bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion
Authors: Dodge Andie , Peters Melinda M. , Greene Hayden E. , Dietrick Clifton , Botelho Robert , Chung Diana , Willman Jonathan , Nenninger Austin W. , Ciarlone Stephanie , Kamath Siddharth G. , Houdek Pavel , Sumová Alena , Anderson Anne E. , Dindot Scott V. , Berg Elizabeth L. , O'Geen Henriette , Segal David J. , Silverman Jill L. , Weeber Edwin J. , Nash Kevin R.
Published: January 2020

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397–409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc.

Lay Summary

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS.
Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection
Authors: Delayre T , Guilbaud T , Resseguier N , Mamessier E , Rubis M , Moutardier V , Fara R , Berdah S V , Garcia S , Birnbaum D J
Published: January 2020

Background

The prognosis of patients with pancreatic cancer remains poor and novel therapeutic targets are required urgently. Treatment resistance could be due to the tumour microenvironment, a desmoplastic stroma consisting of cancer-associated fibroblasts and tumour-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and cancer-associated fibroblasts (CAFs) in pancreatic cancer of the body and tail.

Methods

Using tissue microarray from resected left-sided pancreatic cancer specimens, the immunohistochemistry of TILs (cluster of differentiation (CD) 45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and α-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki-67) was examined, and the association with disease-free (DFS) and overall (OS) survival investigated using a computer-assisted quantitative analysis. Patients were classified into two groups, with low or high levels or ratios, using the 75th percentile value as the cut-off.

Results

Forty-three patients were included in the study. Their median DFS and OS were 9 and 27 months respectively. A high CD4/CD3 lymphocyte ratio was associated with poorer DFS (8 months versus 11 months for a low ratio) (hazard ratio (HR) 2·23, 95 per cent c.i. 1·04 to 4·61; P = 0·041) and OS (13 versus 27 months respectively) (HR 2·62, 1·11 to 5·88; P = 0·028). A low αSMA/vimentin ratio together with a high CD4/CD3 ratio was correlated with poorer outcomes. No significant association was found between Ki-67, PD-L1 and survival.

Conclusion

In patients with resected left-sided pancreatic cancer, a tumour microenvironment characterized by a high CD4/CD3 lymphocyte ratio along with a low αSMA/vimentin ratio is correlated with poorer survival.
Metabolic responses of BV‐2 cells to puerarin on its polarization using ultra‐performance liquid chromatography–mass spectrometry
Authors: Li Ling , Wang Yan , Wang Hui , Lv Lei , Zhu Zhen‐Yu
Published: January 2020

Microglia are the primary immune cells in the central nervous system with functional plasticity. They can be activated into M1 and M2 phenotypes when neuroinflammation‐related diseases occur. M1 phenotype cells produce pro‐inflammatory mediators that cause neuroinflammation and the M2 phenotype can secrete anti‐inflammatory cytokines that protect neurons from damage. Therefore, inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for treating neuroinflammation‐related diseases. Puerarin has been demonstrated to exert anti‐inflammatory and neuroprotective effects. However, the role of puerarin in regulating microglia polarization and its reaction mechanism has not been fully elucidated. In this paper, a metabolomics approach with ultra‐performance liquid chromatography–mass spectrometry was performed to investigate the metabolic changes of BV‐2 cells in different phenotypes and test the effects of puerarin on polarization. Thirty‐nine metabolites were identified as the biomarkers related to the polarization of BV‐2 cells and puerarin intervention reverted the content of most of the biomarkers. Our study demonstrated that puerarin could play a key role in M1/M2 polarization of BV‐2 cells from a perspective of metabolomics, and it could regulate the balance between promotion and suppression of inflammation.
Does the configuration of macro‐ and micro‐institutional environments affect the effectiveness of green supply chain integration?
Authors: Yang Qian , Geng Ruoqi , Feng Taiwen
Published: January 2020

Despite the importance of the general environment in affecting the effectiveness of green supply chain integration (GSCI), our understanding of the roles of different configurations of macro‐ and micro‐institutional environments remains limited. Based on institutional theory and resource mobilization theory, this study examined the moderating effects of the configurations of macro‐ and micro‐institutional environments on the GSCI performance link employing both a configuration and a contingency perspective. Our findings from a longitudinal survey of 206 Chinese manufacturing firms provide empirical evidence for the coexistence and nature of macro‐ and micro‐institutional environments and their moderating effect on the GSCI performance link. Specifically, the results revealed that Chinese manufacturers can be clustered into three groups with different macro‐ and micro‐institutional environments (i.e., cognizant, sensible, and conscious manufacturers). Furthermore, the configuration of macro‐ and micro‐institutional environments moderates the effect of green supplier integration on social performance, as well as the effects of green customer integration on financial, environmental, and social performance. This study contributes to both the GSCI literature and practices.
Anatomy, physiology, and updates on the clinical management of constipation
Authors: Dupont Graham , Wahl Lauren , Alcala Dominguez Tamara , Wong TL , Haładaj Robert , Wysiadecki Grzegorz , Iwanaga Joe , Tubbs R. Shane
Published: January 2020

Clinical management of constipation has evolved from the prescription of dietary supplements, to potent stimulant laxatives, to corrective surgeries for organic blockage. Yet constipation does not respond to a one‐size‐fits‐all treatment. In recent decades, the Bristol Stool Form Scale and Rome III diagnostic criteria have allowed for algorithmic diagnosis, yet these criteria could benefit from further extension and meaningful discussion. This review incorporates pertinent clinical updates and uses the anatomy and physiology of constipation as helpful signposts for the practicing clinician.
Breast cancer stromal clotting activation (Tissue Factor and thrombin): A pre‐invasive phenomena that is prognostic in invasion
Authors: Shaker Hudhaifah , Bundred Nigel J. , Landberg Göran , Pritchard Susan A. , Albadry Harith , Nicholson Sarah L. , Harries Lauren J. , Heah Jing Y. E. , Castle John , Kirwan Cliona C.
Published: January 2020

Background

Tumor stroma, of which fibroblasts are the most abundant cell, resembles a non‐healing wound, where a procoagulant environment creates a permissive milieu for cancer growth. We aimed to determine if tumor expression of coagulation factors (procoagulant phenotype), and systemic hypercoagulability, occur at the preinvasive (ductal carcinoma in situ; DCIS) stage and correlate with breast cancer subtype, disease‐free survival (DFS), and overall survival (OS).

Methods

In a prospective cohort of early breast cancer (DCIS, n = 76; invasive, n = 248) tumor, normal breast and plasma were examined. Fibroblast and epithelial expression of Tissue Factor (TF), thrombin, PAR1, PAR2, and plasma thrombin‐antithrombin (TAT) and D‐dimer were correlated with clinicopathological data, and 5‐year survival.

Results

Fibroblast expression of TF, thrombin, and PAR1 was increased in DCIS and invasive cancer compared to normal breast fibroblasts (P ≤ .003, all). Fibroblast TF, thrombin, PAR1, and PAR2 was increased in cancers with high Ki67, high grade, ER‐ (vs ER+), and HER2+ (vs HER2‐) (all P < .05). On univariate analysis, fibroblast TF expression was inversely associated with DFS (P = .04) and OS (P = .02). D‐dimer was higher in node positive (507 (CI: 411‐625) ng/mL, n = 68) vs negative patients (428 (CI: 387‐472) ng/mL, n = 171, P = .004) and inversely associated with OS (P = .047). On multivariate analysis, plasma TAT was associated with reduced OS (HR 3.26, CI 1.16‐3.1, P = .02), with a high plasma TAT (≥3.2 ng/mL) associated with > 3‐fold mortality risk compared to low TAT.

Conclusion

This demonstrates procoagulant phenotypic changes occur in fibroblasts at the preinvasive stage. Fibroblast procoagulant phenotype is associated with aggressive breast cancer subtypes and reduced survival. Coagulation may be a therapeutic target in breast cancer.
The Same but Different? Exploring the Links between Gender, Trauma, Sexual Exploitation and Harmful Sexual Behaviours
Authors: Hallett Sophie , Deerfield Kat , Hudson Kirsty
Published: January 2020

This article presents data on 1550 children and young people with experiences of child sexual exploitation or who are displaying harmful sexual behaviours (HSB). Data were collected from two recently merged services operating across Wales: one working with children and young people who are at risk of, or abused through, sexual exploitation; and the other providing assessment and intervention services for children and young people displaying HSB. Importantly, the research provided an opportunity for a comparative analysis of key demographic characteristics and abuse histories of two separate cohorts of children and young people. Clear differences exist across the two cohorts in terms of gender. However, our analysis revealed similar patterns in relation to their experiences of prior abuse, and the prevalence of a family history of domestic violence is near identical. We consider how these findings speak to a need to understand the role of gender, and to recognise potential gendered understandings and gendered trajectories of harm for children. Findings also indicate the importance of directing attention to the wellbeing needs of children and young people who have experienced trauma, regardless of the presenting issues of concern.

‘Presents data on 1550 children and young people with experiences of child sexual exploitation or who are displaying harmful sexual behaviours’

Key Practitioner Messages

CSE and HSB are different welfare concerns, but the children and young people referred to services for CSE and HSB may have similarly high levels of similar past trauma.

There is a need for a greater understanding of how behavioural responses to trauma can be different for boys and girls, and may lead to different risk trajectories.

Practitioners should be encouraged to be reflexive about their assumptions of sexual norms and behaviours among children, particularly in relation to gender and their ideas about vulnerability and risk.

Practice with children and young people would benefit from recognising and responding to trauma experiences, and also from directing attention to the specific wellbeing needs of individual children and young people, regardless of the presenting areas of concern, that is, CSE or HSB (and gender).

Assessment data collected should also reflect the backgrounds, needs and strengths of these children and young people, addressing the underlying issues behind potential vulnerability and harms, and not simply the risks that children and young people may pose or in which they may engage.
Safeguarding Children in South African Townships Against Child Sexual Abuse: The Voices of Our Children
Authors: Fouché Ansie , Truter Elmien , Fouché Daniel F.
Published: January 2020

This qualitative study explored the views of children about how their township communities should change to safeguard children from child sexual abuse (CSA). In 2014, 18 North‐West University student social workers, placed at four organisations for practical work in Gauteng, South Africa, were trained to purposefully recruit participants and employ a draw‐and‐write visual research method. Ninety participants between 13 and 18 years from South African townships whose families were receiving social work services participated. Seventy‐eight participants' (males = 44.9%; females = 55.1%) drawings and narratives were analysed by means of the analytical framework method. They identified the following role players and their duties in creating safer township communities, namely: (1) community members – safeguard the environment and are committed to a changed value system where children are respected and social problems are alleviated; (2) police and security personnel – trustworthy, visible and quick to intervene; (3) families – committed and equipped to protect their children; (4) professionals – approachable and accessible to intervene; and (5) children – empowered to protect themselves and other children. Children in this study experience their environment as unsafe and expressed the need for constant protection. Social ills must be addressed in township communities and mentioned role players must honour their tasks in combatting CSA.

‘This qualitative study explored the views of children about how their township communities should change to safeguard children from child sexual abuse’

Key Practitioner Messages

Children living in South African townships experience their environment as an unsafe space where they need constant protection against criminals.

Effective safety measures in which the police, social workers, family and community members play a crucial role should be implemented.

Social problems such as poverty, unemployment and substance abuse need to be addressed.

Children can take proactive measures to protect themselves against CSA in partnership with key role players.
Properties and bread‐baking performance of wheat flour composited with germinated pulse flours
Authors: Setia Rashim , Dai Zhixin , Nickerson Michael T. , Sopiwnyk Elaine , Malcolmson Linda , Ai Yongfeng
Published: January 2020

Background and objectives

Germination of pulse seeds can effectively improve the functional and nutritional properties of resultant flours for broader food applications to deliver multiple health benefits. However, there is a lack of understanding on the performance of germinated pulse flours in bakery goods, particularly in bread. This study aimed to determine the flour quality, dough properties, and baking performance of composite flours prepared by blending raw or germinated pulse flours and hard wheat flour at 10:90 and 20:80 ratios (w/w).

Findings

The incorporation of both raw and germinated yellow pea and faba bean flours reduced the starch level but increased the protein level of the flours. The inclusion of the pulse flours progressively decreased the pasting viscosities of the composite flours—with more noticeable changes being observed with the germinated samples, corresponding well with the decreases in their falling numbers. The incorporation of the raw and germinated pulse flours diminished the solvent retention capacity with 5% lactic acid and gluten performance index, and thus, the generated doughs showed shortened dough development time, poorer dough stability, and less elastic structure than the control. The breads baked from the wheat–pulse flour blends—despite the addition of 2% wheat gluten—exhibited decreased loaf volumes and smaller numbers of cells per slice but greater crumb firmness, and the use of 20% germinated pulse flours showed the most significant impact.

Conclusions

The inclusion of germinated yellow pea and faba bean flours into hard wheat flour weakened the dough structure and caused poorer bread‐baking performance.

Significance and novelty

The findings from this research greatly advanced our understanding of the roles that germinated pulse flours played in the flour and dough systems after being composited with hard wheat flour as well as their influence on the quality attributes of the baked bread products.
Successful closure of chronic recurrent Enterocutaneous fistula with a concurrent over‐the‐scope closure and a stent placement
Authors: Issak Abdulfatah , Musleh Mustafa
Published: January 2020

Gastrointestinal ulcers and perforations can occur as a complication of nonsteroidal anti‐inflammatory drugs (NSAID). Emerging endoscopic technologies can be utilized to successfully intervene perforations that fail surgical intervention. We report a case of perforated duodenal ulcer that failed surgical intervention and, however, was successfully closed with over‐the‐scope clip (OTSC) closure with concomitant placement of fully covered stent.
A giant umbilical cord: Benign finding or surgical emergency?
Authors: Mugarab Samedi Veronica , Miller Grant , Saade Edouard , Kalaniti Kaarthigeyan
Published: January 2020

Congenital urachal anomalies are usually asymptomatic. However, infection or obstruction of urachal remnant may result in serious complications. The giant umbilical cords with suspected internal communications could contain remnants and require surgical exploration. With timely recognition and surgical intervention, the outcome is generally good.
Immobilised Enzymes for Sesquiterpene Synthesis in Batch and Flow Systems
Authors: Valikhani Donya , Srivastava Prabhakar Lal , Allemann Rudolf K. , Wirth Thomas
Published: January 2020

Sesquiterpene synthases catalyse the bioconversion of farnesyl diphosphate into sesquiterpenes. The immobilisation of sesquiterpene synthases on controlled porosity glass through metal‐ion affinity binding is reported. The immobilised sesquiterpene synthases were able to maintain 50 % catalytic activity for at least 50 cycles under continuous flow conditions.
Humulene Diepoxides from the Australian Arid Zone Herb Dysphania: Assignment of Aged Hops Constituents
Authors: Tan Yuen Ping , Agnew‐Francis Kylie A. , Hofmann Julian , Savchenko Andrei I. , Lafontaine Scott R. , Boyle Glen M. , Bernhardt Paul V. , Fraser James A. , Shellhammer Thomas H. , Williams Craig M.
Published: January 2020

Dysphania is an abundant genus of plants, many of which are endemic to the Australian continent, occurring primarily in arid and temperate zones. Despite their prevalence, very few investigations into the phytochemistry of native Dysphania have been undertaken. Described herein, is the isolation and elucidation of two enantiomeric diastereomers of humulene diepoxide C from D. kalpari and D. rhadinostachya, of which unassigned diastereomers of humulene diepoxide C have been previously reported as components in beer brewed from aged hops. In addition, two (+)‐humulene diepoxiols (humulene diepoxiol C‐I and C‐II) were isolated from D. rhadinostachya. Analysis of Chinook hops oil confirmed the presence of both humulene diepoxide C‐I and C‐II as trace components, and in turn enabled GC‐MS peak assignment to the relative stereochemistry. Anticancer assays did not reveal any significant activity for the (+)‐humulene diepoxides. Antifungal assays showed good activity against a drug‐resistant strain of C. auris, with MIC50 values of 8.53 and 4.91 μm obtained for (+)‐humulene diepoxide C‐I and C‐II, respectively.
Highly Selective, Amine‐Derived Cannabinoid Receptor 2 Probes
Authors: Westphal Matthias V. , Sarott Roman C. , Zirwes Elisabeth A. , Osterwald Anja , Guba Wolfgang , Ullmer Christoph , Grether Uwe , Carreira Erick M.
Published: January 2020

The endocannabinoid (eCB) system is implied in various human diseases ranging from central nervous system to autoimmune disorders. Cannabinoid receptor 2 (CB2R) is an integral component of the eCB system. Yet, the downstream effects elicited by this G protein‐coupled receptor upon binding of endogenous or synthetic ligands are insufficiently understood—likely due to the limited arsenal of reliable biological and chemical tools. Herein, we report the design and synthesis of CB2R‐selective cannabinoids along with their in vitro pharmacological characterization (binding and functional studies). They combine structural features of HU‐308 and AM841 to give chimeric ligands that emerge as potent CB2R agonists with high selectivity over the closely related cannabinoid receptor 1 (CB1R). The synthesis work includes convenient preparation of substituted resorcinols often found in cannabinoids. The utility of the synthetic cannabinoids in this study is showcased by preparation of the most selective high‐affinity fluorescent probe for CB2R to date.
Distance Matters: Effect of the Spacer Length on the Photophysical Properties of Multimodular Perylenediimide–Silicon Phthalocyanine–Fullerene Triads
Authors: Martín‐Gomis Luis , Díaz‐Puertas Rocío , Seetharaman Sairaman , Karr Paul A. , Fernández‐Lázaro Fernando , D'Souza Francis , Sastre‐Santos Ángela
Published: January 2020

A multimodular donor–acceptor conjugate featuring silicon phthalocyanine (SiPc) as the electron donor, and two electron acceptors, namely tetrachloroperylenediimide (PDI) and C60, placed at the opposite ends of the SiPc axial positions, was newly designed and synthesized, and the results were compared to the earlier reported PDI‐SiPc‐C60 triad. Minimal intramolecular interactions between the entities was observed. Absorption, fluorescence, computational and electrochemical studies were performed to evaluate the excitation energy, geometry and electronic structure, and energy levels of different photoevents. Steady‐state absorption, fluorescence and excitation spectral studies revealed efficient singlet–singlet energy transfer from 1PDI* to SiPc in the PDI‐SiPc dyad and the PDI‐SiPc‐C60 triad. The measured rates for these photochemical events were found to be much higher than those reported earlier for the triad, due to closer proximity between the PDI and SiPc entities. The distance also affected the charge separation path in which involvement of PDI, and not C60, in charge separation in the present triad was witnessed. The present investigation brings out the importance of donor–acceptor distances in channeling photochemical events in a multimodular system.
Gasmenge präzise regeln
Authors: Haasler Claudia
Published: January 2020

Die Massendurchflussregler von Bürkert haben einen großen Stellbereich, eine sehr gute Wiederholgenauigkeit und sind konform zu USP Class VI, FDA, 3.1 Zeugnis und EG 1935.
Mehr als nur Mischen
Authors:   amixon
Published: January 2020

Zu einer Mischertagung trafen sich 80 Experten am 18. September bei Amixon in Paderborn, um über Schüttgutbehandlung und ‐veredelung zu sprechen.
Fasspumpen im Ex‐Bereich
Authors: Jessberger Kurt
Published: January 2020

Jessberger hat neue explosionsgeschützte Fasspumpenmotoren entwickelt, die sich neben einem geringen Gewicht durch Kompaktheit auszeichnen.
Rational Design of Single Atomic Co in CoNx Moieties on Graphene Matrix as an Ultra‐Highly Efficient Active Site for Oxygen Reduction Reaction
Authors: Shu Yasuhiro , Miyake Koji , Quílez‐Bermejo Javier , Zhu Yexin , Hirota Yuichiro , Uchida Yoshiaki , Tanaka Shunsuke , Morallón Emilia , Cazorla‐Amorós Diego , Kong Chang Yi , Nishiyama Norikazu
Published: January 2020

The sharp increase in current energy consumption needs the development of fuel cells (FCs) as one of sustainable, renewable, efficient and eco‐friendly electrochemical conversion systems of energy. The performance of electrocatalysts is crucially important for commercialization of FCs. Commercial Pt based catalysts are used due to their high catalytic activity. However, widespread commercialization is impossible because of the scarcity and poor durability of Pt based catalysts. We are on our quest to find a more stable and affordable alternative catalyst of Pt based catalysts. In particular, single‐atom catalysts supported on graphene are greatly attractive because of their unique characteristic and high catalytic activity. In this work, graphene is hydrothermally treated by sulfuric acid to introduce the ion‐exchanging sites. Then, Co2+ ion‐exchanging, 2‐methylimidazole coordination and pyrolysis process are subsequently conducted to prepare highly‐dispersed single‐atom Co species catalyst with outstanding ORR activity and durability. This work presents a new direction for a rational design of single‐atom catalyst on carbon matrix.
The prevalence of cardiovascular disease by vascular bed and impact on healthcare costs in a large, real‐world population with type 2 diabetes
Authors: Weng Wayne , Kong Sheldon X. , Ganguly Rahul , Hersloev Malene , Brett Jason , Hobbs Todd , Baeres Florian M.M.
Published: January 2020

Introduction

The purpose of this study was to assess prevalence of atherosclerotic cardiovascular disease (ASCVD) according to number of affected vascular beds and the impact on healthcare utilization and costs in persons with type 2 diabetes mellitus (type 2 DM) and established ASCVD.

Methods

In this retrospective, cross‐sectional analysis, adults with type 2 DM and ASCVD in a large US administrative claims database were categorized by number of ASCVD‐affected vascular beds (brain, heart, peripheral vasculature). Annual healthcare utilization and costs for 2015 were determined, including subgroup analyses by age group (18‐44, 45‐64, ≥65 years).

Results

Among 539 089 individuals with type 2 DM and ASCVD, 47.0% had ASCVD affecting >1 vascular bed. The most prevalent ASCVD diagnoses were acute coronary syndrome (26.6%), peripheral arterial disease (24.5%) and stroke (18.6%). Mean annual total healthcare costs per person increased with increasing number of vascular beds, from 1 ($17 741) to 2 ($25 877) to 3 ($33 412). A similar pattern of increased healthcare utilization with increasing number of vascular beds was observed. Among individuals with 1 affected vascular bed, mean total healthcare costs per person were comparable across age subgroups; however, if >1 vascular bed was affected, the mean total healthcare costs were highest in the youngest age cohort.

Conclusions

These real‐world data showed that almost half of individuals with type 2 DM and ASCVD had ASCVD affecting >1 vascular bed. A higher number of affected vascular beds were associated with higher mean total healthcare costs and utilization, with a disproportionate increase noted in younger relative to older people.
Extraction of protein and carbohydrates from soybean meal using acidic and alkaline solutions produced by electro‐activation
Authors: Gerliani Natela , Hammami Riadh , Aïder Mohammed
Published: January 2020

This main objective of this work was to study the extraction of proteins and soluble carbohydrates and minerals from soybean meal by using acidic (anolyte) and alkaline (catholyte) extracting solutions produced by electro‐activation technology. The extracting solutions (anolyte and catholyte) were produced by electro‐activation at current intensities of 150, 300, and 450 mA during 10, 30, and 50 min. Both extraction methods were effective in extracting soluble dry matter. The catholyte was the most efficient in extracting proteins with a maximal yield of 45.55 ± 2.77%. Moreover, protein content increased with treatment time in catholyte extracts but decreased in anolyte‐extracted samples. SDS‐PAGE confirmed catholyte effectiveness in extracting more proteins with better quality than the anolyte. Similar results were observed for amino acid profiles, with samples extracted by the catholyte being the richest in both essential and nonessential amino acids. While the anolyte extracted the highest amounts of Mg2+ (78%), Ca2+ (37%), and P3− (37%) from the soybean meal, catholyte was more efficient in extracting Zn2+ (65%), Fe2+ (62%), and Cu2+ (42%) ions. The obtained samples by both anolytes and catholytes exhibited good carbohydrate profiles containing some prebiotic monosaccharides. The carbohydrate profile varied with voltage used for the production of electro‐activated solutions and time. Stachyose and raffinose content increased with voltage used for anolytes production while decreasing in catholytes samples. Similarly, the highest stachyose and raffinose contents were observed for catholyte‐treated samples for 10 min, with respective ranges of 206.64–222.49 and 31.17–34.29 mg/g. To a lesser extent, anolyte‐treated samples for a longer time (30–50 min) were more efficient in extracting those sugars.
The Role of 1‐Methylcyclopropene in the regulation of ethylene biosynthesis and ethylene receptor gene expression in Mangifera indica L. (Mango Fruit)
Authors: Li Li , Shuai Liang , Sun Jian , Li Changbao , Yi Ping , Zhou Zhugui , He Xuemei , Ling Dongning , Sheng Jinfeng , Kong Kin‐Weng , Zheng Fengjin , Li Jiemin , Liu Guoming , Xin Ming , Li Zhichun , Tang Yayuan
Published: January 2020

Mango (Mangifera indica L.) is respiratory climacteric fruit that ripens and decomposes quickly following their harvest. 1‐methylcyclopropene (1‐MCP) is known to affect the ripening of fruit, delaying the decay of mango stored under ambient conditions. The objective of this study was to clarify the role of 1‐MCP in the regulation of ethylene biosynthesis and ethylene receptor gene expression in mango. 1‐MCP significantly inhibited the 1‐aminocyclopropane‐1‐carboxylic acid (ACC) content. The activity of ACC oxidase (ACO) increased on days 6, 8, and 10 of storage, whereas delayed ACC synthase (ACS) activity increased after day 4. The two homologous ethylene receptor genes, ETR1 and ERS1 (i.e., MiETR1 and MiERS1), were obtained and deposited in GenBank® (National Center for Biotechnology Information‐National Institutes of Health [NCBI‐NIH]) (KY002681 and KY002682). The MiETR1 coding sequence was 2,220 bp and encoded 739 amino acids (aa). The MiERS1 coding sequence was 1,890 bp and encoded 629 aa, similar to ERS1 in other fruit. The tertiary structures of MiETR1 and MiERS1 were also predicted. MiERS1 lacks a receiver domain and shares a low homology with MiETR1 (44%). The expression of MiETR1 and MiERS1 mRNA was upregulated as the storage duration extended and reached the peak expression on day 6. Treatment with 1‐MCP significantly reduced the expression of MiETR1 on days 4, 6, and 10 and inhibited the expression of MiETR1 on days 2, 4, 6, and 10. These results indicated that MiETR1 and MiERS1 had important functions in ethylene signal transduction. Treatment with 1‐MCP might effectively prevent the biosynthesis of ethylene, as well as ethylene‐induced ripening and senescence. This study presents an innovative method for prolonging the storage life of mango after their harvest through the regulation of MiETR1 and MiERS1 expression.
Clinical and sociodemographic factors associated with oral health‐related quality of life in survivors of head and neck cancer
Authors: Soldera Eloisa B. , Ortigara Gabriela B. , Bonzanini Laura I. L. , Schulz Riéli E. , Danesi Cristiane C. , Antoniazzi Raquel P. , Linhares Ferrazzo Kívia
Published: January 2020

Background

Factors related to head and neck cancer and the treatment of the disease can affect quality of life. The aim of this study was to determine factors associated with the severity of impact on oral health‐related quality of life (OHRQoL) in survivors of head and neck cancer using a multivariate analysis.

Methods

This cross‐sectional study evaluated 90 volunteers who had completed radiotherapy at least 3 months earlier. OHRQoL was assessed using oral health impact profile (OHIP‐14) and the data were analyzed using robust variance poisson regression models.

Results

The mean total OHIP‐14 score was 23.98 ± 12.55. Patients with hyposalivation had 56% higher (worse) mean OHIP‐14 total scores (CI:1.11‐2.18) and patients with advanced stage tumors had 31% higher mean OHIP‐14 total scores (CI:1.03‐1.66) in multivariate analyses.

Conclusion

OHRQoL of survivors of head and neck cancer experienced a negative impact following radiotherapy. The impact was associated with hyposalivation and advanced stage tumors.
A rare case of binocular persistent hyperplastic primary vitreous (PHPV) in a pregnant woman during two consecutive pregnancies
Authors: Zhu Haiying , Jiang Wenbin , Zheng Xin
Published: January 2020

This study presents a very rare case of a patient with three consecutive pregnancies, in which abortion was induced twice due to a finding of binocular persistent hyperplastic primary vitreous; a healthy female infant was subsequently born naturally.
Chronic exposure to arsenite enhances influenza virus infection in cultured cells
Authors: Amouzougan Eva A. , Lira Ricardo , Klimecki Walter T.
Published: January 2020

Arsenic is a ubiquitous environmental toxicant that has been associated with human respiratory diseases. In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well‐established impact of arsenic on epithelial cell biology, we posited that the effect of arsenic exposure in epithelial cells could enhance viral infection. In this study, we characterized influenza virus A/WSN/33 (H1N1) infection in Madin‐Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3‐fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35‐fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite‐exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment‐positive cells (2 hours p.i.) and 224% increase in α‐2,3 sialic acid‐positive cells. Interestingly, chronic exposure to arsenite reduced the effect of the antiviral drug, oseltamivir in MDCK cells. We also found that exposure to sodium arsenite resulted in a 4.4‐fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A/Udorn/72 (H3N2) infected BEAS‐2B cells. This study suggests that chronic arsenite exposure could result in enhanced influenza infection in epithelial cells, and that this may be mediated through increased sialic acid binding. Finally, the decreased effectiveness of the anti‐influenza drug, oseltamivir, in arsenite‐exposed cells raises substantial public health concerns if this effect translates to arsenic‐exposed, influenza‐infected people.
The function of SNHG7/miR‐449a/ACSL1 axis in thyroid cancer
Authors: Guo Linchi , Lu Jixuan , Gao Jie , Li Mingyang , Wang Huihui , Zhan Xiaorong
Published: January 2020

Thyroid cancer (TC) has been characterized as the most common malignant malady of the endocrine system. Small nucleolar RNA host gene 7 (SNHG7) has been reported to serve as a key regulator in a large number of human cancer types, but its role in TC and the underlying regulatory mechanism have never been evaluated yet. The present study indicated that the expression of SNHG7 was markedly higher in TC cell lines. Knockdown of SNHG7 led to a suppression of TC cell progression and migration. Acyl‐CoA synthetase long‐chain family member 1 (ACSL1) has also been demonstrated as an oncogene in many cancers. Herein an inhibition of ACSL1 after SNHG7 knockdown was captured. Further, the suppressing effects of SNHG7 knockdown on TC cell processes were counteracted by ACSL1 overexpression. Data from online bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays validated the interaction between microRNA‐449a (miR‐449a) and SNHG7 or ACSL1. It was also verified that SNHG7 sequestered miR‐449a and therefore elevated ACSL1 expression levels. To conclude, the current study indicated that SNHG7 promoted proliferation and migration of TC cells by sponging miR‐449a and therefore upregulating ACSL1. The present study may provide more explorations about the molecular regulation mechanism of long noncoding RNAs in TC progression.
LncRNA SNHG8 accelerates proliferation and inhibits apoptosis in HPV‐induced cervical cancer through recruiting EZH2 to epigenetically silence RECK expression
Authors: Qu Xiaohui , Li Yuanyuan , Wang Lin , Yuan Ningxia , Ma Meng , Chen Yao
Published: January 2020

Infection of human papillomaviruses (HPVs), such as subtypes HPV16 and HPV18 is carcinogenic to human and is prominent cause of HPV‐positive cervical carcinoma (CC). A closer investigation into the mechanism of HPV‐induced CC may stimulate the generation of an improved therapy treating cervical cancer. Our study herein interrogated the function of a small nucleolar RNA host gene 8 (SNHG8) in HPV‐induced CC. As a result, a notable increase of SNHG8 in HPV‐induced CC cells was found compared with HPV‐negative CC cells. Functionally, it identified that SNHG8 aggravated the cell proliferation and migration in Cell Counting Kit‐8 and transwell assays. Besides, flow cytometry apoptosis assay displayed that blockade of SNHG8 exacerbated apoptosis of HPV‐positive CC cells. As detected by fluorescence in situ hybridization analysis and subcellular fractionation assay, SNHG8 was primarily expressed in the nucleus and exerted suppressive role on reversion inducing cysteine‐rich protein with kazal motifs (RECK) expression, which implied a potential transcriptional regulation of SNHG8 on RECK level. Mechanically, SNHG8 was disclosed to interact with enhancer of zeste homolog 2 (EZH2) based on RNA immunoprecipitation assay. ChIP assay further unveiled the occupancy of EZH2 in the promoter region of RECK. An additional chromatin immunoprecipitation assay highlighted that SNHG8 intensified the enrichment of EZH2 and H3K27me3 in RECK promoter region. Altogether, it reflected that SNHG8 recruited EZH2 to downregulate RECK expression, leading to HPV‐induced CC aggravation.
A robust two‐gene signature for glioblastoma survival prediction
Authors: Pan Yuhualei , Zhang Jian‐Hua , Zhao Lianhe , Guo Jin‐Cheng , Wang Song , Zhao Yushang , Tao Shaoxin , Wang Huan , Zhu Yan‐Bing
Published: January 2020

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. We explored the prognostic gene signature in 443 GBM samples by systematic bioinformatics analysis, using GSE16011 with microarray expression and corresponding clinical data from Gene Expression Omnibus as the training set. Meanwhile, patients from The Chinese Glioma Genome Atlas database (CGGA) were used as the test set and The Cancer Genome Atlas database (TCGA) as the validation set. Through Cox regression analysis, Kaplan‐Meier analysis, t‐distributed Stochastic Neighbor Embedding algorithm, clustering, and receiver operating characteristic analysis, a two‐gene signature (GRIA2 and RYR3) associated with survival was selected in the GSE16011 dataset. The GRIA2‐RYR3 signature divided patients into two risk groups with significantly different survival in the GSE16011 dataset (median: 0.72, 95% confidence interval [CI]: 0.64‐0.98, vs median: 0.98, 95% CI: 0.65‐1.61 years, logrank test P < .001), the CGGA dataset (median: 0.84, 95% CI: 0.70‐1.18, vs median: 1.21, 95% CI: 0.95‐2.94 years, logrank test P = .0017), and the TCGA dataset (median: 1.03, 95% CI: 0.86‐1.24, vs median: 1.23, 95% CI: 1.04‐1.85 years, logrank test P = .0064), validating the predictive value of the signature. And the survival predictive potency of the signature was independent from clinicopathological prognostic features in multivariable Cox analysis. We found that after transfection of U87 cells with small interfering RNA, GRIA2 and RYR3 influenced the biological behaviors of proliferation, migration, and invasion of glioblastoma cells. In conclusion, the two‐gene signature was a robust prognostic model to predict GBM survival.
Identification of microenvironment‐related genes with prognostic value in clear cell renal cell carcinoma
Authors: Zhang Zhao , Li Zeyan , Liu Zhao , Zhang Xiang , Yu Nengwang , Xu Zhonghua
Published: January 2020

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor. Previous studies have shown that the interaction between tumor cells and microenvironment has an important impact on prognosis. Immune and stromal cells are two vital components of the tumor microenvironment. Our study aimed to better understand and explore the genes involved in immune/stromal cells on prognosis. We used the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm to calculate immune/stromal scores. According to the scores, we divided ccRCC patients from The Cancer Genome Atlas database into low and high groups and identified the genes which were differentially expressed and significantly associated with prognosis. The result of functional enrichment analysis and protein‐protein interaction networks indicated that these genes mainly were involved in extracellular matrix and regulation of cellular activities. Then another independent cohort from the International Cancer Genome Consortium database was used to validate these genes. Finally, we acquired a list of microenvironment‐related genes that can predict prognosis for ccRCC patients.
All‐trans‐retinoid acid induces the differentiation of P19 cells into neurons involved in the PI3K/Akt/GSK3β signaling pathway
Authors: Fu Fang , Li Lu‐Shan , Li Ru , Deng Qiong , Yu Qiu‐Xia , Yang Xin , Pan Min , Han Jin , Zhen Li , Zhang Li‐Na , Lei Ting‐Ying , Li Dong‐Zhi , Liao Can
Published: January 2020

The pluripotent mouse embryonal carcinoma cell line P19 is widely used as a model for research on all‐trans‐retinoid acid (RA)‐induced neuronal differentiation; however, the signaling pathways involved in this process remain unclear. This study aimed to reveal the molecular mechanism underlying the RA‐induced neuronal differentiation of P19 cells. Real‐time quantitative polymerase chain reaction and Western blot analysis were used to determine the expression of neuronal‐specific markers, whereas flow cytometry was used to analyze cell cycle and cell apoptosis. The expression profiles of messenger RNAs (mRNAs) in RA‐induced neuronal differentiation of P19 cells were analyzed using high‐throughput sequencing, and the functions of differentially expressed mRNAs (DEMs) were determined by bioinformatics analysis. RA induced an increase in both class III β‐tubulin (TUBB3) and neurofilament medium (NEFM) mRNA expression, indicating that RA successfully induces neuronal differentiation of P19 cells. Cell apoptosis was not affected; however, cell proliferation decreased. We found 4117 DEMs, which were enriched in the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway, Wnt signaling pathway, and cell cycle. Particularly, a few DEMs could be identified in the PI3K/Akt signaling pathway networks, such as PI3K, Akt, glycogen synthase kinase‐3β (GSK3β), cyclin‐dependent kinase 4 (CDK4), P21, and Bax. RA significantly increased the protein expression of PI3K, Akt, phosphorylated Akt, GSK3β, phosphorylated GSK3β, CDK4, and P21, but it reduced Bax protein expression. The Akt inhibitor affected the increase of TUBB3 and NEFM mRNA expression in RA‐induced P19 cells. The molecular mechanism underlying the RA‐induced neuronal differentiation of P19 cells is potentially involved in the PI3K/Akt/GSK3β signaling pathway. The decreased cell proliferation ability of neuronally differentiated P19 cells could be associated with the expression of cell cycle proteins.
Autophagy decreases alveolar epithelial cell injury by regulating the release of inflammatory mediators
Authors: Fan Tao , Yang Shuo , Huang Zhixin , Wang Wei , Guo Xiaobo , Pan Shize , Zhang Boyou , Xu Yao , Fang Yifan , Mao Zhangfan , Hu Hao , Geng Qing
Published: January 2020

To research the impact of autophagy on alveolar epithelial cell inflammation and its possible mechanism in the early stages of hypoxia, we established a cell hypoxia–reoxygenation model and orthotopic left lung ischemia–reperfusion model. Rat alveolar epithelial cells stably expressing GFP‐LC3 were treated with an autophagy inhibitor (3‐MA) or an autophagy promoter (rapamycin), followed by hypoxia–reoxygenation treatment for 2, 4, and 6 hr in vitro. In vivo, 20 male Sprague Dawley rats were randomly divided into four groups (model group: No blocking of the hilum in the left lung; control group: Blocking of the hilum in the left lung for 1 hr with dimethyl sulfoxide lavage; 3‐MA group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of 3‐MA (5 μmol/L) solution lavage; and rapamycin group: Blocking of the hilum in the left lung for 1 hr with 100 ml/kg of rapamycin (250 nmol/L) solution lavage) to establish an orthotopic left lung ischemia model. This study demonstrated that rapamycin significantly suppressed the nuclear factor kappa B signaling pathway and limited the expression of proinflammatory factors. A contrary result was found after the 3‐MA pretreatment. These findings indicate that autophagy reduces ischemia–reperfusion injury by repressing inflammatory signaling pathways in the early stages of hypoxia in vitro and in vivo. Autophagy could be a new protective method for application in lung ischemia–reperfusion injury.
miR‐873‐3p targets HDAC4 to stimulate matrix metalloproteinase‐13 expression upon parathyroid hormone exposure in rat osteoblasts
Authors: Malavika Desai , Shreya Srinivasan , Raj Priya Vembar , Rohini Muthukumar , He Zhiming , Partridge Nicola C. , Selvamurugan Nagarajan
Published: January 2020

Matrix metalloproteinase‐13 (MMP‐13) plays a predominant role in endochondral bone formation and bone remodeling. Parathyroid hormone (PTH) stimulates the expression of MMP‐13 via Runx2, a bone transcription factor in rat osteoblastic cells (UMR106‐01), and histone deacetylase 4 (HDAC4) acts as a corepressor of Runx2. Moreover, microRNAs (miRNAs) play an important role in regulating genes posttranscriptionally. Here, we hypothesized that PTH upregulates the miRNAs targeting HDAC4, which could lead to increased Runx2 activity and MMP‐13 expression in rat osteoblastic cells. We identified several miRNAs that putatively target rat HDAC4 using bioinformatics tools. miR‐873‐3p was significantly upregulated by PTH in rat osteoblasts. miR‐873‐3p overexpression downregulated HDAC4 protein expression, increased Runx2 binding at the MMP‐13 promoter, and increased MMP‐13 messenger RNA expression in UMR106‐01 cells. A luciferase reporter assay identified the direct targeting of miR‐873‐3p at the 3′‐untranslated region of HDAC4. Thus, miR‐873‐3p targeted HDAC4 and relieved the corepressor effect of HDAC4 on Runx2 for MMP‐13 expression in rat osteoblasts. This study advances our knowledge of posttranscriptional gene regulation occurring in bone and bone‐related diseases and clarifies the role of miRNAs as diagnostic biomarkers.