bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothermically Stored Adipose-Derived Mesenchymal Stromal Cell Alginate Bandages Facilitate Use of Paracrine Molecules for Corneal Wound Healing
Authors: Al-Jaibaji Olla , Swioklo Stephen , Shortt Alex , Figueiredo Francisco C. , Connon Che J.
Published: August 2020

Adipose-derived mesenchymal stromal cells (Ad-MSCs) may alleviate corneal injury through the secretion of therapeutic factors delivered at the injury site. We aimed to investigate the therapeutic factors secreted from hypothermically stored, alginate-encapsulated Ad-MSCs’ bandages in in vitro and in vivo corneal wounds. Ad-MSCs were encapsulated in 1.2% w/v alginate gels to form bandages and stored at 15 °C for 72 h before assessing cell viability and co-culture with corneal scratch wounds. Genes of interest, including HGF, TSG-6, and IGF were identified by qPCR and a human cytokine array kit used to profile the therapeutic factors secreted. In vivo, bandages were applied to adult male mice corneas following epithelial debridement. Bandages were shown to maintain Ad-MSCs viability during storage and able to indirectly improve corneal wound healing in vivo. Soluble protein concentration and paracrine factors such as TSG-6, HGF, IL-8, and MCP-1 release were greatest following hypothermic storage. In vivo, Ad-MSCs bandages-treated groups reduced immune cell infiltration when compared to untreated groups. In conclusion, bandages were shown to maintain Ad-MSCs ability to produce a cocktail of key therapeutic factors following storage and that these soluble factors can improve in vitro and in vivo corneal wound healing.
Structural Characterization of Covalently Stabilized Human Cystatin C Oligomers
Authors: Chrabąszczewska Magdalena , Sieradzan Adam K. , Rodziewicz-Motowidło Sylwia , Grubb Anders , Dobson Christopher M. , Kumita Janet R. , Kozak Maciej
Published: August 2020

Human cystatin C (HCC), a cysteine-protease inhibitor, exists as a folded monomer under physiological conditions but has the ability to self-assemble via domain swapping into multimeric states, including oligomers with a doughnut-like structure. The structure of the monomeric HCC has been solved by X-ray crystallography, and a covalently linked version of HCC (stab-1 HCC) is able to form stable oligomeric species containing 10–12 monomeric subunits. We have performed molecular modeling, and in conjunction with experimental parameters obtained from atomic force microscopy (AFM), transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) measurements, we observe that the structures are essentially flat, with a height of about 2 nm, and the distance between the outer edge of the ring and the edge of the central cavity is ~5.1 nm. These dimensions correspond to the height and diameter of one stab-1 HCC subunit and we present a dodecamer model for stabilized cystatin C oligomers using molecular dynamics simulations and experimentally measured parameters. Given that oligomeric species in protein aggregation reactions are often transient and very highly heterogeneous, the structural information presented here on these isolated stab-1 HCC oligomers may be useful to further explore the physiological relevance of different structural species of cystatin C in relation to protein misfolding disease.
Signaling Molecules Regulating Pancreatic Endocrine Development from Pluripotent Stem Cell Differentiation
Authors: Huang Hui , Bader Taylor N. , Jin Sha
Published: August 2020

Diabetes is one of the leading causes of death globally. Currently, the donor pancreas is the only source of human islets, placing extreme constraints on supply. Hence, it is imperative to develop renewable islets for diabetes research and treatment. To date, extensive efforts have been made to derive insulin-secreting cells from human pluripotent stem cells with substantial success. However, the in vitro generation of functional islet organoids remains a challenge due in part to our poor understanding of the signaling molecules indispensable for controlling differentiation pathways towards the self-assembly of functional islets from stem cells. Since this process relies on a variety of signaling molecules to guide the differentiation pathways, as well as the culture microenvironments that mimic in vivo physiological conditions, this review highlights extracellular matrix proteins, growth factors, signaling molecules, and microenvironments facilitating the generation of biologically functional pancreatic endocrine cells from human pluripotent stem cells. Signaling pathways involved in stepwise differentiation that guide the progression of stem cells into the endocrine lineage are also discussed. The development of protocols enabling the generation of islet organoids with hormone release capacities equivalent to native adult islets for clinical applications, disease modeling, and diabetes research are anticipated.
p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation
Authors: Formiga Rodrigo de Oliveira , Alves Júnior Edvaldo Balbino , Vasconcelos Roseane Carvalho , Guerra Gerlane Coelho Bernardo , Antunes de Araújo Aurigena , Carvalho Thaís Gomes de , Garcia Vinícius Barreto , de Araújo Junior Raimundo Fernandes , Gadelha Francisco Allysson Assis Ferreira , Vieira Giciane Carvalho , Sobral Marianna Vieira , Barbosa Filho José Maria , Spiller Fernando , Batista Leônia Maria
Published: August 2020

p-Cymene (p-C) and rosmarinic acid (RA) are secondary metabolites that are present in medicinal herbs and Mediterranean spices that have promising anti-inflammatory properties. This study aimed to evaluate their intestinal anti-inflammatory activity in the trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. p-C and RA (25–200 mg/kg) oral administration reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. Both compounds (200 mg/kg) decreased malondialdehyde (MDA) and myeloperoxidase (MPO), restored glutathione (GSH) levels, and enhanced fluorescence intensity of superoxide dismutase (SOD). They also decreased interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and maintained IL-10 basal levels. Furthermore, they modulated T cell populations (cluster of differentiation (CD)4+, CD8+, or CD3+CD4+CD25+) analyzed from the spleen, mesenteric lymph nodes, and colon samples, and also decreased cyclooxigenase 2 (COX-2), interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), and nuclear transcription factor kappa B subunit p65 (NFκB-p65) mRNA transcription, but only p-C interfered in the suppressor of cytokine signaling 3 (SOCS3) expression in inflamed colons. An increase in gene expression and positive cells immunostained for mucin type 2 (MUC-2) and zonula occludens 1 (ZO-1) was observed. Altogether, these results indicate intestinal anti-inflammatory activity of p-C and RA involving the cytoprotection of the intestinal barrier, maintaining the mucus layer, and preserving communicating junctions, as well as through modulation of the antioxidant and immunomodulatory systems.
Role of Leptin in Inflammation and Vice Versa
Authors: Pérez-Pérez Antonio , Sánchez-Jiménez Flora , Vilariño-García Teresa , Sánchez-Margalet Víctor
Published: August 2020

Inflammation is an essential immune response for the maintenance of tissue homeostasis. In a general sense, acute and chronic inflammation are different types of adaptive response that are called into action when other homeostatic mechanisms are insufficient. Although considerable progress has been made in understanding the cellular and molecular events that are involved in the acute inflammatory response to infection and tissue injury, the causes and mechanisms of systemic chronic inflammation are much less known. The pathogenic capacity of this type of inflammation is puzzling and represents a common link of the multifactorial diseases, such as cardiovascular diseases and type 2 diabetes. In recent years, interest has been raised by the discovery of novel mediators of inflammation, such as microRNAs and adipokines, with different effects on target tissues. In the present review, we discuss the data emerged from research of leptin in obesity as an inflammatory mediator sustaining multifactorial diseases and how this knowledge could be instrumental in the design of leptin-based manipulation strategies to help restoration of abnormal immune responses. On the other direction, chronic inflammation, either from autoimmune or infectious diseases, or impaired microbiota (dysbiosis) may impair the leptin response inducing resistance to the weight control, and therefore it may be a cause of obesity. Thus, we are reviewing the published data regarding the role of leptin in inflammation, and the other way around, the role of inflammation on the development of leptin resistance and obesity
History of Nonalcoholic Fatty Liver Disease
Authors: Lonardo Amedeo , Leoni Simona , Alswat Khalid A. , Fouad Yasser
Published: August 2020

Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig’s seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of “NAFLD as a manifestation of the Metabolic Syndrome”, to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.
NECTIN4 Expression in Extramammary Paget’s Disease: Implication of a New Therapeutic Target
Authors: Murata Maho , Ito Takamichi , Tanaka Yuka , Kaku-Ito Yumiko , Furue Masutaka
Published: August 2020

Extramammary Paget’s disease (EMPD) is a rare skin cancer arising in the anogenital area. Most EMPD tumors remain dormant as in situ lesions, but the outcomes of patients with metastatic EMPD are poor because of the lack of effective systemic therapies. Nectin cell adhesion molecule 4 (NECTIN4) has attracted attention as a potential therapeutic target for some cancers. Urothelial cancer is one such cancer, and clinical trials of enfortumab vedotin, a drug-conjugated anti-NECTIN4 antibody, are ongoing. However, little is known regarding the role of NECTIN4 in EMPD. In this study, we conducted immunohistochemical analysis of NECTIN4 expression in 110 clinical EMPD samples and normal skin tissue. In normal skin, positive signals were observed in epidermal keratinocytes (particularly in the lower part of the epidermis), eccrine and apocrine sweat glands, inner and outer root sheaths, and matrix of the hair follicles. The most EMPD lesions exhibited strong NECTIN4 expression, and high NECTIN4 expression was significantly associated with increased tumor thickness, advanced TNM stage, and worse disease-specific survival. These results support the potential use of NECTIN4-targeted therapy for EMPD. Our report contributes to the better understanding of the pathobiology of NECTIN4 in the skin and the skin-related adverse effects of NECTIN4-targeted therapy.
Combinational Analyses with Multiple Methods Reveal the Existence of Several Forms of Polysialylated Neural Cell Adhesion Molecule in Mouse Developing Brains
Authors: Mori Airi , Yang Yi , Takahashi Yuka , Hane Masaya , Kitajima Ken , Sato Chihiro
Published: August 2020

Polysialic acid (polySia/PSA) is an anionic glycan polymer of sialic acid, and it mostly modifies the neural cell adhesion molecule (NCAM) in mammalian brains. Quality and quantity of the polySia of the polySia–NCAM is spatio-temporally regulated in normal brain development and functions, and their impairments are reported to be related to diseases, such as psychiatric disorders and cancers. Therefore, precise understanding of the state of polySia–NCAM structure would lead to the diagnosis of diseases for which their suitable evaluation methods are necessary. In this study, to develop these evaluation methods, structures of polySia–NCAM from mouse brains at six different developmental stages were analyzed by several conventional and newly developed methods. Integrated results of these experiments clearly demonstrated the existence of different types of polySia–NCAMs in developing brains. In addition, combinational analyses were shown to be useful for precise understanding of the quantity and quality of polySia, which can provide criteria for the diagnosis of diseases.
Downregulation of ORP3 Correlates with Reduced Survival of Colon Cancer Patients with Advanced Nodal Metastasis and of Female Patients with Grade 3 Colon Cancer
Authors: Xu Pengfei , Richter Julia , Blatz Annette , Gärtner Fabian , Alberts Roland , Azoitei Anca , Makori Wycliffe Arika , Meessen Sabine , Knippschild Uwe , Günes Cagatay
Published: August 2020

Genome instability is an essential hallmark in tumor development, including colorectal cancer. We have recently identified the oxysterol binding protein-related protein 3 (ORP3), also known as oxysterol binding protein-like 3 (OSBPL3), as a novel ploidy-control gene, whose knock-out leads to aneuploidy induction and promotes tumor formation, indicating that ORP3 is a bona fide tumor suppressor protein. Here we analyzed expression of ORP3 in a cohort (n = 206) of colon cancer patients in relation to patient survival. We show that low ORP3 mRNA levels correlate with reduced survival of patients with advanced nodal metastasis (N2). While patient survival does not associate with grading when the whole cohort is evaluated, importantly, low ORP3 mRNA levels associate with worse survival of female patients with grade 3 colon cancer. Similarly, low ORP3 mRNA levels associate with worse survival of grade 3 colon cancer patients 70 years of age and younger while low ORP3 mRNA levels seem to be beneficial for colon cancer patients with a T2 tumor size. Together, the data show that ORP3 expression is downregulated during colon cancer progression, which correlates with reduced patient survival. Thus, ORP3 mRNA levels may be a prognostic marker for better stratification of colon cancer patients.
Cellular Localization of Two Rickettsia Symbionts in the Digestive System and within the Ovaries of the Mirid Bug, Macrolophous pygmaeus
Authors: Dally Maria , Lalzar Maya , Belausov Eduard , Gottlieb Yuval , Coll Moshe , Zchori-Fein Einat
Published: August 2020

Bacterial symbionts in arthropods are common, vary in their effects, and can dramatically influence the outcome of biological control efforts. Macrolophus pygmaeus (Heteroptera: Miridae), a key component of biological control programs, is mainly predaceous but may also display phytophagy. M. pygmaeus hosts symbiotic Wolbachia, which induce cytoplasmic incompatibility, and two Rickettsia species, R. bellii and R. limoniae, which are found in all individuals tested. To test possible involvement of the two Rickettsia species in the feeding habits of M. pygmaeus, we first showed that the microbiome of the insect is dominated by these three symbionts, and later described the distribution pattern of the two Rickettsia species in its digestive system. Although both Rickettsia species were located in certain gut bacteriocyes, in caeca and in Malpighian tubules of both sexes, each species has a unique cellular occupancy pattern and specific distribution along digestive system compartments. Infrequently, both species were found in a cell. In females, both Rickettsia species were detected in the germarium, the apical end of the ovarioles within the ovaries, but not in oocytes. Although the cause for these Rickettsia distribution patterns is yet unknown, it is likely linked to host nutrition while feeding on prey or plants.
The Role of Iron and Erythropoietin in the Association of Fibroblast Growth Factor 23 with Anemia in Chronic Kidney Disease in Humans
Authors: Bielesz Bernhard , Reiter Thomas , Hammerle Fabian Peter , Winnicki Wolfgang , Bojic Marija , Gleiss Andreas , Kieweg Heidi , Ratzinger Franz , Sunder-Plassmann Gere , Marculescu Rodrig
Published: August 2020

Anemia in chronic kidney disease (CKD) is an almost universal complication of this condition. Fibroblast growth factor 23 (FGF23), a key-player in mineral metabolism, is reportedly associated with anemia and hemoglobin levels in non-dialysis CKD patients. Here, we sought to further characterize this association while taking into account the biologically active, intact fraction of FGF23, iron metabolism, and erythropoietin (EPO). Hemoglobin, EPO, iron, and mineral metabolism parameters, including both intact and c-terminal-FGF23 (iFGF23 and cFGF23, respectively) were measured cross-sectionally in 225 non-dialysis CKD patients (stage 1–5, median eGFR: 30 mL/min./1.73m2) not on erythropoiesis stimulating agents or intravenous iron therapy. Statistical analysis was performed by multiple linear regression. After adjustment for eGFR and other important confounders, only cFGF23 but not iFGF23 was significantly associated with hemoglobin levels and this association was largely accounted for by iron metabolism parameters. cFGF23 but not iFGF23 was also associated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), again in dependence on iron metabolism parameters. Similarly, EPO concentrations were associated with cFGF23 but not iFGF23, but their contribution to the association of cFGF23 with hemoglobin levels was marginal. In pre-dialysis CKD patients, the observed association of FGF23 with hemoglobin seems to be restricted to cFGF23 and largely explained by the iron status.
Liver Steatosis, Gut-Liver Axis, Microbiome and Environmental Factors. A Never-Ending Bidirectional Cross-Talk
Authors: Di Ciaula Agostino , Baj Jacek , Garruti Gabriella , Celano Giuseppe , De Angelis Maria , Wang Helen H. , Di Palo Domenica Maria , Bonfrate Leonilde , Wang David Q-H , Portincasa Piero
Published: August 2020

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and parallels comorbidities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. Recent studies describe the presence of NAFLD in non-obese individuals, with mechanisms partially independent from excessive caloric intake. Increasing evidences, in particular, point towards a close interaction between dietary and environmental factors (including food contaminants), gut, blood flow, and liver metabolism, with pathways involving intestinal permeability, the composition of gut microbiota, bacterial products, immunity, local, and systemic inflammation. These factors play a critical role in the maintenance of intestinal, liver, and metabolic homeostasis. An anomalous or imbalanced gut microbial composition may favor an increased intestinal permeability, predisposing to portal translocation of microorganisms, microbial products, and cell wall components. These components form microbial-associated molecular patterns (MAMPs) or pathogen-associated molecular patterns (PAMPs), with potentials to interact in the intestine lamina propria enriched in immune cells, and in the liver at the level of the immune cells, i.e., Kupffer cells and stellate cells. The resulting inflammatory environment ultimately leads to liver fibrosis with potentials to progression towards necrotic and fibrotic changes, cirrhosis. and hepatocellular carcinoma. By contrast, measures able to modulate the composition of gut microbiota and to preserve gut vascular barrier might prevent or reverse NAFLD.
Effect of Children’s Weight Status on Physical Activity and Sedentary Behavior during Physical Education, Recess, and After School
Authors: Pope Zachary C. , Huang Charles , Stodden David , McDonough Daniel J. , Gao Zan
Published: August 2020

Children’s body mass index may affect physical activity (PA) participation. Therefore, this study examined the effect of children’s weight status on underserved elementary school children’s PA and sedentary behavior (SB) throughout the segmented day. Participants were 138 children (X¯age = 8.14 years). Children’s height and weight were measured with subsequent classification of children as healthy weight or overweight/obese. Durations of moderate-to-vigorous PA (MVPA), light PA (LPA), and SB during physical education (PE), morning recess, lunch recess, after school, and overall were assessed via accelerometry over three days. Independent t-tests evaluated differences in children’s MVPA, LPA, and SB during each daily segment by weight status. Significantly higher MVPA was observed for children of healthy weight status versus children with overweight/obesity during morning recess, t(136) = 2.15, p = 0.03, after school, t(136) = 2.68, p < 0.01, and overall, t(136) = 2.65, p < 0.01. Interestingly, comparisons of children of healthy weight status and children with overweight/obesity’s LPA and SB during the after-school segment revealed a trend wherein children with overweight/obesity participated in slightly greater LPA/less SB than children of healthy weight status. Higher MVPA was observed among children of healthy weight versus children with overweight/obesity during most daily segments. Concerted efforts should focus on increasing MVPA among children with overweight/obesity.
Palmitic Acid Targets Human Testicular Peritubular Cells and Causes a Pro-Inflammatory Response
Authors: Mayerhofer Artur , Dietrich Kim-Gwendolyn , Urbanski Henryk F. , Köhn Frank-Michael , Pickl Ulrich , Trottmann Matthias , Kievit Paul , Welter Harald
Published: August 2020

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta (IL1beta) were not affected. The contractility marker calponin (CNN1) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys (n = 3), fed with a Western Style diet. They had elevated 2–5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.
Association of Regional Bone Synthetic Activities of Vertebral Corners and Vertebral Bodies Quantified Using 18F-Fluoride Positron Emission Tomography with Bone Mineral Density on Dual Energy X-ray Absorptiometry in Patients with Ankylosing Spondylitis
Authors: Kim Keunyoung , Pak Kyoungjune , Kim In-Joo , Kim Seong-Jang , Sohn Dong Hyun , Kim Aran , Lee Seung-Geun
Published: August 2020

We investigated whether the bone-synthetic activities of vertebral bodies or vertebral corners quantified using 18F-fluoride positron emission tomography (PET) was associated with bone mineral density (BMD) at the corresponding lumbar vertebrae in ankylosing spondylitis (AS) at each vertebra level. We analyzed 48 lumbar vertebrae in 12 AS patients who underwent 18F-fluoride PET and dual energy X-ray absorptiometry (DXA). The mean standardized uptake values (SUVmean) of the vertebral body and corners from L1 to L4 were measured using the spatially separated region of interest (ROI). The L1–L4 BMDs were calculated based on the DXA (“conventional BMD”). The BMD of the internal vertebral bodies was measured by manually drawing ROIs to represent the trabecular BMD (“alternative BMD”). After adjusting the within-patient correlation, the 18F-fluoride SUVmean of the vertebral corners but not that of vertebral bodies was significantly related with the conventional BMD of the vertebra. Otherwise, the 18F-fluoride uptake of both the vertebral and vertebral bodies was significantly related with the alternative BMD. The bone-synthetic activities of the vertebral corners may be more closely related with BMD than those of the vertebral bodies, suggesting that the effects of regional bone metabolism at the vertebral corners and bodies on BMD differ in AS.
Effects of Ethinylestradiol (EE2) and an Organophosphorus Flame Retardant (TCPP) on Gonadal Maturation in the Sea Urchin, Paracentrotus lividus
Authors: Campoy-López Pedro , Pereira-Pinto Estefanía , Mantilla-Aldana Leonardo , Beiras Ricardo
Published: August 2020

The sea urchin (Paracentrotus lividus) was used to test the effects of one of the most abundant flame retardant additives for plastics, tris (1-chloro-2-propyl) phosphate (TCPP), and the synthetic hormone ethinylestradiol (EE2) on gametogenesis and gonad development of adults. With this aim, 403 individuals of both sexes were exposed to TCPP concentrations ranging from 0.2 to 10 µg/L, EE2 (0.01 µg/L), seawater and solvent controls for 7 and 28 days. EE2 and TCPP exposure did not cause histological damage in the gonads. Some evidence of estrogenic effects of TCPP within the µg/L range and EE2 within the ng/L range is reported. Females exposed to 1 µg/L TCPP for 7 days showed a significant increase in gonad development assessed as gametogenic stage, females exposed to 10 µg/L TCPP showed increased gonad development both in terms of weight (Gonad Index, GI, at both 7 and 28 days) and maturation (Pixelar Index, PI), and females exposed to 10 ng/L EE2 showed increased PI after 28 days exposure. Male sea urchins exposed to both TCPP and EE2 for 7 days showed increased frequencies of low development gonad stage. However, the patterns of response are affected by the high inter-individual variability, the differing initial stage of the gonad, as well as the dosage administered.
The Evolution and Outcomes of a Collaborative Testbed for Predicting Coastal Threats
Authors: Nichols Charles Reid , Wright Lynn Donelson
Published: August 2020

Beginning in 2003, the Southeastern Universities Research Association (SURA) enabled an open-access network of distributed sensors and linked computer models through the SURA Coastal Ocean Observing and Predicting (SCOOP) program. The goal was to support collaborations among universities, government, and industry to advance integrated observation and modeling systems. SCOOP improved the path to operational real-time data-guided predictions and forecasts of coastal ocean processes. This was critical to the maritime infrastructure of the U.S. and to the well-being of coastal communities. SCOOP integrated and expanded observations from the Gulf of Mexico, the South Atlantic Bight, the Middle Atlantic Bight, and the Chesapeake Bay. From these successes, a Coastal and Ocean Modeling Testbed (COMT) evolved with National Oceanic and Atmospheric Administration (NOAA) funding via the Integrated Ocean Observing System (IOOS) to facilitate the transition of key models from research to operations. Since 2010, COMT has been a conduit between the research community and the federal government for sharing and improving models and software tools. SCOOP and COMT have been based on strong partnerships among universities and U.S. agencies that have missions in ocean and coastal environmental prediction. During SURA’s COMT project, which ended September 2018, significant progress was made in evaluating the performance of models that are progressively becoming operational. COMT successes are ongoing.
Relative Frequency of Paradoxical Growth and Trailing Effect with Caspofungin, Micafungin, Anidulafungin, and the Novel Echinocandin Rezafungin against Candida Species
Authors: Tóth Zoltán , Forgács Lajos , Kardos Tamás , Kovács Renátó , Locke Jeffrey B. , Kardos Gábor , Nagy Fruzsina , Borman Andrew M. , Adnan Awid , Majoros László
Published: August 2020

Rezafungin is a next-generation echinocandin that has favorable pharmacokinetic properties. We compared the occurrence of paradoxical growth (PG) and trailing effect (TE) characteristics to echinocadins with rezafungin, caspofungin, micafungin and anidulafungin using 365 clinical Candida isolates belonging to 13 species. MICs were determined by BMD method according to CLSI (M27 Ed4). Disconnected growth (PG plus TE) was most frequent with caspofungin (49.6%), followed by anidulafungin (33.7%), micafungin (25.7%), while it was least frequent with rezafungin (16.9%). PG was relatively common in the case of caspofungin (30.1%) but was rare in the case of rezafungin (3.0%). C. tropicalis, C. albicans, C. orthopsilosis and C. inconspicua exhibited PG most frequently with caspofungin, micafungin or anidulafungin. PG never occurred in the case of C. krusei isolates. Against C. tropicalis and C. albicans, echinocandins frequently showed PG after 24 h followed by TE after 48 h. All four echinocandins exhibited TE for the majority of C. auris and C. dubliniensis isolates. Disconnected growth was common among Candida species and was echinocandin- and species-dependent. In contrast to earlier echinocandins, PG was infrequently found with rezafungin.
Observed Vegetation Greening and Its Relationships with Cropland Changes and Climate in China
Authors: Zhang Yuzhen , Liang Shunlin , Xiao Zhiqiang
Published: August 2020

Chinese croplands have changed considerably over the past decades, but their impacts on the environment remain underexplored. Meanwhile, understanding the contributions of human activities to vegetation greenness has been attracting more attention but still needs to be improved. To address both issues, this study explored vegetation greening and its relationships with Chinese cropland changes and climate. Greenness trends were first identified from the normalized difference vegetation index and leaf area index from 1982–2015 using three trend detection algorithms. Boosted regression trees were then performed to explore underlying relationships between vegetation greening and cropland and climate predictors. The results showed the widespread greening in Chinese croplands but large discrepancies in greenness trends characterized by different metrics. Annual greenness trends in most Chinese croplands were more likely nonlinearly associated with climate compared with cropland changes, while cropland percentage only predominantly contributed to vegetation greening in the Sichuan Basin and its surrounding regions with leaf area index data and, in the Northeast China Plain, with vegetation index data. Results highlight both the differences in vegetation greenness using different indicators and further impacts on the nonlinear relationships with cropland and climate, which have been largely ignored in previous studies.
Exogenous Polyamines Only Indirectly Induce Stress Tolerance in Wheat Growing in Hydroponic Culture under Polyethylene Glycol-Induced Osmotic Stress
Authors: Marcińska Izabela , Dziurka Kinga , Waligórski Piotr , Janowiak Franciszek , Skrzypek Edyta , Warchoł Marzena , Juzoń Katarzyna , Kapłoniak Kamila , Czyczyło-Mysza Ilona Mieczysława
Published: August 2020

The aim of the present study was to evaluate the effect of osmotic stress caused by polyethylene glycol (PEG) 6000 in hydroponic culture on wheat seedlings of drought-resistant Chinese Spring (CS) and drought-susceptible SQ1 cultivar, and to examine the alleviative role of exogenous polyamines (PAs) applied to the medium. The assessment was based on physiological (chlorophyll a fluorescence kinetics, chlorophyll and water content) as well as biochemical (content of carbohydrates, phenols, proline, salicylic and abscisic acid, activity of low molecular weight antioxidants) parameters, measured after supplementation with PAs (putrescine, spermidine and spermine) on the 3rd, 5th and 7th day of the treatment. The results indicate that PAs ameliorate the effects of stress, indirectly and conditionally inducing stress tolerance of wheat seedlings. In contrast to the susceptible SQ1, the resistant CS cultivar activated its protective mechanisms, adjusting the degree of their activation to the level of the stress, depending on the genetic resources of the plant. Increased accumulation of antioxidants in the resistant CS in response to stress after the application of PAs confirms the hypothesis that PAs are involved in the signaling pathway determining the antioxidative response and the tolerance of wheat plants to drought stress.
Preparation and Photocatalytic Properties of Metal-Doped ZnO Nanofilms Grown on Graphene-Coated Flexible Substrates
Authors: Rong Ping , Ren Shuai , Jiang Jianchao , Yu Qi , Jiang Liyun , Zhang Yonghong
Published: August 2020

A series of metal element (Al, Fe, Mg and Ni)-doped ZnO (M-ZnO) photocatalysts have been successfully synthesized on graphene-coated polyethylene terephthalate (GPET) flexible substrate via the hydrothermal method. The effects of doped metals in ZnO were also studied on the crystal structure, morphology and photocatalytic performance. The photocatalytic experiment results indicated that, compared with Al-, Mg- and Fe-ZnO/GPET photocatalysts under ultraviolet (UV) light irradiation, Ni-ZnO/GPET had better photocatalytic activity, and the degradation rate of methylene blue (MB) was 81.17%. Meanwhile, the mechanism of enhancing the photocatalytic activity of metal element-doped ZnO is also discussed. It is concluded that, after doping with metal elements, electrons and holes are prevented from recombination by trapping electrons of the ZnO/GPET conductive band, thereby improving the photocatalytic activity.
Expanding Canonical Spider Silk Properties through a DNA Combinatorial Approach
Authors: Jaleel Zaroug , Zhou Shun , Martín-Moldes Zaira , Baugh Lauren M. , Yeh Jonathan , Dinjaski Nina , Brown Laura T. , Garb Jessica E. , Kaplan David L.
Published: August 2020

The properties of native spider silk vary within and across species due to the presence of different genes containing conserved repetitive core domains encoding a variety of silk proteins. Previous studies seeking to understand the function and material properties of these domains focused primarily on the analysis of dragline silk proteins, MaSp1 and MaSp2. Our work seeks to broaden the mechanical properties of silk-based biomaterials by establishing two libraries containing genes from the repetitive core region of the native Latrodectus hesperus silk genome (Library A: genes masp1, masp2, tusp1, acsp1; Library B: genes acsp1, pysp1, misp1, flag). The expressed and purified proteins were analyzed through Fourier Transform Infrared Spectrometry (FTIR). Some of these new proteins revealed a higher portion of β-sheet content in recombinant proteins produced from gene constructs containing a combination of masp1/masp2 and acsp1/tusp1 genes than recombinant proteins which consisted solely of dragline silk genes (Library A). A higher portion of β-turn and random coil content was identified in recombinant proteins from pysp1 and flag genes (Library B). Mechanical characterization of selected proteins purified from Library A and Library B formed into films was assessed by Atomic Force Microscopy (AFM) and suggested Library A recombinant proteins had higher elastic moduli when compared to Library B recombinant proteins. Both libraries had higher elastic moduli when compared to native spider silk proteins. The preliminary approach demonstrated here suggests that repetitive core regions of the aforementioned genes can be used as building blocks for new silk-based biomaterials with varying mechanical properties.
A Study on Explosion Separation Technology of Carbon Fiber Reinforced Epoxy Resin-Based Composite Laminate
Authors: Wang Zhifu , Wang Meng , Hu Kunlun , Xia Zhiyuan , Ma Liubo
Published: August 2020

In an aeroengine casing containment experiment, in order to explode and separate unidirectional carbon fiber reinforced epoxy resin-based laminate, with uneven thickness, without excessive residual speed and fragment spattering, blades were subjected to three types of blasting and cutting pretests, including normal and lateral opening charge explosive tests on the laminate and linear charge-shaped jet cutting. The linear charge-shaped method was found to be the most suitable method for separating the laminate. The finite-element analysis program AUTODYN was used to simulate and optimize the effect of shaped jet cutting. When the explosive height of the shaped jet cutter was set to 90 mm, the laminate broke with the least number of fragments and the residual velocity of the plate was the smallest. At this time, we obtained the relationship between the total amount of explosive and the thickness of the composite plate when the composite plates of different thicknesses were just broken, and the rationality of the relationship was verified by experiments. The research method, in this paper, provides a reference scheme to design explosive separation composite materials in complex engineering environments.
Microstructure and Mechanical Properties of Al/Steel Butt Joint by Hybrid CMT Welding with External Axial Magnetic Field
Authors: Kang Kexin , Liu Yibo , Li Junzhao , Liu Chao , Zhen Zuyang , Wang Yaxin , Sun Qingjie
Published: August 2020

The 6061 aluminum alloy and 304 stainless steel were welded by hybrid cold metal transfer (CMT) welding with external axial magnetic field. The effects of magnetic intensity and frequency on joint microstructure and mechanical properties were studied. It was found that the magnetic field can promote the spreading of aluminum weld metal on the steel surface and thus increase the bonding area of Al/steel butt joint. The welding process stability improved, while the wetting behavior worsened with the introduction of alternating frequencies. The thickness of the intermetallic compound (IMC) layer at Al/steel interface was reduced to 3 μm with the coil current of 2 A. The application of the magnetic field promoted the aggregation of Si atoms at the interface and inhibited the formation of brittle (Al, Si)13Fe4 phase. The fracture paths were transformed from (Al, Si)13Fe4 layer to Al8Fe2Si layer with the application of the magnetic field. The maximum tensile strength reached 130.2 MPa, an increase of 61.6% in comparison to the normal CMT process.
A Review of Current Challenges and Case Study toward Optimizing Micro-Computed X-Ray Tomography of Carbon Fabric Composites
Authors: Rashidi Armin , Olfatbakhsh Tina , Crawford Bryn , Milani Abbas S.
Published: August 2020

X-ray computed tomography provides qualitative and quantitative structural and compositional information for a broad range of materials. Yet, its contribution to the field of advanced composites such as carbon fiber reinforced polymers is still limited by factors such as low imaging contrast, due to scarce X-ray attenuation features. This article, through a review of the state of the art, followed by an example case study on Micro-computed tomography (CT) analysis of low X-ray absorptive dry and prepreg carbon woven fabric composites, aims to highlight and address some challenges as well as best practices on performing scans that can capture key features of the material. In the case study, utilizing an Xradia Micro-CT-400, important aspects such as obtaining sufficient contrast, an examination of thin samples, sample size/resolution issues, and image-based modeling are discussed. The outcome of an optimized workflow in Micro-CT of composite fabrics can assist in further research efforts such as the generation of surface or volume meshes for the numerical modeling of underlying deformation mechanisms during their manufacturing processes.
Multi-Wavelets Galerkin Method for Solving the System of Volterra Integral Equations
Authors: Long Hoang Viet , Jebreen Haifa Bin , Tomasiello Stefania
Published: August 2020

In this work, an efficient algorithm is proposed for solving the system of Volterra integral equations based on wavelet Galerkin method. This problem is reduced to a set of algebraic equations using the operational matrix of integration and wavelet transform matrix. For linear type, the computational effort decreases by thresholding. The convergence analysis of the proposed scheme has been investigated and it is shown that its convergence is of order O(2−Jr), where J is the refinement level and r is the multiplicity of multi-wavelets. Several numerical tests are provided to illustrate the ability and efficiency of the method.
Perturbation Observer-Based Robust Control Using a Multiple Sliding Surfaces for Nonlinear Systems with Influences of Matched and Unmatched Uncertainties
Authors: Thanh Ha Le Nhu Ngoc , Vu Mai The , Mung Nguyen Xuan , Nguyen Ngoc Phi , Phuong Nguyen Thanh
Published: August 2020

This paper presents a lumped perturbation observer-based robust control method using an extended multiple sliding surface for a system with matched and unmatched uncertainties. The fundamental methodology is to apply the multiple surfaces to approximate the unknown lumped perturbations simultaneously influencing on a nonlinear single input–single output (SISO) system. Subsequently, a robust controller, based on the proposed multi-surface and the approximated values, is designed to highly improve the control performance of the system. A general stability of the lumped perturbation observer and closed-loop control system is obtained through the Lyapunov theory. Results of a numerical simulation of an illustrative example demonstrate the soundness of the proposed algorithm.
Capacity Random Forest for Correlative Multiple Criteria Decision Pattern Learning
Authors: Wu Jian-Zhang , Chen Feng-Feng , Li Yan-Qing , Huang Li
Published: August 2020

The Choquet capacity and integral is an eminent scheme to represent the interaction knowledge among multiple decision criteria and deal with the independent multiple sources preference information. In this paper, we enhance this scheme’s decision pattern learning ability by combining it with another powerful machine learning tool, the random forest of decision trees. We first use the capacity fitting method to train the Choquet capacity and integral-based decision trees and then compose them into the capacity random forest (CRF) to better learn and explain the given decision pattern. The CRF algorithms of solving the correlative multiple criteria based ranking and sorting decision problems are both constructed and discussed. Two illustrative examples are given to show the feasibilities of the proposed algorithms. It is shown that on the one hand, CRF method can provide more detailed explanation information and a more reliable collective prediction result than the main existing capacity fitting methods; on the other hand, CRF extends the applicability of the traditional random forest method into solving the multiple criteria ranking and sorting problems with a relatively small pool of decision learning data.
Lipidomic-Based Advances in Diagnosis and Modulation of Immune Response to Cancer
Authors: Gil-de-Gómez Luis , Balgoma David , Montero Olimpio
Published: August 2020

While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed.
Analysis of Current Variation with Work Function Variation in L-Shaped Tunnel-Field Effect Transistor
Authors: Kim Jang Hyun , Kim Hyun Woo , Song Young Suh , Kim Sangwan , Kim Garam
Published: August 2020

In this paper, an investigation is performed to analyze the L-shaped tunnel field-effect transistor (TFET) depending on a gate work function variation (WFV) with help of technology computer-aided design (TCAD) simulation. Depending on the gate voltage, the three variations occur in transfer curves. The first one is the on-state current (ION) variation, the second one is the hump current (IHUMP) variation, and the last one is ambipolar current (IAMB) variation. According to the simulation results, the ION variation is sensitive depending on the size of the tunneling region and could be reduced by increasing the tunneling region. However, the IHUMP and IAMB variations are relatively irrelevant to the size of the tunneling region. In order to analyze the cause of this difference, we investigated the band-to-band tunneling (BTBT) rate according to WFV cases. The results show that when ION is formed in L-shaped TFET, the BTBT rate relies on the WFV in the whole region of the gate because the tunnel barrier is formed in the entire area where the source and the gate meet. On the other hand, when the IHUMP and IAMB are formed in L-shaped TFET, the BTBT rate relies on the WFV in the edge of the gate.