , Chen Sin-An , Chen Liang-Yu , Liu Ping-Cheng , Chin Yuan-Fan , Chen An-Yu , Hsieh Po-Shiuan , Hung Yi-Jen , Chen Cheng-Cheung , Wang Yu-Chie , Lee Guan-Chiun
Published: November 2022

(Background) The coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries high infectivity and mortality. Efficient intervention strategies are urgently needed. Avian immunoglobulin Y (IgY) showed efficacy against viral infection whereas the in vivo efficacy remains unclear. (Methods) We immunized laying hens with S1, S1 receptor-binding domain (S1-RBD), or S2 subunits of the SARS-CoV-2 spike (S) protein. After immunization, IgYs were collected and extracted from the egg yolks. The neutralization potential of IgYs was examined by the plaque reduction neutralization test (PRNT). The bioutility of IgYs was examined in Syrian hamsters in vivo. (Results) IgYs exhibited typical banding patterns in SDS-PAGE and Western blot and were immunoreactive against S1, S1-RBD, and S2 subunits. The plaque reduction neutralization test (PRNT) showed that all purified IgYs potently neutralized different SARS-CoV-2 strains in vitro. In Syrian hamsters, the combination of IgYs for S1-RBD and S2 subunits administered before or after SARS-CoV-2 infection effectively restored body weight loss and reduced intrapulmonary lesions and the amount of immunoreactive N protein-positive cells, which were caused by SARS-CoV-2 infection. (Conclusions) Collectively, IgYs specific for S protein subunits effectively neutralized SARS-CoV-2 in vitro and in vivo and may serve as prophylactic or therapeutic antibodies in the prevention or treatment of COVID-19.
GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration
Authors: Kropp Martina , Harmening Nina , Bascuas Thais , Johnen Sandra , De Clerck Eline , Fernández Verónica , Ronchetti Mattia , Cadossi Ruggero , Zanini Cristina , Scherman Daniel , Ivics Zoltán , Marie Corinne , Izsvák Zsuzsanna , Thumann Gabriele
Published: November 2022

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration. Instead of patient iris pigment epithelial cells, human donor tissue was used to produce the transfected cell product (“tIPE”). We implemented an extended validation of 104 tIPE productions. Procedure, operators and devices have been validated and qualified by determining cell number, viability, extracellular DNA, sterility, duration, temperature and volume. Transfected autologous cells were transplanted to rabbits verifying feasibility of the treatment. A container has been engineered to ensure a safe transport from the production to the surgery site. Criteria for successful validation and qualification were based on tIPE’s Critical Quality Attributes and Process Parameters, its manufacture and release criteria. The validated process and qualified operators are essential to bring the ATMP into clinic and offer a general strategy for the transfer to other manufacture centers and personalized ATMPs.
Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer’s Disease
Authors: Ameen Aishat O. , Freude Kristine , Aldana Blanca I.
Published: November 2022

Characterising Alzheimer’s disease (AD) as a metabolic disorder of the brain is gaining acceptance based on the pathophysiological commonalities between AD and major metabolic disorders. Therefore, metabolic interventions have been explored as a strategy for brain energetic rescue. Amongst these, medium-chain fatty acid (MCFA) supplementations have been reported to rescue the energetic failure in brain cells as well as the cognitive decline in patients. Short-chain fatty acids (SCFA) have also been implicated in AD pathology. Due to the increasing therapeutic interest in metabolic interventions and brain energetic rescue in neurodegenerative disorders, in this review, we first summarise the role of SCFAs and MCFAs in AD. We provide a comparison of the main findings regarding these lipid species in established AD animal models and recently developed human cell-based models of this devastating disorder.
Transvenous Lead Extraction Procedure—Indications, Methods, and Complications
Authors: Boarescu Paul-Mihai , Roşian Adela-Nicoleta , Roşian Ştefan Horia
Published: November 2022

Transvenous lead extraction (TLE) is a complex and technically challenging procedure useful in the management strategy for many complications related to the presence of cardiac implantable electronic devices (CIEDs). The decision to perform lead extraction should take into consideration the clinical indication for the procedure, risks versus benefits, extractor and team experience, and also patient preference for the procedure. A variety of techniques can be used when performing TLE procedures, such as simple traction, traction devices, and various types of sheaths or snares. TLE is a procedure with a potentially high risk of complications that can be divided into major complications, which require rapid intervention, and minor complications, which are more frequent but are not life-threatening. The present review aims to highlight the indications, contraindications, methods, and complications of transvenous lead extraction procedures.
Metformin Prevents Endothelial Dysfunction in Endometriosis through Downregulation of ET-1 and Upregulation of eNOS
Authors: Martins Ana Filipa , Neto Ana Catarina , Rodrigues Adriana Raquel , Oliveira Sandra Marisa , Sousa-Mendes Cláudia , Leite-Moreira Adelino , Gouveia Alexandra Maria , Almeida Henrique , Neves Delminda
Published: November 2022

This study aimed to evaluate if the treatment with metformin affects the morphologic structure, endothelial function, angiogenesis, inflammation and oxidation-responsive pathways in the heart of mice with surgically induced endometriosis. B6CBA/F1 mice (n = 37) were divided into four groups; Sham (S), Metformin (M), Endometriosis (E) and Metformin/Endometriosis (ME). The cross-sectional area of cardiomyocytes was assessed after Hematoxylin–Eosin staining and fibrosis after Picrosirius-Red staining. ET-1, nitric oxide synthases-iNOS and eNOS, and VEGF and VEGFR-2 were detected by immunofluorescence. Semi-quantification of ET-1, eNOS, VEGF, NF-kB, Ikβα and KEAP-1 was performed by Western blotting. MIR199a, MIR16-1, MIR18a, MIR20a, MIR155, MIR200a, MIR342, MIR24-1 and MIR320a were quantified by Real-Time qPCR. The interaction of endometriosis and metformin effects was assessed by a two-way ANOVA test. Compared with the other groups, M-treated mice presented a higher cross-sectional area of cardiomyocytes. Heart fibrosis increased with endometriosis. Treatment of endometriosis with metformin in the ME group downregulates ET-1 and upregulates eNOS expression comparatively with the E group. However, metformin failed to mitigate NF-kB expression significantly incremented by endometriosis. The expression of MIR199a, MIR16-1 and MIR18a decreased with endometriosis, whereas MIR20a showed an equivalent trend, altogether reducing cardioprotection. In summary, metformin diminished endometriosis-associated endothelial dysfunction but did not mitigate the increase in NF-kB expression and cardiac fibrosis in mice with endometriosis.
Gold-Nanoparticle-Based Chiral Plasmonic Nanostructures and Their Biomedical Applications
Authors: Li Hanbo , Gao Xinshuang , Zhang Chenqi , Ji Yinglu , Hu Zhijian , Wu Xiaochun
Published: November 2022

As chiral antennas, plasmonic nanoparticles (NPs) can enhance chiral responses of chiral materials by forming hybrid structures and improving their own chirality preference as well. Chirality-dependent properties of plasmonic NPs broaden application potentials of chiral nanostructures in the biomedical field. Herein, we review the wet-chemical synthesis and self-assembly fabrication of gold-NP-based chiral nanostructures. Discrete chiral NPs are mainly obtained via the seed-mediated growth of achiral gold NPs under the guide of chiral molecules during growth. Irradiation with chiral light during growth is demonstrated to be a promising method for chirality control. Chiral assemblies are fabricated via the bottom-up assembly of achiral gold NPs using chiral linkers or guided by chiral templates, which exhibit large chiroplasmonic activities. In describing recent advances, emphasis is placed on the design and synthesis of chiral nanostructures with the tuning and amplification of plasmonic circular dichroism responses. In addition, the review discusses the most recent or even emerging trends in biomedical fields from biosensing and imaging to disease diagnosis and therapy.
The Rostral Ventromedial and Lateral Medulla Are the Major Areas Responsive to Lung Cancer Progression among Brainstem Lung-Innervating Nuclei
Authors: Chen Mo , Jiao Yingfu , Shi Yumiao , Xu Saihong , Tang Dan , Chen Sihan , Gao Po , Zhang Xindi , Zhao Xiaojing , Cai Mengmeng , Yu Weifeng , Xie Kangjie
Published: November 2022

In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain–gut axis, brain–lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.
Features and Conditions of Building Information Modeling Contracts
Authors: Nilchian Siamak , Majrouhi Sardroud Javad , Darabpour Mehrab , Tavousi Tafreshi Shahriar
Published: November 2022

Building information modeling (BIM) has improved efficiency in construction projects by utilizing digital instrument capabilities. However, the use of this technology has brought new challenges, particularly legal and contract issues. Conventional construction contracts cannot respond to specific BIM conditions. Therefore, several contract solutions have been proposed to tackle this problem. Despite significant efforts, researchers are still attempting to develop a suitable contract framework and conditions due to the complexities of BIM technical and legal aspects. The present study reviews the solutions developed within seven pioneer countries in BIM and collects the views of construction experts selected by the snowball sampling method in order to identify the most crucial factors that should be considered in BIM contracts. This work incorporated and analyzed 47 questions relating to BIM legal and contract factors in five groups, including BIM contractual basics, BIM contractual obligations and approvals, BIM ownership and copyright, general rules, and other contractual topics. The findings could be exploited to develop a proper BIM contract framework in compliance with construction rules and conditions.
Barriers to the Effective Integration of Developed ICT for SMEs in Rural NIGERIA
Authors: Sadiq Olusegun , Hack-Polay Dieu , Fuller Ted , Rahman Mahfuzur
Published: November 2022

This study investigated three key factors (technological-related, organisational-related and environmental-related barriers) affecting the adaptation to or integration of developed ICT. It also examined how SMEs in less developed countries can explore the different stages of developed ICT by moving from one stage to the other. The integration of ICT in SMEs is important as technologies have become competitive tools in contemporary business practices. This study is based on a survey of 322 Nigerian SMEs which was successfully validated using the SmartPLS3 software. The quantitative analysis centred on the three hypothesised barriers to measure the extent to which SMEs’ internal and external variables could limit their competitiveness in relation to business expansion and organisational growth. The analysis helped explain some of the critical challenges faced by rural SMEs in an emerging economy such as Nigeria despite the literature’s previous emphasis on the impacts of ICT on the SMEs’ growth and expansion. A major contribution of the study is the development of a distinct model to help SMEs identify the significance of developed ICT and propose a strategy for SMEs to navigate the stages of developed ICT.
Minimising the Toxicities of First Line Hodgkin Lymphoma Treatment in the Modern Era
Authors: Follows Annabel M. , Santarsieri Anna
Published: November 2022

Striking advances in the treatment of Hodgkin lymphoma over the last 30 years have culminated in high rates of disease-free survival in younger patients with early and advanced stage disease. In this review we focus on strategies that have evolved over recent years to reduce short and long-term toxicities of treatment. These strategies include the selection of first-line chemotherapy, the stratification of patients based on initial response and subsequent adaptation of treatment, the addition of novel agents (e.g., brentuximab vedotin), the removal of specific drugs (e.g., bleomycin), the use of drug substitution, and the removal of consolidation radiotherapy based on interim and end of treatment PET assessment. While these strategies have successfully reduced toxicity of Hodgkin lymphoma therapy, the cornerstone of treatment continues to be combination chemotherapy and radiotherapy with significant short- and long-term side effects. To further reduce toxicity while maintaining or improving efficacy, we shall need to incorporate novel agents into our first-line treatment algorithms, and several such potentially practice-changing trials are underway.
The Validity of Surrogate Endpoints in Sub Groups of Metastatic Colorectal Cancer Patients Defined by Treatment Class and KRAS Status
Authors: Poad Heather , Khan Sam , Wheaton Lorna , Thomas Anne , Sweeting Michael , Bujkiewicz Sylwia
Published: November 2022

Background and Aim: Findings from the literature suggest that the validity of surrogate endpoints in metastatic colorectal cancer (mCRC) may depend on a treatments’ mechanism of action. We explore this and the impact of Kirsten rat sarcoma (KRAS) status on surrogacy patterns in mCRC. Methods: A systematic review was undertaken to identify randomized controlled trials (RCTs) for pharmacological therapies in mCRC. Bayesian meta-analytic methods for surrogate endpoint evaluation were used to evaluate surrogate relationships across all RCTs, by KRAS status and treatment class. Surrogate endpoints explored were progression free survival (PFS) as a surrogate endpoint for overall survival (OS), and tumour response (TR) as a surrogate for PFS and OS. Results: 66 RCTs were identified from the systematic review. PFS showed a strong surrogate relationship with OS across all data and in subgroups by KRAS status. The relationship appeared stronger within individual treatment classes compared to the overall analysis. The TR-PFS and TR-OS relationships were found to be weak overall but stronger within the Epidermal Growth Factor Receptor + Chemotherapy (EGFR + Chemo) treatment class; both overall and in the wild type (WT) patients for TR-PFS, but not in patients with the mutant (MT) KRAS status where data were limited. Conclusions: PFS appeared to be a good surrogate endpoint for OS. TR showed a moderate surrogate relationship with PFS and OS for the EGFR + Chemo treatment class. There was some evidence of impact of the mechanism of action on the strength of the surrogacy patterns in mCRC, but little evidence of the impact of KRAS status on the validity of surrogate endpoints.
Ni and Ce Grafted Ordered Mesoporous Silica KIT-6 for CO2 Adsorption
Authors: Suba Mariana , Popa Alexandru , Verdeș Orsina , Borcănescu Silvana , Barvinschi Paul
Published: November 2022

In this study, the Ni/KIT-6 and Ce/KIT-6 materials were prepared through the impregnation method and then amino-functionalized materials were obtained by the grafting of an amino-silane coupling agent 3-aminopropyl triethoxysilane (APTES). The samples were characterized by thermogravimetric analysis (TGA-DTA), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscopy (SEM) and nitrogen adsorption at 77 K. The study of CO2 adsorption–desorption on prepared materials was investigated using thermogravimetric analysis (TGA-DTA) coupled with mass spectrometry (MS). The influence of metal oxides on the performance of CO2 adsorption on functionalized mesoporous silica was presented. The results showed that doping the molecular sieve with cerium oxide can significantly increase the adsorption capacity of the amino-functionalized KIT-6. As the CO2 adsorbents were prepared by functionalization through grafting with APTES, the amount of amine loading is one of the important factors which improves CO2 adsorption capacity. Additionally, CO2 adsorption performance depends on the textural properties and the temperature used for the adsorption process. The maximum adsorption capacity of Ce/KIT-6 Sil is 3.66 mmol/g, which is 2.4 times higher than Ni/KIT-6 Sil. After the nine cycles of cyclic CO2 adsorption/desorption, the Ce/KIT-6 Sil still had higher adsorption capacities, indicating their good cyclical stability.