bluuebunny/crossref_metadata_2025 huggingface dataset:
A new potential anti‐cancer beta‐carboline derivative decreases the expression levels of key proteins involved in glioma aggressiveness: A proteomic investigation
Authors: Carvalho Annelise , Viaene Johan , Vandenbussche Guy , De Braekeleer Kris , Masereel Bernard , Wouters Johan , Souard Florence , Vander Heyden Yvan , Van Antwerpen Pierre , Delporte Cédric , Mathieu Véronique
Published: September 2019

Gliomas remain highly fatal due to their high resistance to current therapies. Deregulation of protein synthesis contributes to cancer onset and progression and is a source of rising interest for new drugs. CM16, a harmine derivative with predicted high blood–brain barrier penetration, exerts antiproliferative effects partly through translation inhibition. We evaluated herein how CM16 alters the proteome of glioma cells. The analysis of the gel‐free LC/MS and auto‐MS/MS data showed that CM16 induces time‐ and concentration‐dependent significant changes in the total ion current chromatograms. In addition, we observed spontaneous clustering of the samples according to their treatment condition and their proper classification by unsupervised and supervised analyses, respectively. A two‐dimensional gel‐based approach analysis allowed us to identify that treatment with CM16 may downregulate four key proteins involved in glioma aggressiveness and associated with poor patient survival (HspB1, BTF3, PGAM1, and cofilin), while it may upregulate galectin‐1 and Ebp1. Consistently with the protein synthesis inhibition properties of CM16, HspB1, Ebp1, and BTF3 exert known roles in protein synthesis. In conclusion, the downregulation of HspB1, BTF3, PGAM1 and cofilin bring new insights in CM16 antiproliferative effects, further supporting CM16 as an interesting protein synthesis inhibitor to combat glioma.
Co‐occurrence of breast cancer and neuroendocrine tumours: New genetic insights beyond Multiple Endocrine Neoplasia syndromes
Authors: Larouche Vincent , Akirov Amit , Thain Emily , Kim Raymond H. , Ezzat Shereen
Published: September 2019

Objective

Age‐standardized incidence of female breast cancer is 145.1 per 100000/year and 5.86 per 100000/year for neuroendocrine tumours (NET) in Canada. Evidence is scarce about gene variants that may predispose patients to develop both neoplasms. The objective of this study was to identify germline gene variants associated with this combination of tumours.

Design and patients

A retrospective chart review (2007‐2018) in a tertiary NET referral centre was completed. A series of 9 female patients with concurrent breast cancer and NET is presented. All patients underwent a 37 gene hereditary cancer next‐generation sequencing panel.

Results

Mean age was 61.4 years (35‐85) at breast cancer diagnosis and 63.4 years (51‐89) at NET diagnosis. Four patients had a pancreatic, three had a small bowel and two had a lung NET. Two patients were known cases of MEN1, and one patient was found to harbour a pathogenic variant in MEN1 and a variant of unknown significance (VUS) in ATM. A second patient was found to harbour a pathogenic variant in APC. A third patient was found to carry a pathogenic variant in PALB2 as well as a VUS in FANCM, MLH1 and STK11. Another patient was found to harbour a VUS in MSH2. One patient was found to carry a pathogenic variant in NTHL1.

Conclusion

The first cases of a PALB2, an APC and a NTHL1 pathogenic variants in patients with both breast cancer and NET were presented. NGS testing should be considered in specific patients with this combination of neoplasms, as certain germline variants beyond MEN1, have important implications for cancer surveillance.
Canola Oil with High Antioxidant Content Obtained by Combining Emerging Technologies: Microwave, Ultrasound, and a Green Solvent
Authors: Sánchez Ramiro J. , Fernández María B. , Nolasco Susana M.
Published: September 2019

In this work, the ultrasound‐assisted extraction (UAE) of canola oil from canola seeds pretreated with microwaves using ethanol 99% as solvent is studied. Different process parameters are evaluated, such as extraction time, temperature, solid:solvent ratio, and ultrasound amplitude, optimizing the process using response surface methodology. Under optimum conditions, the extraction time is decreased by up to 75% with respect to conventional extractions, obtaining an oil with a higher content of total tocopherols and canolol, and with oxidation indexes within the established standard limits. The addition of a microwave pretreatment to the UAE with ethanol 99% shows a synergic effect between both processes, improving the oil yield. The results obtained in this study show the potential of the use of UAE for the extraction of canola oil using a green solvent, reducing processing times, environmental pollution, and achieving an oil of high quality and antioxidant concentration.

Practical Application: The industrial use of petroleum‐derived solvents such as hexane has problems concerning sustainability, environment, and safety. In recent years, the use of “green” solvents for the extraction of vegetable oils began to be studied; however, it is necessary to develop stages that allow improving the extraction process by increasing the yield, reducing the processing times, and optimizing the oil quality. In this sense, ultrasound allows to shorten the extraction times while microwave pretreatments applied to canola seeds generate an increase in the concentration of antioxidants in the oil, facilitating the implementation of a “green” process in the industrial production.
Does Authenticity of Virgin Olive Oil Sensory Quality Require Input from Chemistry?
Authors: Aparicio‐Ruiz Ramón , Morales María T. , Aparicio Ramón
Published: September 2019

The methodology of sensory assessment (“panel test”) of virgin olive oil (VOO) is the sensory method included in international regulations and its application is compulsory in trading. Despite its application has been a success in authenticity of VOO quality, the application of panel test is not exempt of heated debates and controversies among olive oil actors that sometimes surpasses scientific arguments. Problems are consequence of some disagreements in the evaluation of the same VOOs from different testing laboratories, and today, there is a clamor for its enhancement from a considerable part of the industrial sector. The thin line that exists between the absence of sensory defects in extra‐VOOs and a very slight sensory defect that may be perceived in some VOOs by some tasters is in the origin of the controversy. Thus, this work is focuses on providing practical solutions to the current concerns of Panel Test after analyzing proposals evaluating aroma descriptors from chemistry, examining flaws of panel test and strengthening its weak points.

Practical Applications: The work describes a strategy that combines volatiles and sensory descriptors for avoiding disagreements with results provided by non‐recognized testing laboratories, and proposes a blueprint for improving the process of training tasters with reference materials.
Soluble Guanylyl Cyclase Alpha1 Subunit: A New Marker for Estrogenicity of Endocrine Disruptor Compounds
Authors: Pino María Teresa L. , Ronchetti Sonia A. , Cordeiro Georgina , Bollani Sabrina , Duvilanski Beatriz H. , Cabilla Jimena P.
Published: September 2019

Endocrine-disrupting chemicals (EDCs) include widespread naturally occurring and synthetic substances in the environment that adversely affect humans and wildlife. Because of the increasing numbers of EDCs, screening methods and ideal biomarkers to determine EDC potencies at relevant environmental concentrations need to be drastically improved. Soluble guanylyl cyclase α1 subunit (sGCα1) is an abundant cytosolic protein ubiquitously expressed in most tissues. We previously showed that sGCα1 is specifically and highly up-regulated by estrogen (E2) in vivo and in vitro, even though it lacks estrogen-responsive elements. The aim of the present study was to evaluate sGCα1 protein expression as a potential marker for xenoestrogenic EDC exposure in the E2-responsive lactosomatotroph-derived pituitary cell line GH3. Cells were incubated with a wide variety of EDCs such as heavy metals and a metalloid, synthetic E2 derivatives, plastic byproducts, and pesticides at a range of doses including those with proven xenoestrogenic activity. We demonstrated that E2 increased sGCα1 expression in GH3 cells as well as in other E2-responsive tumor cell lines. Moreover, this effect was fully dependent on estrogen receptor (ER) activation. Importantly, sGCα1 protein levels were strongly up-regulated by all the EDCs tested, even by those exhibiting low or null ER binding capacity. We provide evidence that the in vitro sGCα1 protein assay may be a very sensitive and powerful tool to identify compounds with estrogenic activity, which could improve current mammalian-based screening methods. Environ Toxicol Chem 2019;38:2719–2728. © 2019 SETAC
Developmental responses to early‐life adversity: Evolutionary and mechanistic perspectives
Authors: Lu Amy , Petrullo Lauren , Carrera Sofia , Feder Jacob , Schneider‐Crease India , Snyder‐Mackler Noah
Published: September 2019

Adverse ecological and social conditions during early life are known to influence development, with rippling effects that may explain variation in adult health and fitness. The adaptive function of such developmental plasticity, however, remains relatively untested in long‐lived animals, resulting in much debate over which evolutionary models are most applicable. Furthermore, despite the promise of clinical interventions that might alleviate the health consequences of early‐life adversity, research on the proximate mechanisms governing phenotypic responses to adversity have been largely limited to studies on glucocorticoids. Here, we synthesize the current state of research on developmental plasticity, discussing both ultimate and proximate mechanisms. First, we evaluate the utility of adaptive models proposed to explain developmental responses to early‐life adversity, particularly for long‐lived mammals such as humans. In doing so, we highlight how parent‐offspring conflict complicates our understanding of whether mothers or offspring benefit from these responses. Second, we discuss the role of glucocorticoids and a second physiological system—the gut microbiome—that has emerged as an additional, clinically relevant mechanism by which early‐life adversity can influence development. Finally, we suggest ways in which nonhuman primates can serve as models to study the effects of early‐life adversity, both from evolutionary and clinical perspectives.
Characterization of key aroma compounds in Laobaigan Chinese Baijiu by GC×GC‐TOF/MS and means of molecular sensory science
Authors: Fan Qian , Wang Xinlei , Zhao Yuefeng , Zheng Fuping , Li Hehe , Zhang Fuyan , Zhang Yuhang , Chen Feng
Published: September 2019

Laobaigan (LBG) Baijiu is recognized as one of the famous Chinese liquors due to its unique flavor characteristics. However, its key aroma‐active volatiles are still unknown. In this study, 414 volatile chemicals in the LBG Baijiu were initially detected by comprehensive two‐dimensional gas chromatography‐time‐of‐flight mass spectrometry (GC×GC‐TOF/MS). Then, 52 of them were determined by sample dilution analysis (SDA) for screen of aroma‐active compounds. Based on their odor–activity values (OAVs) that were determined by the external standard method performed on the GC×GC‐TOF/MS, 32 volatile compounds were further recognized as important odorants, which were reconstituted to simulate and validate the aroma profile of the LBG Baijiu. Moreover, omission experiments were conducted to corroborate the importance of key odorants. As a result, nine aroma compounds were finally confirmed as the key aroma‐active compounds of the LBG Baijiu.
Monte Carlo analysis of methods for extracting risk‐neutral densities with affine jump diffusions
Authors: Lu Shan
Published: September 2019

This article compares several widely used and recently developed methods to extract risk‐neutral densities (RNDs) from option prices in terms of estimation accuracy. It shows that the positive convolution approximation method consistently yields the most accurate RND estimates, and is insensitive to the discreteness of option prices. RND methods are less likely to produce accurate RND estimates when the underlying process incorporates jumps and when estimations are performed on sparse data, especially for short time‐to‐maturities, though sensitivity to the discreteness of the data differs across different methods.
Development of an Alliance Supporting Native American and Alaska Native Graduate Students in Science, Technology, Engineering, and Mathematics
Authors: McMurtry Jerry R.
Published: September 2019

This chapter presents the genesis of the Pacific Northwest Circle of Success in Mentoring Opportunities in STEM (Science, Technology, Engineering, and Mathematics) Alliance and its recommendation on sustaining the Alliance during and beyond its initial conception.
Developing an Indigenous Knowledge Field Camp
Authors: McMurtry Jerry R. , Arouca Raquel A. , Thomas Aaron
Published: September 2019

This chapter describes a field‐based experience based on Native American best mentoring practices that brings together traditional ecological knowledge and Western science to build relationships and understanding between Native students and faculty mentors.
Designing and Implementing an Indigenous Mentoring Program for Faculty Who Mentor AI/AN Students in STEM Fields: Process, Outcomes, and Lessons Learned
Authors: Brown Blakely , Komlos Barbara Z.
Published: September 2019

This chapter describes the development and implementation of an Indigenous Mentoring Program (IMP) for faculty who mentor American Indian/Alaska Native graduate students in science, technology, engineering, and mathematics (STEM) fields. The chapter also reviews steps taken in adapting and translating the IMP to non‐Montana institutions that are part of the Pacific Northwest Circle of Success in Mentoring Opportunities in STEM Alliance.
Inhibition of tropomyosine receptor kinase B on the migration of human Schwann cell and dispersion of oral tongue squamous cell carcinoma in vitro
Authors: Ein Liliana , Bracho Olena , Mei Christine , Patel Jaimin , Boyle Thomas , Monje Paula , Fernandez‐Valle Cristina , Bas Esperanza , Thomas Giovana , Weed Donald , Sargi Zoukaa , Dinh Christine
Published: September 2019

Background

Schwann cells (SC) may play an important role in perineural invasion (PNI) by promoting cancer cell dispersion. Brain‐derived neurotrophic factor (BDNF) may contribute to these cellular events by activating tropomyosine receptor kinase B (TrkB). This study examines the effect of TrkB inhibition on SC migration and oral cancer cell dispersion in vitro.

Methods

Human tongue squamous cell carcinoma (SCC‐9) and human SCs were cocultured in three different conditioned mediums: control, BDNF, and TrkB inhibitor. Cell migration, cancer cell dispersion, and SC dedifferentiation were measured on time‐lapse and immunofluorescence images.

Results

Cancer cell migration exceeded SC migration in all conditions. TrkB inhibition promoted SC dedifferentiation and significantly increased SC migration, when compared to BDNF conditions. TrkB inhibition also reduced cancer cell dispersion, when compared to control and BDNF‐treated cultures.

Conclusion

SCs may have importance in the pathophysiology of PNI. TrkB inhibition may be a potential avenue for therapeutic intervention.
The role of the hippocampus in the semantic variant of primary progressive aphasia: A resting‐state fcMRI study
Authors: Chapleau Marianne , Montembeault Maxime , Boukadi Mariem , Bedetti Christophe , Laforce Robert , Wilson Maximiliano , Brambati Simona M.
Published: September 2019

The goal of the study was to determine whether the semantic variant of primary progressive aphasia (svPPA) affects the intrinsic connectivity network anchored to left and right anterior hippocampus, but spares the posterior hippocampus. A resting‐state functional connectivity MRI (rs‐fcMRI) study was conducted in a group of patients with svPPA and in controls, using a seed‐to‐voxel approach. In comparison to controls, massively reduced connectivity was found in the anterior hippocampus, mainly the left one, for svPPA patients but not in the left or right posterior hippocampus. In svPPA, the anterior hippocampus showed reduced functional connectivity with regions implicated in the semantic memory network. Significant correlation was also found between the functional connectivity strength of the left anterior hippocampus and the ventromedial cortex, and performance in semantic tasks. These findings indicate that the functional disconnection of the anterior hippocampus may be a promising in vivo biomarker of svPPA and illustrate the role of this hippocampal subregion in the semantic memory system.
Effects of climate‐related variability in storage on streamwater solute concentrations and fluxes in a small forested watershed in the Southeastern United States
Authors: Aulenbach Brent T.
Published: September 2019

Streamwater quality can be affected by climate‐related variability in hydrologic state, which controls flow paths and affects biogeochemical processes. Thirty‐one years of input/output solute fluxes at Panola Mountain Research Watershed, a small, forested, seasonally water‐limited watershed near Atlanta, Georgia, were used to quantify the effects of climatic‐related variability in storage on streamwater solute concentrations and fluxes. Streamwater fluxes were estimated for ten solutes from weekly and event sample concentrations using regression‐based methods. The most pertinent storage attribute (current or antecedent watershed, shallow, and deep storage) for each solute was determined by fitting separate concentration relationships. The concentration‐discharge relationships varied more for reactive solutes such as potassium, sulfate, and DOC and less for weathering products (base cations and dissolved silica) and conservative chloride. Many solutes exhibited higher concentrations when storage levels were lower or wetting up, which was likely the result of the concentrating effects of evapotranspiration and/or the buildup and flushing of weathering products associated with longer residence times. The impacts of storage modeling on annual fluxes varied by solute, ranging from about 5% (magnesium) to 52% (nitrate) as relative standard deviations, and sufficiently removed climate‐related patterns observed in streamwater concentrations. Sulfate was particularly mobilized following growing season droughts but only if deep storage was sufficiently recharged, possibly indicating that sulfides in the deep storage pool were oxidized to sulfate during droughts and mobilized when re‐wetted. The lack of streamwater sulfate response to 61% declines in atmospheric deposition indicates the importance of watershed biogeochemical processes on controls of streamwater export of sulfate. The approach of explicitly incorporating storage in the streamwater concentration modeling elucidated the effects of climate on streamwater water‐quality and may provide insight into the effects of climatic change on future fluxes.
Association of MAD1L1 polymorphism (rs871925) with prenatal famine exposure and schizophrenia in a Chinese population: A case–control study
Authors: Sun Yaoyao , Kang Guojun , Zhu Xiaojing , Li Rixin , Kang Qi , Zhang Mingyuan , Wang Yueying , Chen Xin , Yu Yaqin , Yu Qiong
Published: September 2019

Schizophrenia (SCZ) is a complex, frequently disabling psychiatric disorder. Prenatal exposure to famine, an environmental factor, plays a significant role in the cause of SCZ. We used DNA methylation related sites to analyze their association with prenatal famine exposure and SCZ risk in a Northeast Han Chinese population. A total of 967 subjects (446 patients with SCZ/521 health controls) were recruited. Five single‐nucleotide polymorphisms (rs2300149 in ITIH1, rs2675956 in NGEF, rs3758543 in NT5C2, rs7003288 in NA, and rs871925 in MAD1L1) were selected and genotyped. Genotype distribution and allele frequency analysis indicated that rs871925 was significantly associated with SCZ. We also found a significant association between prenatal exposure to famine and rs871925 in the recessive model in the health control group. The generalized multifactor dimensionality reduction analysis suggested a five‐locus interaction model association with the risk of developing SCZ. Our data suggested that MAD1L1 rs871925 was associated with prenatal famine exposure and SCZ susceptibility in a Northeast Han Chinese population.
Doxycycline containing hydroxyapatite ceramic microspheres as a bone‐targeting drug delivery system
Authors: Soriano‐Souza Carlos , Valiense Helder , Mavropoulos Elena , Martinez‐Zelaya Victor , Costa Andrea Machado , Alves Adriana T. , Longuinho Mariana , Resende Rodrigo , Mourão Carlos , Granjeiro Jose , Rocha‐Leao Maria H. , Rossi Alexandre , Calasans‐Maia Mônica
Published: September 2019

Drug delivery technology is a promising way to enhance the therapeutic efficacy of drugs. The purpose of this study is to evaluate the physical and chemical properties of hydroxyapatite ceramic microspheres loaded with doxycycline (HADOX), their effects on in vitro osteoblast viability, and their antimicrobial activity, and to determine the effects of DOX on the healing of rat sockets after tooth extraction. The internal microsphere porosity was sensitive to the treatment used to adsorb DOX onto microsphere surface; HA microspheres without DOX presented 26% of pores, whereas HADOX0.15 microspheres presented 52.0%. An initial drug release of 49.15 μg/ml was observed in the first 24 hr. The minimal inhibitory concentration (MIC) tested against Enterococcus faecalis demonstrated that bacterial growth was inhibited for up to 7 days. Results of cell viability and cell proliferation did not indicate statistical differences in the metabolic activity of HADOX samples relative to HA without DOX microspheres (p > .05). After 1 week, a discreet inflammation reaction was observed in the control group, and after 6 weeks, newly‐formed bone was observed in the HADOX0.15 (p < .05). The HADOX did not interfere in the bone repair and controlled the early inflammatory response. HADOX could be a promising biomaterial to promote bone repair in infected sites.
Relationship Between the Supervisory Working Alliance and Outcomes: A Meta‐Analysis
Authors: Park Eun Hye , Ha Gyuyoung , Lee Sujung , Lee Yu Young , Lee Sang Min
Published: September 2019

This study investigated the relationships between the supervisory working alliance and supervision outcome variables using meta‐analysis. The authors reviewed 27 articles, dissertations, and theses published between 1990 and 2018. The authors used the MIX program to calculate the meta‐analyses. The results indicate that the supervisory working alliance is positively related to supervision outcome variables. Supervisees’ perceived relationship with the supervisor was positively related to the relationship with the client. This shows that the phenomenon of isomorphism is a repeated pattern in the relationships in supervision and counseling. The authors discuss the limitations and implications.
miR‐4735‐3p regulates phenotypic modulation of vascular smooth muscle cells by targeting HIF‐1‐mediated autophagy in intracranial aneurysm
Authors: Gao Ge , Zhang Yang , Chao Yingjiu , Niu Chaoshi , Fu Xianming , Wei Jianjun
Published: September 2019

Intracranial aneurysm (IA) is recognized as a lethal form of cerebrovascular disease mainly featured with a modulated phenotype of vascular smooth muscle cells (SMCs). It is generally believed that enhanced SMC proliferation and migration capabilities are the main characteristics in this process. In this study, we revealed that microRNA‐4735 (miR‐4735) participates in phenotypic modulation in a hypoxia‐inducible factor‐1 (HIF‐1)‐dependent manner of SMCs. miR‐4735 targets the 3′‐untranslated region of HIF‐1. The downregulated expression of miR‐4735 in IA tissues leads to elevated expression of HIF‐1, which activates autophagy and promotes autophagy‐mediated SMC proliferation and migration. Overexpression of miR‐4735 suppressed HIF‐1 expression and HIF‐1‐mediated autophagy, which led to impaired SMC proliferation and migration abilities. Forced expression of HIF‐1 in miR‐4735‐overexpressed SMCs rescued the impaired SMC proliferation and migration abilities. In conclusion, miR‐4735 plays an important role in phenotypic modulation in IA by regulating autophagy‐promoted SMC proliferation and migration.
Identification of aberrantly expressed lncRNA and the associated TF‐mRNA network in hepatocellular carcinoma
Authors: Wang Bin , Tang Dongyang , Zhang Ziyang , Wang Zhiwei
Published: September 2019

Emerging evidence has indicated that long noncoding RNA (lncRNA) plays crucial roles in regulating hepatocellular carcinoma (HCC) progression. However, a comprehensive lncRNA‐transcription factor (TF)‐message RNA (mRNA) in HCC remains absent. The aim of this study was to identify aberrantly expressed lncRNAs and the associated TF‐mRNA network in HCC. GSE124535 dataset was downloaded from the Gene Expression Omnibus database. Limma package in R was conducted to analyze abnormally expressed lncRNAs (differentially expressed lncRNAs [DELs]) and mRNAs (differentially expressed genes). The prognostic roles of screened DELs in HCC were evaluated at GEPIA. The expression of DELs that correlated with overall survival of HCC patients was further validated using circlncRNAnet, GEPIA, and StarBase. LncRNA‐TF‐mRNA potential triplets in HCC were predicted by LncMAP. After that, lncRNA‐TF‐mRNA networks were established using Cytoscape. A total of 20 upregulated and 17 downregulated DELs were identified in HCC tissues compared with adjacent noncancerous tissues. Six out of 20 upregulated and 6 out of 17 downregulated DELs were identified have significant impact on the overall survival of HCC patients. Results in circlncRNAnet, GEPIA, and Starbase confirmed the expression level of DELs obtained from GSE124535. Finally, the LncRNA‐TF‐mRNA regulatory networks for upregulated and downregulated lncRNA were established based on these analyses results. Among these lncRNAs in the network, the aberrantly expression of lncRNAs including LINC00511, RP11‐290F5.1, MIR4435‐2HG, and CTC‐537E7.3 in HCC was first time reported to date. In the study, potential LncRNA‐TF‐mRNA regulatory networks were identified, which will advance our understanding concerning the progression of HCC.
Homolytic Versus Heterolytic Bond Breaking in Functionalized [R‐C20H10]+ Systems
Authors: Li Jingbai , Rogachev Andrey Yu.
Published: September 2019

The comprehensive theoretical investigation of stability of functionalized corannulene cations [R‐C20H10]+ with respect to two alternative bond‐breaking mechanisms, namely, homolytic or radical ([R‐C20H10]+ → R• + C20H10+•) and heterolytic or cationic ([R‐C20H10]+ → R+ + C20H10), was accomplished. The special focus was on the influence of the nature of R‐group on the energetics of the bond cleavage. Detailed study of energetics of both mechanisms has revealed that the systems with small alkyl groups such as methyl tend to undergo bond breaking in accordance with homolytic mechanism. Subsequent elongation of the chain of the R‐group resulted in shifting the paradigm, making heterolytic path more energetically favorable. Subsequent analysis of different components of the bonding between R‐group and corannulene polyaromatic core helped to shed light on trends observed. In both mechanisms, the covalent contribution was found to be dominating, whereas ionic part contributes ~25–27%. Two leading components of ΔEorb, C20H10 → R and R → C20H10, were identified with NOCV‐EDA approach. While the homolytic pathway is best described as R → C20H10 process, the heterolytic mechanism shows domination of the C20H10 → R term. Surprisingly, the preparation energy (ΔEprep) was identified as a key player in stability tendencies found. In other words, the relative stability of corresponding molecular fragments (here R‐groups as the corannulene fragment remains the same for all systems) in their cationic or radical forms determine the preference given to a specific bond breaking path and, as consequence, the total stability of target functionalized cations. These conclusions were further confirmed by extending a set of R‐groups to conjugated (allyl, phenyl), bulky (iPr, tBu), β‐silyl (CH2SiH3, CH2SiMe3), and benzyl (CH2Ph) groups. © 2019 Wiley Periodicals, Inc.
Glycochenodeoxycholate induces cell survival and chemoresistance via phosphorylation of STAT3 at Ser727 site in HCC
Authors: Wang Jue , Zhou Maojun , Jin Xin , Li Bingxin , Wang Chengzhi , Zhang Qi , Liao Mingmei , Hu Xuan , Yang Manyi
Published: September 2019

Glycochenodeoxycholate (GCDA) is closely associated with carcinogenesis and chemoresistance of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3), a transcription factor, is involved in various human tumors. Whether GCDA induces chemoresistance through STAT3 and the mechanism of action remains elusive. In this study, we firstly found that the expression level of STAT3 has a positive correlation with chemoresistance of HCC cells. Moreover, GCDA can upregulate the expression of STAT3 protein. Hence, we suspect that GCDA may induce chemoresistance of HCC cells via STAT3. Mechanistically, GCDA stimulates phosphorylation of STAT3 at Ser727 site and mediates pSer727‐STAT3 protein to translocate and aggregate in the nucleus, which is important for cell survival. When Ser727 of STAT3 mutated to Asp, the capacity of STAT3 to accumulate in the nucleus was attenuated, STAT3‐induced cell survival was impaired and GCDA‐induced chemoresistance was abolished. In addition, while activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) was inhibited by PD98059, phosphorylation of STAT3 at Ser727 induced by GCDA was suppressed. Taken together, these data demonstrate that GCDA‐enhanced survival of liver cancer cells may occur through the activation of STAT3 by phosphorylation at Ser727 site via mitogen‐activated protein kinase/ERK1/2 pathway, which may contribute to the progression of human liver cancer and chemoresistance.
Continuous natamycin production by using immobilized Streptomyces gilvosporeus Z8 via repeated batch culture
Authors: Zeng Xin , Zeng Huawei , Meng Yi , Xu Dayong , Zhang Biao , Xin Bingyue , Liu Shuai , Zhai Bo , Yu Feiyang , Zhu Mingzhi , Li Feng
Published: September 2019

BACKGROUND

Natamycin is an antibiotic which shows strong inhibition and wide spectrum against most fungi. It is produced mainly through batch and fed‐batch fermentations, which are characterized by long culture time, low productivity and enormous discharge of waste biomass. In the present study, a new strategy using immobilized cells was proposed for continuous natamycin production via repeated batch culture to address these shortcomings.

RESULTS

A combination of cell immobilization and repeated batch culture was employed to continuously produce natamycin in both flasks and a 5‐L fermenter. The immobilized cells served as seeds and producing strains, and exhibited high vitality of cell growth and natamycin biosynthesis during six cycles of repeated batch culture. The application of the new strategy led to remarkable decrease of lag phase and removal of time intervals among traditional multiple batch cultures, resulting in a 32.10% reduction of total culture time. In addition, the new strategy showed 1.8‐fold higher natamycin titre and 195.24% productivity improvement relative to traditional strategies, and decreased waste biomass discharge, thus consituting a high‐efficiency, environmentally friendly strategy for natamycin production.

CONCLUSION

This study proposes a new approach to continuous natamycin production, which not only promoted natamycin productivity, but also reduced the fermentation time and the biomass residue discharge. Moreover, it provides reference points for the continuous production of other biochemicals by filamentous bacteria or funguses, which could be of great significance in industrial antibiotics production. © 2019 Society of Chemical Industry
Copper(II) Oxide Nanoparticles Impregnated on Melamine‐Modified UiO‐66‐NH2 Metal–Organic Framework for C–N Cross‐Coupling Reaction and Synthesis of 2‐Substituted Benzimidazoles
Authors: Najari Susan , Jafarzadeh Mohammad , Bahrami Kiumars
Published: September 2019

A zirconium‐based metal–organic framework, UiO‐66‐NH2, modified by melamine (Mlm) was used as a support for CuO nanoparticles (NPs). Melamine offered a platform for uniform and homogeneous distribution of NPs on the surface of the frameworks and made a strong bonding to the NPs to avoid undesirable leaching. UiO‐66‐NH2‐Mlm/CuO NPs were used for the Buchwald–Hartwig C–N cross‐coupling reaction to synthesize arylated anilines from phenyl iodide, bromide, and chloride and primary and secondary amines in DMF at 110°C. The catalyst was also employed for the synthesis of 2‐substituted benzimidazole derivatives from various aromatic aldehydes and o‐phenylenediamine in the absence of an oxidant in EtOH at room temperature. The catalyst was recyclable and reusable for several times and exhibited good stability (examined by BET, XRD, and SEM–EDX) in reaction conditions.
Perinatal outcomes following maternal pre‐exposure prophylaxis (PrEP) use during pregnancy: results from a large PrEP implementation program in Kenya
Authors: Dettinger Julia C , Kinuthia John , Pintye Jillian , Abuna Felix , Begnel Emily , Mugwanya Kenneth , Sila Joseph , Lagat Harison , Baeten Jared M , John‐Stewart Grace
Published: September 2019

Introduction

The World Health Organization, while recommending pre‐exposure prophylaxis (PrEP) for HIV‐negative pregnant and postpartum women in HIV high‐burden settings, advocates for continued safety evaluation of PrEP in this population.

Methods

The PrEP Implementation in Young Women and Adolescents (PrIYA) program delivered PrEP to pregnant and postpartum women integrated within routine maternal and child health clinics (MCH) at 16 sites in Western Kenya. PrEP exposure and perinatal outcome data were collected among women obtaining postnatal services during programme evaluation. PrEP use was self‐reported and confirmed with clinical records. Perinatal outcomes including gestational age at birth, birthweight, congenital malformations and infant growth outcomes were abstracted from clinical records for mother‐infant pairs attending the six week visit. Associations between infant outcomes and maternal prenatal PrEP use were assessed using univariate and multivariate logistic and linear regression.

Results

The PrIYA evaluation identified 1530 postpartum mother‐infant pairs with data on prenatal PrEP exposure: 206 with prenatal PrEP use, 1324 without. Median maternal age was 24 years in both groups. PrEP users (any reported PrEP use) were significantly more likely to report HIV risk factors such as: intimate partner violence, sexually transmitted infections and having a partner with positive or unknown HIV status. Most mothers initiated PrEP during the second trimester (n = 116, 57%) and used PrEP for more than one month (n = 110, 58%). The mean birthweight was 3.3 kg and gestational age at birth was 38.5 weeks in both groups. There were no major differences between PrEP exposed and unexposed infants in rates of preterm birth and low birthweight. There were no congenital malformations identified in the PrEP‐exposed group and five reported in the PrEP unexposed group. At six weeks postpartum, infants in both groups had similar growth. No differences in infant outcomes were found by duration PrEP exposure, trimester of PrEP initiation, a subset analysis of women 15 to 24 years old or in multivariate analyses. This analysis demonstrates that monitoring of infant outcomes is feasible within large‐scale programmatic implementation of PrEP among pregnant and postpartum populations.

Conclusions

Pregnancy outcomes and early infant growth did not differ by PrEP exposure.
Radiolabeling and in vitro evaluation of a new 5‐fluorouracil derivative with cell culture studies
Authors: Ilem‐Ozdemir Derya , Atlihan‐Gundogdu Evren , Ekinci Meliha , Halay Erkan , Ay Kadir , Karayildirim Tamer , Asikoglu Makbule
Published: September 2019

The clinical impact and accessibility of 99mTc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5‐Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5‐Fluorouracil was synthesized as (1‐[{1′‐(1′′‐deoxy‐2′′,3′′:4′′,5′′‐di‐O‐isopropylidene‐β‐D‐fructopyranose‐1′′‐yl)‐1′H‐1′,2′, 3′‐triazol‐4′‐yl}methyl]‐5‐fluorouracil) (E) and radiolabeled with 99mTc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell‐binding studies to determine healthy and cancer cell affinity using HaCaT and MCF‐7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF‐5 cells. The radiochemical purity of the [99mTc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF‐7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 μM and 20.7 ± 2.77 μM for MCF‐7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99mTc has selective for breast cancer cells.
Analysis of tetrahydrocannabinol derivative from cannabis‐infused chocolate by QuEChERS‐thin layer chromatography‐desorption electrospray ionization mass spectrometry
Authors: Yousefi‐Taemeh Maryam , Ifa Demian R.
Published: September 2019

Recently in Canada and some states of the United States, marijuana (cannabis) has become fully legalized and regulated, for both medical and recreational purposes. This fact is going to make cannabis products such as edibles even more popular than ever before. Therefore, it is assumed that there will be a high demand for analytical methods, which are accurate and sensitive enough to be used in different forensic and pharmaceutical cannabis–related applications. Cannabis derivatives have an extreme range and number of constituents with possible interactions with one another. Thus, this characteristic leads to their vast and highly complex chemistry, which requires robust analytical tools to be able to precisely and accurately quantify and qualify them. We developed and validated an analytical method using desorption electrospray ionization (DESI)–mass spectrometry (MS) to accurately detect, characterize, and quantify cannabinoids and also offer an easy, cost‐effective, and reliable technique, which can be performed in a short time for infused edibles in complex matrices such as chocolate. We evaluated a quantitative analysis of tetrahydrocannabinol (THC) in cannabis‐infused chocolate with thin‐layer chromatography (TLC)–DESI‐MS and QuEChERS extraction method. Both techniques of TLC and QuEChERS are cost‐effective and can be run in short time.
High prevalence of equine‐like G3P[8] rotavirus in children and adults with acute gastroenteritis in Thailand
Authors: Tacharoenmuang Ratana , Komoto Satoshi , Guntapong Ratigorn , Upachai Sompong , Singchai Phakapun , Ide Tomihiko , Fukuda Saori , Ruchusatsawast Kriangsak , Sriwantana Busarawan , Tatsumi Masashi , Motomura Kazushi , Takeda Naokazu , Murata Takayuki , Sangkitporn Somchai , Taniguchi Koki , Yoshikawa Tetsushi
Published: September 2019

Group A rotavirus (RVA) is a major cause of acute gastroenteritis in infants and young children worldwide. This study aims to clarify the distribution of G/P types and genetic characteristics of RVAs circulating in Thailand. Between January 2014 and September 2016, 1867 stool specimens were collected from children and adults with acute gastroenteritis in six provinces in Thailand. RVAs were detected in 514/1867 (27.5%) stool specimens. G1P[8] (44.7%) was the most predominant genotype, followed by G3P[8] (33.7%), G2P[4] (11.5%), G8P[8] (7.0%), and G9P[8] (1.3%). Unusual G3P[9] (0.8%), G3P[10] (0.4%), G4P[6] (0.4%), and G10P[14] (0.2%) were also detected at low frequencies. The predominant genotype, G1P[8] (64.4%), in 2014 decreased to 6.1% in 2016. In contrast, the frequency of G3P[8] markedly increased from 5.5% in 2014 to 65.3% in 2015 and 89.8% in 2016. On polyacrylamide gel electrophoresis, most (135/140; 96.4%) of the G3P[8] strains exhibited a short RNA profile. Successful determination of the nucleotide sequences of the VP7 genes of 98 G3P[8] strains with a short RNA profile showed that they are all equine‐like G3P[8] strains. On phylogenetic analysis of genome segments of two representative Thai equine‐like G3P[8] strains, it was noteworthy that they possessed distinct NSP4 genes, one bovine‐like and the other human‐like. Thus, we found that characteristic equine‐like G3P[8] strains with a short RNA electropherotype are becoming highly prevalent in children and adults in Thailand.
Office‐based CO2 laser surgery for benign and premalignant laryngeal lesions
Authors: Wellenstein David J. , Honings Jimmie , Schimberg Anouk S. , Schutte Henrieke W. , Herruer Jasmijn M. , van den Hoogen Frank J.A. , Takes Robert P. , van den Broek Guido B.
Published: September 2019

Objective

Patients with laryngeal pathology are often treated with CO2 laser surgery, usually in the operating room under general anesthesia. Although office‐based laser surgery using several other laser types has been investigated, prospective studies on office‐based CO2 laser surgery are scarce. Our goal was to investigate the feasibility of office‐based CO2 laser surgery for benign and premalignant laryngeal pathology by analyzing completion rate, safety, effect on voice quality, and success rate (i.e., no residual or recurrent disease).

Methods

A prospective cohort study was performed of 30 consecutive procedures. Inclusion started in June 2016 and was completed in August 2018. Adult patients with clinically benign or premalignant laryngeal lesions who could not undergo transoral laser microsurgery in the operating room under general anesthesia were included. Reasons were either contraindications for general anesthesia, previously failed therapeutic laryngoscopy under general anesthesia, and preference of a procedure under topical anesthesia by the patient. The mean follow‐up was 9 months.

Results

Thirty procedures were performed in 27 patients (24 males) with an average age of 62 years. Twenty‐nine (97%) procedures were fully completed without complications. The mean preoperative Voice Handicap Index (VHI) score (VHI 44) significantly decreased 2 months (VHI 28, P = 0.032) and 6 months (VHI 14, P < 0.001) after the procedure. Almost two‐thirds of patients showed no residual or recurrent disease at their follow‐up visits.

Conclusion

Office‐based CO2 laser surgery is a feasible and safe procedure that results in significant voice‐quality improvement. Almost two‐thirds of patients did not require further treatment.

Level of Evidence

2 Laryngoscope, 130:1503–1507, 2020
Trace metals in Antarctic clam shells record the chemical dynamics of changing sea ice conditions
Authors: Wing Stephen R. , O'Connell‐Milne Sorrel A. , Wing Lucy C. , Reid Malcolm R.
Published: September 2019

The dynamics of freeze and thaw events in Antarctic sea ice impart chemical changes in the underlying sea water. Trace metals in sea ice and accumulated through deposition of dust are released into sea water as sea ice breaks up in spring. Clams such as Laternula elliptica incorporate a record of these and associated chemical dynamics in their carbonate shells. In 2012, we collected samples of L. elliptica from three sites along a sea ice persistence gradient in McMurdo Sound, Ross Sea Antarctica. Concentrations of trace metals in the chondrophore of each shell were measured by laser ablation inductively coupled plasma mass spectrometry. Ablations transected annual growth increments creating time series ranging in length from 13 to 25 yr. An 8‐yr time period of persistent sea ice, associated with presence of the B‐15 and C‐19 icebergs at the entrance of McMurdo Sound, was clearly resolved in the trace element time series. Conservative trace metals (Sr, Ba) were found at higher concentrations, and highly scavenged elements (Pb, Cu) were found at lower concentrations at sites with more persistent sea ice and during the 8‐yr period of iceberg‐influenced sea ice persistence. Bioactive trace metals (Fe, Ni) were found in higher concentrations during ice free conditions, associated with a period of high pelagic productivity. Our results provide an important case study for understanding the chemical signature of changing sea ice dynamics as reflected in bivalve shell material under a changing Antarctic climate.
Nonunion Vulnerability Analysis—Part 1
Authors: DeMaria Alfred T.
Published: September 2019

Many union free companies periodically undertake objective assessments of their vulnerability to third‐party activity. The assessment, which may be annual, biennial, or at any other frequency suited to a firm's circumstances, assigns numerical values to various vulnerability factors. The analysis may produce an overall vulnerability rating to be compared over time, or it may assess plant sites separately to provide relative ratings for that cycle only. The assessment may be based on one source of data (for example, a selection of questions from the employee opinion survey) or it may combine data from several sources. Any combination of these characteristics is considered a vulnerability analysis.
LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY BOTTOM‐UP PROTEOMIC METHODS IN ANIMAL SPECIES ANALYSIS OF PROCESSED MEAT FOR FOOD AUTHENTICATION AND THE DETECTION OF ADULTERATIONS
Authors: Stachniuk Anna , Sumara Agata , Montowska Magdalena , Fornal Emilia
Published: September 2019

This review offers an overview of the current status and the most recent advances in liquid chromatography–mass spectrometry (LC‐MS) techniques with both high‐resolution and low‐resolution tandem mass analyzers applied to the identification and detection of heat‐stable species‐speciﬁc peptide markers of meat in highly processed food products. We present sets of myofibrillar and sarcoplasmic proteins, which turned out to be the source of 105 heat‐stable peptides, detectable in processed meat using LC‐MS/MS. A list of heat‐stable species‐specific peptides was compiled for eleven types of white and red meat including chicken, duck, goose, turkey, pork, beef, lamb, rabbit, buffalo, deer, and horse meat, which can be used as markers for meat authentication. Among the 105 peptides, 57 were verified by multiple reaction monitoring, enabling identification of each species with high specificity and selectivity. The most described and monitored species by LC‐MS/MS so far are chicken and pork with 26 confirmed heat‐stable peptide markers for each meat. In thermally processed samples, myosin, myoglobin, hemoglobin, l‐lactase dehydrogenase A and β‐enolase are the main protein sources of heat‐stable markers. © 2019 John Wiley & Sons Ltd. Mass Spec Rev
Microstructures and corrosion resistance of as‐cast aluminum‐10 wt.% silicon and aluminum‐20 wt.% silicon alloys
Authors: Zhao Z.L. , Yin S.Q. , Liu Y.D. , Zhang Z.Q. , Ren R.F.
Published: September 2019

The microstructures and corrosion resistance of two as‐cast alloys, aluminum‐10 wt.% silicon hypoeutectic alloy and aluminum‐20 wt.% silicon (weight percent) hypereutectic alloy are investigated by conventional casting, the scanning electron microscope equipped with oxford X‐ray energy dispersive spectroscopy system and transmission electron microscope are applied for analysis. The results show that the microstructures change from the strip‐like into lump shape with the increase of silicon content from 10 % to 20 %. The electrochemical polarization curves prove that the aluminum‐20 wt.% hypereutectic silicon alloy had the better resistance with the corrosion potential of −1.414 V and corrosion current density of 5.41 ⋅ 10−5 ampere compared with the aluminum‐10 wt.% silicon hypoeutectic alloy.