bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Extracellular Vesicles in the Development, Diagnosis, and Possible Therapeutic Application of Esophageal Squamous Cell Carcinoma
Authors: Zhao Zheng , Yang Shuyue , Zhou Anni , Li Xiao , Fang Rui , Zhang Shutian , Zhao Guiping , Li Peng
Published: September 2021

Esophageal squamous cell carcinoma (ESCC) persists among the most lethal and broad-spreading malignancies in China. The exosome is a kind of extracellular vesicle (EV) from about 30 to 200 nm in diameter, contributing to the transfer of specific functional molecules, such as metabolites, proteins, lipids, and nucleic acids. The paramount role of exosomes in the formation and development of ESCC, which relies on promoting intercellular communication in the tumor microenvironment (TME), is manifested with immense amounts. Tumor-derived exosomes (TDEs) participate in most hallmarks of ESCC, including tumorigenesis, invasion, angiogenesis, immunologic escape, metastasis, radioresistance, and chemoresistance. Published reports have delineated that exosome-encapsulated cargos like miRNAs may have utility in the diagnosis, as prognostic biomarkers, and in the treatment of ESCC. This review summarizes the function of exosomes in the neoplasia, progression, and metastasis of ESCC, which improves our understanding of the etiology and pathogenesis of ESCC, and presents a promising target for early diagnostics in ESCC. However, recent studies of exosomes in the treatment of ESCC are sparse. Thus, we introduce the advances in exosome-based methods and indicate the possible applications for ESCC therapy in the future.
A Multidisciplinary Approach in Prenatal Diagnosis of TSC With Cardiac Rhabdomyoma as the Initial Symptom
Authors: Qi Yiming , Ding Hongke , Huang Yanlin , Zeng Yukun , Yu Lihua , Liu Ling , Zhang Yan , Yin Aihua
Published: September 2021

The long-term prognosis of a fetus with cardiac rhabdomyoma (CR) depends on the correlation with tuberous sclerosis complex (TSC). In recent years, the numerous variations of uncertain significance (VUS) of TSC genes produced by high-throughput sequencing have made counseling challenging, studies until now have tended to side-step the tricky topics. Here, we integrated detailed parental phenotype, echocardiography, neuro MRI, and genetic information to conduct a comprehensive evaluation of 61 CR fetuses. As a result, multiple CRs and cerebral lesions appeared in 90 and 80%, respectively of fetuses with pathogenic (P)/likely pathogenic (LP) TSC1/TSC2 variations. Overall, 85.7% of the live-born infants with P/LP presented with TSC-associated signs. While, 85.7% of VUS without nervous findings had good prognoses. Genetic evidence and cerebral MRI findings are the most sensitive index to assess long-term prognosis, which complement and confirm each other for a TSC diagnosis. In total, 68.9% of fetuses with CR could benefit from this multidisciplinary approach, which turned out to be potentially clinically actionable with precise clinical/genetic diagnosis or had a foreseeable outcome. Our practice provides a practical and feasible solution for perinatal management and prognostic guidance for fetuses with CR.
Factors Associated With Weight, Length, and BMI Change in Adolescents' Offspring in Their First Year of Life
Authors: Sámano Reyna , Chico-Barba Gabriela , Martínez-Rojano Hugo , Hernández-Trejo María , Birch Mery , López-Vázquez Maribel , García-López Gabriela Eurídice , Díaz de León Jesús , Mendoza-González Cynthia Vanessa
Published: September 2021

Background: Young maternal age is associated with negative outcomes at birth and with offspring's growth. In low- and middle-income countries, adolescents' offspring growth little has been studied.

Objective: To determine the association of maternal sociodemographic characteristics with weight, length, and BMI change in adolescents' offspring in their first year of life.

Methods: This is a one-year follow-up study that included adolescent mothers and their offspring from 2010 to 2017. The infant anthropometric variables were performed at birth, 3, 6, and 12 months. Maternal health, pregnancy, and social variables were evaluated as well as birth outcomes. Crude, percentage, Z score, and percentile changes of weight, length, and BMI were evaluated from birth to 1-year-old. Statistical analyses were adjusted by maternal chronological age, socioeconomic status, breastfeeding duration, the timing of introduction of complementary feeding, among other variables.

Results: We examined 186 dyads (mother-infant). The median maternal age was 15.5 years, and the mean pre-pregnancy BMI was 20. The mean gestational age was 39.1 weeks for infants, birth weight was 3,039 g, and length at birth was 49.5-cm. Maternal chronological age, the timing of introduction of complementary feeding, socioeconomic status, and maternal occupation were associated with offspring's weight gain at 12 months. Length gain was associated with exclusive breastfeeding. Socioeconomic status and occupation were associated with offspring's BMI change. When performing adjusted multivariable analyses, weight and length at birth were associated weight and BMI at 12 months.

Conclusions: Weight at birth may negatively predict infant's weight and BMI changes at 12 months, while length at birth may positively predict the changes. Maternal chronological age, socioeconomic level, occupation, and the timing of the introduction of complementary feeding were associated with the weight change. Only exclusive breastfeeding was associated with length Z-score change in adolescents' offspring in their first 12-months of life.
Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study
Authors: Huang Yen-Chu , Wu Meng-Che , Wang Yu-Hsun , Wei James Cheng-Chung
Published: September 2021

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.

Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.

Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).

Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.
Identification of Novel Gene Signatures using Next-Generation Sequencing Data from COVID-19 Infection Models: Focus on Neuro-COVID and Potential Therapeutics
Authors: Pushparaj Peter Natesan , Abdulkareem Angham Abdulrahman , Naseer Muhammad Imran
Published: September 2021

SARS-CoV-2 is the causative agent for coronavirus disease-19 (COVID-19) and belongs to the family Coronaviridae that causes sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients. The gene expression profiles of COVID-19 infection models can be used to decipher potential therapeutics for COVID-19 and related pathologies, such as Neuro-COVID. Here, we used the raw RNA-seq reads (Single-End) in quadruplicates derived using Illumina Next Seq 500 from SARS-CoV-infected primary human bronchial epithelium (NHBE) and mock-treated NHBE cells obtained from the Gene Expression Omnibus (GEO) (GSE147507), and the quality control (QC) was evaluated using the CLC Genomics Workbench 20.0 (Qiagen, United States) before the RNA-seq analysis using BioJupies web tool and iPathwayGuide for gene ontologies (GO), pathways, upstream regulator genes, small molecules, and natural products. Additionally, single-cell transcriptomics data (GSE163005) of meta clusters of immune cells from the cerebrospinal fluid (CSF), such as T-cells/natural killer cells (NK) (TcMeta), dendritic cells (DCMeta), and monocytes/granulocyte (monoMeta) cell types for comparison, namely, Neuro-COVID versus idiopathic intracranial hypertension (IIH), were analyzed using iPathwayGuide. L1000 fireworks display (L1000FWD) and L1000 characteristic direction signature search engine (L1000 CDS2) web tools were used to uncover the small molecules that could potentially reverse the COVID-19 and Neuro-COVID-associated gene signatures. We uncovered small molecules such as camptothecin, importazole, and withaferin A, which can potentially reverse COVID-19 associated gene signatures. In addition, withaferin A, trichostatin A, narciclasine, camptothecin, and JQ1 have the potential to reverse Neuro-COVID gene signatures. Furthermore, the gene set enrichment analysis (GSEA) preranked method and Metascape web tool were used to decipher and annotate the gene signatures that were potentially reversed by these small molecules. In conclusion, our study unravels a rapid approach for applying next-generation knowledge discovery (NGKD) platforms to discover small molecules with therapeutic potential against COVID-19 and its related disease pathologies.
Pro-Oncogenic c-Met/EGFR, Biomarker Signatures of the Tumor Microenvironment are Clinical and Therapy Response Prognosticators in Colorectal Cancer, and Therapeutic Targets of 3-Phenyl-2H-benzo[e][1,3]-Oxazine-2,4(3H)-Dione Derivatives
Authors: Lawal Bashir , Wang Yu-Chi , Wu Alexander T. H. , Huang Hsu-Shan
Published: September 2021

Genetic and environmental factors play important roles in cancer progression, metastasis, and drug resistance. Herein, we used a multiomics data analysis to evaluate the predictive and prognostic roles of genetic and epigenetic modulation of c-MET (hepatocyte growth factor receptor)/epidermal growth factor receptor (EGFR) in colorectal cancer (CRC). First, we found that overexpressions of c-MET/EGFR were associated with the infiltration of tumor immune cells and cancer-associated fibroblasts, and were of prognostic relevance in CRC cohorts. We also observed that genetic alterations of c-MET/EGFR in CRC co-occurred with other gene alterations and were associated with overexpression of messenger (m)RNA of some cancer hallmark proteins. More specifically, DNA-methylation and somatic copy number alterations of c-MET/EGFR were associated with immune infiltration, dysfunctional T-cell phenotypes, and poor prognoses of the cohorts. Moreover, we describe two novel gefitinib-inspired small molecules derivatives of 3-phenyl-2H-benzo[e] [1,3]-oxazine-2,4(3H)-dione, NSC777205 and NSC777207, which exhibited wide-spectrum antiproliferative activities and selective cytotoxic preference for drug-sensitive and multidrug-resistant melanoma, renal, central nervous system, colon, and non-small cell lung cancer cell lines. We further provided in silico mechanistic evidence implicating c-MET/EGFR/phosphatidylinositol 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibition in anticancer activities of those compounds. Our overall structure-activity relationship study revealed that the addition of an –OCH3 group to salicylic core of NSC777207 was not favorable, as the added moiety led to overall less-favorable drug properties as well as weaker anticancer activities compared to the properties and activities demonstrated by NSC777205 that has no –OCH3 substituent group. Further in vitro and in vivo analyses in tumor-bearing mice are ongoing in our lab to support this claim and to unravel the full therapeutic efficacies of NSC777205 and NSC777207 in CRC.
Traditional Chinese Medicine Intervenes Ventricular Remodeling Following Acute Myocardial Infarction: Evidence From 40 Random Controlled Trials With 3,659 Subjects
Authors: Zhang Xiao-Xiao , Liang Bo , Shao Chang-Le , Gu Ning
Published: September 2021

Objectives: We intend to conduct a meta-analysis on the systematic evaluation of traditional Chinese medicine (TCM) in the treatment of ventricular remodeling following acute myocardial infarction (AMI). Our findings may provide certain references for the clinical treatment of ventricular remodeling.

Methods: A systematic literature search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang Data, CQVIP, and CBM before 20 July 2020. Data were analyzed using a random/fixed-effect model. Primary outcomes included the effectiveness and TCM syndrome score (TCMSS). Secondary outcomes included 1) echocardiography data, including the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular ejection fraction (LVEF), E/A, stroke volume (SV), and wall motion score (WMS); 2) serum indicators, including the B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) or high sensitivity CRP (hs-CRP); (3) major adverse cardiovascular events (MACE) and other adverse events

Results: Forty RCTs involving 3,659 subjects were recruited. Our findings proved that a combination of TCM or TCM preparations with conventional Western medicine for preventing and reversing ventricular remodeling at post-AMI could remarkably enhance the total effectiveness and reduced TCMSS. Moreover, myocardial functions (LVEF, E/A, and SV), ventricular remodeling (LVEDVi, LVESVi, LVEDV, LVESV, LVEDD, LVESD, LVPWT, and WMS), serum levels of BNP and CRP, and MACE were significantly improved by the combination of TCM or TCM preparations with conventional Western medicine. Nevertheless, IVST and the incidence of other adverse events were comparable between control and experimental groups

Conclusion: The combination of TCM or TCM preparations and conventional Western medicine can alleviate the process of ventricular remodeling, enhance cardiac function, and reduce the incidence of MACE in AMI patients.
The Downregulation of eIF3a Contributes to Vemurafenib Resistance in Melanoma by Activating ERK via PPP2R1B
Authors: Jiang Shi-Long , Wang Zhi-Bin , Zhu Tao , Jiang Ting , Fei Jiang-Feng , Liu Chong , Luo Chao , Cheng Yan , Liu Zhao-Qian
Published: September 2021

Vemurafenib, a BRAF V600E inhibitor, provides therapeutic benefits for patients with melanoma, but the frequent emergence of drug resistance remains a challenge. An understanding of the mechanisms underlying vemurafenib resistance may generate novel therapeutic strategies for patients with melanoma. Here, we showed that eIF3a, a translational regulatory protein, was an important mediator involved in vemurafenib resistance. eIF3a was expressed at significantly lower levels in vemurafenib-resistant A375 melanoma cells (A375R) than in parental A375 cells. Overexpression of eIF3a enhanced the sensitivity to BRAF inhibitors by reducing p-ERK levels. Furthermore, eIF3a controlled ERK activity by regulating the expression of the phosphatase PPP2R1B via a translation mechanism, thus determining the sensitivity of melanoma cells to vemurafenib. In addition, a positive correlation between eIF3a and PPP2R1B expression was also observed in tumor samples from the Human Protein Atlas and TCGA databases. In conclusion, our studies reveal a previously unknown molecular mechanism of BRAF inhibitor resistance, which may provide a new strategy for predicting vemurafenib responses in clinical treatment.
The Prognostic Effect of Dexamethasone on Patients With Glioblastoma: A Systematic Review and Meta-Analysis
Authors: Zhou Lingling , Shen Yang , Huang Tingting , Sun Yangyang , Alolga Raphael N. , Zhang Gang , Ge Yuqiu
Published: September 2021

Background: Dexamethasone (DEX) is widely adopted to reduce tumor-associated edema in glioblastoma (GBM) patients despite its side effects. However, the benefits of using DEX in GBM patients remains elusive.

Methods: In this study, we performed a comprehensive meta-analysis to address this concern. We searched the relevant studies from PubMed, Web of Science, and EMBASE databases, and then applied random or fixed-effects models to generate estimated summary hazard radios (HRs) and the 95% confidence intervals (CIs). Moreover, subgroup and sensitivity analysis were conducted and publication bias were further evaluated.

Results: Ten articles with a total of 2,230 GBM patients were eligible according to the inclusion criteria. In the assessment of overall survival (OS), meta-analysis data revealed that DEX was significantly associated with the poor prognosis of GBM patients (HR=1.44, 95% CI=1.32−1.57). In the progression-free survival (PFS), the pooled results indicated that the use of DEX can increase 48% death risk for GBM patients (HR=1.48, 95% CI=1.11−1.98). Subgroup analyses revealed that DEX was associated with poorer outcome of GBM in subgroup of newly diagnosed patients and GBM patients treated with ≥ 2mg/day. Sensitivity analyses showed that no study changed the pooled results materially for both OS and PFS analyses. The funnel plot had no obvious asymmetry.

Conclusion: Our findings partly confirmed that use of DEX was associated with poor treatment outcome in GBM patients. To reach a definitive conclusion, large samples from multi-centers are urgent to address this concern.
Sulfonylureas for Treatment of Periodontitis-Diabetes Comorbidity-Related Complications: Killing Two Birds With One Stone
Authors: Yang Luxi , Ge Qing , Ye Zhitong , Wang Lijing , Wang Liping , Mashrah Mubarak Ahmed , Pathak Janak L.
Published: September 2021

Periodontitis is one of the most prevalent oral inflammatory diseases leading to teeth loss and oral health problems in adults. Periodontitis mainly affects periodontal tissue by affecting the host immune system and bone homeostasis. Moreover, periodontitis is associated with various systemic diseases. Diabetes is a metabolic disease with systemic effects. Both periodontitis and diabetes are common inflammatory diseases, and comorbidity of two diseases is linked to exacerbation of the pathophysiology of both diseases. Since bacterial dysbiosis is mainly responsible for periodontitis, antibiotics are widely used drugs to treat periodontitis in clinics. However, the outcomes of antibiotic treatments in periodontitis are not satisfactory. Therefore, the application of anti-inflammatory drugs in combination with antibiotics could be a treatment option for periodontitis-diabetes comorbidity. Anti-diabetic drugs usually have anti-inflammatory properties and have shown beneficial effects on periodontitis. Sulfonylureas, insulin secretagogues, are the earliest and most widely used oral hypoglycemic drugs used for type-2 diabetes. Studies have found that sulfonylurea drugs can play a certain role in the mitigation of periodontitis and inflammation. This article reviews the effects of sulfonylurea drugs on the mitigation of periodontitis-diabetes comorbidity-related inflammation, bone loss, and vascular growth as well as the involved molecular mechanisms. We discuss the possibility of a new application of sulfonylureas (old drug) to treat periodontitis-diabetes comorbidity.
Mechanism of Paeoniflorin on ANIT-Induced Cholestatic Liver Injury Using Integrated Metabolomics and Network Pharmacology
Authors: Chen Lisheng , Zhao Xu , Wei Shizhang , Ma Xiao , Liu Honghong , Li Jianyu , Jing Manyi , Wang Min , Zhao Yanling
Published: September 2021

Background: Paeoniflorin (PF), the major active compound isolated from the roots of Paeonia lactiflora Pall., has been used in the treatment of severe hepatic diseases for several decades and displays bright prospects in liver protective effect. However, its biological mechanism that regulates bile acid metabolism and cholestatic liver injury has not been fully elucidated. Our study aims to investigate the mechanism by which PF in the treatment of cholestatic liver injury using a comprehensive approach combining metabolomics and network pharmacological analysis.

Methods: The hepatoprotective effect of PF against cholestasis liver injury, induced by α-naphthylisothiocyanate (ANIT), was evaluated in rats. The serum biochemical indices including ALT, AST, TBA, TBIL, ALP, ALB, and the pathological characteristics of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to explore the feces of rats with ANIT-induced cholestatic liver injury treated with PF and the potential biomarkers were screened by metabolomics. The targets for the regulation of potential biomarkers by PF were screened by network pharmacology, and then the relevant key targets were verified by immunohistochemical and western blotting methods.

Results: PF significantly improved serum indexes and alleviated liver histological damage. Metabolomics analyses showed that the therapeutic effect of PF is mainly associated with the regulation of 13 metabolites involved in 16 metabolic pathways. The “PF-targets-metabolites” interaction network was constructed, and then five key targets including CDC25B, CYP2C9, MAOB, mTOR, and ABCB1 that regulated the potential biomarkers were obtained. The above five targets were further verified by immunohistochemistry and western blotting, and the results showed that PF significantly improved the expression of key proteins regulating these biomarkers.

Conclusion: Our study provides direct evidence for the modulatory properties of PF treatment on ANIT-induced cholestatic liver injury using metabolomics and network pharmacology analyses. PF exhibits favorable pharmacological effect by regulating related signal pathways and key targets for biomarkers. Therefore, these findings may help better understand the complex mechanisms and provide a new and effective approach to the treatment of cholestatic liver injury.
Pattern Dynamics of Vegetation Growth With Saturated Water Absorption
Authors: Li Li , Cao Jia-Hui , Bao Xin-Yue
Published: September 2021

Regular pattern is a typical feature of vegetation distribution and thus it is important to study the law of vegetation evolution in the fields of desertification and environment conservation. The saturated water absorption effect between the soil water and vegetation plays an crucial role in the vegetation patterns in semi-arid regions, yet its influence on vegetation dynamics is largely ignored. In this paper, we pose a vegetation-water model with saturated water absorption effect of vegetation. Our results show that the parameter 1/P, which is conversion coefficient of water absorption, has a great impact on pattern formation of vegetation: with the increase of P, the density of vegetation decrease, and meanwhile it can induce the transition of different patterns structures. In addition, we find that the increase of appropriate precipitation can postpone the time on the phase transition of the vegetation pattern. The obtained results systematically reveal the effect of saturated water absorption on vegetation systems which well enrich the findings in vegetation dynamics and thus may provide some new insights for vegetation protection.
Wave Transport and Localization in Prime Number Landscapes
Authors: Dal Negro Luca , Henderson David Taylor , Sgrignuoli Fabrizio
Published: September 2021

In this paper, we study the wave transport and localization properties of novel aperiodic structures that manifest the intrinsic complexity of prime number distributions in imaginary quadratic fields. In particular, we address structure-property relationships and wave scattering through the prime elements of the nine imaginary quadratic fields (i.e., of their associated rings of integers) with class number one, which are unique factorization domains (UFDs). Our theoretical analysis combines the rigorous Green’s matrix solution of the multiple scattering problem with the interdisciplinary methods of spatial statistics and graph theory analysis of point patterns to unveil the relevant structural properties that produce wave localization effects. The onset of a Delocalization-Localization Transition (DLT) is demonstrated by a comprehensive study of the spectral properties of the Green’s matrix and the Thouless number as a function of their optical density. Furthermore, we employ Multifractal Detrended Fluctuation Analysis (MDFA) to establish the multifractal scaling of the local density of states in these complex structures and we discover a direct connection between localization, multifractality, and graph connectivity properties. Finally, we use a semi-classical approach to demonstrate and characterize the strong coupling regime of quantum emitters embedded in these novel aperiodic environments. Our study provides access to engineering design rules for the fabrication of novel and more efficient classical and quantum sources as well as photonic devices with enhanced light-matter interaction based on the intrinsic structural complexity of prime numbers in algebraic fields.
Multi-Spectral Clinical Prototype for Fluorophore Detection
Authors: Grygoryev Konstantin , Lu Huihui , Li Celina L. , Zhdanov Alexander V. , Burke Ray , Andersson-Engels Stefan
Published: September 2021

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Current methods of tumour identification use 5-ALA, an exogenous precursor, metabolized to fluorescent PpIX in tumour tissue. Although visible under fluorescent microscope, PpIX is easily photo-bleached and tumour tagging is subjective, resulting in tumour under-resection and accelerated recurrence. To address this issue, photo-bleaching resistant and quantitative method is required. This study describes the characterization of a pulsed, multi-wavelengths system designed to measure diffuse reflectance and auto-fluorescence under strong ambient illumination conditions. The performance was tested on n = 400 liquid tissue phantoms containing a wide concentration range of absorber, scatterer and two fluorophores as well as on ex-vivo samples of gray and white matter. The background subtraction technique was shown to be efficient for a range of ambient illumination intensities. A linear relationship was observed between system response and predicted fluorophore concentrations as well as 97.8% accuracy of tissue classification by 5-fold cross-correlation, linear SVM.
Effect of Valve Height on the Opening and Closing Performance of the Aortic Valve Under Aortic Root Dilatation
Authors: Hou Qianwen , Liu Guimei , Liu Ning , Zhang Honghui , Qu Zhuoran , Zhang Hanbing , Li Hui , Pan Youlian , Qiao Aike
Published: September 2021

Patients with aortic valve disease can suffer from valve insufficiency after valve repair surgery due to aortic root dilatation. The paper investigates the effect of valve height (Hv) on the aortic valve opening and closing in order to select the appropriate range of Hv for smoother blood flow through the aortic valve and valve closure completely in the case of continuous aortic root dilatation. A total of 20 parameterized three-dimensional models of the aortic root were constructed following clinical surgical guidance. Aortic annulus diameter (DAA) was separately set to 26, 27, 28, 29, and 30 mm to simulate aortic root dilatation. HV value was separately set to 13.5, 14, 14.5, and 15 mm to simulate aortic valve alterations in surgery. Time-varying pressure loads were applied to the valve, vessel wall of the ascending aorta, and left ventricle. Then, finite element analysis software was employed to simulate the movement and mechanics of the aortic root. The feasible design range of the valve size was evaluated using maximum stress, geometric orifice area (GOA), and leaflet contact force. The results show that the valve was incompletely closed when HV was 13.5 mm and DAA was 29 or 30 mm. The GOA of the valve was small when HV was 15 mm and DAA was 26 or 27 mm. The corresponding values of the other models were within the normal range. Compared with the model with an HV of 14 mm, the model with an HV of 14.5 mm could effectively reduce maximum stress and had relatively larger GOA and less change in contact force. As a result, valve height affects the performance of aortic valve opening and closing. Smaller HV is adapted to smaller DAA and vice versa. When HV is 14.5 mm, the valve is well adapted to the dilatation of the aortic root to enhance repair durability. Therefore, more attention should be paid to HV in surgical planning.
Urinary Steroid Profile in Elite Female Athletes in Relation to Serum Androgens and in Comparison With Untrained Controls
Authors: Eklund Emma , Andersson Alexander , Ekström Lena , Hirschberg Angelica Lindén
Published: September 2021

Introduction

In female athletes, the interpretation of doping tests is complex due to hormonal variations during the menstrual cycle and hormonal contraceptive use, both influencing the urinary steroid profile. Exercise is suggested to affect circulating steroid hormone levels, and in women, the urinary steroid profile differs between in competition testing and out of competition testing. No previous study has investigated the relationship between amount of exercise and the urinary steroid profile in female elite athletes.

Purpose

To compare the urinary steroid profile between female Olympic athletes and age- and BMI-matched untrained controls, and to study the urinary steroid profile in relation to serum hormones and amount of exercise.

Methods

In this cross-sectional study conducted at the Women’s Health Research Unit, Karolinska University Hospital, Stockholm, 94 female elite athletes and 86 untrained controls were included. Serum estrogens and testosterone and the urinary steroid profile were analyzed by liquid chromatography–tandem mass spectrometry and gas chromatography-tandem mass spectrometry, respectively. Exercise hours/week were evaluated by questionnaire.

Results

Although serum steroid hormones were comparable between groups, the athletes demonstrated approximately 30% lower urinary steroid metabolites of testosterone, epitestosterone, androsterone, etiocholanolone, 5α-androstan-3α, 17β-diol, and 5β-androstan-3α, 17β-diol compared to the controls. The urinary steroid metabolites correlated positively with serum steroid hormones. In the athletes, urinary steroid metabolites: androsterone (rs = −0.28, p = 0.007), epitestosterone (rs = −0.22, p = 0.034), 5αAdiol (rs = −0.31, p = 0.002) and testosterone (rs = −0.24, p = 0.026), were negatively correlated with amount of training (hours per week).

Conclusion

The urinary concentrations of steroid metabolites were lower in elite athletes than in sedentary controls, although serum steroids were comparable between groups. Moreover, exercise time was negatively associated with the urinary concentrations. Our findings suggest alternative excretion routes of androgens in the athletes related to training.
Dietary Polyphenol and Methylsulfonylmethane Supplementation Improves Immune, DAMP Signaling, and Inflammatory Responses During Recovery From All-Out Running Efforts
Authors: McFarlin Brian K. , Hill David W. , Vingren Jakob L. , Curtis John H. , Tanner Elizabeth A.
Published: September 2021

Nutritional ingredients with defined mechanisms of action can be useful in the recovery of the body from the physical demands of a habitual training plan. The purpose of this study was to determine the effect of dietary supplementation with optimized curcumin, pomegranate ellagitannins, and MSM (R + MSM) on immune-associated mRNA during early recovery (i.e., up to 8 h post-exercise) following all-out running efforts (5-km, 10-km, and 21.1-km). Subjects (N = 14) were randomized to either a supplement (R + MSM) or a control group using an open label design. The study was completed over a period of 31-day prior to a scheduled half-marathon race. Venous blood samples were collected into PAXgene tubes at baseline, subsequent samples were collected at 2, 4, and 8 h after each running effort. A 574-plex mRNA Immunology Array (NanoString) was measured for each sample and ROSALIND® Advanced Analysis Software was used to examined changes in 31 annotated immune response pathways and specific mRNA changes. The greatest change in immune pathways occurred at 2 h (GSS > 3) followed by 4 h (GSS 2–3) and 8 h (GSS 1–2). R + MSM was associated with an increase in innate immunity (CAMP, LTF, TIRAP, CR1, IL1R1, CXCR1, PDCDILG2, and GNLY) and a blunted/smaller increase in damage-associated molecular pattern (DAMP) signaling/inflammation (TLR4, TLR5, S100A8, S100A9, and IFP35). We also found changes in immune-associated mRNA that have not been previously linked to exercise recovery (SOCS1, SOCS2, MME, CECAM6, MX1, IL-1R2, KLRD1, KLRK1, and LAMP3). Collectively these results demonstrate that supplementation with a combination of optimized curcumin, pomegranate ellagitannins, and methylsulfonylmethane resulted in changes that may improve biological recovery from all-out running efforts.
The Use of Tissue Engineering to Fabricate Perfusable 3D Brain Microvessels in vitro
Authors: Galpayage Dona Kalpani N. Udeni , Hale Jonathan Franklin , Salako Tobi , Anandanatarajan Akanksha , Tran Kiet A. , DeOre Brandon J. , Galie Peter Adam , Ramirez Servio Heybert , Andrews Allison Michelle
Published: September 2021

Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models.
The Performance of a Spherical-tip Catheter for Stent Post-dilation: Finite Element Analysis and Experiments
Authors: Qi Lin , Zhu Wenbo , Qian Wei , Xu Lisheng , He Ying , Zhao Feihu
Published: September 2021

At present, percutaneous coronary intervention (PCI) is the most effective treatment of coronary artery stenosis. However, in case post-dilation of the stent is needed, the tip of the commonly used post-dilation balloon catheter cannot always pass through the stent smoothly, especially when it is situated in the curved part of the vessel. To improve the performance of traditional post-dilation balloon catheter, a preliminary design of a novel catheter with a spherical-tip is proposed. Since the performance of this spherical-tip catheter is still unclear, in this study, finite element analysis (FEA) and experimental validation of blood vessel with different curvature radii were performed to test and evaluate the performance of the spherical-tip catheter design. The comparative results between the two types of catheters demonstrate that in the simulated post-dilation process, the spherical-tip catheter is easier to pass through the stent placed in the curved vessel without the deformation of the stent strut, and can theoretically reduce the operation time and improve the safety of the operation. Furthermore, the strong consistency between simulation and experiment indicates that the finite element (FE) model can be a helpful tool for future optimization and evaluation of novel catheters, so as to save time and budget in product development and reduce/replace animal studies.
Claudin-5 Affects Endothelial Autophagy in Response to Early Hypoxia
Authors: Yu Ping , Li Yanyu , Zhong Gaoliang , Li Wen , Chen Bing , Zhang Jingjing
Published: September 2021

Hypoxic injury to cerebrovascular endothelial cells (ECs) after stroke leads to blood-brain barrier (BBB) dysfunction, which is commonly associated with disruptions of endothelial tight junctions (TJs) and increased permeability. Therefore, maintaining the structural integrity and proper function of the BBB is essential for the homeostasis and physiological function of the central nervous system (CNS). Our previous study revealed that autophagy functions on protecting the BBB by regulating the dynamics of Claudin-5, the essential TJ protein, under short-term starvation or hypoxia conditions. Here, we show that in zebrafish and in vitro cells, loss of membranous Claudin-5 conversely determine the occurrence of hypoxia-induced autophagy in cerebrovascular ECs. Absence of endothelial Claudin-5 could partly attenuate endothelial cell apoptosis caused by short-term hypoxic injury. Mechanism studies revealed that under hypoxic conditions, the existence of membranous Claudin-5 affects the stimulation of hypoxia inducible factor 1 subunit alpha (HIF-1a) and the inducible nitric oxide synthase (iNOS), which are responsible for the translocation of and endocytosis of caveole-packaged Claudin-5 into cytosol. Meanwhile, loss of Claudin-5 affects the generation of reactive oxygen species (ROS) and the downstream expression of BCL2/adenovirus E1B 19kDa protein interacting protein 3 (Bnip3). These together suppress the endothelial autophagy under hypoxia. This finding provides a theoretical basis for clarifying the mechanism of hypoxia-induced BBB injury and its potential protection mechanisms.
Genome-Wide Analysis of the R2R3-MYB Gene Family in Fragaria × ananassa and Its Function Identification During Anthocyanins Biosynthesis in Pink-Flowered Strawberry
Authors: Liu Jiaxin , Wang Jian , Wang Mingqian , Zhao Jun , Zheng Yang , Zhang Tian , Xue Li , Lei Jiajun
Published: September 2021

The strawberry (Fragaria × ananassa) is an economically important fruit throughout the world. The large R2R3-MYB gene family participates in a variety of plant functions, including anthocyanin biosynthesis. The present study is the first genome-wide analysis of the MYB gene family in the octoploid strawberry and describes the identification and characterization of the family members using the recently sequenced F. × ananassa genome. Specifically, we aimed to identify the key MYBs involved in petal coloration in the pink-flowered strawberry, which increases its ornamental value. A comprehensive, genome-wide analysis of F. × ananassa R2R3-FaMYBs was performed, investigating gene structures, phylogenic relationships, promoter regions, chromosomal locations, and collinearity. A total of 393 R2R3-FaMYB genes were identified in the F. × ananassa genome and divided into 36 subgroups based on phylogenetic analysis. Most genes with similar functions in the same subgroup exhibited similar exon-intron structures and motif compositions. These R2R3-FaMYBs were unevenly distributed over 28 chromosomes. The expansion of the R2R3-FaMYB gene family in the F. × ananassa genome was found to be caused mainly by segmental duplication. The Ka/Ks analysis indicated that duplicated R2R3-FaMYBs mostly experienced purifying selection and showed limited functional divergence after the duplication events. To elucidate which R2R3-FaMYB genes were associated with anthocyanin biosynthesis in the petals of the pink-flowered strawberry, we compared transcriptional changes in different flower developmental stages using RNA-seq. There were 131 differentially expressed R2R3-FaMYB genes identified in the petals, of which three genes, FaMYB28, FaMYB54, and FaMYB576, appeared likely, based on the phylogenetic analysis, to regulate anthocyanin biosynthesis. The qRT-PCR showed that these three genes were more highly expressed in petals than in other tissues (fruit, leaf, petiole and stolon) and their expressions were higher in red compared to pink and white petals. These results facilitate the clarification on the roles of the R2R3-FaMYB genes in petal coloration in the pink-flowered strawberry. This work provides useful information for further functional analysis on the R2R3-FaMYB gene family in F. × ananassa.
Comparative Proteomics at the Critical Node of Vigor Loss in Wheat Seeds Differing in Storability
Authors: Chen Xiuling , Börner Andreas , Xin Xia , Nagel Manuela , He Juanjuan , Li Jisheng , Li Na , Lu Xinxiong , Yin Guangkun
Published: September 2021

The critical node (CN, 85% germination) of seed viability is an important threshold for seed regeneration decisions after long-term conservation. Dependent on the germplasm, the storage period until CN is reached varies and information on the divergence of the proteomic profiles is limited. Therefore, the study aims to identify key proteins and mechanisms relevant for a long plateau phase and a late CN during artificial seed aging of wheat. Seeds of the storage-tolerant genotype (ST) TRI 23248, and the storage-sensitive genotype (SS) TRI 10230 were exposed to artificial ageing (AA) and extracted embryos of imbibed seeds were analyzed using an iTRAQ-based proteomic technique. ST and SS required AA for 24 and 18 days to reach the CN, respectively. Fifty-seven and 165 differentially abundant proteins (DAPs) were observed in the control and aged groups, respectively. Interestingly, a higher activity in metabolic processes, protein synthesis, transcription, cell growth/division, and signal transduction were already found in imbibed embryos of control ST seeds. After AA, 132 and 64 DAPs were accumulated in imbibed embryos of both aged ST and SS seeds, respectively, which were mainly associated with cell defense, rescue, and metabolism. Moreover, 78 DAPs of ST appeared before CN and were mainly enriched in biological pathways related to the maintenance of redox and carbon homeostasis and they presented a stronger protein translation ability. In contrast, in SS, only 3 DAPs appeared before CN and were enriched only in the structural constituents of the cytoskeleton. In conclusion, a longer span of plateau phase might be obtained in seeds when proteins indicate an intense stress response before CN and include the effective maintenance of cellular homeostasis, and avoidance of excess accumulation of cytotoxic compounds. Although key proteins, inherent factors and the precise regulatory mechanisms need to be further investigated, the found proteins may also have functional potential roles during long-term seed conservation.
Network Inference of Transcriptional Regulation in Germinating Low Phytic Acid Soybean Seeds
Authors: DeMers Lindsay C. , Raboy Victor , Li Song , Saghai Maroof M. A.
Published: September 2021

The low phytic acid (lpa) trait in soybeans can be conferred by loss-of-function mutations in genes encoding myo-inositol phosphate synthase and two epistatically interacting genes encoding multidrug-resistance protein ATP-binding cassette (ABC) transporters. However, perturbations in phytic acid biosynthesis are associated with poor seed vigor. Since the benefits of the lpa trait, in terms of end-use quality and sustainability, far outweigh the negatives associated with poor seed performance, a fuller understanding of the molecular basis behind the negatives will assist crop breeders and engineers in producing variates with lpa and better germination rate. The gene regulatory network (GRN) for developing low and normal phytic acid soybean seeds was previously constructed, with genes modulating a variety of processes pertinent to phytic acid metabolism and seed viability being identified. In this study, a comparative time series analysis of low and normal phytic acid soybeans was carried out to investigate the transcriptional regulatory elements governing the transitional dynamics from dry seed to germinated seed. GRNs were reverse engineered from time series transcriptomic data of three distinct genotypic subsets composed of lpa soybean lines and their normal phytic acid sibling lines. Using a robust unsupervised network inference scheme, putative regulatory interactions were inferred for each subset of genotypes. These interactions were further validated by published regulatory interactions found in Arabidopsis thaliana and motif sequence analysis. Results indicate that lpa seeds have increased sensitivity to stress, which could be due to changes in phytic acid levels, disrupted inositol phosphate signaling, disrupted phosphate ion (Pi) homeostasis, and altered myo-inositol metabolism. Putative regulatory interactions were identified for the latter two processes. Changes in abscisic acid (ABA) signaling candidate transcription factors (TFs) putatively regulating genes in this process were identified as well. Analysis of the GRNs reveal altered regulation in processes that may be affecting the germination of lpa soybean seeds. Therefore, this work contributes to the ongoing effort to elucidate molecular mechanisms underlying altered seed viability, germination and field emergence of lpa crops, understanding of which is necessary in order to mitigate these problems.
Geneva® Series Rootstocks for Apple Trees Under Extreme Replanting Conditions in Southern Brazil
Authors: Rufato Leo , da Silva Pricila Santos , Kretzschmar Aike Anneliese , Bogo Amauri , de Macedo Tiago Afonso , Welter Juliana Fátima , Fazio Gennaro , Petry Daiana
Published: September 2021

Geneva® rootstocks in Brazil are known to be efficient in controlling vigor, and are precocious and resistant to diseases. The objective of this study was to evaluate the performance of apple tree cultivars grafted on the Geneva® rootstocks in severe replant disease areas, by planting 60 days after the eradication. The experiments were implemented in 2017, in São Joaquim and Vacaria. The Gala Select and Fuji Suprema cultivars were grafted onto ‘G.202’, ‘G.814’, ‘G.210’, and ‘G.213’ rootstocks in the Tall Spindle training system. In 2018/2019, total thinning was carried out to promote plant growth. In São Joaquim, partial thinning was carried out in 2019/2020 harvest of ‘Gala Select’. The rootstocks were divided into two groups based on vigor, for both areas and cultivars. ‘G.202’ and ‘G.213’ were 40% less vigorous than ‘G.210’ and ‘G.814’. For ‘Gala Select’, the extreme non-fallow condition mainly affected the vigor and productivity of ‘G.213’ in both areas. At the end of two harvests, ‘G.213’ was 17% less productive than ‘G.210’, contrary to what is observed in areas where the fallow period is respected. However, ‘G.213’ confirmed a greater yield efficiency, which was 27% higher than ‘G.210’. This suggests that a perspective of forecasting production for the third crop is higher for ‘G.213’ than for ‘G.210’. In the case of ‘Fuji Suprema’, the G.210 rootstock was the most productive in both areas. In São Joaquim, ‘G.202’ matched ‘G.210’ in productivity and efficiency as it sprouts better in colder regions. Considering the fruit quality, ‘G.213’ anticipated the maturation with fruits of larger size and higher total soluble solids (TSS) in both areas and cultivars, making it possible to anticipate the harvest. It was concluded that the non-fallow condition does not alter the relative differences in vigor and fruit quality among the rootstocks. However, notwithstanding the overall replant tolerance of these rootstocks, it does reduce productivity by mainly affecting less vigorous rootstocks that need about three crops to overcome the allelopathic effects of the soil and start growing normally. The G.210 semi-dwarfing rootstock is an alternative for the immediate conversion of apple orchards of Gala Select and Fuji Suprema cultivars in southern Brazil.