bluuebunny/crossref_metadata_2025 huggingface dataset:
Hillslope and point based soil erosion – an evaluation of a Landscape Evolution Model
Authors: Hancock G.R. , Wells T. , Dever C. , Braggins M.
Published: December 2018

Excessive soil erosion and deposition is recognised as a significant land degradation issue. Quantifying soil erosion and deposition is a non‐trivial task. One of these methods has been the mathematical modelling of soil erosion and deposition patterns and the processes that drive them. Here we examine the capability of a landscape evolution model to predict both soil erosion rate and pattern of erosion and deposition. This numerical model (SIBERIA) uses a Digital Elevation Model (DEM) to represent the landscape and calculates erosion and deposition at each grid point in the DEM. To assess field soil redistribution rates (SRR) and patterns the distribution of the environmental tracer 137Cs has been analysed. Net hill slope SRR predicted by SIBERIA (a soil loss rate of 1.7 to 4.3 t ha‐1 yr‐1) were found to be in good agreement with 137Cs based estimates (2.1 – 3.4 t ha‐1 yr‐1) providing confidence in the predictive ability of the model at the hillslope scale. However some differences in predicted erosion/deposition patterns were noted due to historical changes in landscape form (i.e. the addition of a contour bank) and possible causes discussed, as is the finding that soil erosion rates are an order of magnitude higher than likely soil production rates. The finding that SIBERIA can approximate independently quantified erosion and deposition patterns and rates is encouraging, providing confidence in the employment of DEM based models to quantify hillslope erosion rates and demonstrating the potential to upscale for the prediction of whole catchment erosion and deposition. The findings of this study suggest that LEMs can be a reliable alternative to complex and time consuming methods such as that using environmental tracers for the determination of erosion rates. The model and approach demonstrates a new approach to assessing soil erosion that can be employed elsewhere. © 2018 John Wiley & Sons, Ltd.
A combined finite volumes ‐ finite elements method for a low‐Mach model
Authors: Calgaro Caterina , Colin Claire , Creusé Emmanuel
Published: December 2018

In this paper, we develop a finite volumes ‐ finite elements method based on a time splitting to simulate some low‐Mach flows. The mass conservation equation is solved by a vertex‐based finite volume scheme using a τ‐limiter. The momentum equation associated with the compressibility constraint is solved by a finite element projection scheme. The originality of the approach is twofold. First, the state equation linking the temperature, the density, and the thermodynamic pressure is imposed implicitly. Second, the proposed combined scheme preserves the constant states, in the same way as a similar one previously developed for the variable density Navier‐Stokes system. Some numerical tests are performed to exhibit the efficiency of the scheme. On the one hand, academic tests illustrate the ability of the scheme in term of convergence rates in time and space. On the other hand, our results are compared to some of the literature by simulating a transient injection flow as well as a natural convection flow in a cavity.
The term structure of systematic and idiosyncratic risk
Authors: Hollstein Fabian , Prokopczuk Marcel , Wese Simen Chardin
Published: December 2018

We study the term structure of variance (total risk), systematic, and idiosyncratic risk. Consistent with the expectations hypothesis, we find that, for the entire market, the slope of the term structure of variance is mainly informative about the path of future variance. Thus, there is little indication of a time‐varying term premium. Turning the focus to individual stocks, we cannot reject the expectations hypothesis for systematic variance, but we strongly reject it for idiosyncratic variance. Our results are robust to jumps and potential statistical biases.
Functional fat injection under local anesthesia to treat severe postsurgical dysphagia, case report
Authors: Ottaviani Francesco , Schindler Antonio , Klinger Francesco , Scarponi Letizia , Succo Giovanni , Mozzanica Francesco
Published: December 2018

Background

In this study, we present the first application of functional fat injection performed under local anesthesia in the treatment of severe dysphagia secondary to head and neck cancer surgery.

Methods

Functional fat injection was performed using a transcervical approach. Control of injection depth and site was performed through a transnasal flexible endoscope. The effect of surgery was evaluated through videofluoroscopy (VFS), Fiberendoscopic Evaluation of Swallowing (FEES), Functional Oral Intake Scale (FOIS), and Eating Assessment Tool‐10 (EAT‐10).

Results

Before the functional fat injection, the patient was dependent on permanent tube feeding; the VFS and FEES revealed a severe impairment of swallowing abilities. The EAT‐10 scored 26. Twelve months after surgery, the patient was on oral diet, the VFS demonstrated mild to moderate dysphagia, the FEES demonstrated aspiration only with liquids and the EAT‐10 improved.

Conclusion

Functional fat injection under local anesthesia could be useful in the treatment of chronic dysphagia in selected patients.
Activity and pharmacology of homemade silver nanoparticles in refractory metastatic head and neck squamous cell cancer
Authors: Singh Jasmine , Moore William , Fattah Farjana , Jiang Xingya , Zheng Jie , Kurian Pamela , Beg Muhammad S. , Khan Saad A.
Published: December 2018

Background

Silver nanoparticles (AgNP) show efficacy in cancer cell lines. We present the first in‐human outcome of AgNP in a cancer patient.

Methods

Homemade AgNP solution is manufactured using online instructions by a 78‐year old male. He started consuming AgNP while on hospice after he developed nasal cavity squamous cell cancer metastatic to liver and lung.

Results

Electron microscopy of AgNP solution revealed bimodal nanoparticle size distribution: 3 and 12 nm. Inductively coupled plasma mass spectrometry showed basal silver ion concentrations of 32 ng/g, rising to 46 ng/g 1 hour after ingesting 60 mL of AgNP solution. Urine showed no AgNP. No toxicities were observed and he had complete radiographic resolution of his cancer. He remains without evidence of cancer 18 months later.

Conclusions

AgNP ingestion was associated with sustained radiographic resolution of cancer. Further testing of AgNP should be done to confirm its efficacy in head and neck cancer.
Outcomes of relapsed human papillomavirus‐related oropharyngeal squamous cell carcinoma treated with curative intent
Authors: Pipkorn Patrik , Sinha Parul , Kallogjeri Dorina , Adkins Douglas , Thorstad Wade T. , Rich Jason T. , Jackson Ryan S.
Published: December 2018

Background

With most centers reporting excellent disease control following transoral surgery for human papillomavirus (HPV)‐related oropharyngeal cancer, data are still lacking regarding management and outcomes in patients who relapse. We describe the treatment outcomes after curative intent therapy for locoregional and distant relapse following transoral surgery for HPV‐related oropharyngeal squamous cell carcinoma (OPSCC).

Methods

A single institution retrospective study in which patients were identified with curatively treated loco‐regional or single site distant relapse of HPV‐related OPSCC treated initially with transoral surgery (TOS) between 1996 and 2014.

Results

Among 279 patients, 38 (13.6%) relapsed. 21 (7.5%) had local‐regional relapse and 18 were treated with curative intent. Three‐year overall survival for loco‐regional recurrence with curatively intended treatment was 75.3% (95% confidence intervals 54.3‐96.0) with a median follow‐up 33 (range: 5‐65) months. Among 4 patients with isolated distant metastasis who were treated with curative intent, all subsequently developed second relapse of disease.

Conclusion

Salvage curative treatment of isolated local‐regional relapse after TOS is associated with favorable prognosis and should be offered in appropriate candidates.
Glioma exosomes mediate the expansion and function of myeloid‐derived suppressor cells through microRNA‐29a/Hbp1 and microRNA‐92a/Prkar1a pathways
Authors: Guo Xiaofan , Qiu Wei , Wang Jian , Liu Qinglin , Qian Mingyu , Wang Shaobo , Zhang Zongpu , Gao Xiao , Chen Zihang , Guo Qindong , Xu Jianye , Xue Hao , Li Gang
Published: December 2018

Myeloid‐derived suppressor cells (MDSCs) play a pivotal role in mediating the formation of an immunosuppressive environment and assisting tumors in evading the host immune response. However, the mechanism through which tumors manipulate the differentiation and function of MDSCs remains unclear. Here, we report that hypoxia‐induced glioma cells can stimulate the differentiation of functional MDSCs by transferring exosomal miR‐29a and miR‐92a to MDSCs. Our results showed that glioma‐derived exosomes (GEXs) can enhance the differentiation of functional MDSCs both in vitro and in vivo, and hypoxia‐induced GEXs (H‐GEXs) demonstrated a stronger MDSCs induction ability than did normoxia‐induced GEXs (N‐GEXs). A subsequent miRNA sequencing analysis of N‐GEXs and H‐GEXs revealed that hypoxia‐induced exosomal miR‐29a and miR‐92a expression induced the propagation of MDSCs. miR‐29a and miR‐92a activated the proliferation and function of MDSCs by targeting high‐mobility group box transcription factor 1 (Hbp1) and protein kinase cAMP‐dependent type I regulatory subunit alpha (Prkar1a), respectively. Altogether, the results of our study provide new insights into the role of glioma exosomal miRNAs in mediating the formation of immunosuppressive microenvironments in tumors and elucidate the underlying exosomal miR‐29a/miR‐92a‐based regulatory mechanism responsible for the modulation of functional MDSC induction.
Gene–environment interactions and colorectal cancer risk: An umbrella review of systematic reviews and meta‐analyses of observational studies
Authors: Yang Tian , Li Xue , Montazeri Zahra , Little Julian , Farrington Susan M. , Ioannidis John P.A. , Dunlop Malcolm G. , Campbell Harry , Timofeeva Maria , Theodoratou Evropi
Published: December 2018

The cause of colorectal cancer (CRC) is multifactorial, involving both genetic variants and environmental risk factors. We systematically searched the MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases from inception to December 2016, to identify systematic reviews and meta‐analyses of observational studies that investigated gene–environment (G×E) interactions in CRC risk. Then, we critically evaluated the cumulative evidence for the G×E interactions using an extension of the Human Genome Epidemiology Network's Venice criteria. Overall, 15 articles reporting systematic reviews of observational studies on 89 G×E interactions, 20 articles reporting meta‐analyses of candidate gene‐ or single‐nucleotide polymorphism‐based studies on 521 G×E interactions, and 8 articles reporting 33 genome‐wide G×E interaction analyses were identified. On the basis of prior and observed scores, only the interaction between rs6983267 (8q24) and aspirin use was found to have a moderate overall credibility score as well as main genetic and environmental effects. Though 5 other interactions were also found to have moderate evidence, these interaction effects were tenuous due to the lack of main genetic effects and/or environmental effects. We did not find highly convincing evidence for any interactions, but several associations were found to have moderate strength of evidence. Our conclusions are based on application of the Venice criteria which were designed to provide a conservative assessment of G×E interactions and thus do not include an evaluation of biological plausibility of an observed joint effect.
Toll‐like receptor 2 regulates metabolic reprogramming in gastric cancer via superoxide dismutase 2
Authors: Liu You Dong , Yu Liang , Ying Le , Balic Jesse , Gao Hugh , Deng Nian Tao , West Alison , Yan Feng , Ji Cheng Bo , Gough Daniel , Tan Patrick , Jenkins Brendan J. , Li Ji Kun
Published: December 2018

Toll‐like receptors (TLRs) play critical roles in host defense after recognition of conserved microbial‐ and host‐derived components, and their dysregulation is a common feature of various inflammation‐associated cancers, including gastric cancer (GC). Despite the recent recognition that metabolic reprogramming is a hallmark of cancer, the molecular effectors of altered metabolism during tumorigenesis remain unclear. Here, using bioenergetics function assays on human GC cells, we reveal that ligand‐induced activation of TLR2, predominantly through TLR1/2 heterodimer, augments both oxidative phosphorylation (OXPHOS) and glycolysis, with a bias toward glycolytic activity. Notably, DNA microarray‐based expression profiling of human cancer cells stimulated with TLR2 ligands demonstrated significant enrichment of gene‐sets for oncogenic pathways previously implicated in metabolic regulation, including reactive oxygen species (ROS), p53 and Myc. Moreover, the redox gene encoding the manganese‐dependent mitochondrial enzyme, superoxide dismutase (SOD)2, was strongly induced at the mRNA and protein levels by multiple signaling pathways downstream of TLR2, namely JAK‐STAT3, JNK MAPK and NF‐κB. Furthermore, siRNA‐mediated suppression of SOD2 ameliorated the TLR2‐induced metabolic shift in human GC cancer cells. Importantly, patient‐derived tissue microarrays and bioinformatics interrogation of clinical datasets indicated that upregulated expression of TLR2 and SOD2 were significantly correlated in human GC, and the TLR2‐SOD2 axis was associated with multiple clinical parameters of advanced stage disease, including distant metastasis, microvascular invasion and stage, as well as poor survival. Collectively, our findings reveal a novel TLR2‐SOD2 axis as a potential biomarker for therapy and prognosis in cancer.
Orange is the new black: Kinases are the new master regulators of tumor suppression
Authors: An Elvira , Brognard John
Published: December 2018

For many decades, kinases have predominantly been characterized as oncogenes and drivers of tumorigenesis, because activating mutations in kinases occur in cancer with high frequency. The oncogenic functions of kinases relate to their roles as growth factor receptors and as critical mediators of mitogen‐activated pathways. Indeed, some of the most promising cancer therapeutic agents are kinase inhibitors. However, cancer genomics studies, especially screens that utilize high‐throughput identification of loss‐of‐function somatic mutations, are beginning to shed light on a widespread role for kinases as tumor suppressors. The initial characterization of tumor‐suppressing kinases— in particular members of the protein kinase C (PKC) family, MKK4 of the mitogen‐activated protein kinase kinase family, and DAPK3 of the death‐associated protein kinase family— laid the foundation for bioinformatic approaches that enable the identification of other tumor‐suppressing kinases. In this review, we discuss the important role that kinases play as tumor suppressors, using several examples to illustrate the history of their discovery and highlight the modern approaches that presently aid in the identification of tumor‐suppressing kinases. © 2018 IUBMB Life, 71(6):738–748, 2019
Induction of CRMP‐2 phosphorylation by CDK5 restricts the repair of damaged optic nerve
Authors: Chen Xiaofan , Yuan Rongdi , Gao Ling , Huang Chanjuan , Fan Wei , Ye Jian , Chen Chunlin
Published: December 2018

Objective

To study the mechanism of collapsin response mediator protein‐2 (CRMP‐2) phosphorylation changes and cyclin‐dependent kinase 5 (CDK5) expression after optic nerve injury.

Methods

Optic nerve injury rat models were constructed, the messenger RNA (mRNA) level of CRMP‐2 in optic nerve tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) after building models 0, 3, 7, and 14 days. The protein expression of CRMP‐2, phospho‐CRMP‐2 (p‐CRMP‐2), and CDK5 were also determined by western blot analysis. Lentivirus overexpressing CRMP‐2 and CRMP‐2 small interfering RNA (siRNA) plasmid were designed and transfected to retina ganglion cells (RGCs), and then the neurites outgrowth of RGCs were cultured with CDK5 inhibitor or CDK5 activator was determined by tubulin staining. Inhibition on CDK5 promotes injured optic nerve by using carrying CDK5 siRNA inject into vitreous chamber.

Results

There was no significant change in CRMP‐2 expression in optic nerve injury rat, while p‐CRMP‐2 expression was evidently increased compared with sham operation group. The expression level of CDK5 in optic nerve tissue was upregulated after optic nerve injury in rat, and the upward trend of p‐CRMP‐2 and CDK5 was consistent with the time after the injury was prolonged. Inhibition on CDK5 evidently decreased the expression of p‐CRMP‐2. CDK5 siRNA had an obvious repair effect on the injured optic nerve.

Conclusion

The increase of CDK5 activity can lead to CRMP‐2 hyperphosphorylation, which results in the difficult repair of damaged optic nerve. Therefore, inhibition on CDK5 could promote the repair of damaged optic nerve.
Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor‐positive, advanced breast cancer: A real‐world experience
Authors: Pizzuti Laura , Giordano Antonio , Michelotti Andrea , Mazzotta Marco , Natoli Clara , Gamucci Teresa , De Angelis Claudia , Landucci Elisabetta , Diodati Lucrezia , Iezzi Laura , Mentuccia Lucia , Fabbri Agnese , Barba Maddalena , Sanguineti Giuseppe , Marchetti Paolo , Tomao Silverio , Mariani Luciano , Paris Ida , Lorusso Vito , Vallarelli Simona , Cassano Alessandra , Aroldi Francesca , Orlandi Armando , Moscetti Luca , Sergi Domenico , Sarobba Maria Giuseppina , Tonini Giuseppe , Santini Daniele , Sini Valentina , Veltri Enzo , Vaccaro Angela , Ferrari Laura , De Tursi Michele , Tinari Nicola , Grassadonia Antonino , Greco Filippo , Botticelli Andrea , La Verde Nicla , Zamagni Claudio , Rubino Daniela , Cortesi Enrico , Magri Valentina , Pomati Giulia , Scagnoli Simone , Capomolla Elisabetta , Kayal Ramy , Scinto Angelo Fedele , Corsi Domenico , Cazzaniga Marina , Laudadio Lucio , Forciniti Samantha , Mancini Maria , Carbognin Luisa , Seminara Patrizia , Barni Sandro , Samaritani Riccardo , Roselli Mario , Portarena Ilaria , Russo Antonio , Ficorella Corrado , Cannita Katia , Carpano Silvia , Pistelli Mirco , Berardi Rossana , De Maria Ruggero , Sperduti Isabella , Ciliberto Gennaro , Vici Patrizia
Published: December 2018

Data from 423 human epidermal growth factor receptor 2‐negative (HER2−), hormone receptor‐positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (
p = 0.002) and favorably influenced by early line‐treatment (
p < 0.0001). At 6 months, median progression‐free survival was 12 months (95% CI, 8–16) and median overall survival was 24 months (95% CI, 17–30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2−, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.
Uric acid and angiotensin II additively promote inflammation and oxidative stress in human proximal tubule cells by activation of toll‐like receptor 4
Authors: Milanesi Samantha , Verzola Daniela , Cappadona Francesca , Bonino Barbara , Murugavel Abitha , Pontremoli Roberto , Garibotto Giacomo , Viazzi Francesca
Published: December 2018

Renal proximal tubular cells (PTECs) participate in several mechanisms of innate immunity, express toll‐like receptors (TLRs), and proinflammatory cytokines. Hyperuricemia may be a promoter of inflammation and renal damage. Angiotensin II (Ang II) modulate immune and inflammatory responses in renal tubular cells. With the aim to evaluate the effect of uric acid (UA) and Ang II on oxidative stress and inflammation mediated by toll‐like receptor 4 (TLR4) activation in human PTECs, human kidney 2 (HK2) were incubated for 24 hr with UA (12 mg/dl) and Ang II (10
−7 M). HK2 were pretreated with an antagonist of TLR4 (TAK 242), valsartan or losartan. The genic expression of TLR4, monocyte chemoattractant protein‐1 (MCP1), and Nox4 was quantified with reverse transcription polymerase chain reaction, proteins were evaluated with Western blot. The incubation of HK2 either with UA or with Ang II determines an increased expression of TLR4, production of proinflammatory cytokines as MCP1 and pro‐oxidants as Nox4 (
p < 0.05). TAK 242 attenuates the expression of MCP1 induced both by UA and Ang II. Valsartan attenuated all the effects we described after exposure to Ang II but not those observed after UA exposure. At variance, pretreatment with losartan, which inhibits UA internalization, attenuates the expression of TLR4, MCP1, and Nox4 in cells previously treated with UA, Ang II, and UA plus Ang II. Proinflammatory pathways are induced in an additive manner by UA and Ang II (
p < 0.05) and might be mediated by TLR4 in PTECs. Renin–angiotensin–aldosterone system (RAAS) activation, hyperuricemia, and innate immunity interplay in the development of chronic tubular damage and the interaction of several nephrotoxic mechanisms blunt the protective effect of RAAS inhibition.
Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer
Authors: Abdollahzadeh Rasoul , Daraei Abdolreza , Mansoori Yaser , Sepahvand Masoumeh , Amoli Mahsa M. , Tavakkoly‐Bazzaz Javad
Published: December 2018

Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood. In the recent years, the newly discovered mechanism in the RNA world is “competing endogenous RNA (ceRNA)” which proposes regulatory dialogues between different RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), transcribed pseudogenes, and circular RNAs (circRNAs). In the latest BC research, various studies have revealed that dysregulation of several ceRNA networks (ceRNETs) between these ncRNAs has fundamental roles in establishing the hallmarks of BC development. And it is thought that such a discovery could open a new window for a better understanding of the hidden aspects of breast tumors. Besides, it probably can provide new biomarkers and potential efficient therapeutic targets for BC. This review will discuss the existing body of knowledge regarding the key functions of ceRNETs and then highlights the emerging roles of some recently discovered ceRNETs in several hallmarks of BC. Moreover, we propose for the first time the “ceRnome” as a new term in the present article for RNA research.
Long noncoding RNA GACAT3 promotes glioma progression by sponging miR‐135a
Authors: Wang Jing , Zhang Ming , Lu Weifeng
Published: December 2018

The long noncoding RNA (lncRNA) gastric cancer associated transcript 3 (GACAT3) has been reported to play important roles in human tumorigenesis. However, its expression pattern, functions, and underlying mechanism in glioma remain unclear. In the present study, we showed that GACAT3 is upregulated in glioma tissues and cell lines. Through online databases, luciferase reporter assays and RNA immunoprecipitation (RIP) assays, we determined that GACAT3 acts as a competing endogenous RNA (ceRNA) for microRNA (miR)‐135a, which was downregulated and performed as a tumor inhibitor in glioma. Further, nicotinamide phosphoribosyl transferase (NAMPT) was confirmed as a target gene of miR‐135a by a series of gain‐ and loss‐of‐function assays. Overall, the present study was the first to show that GACAT3 regulates the expression of NAMPT to promote glioma progression by sponging miR‐135a. These findings provide a promising therapy strategy for glioma.
The clinical impact of exosomes in cardiovascular disorders: From basic science to clinical application
Authors: Ghafarian Farzaneh , Pashirzad Mehran , Khazaei Majid , Rezayi Majid , Hassanian Seyed Mahdi , Ferns Gordon A , Avan Amir
Published: December 2018

Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of a valid biomarker that accurately predicts the risk of developing CVD, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, messenger RNAs, noncoding RNA, and nucleic acid contents that are important players in intercellular communication, and that act via long‐range signals or cell‐to‐cell contact. The discovery of exosomes provides potential strategies for the diagnosis and treatment of CVD. In the current review, we have explored the potential impact of exosomes on cardiovascular physiology, and their therapeutic potential in cardiovascular disorders with an emphasis on the existing preclinical studies.
Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets
Authors: Ghanaatian Negar , Lashgari Naser‐Aldin , Abdolghaffari Amir Hossein , Rajaee Seyed M. , Panahi Yunes , Barreto George E. , Butler Alexandra E. , Sahebkar Amirhossein
Published: December 2018

Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood–brain barrier (BBB) through the disrupted tight junctions. Coupling of interleukin (IL)‐17 and IL‐22 to their receptors in the BBB layer facilitates this migration. Subsequently, axon degeneration and the various manifestations of nerve–muscle disorders appear. Curcumin, a major component of turmeric, is derived from Curcuma longa, which belongs to the Zingiberaceae family. Numerous properties of curcumin have been identified recently, some of which can be effective in the treatment of MS, particularly the anti‐inflammatory properties via inhibition of secretion of proinflammatory cytokines. In this paper, we will review the various properties and key effects of curcumin for the treatment of MS.
An in vitro assessment for evaluating the efficiency of β‐d‐mannuronic acid (M2000) in myelodysplastic syndrome
Authors: Bakhtiari Tahereh , Ghaderi Afshin , Safaee Nodehi Sayyed Reza , Aghazadeh Zahra , Tofighi Zavareh Farzaneh , Jafarnezhad‐Ansariha Fahimeh , Barati Anis , Mirshafiey Abbas
Published: December 2018

β‐d‐Mannuronic acid (M2000), a novel non‐steroidal anti‐inflammatory drug (NSAID) with immunosuppressive properties, has been previously shown to exhibit potential therapeutic effects on autoimmune diseases. Immunosuppression therapy has been a standard approach for myelodysplastic syndrome (MDS) for many years. We evaluated the effect of M2000 on isolated peripheral blood mononuclear cells (PBMCs) from patients with MDS. The PBMCs were isolated from 13 patients with MDS and 13 normal donors. The cells were then treated with low, moderate, and high doses of M2000 and diclofenac as a control group. The level of interleukin (IL)‐6, tumor necrosis factor alpha (TNF‐α), IL‐3, granulocyte colony‐stimulating factor (G‐CSF) gene expression and the serum level of IL‐6 and TNF‐α production were evaluated by real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay methods, respectively. Our findings indicated a significant reduction in the production of IL‐6 and TNF‐α as inflammatory cytokines. Furthermore, the level of G‐CSF gene expression was significantly increased. In conclusion, M2000, a newly designed NSAID, has a remarkable effect on isolated PBMC in patients with MDS, which might bring a potential hope for its oral administrations in these patients.
microRNA‐16‐5p enhances radiosensitivity through modulating Cyclin D1/E1–pRb–E2F1 pathway in prostate cancer cells
Authors: Wang Fang , Mao Aihong , Tang Jinzhou , Zhang Qianjing , Yan Junfang , Wang Yupei , Di Cuixia , Gan Lu , Sun Chao , Zhang Hong
Published: December 2018

Prostate cancer (CaP) is the second most common cancer in men worldwide in 2012, and radiation therapy is one of the most common definitive treatment options for localized CaP. However, radioresistance is a major challenge for the current radiotherapy, accumulating evidences suggest microRNAs (miRNAs), as an important regulator in cellular ionizing radiation (IR) responses, are closely correlated with radiosensitivity in many cancers. Here, we identified microRNA‐16‐5p(miR‐16‐5p) is significantly upregulated in CaP LNCaP cells following IR and can enhance radiosensitivity through modulating Cyclin D1/E1–pRb–E2F1 pathway. To identify the expression profile of miRNAs in CaP cells exposed to IR, we performed human miRNA probe hybridization chip analysis and miR‐16‐5p was found to be significantly overexpressed in all treatment groups that irradiated with different doses of X‐rays and heavy ions (12C6+). Furthermore, overexpression of miR‐16‐5p suppressed cell proliferation, reduced cell viability, and induced cell cycle arrest at G0/G1 phase, resulting in enhanced radiosensitivity in LNCaP cells. Additionally, miR‐16‐5p specifically targeted the Cyclin D1/E1–3′‐UTR in LNCaP cells and affected the expression of Cyclin D1/E1 in both mRNA and protein levels. Taken together, miR‐16‐5p enhanced radiosensitivity of CaP cells, the mechanism may be through modulating Cyclin D1/Cyclin E1/pRb/E2F1 pathway to cause cell cycle arrest at G0/G1 phase. These findings provided new insight into the correlation between miR‐16‐5p, cell cycle arrest, and radiosensitivity in CaP, revealed a previously unrecognized function of miR‐16‐5p–Cyclin D1/E1–pRb–E2F1 regulation in response to IR and may offer an alternative therapy to improve the efficiency of conventional radiotherapy.
Opioid receptors and opioid peptides in the cardiomyogenesis of mouse embryonic stem cells
Authors: Šínová Romana , Kudová Jana , Nešporová Kristina , Karel Sergej , Šuláková Romana , Velebný Vladimír , Kubala Lukáš
Published: December 2018

The stimulation of myocardium repair is restricted due to the limited understanding of heart regeneration. Interestingly, endogenous opioid peptides such as dynorphins and enkephalins are suggested to support this process. However, the mechanism—whether through the stimulation of the regenerative capacity of cardiac stem cells or through effects on other cell types in the heart—is still not completely understood. Thus, a model of the spontaneous cardiomyogenic differentiation of mouse embryonic stem (mES) cells via the formation of embryoid bodies was used to describe changes in the expression and localization of opioid receptors within cells during the differentiation process and the potential of the selected opioid peptides, dynorphin A and B, and methionin‐enkephalins and leucin‐enkephalins, to modulate cardiomyogenic differentiation in vitro. The expressions of both κ‐ and δ‐opioid receptors significantly increased during mES cell differentiation. Moreover, their primary colocalization with the nucleus was followed by their growing presence on the cytoplasmic membrane with increasing mES cell differentiation status. Interestingly, dynorphin B enhanced the downregulation gene expression of Oct4 characteristic of the pluripotent phenotype. Further, dynorphin B also increased cardiomyocyte‐specific Nkx2.5 gene expression. However, neither dynorphin A nor methionin‐enkephalins and leucin‐enkephalins exhibited any significant effects on the course of mES cell differentiation. In conclusion, despite the increased expression of opioid receptors and some enhancement of mES cell differentiation by dynorphin B, the overall data do not support the notion that opioid peptides have a significant potential to promote the spontaneous cardiomyogenesis of mES cells in vitro.
Complement factor and T-cell interactions during alloimmune inflammation in transplantation
Authors: Khan Mohammad Afzal , Shamma Talal
Published: December 2018

Complement factor and T-cell signaling during an effective alloimmune response plays a key role in transplant-associated injury, which leads to the progression of chronic rejection (CR). During an alloimmune response, activated complement factors (C3a and C5a) bind to their corresponding receptors (C3aR and C5aR) on a number of lymphocytes, including T-regulatory cells (Tregs), and these cell-molecular interactions have been vital to modulate an effective immune response to/from Th1-effector cell and Treg activities, which result in massive inflammation, microvascular impairments, and fibrotic remodeling. Involvement of the complement-mediated cell signaling during transplantation signifies a crucial role of complement components as a key therapeutic switch to regulate ongoing inflammatory state, and further to avoid the progression of CR of the transplanted organ. This review highlights the role of complement-T cell interactions, and how these interactions shunt the effector immune response during alloimmune inflammation in transplantation, which could be a novel therapeutic tool to protect a transplanted organ and avoid progression of CR.
The E‐Revolution in Higher Education: E‐Learning and E‐Leaders
Authors: Cordie Leslie , Lin Xi
Published: December 2018

Technology is transforming higher education. In order to take full advantage of these changes, capable leaders who create a shared vision of the future, harness e‐technologies for learning, and support 21st‐century learning outcomes are more critical now than ever. To address this need, e‐leadership is emerging as a popular topic in higher education. Individuals who employ technology to enable transformative learning, are called e‐leaders. The growth of e‐learning has been influenced by various factors, including costs, availability of a variety of instructional technologies, and the innate technological skills of the modern learner. The prevalence of e‐learning leads to unique challenges, including dealing with various stakeholders, providing an effective product to learners, and establishing new paradigms on how to provide educational components. The current paper discusses the crucial elements to consider for effective e‐leadership in higher education institutions.
Preparation and partial characterization of films made with dual‐modified (acetylation and crosslinking) potato starch
Authors: González‐Soto Rosalía A , Núñez‐Santiago María C , Bello‐Pérez Luis A
Published: December 2018

Background

Starch is an alternative material for the production of biodegradable plastics; however, native starches have drawbacks due to their hydrophilic nature. Chemical modifications such as acetylation and crosslinking are used to broaden the potential end‐uses of starch. Dual modification of starches increases their functionality compared to that of starches with similar single modifications. In this study, a dual‐modified potato starch (acetylated and crosslinked) was used to produce films by casting.

Results

Changes in the arrangement of the amylopectin double helices of dual‐modified starch were evident from X‐ray diffraction patterns, pasting profiles and thermal properties. The degree of substitution for acetyl groups was low (0.058 ± 0.006) because crosslinking dominated acetylation. Modified starch film had higher elongation percentage (82.81%) than its native counterpart (57.4%), but lower tensile strength (3.51 MPa for native and 2.17 MPa for dual‐modified) and lower crystallinity in fresh and stored films. The sorption isotherms indicated that the dual modification decreased the number of reactive sites for binding water, resulting in a reduction in the monolayer value and a decrease in the solubility and water vapor permeability.

Conclusions

Dual modification of starch may be a feasible option for improving the properties of biodegradable starch films. © 2018 Society of Chemical Industry
Draft genome sequence of Candida versatilis and osmotolerance analysis in soy sauce fermentation
Authors: Ruan Luchen , Meng Meng , Wang Cong , Hou Lihua
Published: December 2018

BACKGROUND

The salt‐tolerant yeast strain Candida versatilis is usually added to high‐salt, liquid‐state soy sauce fermentation. The genome of C. versatilis was sequenced in our previous study but the reason for its high‐osmolarity ability was not clear.

RESULTS

The 9.7 Mbp genome of C. versatilis contained 4711 CDS. Candida versatilis was the closest to another yeast, Zygosaccharomyces rouxii, added to soy sauce fermentation. The protein sequence of the whole genome was divided into 4338 groups, accounting for 92.1% of all the predicted protein of C. versatilis using OrthoMCL. Mitogen‐activated protein kinase (MAPK) signal pathways, including high osmolarity and cell integrity, were predicted and proved by investigating the expression changes of the key genes CvHOG1, CvGPD1, and CvFPS1 in a high osmotic environment and by testing the variations of intracellular glycerol and extracellular glycerol.

CONCLUSION

Candida versatilis exhibited strong osmotolerance because it could synthesize intracellular glycerol and absorb glycerol from the environment cooperated with the shut down of glycerol efflux channel in membrane. © 2018 Society of Chemical Industry
Liver Stiffness Measured by 2‐Dimensional Shear Wave Elastography: Prospective Evaluation of Healthy Volunteers and Patients With Liver Cirrhosis
Authors: Petzold Golo , Hofer Johannes , Ellenrieder Volker , Neesse Albrecht , Kunsch Steffen
Published: December 2018

Objectives

We aimed to establish normal values for liver stiffness measurement, performed by 2‐dimensional shear wave elastography (LOGIQ E9; GE Healthcare, Wauwatosa, WI), in healthy volunteers, patients with nonhepatic morbidities, and patients with histologically confirmed liver cirrhosis.

Methods

A total of 175 participants were included between July 2016 and February 2018. Three cohorts were analyzed: healthy volunteers (n = 68), patients with healthy livers but nonhepatic morbidities (n = 57), and patients with liver cirrhosis (n = 50). Liver stiffness measurement was performed by 2 observers with different levels of experience to determine interobserver agreement.

Results

Of the 175 participants included, 91 were male, and the mean age ± SD was 44.4 ± 19.4 years. The success rate for 175 liver stiffness measurements was 95.4%. The number of unsuccessful measurements was significantly higher in the liver cirrhosis cohort (P = .04). The interobserver agreement was excellent (intraclass correlation coefficient, 0.87). Liver stiffness in the healthy‐liver patient cohort (4.93 ± 0.83 kPa) was not significantly different from that in the healthy‐volunteer cohort (5.19 ± 1.03 kPa; P = .13). Apart from male sex in the healthy‐volunteer cohort, age, body mass index, mild steatosis, and nonhepatic morbidities had no significant impact on liver stiffness. Liver stiffness values in participants without liver disease (healthy volunteers and healthy‐liver patients; n = 125) ranged from 3.62 to 7.02 kPa (2.5th–97.5th percentiles). Notably, there was no overlap of liver stiffness measurements between the patients without liver disease and the cirrhosis cohort (13.29 ± 3.27 kPa [7.76–19.49 kPa]).

Conclusions

Liver stiffness values in healthy individuals vary widely and are not dependent on age, body mass index, or specific nonhepatic comorbidities. Liver stiffness values within the normal range can noninvasively rule out cirrhosis, as liver stiffness is significantly higher in cirrhotic patients (P < .001). Two‐dimensional shear wave elastography has excellent interobserver agreement.
An In‐depth Perspective of Aortic Arch Branching in Fetal Vascular Rings Using Spatiotemporal Image Correlation Combined With High‐definition Flow Imaging: Report of 4 Cases
Authors: Tseng Jenn‐Jhy , Peng Hsien‐Wen , Jan Shen‐Ling
Published: December 2018

On the basis of 2‐dimensional fetal echocardiographic findings, we investigated 4 different fetal vascular ring cases using spatiotemporal image correlation (STIC) combined with high‐definition (HD) flow imaging. An in‐depth 3‐dimensional perspective of aortic arch branching (ie, the brachiocephalic arteries) was created by application of glass body and HDlive flow rendering algorithms (GE Healthcare, Zipf, Austria). Additionally, complete (U‐ or O‐shaped) or incomplete (C‐shaped) vascular rings were clearly differentiated in utero, and articulations around the trachea and esophagus were more easily imaged. In conclusion, spatiotemporal image correlation combined with HD flow imaging could classify fetal vascular rings with accuracy and facilitate decision making during postnatal management.
Preparation and tribological properties of chemically decorated MoS2 nanosheets with oleic diethanolamide
Authors: Wu Pei‐Rong , Li Wei , Ge Ting , Feng Yu‐Mei , Liu Zan , Cheng Zhi‐Lin
Published: December 2018

In this paper, we attempted to modify the self‐made two‐dimensional MoS2 nanosheets by oleic diethanolamide (OD) with a simple one‐step route to obtain OD‐MoS2. The OD‐MoS2 nanosheets were confirmed by a series of characterizations. The results showed that the MoS2 nanosheets could be chemically covered with OD molecules to form CS bond, so as to distinctly improve the dispersibility and stability of OD‐MoS2 nanosheets in base oil. Furthermore, the tribological properties of OD‐MoS2 nanosheets in base oil were comprehensively studied by four‐ball tester. In detail, the average friction coefficient and average wear scar diameter of 0.08 wt.% OD‐MoS2‐based oil were decreased by about 36.8% and 15.4% as compared with base oil, respectively, while its extreme pressure performance also was increased by about 15.2%. The results showed that OD‐MoS2 nanosheets exhibited the better tribological properties in oil because of the solved dispersibility.
Enhanced Molecular Alignment in Poly‐l‐Lactic Acid Nanotubes Induced via Melt‐Press Template‐Wetting
Authors: Smith Michael , Lindackers Cathrin , McCarthy Kevin , Kar‐Narayan Sohini
Published: December 2018

Molecular ordering in polymers can have a drastic effect on their properties and can be used to induce or enhance functionality. In the case of poly‐l‐lactic acid (PLLA), which is a widely used polymer in biomedicine, sensors, and actuators, preferential orientation of chains can lead to significantly enhanced electromechanical properties. In this context, template‐wetting is a straightforward method of producing polymer nanostructures, which can lead to some degree of molecular order in the polymer. Template‐wetting of PLLA has not been fully explored, especially in terms of morphological and/or structural characterization. In this work, PLLA nanotubes are grown via a modification of the template‐wetting process, referred to here as melt‐press template‐wetting. The nanotubes are thoroughly characterized with wide‐angle X‐ray diffraction, isothermal differential scanning calorimetry, and polarized light optical microscopy. This characterization indicates that the polymer chains in these PLLA nanotubes are aligned parallel to the cylindrical axis of the nanotube, which may be beneficial in certain applications.
Effect of heat treatment on microstructure and property of high vanadium wear‐resistant alloy
Authors: Hui L. , Han‐Guang F. , Jiang J. , Jun W.
Published: December 2018

In order to improve the properties of high vanadium wear‐resistant alloy and obtain the optimal process parameters, the effect of heat treatment on the microstructure and properties of high vanadium wear‐resistant alloy was studied by means of optical microscope, the scanning electron microscope, X‐ray diffraction, energy dispersive spectrometer, Rockwell and Vickers hardness tester. The results show that the microstructure of as‐cast high vanadium wear‐resistant alloy was composed of matrix and eutectic structure. The matrix was mainly composed of martensite and retained austenite, and the eutectics mainly included M7C3 and VC type carbide. After quenching, the matrix structure of the alloy remains martensite and retained austenite. M23C6 type carbide was precipitated while quenching at 1100 °C. The type of eutectic structure has no obvious change after tempering. Tempering has great influence on the amount of retained austenite in the matrix. The hardness of the alloy is the highest (about 69.1 HRC) when the quenching temperature and tempering temperature are 1000 °C and 550 °C respectively.
Effect of martensite transformation on chemical composition, semiconductor property and corrosion resistance of passive film on SAE 304 stainless steel
Authors: He S.L. , Liu Y. , Jiang D.M.
Published: December 2018

The chemical composition, semiconductor property and corrosion resistance of passive films on cold‐worked 304 stainless steel containing varying amounts of martensite (0 %, 0.6 %, 6 %, 12 % and 20 %) are investigated using X‐ray photoelectron spectroscopy, Mott‐Schottky analyses and electrochemical impedance spectroscopy. The results indicate that after cold rolling, the microstructure in the sample transforms from single austenite into compound of martensite and original austenite. For the martensite content of 6 %, the passive film formed on the sample contains the least amount of oxide and shows the highest acceptor and donor densities; according to the inverse relationship between corrosion resistance and both acceptor and donor density, these results indicate that the passive film shows the poorest corrosion resistance among all the samples measured. When the content of martensite decrease below 6 %, the acceptor and donor densities for the passive film increase with increasing martensite content; however, for samples with the martensite content higher than 6 %, the acceptor and donor densities decrease with increasing martensite content. The oxide content and corrosion resistance show the opposite behavior with increasing martensite content: the monotonic decrease for martensite content lower than 6 % and gradual increase when the martensite content exceeds 6 %.