bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of New Markers of Alcohol-Derived DNA Damage in Humans
Authors: Guidolin Valeria , Carlson Erik S. , Carrà Andrea , Villalta Peter W. , Maertens Laura A. , Hecht Stephen S. , Balbo Silvia
Published: February 2021

Alcohol consumption is a risk factor for the development of several cancers, including those of the head and neck and the esophagus. The underlying mechanisms of alcohol-induced carcinogenesis remain unclear; however, at these sites, alcohol-derived acetaldehyde seems to play a major role. By reacting with DNA, acetaldehyde generates covalent modifications (adducts) that can lead to mutations. Previous studies have shown a dose dependence between levels of a major acetaldehyde-derived DNA adduct and alcohol exposure in oral-cell DNA. The goal of this study was to optimize a mass spectrometry (MS)-based DNA adductomic approach to screen for all acetaldehyde-derived DNA adducts to more comprehensively characterize the genotoxic effects of acetaldehyde in humans. A high-resolution/-accurate-mass data-dependent constant-neutral-loss-MS3 methodology was developed to profile acetaldehyde-DNA adducts in purified DNA. This resulted in the identification of 22 DNA adducts. In addition to the expected N2-ethyldeoxyguanosine (after NaBH3CN reduction), two previously unreported adducts showed prominent signals in the mass spectra. MSn fragmentation spectra and accurate mass were used to hypothesize the structure of the two new adducts, which were then identified as N6-ethyldeoxyadenosine and N4-ethyldeoxycytidine by comparison with synthesized standards. These adducts were quantified in DNA isolated from oral cells collected from volunteers exposed to alcohol, revealing a significant increase after the exposure. In addition, 17 of the adducts identified in vitro were detected in these samples confirming our ability to more comprehensively characterize the DNA damage deriving from alcohol exposures.
Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles Containing Hybrid Insulin Peptides
Authors: DiLisio James E. , Haskins Kathryn
Published: February 2021

Autoreactive T cells are thought to orchestrate the onset and progression of autoimmune diabetes. Key cognate antigens of these diabetogenic T cells include hybrid insulin peptides, formed by the fusion of insulin fragments to cleavage products of other β-cell granule proteins. Here we review initial work exploring tolerance induction to a hybrid insulin peptide using a biodegradable, nanoparticle delivery system in non-obese diabetic (NOD) mice. The immune phenotype(s) and possible mechanism(s) behind antigen-specific tolerance induction were dissected with a disease transfer model using transgenic autoreactive mouse T cells. Treatment of NOD mice with peptide-coupled nanoparticles appeared to have a dual function in preventing diabetes onset, inducing anergy in effector T cells and enhancing the activity of regulatory T cells. Importantly, the ratio of these two cell types in the pancreas was pushed toward tolerance. Antigen-specific tolerance induction to hybrid insulin peptides has the translational potential to preserve islet β-cells in new-onset or at-risk patients and prevent recurrent autoimmunity in transplant patients.
Noninvasive Monitoring of Glucose Using Near-Infrared Reflection Spectroscopy of Skin—Constraints and Effective Novel Strategy in Multivariate Calibration
Authors: Heise H. Michael , Delbeck Sven , Marbach Ralf
Published: February 2021

For many years, successful noninvasive blood glucose monitoring assays have been announced, among which near-infrared (NIR) spectroscopy of skin is a promising analytical method. Owing to the tiny absorption bands of the glucose buried among a dominating variable spectral background, multivariate calibration is required to achieve applicability for blood glucose self-monitoring. The most useful spectral range with important analyte fingerprint signatures is the NIR spectral interval containing combination and overtone vibration band regions. A strategy called science-based calibration (SBC) has been developed that relies on a priori information of the glucose signal (“response spectrum”) and the spectral noise, i.e., estimates of the variance of a sample population with negligible glucose dynamics. For the SBC method using transcutaneous reflection skin spectra, the response spectrum requires scaling due to the wavelength-dependent photon penetration depth, as obtained by Monte Carlo simulations of photon migration based on estimates of optical tissue constants. Results for tissue glucose concentrations are presented using lip NIR-spectra of a type-1 diabetic subject recorded under modified oral glucose tolerance test (OGTT) conditions. The results from the SBC method are extremely promising, as statistical calibrations show limitations under the conditions of ill-posed equation systems as experienced for tissue measurements. The temporal profile differences between the glucose concentration in blood and skin tissue were discussed in detail but needed to be further evaluated.
Prediction of Aphasia Severity in Patients with Stroke Using Diffusion Tensor Imaging
Authors: Lee Jin-Kook , Ko Myoung-Hwan , Park Sung-Hee , Kim Gi-Wook
Published: February 2021

This study classified the severity of aphasia through the Western Aphasia Battery and determined the optimal cut-off value for each Language-Related White Matter fiber and their combinations, we further examined the correlations between Language-Related White Matter and Western Aphasia Battery subscores. This retrospective study recruited 64 patients with aphasia. Mild/moderate and severe aphasia were classified according to cut-off Aphasia Quotient score of 51 points. Diffusion tensor imaging and fractional anisotropy reconstructed Language-Related White Matter in multiple fasciculi. We determined the area under the covariate-adjusted receiver operating characteristic curve to evaluate the accuracy of predicting aphasia severity. The optimal fractional-anisotropy cut-off values for the individual fibers of the Language-Related White Matter and their combinations were determined. Their correlations with Western Aphasia Battery subscores were analyzed. The arcuate and superior longitudinal fasciculi showed fair accuracy, the inferior frontal occipital fasciculus poor accuracy, and their combinations fair accuracy. Correlations between Language-Related White Matter parameters and Western Aphasia Battery subscores were found between the arcuate, superior longitudinal, and inferior frontal occipital fasciculi and spontaneous speech, auditory verbal comprehension, repetition, and naming. Diffusion-tensor-imaging-based language-Related White Matter analysis may help predict the severity of language impairment in patients with aphasia following stroke.
Type and Gene Location of KIT Mutations Predict Progression-Free Survival to First-Line Imatinib in Gastrointestinal Stromal Tumors: A Look into the Exon
Authors: Incorvaia Lorena , Fanale Daniele , Vincenzi Bruno , De Luca Ida , Bartolotta Tommaso Vincenzo , Cannella Roberto , Pantuso Gianni , Cabibi Daniela , Russo Antonio , Bazan Viviana , Badalamenti Giuseppe
Published: February 2021

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and investigated the predictive role of type and gene location of the KIT exon 11 mutations in metastatic patients treated with first-line imatinib. Our data showed a predictive impact of KIT exon 11 pathogenic variant on PFS to imatinib treatment: patients with deletion or insertion/deletion (delins) in 557/558 codons had a shorter PFS (median PFS: 24 months) compared to the patients with a deletion in other codons, or duplication/insertion/SNV (median PFS: 43 and 49 months, respectively) (p < 0.001). These results reached an independent value in the multivariate model, which showed that the absence of exon 11 deletions or delins 557/558, the female gender, primitive tumor diameter (≤5 cm) and polymorphonuclear leucocytosis (>7.5 109/L) were significant prognostic factors for longer PFS. Analysis of the predictive role of PDGFRA PVs showed no significant results. Our results also confirm the aggressive biology of 557/558 deletions/delins in the metastatic setting and allow for prediction at the baseline which GIST patients would develop resistance to first-line imatinib treatment earlier.
Down-Conversion Polymer Composite Coatings with Multipeak Absorption and Emission
Authors: Fang Jun , Liu Wenting , Zhou Wenying , Zhu Cheng , Ni Yaru , Fang Liang , Lu Chunhua
Published: February 2021

Spectral adjustment is an effective method to increase light conversion efficiency of solar cells and to promote the growth of plants. Down-converter (DC) materials are considered to be one of the most effective methods of spectral modification. The focus of this work was to expand the spectral response range of down-conversion layers to achieve multipeak absorption and emission. Sr2CaMoO6:Sm,Na and YVO4:Bi,Eu, which have different excitation peaks in the UV-blue region and varied emission peaks in visible light regions, were prepared in this work. Sr2CaMoO6:Sm,Na can effectively produce red light at 648 nm upon excitation at 408 nm, while YVO4:Bi,Eu can produce red light at 618 nm upon excitation at 365 nm. Polymeric luminescent coatings with one single kind of phosphor were prepared separately before the two phosphors were mixed together in uniform polymer coatings. The two phosphors were also assembled in bilayer coatings with different concentrations. The results showed that high transmittances over 90% were achieved for the two composite coatings with the thickness of 20 and 30 μm. The increase in particle loadings from 1‰ to 4‰ slightly decreased coating transmittance but increased luminescence intensity. The increase in the ratio of Sr2CaMoO6:Sm,Na and YVO4:Bi,Eu from 5/1 to 10/1 resulted in high transmittance of the DC coatings, independent of total filler loadings (3‰ and 4‰) and coating thickness. The relative intensities of emission peaks can be adjusted conveniently by changing filler ratios. In addition, the transmittance and luminescent intensities of the coatings where the two phosphors were assembled in two layers were close to the uniform coatings, suggesting the negligible effect of UV light irradiation order. This work proved that the prepared coatings presented multipeak absorption and emission upon UV light excitation. These coatings can be expected to be applied in fields such as solar cells and agriculture greenhouses.
Experimental Study on Effective Chloride Diffusion Coefficient of Cement Mortar by Different Electrical Accelerated Measurements
Authors: Chen Jianlan , Wang Jiandong , He Rui , Shu Huaizhu , Fu Chuanqing
Published: February 2021

This study investigated the effective chloride diffusion coefficient of cement mortar with different water-to-cement ratio (w/c) under electrical accelerated migration measurement. The cumulative chloride concentration in anode cell solution and the cumulative chloride concentration drop in the cathode cell solution was measured by RCT measurement and the results were further used to calculate the chloride diffusion coefficient by Nordtest Build 355 method and Truc method. The influence of w/c on cement mortar’s chloride coefficient was investigated and the chloride diffusion coefficient under different determination methods were compared with other researchers’ work, a good consistency between this work’s results and literatures’ results was obtained. The results indicated that the increased w/c of cement mortar samples will have a higher chloride diffusion coefficient. The cumulative chloride concentration drop in the cathode cell solution will have deviation in early stage measurement (before 60 h) which will result in overestimation of the effective chloride diffusion coefficient.
Unidimensional Two-Way Continuous-Variable Quantum Key Distribution Using Coherent States
Authors: Bian Yiming , Huang Luyu , Zhang Yichen
Published: February 2021

We propose a unidimensional two-way continuous-variable quantum key distribution protocol with coherent states, where the sender modulates a single quadrature of the coherent states rather than both quadratures to simplify the structure of a two-way system. Security analysis is performed with a general attack strategy, known as two-mode attack, which helps to reduce limitations in the analysis. The performance of the protocol under all accessible two-mode attacks at fixed distance is illustrated. Further, two typical two-mode attack strategies are obtained from it, which are one-mode attack strategy and optimal two-mode attack strategy. Between them, the one-mode attack is the simplest form of the two-mode attack, while the optimal two-mode attack is the most complicated one. Simulations show that though the system is simplified, the performance of the two-way protocol with unidimensional modulation is still comparable to that of the counterpart with Gaussian modulation even against the optimal two-mode attack when Eve’s ability is maximized. Thus, the proposed protocol simplifies the two-way system while guaranteeing its performance to a certain extent. Especially in a practical system with short transmission distance and high excess noise, the protocol has a good application prospect.
Reliability Analysis and Repair Activity for the Components of 350 kW Inverters in a Large Scale Grid-Connected Photovoltaic System
Authors: Spertino Filippo , Amato Angela , Casali Gabriele , Ciocia Alessandro , Malgaroli Gabriele
Published: February 2021

The reliability of photovoltaic (PV) generators is strongly affected by the performance of Direct Current/Alternating Current (DC/AC) converters, being the major source of PV underperformance. However, generally, their reliability is not investigated at component level: thus, the present work presents a reliability analysis and the repair activity for the components of full bridge DC/AC converters. In the first part of the paper, a reliability analysis using failure rates from literature is carried out for 132 inverters (AC rated power of 350 kW each) with global AC power of 46 MW in a large scale grid-connected PV plant. Then, in the second part of the work, results from literature are compared with data obtained by analyzing industrial maintenance reports in the years 2015–2017. In conclusion, the yearly energy losses involved in the downtime are quantified, as well as their availability.
CellS: A Cell-Inspired Efficient Software Framework for AI-Enabled Application on Resources-Constrained Mobile System
Authors: Chen Ching-Han , Wu Mu-Che
Published: February 2021

Today’s mobile processors generally have multiple cores and sufficient hardware resources to support AI-enabled software operation. However, very few AI applications make full use of the computing performance of mobile multiprocessors. This is because the typical software development is sequential, and the degree of parallelism of the program is very low. In the increasingly complex AI-driven and software development projects with natural human–computer interaction, this will undoubtedly cause a waste of mobile computing resources that are originally limited. This paper proposes an intelligent system software framework, CellS, to improve smart software development on multicore mobile processor systems. This software framework mimics the cell system. In this framework, each cell can autonomously aware changes in the environment (input) and reaction (output) and may change the behavior of other cells. Smart software can be regarded as a large number of cells interacting with each other. Software developed based on the CellS framework has a high degree of scalability and flexibility and can more fully use multicore computing resources to achieve higher computing efficiency.
The Role of the Reanalysis of Genetic Test Results in the Diagnosis of Dysmorphic Syndrome Caused by Inherited Xq24 Deletion including the UBE2A and CXorf56 Genes
Authors: Wolańska Ewelina , Pollak Agnieszka , Rydzanicz Małgorzata , Pesz Karolina , Kłaniewska Magdalena , Rozensztrauch Anna , Skiba Paweł , Stawiński Piotr , Płoski Rafał , Śmigiel Robert
Published: February 2021

Psychomotor delay, hypotonia, and intellectual disability, as well as heart defects, urogenital malformations, and characteristic cranio-facial dysmorphism are the main symptoms of dysmorphic syndrome associated with intergenic deletion in the Xq24 chromosome region including the UBE2A and CXorf56 genes. To date, there is limited information in the literature about the symptoms and clinical course of the Xq24 deletion. Here, we present a case of Xq24 deletion including the UBE2A and CXorf56 genes in a nine-year-old boy, in whom the array comparative genomic hybridization (array-CGH) and whole exome sequencing (WES) tests were performed in 2015 with normal results. The WES results were reanalyzed in 2019. Intergenic, hemizygous deletion in the Xq24 chromosome region including the UBE2A and CXorf56 genes was revealed and subsequently confirmed in the array-CGH study as the deletion of 35kb in the Xq24 region. Additionally, the carriership of deletion in the mother of the child was confirmed.
Changes of Gambling Patterns during COVID-19 in Sweden, and Potential for Preventive Policy Changes. A Second Look Nine Months into the Pandemic
Authors: Håkansson Anders , Widinghoff Carolina
Published: February 2021

Gambling has been suggested as one of the potential mental health consequences of the COVID-19 pandemic. In earlier self-report studies, increased gambling has been reported by a limited proportion of respondents characterized with a high degree of problem gambling. The present study, carried out with the same methodology and in the same geographical setting, around seven months later in the pandemic, aimed to repeat and to extend the understanding of potential gambling changes in the population during COVID-19. An anonymous sample of web panel members was assessed, altogether 2029 individuals (52% women, 10% moderate-risk or problem gamblers). Results indicated that 6% reported increased gambling, and 4% reported decreased gambling during the pandemic. Having increased gambling was associated with more severe gambling problems (OR 2.78, 95% confidence interval 2.27–3.40), increased alcohol consumption (OR 2.92, 1.71–4.98), and psychological distress (OR 3.38, 1.83–6.23). In the group reporting increased gambling during COVID-19, moderate-risk/problem gambling was very common (62%). Recent governmental policy interventions in the area were known to a minority (30%) of respondents, but awareness of the regulations was markedly more common in individuals with at least moderate-risk gambling (56%) and in self-excluders (78%). Reporting of any perceived influence from policy changes was low (3%), and divided between those reporting an increasing and decreasing effect, respectively. Increased gambling may be a consequence of COVID-19-related changes in everyday lives of individuals with problematic gambling patterns. Thus, a vulnerable group demonstrates higher rates of gambling migration and psychosocial problems, and may require particular attention in screening and treatment contexts, and further scientific evaluations.
Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults
Authors: Hsieh Sun-Wung , Wu Da-Wei , Wang Chih-Wen , Chen Szu-Chia , Hung Chih-Hsing , Kuo Chao-Hung
Published: February 2021

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.
Structure of Bacterial Community with Resistance to Antibiotics in Aquatic Environments. A Systematic Review
Authors: Sánchez-Baena Ana María , Caicedo-Bejarano Luz Dary , Chávez-Vivas Mónica
Published: February 2021

Aquatic environments have been affected by the increase in bacterial resistant to antibiotics. The aim of this review is to describe the studies carried out in relation to the bacterial population structure and antibiotic resistance genes in natural and artificial water systems. We performed a systematic review based on the PRISMA guideline (preferred reporting items for systematic reviews and meta-analyzes). Articles were collected from scientific databases between January 2010 and December 2020. Sixty-eight papers meeting the inclusion criteria, i.e., “reporting the water bacterial community composition”, “resistance to antibiotics”, and “antibiotic resistance genes (ARG)”, were evaluated according to pre-defined validity criteria. The results indicate that the predominant phyla were Firmicutes and Bacteroidetes in natural and artificial water systems. Gram-negative bacteria of the family Enterobacteraceae with resistance to antibiotics are commonly reported in drinking water and in natural water systems. The ARGs mainly reported were those that confer resistance to β-lactam antibiotics, aminoglycosides, fluoroquinolones, macrolides and tetracycline. The high influence of anthropogenic activity in the environment is evidenced. The antibiotic resistance genes that are mainly reported in the urban areas of the world are those that confer resistance to the antibiotics that are most used in clinical practice, which constitutes a problem for human and animal health.
Superior Osteo-Inductive and Osteo-Conductive Properties of Trabecular Titanium vs. PEEK Scaffolds on Human Mesenchymal Stem Cells: A Proof of Concept for the Use of Fusion Cages
Authors: Ragni Enrico , Perucca Orfei Carlotta , Bidossi Alessandro , De Vecchi Elena , Francaviglia Natale , Romano Alberto , Maestretti Gianluca , Tartara Fulvio , de Girolamo Laura
Published: February 2021

Fusion cages composed of titanium and its alloys are emerging as valuable alternative to standard polyetheretherketone (PEEK) ones routinely used in cervical and lumbar spine surgery. Aim of this study was to evaluate osteo-inductive and osteo-conductive ability of an innovative trabecular titanium (T-Ti) scaffold on human mesenchymal stem cells (hMSCs), in both absence and presence of biochemical osteogenic stimuli. Same abilities were assessed on PEEK and standard 2D plastic surface, the latter meant as gold-standard for in vitro differentiation studies. hMSCs adhered and colonized both T-Ti and PEEK scaffolds. In absence of osteogenic factors, T-Ti triggered osteogenic induction of MSCs, as demonstrated by alkaline phosphatase activity and calcium deposition increments, while PEEK and standard 2D did not. Addition of osteogenic stimuli reinforced osteogenic differentiation of hMSCs cultured on T-Ti in a significantly higher manner with respect to standard 2D plastic culture surfaces, whereas PEEK almost completely abolished the process. T-Ti driven differentiation towards osteoblasts was confirmed by gene and marker expression analyses, even in absence of osteogenic stimuli. These results clearly indicate superior in vitro osteo-inductive and osteo-conductive capacity of T-Ti compared to PEEK, and make ground for further studies supporting the use of T-Ti cages to improve bone fusion.
Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation
Authors: Song Hui-Yung , Yang Yi-Ping , Chien Yueh , Lai Wei-Yi , Lin Yi-Ying , Chou Shih-Jie , Wang Mong-Lien , Wang Chien-Ying , Leu Hsin-Bang , Yu Wen-Chung , Chien Chian-Shiu
Published: February 2021

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications.
Genetic Architecture Underlying the Metabolites of Chlorogenic Acid Biosynthesis in Populus tomentosa
Authors: Yao Liangchen , Li Peng , Du Qingzhang , Quan Mingyang , Li Lianzheng , Xiao Liang , Song Fangyuan , Lu Wenjie , Fang Yuanyuan , Zhang Deqiang
Published: February 2021

Chlorogenic acid (CGA) plays a crucial role in defense response, immune regulation, and the response to abiotic stress in plants. However, the genetic regulatory network of CGA biosynthesis pathways in perennial plants remains unclear. Here, we investigated the genetic architecture for CGA biosynthesis using a metabolite-based genome-wide association study (mGWAS) and expression quantitative trait nucleotide (eQTN) mapping in a population of 300 accessions of Populus tomentosa. In total, we investigated 204 SNPs which were significantly associated with 11 metabolic traits, corresponding to 206 genes, and were mainly involved in metabolism and cell growth processes of P. tomentosa. We identified 874 eQTNs representing 1066 genes, in which the expression and interaction of causal genes affected phenotypic variation. Of these, 102 genes showed significant signatures of selection in three geographical populations, which provided insights into the adaptation of CGA biosynthesis to the local environment. Finally, we constructed a genetic network of six causal genes that coordinately regulate CGA biosynthesis, revealing the multiple regulatory patterns affecting CGA accumulation in P. tomentosa. Our study provides a multiomics strategy for understanding the genetic basis underlying the natural variation in the CGA biosynthetic metabolites of Populus, which will enhance the genetic development of abiotic-resistance varieties in forest trees.
Comparison of Decellularization Protocols to Generate Peripheral Nerve Grafts: A Study on Rat Sciatic Nerves
Authors: El Soury Marwa , García-García Óscar Darío , Moretti Matteo , Perroteau Isabelle , Raimondo Stefania , Lovati Arianna Barbara , Carriel Víctor
Published: February 2021

In critical nerve gap repair, decellularized nerve allografts are considered a promising tissue engineering strategy that can provide superior regeneration results compared to nerve conduits. Decellularized nerves offer a well-conserved extracellular matrix component that has proven to play an important role in supporting axonal guiding and peripheral nerve regeneration. Up to now, the known decellularized techniques are time and effort consuming. The present study, performed on rat sciatic nerves, aims at investigating a novel nerve decellularization protocol able to combine an effective decellularization in short time with a good preservation of the extracellular matrix component. To do this, a decellularization protocol proven to be efficient for tendons (DN-P1) was compared with a decellularization protocol specifically developed for nerves (DN-P2). The outcomes of both the decellularization protocols were assessed by a series of in vitro evaluations, including qualitative and quantitative histological and immunohistochemical analyses, DNA quantification, SEM and TEM ultrastructural analyses, mechanical testing, and viability assay. The overall results showed that DN-P1 could provide promising results if tested in vivo, as the in vitro characterization demonstrated that DN-P1 conserved a better ultrastructure and ECM components compared to DN-P2. Most importantly, DN-P1 was shown to be highly biocompatible, supporting a greater number of viable metabolically active cells.
Quantitative Proteomics Reveals Changes Induced by TIMP-3 on Cell Membrane Composition and Novel Metalloprotease Substrates
Authors: Carreca Anna Paola , Pravatà Veronica Maria , D’Apolito Danilo , Bonelli Simone , Calligaris Matteo , Monaca Elisa , Müller Stephan A. , Lichtenthaler Stefan F. , Scilabra Simone Dario
Published: February 2021

Ectodomain shedding is a key mechanism of several biological processes, including cell-communication. Disintegrin and metalloproteinases (ADAMs), together with the membrane-type matrix metalloproteinases, play a pivotal role in shedding transmembrane proteins. Aberrant shedding is associated to several pathological conditions, including arthritis. Tissue inhibitor of metalloproteases 3 (TIMP-3), an endogenous inhibitor of ADAMs and matrix metalloproteases (MMPs), has been proven to be beneficial in such diseases. Thus, strategies to increase TIMP-3 bioavailability in the tissue have been sought for development of therapeutics. Nevertheless, high levels of TIMP-3 may lead to mechanism-based side-effects, as its overall effects on cell behavior are still unknown. In this study, we used a high-resolution mass-spectrometry-based workflow to analyze alterations induced by sustained expression of TIMP-3 in the cell surfaceome. In agreement with its multifunctional properties, TIMP-3 induced changes on the protein composition of the cell surface. We found that TIMP-3 had differential effects on metalloproteinase substrates, with several that accumulated in TIMP-3-overexpressing cells. In addition, our study identified potentially novel ADAM substrates, including ADAM15, whose levels at the cell surface are regulated by the inhibitor. In conclusion, our study reveals that high levels of TIMP-3 induce modifications in the cell surfaceome and identifies molecular pathways that can be deregulated via TIMP-3-based therapies.
Effects of Omega-3 Polyunsaturated Fatty Acids and Their Metabolites on Haemostasis—Current Perspectives in Cardiovascular Disease
Authors: Golanski Jacek , Szymanska Patrycja , Rozalski Marcin
Published: February 2021

The beneficial effects of long-chain polyunsaturated omega-3 fatty acids (omega-3 PUFAs) in cardioprotection are widely known and generally accepted. In this literature review, we have focused on the known and postulated mechanisms of action of omega-3 PUFAs and their metabolites on various components of the haemostatic system, in particular on blood platelets and endothelium. We have also made an attempt to provide a comprehensive review of epidemiological studies with particular regard to clinical trials. Notably, the results of these studies are contradictory, and some of them failed to report the beneficial effects of taking or supplementing omega-3 PUFAs in the diet. A potential explanation, in our opinion, could be the need to use higher doses of omega-3 PUFAs and a proper ratio of omega-3 and omega-6 PUFAs. An additional problem which is difficult to solve is the use of a proper neutral placebo for interventional studies. Despite some controversies regarding the beneficial effects of supplementation of omega-3 PUFAs in cardiovascular disease, our review suggests that a promising aspect of future studies and applications is to focus on the anti-thrombotic properties of these compounds. An argument supporting this assumption is the recent use of omega-3 PUFAs as a supporting tool for the treatment of COVID-19 complications.
The Functional Role of Loops and Flanking Sequences of G-Quadruplex Aptamer to the Hemagglutinin of Influenza a Virus
Authors: Bizyaeva Anastasia A. , Bunin Dmitry A. , Moiseenko Valeria L. , Gambaryan Alexandra S. , Balk Sonja , Tashlitsky Vadim N. , Arutyunyan Alexander M. , Kopylov Alexey M. , Zavyalova Elena G.
Published: February 2021

Nucleic acid aptamers are generally accepted as promising elements for the specific and high-affinity binding of various biomolecules. It has been shown for a number of aptamers that the complexes with several related proteins may possess a similar affinity. An outstanding example is the G-quadruplex DNA aptamer RHA0385, which binds to the hemagglutinins of various influenza A virus strains. These hemagglutinins have homologous tertiary structures but moderate-to-low amino acid sequence identities. Here, the experiment was inverted, targeting the same protein using a set of related, parallel G-quadruplexes. The 5′- and 3′-flanking sequences of RHA0385 were truncated to yield parallel G-quadruplex with three propeller loops that were 7, 1, and 1 nucleotides in length. Next, a set of minimal, parallel G-quadruplexes with three single-nucleotide loops was tested. These G-quadruplexes were characterized both structurally and functionally. All parallel G-quadruplexes had affinities for both recombinant hemagglutinin and influenza virions. In summary, the parallel G-quadruplex represents a minimal core structure with functional activity that binds influenza A hemagglutinin. The flanking sequences and loops represent additional features that can be used to modulate the affinity. Thus, the RHA0385–hemagglutinin complex serves as an excellent example of the hypothesis of a core structure that is decorated with additional recognizing elements capable of improving the binding properties of the aptamer.
Relative Contribution of Citizen Science, Museum Data and Publications in Delineating the Distribution of the Stag Beetle in Spain
Authors: Méndez Marcos , Cortés-Fossati Fernando
Published: February 2021

Reliable distribution maps are in the basis of insect conservation, but detailed chorological information is lacking for many insects of conservation concern (the Wallacean shortfall). Museum collections, entomological publications and citizen science projects can contribute to solve this Wallacean shortfall. Their relative contribution to the knowledge on the distribution of threatened insects has been scarcely explored, but it is important given that each of these three sources of information has its own biases and costs. Here we explore the contribution of museum data, entomological publications and citizen science in delineating the distribution of the European stag beetle in Spain. Citizen science contributed the highest number of records and grid cells occupied, as well as the highest number of grid cells not contributed by any other information source (unique grid cells). Nevertheless, both museum data and publications contributed almost 25% of all unique grid cells. Furthermore, the relative contribution of each source of information differed in importance among Spanish provinces. Given the pros and cons of museum data, publications and citizen science, we advise their combined use in cases, such as the European stag beetle in Spain, in which a broad, heterogeneous, sparsely populated territory has to be prospected.
Conservation Education: Are Zoo Animals Effective Ambassadors and Is There Any Cost to Their Welfare?
Authors: Spooner Sarah L. , Farnworth Mark J. , Ward Samantha J. , Whitehouse-Tedd Katherine M.
Published: February 2021

Animal ambassador encounters (AAE), where visitors come into close-contact with animals, are popular in zoos and are advocated as promoting connection to wild species. However, educational and animal-welfare implications are relatively unknown. We conducted a systematic literature review (PRISMA) to investigate visitor and animal outcomes of AAE. We identified 19 peer reviewed articles and 13 other records focused on AAEs. Although we found net positive or neutral impacts overall, several studies indicated that high-intensity visitor contact and long-term exposure may be detrimental to animal welfare. Most studies lacked rigour and claims were based on an absence of negative impacts rather than evidence of benefits. Multiple publications were derived from the same datasets and there were no standardised measures for either welfare or education impacts. Of the peer-reviewed articles, just two considered both education and welfare. Education studies often used perceived learning or only post-experience testing. Welfare studies used small samples (median n = 4; range 1–59), and limited measures of welfare. In order to justify the continued use of AAEs in modern zoos, animal welfare costs must be proven to be minimal whilst having demonstrable and substantial visitor educational value. Large-scale, standardised impact assessments of both education and welfare impacts are needed.
Comparative Analysis of Slip Resistance Test Methods for Granite Floors
Authors: Sudoł Ewa , Szewczak Ewa , Małek Marcin
Published: February 2021

This paper attempts to compare three methods of testing floor slip resistance and the resulting classifications. Polished, flamed, brushed, and grained granite slabs were tested. The acceptance angle values (αob) obtained through the shod ramp test, slip resistance value (SRV), and sliding friction coefficient (μ) were compared in terms of the correlation between the series, the precision of each method, and the classification results assigned to each of the three obtained indices. It was found that the evaluation of a product for slip resistance was strongly related to the test method used and the resulting classification method. This influence was particularly pronounced for low roughness slabs. This would result in risks associated with inadequate assessments, which could affect the safe use of buildings facilities.
Utilization of Solid Waste from Brick Industry and Hydrated Lime in Self-Compacting Cement Pastes
Authors: Shah Mati Ullah , Usman Muhammad , Hanif Muhammad Usman , Naseem Iqra , Farooq Sara
Published: February 2021

The huge amount of solid waste from the brick manufacturing industry can be used as a cement replacement. However, replacement exceeding 10% causes a reduction in strength due to the slowing of the pozzolanic reaction. Therefore, in this study, the pozzolanic potential of brick waste is enhanced using ultrafine brick powder with hydrated lime (HL). A total of six self-compacting paste mixes were studied. HL 2.5% by weight of binder was added in two formulations: 10% and 20% of waste burnt brick powder (WBBP), to activate the pozzolanic reaction. An increase in the water demand and setting time was observed by increasing the replacement percentage of WBBP. It was found that the mechanical properties of mixes containing 5% and 10% WBBP performed better than the control mix, while the mechanical properties of the mixes containing 20% WBBP were found to be almost equal to the control mix at 90 days. The addition of HL enhanced the early-age strength. Furthermore, WBBP formulations endorsed improvements in both durability and rheological properties, complemented by reduced early-age shrinkage. Overall, it was found that brick waste in ultrafine size has a very high degree of pozzolanic potential and can be effectively utilized as a supplementary cementitious material.
Titania-Containing Bone Cement Shows Excellent Osteoconductivity in A Synovial Fluid Environment and Bone-Bonding Strength in Osteoporosis
Authors: Kawata Tomotoshi , Goto Koji , Imamura Masashi , Okuzu Yaichiro , Kawai Toshiyuki , Kuroda Yutaka , Matsuda Shuichi
Published: February 2021

Titania bone cement (TBC) reportedly has excellent in vivo bioactivity, yet its osteoconductivity in synovial fluid environments and bone-bonding ability in osteoporosis have not previously been investigated. We aimed to compare the osteoconductivity of two types of cement in a synovial fluid environment and determine their bone-bonding ability in osteoporosis. We implanted TBC and commercial polymethylmethacrylate bone cement (PBC) into rabbit femoral condyles and exposed them to synovial fluid pressure. Rabbits were then euthanized at 6, 12, and 26 weeks, and affinity indices were measured to evaluate osteoconductivity. We generated a rabbit model of osteoporosis through bilateral ovariectomy (OVX) and an 8-week treatment with methylprednisolone sodium succinate (PSL). Pre-hardened TBC and PBC were implanted into the femoral diaphysis of the rabbits in the sham control and OVX + PSL groups. Affinity indices were significantly higher for TBC than for PBC at 12 weeks (40.9 ± 16.8% versus 24.5 ± 9.02%) and 26 weeks (40.2 ± 12.7% versus 21.2 ± 14.2%). The interfacial shear strength was significantly higher for TBC than for PBC at 6 weeks (3.69 ± 1.89 N/mm2 versus 1.71 ± 1.23 N/mm2) in the OVX + PSL group. These results indicate that TBC is a promising bioactive bone cement for prosthesis fixation in total knee arthroplasty, especially for osteoporosis patients.
Thermoelectric and Transport Properties of Permingeatite Cu3SbSe4 Prepared Using Mechanical Alloying and Hot Pressing
Authors: Lee Go-Eun , Kim Il-Ho
Published: February 2021

Permingeatite (Cu3SbSe4) is a promising thermoelectric material because it has a narrow band gap, large carrier effective mass, and abundant and nontoxic components. Mechanical alloying (MA), which is a high-energy ball mill process, has various advantages, e.g., segregation/evaporation is not required and homogeneous powders can be prepared in a short time. In this study, the effects of MA and hot-pressing (HP) conditions on the synthesis of the Cu3SbSe4 phase and its thermoelectric properties were evaluated. The electrical conductivity decreased with increasing HP temperature, while the Seebeck coefficient increased. The power factor (PF) was 0.38–0.50 mW m−1 K−2 and the thermal conductivity was 0.76–0.78 W m−1 K−1 at 623 K. The dimensionless figure of merit, ZT, increased with increasing temperature, and a reliable and maximum ZT value of 0.39 was obtained at 623 K for Cu3SbSe4 prepared using MA at 350 rpm for 12 h and HP at 573 K for 2 h.
Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation
Authors: Khokhani Paree , Rahmani Nada R. , Kok Anne , Öner F. Cumhur , Alblas Jacqueline , Weinans Harrie , Kruyt Moyo C. , Croes Michiel
Published: February 2021

Therapeutic pathogen recognition receptor (PRR) ligands are reaching clinical practice following their ability to skew the immune response in a specific direction. We investigated the effects of various therapeutic PRR ligands on bone cell differentiation and inflammation. Following stimulation, alkaline phosphatase (ALP) activity (Day 10), osteocalcin, osteonectin expression (Day 14), and calcium deposition (Day 21) were quantified in bone marrow-derived human mesenchymal stem cells (hMSCs). The osteoclastogenic response was determined by measuring tartrate-resistant acid phosphate (TRAP) activity in human monocytes. TNF-α, IL-6, IL-8, and IL-10 expressions were measured by enzyme-linked immunosorbent assay as an indicator of the ligands’ inflammatory properties. We found that nucleic acid-based ligands Poly(I:C) and CpG ODN C increased early ALP activity in hMSCs by 4-fold without affecting osteoclast formation. These ligands did not enhance expression of the other, late osteogenic markers. MPLA, Curdlan, and Pam3CSK4 did not affect osteogenic differentiation, but inhibited TRAP activity in monocytes, which was associated with increased expression of all measured cytokines. Nucleic acid-based ligands are identified as the most promising osteo-immunomodulators, as they favor early osteogenic differentiation without inducing an exaggerated immune-cell mediated response or interfering in osteoclastogenesis and thus can be potentially harnessed for multifunctional coatings for bone biomaterials.
Experimental Study on Optimization of Phosphogypsum Suspension Decomposition Conditions under Double Catalysis
Authors: Xu Pinjing , Li Hui , Chen Yanxin
Published: February 2021

Phosphogypsum (PG) is not only a solid waste discharged from the phosphate fertilizer industry, but also a valuable resource. After high-temperature heat treatment, it can be decomposed into SO2 and CaO; the former can be used to produce sulfuric acid, and the latter can be used as building materials. In this paper, the catalytic thermal decomposition conditions of phosphogypsum were optimized, and the effects of the reaction temperature, reaction atmosphere, reaction time and carbon powder content on the decomposition of phosphogypsum were studied. The research shows that the synergistic effect of carbon powder and CO reducing atmosphere can effectively reduce the decomposition temperature of phosphogypsum. According to the results of the orthogonal test under simulated suspended laboratory conditions, the factors affecting the decomposition rate of phosphogypsum are temperature, time, atmosphere and carbon powder content in turn, and the factors affecting the desulfurization rate are time, temperature, atmosphere and carbon powder content in turn. Under laboratory conditions, the highest decomposition rate and desulfurization rate of phosphogypsum are 97.73% and 97.2%, and the corresponding reaction conditions are as follows: calcination temperature is 1180 °C, calcination time is 15 min, carbon powder content is 4%, and CO concentration is 6%. The results of thermal analysis of phosphogypsum at different temperature rising rates show that the higher the temperature rising rate, the higher the initial temperature of decomposition reaction and the temperature of maximum thermal decomposition rate, but the increase in the temperature rising rate will not reduce the decomposition rate of phosphogypsum.