bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Elongation Factor-2 as a Novel Regulator of Mitochondrial Fission
Authors: Kim Jinhwan , Cheng Yan , Li Yanfeng , Zhang Yi , Cheng Ji , Zhu Hua , Takahashi Yoshinori , Xiong Xingdong , Gu Lixiang , Ngule Chrispus , Ren Xingcong , Xiong Xiaofang , Song Jianxun , Liu Xiaoqi , Yang Jin-Ming 
Published: August 2021

Abstract
Mitochondria continuously undergo morphologically dynamic processes of fusion and fission to maintain their size, shape, amount, and function; yet the precise molecular mechanisms by which mitochondrial dynamics is regulated remain to be fully elucidated. Here, we report a previous unappreciated but critical role of eukaryotic elongation factor 2 (eEF2) in regulating mitochondrial fission. eEF2, a G-protein superfamily member encoded by EEF2 gene in human, has long been appreciated as a promoter of the GTP-dependent translocation of the ribosome during protein synthesis. We found unexpectedly in several types of cells that eEF2 was not only present in the cytosol but also in the mitochondria. Furthermore, we showed that mitochondrial length was significantly increased when the cells were subjected to silencing of eEF2 expression, suggesting a promotive role for eEF2 in the mitochondrial fission. Inversely, overexpression of eEF2 decreased mitochondrial length, suggesting an increase of mitochondrial fission. Inhibition of mitochondrial fission caused by eEF2 depletion was accompanied by alterations of cellular metabolism, as evidenced by a reduction of oxygen consumption and an increase of oxidative stress in the mitochondria. We further demonstrated that eEF2 and Drp1, a key driver of mitochondrial fission, co-localized at the mitochondria, as evidenced by microscopic observation, co-immunoprecipitation, and GST pulldown assay. Deletion of the GTP binding motif of eEF2 decreased its association with Drp1 and abrogated its effect on mitochondria fission. Moreover, we showed that wild-type eEF2 stimulated GTPase activity of Drp1, whereas deletion of the GTP binding site of eEF2 diminished its stimulatory effect on GTPase activity. This work not only reveals a previously unrecognized function of eEF2 (i.e., promoting mitochondrial fission), but also uncovers the interaction of eEF2 with Drp1 as a novel regulatory mechanism of the mitochondrial dynamics. Therefore, eEF2 warrants further exploration for its potential as a therapeutic target for the mitochondria-related diseases.
A Mixed-Methods Evaluation of The ¡Vamos Por Más! Parenting Program Implementation in Chile
Authors: Meyer Jessica K.V. , Diaspro Gabriela , Muñoz Iván , Burmeister Catalina , Garcia-Huidobro Diego 
Published: August 2021

Abstract
Introduction:

Substance use is a significant global concern. Strengthening parenting in families with adolescents has been shown to reduce substance use initiation. The ¡Vamos por Más! (¡VxM!) program is a positive-parenting program developed in Chile to improve family relations and reduce adolescent substance use that combines in-person school workshops, multimedia messaging and personalized support.
Objective

This manuscript reports a mixed-methods evaluation of the pilot implementation of the ¡VxM! program utilizing the Consolidated Framework for Implementation Research and Proctor’s taxonomy for process outcomes.
Methods

An explanatory sequential design was used. Quantitative methods evaluated program use, acceptability, appropriateness, and fidelity, and were followed by qualitative focus groups (FGs) to assess the implementation process and understand these outcomes. Thirteen FGs stratified by school and role, including school leaders (n = 7), program facilitators (n = 19), participants (n = 36), and researchers (n = 4), were conducted.
Results

The program was implemented in three schools, reaching 253 families with in-person workshops (40.5% of potential participants), 257 parents who viewed on average 72.1% of sent multimedia messages, and 2 families who used the personalized support (0.3%). Overall, the program was viewed as acceptable and appropriate by participants and implementers due to the high quality of program materials, targeted content, and activities. Implementation differed by schools. Key implementation factors were the outer context, inner school setting, and implementation processes.
Conclusion

This comprehensive evaluation, including both intervention implementers and participants, identified implementation facilitators, barriers, and outcomes. Future ¡VxM! implementations should alter program components of schools with lower engagement to improve program implementation and outcomes.
Analysis of Genotypic Variation and Selection of Superior Genotypes of Balanites roxburghii Planch. from South India
Authors: Yadav Guggalada Govardhana , Hosakatte Niranjana Murthy 
Published: August 2021

Abstract
Balanites roxburghii is an important medicinal plant of India and is used in the treatment of various diseases and disorders. Seeds possess a high amount of oil and could be used in biodiesel production. This plant is also a source of diosgenin, a therapeutically useful compound. Domestication of this plant provides opportunities for the commercial production of those valuable products. Hence the present study was planned to assess the variability of B. roxburghii in Southern India and identifying the superior genotypes based on the morphological characterization. A total of 45 accessions from 35 populations were collected and variation in 9 quantitative and 3 qualitative morphological traits related to fruits was analyzed. Fruit weight showed the highest variation, ranging from 10.23 g in the accession KA-04C to 37.69 g in TN-03. Pulp weight was ranged from 1.71 g in KA-04C to 10.24 g in TN-03. Seed kernel weight was highest in TE-04 (3.87 g) followed by KA-04A (3.21 g) and TE-05A (2.98 g). PCA analysis showed that fruit weight, fruit length, fruit width, pulp weight, rind weight, and endocarp weight were the major traits contributing to the diversity. Cluster analysis resulted in the formation of 4 groups and among them, 2 accessions of clusters 3 and 6 accessions of cluster 4 showed superior fruit characters by having the highest fruit weight, pulp weight, and seed kernel weight. Accessions of these groups could be considered in future domestication programs.
Hsa-miR-1-2/miR-133a-1 Cluster Expression Silencing by DNA Hypermethylation Triggers Oncogenes Contributing to Prostate Cancer Aggressiveness
Authors: Massillo Cintia , Duca Rocío Belén , Farré Paula Lucía , Gardner Kevin , Lacunza Ezequiel , De Siervi Adriana 
Published: August 2021

Abstract
Background: Prostate cancer (PCa) is currently the most commonly diagnosed type of cancer. The incidence and mortality of PCa worldwide correlate with increasing age and bad dietary habits. Previously, we investigated the mRNA/miRNA role on PCa development and progression using high fat diet (HFD) chronically fed mice models. Here our main goal was to investigate the effect of HFD on the expression of prostate cancer-related miRNAs and their relevance in PCa patients. Methods: Using microarray data from mice prostate tumors generated by TRAMP-C1 cell inoculation, we focused on the role of three candidate miRNAs (miR-133a-3p/133b/1-3p) and their target genes. Based on data from public databases, we examined the expression levels of hsa-miR-133a-3p/133b/1-3p and their correlation with clinicopathological features in PCa patients. The biological roles of hsa-miR-133a-3p/133b/1-3p and their relevant target genes were investigated by bioinformatics approaches. The promoter methylation of hsa-miR-133a-3p/133b/1-3p host genes and their correlation with mature miRNA expression was further evaluated.Results: We identified 6 up- and 18 down-regulated miRNAs in TRAMP-C1 mice prostate tumors under HFD conditions using miRNA microarrays. Target genes (1,278) of down-regulated miRNAs involved in cancer-related biological processes were identified using DIANA-TarBase and STRING databases. Three down-regulated miRNAs: hsa-miR-133a-3p, 133b and 1a-3p showed nine common target genes that negatively correlated with miRNA expression in prostate tumors from patients. Hsa-miR-133a-3p/133b/1-3p expression levels were significantly decreased in PCa compared to normal tissues and their low expression correlated with bad clinicopathological features in patients. We also examined the promoter region of hsa-miR-133a-3p/133b/1-3p encoding genes in PCa patients and then compared methylation at these loci with mature miRNA expression. This analysis revealed that hsa-miR-1-2/miR-133a-1 cluster promoter hypermethylation decreased hsa-miR-133a-3p/1-3p expression in prostate tumors. Furthermore, CENPF and WHSC1, two common hsa-miR-133a-3p/133b/1-3p target genes, were found significantly up-regulated in PCa and positively correlated with advanced clinicopathological characteristics in PCa patients.Conclusion: Our results provide an explanation for the aggressiveness of PCa and link it mechanistically to the attenuation of hsa-miR-133a-3p/133b/1-3p expression by promoter hypermethylation. Hsa-miR-133a-3p/133b/1-3p downregulation may enhance PCa aggressiveness in part by targeting CENPF and WHSC1. Therefore, hsa-miR-133a-3p/133b/1-3p might be potential therapeutic targets for lethal PCa.
Single-Cell RNA-seq Reveals LGALS1 and LAG3 as Novel Drivers of Ibrutinib Resistance in Chronic Lymphocytic Leukemia
Authors: Jin Hui , Huang Bin , Wu Zijuan , Zhu Huayuan , Tang Hanning , Wu Jiazhu , Gu Danling , Cai Yun , Wang Luqiao , Lu Xueying , Xu Wei , Li Kening , Wang Qianghu , Li Jian-Yong 
Published: August 2021

Abstract
BackgroundChronic lymphocytic leukemia (CLL) is a highly heterogeneous malignant lymphoproliferative B-cell disorder that can be treated using ibrutinib, a Bruton’s tyrosine kinase inhibitor. However, the ibrutinib resistance of CLL patients has caused widespread concerns, necessitating the development of novel treatment strategies. MethodsHere, we identified lectin galactoside-binding soluble 1 (LGALS1) and lymphocyte-activating gene 3 (LAG3) as potential markers for ibrutinib-resistant CLL using single-cell RNA sequencing (scRNA-seq), and the results were validated in an ibrutinib-resistant CLL cell line (MEC1-IR) and primary cells from CLL patients. Marker-gene expression was detected while functional analyses were conducted with or without OTX008, a selective Galectin-1 inhibitor. ScRNA-seq revealed that the biological features, gene expression profiles, and clonal signatures of peripheral blood mononuclear cells (PBMCs) from patients with ibrutinib-resistant CLL were distinct from those displayed by PBMCs from ibrutinib-sensitive patients.ResultsA close correlation between LGALS1 and LAG3 expression was observed and these factors were found to be highly expressed in ibrutinib-resistant CLL, with diagnostic and prognostic stratification, indicating that they may serve as drivers of ibrutinib-resistant CLL. Concordantly, LGALS1 and LAG3 expression was higher in ibrutinib-resistant CLL cells and primary cells, and OTX008 suppressed proliferation and induced apoptosis in both cells.ConclusionLGALS1 and LAG3 gene panel is promising indicator of ibrutinib-sensitivity and prognosis marker of CLL. LGALS1 inhibitor OTX008 is effective in CLL patients, both those naïve to and those resistant to ibrutinib.
Genomic Association Between Angiotensin-Converting Enzyme, Angiotensinogen And ARNT-Like Protein-1Genes With Susceptibility To Gestational Diabetes In Egyptian Women
Authors: Ashour Esmat , Gouda Weaam , Mageed Lamiaa , Okasha Ahmed , Afify Mie , Shaker Yehia M , Fawzi Olfat M 
Published: August 2021

Abstract
Background and aims: Gestational diabetes mellitus (GDM) is well-defined as glucose intolerance first documented during pregnancy. In the present study, we examined the possible associations between I/D polymorphism of the angiotensin-converting enzyme (ACE) gene, the M235T variant of angiotensinogen (AGT) gene, and the rs7950226 polymorphism of the ARNT-like protein-1 (BMAL1) gene and the risk for GDM, in Egyptian pregnant women. Subjects and methods: This study recruited 160 GDM cases and165 controls. Genomic DNA was derived from peripheral blood leukocytes and ACE gene (I/D) genotyping was performed using the method of polymerase chain reaction (PCR) and the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used for identifying the M235T variant of AGT gene and the rs7950226 polymorphism of the BMAL1. Results: The II, ID, and DD genotypes of the ACE gene have significant differences in GDM compared to controls (p= 0.000 and X2= 81.77). The M235T polymorphism of the AGT gene was increased with GDM risk. Furthermore, the AA genotype of the BMAL1 rs7950226 gene was significantly related to the GDM risk (P = 0.000 and X2= 52.82). The allele frequencies of the three variants vary significantly between women with gestational diabetes mellitus and control additionally; the risk factors of body mass index (BMI), family history, hypertension, and diabetes were significantly correlated with the GDM risk with a p-value of 0.001. Conclusion: The present study suggested significant associations between ACE (DD), AGT (TT), and BMAL1 rs7950226 (AA) gene polymorphisms with GDM susceptibility in Egyptian pregnant women and there was a possibility to identify that II + MM + GG as protective haplotypes and DD + TT + AA as risk haplotypes for GDM.
Characteristics of Cirrhosis Patients With Left Ventricular Diastolic Dysfunction In China: A Single-Center Retrospective Study.
Authors: Hu Jingjing , Cai Zhaobin 
Published: August 2021

Abstract
Objective: Mounting evidence links cirrhosis patients with left ventricular diastolic dysfunction（LVDD） has a poor prognosis. However, little is known about these particular individuals. Therefore, we conducted this cross-sectional study to assess the prevalence of LVDD and its associated risk factors.Methods: Consecutive cirrhosis patient who were attending Hangzhou Xixi hospital from January 2018 to December 2019 were included in this study. According to the American Society of Echocardiography 2016 criteria, cirrhosis patients were sorted into two group: the left ventricular diastolic dysfunction(LVDD) group and left ventricular diastolic function normal(LVDDn) group. Patients’ demographic data, clinical characteristics, laboratory data were recorded. Furthermore, we conducted a multi-factor analysis.Results: A total of 398cirrhosis patients were included in the study. The incidence of LVDD in this study was 49.7% (198 cases). In this study, the mean age and BMI of the patients were 52.9±8.2 years and 23.0±3.3kg/m2，respectively. Of 398 patients, 255(64.1%) of them were males. With regard to etiology, there were 296 patients (74.4%) with hepatitis B cirrhosis and 59 patients (14.8%) with alcoholic cirrhosis. The LVDD group had higher age, higher BMI, greater frequency of ascites and esophageal varices, prolonged prothrombin time, increased international normalized ratio, increased bilirubin, increased CK and AST, and longer QT interval than the LVDDn group(p<0.05, both). In terms of echocardiography, the LVDD group had larger aortic inner diameter, left atrial inner diameter and left ventricular wall diastolic thickness than LVDDn group(p<0.05, both). The multivariate analysis showed age>55 years, BMI>24kg/m2, hepatic decompensated, QTcB>440ms were independently associated with risk of LVDD.Conclusion: The prevalence of LVDD among cirrhosis patients was 49.8%. Cirrhosis patients with LVDD had worse liver function. Further, age>55 years, BMI>24kg/m2, hepatic decompensated, QTcB>440ms were independent predictors of LVDD.
A Pseudo-SBAS Method To Invert 2D Deformations of The 2021 Central Greece Earthquake Sequence Using Multi-Track And Multi-Temporal Sentinel-1 SAR Data
Authors: Ma Zhangfeng , Liu Xiaojie , Huang Qihuan , Li Guihua , Liu Jihong , Zhou Cheng , Hu Jia , Gao Zhuang , Sha Pengcheng , Cui Yan , Qin Shuhong , Huang Teng , Gao Jiandong 
Published: August 2021

Abstract
Multi-track InSAR data have been widely applied to decompose 2D (East-West and Up-Down) co-seismic deformation in order to intuitively interpret the co-seismic deformation. Most of the previous efforts well studied the decomposition of single earthquake deformation using a pair of ascending and descending InSAR data. However, the deformation decomposition of multiple earthquake events in a short time period is rarely discussed and hard to implement. That's because it's hard to make sure that deformation related to each earthquake can be imaged by a pair of ascending and descending track. In this paper, a Pseudo-Small BASeline (SBAS) method is developed to decompose 2D deformation of each earthquake in a sequence event. The rationale behind is that several interferograms with different imaging geometries contain co-seismic deformation related to single or multiple earthquakes, and it provides us the opportunity to separate the 2D deformation of a single or multiple events by fusing the short temporal baseline interferograms from multi-track and multi-temporal SAR observations. The proposed method has two parts. The first part is to correct phase unwrapping errors using a compressed sensing method based on redundant SBAS interferograms. In the second part, we incorporate strain model and the conception of SBAS technique into 2D deformation decomposition. We used our proposed Pseudo-SBAS method and four tracks Sentinel-1 data to study the deformation decomposition of an earthquake sequence hit the Central Greece in March 2021. The comprehensive comparisons on synthetic and real Sentinel-1 data confirm the validity of the proposed method. The experimental results also indicate that a triggering mechanism of cascading rupture process can explain the occurrence of these three sequent earthquakes, and the decomposed post-seismic deformation of the first earthquake in EW direction move towards the opposite direction to the co-seismic deformation.
FAM96A and FAM96B Suppress Breast Cancer Proliferation and Migration via the Wnt/β-Catenin Signaling Pathway
Authors: Zhang Di-Di , Sun Xiao-Lin , Liang Zhao-Yuan , Zhang Li-Na 
Published: August 2021

Abstract
Background: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Many studies have shown that FAM96A and FAM96B play many different functions mainly through interacting with other different proteins. Recently, several studies show that FAM96A and FAM96B are significantly down-regulated compared in human gastrointestinal stromal tumors, colon cancer, liver cancer and gastric cancer with corresponding normal tissues. However, the molecular regulatory mechanisms of FAM96A and FAM96B in breast cancer development and metastasis are still unclear. In this work, we aimed to explore the molecular mechanisms of FAM96A and FAM96B in breast cancer progression.Methods: We used specific siRNAs to down-regulate FAM96A and FAM96B expression, and used recombinant plasmids to up-regulate FAM96A and FAM96B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry analysis. Wound healing and transwell assays were used to examine cell migration and invasion abilities. The relationships among FAM96A/B, EMT and Wnt/β-catenin signaling pathway were determined by analyzing the expression changes of classical markers and biological functional changes after XAV-939 inhibitor treatment. Results: We found that FAM96A and FAM96B expression in breast cancer was down-regulated. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and led to cell cycle arrested in G0/G1 phase. Conversely, FAM96A/B knockdown exhibited the opposite effects on breast cancer cells. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/β-catenin signaling pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/β-catenin signaling pathway in breast cancer cells. Furthermore, a Wnt pathway inhibitor, XAV-939 treatment reversed the promoting effects of FAM96A and FAM96B knockdown on breast cancer cell proliferation, invasion and migration.Conclusions: Our findings revealed that FAM96A and FAM96B may act as tumor suppressor genes and inhibit breast cancer progression via modulating the Wnt/β-catenin pathway, which can provide the potential markers for the diagnosis and treatment of breast cancer.
Visceral Fat is Better Related To Liver Function and Lipid Metabolism Than Body Mass Index and Waist Circumference: A Cross-Sectional Study
Authors: Zhou Haiteng , Sun Guiju , Pan Youwen , Wang Bin , Wang Wei , Xia Hui 
Published: August 2021

Abstract
Objective: The role of visceral fat area (VFA) in the metabolism of lipid and liver function was not known. To compare and evaluate the correlation of VFA, waist circumference (WC) and Body mass index (BMI) measured by Bioelectrical impedance (BIA) in terms of lipid metabolism and liver function. Receiver operating characteristic curve (ROC curve), optimum cut-off points and odds ratio (OR) for liver function and lipid metabolism variables were recommended.Methods: A cross-sectional study was conducted on the subjects with the diagnose of obesity, including normal, overweight and obesity groups Direct Segmental Multi-Frequency Biolectrical Impedance technology was used to analysze body composition and biochemical indicators were tested. Participants were divided into normal and unnormal groups by lipid and liver indicators, cut off value of VFA and related variables was calculated by ROC analysis and multiple logistic regression analysis were conducted. Results: Ninety-five participants were enrolled in this study, fifty-seven (60%) were male, and the average age was thirty-four years old. Compared with normal group, high density lipoprotein (HDL) and low density lipoprotien (LDL) disorder groups have a higher VFA (normal HDL group 87.3cm2< unnormal HDL group 115.8cm2; normal LDL group 90.5cm2< unnormal LDL group 109.0cm2, p<0.05). VFA was higher in the lactate dehydrogenase (LDH) disorder group than in the normal, and the difference was significant (144.6cm2>96.2cm2, p=0.016). BMI, WC and VFA values was manifested positively correlated to glutamic oxaloacetic transaminase (AST) and alanine aminotransferase (ALT), respectively. Area under the curve (AUC) of VFA was over than 0.7 revealed great ability of related to lipid HDL metabolism (p=0.004). VFA (AUC= 0.701, 95% CI 0.577-0.826, p =0.004) provides a better diagnostic accuracy to distinguish between HDL disorder and normal groups. The optimal cut-off value for VFA was 80.2cm2 with 81.3% sensitivity and 56.8% specificity. For LDH disorder, a cut-off value of VFA 125.3 cm2 shows a sensitivity of 83.3% and specificity of 78.9% (AUC=0.792, 95% CI 0.595-0.989, p=0.019). The risk of lipid metabolism disorder and liver dysfunction were explored, and Multivariate analysis showed that VFA>80.2cm2 (OR=2.81, p=0.034) was a significantly risk factor related to HDL disorder and VFA>125.3cm2 (OR=18.75, P=0.01) was the risk factor for LDH disorder. While, WC and BMI wasn’t in the regression equation.Conclusion: VFA was more reliable and related to the lipid metabolism and liver function. VFA could be used as an independent indicator for the evaluation of the risk lipid metabolism disorder and liver dysfunction.