bluuebunny/crossref_metadata_2025 huggingface dataset:
MPC-Based Prediction of Anti-Mutant Effectiveness of Antibiotic Combinations: In Vitro Model Study with Daptomycin and Gentamicin against Staphylococcus aureus
Authors: Golikova Maria V. , Strukova Elena N. , Portnoy Yury A. , Zinner Stephen H. , Firsov Alexander A.
Published: September 2021

To explore whether combined treatments with daptomycin and gentamicin can prevent the development of Staphylococcus aureus resistance, and whether the possible restriction is associated with changes in antibiotic mutant prevention concentrations (MPCs), the enrichment of daptomycin- and gentamicin-resistant mutants was studied by simulating 5-day single and combined treatments in an in vitro dynamic model. The MPCs of the antibiotics in the combination were determined at concentration ratios equal to the ratios of 24 h areas, under the concentration–time curve (AUCs) of the antibiotics, as simulated in pharmacodynamic experiments. The MPCs of both daptomycin and gentamicin decreased in the presence of each other; this led to an increase in the time when antibiotic concentrations were above the MPC (T>MPC). The increases in T>MPCs were concurrent with increases of the anti-mutant effects of the combined antibiotics. When anti-mutant effects of the antibiotics in single and combined treatments were plotted against the T>MPCs, significant sigmoid relationships were obtained. These findings suggest that (1) daptomycin–gentamicin combinations prevent the development of S. aureus resistance to each antibiotic; (2) the anti-mutant effects of antibiotic combinations can be predicted using MPCs determined at pharmacokinetic-based antibiotic concentration ratios; (3) T>MPC is a reliable predictor of the anti-mutant efficacy of antibiotic combinations.
Paeonia lactiflora Root Extract and Its Components Reduce Biomarkers of Early Atherosclerosis via Anti-Inflammatory and Antioxidant Effects In Vitro and In Vivo
Authors: Kim Min Jeong , Kang Hyun-Hee , Seo Yeung Jin , Kim Kyung-Min , Kim Young-Jun , Jung Sung Keun
Published: September 2021

Although various physiological activities of compounds obtained from Paeonia lactiflora have been reported, the effects of P. lactiflora extract (PLE) on early atherosclerosis remain unclear. Therefore, in this study, we investigated the in vitro and in vivo antiatherosclerosis and in vitro antioxidant effects of PLE and its compounds. PLE suppresses the tumor necrosis factor (TNF)-α-induced capacity of THP-1 cells to adhere to human umbilical vein endothelial cells (HUVECs), vascular cell adhesion molecule (VCAM)-1 expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in HUVECs. PLE also suppresses TNF-α-induced nuclear translocation of NF-κB p65 from cytosol as well as the enhanced TNFA and C-C motif chemokine ligand 2 (CCL2) mRNA expression in HUVECs. We identified and quantified the following PLE compounds using high-performance liquid chromatography with diode array detection: methyl gallate, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, benzoic acid, benzoylpaeoniflorin, and paeonol. Among these, methyl gallate had the strongest inhibitory effect on monocyte adherence to TNF-α-induced HUVECs and the VCAM-1 expression. Reverse transcriptase real-time quantitative polymerase chain reaction showed that PLE compounds had a dissimilar inhibition effect on TNF-α-induced mRNA expression levels of CCL2, TNFA, and IL6 in HUVECs. Except for paeonol, the compounds inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production in RAW264.7 cells. In vivo, oral administration of PLE improved TNF-α-induced macrophage infiltration to the vascular endothelium and expression of VCAM-1, as well as IL6 and TNFA gene expression in the main artery of mice. PLE could be useful as a nutraceutical material against early atherosclerosis via the combined effects of its components.
Brewing By-Products as a Source of Natural Antioxidants for Food Preservation
Authors: Codina-Torrella Idoia , Rodero Lourdes , Almajano María Pilar
Published: September 2021

Brewer’s spent grain (BSG) and brewer’s spent hops (BSH) are the major solid by-products of the brewing industry. The present work evaluated their potential as an alternative source of natural antioxidants. The efficacy of different solvents (MilliQ water, 0.75% NaOH, 50% MeOH, 50% MeOH + 0.3% HCl and 50% Acetone) for extracting polyphenols of these by-products was firstly evaluated, with NaOH showing the best results. The extraction conditions were optimized using the response surface methodology, and were determined to be 1.45% NaOH and 80 °C. BSG extracts showed the highest total polyphenol content (24.84–38.83 µmol GAE/g), whereas the BSH showed the lowest value (24.84 ± 1.55 µmol GAE/g). In general, BSG extracts presented significantly higher antioxidant capacity (ABTS, ORAC). Ferulic acid was the main polyphenol in all BSG extracts (156.55–290.88 mg/100 g), whereas in BSH, this compound was not detected. The addition of 10% BSG extract in o/w emulsions (stored 14 days) showed a reduction in the formation of primary oxidation products of 97%. In the emulsions covered with polylactic acid active films (1% BSG), this reduction corresponded to 35%. Hence, this study demonstrates the potential of these by-products as natural antioxidant sources for protecting food systems against oxidation.
A Method for the Design of Concrete with Combined Steel and Basalt Fiber
Authors: Dvorkin Leonid , Bordiuzhenko Oleh , Tekle Biruk Hailu , Ribakov Yuri
Published: September 2021

Combining different fiber types may improve the mechanical properties of fiber reinforced concrete. The present study is focused on investigating hybrid fiber reinforced concrete (HFRC) with steel and basalt fiber. Mechanical properties of fiber reinforced fine-grained concrete are investigated. The results demonstrate that using optimal steel and basalt fiber reinforcement ratios avoids concrete mixtures’ segregation and improves their homogeneity. Concrete with hybrid steel and basalt fiber reinforcement has higher strength. Effective methodology for proper design of HFRC compositions was proposed. It is based on the mathematical experiments planning method. The proposed method enables optimal mix proportioning of high-strength fine-grained concrete with hybrid steel and basalt fiber reinforcement.
Physiological and Behavioral Benefits for People and Horses during Guided Interactions at an Assisted Living Residence
Authors: Baldwin Ann , Rector Barbara , Alden Ann
Published: September 2021

Assisted living is a fast-growing living option for seniors who require residence-based activities for maintaining mental and physical health. Guided equine interactions may benefit seniors, so an on-site equine program was started at Hacienda at the River senior living community. For research purposes, twenty-four residents and associates, aged fifty-five or over, consented to physiological measurements before, during and after four guided sessions of stroking one of three horses for 10 min over 4–6 weeks. Heart rate variability (HRV) was measured simultaneously in humans and horses during interactions. We hypothesized that human heart rate (HR) and HRV would increase during stroking and HRV power would shift toward the very low frequency (VLF) range common in horses, indicative of healthy function. During stroking, human HR increased (p < 0.05) but HRV (SDRR) and %VLF of HRV power did not change. Diastolic blood pressure (DBP), an exploratory measure, significantly increased after stroking, consistent with arousal. Two horses showed no significant changes in HR or HRV, but one relaxed. Sixteen horse–human pairs demonstrated synchronized HRV peak frequencies during sessions, suggestive of social connection. Participants used more positive than negative words describing their experience during exit interviews (p < 0.05). These data show that horses animate seniors without causing emotional stress and provide opportunities for social bonding.
Class 1 Histone Deacetylases and Ataxia-Telangiectasia Mutated Kinase Control the Survival of Murine Pancreatic Cancer Cells upon dNTP Depletion
Authors: Nguyen Alexandra , Dzulko Melanie , Murr Janine , Yen Yun , Schneider Günter , Krämer Oliver H.
Published: September 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a dismal prognosis. Here, we show how an inhibition of de novo dNTP synthesis by the ribonucleotide reductase (RNR) inhibitor hydroxyurea and an inhibition of epigenetic modifiers of the histone deacetylase (HDAC) family affect short-term cultured primary murine PDAC cells. We used clinically relevant doses of hydroxyurea and the class 1 HDAC inhibitor entinostat. We analyzed the cells by flow cytometry and immunoblot. Regarding the induction of apoptosis and DNA replication stress, hydroxyurea and the novel RNR inhibitor COH29 are superior to the topoisomerase-1 inhibitor irinotecan which is used to treat PDAC. Entinostat promotes the induction of DNA replication stress by hydroxyurea. This is associated with an increase in the PP2A subunit PR130/PPP2R3A and a reduction of the ribonucleotide reductase subunit RRM2 and the DNA repair protein RAD51. We further show that class 1 HDAC activity promotes the hydroxyurea-induced activation of the checkpoint kinase ataxia-telangiectasia mutated (ATM). Unlike in other cell systems, ATM is pro-apoptotic in hydroxyurea-treated murine PDAC cells. These data reveal novel insights into a cytotoxic, ATM-regulated, and HDAC-dependent replication stress program in PDAC cells.
Acute Valproate Exposure Induces Mitochondrial Biogenesis and Autophagy with FOXO3a Modulation in SH-SY5Y Cells
Authors: Jang Eun-Hye , Lee Jung-Ho , Kim Soon-Ae
Published: September 2021

Valproic acid (VPA) is an antiepileptic drug found to induce mitochondrial dysfunction and autophagy in cancer cell lines. We treated the SH-SY5Y cell line with various concentrations of VPA (1, 5, and 10 mM). The treatment decreased cell viability, ATP production, and mitochondrial membrane potential and increased reactive oxygen species production. In addition, the mitochondrial DNA copy number increased after VPA treatment in a dose-dependent manner. Western blotting showed that the levels of mitochondrial biogenesis-related proteins (PGC-1α, TFAM, and COX4) increased, though estrogen-related receptor expression decreased after VPA treatment. Further, VPA treatment increased the total and acetylated FOXO3a protein levels. Although SIRT1 expression was decreased, SIRT3 expression was increased, which regulated FOXO3 acetylation in the mitochondria. Furthermore, VPA treatment induced autophagy via increased LC3-II levels and decreased p62 expression and mTOR phosphorylation. We suggest that VPA treatment induces mitochondrial biogenesis and autophagy via changes in FOXO3a expression and posttranslational modification in the SH-SY5Y cell line.
The HPSE Gene Insulator—A Novel Regulatory Element That Affects Heparanase Expression, Stem Cell Mobilization, and the Risk of Acute Graft versus Host Disease
Authors: Ostrovsky Olga , Baryakh Polina , Morgulis Yan , Mayorov Margarita , Bloom Nira , Beider Katia , Shimoni Avichai , Vlodavsky Israel , Nagler Arnon
Published: September 2021

The HPSE gene encodes heparanase (HPSE), a key player in cancer, inflammation, and autoimmunity. We have previously identified a strong HPSE gene enhancer involved in self-regulation of heparanase by negative feedback exerted in a functional rs4693608 single-nucleotide polymorphism (SNP) dependent manner. In the present study, we analyzed the HPSE gene insulator region, located in intron 9 and containing rs4426765, rs28649799, and rs4364254 SNPs. Our results indicate that this region exhibits HPSE regulatory activity. SNP substitutions lead to modulation of a unique DNA-protein complex that affects insulator activity. Analysis of interactions between enhancer and insulator SNPs revealed that rs4693608 has a major effect on HPSE expression and the risk of post-transplantation acute graft versus host disease (GVHD). The C alleles of insulator SNPs rs4364254 and rs4426765 modify the activity of the HPSE enhancer, resulting in altered HPSE expression and increased risk of acute GVHD. Moreover, rs4426765 correlated with HPSE expression in activated mononuclear cells, as well as with CD3 levels and lymphocyte counts following G-CSF mobilization. rs4363084 and rs28649799 were found to be associated with CD34+ levels. Our study provides new insight into the mechanism of HPSE gene regulation and its impact on normal and pathological processes in the hematopoietic system.
DNA Barcoding of Penaeidae (Decapoda; Crustacea): Non-Distance-Based Species Delimitation of the Most Economically Important Shrimp Family
Authors: Ramirez Jorge L. , Simbine Luisa , Marques Carla G. , Zelada-Mázmela Eliana , Reyes-Flores Lorenzo E. , López Adolfo S. , Gusmão Jaqueline , Tavares Carolina , Galetti Pedro M. , Freitas Patricia D.
Published: September 2021

The Penaeidae family includes some of the most economic and ecological important marine shrimp, comprising hundreds of species. Despite this importance and diversity, the taxonomic classification for penaeid shrimp has constantly been revised, and issues related to the species identification are common. In this study, we implemented DNA barcoding analyses in addition to single-gene species delimitation analyses in order to identify molecular operational taxonomy units (MOTUs) and to generate robust molecular information for penaeid shrimp based on the cytochrome oxidase subunit I (COI) mitochondrial gene. Our final data set includes COI sequences from 112 taxa distributed in 23 genera of penaeids. We employed the general mixed Yule coalescent (GMYC) model, the Poisson tree processes (PTP), and the Bayesian PTP model (bPTP) for MOTUs delimitation. Intraspecific and interspecific genetic distances were also calculated. Our findings evidenced a high level of hidden diversity, showing 143 MOTUs, with 27 nominal species not agreeing with the genetic delimitation obtained here. These data represent potential new species or highly structured populations, showing the importance of including a non-distance-based species delimitation approach in biodiversity studies. The results raised by this study shed light on the Penaeidae biodiversity, addressing important issues about taxonomy and mislabeling in databases and contributing to a better comprehension of the group, which can certainly help management policies for shrimp fishery activity in addition to conservation programs.
Accuracy of Ultrasonography and Magnetic Resonance Imaging for Preoperative Staging of Cervical Cancer—Analysis of Patients from the Prospective Study on Total Mesometrial Resection
Authors: Stukan Maciej , Buderath Paul , Szulczyński Bartosz , Gębicki Jacek , Kimmig Rainer
Published: September 2021

We aimed to evaluate the accuracy of ultrasonography with gynecologic examination performed by a gynecological oncologist and magnetic resonance imaging (MRI) interpreted by a radiologist for the local and regional staging of patients with early-stage cervical cancer. The study was a single-site sub-analysis of the multi-institutional prospective, observational Total Mesometrial Resection (TMMR) Register Study, which included all consecutive study patients from Gdynia Oncology Center. Imaging results were compared with pathology findings. A total of 58 consecutive patients were enrolled, and 50 underwent both ultrasonography and MRI. The accuracy of tumor detection and measurement errors was comparable across ultrasonography and MRI. There were no significant differences between ultrasonography and MRI in the accuracy of detecting parametrial involvement (92%, confidence interval (CI) 84–100% vs. 76%, CI 64–88%, p = 0.3), uterine corpus infiltration (94%, CI 87–100% vs. 86%, CI 76–96%, p = 0.3), and vaginal fornix involvement (96%, CI 91–100% vs. 76%, CI 64–88%, p = 0.3). The importance of uterine corpus involvement for the first-line lymph node metastases was presented in few cases. The accuracy of ultrasonography was higher than MRI for correctly predicting tumor stage: International Federation of Gynecology and Obstetrics (FIGO)–2018: 69%, CI 57–81% vs. 42%, CI 28–56%, p = 0.002, T (from TNM system): 79%, CI 69–90% vs. 52%, CI 38–66%, p = 0.0005, and ontogenetic tumor staging: 88%, CI 80–96% vs. 70%, CI 57–83%, p = 0.005. For patients with cervical cancer who are eligible for TMMR and therapeutic lymphadenectomy, the accuracy of ultrasonography performed by gynecological oncologists is not inferior to that of MRI interpreted by a radiologist for assessing specific local parameters, and is more accurate for local staging of the disease and is thus more clinically useful for planning adequate surgical treatment.
Robust Asynchronous H∞ Observer-Based Control Design for Discrete-Time Switched Singular Systems with Time-Varying Delay and Sensor Saturation: An Average Dwell Time Approach
Authors: Regaieg Mohamed Amin , Kchaou Mourad , Jerbi Houssem , Boudjemline Attia , Hafaifa Ahmed
Published: September 2021

This work discuss the robust stabilization problem for discrete-time switched singular systems with simultaneous presence of time-varying delay and sensor nonlinearity. To this end, an observer-based controller was synthesized that works under asynchronous switching signals. Investigating the average dwell time approach and using a Lyapunov–Krasovskii functional with triple sum terms, sufficient conditions were derived for achieving the existence of such asynchronous controller and guaranteeing the resulting closed-loop system to be exponentially admissible with H∞ performance level. Subsequently, the effectiveness of the proposed control scheme was verified through two numerical examples.
A Brief Perspective on Environmental Science in the Anthropocene: Recalibrating, Rethinking and Re-Evaluating to Meet the Challenge of Complexity
Authors: Khan Farhan R. , Croft Stephanie Storebjerg , Herrando Elisa Escabia , Kandylas Athanasios , Meyerjuergens Tabea , Rayner Dylan , Schulte Juliane , Valdemarson á Løgmansbø Ingmar
Published: September 2021

A convincing case has been made that the scale of human activity has reached such pervasiveness that humans are akin to a force of nature. How environmental science responds to the many new challenges of the Anthropocene is at the forefront of the field. The aim of this perspective is to describe Anthropocene as a concept and a time period and discuss its relevance to the contemporary study of environmental science. Specifically, we consider areas in environmental science which may need to be revisited to adjust to complexity of the new era: (a) recalibrate the idea of environmental baselines as Anthropogenic baselines; (b) rethink multiple stressor approaches to recognize a system under flux; (c) re-evaluate the relationship of environmental science with other disciplines, particularly Earth Systems Science, but also social sciences and humanities. The all-encompassing nature of the Anthropocene necessitates the need to revise and reorganize to meet the challenge of complexity.
Use of Machine Learning Methods for Indoor Temperature Forecasting
Authors: Ramadan Lara , Shahrour Isam , Mroueh Hussein , Chehade Fadi Hage
Published: September 2021

Improving the energy efficiency of the building sector has become an increasing concern in the world, given the alarming reports of greenhouse gas emissions. The management of building energy systems is considered an essential means for achieving this goal. Predicting indoor temperature constitutes a critical task for the management strategies of these systems. Several approaches have been developed for predicting indoor temperature. Determining the most effective has thus become a necessity. This paper contributes to this objective by comparing the ability of seven machine learning algorithms (ML) and the thermal gray box model to predict the indoor temperature of a closed room. The comparison was conducted on a set of data recorded in a room of the Laboratory of Civil Engineering and geo-Environment (LGCgE) at Lille University. The results showed that the best prediction was obtained with the artificial neural network (ANN) and extra trees regressor (ET) methods, which outperformed the thermal gray box model.
Impact of Blanching, Freezing, and Fermentation on Physicochemical, Microbial, and Sensory Quality of Sugar Kelp (Saccharina latissima)
Authors: Akomea-Frempong Samuel , Skonberg Denise I. , Camire Mary E. , Perry Jennifer J.
Published: September 2021

Low seaweed consumption in the West is due to lack of availability and consumer familiarity. In this study, the effects of preservation processes on quality aspects of Saccharina latissima products were assessed. First, a blanching (100 °C for 1 or 3 min) treatment was used to produce seaweed salad. In a second study, effects of blanching, freezing, and fermentation on kelp quality were assessed and processed kelp was used to produce sauerkraut. Blanching significantly decreased (p ≤ 0.05) the instrumental kelp a* value and firmness. The a* value negatively correlated with overall liking of salads. To prepare sauerkraut, raw, raw/frozen (−20 °C), blanched (100 °C, 1 min), or blanched/frozen kelp were mixed with cabbage, salted, inoculated with starter cultures and fermented. Inconsistent trends in L* values, firmness, and fungi enumeration were observed after fermentation. Consumers evaluated kelp salad (n = 100) and sauerkraut (n = 80) for acceptability. Blanched kelp salad had higher hedonic scores than raw kelp salad. A 100% cabbage sauerkraut control and blanched kelp/cabbage blends were compared; kelp blends were similar to control for appearance, color, and texture but were lower for overall acceptability. Results suggest improved quality and enhanced consumer acceptability of seaweed products with use of minimal processing.
Awareness, Knowledge and Risky Behaviors of Sexually Transmitted Diseases among Young People in Greece
Authors: Voyiatzaki Chrysa , Venetikou Maria S. , Papageorgiou Effie , Anthouli-Anagnostopoulou Fragiski , Simitzis Panagiotis , Chaniotis Dimitrios I. , Adamopoulou Maria
Published: September 2021

Sexually transmitted diseases (STDs) affect mainly young individuals and cause health, social, and economic problems worldwide. The present study used a web questionnaire to assess the awareness, knowledge, sexual behaviors, and common practices regarding STDs in young Greek adults. The 1833 individuals, aged 18–30 years, who responded to the study seem to be particularly knowledgeable regarding STDs such as AIDS (97.7%), warts (97%), Chlamydia (92.2%), genital herpes (89.9%), syphilis (81.9%), and gonorrhea (72.1%), whereas lower percentages were noted for trichomoniasis (39.3%), Molluscum contagiosum (12.9%), mycoplasmosis (11.6%), and amoebiasis (7.4%). Regarding oral STD transmission, participants replied correctly for genital herpes (45%), warts (35.8%), and AIDS (HIV; 33.8%), whereas 30.2% were unfamiliar with oral sexual transmission. Of the participants, 52% were not aware that STDs might cause infertility. Only 40.4% of the respondents reported always using condoms during sexual intercourse, and 48.6% had never been tested for STDs. The majority of the young population (55%) presented a moderate knowledge STD score (41–60%) and was associated with demographic parameters such as age, gender, sexual preference, number of sexual partners, and residence (p < 0.05). These findings provide important information regarding the prevention of STDs and highlight the significance of developing more effective sex education programs for young people in Greece.
Trace Elements and Omega-3 Fatty Acids of Wild and Farmed Mussels (Mytilus galloprovincialis) Consumed in Bulgaria: Human Health Risks
Authors: Peycheva Katya , Panayotova Veselina , Stancheva Rositsa , Makedonski Lubomir , Merdzhanova Albena , Cicero Nicola , Parrino Vincenzo , Fazio Francesco
Published: September 2021

The unique, closed ecosystem of the Black Sea is of significant global importance. The levels and health risk of some trace elements (As, Cd, Cr, Cu, Fe, Ni, Pb and Zn) in wild and farmed mussels (Mytilus galloprovincialis) collected from the Bulgarian part of the Black Sea were determined and using different approaches such as Estimated Daily Intake (EDI), Target Hazard Quotient (THQ), Hazard Index (HI), Target risk (TR), human health risk levels were assessed. The mean maximum concentrations of the elements Cd, Cr, Cu, Fe, Ni, Pb and Zn in all mussel samples were below the maximum permissible limits (MPLs) except that which exceeded the limit of 2.00 mg/kg ww. Eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the major polyunsaturated fatty acids. The fatty acids profile studied mussels showed that the farmed mussels had higher PUFA/SFA ratios, DHA and EPA + DHA content and lower SFA, AI and TI values. The target risk (TR) values for Pb, Cr, Ni and As were calculated, evaluated and showed acceptable or negligible levels. Target hazard quotients (THQs) and hazard index (HI) from elemental intake were below 1 indicated no hazard from consumption. The benefit–risk ratio indicated that wild and cultured M. galloprovincialis are safe for human consumption.
The Jacalin-Related Lectin HvHorcH Is Involved in the Physiological Response of Barley Roots to Salt Stress
Authors: Witzel Katja , Matros Andrea , Bertsch Uwe , Aftab Tariq , Rutten Twan , Ramireddy Eswarayya , Melzer Michael , Kunze Gotthard , Mock Hans-Peter
Published: September 2021

Salt stress tolerance of crop plants is a trait with increasing value for future food production. In an attempt to identify proteins that participate in the salt stress response of barley, we have used a cDNA library from salt-stressed seedling roots of the relatively salt-stress-tolerant cv. Morex for the transfection of a salt-stress-sensitive yeast strain (Saccharomyces cerevisiae YSH818 Δhog1 mutant). From the retrieved cDNA sequences conferring salt tolerance to the yeast mutant, eleven contained the coding sequence of a jacalin-related lectin (JRL) that shows homology to the previously identified JRL horcolin from barley coleoptiles that we therefore named the gene HvHorcH. The detection of HvHorcH protein in root extracellular fluid suggests a secretion under stress conditions. Furthermore, HvHorcH exhibited specificity towards mannose. Protein abundance of HvHorcH in roots of salt-sensitive or salt-tolerant barley cultivars were not trait-specific to salinity treatment, but protein levels increased in response to the treatment, particularly in the root tip. Expression of HvHorcH in Arabidopsis thaliana root tips increased salt tolerance. Hence, we conclude that this protein is involved in the adaptation of plants to salinity.
Chrysin Ameliorates Cyclosporine-A-Induced Renal Fibrosis by Inhibiting TGF-β1-Induced Epithelial–Mesenchymal Transition
Authors: Nagavally Rohan Reddy , Sunilkumar Siddharth , Akhtar Mumtaz , Trombetta Louis D. , Ford Sue M.
Published: September 2021

Cyclosporine A (CsA) is a nephrotoxicant that causes fibrosis via induction of epithelial–mesenchymal transition (EMT). The flavonoid chrysin has been reported to have anti-fibrotic activity and inhibit signaling pathways that are activated during EMT. This study investigated the nephroprotective role of chrysin in the prevention of CsA-induced renal fibrosis and elucidated a mechanism of inhibition against CsA-induced EMT in proximal tubule cells. Treatment with chrysin prevented CsA-induced renal dysfunction in Sprague Dawley rats measured by blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Chrysin inhibited CsA-induced tubulointerstitial fibrosis, characterized by reduced tubular damage and collagen deposition. In vitro, chrysin significantly inhibited EMT in LLC-PK1 cells, evidenced by inhibition of cell migration, decreased collagen expression, reduced presence of mesenchymal markers and elevated epithelial junction proteins. Furthermore, chrysin co-treatment diminished CsA-induced TGF-β1 signaling pathways, decreasing Smad 3 phosphorylation which lead to a subsequent reduction in Snail expression. Chrysin also inhibited activation of the Akt/ GSK-3β pathway. Inhibition of both pathways diminished the cytosolic accumulation of β-catenin, a known trigger for EMT. In conclusion, flavonoids such as chrysin offer protection against CsA-induced renal dysfunction and interstitial fibrosis. Chrysin was shown to inhibit CsA-induced TGF-β1-dependent EMT in proximal tubule cells by modulation of Smad-dependent and independent signaling pathways.
The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations
Authors: Amodeo Giada , Verduci Benedetta , Sartori Patrizia , Procacci Patrizia , Conte Vincenzo , Balboni Gianfranco , Sacerdote Paola , Franchi Silvia
Published: September 2021

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.
Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents
Authors: Horchani Mabrouk , Heise Niels V. , Hoenke Sophie , Csuk René , Harrath Abdel Halim , Ben Jannet Hichem , Romdhane Anis
Published: September 2021

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV–Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.
Genome-Wide Identification and Characterization of the Cystatin Gene Family in Bread Wheat (Triticum aestivum L.)
Authors: He Long , Chen Xuan , Xu Miaoze , Liu Tingting , Zhang Tianye , Li Juan , Yang Jian , Chen Jianping , Zhong Kaili
Published: September 2021

Cystatins, as reversible inhibitors of papain-like and legumain proteases, have been identified in several plant species. Although the cystatin family plays crucial roles in plant development and defense responses to various stresses, this family in wheat (Triticum aestivum L.) is still poorly understood. In this study, 55 wheat cystatins (TaCystatins) were identified. All TaCystatins were divided into three groups and both the conserved gene structures and peptide motifs were relatively conserved within each group. Homoeolog analysis suggested that both homoeolog retention percentage and gene duplications contributed to the abundance of the TaCystatin family. Analysis of duplication events confirmed that segmental duplications played an important role in the duplication patterns. The results of codon usage pattern analysis showed that TaCystatins had evident codon usage bias, which was mainly affected by mutation pressure. TaCystatins may be regulated by cis-acting elements, especially abscisic acid and methyl jasmonate responsive elements. In addition, the expression of all selected TaCystatins was significantly changed following viral infection and cold stress, suggesting potential roles in response to biotic and abiotic challenges. Overall, our work provides new insights into TaCystatins during wheat evolution and will help further research to decipher the roles of TaCystatins under diverse stress conditions.
Incidence, Outcomes and Sex-Related Disparities in Pneumonia: A Matched-Pair Analysis with Data from Spanish Hospitals (2016–2019)
Authors: de Miguel-Yanes Jose M. , Lopez-de-Andres Ana , Jiménez-Garcia Rodrigo , Hernandez-Barrera Valentin , de Miguel-Diez Javier , Carabantes-Alarcon David , Perez-Farinos Napoleon , Wärnberg Julia
Published: September 2021

(1) Background: the purpose of this study is to analyze the incidence and in-hospital mortality (IHM) of community-acquired pneumonia (CAP) needing hospital admission and hospital-acquired pneumonia (HAP) in Spain (2016–2019). (2) Methods: using the Spanish Register of Specialized Care-Basic Minimum Database, we estimated the incidence of CAP and HAP. We matched each woman with a man with an identical age, according to comorbidities. (3) Results: we analyzed 518,838 cases of CAP and 38,705 cases of HAP, and 5192 ventilator-associated HAPs (13.4%). The incidence of CAP increased over time in both men (from 384.5 to 449.8 cases/105 population) and women (from 244.9 to 301.2 cases/105 population). Men showed a 47% higher adjusted incidence of CAP than women. The incidence of HAP increased over time in both men (from 302.3 to 342.2 cases/105 population) and women (from 139.2 to 167.6 cases/105 population). Men showed a 98% higher adjusted incidence of HAP than women. IHM was higher in men admitted for CAP than in women (12.9% vs. 12.2%; p < 0.001), but not in men who developed HAP (28.9% vs. 28.0%; p = 0.107). Men admitted for CAP (OR: 1.13; 95% CI: 1.10–1.15) and men who developed HAP (OR: 1.05; 95% CI: 1.01–1.10) had higher IHM than women. (4) Conclusions: men had higher incidence rates of CAP and HAP than women. Men admitted for CAP and men who developed HAP had higher IHM than women.
The Rich Get Richer and the Poor Get Poorer: Social Media and the Post-IPO Behavior of Investors in Biotechnology Firms: The Relationship with Twitter Volume
Authors: Siev Smadar
Published: September 2021

This paper analyzes stock returns for biotechnology firms after initial public offering (IPO) and explores the effect of social media—specifically, Twitter—on these returns. The results indicate positive yet insignificant cumulative average abnormal returns (CAARs) of 1.97% in the first 25 days post-IPO and a decline of tens of percentage points over the following three years. However, after dividing the sample firms into two subsamples according to size, either under or over USD 500 million in market value, the overall results change dramatically. Firms with a market value lower than USD 500 million yield negative CAARs immediately following the IPO; however, this negative CAAR becomes significant only from day 50 onward. Firms with a market value over USD 500 million yield positive CAARs immediately following the IPO, which become significant from day 50, remaining so throughout the following year. These findings can be attributed to the limited duration of investors’ attention, which increases until the end of quiet period and, with small-sized firms, diminishes during the post-IPO years. An examination of Twitter activity and share returns demonstrates a robust correlation between the two, suggesting that investors’ attention to firms may be reflected in their Twitter usage.
Vulnerability Variables and Their Effect on Wildfires in Galicia (Spain). A Panel Data Analysis
Authors: de Diego Jaime , Rúa Antonio , Fernández Mercedes
Published: September 2021

This paper studied the effect of the socio-economic variables related to social vulnerability on wildfire characteristics (ignitions, hectares burned, and ratio hectares burned/ignitions) in Galicia, Spain. The study recognized that wildfires present threats to people and communities, so actions might be taken to address vulnerabilities in ways that mitigate the negative impacts of such fires. Our final aim was to identify those variables that are relevant to the starting and spreading of wildfires that can help improve the prevention and mitigation of wildfires. Panel data collected over 15 years (2001–2015) for the municipalities of Galicia were used in this study. The results show that vulnerability-related socio-economic factors affect the number of wildfires and the extent of the destruction they cause. Indeed, the progressive abandonment of rural areas is one of the most important problems that increases the occurrence of wildfires. This abandonment is connected to population factors such as aging or low density of population, economic factors such as the decrease in income or low cadastral value, and territorial factors such as the decrease in rustic hectares and ranches. We conclude that prevention and mitigation focused on areas prone to wildfires could be enhanced by taking into account these variables.
Halloysite in Different Ceramic Products: A Review
Authors: Lampropoulou Paraskevi , Papoulis Dimitrios
Published: September 2021

The increased demands of our rapidly developing way of life lead to the broadening of the ceramic market among other effects. Due to the advanced ceramic properties of halloysite and its abundance, combined with its good synergistic effect with other materials, it has been investigated for multifarious possible applications to produce traditional and advanced ceramics as well as ceramic composites. In this review, a substantial number of studies by several investigators into halloysite-based ceramics were are summarized. The possibilities and limitations of different halloysite-based ceramic materials for future applications are also discussed in this manuscript and new fields of research are proposed. The summarization of published results indicates a constant scientific interest in halloysite-based traditional ceramics and new potential uses in the future. Additionally, investigations on different novel ceramic composites with low cost halloysite nanotubes (HNTS) have rapidly increased, covering different scientific and technological areas. On the other hand, research into advanced ceramics (SiAlONS) has been pursued due to its highly cost effective technology treatments on a large scale.
Effect of Sodium Disilicate and Metasilicate on the Microstructure and Mechanical Properties of One-Part Alkali-Activated Copper Slag/Ground Granulated Blast Furnace Slag
Authors: Lemougna Patrick Ninla , Dilissen Nicole , Hernandez Guillermo Meza , Kingne Felicite , Gu Jun , Rahier Hubert
Published: September 2021

Copper slag (CS) remains a challenging industrial by-product with a relatively small utilization fraction. The present study investigated the development of one-part alkali-activated cements based on CS, ground granulated blast furnace slag (GGBS) and a mixture of the two as a precursor. We investigated 5 to 15 wt% solid sodium metasilicate (Na2SiO3) and disilicate (Na2Si2O5) as alkaline reagents. Isothermal calorimetry showed that the reactivity of the system was higher for the metasilicate based samples, with early reaction and higher cumulative heat released. Metasilicate based samples also presented a more densified microstructure, lower porosity and higher strength. Better performances were observed with 10 wt% metasilicate/disilicate with respect to the 5 and 15 wt%. The 28-day compressive strength and elastic modulus of 10 wt% metasilicate samples reached 75 MPa and 25 GPa, respectively, and, for paste samples, ranged from 100 wt% GGBS to 50/50 wt% CS/GGBS. The microstructure and calorimetry of the pastes showed that GGBS actively participated in the binding process, whereas CS played a smaller role and acted as a filler and catalyst. The substitution of commercial GGBS by CS up to 50 wt% did not affect the overall performance, thus, bringing CS forward as an economically interesting precursor.
pH-Triggered Release Performance of Microcapsule-Based Inhibitor and Its Inhibition Effect on the Reinforcement Embedded in Mortar
Authors: Huang Jinzhen , Zhu Yangyang , Ma Yuwei , Hu Jie , Huang Haoliang , Wei Jiangxiong , Yu Qijun
Published: September 2021

The smart release of healing agents is a key factor determining the inhibition efficiency of microcapsules-based corrosion inhibitors for reinforced concrete. In this study, the release behavior of benzotriazole (BTA) in microcapsule-based inhibitors was investigated in mortar sample to clarify the influence of different hydration products on the release process. The results indicated that under high pH environment (pH > 12.4), only about 5% reserved BTA was released from the mortar sample. pH drop resulted in the increased release of BTA from mortar sample. Most BTA in the microcapsule-based inhibitors was released from mortar sample in low pH environment, which was closely related to morphology/composition alterations of hydration products caused by pH drop of the environment. The smart release of BTA dramatically delayed corrosion initiation of reinforced mortar and halted corrosion product accumulation on the steel surface. Therefore, the corrosion resistance of the reinforced mortar was improved after corrosion initiation.
Multi-Objective Optimization Design of a Novel Integral Squeeze Film Bearing Damper
Authors: Zhang Yipeng , He Lidong , Yang Jianjiang , Zhu Gang , Jia Xingyun , Yan Wei
Published: September 2021

In order to better control the vibration of the rotor system so as to improve the stability and safety of the rotor, a novel vibration control solution is needed. In this paper, the multi-objective optimization problem is used for designing a novel integral squeeze film bearing damper (ISFBD). The method attempts to reduce the stiffness and stress convergence of ISFBD, which can greatly decrease the transmitted force of the rotor system and better use the damping effect to dissipate the vibration energy. The finite element model of ISFBD is established to analyze the stiffness and stress, and the correctness of the calculation is verified by setting up a stiffness test platform. The sensitivity of different structural parameters of stiffness and stress is analyzed by ANOVA. Meanwhile, the non-dominated sorting genetic algorithm (NSGA-II) and grey correlation analysis (GRA) algorithms are coupled for multi-objective optimization of stiffness and stress. The results indicate that optimized ISFBD can distribute 26.6% of the rotor system’s energy and reduce 59.3% of the transmitted force at the bearing location. It is also proved that the optimization strategy is effective, which can provide a useful method for ISFBD design in practical applications.
Generic Design Methodology for Smart Manufacturing Systems from a Practical Perspective, Part I—Digital Triad Concept and Its Application as a System Reference Model
Authors: Bi Zhuming , Zhang Wen-Jun , Wu Chong , Luo Chaomin , Xu Lida
Published: September 2021

Rapidly developed information technologies (IT) have continuously empowered manufacturing systems and accelerated the evolution of manufacturing system paradigms, and smart manufacturing (SM) has become one of the most promising paradigms. The study of SM has attracted a great deal of attention for researchers in academia and practitioners in industry. However, an obvious fact is that people with different backgrounds have different expectations for SM, and this has led to high diversity, ambiguity, and inconsistency in terms of definitions, reference models, performance matrices, and system design methodologies. It has been found that the state of the art SM research is limited in two aspects: (1) the highly diversified understandings of SM may lead to overlapped, missed, and non-systematic research efforts in advancing the theory and methodologies in the field of SM; (2) few works have been found that focus on the development of generic design methodologies for smart manufacturing systems from the practice perspective. The novelty of this paper consists of two main aspects which are reported in two parts respectively. In the first part, a simplified definition of SM is proposed to unify the existing diversified expectations, and a newly developed concept named digital triad (DT-II) is adopted to define a reference model for SM. The common features of smart manufacturing systems in various applications are identified as functional requirements (FRs) in systems design. To model a system that is capable of reconfiguring itself to adapt to changes, the concept of IoDTT is proposed as a reference model for smart manufacturing systems. In the second part, these two concepts are used to formulate a system design problem, and a generic methodology, based on axiomatic design theory (ADT), is proposed for the design of smart manufacturing systems.
Generic Design Methodology for Smart Manufacturing Systems from a Practical Perspective. Part II—Systematic Designs of Smart Manufacturing Systems
Authors: Bi Zhuming , Zhang Wen-Jun , Wu Chong , Luo Chaomin , Xu Lida
Published: September 2021

In a traditional system paradigm, an enterprise reference model provides the guide for practitioners to select manufacturing elements, configure elements into a manufacturing system, and model system options for evaluation and comparison of system solutions against given performance metrics. However, a smart manufacturing system aims to reconfigure different systems in achieving high-level smartness in its system lifecycle; moreover, each smart system is customized in terms of the constraints of manufacturing resources and the prioritized performance metrics to achieve system smartness. Few works were found on the development of systematic methodologies for the design of smart manufacturing systems. The novel contributions of the presented work are at two aspects: (1) unified definitions of digital functional elements and manufacturing systems have been proposed; they are generalized to have all digitized characteristics and they are customizable to any manufacturing system with specified manufacturing resources and goals of smartness and (2) a systematic design methodology has been proposed; it can serve as the guide for designs of smart manufacturing systems in specified applications. The presented work consists of two separated parts. In the first part of paper, a simplified definition of smart manufacturing (SM) is proposed to unify the diversified expectations and a newly developed concept digital triad (DT-II) is adopted to define a generic reference model to represent essential features of smart manufacturing systems. In the second part of the paper, the axiomatic design theory (ADT) is adopted and expanded as the generic design methodology for design, analysis, and assessment of smart manufacturing systems. Three case studies are reviewed to illustrate the applications of the proposed methodology, and the future research directions towards smart manufacturing are discussed as a summary in the second part.