bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Sleep Quality and Frailty among the Older Adults with Chronic Disease in China: The Mediation Effect of Psychological Distress
Authors: Fu Peipei , Zhou Chengchao , Meng Qingyue
Published: July 2020

Frailty affects the elderly and leads to adverse health outcomes. Preliminary evaluations have suggested that sleep quality and psychological distress are predictors of frailty among older adults. However, the mechanisms by which sleep quality affect frailty had not been fully addressed in the previous research. This study aimed to explore the mediation effect of psychological distress on the association between sleep quality and frailty among the elderly with chronic diseases in rural China. A total of 2346 old adults were included in the analysis. Frailty status was measured by Fried Phenotype criteria. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI), and psychological distress was examined by Kessler Psychological Distress Scale (K10). Ordinal logistic regressions were performed to assess the relationships between sleep quality and frailty. Mediation test was also conducted by bootstrap method. The prevalence rate of frailty among the elderly with chronic diseases was 21% in rural China. Compared with the elder of robust status, respondents identified as having frailty have lower SES, less vigorous physical activity, and worse self-reported health status. Poor sleep quality was a significant predictor of frailty with mediators (OR = 1.44, 95% CI = 1.19–1.76). Mediation analysis suggested that psychological distress mediated 41.81% of total effect between sleep quality and frailty. This study indicated that poor sleep quality was significantly related to frailty, and psychological was a mediator of this association. However, we could not investigate causal relationships between variables since this was one cross-sectional study. These findings suggested that an early detection of sleep problems and also psychological disorders should be taken to prevent frailty among the rural older adults in China.
A Deep Learning Approach to Urban Street Functionality Prediction Based on Centrality Measures and Stacked Denoising Autoencoder
Authors: Noori Fatemeh , Kamangir Hamid , A. King Scott , Sheta Alaa , Pashaei Mohammad , SheikhMohammadZadeh Abbas
Published: July 2020

In urban planning and transportation management, the centrality characteristics of urban streets are vital measures to consider. Centrality can help in understanding the structural properties of dense traffic networks that affect both human life and activity in cities. Many cities classify urban streets to provide stakeholders with a group of street guidelines for possible new rehabilitation such as sidewalks, curbs, and setbacks. Transportation research always considers street networks as a connection between different urban areas. The street functionality classification defines the role of each element of the urban street network (USN). Some potential factors such as land use mix, accessible service, design goal, and administrators’ policies can affect the movement pattern of urban travelers. In this study, nine centrality measures are used to classify the urban roads in four cities evaluating the structural importance of street segments. In our work, a Stacked Denoising Autoencoder (SDAE) predicts a street’s functionality, then logistic regression is used as a classifier. Our proposed classifier can differentiate between four different classes adopted from the U.S. Department of Transportation (USDT): principal arterial road, minor arterial road, collector road, and local road. The SDAE-based model showed that regular grid configurations with repeated patterns are more influential in forming the functionality of road networks compared to those with less regularity in their spatial structure.
An Event-Based Inventory Approach in Landslide Hazard Assessment: The Case of the Skolis Mountain, Northwest Peloponnese, Greece
Authors: Litoseliti Aspasia , Koukouvelas Ioannis K. , Nikolakopoulos Konstantinos G. , Zygouri Vasiliki
Published: July 2020

Assessment of landslide hazard across mountains is imperative for public safety. Pre- and post-earthquake landslide mapping envisage that landslides show significant size changes during earthquake activity. One of the purposes of earthquake-induced landslide investigation is to determine the landslide state and geometry and draw conclusions on their mobility. This study was based on remote sensing data that covered 72 years, and focused on the west slopes of the Skolis Mountains, in the northwest Peloponnese. On 8 June 2008, during the strong Movri Mountain earthquake (Mw = 6.4), we mapped the extremely abundant landslide occurrence. Historical seismicity and remote sensing data indicate that the Skolis Mountain west slope is repeatedly affected by landslides. The impact of the earthquakes was based on the estimation of Arias intensity in the study area. We recognized that 89 landslides developed over the last 72 years. These landslides increased their width (W), called herein as inflation or their length (L), termed as enlargement. Length and width changes were used to describe their aspect ratio (L/W). Based on the aspect ratio, the 89 landslides were classified into three types: I, J, and Δ. Taluses, developed at the base of the slope and belonging to the J- and Δ-landslide types, are supplied by narrow or irregular channels. During the earthquakes, the landslide channels migrated upward and downward, outlining the mobility of the earthquake-induced landslides. Landslide mobility was defined by the reach angle. The reach angle is the arctangent of the landslide’s height to length ratio. Furthermore, we analyzed the present slope stability across the Skolis Mountain by using the landslide density (LD), landslide area percentage (LAP), and landslide frequency (LF). All these parameters were used to evaluate the spatial and temporal landslide distribution and evolution with the earthquake activity. These results can be considered as a powerful tool for earthquake-induced landslide disaster mitigation
Synergistic Interaction of Phytohormones in Determining Leaf Angle in Crops
Authors: Li Xi , Wu Pingfan , Lu Ying , Guo Shaoying , Zhong Zhuojun , Shen Rongxin , Xie Qingjun
Published: July 2020

Leaf angle (LA), defined as the angle between the plant stem and leaf adaxial side of the blade, generally shapes the plant architecture into a loosen or dense structure, and thus influences the light interception and competition between neighboring plants in natural settings, ultimately contributing to the crop yield and productivity. It has been elucidated that brassinosteroid (BR) plays a dominant role in determining LA, and other phytohormones also positively or negatively participate in regulating LA. Accumulating evidences have revealed that these phytohormones interact with each other in modulating various biological processes. However, the comprehensive discussion of how the phytohormones and their interaction involved in shaping LA is relatively lack. Here, we intend to summarize the advances in the LA regulation mediated by the phytohormones and their crosstalk in different plant species, mainly in rice and maize, hopefully providing further insights into the genetic manipulation of LA trait in crop breeding and improvement in regarding to overcoming the challenge from the continuous demands for food under limited arable land area.
Integrated Analysis of Tissue-Specific Promoter Methylation and Gene Expression Profile in Complex Diseases
Authors: Lee Kibaick , Moon Sanghoon , Park Mi-Jin , Koh In-Uk , Choi Nak-Hyeon , Yu Ho-Yeong , Kim Young Jin , Kong Jinhwa , Kang Hee Gyung , Kim Song Cheol , Kim Bong-Jo
Published: July 2020

This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene–disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs’ expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.
Ubiquitin Pathway Is Associated with Worsening Left Ventricle Function after Mitral Valve Repair: A Global Gene Expression Study
Authors: Tsai Feng-Chun , Chang Gwo-Jyh , Lai Ying-Ju , Chang Shang-Hung , Chen Wei-Jan , Yeh Yung-Hsin
Published: July 2020

The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and p70S6K signaling. In addition, worsening-LVF was associated with altered expressions of genes pathologically relevant to heart failure, such asdownregulated apelin receptors and upregulated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). HL-1 cardiomyocyte cells transfected with ubiquitination-related genes demonstrated activation of the protein ubiquitination pathwaywith an increase in the ubiquitin activating enzyme E1 (UAE-E1). It also led to increased apoptosis, downregulated and ubiquitinated X-linked inhibitor of apoptosis protein (XIAP), and reduced cell viability. Overexpression of ubiquitination-related genes also resulted in degradation and increased ubiquitination of α-smooth muscle actin (SMA). In conclusion, worsening-LVF presented differential gene expression profiles from preserved-LVF after MV repair. Upregulation of protein ubiquitination-related genes associated with worsening-LVF after MV repair may exert adverse effects on LV through increased apoptosis and contractile protein degradation.
Expression Profiling and Functional Characterization of miR-26a and miR-130a in Regulating Zhongwei Goat Hair Development via the TGF-β/SMAD Pathway
Authors: Ding Yangyang , Xue Xianglan , Liu Zhanfa , Ye Yong , Xiao Ping , Pu Yabin , Guan Weijun , Mwacharo Joram Mwashigadi , Ma Yuehui , Zhao Qianjun
Published: July 2020

The Zhongwei goat is an important and unique goat breed indigenous to China. It has a natural hair curling phenotype at birth, but the degree of curling gradually decreases with growth. The molecular mechanism underlying the dynamic changes in the wool curvature in Zhongwei goats is poorly understood. MicroRNAs (miRNAs) play important roles in many biological processes, including hair growth and development. In this study, we selected skins from Zhongwei goats at different ages (45 and 108 days) that exhibited different levels of hair curvature and performed miRNA sequencing to explore the molecular mechanism of hair bending. In total, 28 significantly differentially expressed miRNAs (DE miRNAs) were identified in the three groups of samples between the two developmental stages. An analysis of the target genes of the above-mentioned DE miRNAs by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the DE miRNAs were involved in signal pathways which were previously associated with hair bending and hair follicle development, such as the TGF-β/SMAD, PI3K-Akt, JAK-STAT, and MAPK pathways. A comprehensive analysis of the correlations between the miRNA-seq results and issued transcriptional findings indicated that SMAD1 was a target gene of miR-26a and SMAD5 was a target gene of miR-130a. Furthermore, goat dermal papilla cells were successfully isolated and purified to determine the role of miRNAs in follicle development in vitro. The study results demonstrated that miR-130a and miR-26a had significant effects on the proliferation of dermal papilla cells. In addition, the detection results of mRNA and protein levels indicate that the overexpression of miR-26a can promote the expression of related genes in the TGF-β/SMAD pathway, while miR-130a has the opposite substitution effect. The dual luciferase report test showed that miR-26a targeted the SMAD1 gene and reduced the expression of the SMAD1 protein in hair papillary cells. Our results identified DE microRNAs which perhaps change at the time of hair straightening in Zhongwei goats and explore the role of miR-26a and miR-130a in dermal papilla cells proliferation. The present study provided a theoretical basis to explore the mechanisms underlying the Zhongwei hair growth and curly phenotype.
The Effects of Ozone on Atlantic Salmon Post-Smolt in Brackish Water—Establishing Welfare Indicators and Thresholds
Authors: Stiller Kevin T. , Kolarevic Jelena , Lazado Carlo C. , Gerwins Jascha , Good Christopher , Summerfelt Steven T. , Mota Vasco C. , Espmark Åsa M. O.
Published: July 2020

Ozone is a strong oxidant, and its use in aquaculture has been shown to improve water quality and fish health. At present, it is predominantly used in freshwater systems due to the high risk of toxic residual oxidant exposure in brackish water and seawater. Here, we report the effects of ozone on Atlantic salmon (Salmo salar) post-smolts (~100 g), in a brackish water (12 ppt) flow-through system. Salmon were exposed to oxidation reduction potential concentrations of 250 mV (control), 280 mV (low), 350 mV (medium), 425 mV (high) and 500 mV (very high). The physiological impacts of ozone were characterized by blood biochemical profiling, histopathologic examination and gene expression analysis in skin and gills. Fish exposed to 425 mV and higher showed ≥33% cumulative mortality in less than 10 days. No significant mortalities were recorded in the remaining groups. The skin surface quality and the thickness of the dermal and epidermal layers were not significantly affected by the treatments. On the other hand, gill histopathology showed the adverse effects of increasing ozone doses and the changes were more pronounced in the group exposed to 350 mV and higher. Cases of gill damages such as necrosis, lamellar fusion and hypertrophy were prevalent in the high and very high groups. Expression profiling of key biomarkers for mucosal health supported the histology results, showing that gills were significantly more affected by higher ozone doses compared to the skin. Increasing ozone doses triggered anti-oxidative stress and inflammatory responses in the gills, where transcript levels of glutathione reductase, copper/zinc superoxide dismutase, interleukin 1β and interleukin were significantly elevated. Heat shock protein 70 was significantly upregulated in the skin of fish exposed to 350 mV and higher. Bcl-2 associated x protein was the only gene marker that was significantly upregulated by increasing ozone doses in both mucosal tissues. In conclusion, the study revealed that short-term exposure to ozone at concentrations higher than 350 mV in salmon in brackish water resulted in significant health and welfare consequences, including mortality and gill damages. The results of the study will be valuable in developing water treatment protocols for salmon farming.
Generation of Glioblastoma Patient-Derived Intracranial Xenografts for Preclinical Studies
Authors: Kerstetter-Fogle Amber E. , Harris Peggy L. R. , Brady-Kalnay Susann M. , Sloan Andrew E.
Published: July 2020

Glioblastoma multiforme (GBM) is the most malignant primary brain cancer affecting adults. Therapeutic options for GBM have remained the same for over a decade with no significant improvement. Many therapies that are successful in culture have failed in patients, likely due to the complex microenvironment in the brain, which has yet to be reproduced in any culture model. Furthermore, the high passage number of cultured cells and clonal selection fail to recapitulate the molecular and genomic signatures of GBM. We have established orthotopic patient-derived xenografts (PDX) from 37 GBM patients with human GBM. Of the 69 patient samples analyzed, we were successful in passaging 37 lines three or more generations (53.6%). After phenotypic characterization of the xenografted tumor tissue, two different growth patterns emerged highly invasive or localized. The phenotype was dependent on malignancy and previous treatment of the patient from which the xenograft was derived. Physiologically, mice exhibited symptoms more quickly with each subsequent passage, particularly in the localized tumors. Study of these physiologically relevant human xenografts in mice will enable therapeutic screenings in a microenvironment that more closely resembles GBM and may allow development of individualized patient models which may eventually be used for simulating treatment.
Biocatalysis: “A Jack of all Trades...”
Authors: Křen Vladimír , Bojarová Pavla
Published: July 2020

Biotransformation has accompanied mankind since the Neolithic community, when people settled down and began to engage in agriculture [...]
Quipazine Elicits Swallowing in the Arterially Perfused Rat Preparation: A Role for Medullary Raphe Nuclei?
Authors: Bergé-Laval Victor , Gestreau Christian
Published: July 2020

Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working heart-brainstem (in situ) preparation in rats. Systemic injection of quipazine produced single swallows with motor patterns and swallow-breathing coordination similar to spontaneous swallows, and increased swallow rate with moderate changes in cardiorespiratory functions. Methysergide, a 5-HT2 receptor antagonist, blocked the excitatory effect of quipazine on swallowing, but had no effect on spontaneous swallow rate. Microinjections of quipazine in the nucleus of the solitary tract were without effect. In contrast, similar injections in caudal medullary raphe nuclei increased swallow rate without changes in cardiorespiratory parameters. Thus, quipazine may exert an excitatory effect on raphe neurons via stimulation of 5-HT2A receptors, leading to increased excitability of the swallowing network. In conclusion, we suggest that pharmacological stimulation of swallowing by quipazine in situ represents a valuable model for experimental studies. This work paves the way for future investigations on brainstem serotonergic modulation, and further identification of neural populations and mechanisms involved in swallowing and/or swallow-breathing interaction.
Point-of-Use Rapid Detection of SARS-CoV-2: Nanotechnology-Enabled Solutions for the COVID-19 Pandemic
Authors: Rabiee Navid , Bagherzadeh Mojtaba , Ghasemi Amir , Zare Hossein , Ahmadi Sepideh , Fatahi Yousef , Dinarvand Rassoul , Rabiee Mohammad , Ramakrishna Seeram , Shokouhimehr Mohammadreza , Varma Rajender S.
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019. More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment. Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people. Considerable efforts are also directed at detecting and preventing different modes of community transmission. Among them is the rapid detection of virus presence on different surfaces with which people may come in contact. Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces. Nanomaterial-based methods are proven suitable for rapid detection. Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions. In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods. Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented.
Non-Thermal Plasma Application in Tumor-Bearing Mice Induces Increase of Serum HMGB1
Authors: Troitskaya Olga , Golubitskaya Ekaterina , Biryukov Mikhail , Varlamov Mikhail , Gugin Pavel , Milakhina Elena , Richter Vladimir , Schweigert Irina , Zakrevsky Dmitry , Koval Olga
Published: July 2020

The application of cold atmospheric plasma (CAP) in cancer therapy could be one of the new anticancer strategies. In the current work, we used cold atmospheric plasma jet for the treatment of cultured cells and mice. We showed that CAP induced the death of MX−7 mouse rhabdomyosarcoma cells with the hallmarks of immunogenic cell death (ICD): calreticulin and heat shock protein 70 (HSP70) externalization and high-mobility group box 1 protein (HMGB1) release. The intensity of HMGB1 release after the CAP treatment correlated directly with the basal extracellular HMGB1 level. Releasing from dying cells, HMGB1 can act as a proinflammatory cytokine. Our in vivo study demonstrated that cold atmospheric plasma induces a short-term two-times increase in serum HMGB1 level only in tumor-bearing mice with no effect in healthy mice. These findings support our hypothesis that CAP-dependent HMGB1 release from dying cancer cells can change the serum HMGB1 level. At the same time, we showed a weak cytokine response to CAP irradiation in healthy mice that can characterize CAP as an immune-safety physical antitumor approach.
Imidazo[1,2-b]pyrazole-7-Carboxamide Derivative Induces Differentiation-Coupled Apoptosis of Immature Myeloid Cells Such as Acute Myeloid Leukemia and Myeloid-Derived Suppressor Cells
Authors: Kotogány Edit , Balog József Á. , Nagy Lajos I. , Alföldi Róbert , Bertagnolo Valeria , Brugnoli Federica , Demjén András , Kovács Anita K. , Batár Péter , Mezei Gabriella , Szabó Renáta , Kanizsai Iván , Varga Csaba , Puskás László G. , Szebeni Gábor J.
Published: July 2020

Chemotherapy-induced differentiation of immature myeloid progenitors, such as acute myeloid leukemia (AML) cells or myeloid-derived suppressor cells (MDSCs), has remained a challenge for the clinicians. Testing our imidazo[1,2-b]pyrazole-7-carboxamide derivative on HL-60 cells, we obtained ERK phosphorylation as an early survival response to treatment followed by the increase of the percentage of the Bcl-xlbright and pAktbright cells. Following the induction of Vav1 and the AP-1 complex, a driver of cellular differentiation, FOS, JUN, JUNB, and JUND were elevated on a concentration and time-dependent manner. As a proof of granulocytic differentiation, the cells remained non-adherent, the expression of CD33 decreased; the granularity, CD11b expression, and MPO activity of HL-60 cells increased upon treatment. Finally, viability of HL-60 cells was hampered shown by the depolarization of mitochondria, activation of caspase-3, cleavage of Z-DEVD-aLUC, appearance of the sub-G1 population, and the leakage of the lactate-dehydrogenase into the supernatant. We confirmed the differentiating effect of our drug candidate on human patient-derived AML cells shown by the increase of CD11b and decrease of CD33+, CD7+, CD206+, and CD38bright cells followed apoptosis (IC50: 80 nM) after treatment ex vivo. Our compound reduced both CD11b+/Ly6C+ and CD11b+/Ly6G+ splenic MDSCs from the murine 4T1 breast cancer model ex vivo.
Bulk Fill Composites Have Similar Performance to Conventional Dental Composites
Authors: Haugen Håvard J. , Marovic Danijela , Par Matej , Khai Le Thieu Minh , Reseland Janne E. , Johnsen Gaute Floer
Published: July 2020

The aim of the study was to perform comprehensive characterization of two commonly used bulk fill composite materials (SDR Flow (SDR) and Filtek™ Bulk Fill Flowable Restorative (FBF) and one conventional composite material (Tetric EvoCeram; TEC). Eleven parameters were examined: flexural strength (FS), flexural modulus (FM), degree of conversion, depth of cure, polymerisation shrinkage (PS), filler particle morphology, filler mass fraction, Vickers hardness, surface roughness following simulated toothbrush abrasion, monomer elution, and cytotoxic reaction of human gingival fibroblasts, osteoblasts, and cancer cells. The degree of conversion and depth of cure were the highest for SDR, followed by FBF and TEC, but there was no difference in PS between them. FS was higher for bulk fill materials, while their FM and hardness were lower than those of TEC. Surface roughness decreased in the order TEC→SDR→FBF. Bisphenol A-glycidyl methacrylate (BisGMA) and urethane dimethacrylate were found in TEC and FBF eluates, while SDR released BisGMA and triethylene glycol dimethacrylate. Conditioned media accumulated for 24 h from FBF and TEC were cytotoxic to primary human osteoblasts. Compared to the conventional composite, the tested bulk fill materials performed equally or better in most of the tests, except for their hardness, elastic modulus, and biocompatibility with osteoblasts.
The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells
Authors: Kim Jung Eun , Lee Yu Jin , Park Hye Ree , Lee Dong Geon , Jeong Kwan Ho , Kang Hoon
Published: July 2020

Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/β-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/β-catenin signaling pathway, including Lef1 and β-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1β, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/β-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.
Structural Characteristics in the γ Chain Variants Associated with Fibrinogen Storage Disease Suggest the Underlying Pathogenic Mechanism
Authors: Burcu Guven , Bellacchio Emanuele , Sag Elif , Cebi Alper Han , Saygin Ismail , Bahadir Aysenur , Yilmaz Guldal , Corbeddu Marialuisa , Cakir Murat , Callea Francesco
Published: July 2020

Particular fibrinogen γ chain mutations occurring in the γ-module induce changes that hamper γ-γ dimerization and provoke intracellular aggregation of the mutant fibrinogen, defective export and plasma deficiency. The hepatic storage predisposes to the development of liver disease. This condition has been termed hereditary hypofibrinogenemia with hepatic storage (HHHS). So far, seven of such mutations in the fibrinogen γ chain have been detected. We are reporting on an additional mutation occurring in a 3.5-year-old Turkish child undergoing a needle liver biopsy because of the concomitance of transaminase elevation of unknown origin and low plasma fibrinogen level. The liver biopsy showed an intra-hepatocytic storage of fibrinogen. The molecular analysis of the three fibrinogen genes revealed a mutation (Fibrinogen Trabzon Thr371Ile) at exon 9 of the γ chain in the child and his father, while the mother and the brother were normal. Fibrinogen Trabzon represents a new fibrinogen γ chain mutation fulfilling the criteria for HHHS. Its occurrence in a Turkish child confirms that HHHS can present in early childhood and provides relevant epidemiological information on the worldwide distribution of the fibrinogen γ chain mutations causing this disease. By analyzing fibrinogen crystal structures and calculating the folding free energy change (ΔΔG) to infer how the variants can affect the conformation and function, we propose a mechanism for the intracellular aggregation of Fibrinogen Trabzon and other γ-module mutations causing HHHS.
Pro-Fibrotic Phenotype in a Patient with Segmental Stiff Skin Syndrome via TGF-β Signaling Overactivation
Authors: Fusco Carmela , Nardella Grazia , Augello Bartolomeo , Boccafoschi Francesca , Palumbo Orazio , Fusaro Luca , Notarangelo Angelantonio , Barbano Raffaela , Parrella Paola , Annicchiarico Giuseppina , De Meco Carmela , Micale Lucia , Graziano Paolo , Castori Marco
Published: July 2020

Transforming growth factor β (TGF-β) superfamily signaling pathways are ubiquitous and essential for several cellular and physiological processes. The overexpression of TGF-β results in excessive fibrosis in multiple human disorders. Among them, stiff skin syndrome (SSS) is an ultrarare and untreatable condition characterized by the progressive thickening and hardening of the dermis, and acquired joint limitations. SSS is distinct in a widespread form, caused by recurrent germline variants of FBN1 encoding a key molecule of the TGF-β signaling, and a segmental form with unknown molecular basis. Here, we report a 12-year-old female with segmental SSS, affecting the right upper limb with acquired thickening of the dermis evident at the magnetic resonance imaging, and progressive limitation of the elbow and shoulder. To better explore the molecular and cellular mechanisms that drive segmental SSS, several functional studies on patient’s fibroblasts were employed. We hypothesized an impairment of TGF-β signaling and, consequently, a dysregulation of the associated downstream signaling. Lesional fibroblast studies showed a higher phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), increased levels of nuclear factor-kB (NFkB), and a nuclear accumulation of phosphorylated Smad2 via Western blot and microscopy analyses. Quantitative PCR expression analysis of genes encoding key extracellular matrix proteins revealed increased levels of COL1A1, COL3A1, AGT, LTBP and ITGB1, while zymography assay reported a reduced metalloproteinase 2 enzymatic activity. In vitro exposure of patient’s fibroblasts to losartan led to the partial restoration of normal transforming growth factor β (TGF-β) marker protein levels. Taken together, these data demonstrate that in our patient, segmental SSS is characterized by the overactivation of multiple TGF-β signaling pathways, which likely results in altered extracellular matrix composition and fibroblast homeostasis. Our results for the first time reported that aberrant TGF-β signaling may drive the pathogenesis of segmental SSS and might open the way to novel therapeutic approaches.
Propolis Envelope Promotes Beneficial Bacteria in the Honey Bee (Apis mellifera) Mouthpart Microbiome
Authors: Dalenberg Hollie , Maes Patrick , Mott Brendon , Anderson Kirk E. , Spivak Marla
Published: July 2020

Honey bees collect and apply plant resins to the interior of their nest cavity, in order to form a layer around the nest cavity called a propolis envelope. Propolis displays antimicrobial activity against honey bee pathogens, but the effect of propolis on the honey bee microbiome is unknown. Honey bees do not intentionally consume propolis, but they do manipulate propolis with their mouthparts. Because honey bee mouthparts are used for collecting and storing nectar and pollen, grooming and trophallaxis between adults, feeding larvae, and cleaning the colony, they are an important interface between the bees’ external and internal environments and serve as a transmission route for core gut bacteria and pathogens alike. We hypothesized that the antimicrobial activity of an experimentally applied propolis envelope would influence the bacterial diversity and abundance of the worker mouthpart microbiome. The results revealed that the mouthparts of worker bees in colonies with a propolis envelope exhibited a significantly lower bacterial diversity and significantly higher bacterial abundance compared to the mouthparts of bees in colonies without a propolis envelope. Based on the taxonomic results, the propolis envelope appeared to reduce pathogenic or opportunistic microbes and promote the proliferation of putatively beneficial microbes on the honey bee mouthparts, thus reinforcing the core microbiome of the mouthpart niche.
Pathways of Oil Spills from Potential Cuban Offshore Exploration: Influence of Ocean Circulation
Authors: Androulidakis Yannis , Kourafalou Vassiliki , Robert Hole Lars , Le Hénaff Matthieu , Kang HeeSook
Published: July 2020

The DeepWater Horizon oil spill in the Gulf of Mexico (GoM) in 2010 raised the public awareness on potential spills from offshore exploration activities. It became apparent that knowledge of potential oil pathways in the case of a spill is important for preparedness and response. This study focuses on such scenarios from potential oil spills in the Cuban Exclusive Economic Zone (EEZ), a vast area in the GoM and the Straits of Florida that has not received much attention in oil spill studies, even though this region has been under evaluation for oil exploration. The Cuban EEZ is also in the crossroads of heavy tanker traffic, from the areas of intense oil exploration in the Northern GoM to the adjacent Caribbean Sea and Atlantic Ocean. The study also evaluates how the oil transport and fate are influenced by the main circulation patterns of the GoM, such as the Loop Current (LC) system and the mesoscale dynamics inside the Straits of Florida, such as the Florida Current (FC) and the accompanying cyclonic (along the northern Straits) and anticyclonic (along the Cuban coasts) eddies. We used oil spill numerical simulations, in tandem with high resolution data-assimilative ocean simulations, to test the fate of potential oil spills originating from different release sites within the Cuban EEZ during a six-year period (2011–2016) to exhibit certain aspects of interannual variability of ocean dynamics. The LC extended and retracted phases in the GoM interior revealed different impacts on the oil fate depending on the release site. The meandering of the FC, which is strongly related to the mesoscale eddies that evolve inside the Straits of Florida, controlled oil pathways either towards the northern Straits or along the Cuban coast. The most likely scenario for oil stranding at southern Florida is from oil released at the deep central Straits of Florida. Oil release near the Yucatan Strait and in the deep Gulf interior showed the highest risk of overall oil beaching at the Gulf beaches. The regional (e.g., LC) and local (e.g., eddies in the Straits) dynamics are proven to be significant indicators to predict the oil fate and stranding along the Gulf coasts, which should lead to improving planning and preparedness in the case of a spill in the Cuban EEZ.
Effect of Breaking Waves on Near-Surface Mixing in an Ocean-Wave Coupling System under Calm Wind Conditions
Authors: Hong Ji-Seok , Moon Jae-Hong , Kim Taekyun
Published: July 2020

Estimating wave effects on vertical mixing is a necessary step toward improving the accuracy and reliability of upper-ocean forecasts. In this study, we evaluate the wave effects on upper-ocean mixing in the northern East China Sea in summer by analyzing the results of comparative experiments: a stand-alone ocean model as a control run and two ocean–wave coupled models that include the effect of the breaking waves (BW) and of the wave–current interaction (WCI) with a vortex-force formalism. The comparison exhibits that under weak wind conditions, the BW effect prescribed by wave dissipation energy significantly enhances near-surface mixing because of increased downward turbulent kinetic energy (TKE), whereas the WCI has little effect on vertical mixing. Increased TKE results in a mixed-layer depth deepened by ~46% relative to the control run, which provides better agreement with the observed surface thermal structure. An additional experiment with local wind–based BW parameterization confirms the importance of nonlocally generated waves that propagated into the study area upon near-surface mixing. This suggests that under calm wind conditions, waves propagated over distances can largely affect surface vertical mixing; thus, ocean–wave coupling is capable of improving the surface thermal structure.
Patient-Derived Tumor Xenograft Models: Toward the Establishment of Precision Cancer Medicine
Authors: Goto Taichiro
Published: July 2020

Patient-derived xenografts (PDXs) describe models involving the implantation of patient-derived tumor tissue into immunodeficient mice. Compared with conventional preclinical models involving the implantation of cancer cell lines into mice, PDXs can be characterized by the preservation of tumor heterogeneity, and the tumor microenvironment (including stroma/vasculature) more closely resembles that in patients. Consequently, the use of PDX models has improved the predictability of clinical therapeutic responses to 80% or greater, compared with approximately 5% for existing models. In the future, molecular biological analyses, omics analyses, and other experiments will be conducted using recently prepared PDX models under the strong expectation that the analysis of cancer pathophysiology, stem cells, and novel treatment targets and biomarkers will be improved, thereby promoting drug development. This review outlines the methods for preparing PDX models, advances in cancer research using PDX mice, and perspectives for the establishment of precision cancer medicine within the framework of personalized cancer medicine.
Evaluating FDM Process Parameter Sensitive Mechanical Performance of Elastomers at Various Strain Rates of Loading
Authors: Chaudhry Muhammad Salman , Czekanski Aleksander
Published: July 2020

To optimize the mechanical performance of fused deposition modelling (FDM) fabricated parts, it is necessary to evaluate the influence of process parameters on the resulting mechanical performance. The main focus of the study was to characterize the influence of the initial process parameters on the mechanical performance of thermoplastic polyurethane under a quasi-static and high strain rate (~2500 s−1). The effects of infill percentage, layer height, and raster orientation on the mechanical properties of an FDM-fabricated part were evaluated. At a quasi-static rate of loading, layer height was found to be the most significant factor (36.5% enhancement in tensile strength). As the layer height of the sample increased from 0.1 to 0.4 mm, the resulting tensile strength sample was decreased by 36.5%. At a high-strain rate of loading, infill percentage was found to be the most critical factor influencing the mechanical strength of the sample (12.4% enhancement of compressive strength at 100% as compared to 80% infill). Furthermore, statistical analysis revealed the presence of significant interactions between the input parameters. Finally, using an artificial neural networking approach, we evaluated a regression model that related the process parameters (input factors) to the resulting strength of the samples.
Mixed-Mode I-II Fracture Process Zone Characteristic of the Four-Point Shearing Concrete Beam
Authors: Li Guodong , Ren Zhengyi , Yu Jiangjiang
Published: July 2020

The size of the fracture process zone (FPZ) has significance for studying the fracture mechanism and fracture characteristics of concrete. This paper presents the method of assessing the FPZ of Mixed-Mode I-II for quasi-static four-point shearing concrete beams with pre-notched by Lagrangian strain profiles from digital image correlation (DIC). Additionally, it explores the influences of volume rates of the coarse aggregate of 0%, 28%, 48%, and 68%, and the specific surface areas of 0.12 m2/kg, 0.15 m2/kg, and 0.26 m2/kg on the size of the FPZ. It shows that the size of FPZ in four-point shearing concrete beam can be characterized by the displacement field and strain field using DIC. The size of FPZ conforms to linear positive correlation with the volume rate of coarse aggregate, and linear negative correlation with the specific surface area of coarse aggregate. It presents that the crack initiation of the four-point shearing beam with the pre notch is dominated by mode I load, and the propagation and fracture of Mixed-Mode I-II cracks are caused by the combined effect of Mode I and Mode II loading.
Study on the Influence of Surface Temperature Field of Aluminum Alloy Etched by Laser Water Jet Composite Machining
Authors: Chen Xuehui , Xu Xin , Liu Wei , Huang Lei , Li Hao , Wu Chao , Mu Weihao , Li Xiang
Published: July 2020

This paper studies the compound effect of liquid medium and laser on the workpiece and analyses the law of material surface temperature change during the processing. Taking 7075-T6 aluminum alloy as the research object, the surface temperature field of aluminum alloy processed using water-jet-assisted laser machining under different process parameters was simulated using finite element software. In addition, the temperature field of the material surface was detected in real-time using the self-built water-jet-assisted laser machining temperature field detection system, and the processing results were observed and verified using an optical microscope, scanning electron microscope, and energy spectrum analyzer. The results show that when the water jet inflow angle is 45°, the heat-affected area of the material surface is the smallest, and the cooling effect of the temperature field of the material surface is better. Considering the liquidus melting point of 7075 aluminum alloys, it is concluded that the processing effect is better when the water jet velocity is 14 m·s−1, the laser power is 100 W, and the laser scanning speed is 1.2 mm·s−1. At this time, the quality of the tank is relatively good, there are no cracks in the bottom of the tank, and there is less slag accumulation. Compared with anhydrous laser etching, water-jet-assisted laser etching can reduce the problems of micro-cracks, molten slag, and the formation of a recast layer in laser etching and improve the quality of the workpiece, and the composition of the bottom slag does not change. This study provides theoretical guidance and application support for the selection and optimization of process parameters for water-jet-assisted laser etching of aluminum alloy and further enriches the heat transfer mechanism of multi-field coupling in the process of water-jet-assisted laser machining.
Functionalized Wool as an Efficient and Sustainable Adsorbent for Removal of Zn(II) from an Aqueous Solution
Authors: Simonič Marjana , Fras Zemljič Lidija
Published: July 2020

In this paper, the aim of the research was to obtain a highly efficient wool-based sorbent for the removal of zinc Zn(II) from wastewater. To increase the functional groups for metal binding, the wool was functionalized with chitosan. Chitosan has amino groups through which metals can be complexed easily to chelates. The physical and chemical modification of chitosan on wool was performed to analyze the influence of the coating bond on the final ability of the wool to remove metals. The presence of functional chitosan groups onto wool after adsorption was verified by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FT-IR) spectra. The effective binding of chitosan to wool was also determined by potentiometric and polyelectrolyte titration methods. The latter titration was used to analyze the chitosan desorption. The main part of the study was the sorption of Zn(II) on natural and functionalized wool. The influence was investigated as a function of contact time, pH, metal ion concentration and temperature on the sorption process. The absorbent with the highest concentration of protonated amino groups (607.7 mmol/kg) and responding sorption capacity of 1.52 mg/g was obtained with wool physically modified by a macromolecular chitosan solution (1%) at pH = 7. Adsorption of Zn(II) onto pristine and modified wool corresponded to pseudo-second order kinetics (R2 > 0.9884). The Langmuir model was found to be more suitable (R2 > 0.9866) in comparison to the Freundlich model. The Zn(II) sorption process was spontaneous (∆G < 0) and exothermic (∆H < 0). The results found in this study are significant for escalating the possible use of wool modified with polysaccharide coatings as a sustainable source to improve or increase the metal sorption activity of wool.