bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism in the Tumor Microenvironment
Authors: Lau Allison N. , Vander Heiden Matthew G.
Published: November 2019

Experiments in culture systems where one cell type is provided with abundant nutrients and oxygen have been used to inform much of our understanding of cancer metabolism. However, many differences have been observed between the metabolism of tumors and the metabolism of cancer cells grown in monoculture. These differences reflect, at least in part, the presence of nonmalignant cells in the tumor microenvironment and the interactions between those cells and cancer cells. However, less is known about how the metabolism of various tumor stromal cell types differs from that of cancer cells, and how this difference might inform therapeutic targeting of metabolic pathways. Emerging data have identified both cooperative and competitive relationships between different cell types in a tumor, and this review examines how four abundant stromal cell types in the tumor microenvironment, fibroblasts, T cells, macrophages, and endothelial cells, contribute to the metabolism of tumors.
Mitophagy and Mitochondrial Dysfunction in Cancer
Authors: Macleod Kay F.
Published: November 2019

The process of mitophagy, in which mitochondria are selectively turned over at the autophagolysosome, plays a central role in both eliminating dysfunctional mitochondria and reducing mitochondrial mass as an adaptive response to key physiological stresses, such as hypoxia, nutrient deprivation, and DNA damage. Defects in mitophagy have been linked to altered mitochondrial metabolism, production of excess reactive oxygen species and ferroptosis, heightened inflammasome activation, altered cell fate decisions, and senescence, among other cellular consequences. Consequently, functional mitophagy contributes to proper tissue differentiation and repair and metabolic homeostasis, limiting inflammatory responses and modulating tumor progression and metastasis. This review examines the major pathways that control mitophagy, including PINK1-dependent mitophagy and BNIP3/NIX-dependent mitophagy. It also discusses the cellular signaling mechanisms used to sense mitochondrial dysfunction to activate mitophagy and how defective mitophagy results in deregulated tumor cell growth and cancer.
Metabolic Drivers in Hereditary Cancer Syndromes
Authors: Sciacovelli Marco , Schmidt Christina , Maher Eamonn R. , Frezza Christian
Published: November 2019

Cancer is a multifaceted disease in which inherited genetic variants can be important drivers of tumorigenesis. The discovery that germline mutations of metabolic genes predispose to familial forms of cancer caused a shift in our understanding of how metabolism contributes to tumorigenesis, providing evidence that metabolic alterations can be oncogenic. In this review, we focus on mitochondrial enzymes whose mutations predispose to familial cancer, and we fully appraise their involvement in cancer formation and progression. Elucidating the molecular mechanisms that orchestrate transformation in these diverse tumors may answer key biological questions about tumor formation and evolution, leading to the identification of new therapeutic targets of intervention.
Targeting MYC Proteins for Tumor Therapy
Authors: Wolf Elmar , Eilers Martin
Published: November 2019

Targeting the function of MYC oncoproteins holds the promise of achieving conceptually new and effective anticancer therapies that can be applied to a broad range of tumors. The nature of the target however—a broadly, possibly universally acting transcription factor that has no enzymatic activity and is largely unstructured unless complexed with partner proteins—has so far defied the development of clinically applicable MYC-directed therapies. At the same time, lingering questions about exactly which functions of MYC proteins account for their pervasive oncogenic role in human tumors and need to be targeted have prevented the development of effective therapies using surrogate targets that act in critical MYC-dependent pathways. In this review, we therefore argue that rigorous testing of critical oncogenic functions and protein/protein interactions and new chemical approaches to target them are necessary to successfully eradicate MYC-driven tumors.
Big Data in Industrial-Organizational Psychology and Human Resource Management: Forward Progress for Organizational Research and Practice
Authors: Oswald Frederick L. , Behrend Tara S. , Putka Dan J. , Sinar Evan
Published: November 2019

Big data and artificial intelligence (AI) have become quite compelling—and relevant, ideally—to organizations and the consulting services that help manage them. Researchers and practitioners in industrial-organizational psychology (IOP) and human resource management (HRM) can add significant value to big data and AI by offering their substantive expertise in how workforce-relevant data are measured and analyzed and how big data results are professionally, legally, and ethically interpreted and implemented by organizational decision makers, employees, policymakers, and other stakeholders in the employment arena. This article provides a perspective and framework for big data relevant to IOP and HRM that include both micro issues (e.g., linking data sources, decisions about which data to include, big data analytics) and macro issues (e.g., changing nature of big data, developing big data teams, educating professionals and graduate students, ethical and legal considerations). Ultimately, we strongly believe that IOP and HRM researchers and practitioners will become increasingly valuable for their contributions to the substance, technologies, algorithms, and communities that address big data, AI, and machine learning problems and applications in organizations relevant to their expertise.
Long noncoding RNA KCNQ1OT1 induces pyroptosis in diabetic corneal endothelial keratopathy
Authors: Zhang Yanyan , Song Zhen , Li Xuran , Xu Shuo , Zhou Sujun , Jin Xin , Zhang Hong
Published: November 2019

Diabetic corneal endothelial keratopathy is an intractable ocular complication characterized by corneal edema and endothelial decompensation, which seriously threaten vision. It has been suggested that diabetes is associated with pyroptosis, a type of programmed cell death via the activation of inflammation. Long noncoding RNA KCNQ1OT1 is commonly associated with various pathophysiological mechanisms of diabetic complications, including diabetic cardiomyopathy and diabetic retinopathy. However, whether KCNQ1OT1 is capable of regulating pyroptosis and participates in the pathogenesis of diabetic corneal endothelial keratopathy remains unknown. The aim of this study was to investigate the mechanisms of KCNQ1OT1 in diabetic corneal endothelial keratopathy. Here, we reveal that KCNQ1OT1 and pyroptosis can be triggered in diabetic human and rat corneal endothelium, along with the high glucose-treated corneal endothelial cells. However, miR-214 expression was substantially decreased in vivo and in experiments with cultured cells. LDH assay was also used to verify the existence of pyroptosis in high glucose-treated cells. Bioinformatics prediction and luciferase assays showed that KCNQ1OT1 may function as a competing endogenous RNA binding miR-214 to regulate the expression of caspase-1. To further analyze the KCNQ1OT1-mediated mechanism, miR-214 mimic and inhibitor were introduced into the high glucose-treated corneal endothelial cells. The results showed that upregulation of miR-214 attenuated pyroptosis; conversely, knockdown of miR-214 promoted it. In addition, KCNQ1OT1 knockdown by a small interfering RNA decreased pyroptosis factors expressions but enhanced miR-214 expression in corneal endothelial cells. To understand the signaling mechanisms underlying the prepyroptotic properties of KCNQ1OT1, si-KCNQ1OT1 was cotransfected with or without miR-214 inhibitor. The results showed that pyroptosis was repressed after silencing KCNQ1OT1 but was reversed by cotransfection with miR-214 inhibitor, suggesting that KCNQ1OT1 mediated pyroptosis induced by high glucose via targeting miR-214. Therefore, the KCNQ1OT1/miR-214/caspase-1 signaling pathway represents a new mechanism of diabetic corneal endothelial keratopathy progression, and KCNQ1OT1 could potentially be a novel therapeutic target.
Dysregulation of the glutaredoxin/S-glutathionylation redox axis in lung diseases
Authors: Chia Shi B. , Elko Evan A. , Aboushousha Reem , Manuel Allison M. , van de Wetering Cheryl , Druso Joseph E. , van der Velden Jos , Seward David J. , Anathy Vikas , Irvin Charles G. , Lam Ying-Wai , van der Vliet Albert , Janssen-Heininger Yvonne M. W.
Published: November 2019

Glutathione is a major redox buffer, reaching millimolar concentrations within cells and high micromolar concentrations in airways. While glutathione has been traditionally known as an antioxidant defense mechanism that protects the lung tissue from oxidative stress, glutathione more recently has become recognized for its ability to become covalently conjugated to reactive cysteines within proteins, a modification known as S-glutathionylation (or S-glutathiolation or protein mixed disulfide). S-glutathionylation has the potential to change the structure and function of the target protein, owing to its size (the addition of three amino acids) and charge (glutamic acid). S-glutathionylation also protects proteins from irreversible oxidation, allowing them to be enzymatically regenerated. Numerous enzymes have been identified to catalyze the glutathionylation/deglutathionylation reactions, including glutathione S-transferases and glutaredoxins. Although protein S-glutathionylation has been implicated in numerous biological processes, S-glutathionylated proteomes have largely remained unknown. In this paper, we focus on the pathways that regulate GSH homeostasis, S-glutathionylated proteins, and glutaredoxins, and we review methods required toward identification of glutathionylated proteomes. Finally, we present the latest findings on the role of glutathionylation/glutaredoxins in various lung diseases: idiopathic pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease.
Altered immune system in offspring of rat maternal vertical sleeve gastrectomy
Authors: Spann Redin A. , Taylor Erin B. , Welch Bradley A. , Grayson Bernadette E.
Published: November 2019

Obesity in women results in reduced fertility and increased complications during pregnancy. Vertical sleeve gastrectomy (VSG) effectively reduces weight, type 2 diabetes, and dyslipidemia, but is also associated with preterm and small-for-gestational age births. The mechanism by which VSG influences fetal development remains unknown. Here we hypothesize that previously reported immune changes during rat VSG pregnancy are reflected long term in the immune system of the offspring. Offspring of VSG and sham dams were evaluated at postnatal day (PND) 21 and PND60. At PND21, VSG pups have lower numbers of circulating B lymphocytes compared with sham pups ( P < 0.05) and have lower transcription of lymphocyte marker Ptprc ( P < 0.01) in the spleen, while other lymphocyte populations measured are not different. Total plasma IgG is higher ( P < 0.01) and C-reactive protein is lower ( P < 0.05) in VSG offspring compared with sham offspring at PND21. The central nervous system of VSG pups is also affected at PND21, having higher expression of Il1b mRNA ( P < 0.05) and higher immunoreactivity of microglia marker, IBA1, in the hypothalamus. At PND60, the immune-hematological differences are not present; however, mRNA expression of Il1b is elevated ( P < 0.001) in the spleen of VSG offspring along with markers of T cells. These data suggest that the immune system of VSG offspring is compromised early in life, but rebounds after weaning and may even become hyperactive. Future work is needed to determine whether the immune system of VSG offspring is capable of mounting a proper defense and whether other aspects of development are affected.
Study on Pyrolysis Characteristics of Coal and Combustion Gas Release in Inert Environment
Authors: Dong Liang , Wang Ziming , Zhang Yadong , Lu Junyu , Zhou Enhui , Duan Chenlong , Cao Xiaoqiang
Published: November 2019

In this study, thermogravimetric analysis (TGA) coupled with Fourier transform infrared (FTIR) spectroscopy was used to heat the coal samples of six different coalification degrees from room temperature to 1000°C at 20°C·min−1 under nitrogen atmosphere. The influence of coal degree and pyrolysis temperature on the content of pyrolysis products of coal was analyzed by the TG/DTG curve. FTIR spectroscopy was used to obtain the IR spectra of generated gases and study their variation at different temperatures in the process of coal heating without oxygen, and the gas release during pyrolysis was discussed. The results showed that the pyrolysis reaction initiated at 400°C and ended at 800°C. The maximum mass loss occurred in the temperature range of 480 to 500°C. The values of maximum and minimum weight loss rates were 32.72 and 18.89%, respectively. The mass loss during the pyrolysis process corresponded well with the volatile matter contained in the sample. Permanent gas analysis and IR spectrum analysis indicated that when the temperature was 600°C, the peak value of methane (CH4) appeared at 3016 wave, indicating the generation of CH4 at this time. When the temperature reached 700°C, the peak area of 2360 wave increased, all coal samples began to release carbon dioxide (CO2), release rate of CH4 gas decreased, and yield of CO2 was maximized. At 800°C, all peaks of 3160 wave disappeared, indicating that there was no unreacted short-chain release at this temperature. At the same time, the pyrolysis reaction tended to remove the excess hydrogen-oxygen conjugates in the carbon structure and release them in the form of water vapor.
The Involvement of HLA Class II Alleles in Multiple Sclerosis: A Systematic Review with Meta-analysis
Authors: De Silvestri A. , Capittini C. , Mallucci G. , Bergamaschi R. , Rebuffi C. , Pasi A. , Martinetti M. , Tinelli C.
Published: November 2019

Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.
Dihydroartemisinin Protects against Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting the PI3K/AKT and NF-κB Signaling Pathways
Authors: Li Ning , Sun Wenjing , Zhou Xin , Gong Hao , Chen Yuqing , Chen Dongfeng , Xiang Fei
Published: November 2019

Ulcerative colitis is a common inflammatory bowel disease, and the activation of thePI3K/AKT and NF-κB signaling pathways plays a pivotal role in its pathogenesis. Dihydroartemisinin (DHA) is a widely used antimalarial drug and has shown anticancer effect partially through inhibiting the activation of PI3K/AKT and NF-κB. This study aimed to investigate the effect of dihydroartemisinin on ulcerative colitis and its mechanism. Adult male C57 mice were subjected to 3.0% dextran sulfate sodium (DSS) for seven days; simultaneously, dihydroartemisinin or control saline was administered by oral gavage once a day. In vitro, the intestinal epithelial cell-6 was treated with LPS for 24 hours with or without dihydroartemisinin combined with PI3K/Akt activator 740 Y-P or NF-κB activator phorbol myristate acetate. Western blotting was used to test the activation of PI3K/AKT and NF-κB. Dihydroartemisinin significantly ameliorated body weight loss, shortened colon length, and increased DAI in DSS-induced colitis. Meanwhile, histological damage was improved and was accompanied by decreased expression and secretion of proinflammatory cytokines. Moreover, DSS-induced elevation of phosphorylation of PI3K, AKT, IKKα, IκBα, and NF-κB (p65) was remarkably blunted by dihydroartemisinin both in vivo and in vitro, indicating an inhibitive property on the PI3K/AKT and NF-κB signaling pathways. Furthermore, administration of 740 Y-P or PMA significantly blocked protective activity of dihydroartemisinin against colitis in vitro. In conclusion, dihydroartemisinin can attenuate DSS-induced colitis, and its anticolitis effect might be mediated via the PI3K/AKT and NF-κB signaling pathways. DHA might serve as a promising drug for patients with ulcerative colitis.
Hub Genes and Key Pathway Identification in Colorectal Cancer Based on Bioinformatic Analysis
Authors: Lv Jian , Li Lili
Published: November 2019

Colorectal cancer (CRC) is one of the most common malignant tumors. The aim of the present study was to identify key genes and pathways to improve the understanding of the mechanism of CRC. GSE87211, including 203 CRC samples and 160 control samples, was screened to identify differentially expressed genes (DEGs). In total, 853 DEGs were obtained, including 363 upregulated genes and 490 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed to obtain enrichment datasets. GO analysis showed that DEGs were significantly enriched in the extracellular region, cell-cell signaling, hormone activity, and cytokine activity. KEGG pathway analysis revealed that the DEGs were mainly enriched in the cytokine-cytokine receptor interaction, drug metabolism, androgen and estrogen metabolism, and neuroactive ligand-receptor interaction. The Protein-Protein Interaction (PPI) network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes (STRING). The app MCODE plugged in Cytoscape was used to explore the key modules involved in disease development. 43 key genes involved in the top two modules were identified. Six hub genes (CXCL2, CXCL3, PTGDR2, GRP, CXCL11, and AGTR1) were statistically associated with patient overall survival or disease-free survival. The functions of six hub genes were mainly related to the hormone and chemokine activities. In conclusion, the present study may help understand the molecular mechanisms of CRC development.
Pituitary Involvement in Granulomatosis with Polyangiitis: A Retrospective Analysis in a Single Chinese Hospital and a Literature Review
Authors: Liu Shixuan , Xu Yan , Li Naishi , Chen Shi , Zhang Shangzhu , Peng Linyi , Bai Wei , Wang Jinglan , Gao Jinming , Zeng Xiaofeng , Shi Juhong , Wang Mengzhao
Published: November 2019

Purpose. Granulomatosis with polyangiitis (GPA) is an anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis that can involve virtually many organs, including the pituitary. Pituitary involvement in GPA is rare, with only case reports or small case series published previously.Methods. We used the electronic medical record system in our hospital to identify four patients of pituitary involvement in GPA. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the four patients. We further performed a systematic literature review of 66 GPA cases with pituitary involvement that were published on the PubMed database.Results. The four women in our report were between 57 and 73 years of age. All patients had pituitary abnormalities on radiology; three developed diabetes insipidus (DI). All patients had multisystem involvement. After treatment with glucocorticoids and cyclophosphamide (CYC), all patients showed clinical improvement but pituitary function did not resume. Literature review identified 66 additional patients with pituitary involvement in GPA; diabetes insipidus (57/66, 86.4%) and hypogonadism (34/66, 51.5%) were the most frequent pituitary disorders, and the most frequent imaging lesion was an enlarged pituitary (25/64, 39.1%). After treatment with corticosteroids and/or immunosuppressive agents, most patients (45/66, 68.2%) developed remission from systemic disease, 13 patients (13/57, 22.8%) showed remission of DI, and 8 patients (8/46, 17.4%) showed remission of hormone deficiencies.Conclusions. GPA should be carefully considered as a potential cause of pituitary dysfunction (PD), especially when multisystem dysfunction exists. Conventional treatment with corticosteroids and/or immunosuppressive agents improves systemic symptoms, but pituitary disorders persisted in most patients.
Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway
Authors: Ye Wen , Zheng Chenlei , Yu Dinglai , Zhang Fan , Pan Reguang , Ni Xiaofeng , Shi Zhehao , Zhang Zhongjing , Xiang Yukai , Sun Hongwei , Shi Keqing , Chen Bicheng , Zhang Qiyu , Zhou Mengtao
Published: November 2019

Acute lung injury (ALI) is a critical event involved in the pathophysiological process of acute pancreatitis (AP). Many methods have been widely used for the treatment of AP-ALI, but few are useful during early inflammation. Lipoxin A4 (LXA4), a potent available anti-inflammatory and novel antioxidant mediator, has been extensively studied in AP-ALI, but its underlying mechanism as a protective mediator is not clear. This research was conducted to identify the possible targets and mechanisms involved in the anti-AP-ALI effect of LXA4. First, we confirmed that LXA4 strongly inhibited AP-ALI in mice. Next, using ELISA, PCR, and fluorescence detection to evaluate different parameters, LXA4 was shown to reduce the inflammatory cytokine production induced by AP and block reactive oxygen species (ROS) generation in vivo and in vitro. In addition, TNF-α treatment activated the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream gene heme oxygenase-1 (HO-1) in human pulmonary microvascular endothelial cells (HPMECs), and LXA4 further promoted their expression. This study also provided evidence that LXA4 phosphorylates Ser40 and triggers its nuclear translocation to activate Nrf2. Moreover, when Nrf2-knockout (Nrf2-/-) mice and cells were used to further assess the effect of the Nrf2/HO-1 pathway, we found that Nrf2 expression knockdown partially eliminated the effect of LXA4 on the reductions in inflammatory factor levels while abrogating the inhibitory effect of LXA4 on the ROS generation stimulated by AP-ALI. Overall, LXA4 attenuated the resolution of AP-induced inflammation and ROS generation to mitigate ALI, perhaps by modulating the Nrf2/HO-1 pathway. These findings have laid a foundation for the treatment of AP-ALI.
In Situ Endoscopic Analysis of Vascular Supply and Regenerated Alveolar Bone in β-TCP Grafted and Ungrafted Postextraction Sites before Implant Placement: A Prospective Case Control Study
Authors: Beltrán Víctor , Lazzarini Marcio , Figueroa Rodolfo , Sousa Vanessa , Engelke Wilfried
Published: November 2019

Background. Endoscopy has seen a significant development over recent years in various medical fields with its application expanding from the support of minimal invasive surgery to in situ imaging. In this context, the application of endoscopic techniques to assess the quality of the regenerated bone in situ in the drill hole before implant placement is an appealing approach. Aim. The aim of this study was to use short distance support immersion endoscopy (SD-SIE) to compare the quality of regenerated bone in healed postextraction sites, which are grafted with an in situ hardening β-TCP, against ungrafted sites, before implant placement. This assessment was based on microscopic bone analysis in combination with the blood vessel count. Method. 13 spontaneously healed and 13 grafted postextraction sites in 3 men and 6 women, aged 26–83 years, were evaluated using SD-SIE after 4–6 months. SD-SIE was applied in drill holes before implant placement, and videos were taken from representative central buccal areas. The video recordings were analyzed using Image J software for (1) number of blood vessels per area (NBV), (2) relative area of vessels (VA), (3) relative area of mineralized bone (MBA), (4) relative area of unmineralized bone (UMBA), and (5) relative area of bone substitute (BSA). Results. The grafted sites showed more (1) NBV as well as (2) VA (8.6 ± 1.1; 2.03 ± 0.28%) than the ungrafted sites (2.5 ± 0.6; 1.18 ± 0.36%) (independent t-test; p<0.05); (3) MBA and (4) UMBA were similar to those in the grafted sites (86.3 ± 2.2 %; 13.7 ± 2.2 %) and to the ungrafted sites (89.5 ± 3.7%; 10.5 ± 3.6%) (independent t-test; p>0.05); and (5) BSA in the grafted sites was 18.2 ± 5.4%. Conclusion. SD-SIE is an interesting new approach for in situ assessment of bone quality and blood supply before implant placement. The regenerated bone in β-TCP grafted extraction sockets showed an increased vascularization compared to ungrafted sites providing a vital support for subsequent implant placement.
Evidence Supporting the Hypothesis That Inflammation-Induced Vasospasm Is Involved in the Pathogenesis of Acquired Sensorineural Hearing Loss
Authors: Eisenhut Michael
Published: November 2019

Sensorineural hearing loss is mainly acquired and affects an estimated 1.3 billion humans worldwide. It is related to aging, noise, infection, ototoxic drugs, and genetic defects. It is essential to identify reversible and preventable causes to be able to reduce the burden of this disease. Inflammation is involved in most causes and leads to tissue injury through vasospasm-associated ischemia. Vasospasm is reversible. This review summarized evidence linking inflammation-induced vasospasm to several forms of acquired sensorineural hearing loss. The link between vasospasm and sensorineural hearing loss is directly evident in subarachnoid haemorrhage, which involves the release of vasoconstriction-inducing cytokines like interleukin-1, endothelin-1, and tumour necrosis factor. These proinflammatory cytokines can also be released in response to infection, autoimmune disease, and acute or chronically increased inflammation in the ageing organism as in presbyacusis or in noise-induced cochlear injury. Evidence of vasospasm and hearing loss has also been discovered in bacterial meningitis and brain injury. Resolution of inflammation-induced vasospasm has been associated with improvement of hearing in autoimmune diseases involving overproduction of interleukin-1 from inflammasomes. There is mainly indirect evidence for vasospasm-associated sensorineural hearing loss in most forms of systemic or injury- or infection-induced local vascular inflammation. This opens up avenues in prevention and treatment of vascular and systemic inflammation as well as vasospasm itself as a way to prevent and treat most forms of acquired sensorineural hearing loss. Future research needs to investigate interventions antagonising vasospasm and vasospasm-inducing proinflammatory cytokines and their production in randomised controlled trials of prevention and treatment of acquired sensorineural hearing loss. Prime candidates for interventions are hereby inflammasome inhibitors and vasospasm-reducing drugs like nitric oxide donors, rho-kinase inhibitors, and magnesium which have the potential to reduce sensorineural hearing loss in meningitis, exposure to noise, brain injury, arteriosclerosis, and advanced age-related and autoimmune disease-related inflammation.
Generation of Realistic Virtual Garments on Recovery Human Model
Authors: Zhu Yuxiang , Peng Yanjun
Published: November 2019

Displaying a variety of fabrics on a customized character could help customers choose which fabric is more suitable for themselves and help customers choose clothing. However, it is not an easy task to show realistic garment on customized virtual character. As a result, we propose a stable finite element method (FEM) model which is stable to approximate stretching behaviors. At first, we measure four kinds of cloth materials with measurement techniques to research elastic deformations in real cloth samples. Then, we use the parameter optimization method by fitting the model with measurement data. For promoting the display of realistic fabrics, we recover 3D human in shape and pose from a single image automatically. Human body datasets are constructed at first. Then, CNN‐based image retrieval in shape and skeleton‐based template matching method in pose are combined for 3D human model recovery. To enrich human body details, we synthesize the human body and 3D face with spatial transformation. We compared our proposed method of recovering 3D human from a single image with the state‐of‐the‐art methods, and the experimental results show that the proposed method allows the recovered virtual human to put on garment with different fabrics and significantly improves the fidelity of virtual garment.
miR-129-5p Inhibits Adipogenesis through Autophagy and May Be a Potential Biomarker for Obesity
Authors: Fu Xue , Jin Lina , Han Luyu , Yuan Yini , Mu Qian , Wang Hui , Yang Jian , Ning Guang , Zhou Donglei , Zhang Zhiguo
Published: November 2019

Introduction. Obesity has an unclear pathogenesis. MicroRNAs (miRNAs) may function as biologically active molecules for obesity through regulating adipocyte differentiation. This study aimed to identify how miR-129-5p (a specific miRNA) regulates adipogenesis in vitro and explore its possible role in the pathogenesis of obesity in humans.Materials and Methods. The miR-129-5p expression was detected in obese mouse models. The effect of miR-129-5p on adipocyte differentiation was observed, and the adipose markers were analyzed. Bioinformatics and dual-luciferase reporter assay were applied to predict and confirm the target genes of miR-129-5p. The human serum samples were detected and analyzed.Results. miR-129-5p is highly expressed in adipose tissues ofdb/dbmice. Gain- and loss-of-function studies show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets ATG7 which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay. Serum miR-129-5p level was evidently elevated in patients with simple obesity (p<0.01) and correlates with obesity indices, including BMI (r = 0.407,p<0.029) and fat percentage (r = 0.394,p<0.038).Conclusion. miR-129-5p might target on the ATG7-related autophagy signaling network that regulates white and brown adipogenesis. Importantly, the aforementioned results suggest serum miR-129-5p might be a potential biomarker and therapeutic target for obesity.
Semiactive Control of High‐Speed Railway Vehicle Suspension Systems with Magnetorheological Dampers
Authors: Liao Yingying , Liu Yongqiang , Yang Shaopu
Published: November 2019

Using the magnetorheological (MR) damper model, this paper derives a semiactive suspension model for a high‐speed railway vehicle, and a new evaluating method is proposed to analyze the effect of two kinds of time delay existing in control systems on vehicle dynamic performance. The railway vehicle is modeled by a 50 degree‐of‐freedom (DOF) system which considers the full 6 DOF of each wheelset, bogie, car body, and the pitch angle of each axle box. Several control strategies, sky‐hook (SH), acceleration‐driven damping (ADD), and mixed SH‐ADD, are considered in the semiactive suspension system. To evaluate the effect of these semiactive controls and the different kinds of time delay on the lateral ride index of a high‐speed railway vehicle, a 3D surface in a rectangular coordinate system is described. The cross curve between the 3D surface and a horizontal plane which represents the performance of passive suspension is projected on the X‐Y plane, and the area enclosed by the contour line, X‐axis, and Y‐axis can be used to evaluate the performance of semiactive controls. The results show that the new method is convenient to evaluate the performance of semiactive control strategies visually when there is more than one kind of time delay.
Vibration Failure Analysis and Countermeasures of the Inlet Pipelines at a Gas Compressor Station
Authors: Li Shuangshuang , Zhang Liwen , Kong Chunyan
Published: November 2019

A gas compressor station only had its about 35% design processing capacity as a result of the abnormal piping vibrations on the inlet pipelines. Characterization, diagnostics, analysis, and elimination of piping vibration were performed. The root causes and sources of the abnormal vibration were investigated by on‐site measurements and analysis of vibration and pulsation under various load conditions of compressors. The results revealed that it was not mechanical resonance, but the high pressure pulsation and acoustic resonance occurred on the inlet pipelines, which resulted in the severe vibration. Three different modification models against vibration were proposed by shortening the length of the pipe to avoid acoustic resonance, enlarging the volume of the gathering manifold to buffer pressure pulsation, and adding supports to increase the stiffness. A better modification model was applied by performing modal analysis and fluid‐structure interaction (FSI) vibration analysis using the finite element method. The effect of countermeasures was evaluated by vibration and pulsation measurements during operation after modifications, which results showed the level of piping vibration and pressure pulsation was within the allowable limits. The processing capacity of the gas station has reached its design requirement as a result of the desired reduction in vibrations.
Autologous Platelet-Rich Fibrin in the Treatment of Refractory Macular Holes
Authors: Koytak Arif , Nuhoglu Fadime , Bayraktar Havvanur , Ercan Rukiye , Ozdemir Hakan
Published: November 2019

Purpose.To describe a novel method for the treatment of refractory macular holes.Methods.Two case reports on the use of autologous platelet rich fibrin (PRF), followed by sulfur hexafluoride gas tamponade to facilitate closure of refractory macular holes.Results.Macular holes were succesfully closed within a week in both cases. Best corrected Snellen visual acuities improved from counting fingers to 0.16 in the first case, and from 0.05 to 0.2 in the second case. No complication occurred during or after the procedures.Conclusion.The use of autologous PRF seems to be a safe and effective alternative method for the treatment of refractory macular holes. Further experience and studies are required to assess the value of autologous PRF in the management of challenging macular hole cases of different etiologies. To the best of our knowledge, this is the first use of autologous PRF in the treatment of macular holes.
Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing
Authors: Su Shan , Zou Jian-Jun , Zeng Yun-Yun , Cen Wen-Chang , Zhou Wei , Liu Yan , Su Duo-Hua , Zhang Xian-Lan , Huang Hui-Yi , Lei An , Huang Zhi-Hao , Jin Yun , Li Lei , Su Ning , Xie Ya-Lin , Zhao Zhen-Gang , Liu Jian-Xiong
Published: November 2019

Purpose. Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. Materials and Methods. Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. Results. A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. Conclusion. TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.
Development of a HPLC-MS/MS Method to Determine the 13 Elements of Semen Cuscutae and Application to a Pharmacokinetic Study in Rats
Authors: Shen Jiayuan , Jia Qi , Huang Xuhua , Yao Guangzhe , Ma Wenjuan , Zhang Huamei , Ouyang Huizi , He Jun
Published: November 2019

This study developed a method for simultaneous determination of 13 elements of Semen Cuscutae (quercitrin, quercetin, hyperoside, caffeic acid, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercitrin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, astragalin, and rutin) in rat plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in the negative MRM mode. The analytes were analyzed with CORTECS®C18 column (4.6 × 150 mm, 2.7 μm) with mobile phases consisting of 0.1% formic acid in water (A) and acetonitrile (B). The intra- and interday precision of the target compounds were expressed as relative standard deviation (RSD) in the range of 0.5%–10.4%, and the accuracy of the target compounds was expressed as relative error (RE) not exceeding ±14.5% for all analytes. In the meantime, the extraction recovery of the target compounds in plasma samples ranged from 87.4% to 106.2% and matrix effect from 81.0% to 115.5%. The established method was successfully accomplished for the pharmacokinetic study of the analytes in rat plasma samples following oral administration of Semen Cuscutae extract, and the pharmacokinetic parameters of seven compounds were obtained.
Origin, Genetic Diversity, and Population Structure of Rabbits (Oryctolagus cuniculus) in Kenya
Authors: Owuor Sharon Auma , Mamati Edward George , Kasili Remmy Wekesa
Published: November 2019

To evaluate the origin, genetic diversity, and population structure of domesticated rabbits in Kenya, a 263-base pair region of mtDNA D-loop region of 111 rabbits sampled from Kakamega, Vihiga, and Bungoma counties in the western region, Laikipia and Nyandarua counties in the central region, and Kitui, Machakos, and Makueni in the eastern region of the country were analyzed. The average haplotype (0.40702) and nucleotide (0.01494) diversities observed were low, indicating low genetic diversity of domesticated rabbits in Kenya. This study resolved 5 unique haplotypes in the mtDNA D-loop region. A population genetic structure distinguishing Europe grouping and domesticated rabbits in Kenya was obtained on incorporating 32 known haplotypes. Domesticated rabbits in Kenya clustered together with rabbits from other geographic regions, suggesting common origin. The results suggested that the Kenyan domesticated rabbits may have originated from Europe. Integration of exotic breeds into breeding programmes could have contributed to the low genetic diversity. These results provide useful information for breeding and conservation decisions by the relevant stakeholders in the agriculture industry in Kenya.
Aspirin-Mediated Attenuation of Intervertebral Disc Degeneration by Ameliorating Reactive Oxygen Species In Vivo and In Vitro
Authors: Liu Yu , Lin Jiayi , Wu Xiexing , Guo Xiaobin , Sun Houyi , Yu Binqing , Shen Jining , Bai Jiaxiang , Chen Zhanghuan , Yang Huilin , Geng Dechun , Mao Haiqing
Published: November 2019

Intervertebral disc (IVD) degeneration (IDD) is a major cause of low back pain. The pathogenesis of IDD is associated with the disturbance of reactive oxygen species (ROS) equilibrium, inflammation, and matrix loss. Aspirin is a nonsteroidal anti-inflammatory drug that effectively inhibits inflammation and oxidative stress and has been widely used for the treatment of back pain. Therefore, we hypothesize that aspirin reverses the IDD process via antioxidative and anti-inflammatory effects on the AMPK signaling pathway. In vitro, aspirin diminished cellular oxygen free radicals (ROS, nitric oxide (NO)) and inflammatory cytokines (interleukin- (IL-) 1β and IL-6 and tumor necrosis factor alpha (TNF-α)) induced by lipopolysaccharides (LPS) in nucleus pulposus cells (NPCs). We found that aspirin preserved the extracellular matrix (ECM) content of collagen type II (COL2) and aggrecan while inhibiting the expression of matrix-degenerating enzymes, including matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS-4, ADAMTS-5). Aspirin significantly promoted the ratios of p-AMPK to AMPK and p-ACC to ACC expression in NPCs. Furthermore, pretreatment with the AMPK inhibitor compound C abrogated the antioxidant effects of aspirin. In vivo, an IDD model was established in Sprague-Dawley rats via percutaneous disc puncture with the 20-gauge needle on levels 8-9 and 9-10 of the coccygeal vertebrae. Imaging assessment showed that after aspirin treatment, improvements in disc height index (DHI) ranged from 1.22-fold to 1.54-fold and nucleus pulposus signal strength improved from 1.26-fold to 1.33-fold. Histological analysis showed that aspirin treatment prevented the loss of COL2 and decreased MMP-3 and MMP-13, inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and TNF-α expression in the IVD tissues. These results suggest that treatment with aspirin could reverse the IDD process via the AMPK signaling pathway, which provides new insights into the potential clinical applications of aspirin, particularly for IDD treatment.
Lifestyles, Depression, Anxiety, and Stress as Risk Factors in Nursing Apprentices: A Logistic Regression Analysis of 1193 Students in Lima, Peru
Authors: Diaz-Godiño Jessica , Fernández-Henriquez Luz , Peña-Pastor Florencia , Alfaro-Flores Patricia , Manrique-Borjas Gloria , Mayta-Tovalino Frank
Published: November 2019

Currently, it is considered that mental disorders are related to different types of chronic pathologies; for this reason, efforts to improve general health should also focus on preserving mental health. Therefore, the objective of this study was to determine through logistic regression if the independent variables (risk factors) such as (X1) age, (X2) sex, (X3) marital status, (X4) number of children, and (X5) occupation have influence on the dependent variables such as lifestyles, depression, anxiety, and stress in Peruvian nursing students. The research study was descriptive, transversal, and prospective; 1193 nursing students from Chorrillos, Ica, and Chincha were evaluated, which constituted the total population for the 2018 semester. The Health Promoting Life Profile-II (HPLP-II) and the Depression and Anxiety Stress Scale-21 (DASS-21) were used as instruments. 53.9% of nursing students had unhealthy lifestyles; however, they presented moderate (19.7%), slight (14.2%), severe (2.5%), and extremely severe (2.4%) anxiety. With respect to depression, it was found that 61.2% and 59.9% of affected students were stressed. A significant association was found only between depression and age (p=0.040) and OR = 2.0 (95% CI 1.3–3.1), anxiety and marital status (p=0.043) and OR = 1.7 (95% CI 1.0–2.6), and lifestyles and sex of the students (p=0.003) and OR = 1.1 (95% CI 1.1–2.3). Finally, it is concluded that Peruvian nursing students showed levels of anxiety ranging from moderate to extremely severe, while most of them had “normal” states of depression and stress and also showed unhealthy lifestyles.
Is There a Noninvasive Source of MSCs Isolated with GMP Methods with Better Osteogenic Potential?
Authors: Pinheiro Carla C. G. , Leyendecker Junior Alessander , Tanikawa Daniela Y. S. , Ferreira José Ricardo Muniz , Jarrahy Reza , Bueno Daniela F.
Published: November 2019

Background. A new trend in the treatment for alveolar clefts in patients with cleft lip and palate involves the use of bone tissue engineering strategies to reduce or eliminate the morbidity associated with autologous bone grafting. The use of mesenchymal stem cells—autologous cells obtained from tissues such as bone marrow and fat—combined with various biomaterials has been proposed as a viable option for use in cleft patients. However, invasive procedures are necessary to obtain the mesenchymal stem cells from these two sources. To eliminate donor site morbidity, noninvasive stem cell sources such as the umbilical cord, orbicularis oris muscle, and deciduous dental pulp have been studied for use in alveolar cleft bone tissue engineering. In this study, we evaluate the osteogenic potential of these various stem cell types.Methods. Ten cellular strains obtained from each different source (umbilical cord, orbicularis oris muscle, or deciduous dental pulp) were induced to osteogenic differentiationin vitro, and the bone matrix deposition of each primary culture was quantified. To evaluate whether greater osteogenic potential of the established mesenchymal stem cell strains was associated with an increase in the expression profile of neural crest genes, real-time qPCR was performed on the following genes: SRY-box 9, SRY-box 10, nerve growth factor receptor, transcription factor AP-2 alpha, and paired box 3.Results. The mesenchymal stem cells obtained from deciduous dental pulp and orbicularis oris muscle demonstrated increased osteogenic potential with significantly more extracellular bone matrix deposition when compared to primary cultures obtained from the umbilical cord after twenty-one days in culture (p=0.007andp=0.005, respectively). The paired box 3 gene was more highly expressed in the MSCs obtained from deciduous dental pulp and orbicularis oris muscle than in those obtained from the umbilical cord.Conclusion. These results suggest that deciduous dental pulp and orbicularis oris muscle stem cells demonstrate superior osteogenic differentiation potential relative to umbilical cord-derived stem cells and that this increased potential is related to their neural crest origins. Based on these observations, and the distinct translational advantage of incorporating stem cells from noninvasive tissue sources into tissue engineering protocols, greater study of these specific cell lines in the setting of alveolar cleft repair is indicated.