bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Potential Core Genes and Potential Drugs in Vestibular Schwannoma
Authors: Yan Junqiang , Liu Anran , Huang Jiarui , Wu Jiannan , Ma Hongxia , Jiang Menghan , Yang Jianxue
Published: August 2021

Vestibular schwannoma is a common intracranial benign tumor, but the current drug treatment effect is not obvious. Surgical treatment can usually lead to residual problems such as nerve damage. Therefore, there is no clear molecular target to facilitate better clinical treatment. We analyzed three microarray data sets (GSE39645, GSE54934 and GSE108524) derived from the Gene Expression Omnibus database (GEO). The GEO2R was used to screen for the differentially expressed genes (DEG) between vestibular schwannomas and normal tissues. The ontology function of genes and genome pathway enrichment analysis were performed using annotation, visualizative and comprehensive discovery databases to identify the pathways and functional annotation of DEGs. The protein-protein interactions of these DEGs were analyzed by searching the interaction gene database and visualized by Cytoscape software. The potential therapeutic drugs for vestibular schwannoma were searched by online gene drug interaction analysis.A total of 226 up-regulated and 148 down-regulated DEGs were identified. Among them, ten hub genes with high connectivity (EGFR, PPARG, CD86, CSF1R, SPP1, CDH2, CCND1, CAV1, CYBB and NCAM1) were selected as the central genes that may be closely related to the pathogenesis of vestibular schwannoma, which can be potential treatment targets of vestibular schwannoma. Afatinib and osimerinib may be potential therapeutic drugs.
Gene mapping and candidate gene analysis of a novel watermelon lesion mimic mutant clalm
Authors: dong wei , liu kai , wu de feng , Jinggong Guo
Published: August 2021

The leaf is an extremely important plant organ exhibiting a broad range of phenotypic variation. In watermelon (Citrullus lanatus), leaf spotting is a rare, valuable trait that can be used by breeders for selection at early growth stages. In this study, we tested a seven-generation family to determine the inheritance and genetic basis of this trait. As revealed by analysis of the lesion mimic mutant clalm, leaf spotting is controlled by a single dominant gene. Whole genome resequencing–bulked segregant analysis demonstrated that this gene is located on chromosome 4 from 3,760,000 bp to 7,440,000 bp, a region corresponding to a physical distance of 3.68 Mb encompassing approximately 72 annotated genes and eight non-synonymous coding SNPs. According to quantitative real-time PCR analysis, the expression level of ClCG04G001930 was significantly lower in the clalm mutant than in normal watermelon. The predicted target gene, ClCG04G001930, encodes a fatty acid amide hydrolase protein that regulates a variety of neurobehavioral processes in animals. Twelve-five SNPs were identified in the ClCG04G001930 gene of F2 individuals of the clalm mutant. RNA interference of the ClCG04G001930 gene, designated as ClPAD4, yielded transgenic lines whose leaves gradually developed chlorotic lesions over 3 weeks. Our results suggest that ClPAD4 is the gene responsible for leaf spotting in the clalm mutant. Our findings may serve as a foundation for elucidating the mechanism underlying the spotted leaf trait and should be useful for marker-assisted selection breeding in watermelon.
Fibrinogen Like Protein 1 as a Potential Biomarker for Hepatitis B Virus Related Hepatocellular Carcinoma
Authors: Xin Cai , Dongling Tang , Juanjuan Chen , Huan Li , Yuanhui Hu , Pingan Zhang
Published: August 2021

Background
There is an urgent need for new serum biomarkers for early screening of HBV-related hepatocellular carcinoma (HCC). Fibrinogen like protein 1 (FGL1) may develop the potential diagnostic value of alpha fetoprotein (AFP) in HBV-related HCC.
Methods
The TCGA database was used to screen out genes related to liver cancer and perform differential expression analysis. Enzyme-linked immunosorbent assay and chemiluminescence immunoassay were used to detect concentrations of FGL1 and AFP. Using immunofluorescence semi-quantitative method to detect the mean fluorescence intensity of FGL1.
Result
FGL1 is lower in tumor tissues than in normal tissues. The serum levels of FGL1 and AFP in patients with HBV-related HCC are significantly higher than others for each group. Compared with other groups, the area under the receiver operating curve (AUC) of FGL1 is higher than that of AFP when compared with the normal group, and the AUC of other groups is lower than that of AFP. The combination of the two can increase the AUC to 0.862 (95%CI, 0.786 ~ 0.918) in distinguishing benign liver disease from HBV-related HCC. The specificity of FGL1 and AFP in the diagnosis of HBV-related HCC is 98.39% and 70.97%, respectively. The specificity of the combination was 93.55%. In distinguishing the A and B stages in the BCLC staging, the combination of the two increased the AUC from 0.584 to 0.647. When distinguishing benign liver disease from HBV-related HCC, the AUC of FGL1 reached 0.849, with a specificity of 100%.
Conclusion
FGL1 can be used as a non-invasive biomarker for HCC. When combined with AFP, the diagnostic efficiency and specificity were improved.
Evaluation of Kinetic and Equilibrium studies for Phytoremediation of Methylene Blue Dye (Triarylmethane) and Congo Red (Diazo) using Trachyspermum Ammi L.
Authors: Kaur Navjeet , kaushal jyotsna , Mahajan Pooja
Published: August 2021

Phytoremediation developed as a green-clean, solar-driven and innovative technique for the eradication of contaminants from the environment from last two decades. In the present research work, phytoremediation potential of an ornamental plant Trachyspermum ammi L. (T. ammi) was examined for the removal of a triarylmethane-Methylene blue (MB) and di-azo-Congo red (CR) dye. The various parameters such as initial dye concentration, contact time, and pH were focused to explore the dye removal capability of T. ammi. The increase in initial dye concentration affects the decolorization potential of the T. ammi. The decolorization potential of T. ammi found to be reduced with enhancing the initial dye concentration of both the dyes. The plant achieved condition of equilibrium after the 40 h of contact time with both MB and CR dye. The favorable pH for T. ammi for the MB dye was observed as 5 while for CR dye was 6. The kinetics of phytoremediation reaction with both MB and CR dyes were studied with help of pseudo-first order, pseudo-second order, and Elovich models and the results were well appropriated to pseudo-first order with the correlation value R2 ≥ 0.95 for MB and R2 ≥ 0.97 for CR. The Langmuir and Freundlich isotherms studies of phytoremediation reaction found in favor of Freundlich equilibrium isotherm with correlation R2 ≥ 0.99 for both MB and CR dyes. The mechanism of T. ammi for removal of dyes was supported with the help of analytical techniques such as Fourier Transform-Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM).
Mini-CEX Oriented Attending Physician Rounds (Mini-CEX-APR): A New Teaching Model for Standardized Residency Training
Authors: Liu Xin , Xu Weixian , Li Haiyun
Published: August 2021

Background: Mini-CEX is a multifunctional tool to accurately evaluate and improve the clinical competence of residents. It is crucial to explore an appropriate way to combine mini-CEX and clinical practice in order to achieve wide application of mini-CEX in Chinese residency training programs. Objectives: This study was designed to explore the value of mini-CEX oriented attending physician rounds in residency training for cardiology and gastroenterology residents.Design: Single-blind, RCT.Methods: Participants were randomly assigned into the traditional and the mini-CEX-APR group. The traditional group received regular training required by the education department, while the mini-CEX-APR group received additional mini-CEX oriented attending physician rounds on the basis of routine training. The attending physicians in the mini-CEX-APR group conducted real-time evaluation of residents in the process of ward rounds based on the mini-CEX, and provided timely feedback and targeted guidance every 2 weeks. All subjects accepted final mini-CEX assessment when they finished the cardiology or gastroenterology training. Results: The mini-CEX scores of the mini-CEX-APR group was significantly higher than that of the traditional group (50.05±3.19 vs 45.65±3.14, P<0.001), especially in history taking (7.54±0.63 vs 6.60±0.62, P<0.001) and integrated capacity parts (7.46±0.60 vs 6.61±0.59, P<0.001), their satisfaction levels are also higher than those in traditional group (8.81±0.77 vs 7.28±0.67, P<0.001). The overall teaching effect of the mini-CEX-APR was better than traditional teaching methods regardless of in the Grade III-A (51.35±2.69 vs 46.76±2.77, P<0.001) or Grade III-B hospitals (48.67±3.14 vs 44.50±3.12, P<0.001).Conclusion: The mini-CEX-APR model that integrates evaluation and feedback organically can enhance the scientific nature of the clinical evaluation, and especially promote the elevation of residents’ clinical capabilities. Its excellent reliability, validity, versatility and convenience will be a renewed push for incorporating the mini-CEX-APR into residency training.
lncRNA VASH1-AS1/miR-199a-5p/PDCD4 Axis Regulate Proliferation, Apoptosis, and Cell Cycle in PDAC Progress
Authors: Tian BL , li xinglei , huang xing , liu wei
Published: August 2021

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with clinical characterized by short course, rapid progression and rapid deterioration. At present, the studies on the regulatory factors of PDAC are not enough.Methods: In this study, we applied transcriptome sequencing with PDAC tumor and normal tissues (5cases). Expression of miR-199a-5p was detected by qPCR in another 10 pairs of cancer and normal tissues. The miR-199a-5p mimic, miR-199a-5p mimic NC, miR-199a-5p inhibitor, and miR-199a-5p inhibitor NC were used to detect the function of miR-199a-5p in cell lines. Construction of double luciferase reporter vector of VASH1-AS1 and PDCD4 were used to confirm the binding of miR-199a-5p and 3’- UTR of human PDCD4 mRNA and VASH1-AS1, respectively. PDCD4 protein expression was detected by Western Blot. The cell apoptosis assay was performed using the Annexin V-FITC Kit. Cell proliferation was detected using CCK-8assay and EdU fluorescence analysis. Cell cycle and apoptosis analyzed by flow cytometry at excitation and emission wavelengths of 488 and 530 nm, respectively. SPSS software (version 22.0; SPSS, Chicago, USA) and GraphPad Prism 5.0 (GraphPad software, San Diego, California, USA) were used for data analysis.Results: After data preprocessing, differentially expressed lncRNAs (606 up-regulated, 875 down-regulated), miRNAs (171 up-regulated, 188 down-regulated) and genes (4129 up-regulated, 3417 down-regulated) were identified. With dada analysis, a new VASH1-AS1/miR-199a-5p/PDCD4 regulation mode was discovered. In PDAC, the expression level of miR-199a-5p is negatively correlated with VASH1-AS1, and the further binding was performed between miR-199a-5p and PDCD4. The overexpression of miR-199a-5p can promote the proliferation and cycle of tumor cells, inhibit cell apoptosis. If the expression of miR-199a-5p is inhibited, the opposite result was obtained. By using overexpression vectors and siRNA of PDCD4, we also found that the low expression of PDCD4 can promote tumor cell proliferation and cycle, and inhibit cell apoptosis. If PDCD4 is highly expressed, the opposite result is obtained.. Conclusion: These findings suggest that lncRNA VASH1-AS1/miR-199a-5p/PDCD4 axis may regulate the formation of PDAC through synergy, and show potential application as an early diagnostic and prognostic marker for PDAC.
Underweight and Factors Associated Among Lactating Mothers In Dodata District, Arsi Zone, Oromia Regional State, Ethiopia,2021
Authors: Kedir Hawa , Arero Godana
Published: August 2021

Background: An underweight individual is a somebody whose body weight is considered too low (BMI <18.5) to be healthy. The similar idea applies to lactating mothers. However, little is known about underweight status among lactating women in the study area. The objective of study to assess incidence of underweight and related issues among lactating mothers in Dodota district of Arsi Zone, Oromia, Ethiopia, from February 1-28, 2021.Method: The cross-sectional study design was done on 355 lactating mothers. The starata and simple random sampling technique were used. The structured questionnaire and anthropometric measurements were used. Data were entered and cleaned using Epi info version 7.1 and SPSS version 21 for analysis. Bivariate and multivariate analysis were done. Descriptive statistics wree performed. The crude and adjusted odds ratio along with 95%CI were used to measure the strength of association. The level of statistical significance was declared at a p-value < 0.05. Result: Study revealed (14.1) lactating mother were underweight. Rural areas, (AOR=2.5 [95% CI: (1.061, 6.302), the practice of food taboos (AOR= 2.3, [95% CI: (1.045, 5.084) and income level(AOR= 2.1[95% CI: (1.003, 4. 460) were found to be independent determinants of underweight among lactating mothers in the study area. Conclusions: The prevalence of underweight among lactating mothers was lower.
Application of Immunohistochemistry to Monitor the CD3+T Cell Subset Counts in Patients with Sepsis
Authors: Deng Ronghua , Deng Lan , Tian Yamin , Deng Guopeng , Zeng Jiannan , Li Zhuo , Lin Xiaolong , Chen Weisheng
Published: August 2021

[Objective]: To evaluate the application significance of Immunohistochemistry for monitoring peripheral blood CD3 + T cell subset (CD3+/CD3 + CD4+/CD3 + CD8+) counts in patients with sepsis.[Methods]: Two peripheral blood samples of 117 patients with sepsis on the first day of admission (D1) and 20 healthy control subjects were collected, and two peripheral blood samples of 20 patients with sepsis on the fourth day of admission (D4) were randomly collected and used to detect the lymphocyte counts of routine blood tests and CD3 + T cell subset count by Immunohistochemistry; the lymphocyte count levels between the sepsis group and the healthy control group were compared, and the correlation between the two in the same group were analyzed.[Results]:lymphocyte counts by routine blood tests and CD3 + T cell subset counts of patients with sepsis were significantly lower than those in healthy control subjects (P < 0.01). In the surviving group, the mean values of D4 CD3 + T cell subset counts increased significantly compared with D1, while the nonsurviving group did not rebound significantly; There was a significant positive correlation between lymphocyte counts by routine blood tests and CD3 + T lymphocyte subset counts in patients with sepsis and the healthy control subjects. (P < 0.01).[Conclusion]: Detection of CD3 + T cell subset counts by immunohistochemical method can reflect the cellular immune status of patients at a given time, thus it can be used as one of the immune monitoring methods in patients with sepsis.
Online Study: Understanding the Laws of Self-Regulated Study
Authors: Rao Xin , Luo Li , Su Qiaoli , Wang Xingyue
Published: August 2021

Background:The sudden COVID-19 outbreak has posed challenges to the normal development of continuing education for general practitioners. Consequently, an online medical training program for family doctors has emerged. Online study helps us better understand the laws of self-regulated learning because we can track the process and outcome of family physicians and compare it to that of face-to-face training programs. The study track the GPCC online program to reveal this principle.Results:By recording learners’ study behaviors and explore the law of learning progress and analyse the impact of latent variables on learning through structural equation models,the study find that the the impact of teacher support and supervision and of internal motivation on learning input and the influence of teacher support and supervision on internal motivation can be researched through online study.Conclusions:Online study helps us better understand the laws of self-regulated learning. It helps to better understand the impact of teacher support, supervision, and internal motivation on learning input , as well as the influence of teacher support and supervision on internal motivation. Examining online study can also help in making effective use of the self-education characteristics of internal motivation and cultivate the ability of independent thinking and learning self-discipline .
Molecular Mechanism of Danxiong Tongmai Granules in Treatment of Coronary Heart Disease
Authors: Ye Jiahao , Yang Ruiping , Hu Zhixi , Li Lin , Zhong Senjie , Jiang Ruixue
Published: August 2021

Background: Network pharmacology has been widely adopted for mechanistic studies of Traditional Chinese Medicines (TCM). The present study uses network pharmacology to investigate the main ingredients, targets and pathways of Danxiong Tongmai Granules (DXTMG) in the treatment of coronary heart disease (CHD). We aim to validate our findings using molecular docking and molecular dynamics simulations.Methods: TCM compounds and targets were identified via searches in the BATMAN-TCM database, and the GeneCards database were used to obtain the main target genes involved in CHD, We combined disease targets with the drug targets to identify common targets, and draw a Venn diagram to visualize the results. The "TCM-compound-target" network was plotted using Cytoscape 3.7.2 software and a protein-protein interaction (PPI) network was constructed using the STRING database from which core targets were obtained. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for common drug-disease targets using R Version 4.0.4 (64 bit) software. Molecular docking of core protein-small molecule ligand interaction was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal protein-ligand complex obtained by molecular docking using Amber18 software.Results: 162 potential targets of DXTMG involved in CHD were identified. These included INS, ALB, IL-6 and TNF according to PPI network studies. GO enrichment analysis identified a total of 3365 GO pathways, including 3049 biological process pathways (BP) concerned with the heart and circulatory system;109 cellular component (CC) pathways, including cation channels and membrane rafts and 207 molecular function (MF) pathways related to receptor ligands and activators. KEGG analysis revealed a total of 137 pathways (p<0.05), including those related to AGE-RAGE signaling associated with diabetic complications, fluid shear stress and atherosclerosis. Molecular docking revealed the highest binding energy for Neocryptotanshinone Ii (the key compound of DXTMG) and TNF. Molecular dynamics simulation indicated stable binding for TNF-Neocryptotanshinone Ii with strong hydrophobic interactions mediated predominantly by the hydrophobic residues, Leu279, Val280 and Phe278 plus hydrogen-bonding with Leu279.Conclusion: The present study reveals novel insights into the mechanism of DXTMG in treating CHD. DXTMG can influence oxidative stress、inflammation response and regulating cardiomyocytes, thereby reducing the occurrence and development of CHD.
A Novel Approach to Estimate the Air Temperature Through the Air Pollution and Meteorological Conditions in Biskra Under the Parameters Astronomical, and Atmospheric
Authors: Chabane Foued , Arif Ali , Guettaf Abderrazak
Published: August 2021

Propose of the experimental study a found a sufficient model to predict the ambient temperature over the area of Biskra, Algeria, taking into account new air pollution factors such as CO, CO2, O3, and NO2. We found that the effect of air pollution, astronomical and meteorological elements have obvious in the ambient temperature, and be behavior, according to regional characteristics. Using the fitting of the experimental data for establishing a set of prediction data sets of pollutants, astronomical, and meteorological elements at the University of Biskra, Algeria. We recorded the highest NO2 value in March at an estimated value of 1.6.1015 (mole/cm), where the ambient temperature rate is low. The mathematical model obtained gives a satisfactory results, because they were substantially identical and without almost any error with the experimental data. Finally, the latter can be used by engineers and especially those who work in the environmental field which is very sensitive to temperature variation and it can influence the health of the human being.
Application of Ginsenoside-Rg1 Could Not Ameliorate The Hyperoxic-Induced Vascular Endothelial Oxidative Stress and Apoptosis
Authors: Fu Ren-Huei , Tseng Chi-Nan , Cho Yu-Hsueh , Chu Yen
Published: August 2021

Background: Oxygen therapy is necessary to preterm infants with respiratory distress. However, hyperoxia may cause bronchopulmonary dysplasia and retinopathy of prematurity due to suppression of vasogenesis and increase of cell death. Ginsenoside-Rg1, one of the active components of Ginsen, is shown as a proangiogenic factor of vascular endothelial cells. We evaluated whether application of Ginsenoside-Rg1 is able to improve hyperoxic-induced vascular endothelium injury.Materials and methods: Human umbilical vein endothelial cells (HUVECs) were cultured under room air and 60% oxygen for 72 hours, respectively. Gensenoside-Rg1 was added to the medium at 0, 75, 150, 300nM. HUVECs proliferation, oxidative stress and apoptosis under normoxic and hyperoxic conditions were assayed by Western Blot.Results: Under hyperoxia (60% O2), HUVECs proliferation and levels of vascular endothelial growth factor (VEGF) were significantly decreased after ginsenoside-Rg1 treatment. Interestingly, both levels of glucocorticoid receptor (GR) and glutathione peroxidase (GPx) were increased after 72 hr Ginsenoside-Rg1 treatment, but no changed under room air control. The levels of oxidative stress-induced Bax and cytochrome c and apoptosis-related active caspase 3 and poly ADP-ribose polymerase were significantly increased after ginsenoside-Rg1 treatment under hyperoxic condition.Discussion and conclusion: In HUVECs model, Ginsenoside-Rg1 is unable to overcome the major hyperoxic-induced vascular endothelium injury. It might aggravate oxidative stress and endothelial apoptosis caused by oxygen toxicity. However, both elevated levels of GR and GPx indicate that Ginsenoside-Rg1 could be involved in vascular signaling and the regulation of oxidative stress under hyperoxia. Further investigation of Rg1 effects under hyperoxia is required.
Synthesis, Molecular Docking, And Antitumor Evaluation of Some New Pyrazole, Pyridine, And Thiazole Derivatives Incorporating Sulfonamide Residue
Authors: Elgogary Sameh , Radini Ibrahim
Published: August 2021

Cancer is the second leading cause of death worldwide. There is always a huge demand for novel anticancer. New series of pyrazole, pyridine, thiazole derivatives containing sulfonamide moiety were prepared and screened for their antitumor activity against breast cancer cell line (MCF-7). The results of this investigation revealed that compounds 3 and 8 had significant anticancer activity against the MCF-7 cancer cell line with IC50 values 19.2 and 14.2 μM, respectively, in relation to the standard drug, doxorubicin.
CD14 and LBP as Novel Biomarkers for Sarcoidosis by Proteomics of Extracellular Vesicles
Authors: Futami Yu , Takeda Yoshito , Koba Taro , Narumi Ryohei , Nojima Yosui , Ito Mari , Nakayama Mana , Ishida Mimiko , Yoshimura Hanako , Naito Yujiro , Fukushima Kiyoharu , Takimoto Takayuki , Edahiro Ryuya , Matsuki Tomonori , Nojima Satoshi , Hirata Haruhiko , Koyama Shohei , Iwahori Kota , Nagatomo Izumi , Shirai Yuya , Suga Yasuhiko , Satoh Shingo , Futami Shinji , Miyake Kotaro , Shiroyama Takayuki , Inoue Yoshikazu , Adachi Jun , Tomonaga Takeshi , Ueda Koji , Kumanogoh Atsushi
Published: August 2021

Sarcoidosis is an inflammatory granulomatous multi-organ disease of unknown cause. The granulomatous inflammation in sarcoidosis is driven by the interplay between T cells and macrophages. Extracellular vesicles (EVs) play important roles in intercellular communication. Isolated serum EVs from seven patients with sarcoidosis and five control subjects were subjected to non-targeted proteomics analysis. Then 2,292 proteins were detected; 42 proteins were upregulated in patients with sarcoidosis relative to control subjects, and 324 proteins were downregulated. The protein signature of EVs from patients with sarcoidosis reflected disease characteristics such as antigen presentation and immunological disease. Candidate biomarkers were further verified by targeted proteomics analysis in 46 patients and 10 control subjects. CD14 and lipopolysaccharide-binding protein (LBP) were validated by targeted proteomics analysis and upregulation of them was confirmed by immunoblotting. Their expression was also upregulated in macrophages of lung granulomatous lesions. Consistent with these findings, CD14 levels were increased in lipopolysaccharide-stimulated macrophages during multinucleation, concomitant with increased levels of CD14 and LBP in EVs. The area under the curve values of CD14 and LBP were 0.81 and 0.84, respectively. Thus CD14 and LBP in serum EVs, which are associated with granulomatous pathogenesis, can improve the diagnostic accuracy in patients with sarcoidosis.
Identification of Differential Gene Expression and Related Signaling Pathways In SARS-COV-2 Infected Human Cells
Authors: Xie Tian-Ao , Li Hou-He , Lin Zu-En , Lin Xiao-Ye , Meng Xin , Zhong Qi , Guo Xuguang
Published: August 2021

Background: The Corona Virus Disease 2019 (COVID-19) pandemic poses a serious public health threat to the survival and health of people all over the world. We analyzed related mRNA data and gene expression profiles of human cell lines infected with SARS-CoV-2 obtained from GEO (GSE148729), using bioinformatics tools. Differentially expressed genes (DEGs) of human cells infected with SARS-CoV-2 were identified.Method: The GSE148729 datasets were downloaded from the Gene Expression Omnibus (GEO) database. To explore the Biological significance of DEGs, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were constructed by using the STRING database. The hub genes were selected using the Cytoscape Software, and a t-test was performed to validate the hub genes.Result: A total of 1241 DEGs were screened, including 1049 up-regulated genes and 192 down-regulated genes. Besides, 10 hub genes were obtained from the PPI network, among which the expression level of CXCL2, Etv7, and HIST1H2BG was found to be statistically significant.Conclusion: In conclusion, bioinformatics analysis reveals genes and cellular pathways that are significantly altered in SARS-CoV-2 infected cells. This is conducive to further guide the clinical study of SARS-CoV-2 and provides new perspectives for vaccine development.
Enhanced glyoxylate shunt for efficient production of C4 derivatives using fatty acids feedstocks
Authors: Miao Yingchun , liu Jiao , wang Xuanlin , Liu Bo , Liu Weifeng , Tao Yong
Published: August 2021

Biosynthesis of TCA cycle-derived C4 chemicals through glyoxylate shunt is an attractive metabolic route because it can be drived by TCA-glyoxylate cycle force under aerobic conditions. However, yield of this route is low with at least 1/3 carbon loss from glucose. FAs could sufficiently provide acetyl-CoA by β-oxidation without carbon loss and directly enter the TCA-glyoxylate cycle, which is acknowledged as a promising alternative feedstock. Here β-alanine was selected as the target TCA cycle-derived chemical, of which the theoretical yield is 1.391 g/g FAs, much higher than that of glucose(0.49 g/g). By adopting multi-metabolic engineering strategies and relieving the active oxygen damage caused by FAs utilization, β-alanine production reached 78.05 g/L with a yield of 1.2 g/g, about 86% of theoretical yield. Our study establish a promising bioproduction route of β-alanine from waste FAs (such as gutter oil, palm fatty acid distillate etc.), and more importantly, provide an efficient platform for TCA cycle-derived C4 chemicals biosynthesis.
Epidemiological Comparison of Osteoporotic Hip Fractures in Spain and China: A Multicenter Study
Authors: Gao Shuai-Shuai , Capitan-Morales Luis C , Wang Yan-Jun , Yao Yong-Feng , Zhang Ya-Hui , Verdera Aurelio Borrás , Zhang Wen-Ting
Published: August 2021

Objective Compare the epidemiological differences of hip fracture patients in Spain and China. Materials and Method This was a retrospective study. The study population came from patients with hip fractures who underwent surgery between January 1, 2017 and December 30, 2017 at the University Hospital Virgen Macarena (UHVM) in Seville, Spain and Xi’an Daxing Hospital (XDH) in Shaanxi Province, China. Through medical history review and telephone follow-up, the differences of demographic and anthropometric characteristics, lifestyle, personal medical history, variables related to injury, anesthesia, and surgery, length of stay in hospital, days of bed rest, and mortality of patients in the two hospitals were compared. Results A total of 757 patients were enrolled, of which 426 were from UHVM and 331 were from XDH. The average age was 81.4±9.26 years and 76.0±8.08 years, respectively; the male and female distribution was 25.1% and 74.9% vs. 32.0% and 68.0%. The average BMI of Spanish patients was higher than that of Chinese patients. The proportion of drinking and smoking among Spanish patients was significantly higher than that of Chinese patients (p = 0.000, p = 0.000, respectively). The proportion of patients with ≥ 3 comorbidities in Spain was higher than that in China (p = 0.002). The surgery delay time of Spanish patients was significantly longer than that of Chinese patients (p = 0.000). Spanish patients had a shorter hospital stay, but a longer time in bed. During the one-year follow-up, there were 81 deaths in Spain and 43 deaths in China (p = 0.026). Conclusiones There are large epidemiological differences between hip fracture patients in Seville, Spain and Xi'an, China in terms of demographics, lifestyle, comorbidities, surgical methods, and mortality.
On the Greenspan Resonance of Meteotsunamis in the Yellow Sea - Insights from the Newly Discovered 2009 Event
Authors: Kim Jihwan , Choi Byoung-Ju , Omira Rachid
Published: August 2021

The Yellow Sea is recognized as a meteotsunami “hot-spot”, with a relatively high rate of events’ occurrence. The March 2007 and May 2008 meteotsunami events attracted large attention due to their deadly and high impact on the west coast of the Korean Peninsula. However, other small size meteotsunamis remain less known because of their insignificant coastal effect. Yet, a better understanding of meteotsunami hazard in the Yellow Sea requires thorough investigation of both large and small events. This paper reveals the occurrence of a meteotsunami on 11–12 June 2009 in the eastern Yellow Sea. It addresses the analyses of both the recorded sea-level and air-pressure data, the correlation between the atmospheric forcing and the meteotsunami formation, the numerical modeling of meteotsunami propagation, and the resonance effects on the recorded waves. Analysis results evidence a moving air-pressure jump of about 3 hPa that disturbed the sea surface and caused a meteotsunami with wave height up to 0.45 m (crest-to-trough). Both meteorological observations and numerical modeling suggest a speed of 11 to 13 m/s for the atmospheric disturbance propagation, which is much smaller than the optimal condition for Proudman resonance of meteotsunamis in the eastern Yellow Sea. Here, we demonstrate that the Greenspan resonance was responsible for amplifying the incident waves. Despite the insignificant coastal impact of the 11 June 2009 event, its investigation unravels new insights into the formation, amplification, and hazard extent of small size meteotsunamis in the Yellow Sea.
The Effects And Possible Mechanisms of Vortioxetine on Pentylenetetrazole-Induced Seizures In Rats
Authors: Taskiran Ahmet Sevki , Filiz Ahmet Kemal
Published: August 2021

Antidepressants are known to demonstrate various effects on the nervous system. As a new antidepressant, vortioxetine is used for major depression in adult patients, with no clear indication of epileptic seizures. Therefore, the aim here was to examine the impact of vortioxetine on pentylenetetrazole-induced epileptic seizures in rats. The rats were randomly divided into 5 groups, each with 6 rats. Group 1 was control, Group 2 was administered saline (1 mL/kg/day serum physiologic), Group 3 was given (1 mg/kg/day diazepam), and Groups 4 and 5 were administered vortioxetine (2.5 and 5 mg/kg/day). The experimental groups (Groups 2-5) were given the drugs for a total of 7 days. Pentylenetetrazole (45 mg/kg) was administered on day 7 to all but the control group. Behavioral testing was performed using the passive avoidance and open field tasks. Total antioxidant status (TAS), total oxidant status (TOS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1 β), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP) caspase-3, and caspase-9 levels were measured using a commercial kit. The groups receiving vortioxetine (2.5 mg/kg and 5 mg/kg) were found to have delayed epileptic seizure onset times and reduced seizure stages with improved memory impairment after seizures. These groups also had increased TAS levels and decreased TOS levels in the cortex and hippocampus. Additionally, TNF-α, IL-1 β, nNOS, sGC, cGMP, caspase-3, and caspase-9 levels in the cortex and hippocampus were statistically significantly lower for these groups. Vortioxetine was determined to have protective effects on pentylenetetrazole-induced seizures in rats, with alleviated seizures and improved memory impairment, oxidative stress, inflammation, and apoptosis. The mechanisms of vortioxetine may involve the inhibition of oxidative stress, inflammation, and the nNOS/sGC/cGMP signalling pathway.
Modified Levator Muscle Complex Suspension on Treating Pediatric Blepharoptosis with Poor Bell’s Phenomenon
Authors: Li Rui , Zhu Xiao-Wei , Zhang Jia-Ying , Ding Xia , Wu Xu-Sheng , Xing Yue , Lin Ming , Li Jin
Published: August 2021

Purpose: To evaluate the surgical outcomes of pediatric congenital blepharoptosis with poor Bell’s phenomenon (BP) treated with modified levator muscle complex suspension.Methods: Forty-two pediatric congenital blepharoptosis patients with poor BP were treated with modified levator muscle complex suspension, and their major surgical outcomes such as marginal reflex distance1 (MRD1), palpebral fissure height (PFH), and postoperative lagophthalmos were retrospectively reviewed. Results: The mean follow-up was 10.28±9.89 months (range: 3-32 Months). Surgical success was achieved in 54 (87.1%) of 62 eyelids at the final visit, including excellent results in 46 (74.2%) eyelids, good results in 8 (12.9%) eyelids, and poor results in 8 (12.9%) eyelids, respectively. The postoperative PFH of affected eyes (7.97±1.47 mm) was significantly improved compared with that before surgery (3.58±1.31 mm). The mean MRD1 was improved from -1.48±1.36 mm before surgery to 2.94±1.46 mm after surgery. The postoperative MRD1 was ≥ 3 mm in 46 eyelids and < 3 mm in 16 eyelids. The mean lagophthalmos was 1.42±1.20 mm 3 months after surgery. All of the patients presented complete blink postoperatively. Postoperative complications were rarely observed during follow-up. No patient had exposure keratitis, but blepharoptosis recurred in 6 patients (8 eyelids). All patients had satisfactory eyelid symmetry and contour. No complications were observed until the last visit.Conclusions: The modified method results complete blink, mild and quick recovery of lagophthalmos, flexible eyelid motility, stable ocular surface, and it is simple to perform with few complications and a low recurrence rate at 12.9%, which is worth to wide application on poor bell’s phenomenon blepharoptosis.
ACE2 Expression in Lungs of Severe COVID-19 Infection: A Study on Minimally Invasive Post- mortem Tissue Samples
Authors: Gheware Atish , Ray Animesh , Rana Deeksha , Bajpai Prashant , Nambirajan Aruna , Arulselvi S , Mathur Purva , Trikha Anjan , Arava Sudheer , Das Prasenjit , Mridha Asit Ranjan , Singh Geetika , Soneja Manish , Nischal Neeraj , Lalwani Sanjeev , Wig Naveet , Sarkar Chitra , Jain Deepali
Published: August 2021

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
Study of natural aging on nanoparticles and their strengthening effect in Al-Mg-Si alloy
Authors: Cui Zhenjie , Jiang Haichang , Zhang Duo , Song Yuanyuan , Yan Desheng , Rong Lijian
Published: August 2021

Atom probe tomography (APT) and transmission electron microscopy (TEM) were employed simultaneously to study nanoparticles and their strengthening effect in artificial aging (AA) Al-Mg-Si alloy with different natural aging (NA). We discovered that NA leads to formation of different type of nanoparticles meanwhile affect their fraction and dimension. Separation of the contribution from different types of nanoparticles to the alloy strength is conducted. In LNA-AA, β′ with a volume fraction of 0.16% contributions 54MPa to the yield strength while 0.14% β″ contributes 101MPa, which fully demonstrates that β″ is the main strengthening phase. The thermodynamic analysis was conducted for further research and the differential scanning calorimeter (DSC) results show that LNA forms more numerous clusters Ⅰ than SNA and consumes more vacancies and solute atoms then does not have enough driving force to precipitate clusters Ⅱ which are the nucleation sites of nanoparticles. When there is a certain distance between the nucleation sites, preferential growth of few β″ occur then converted to β′. The solute atoms in the region nearly which there is no nucleation site do not have enough driving force to diffuse and precipitate but stay in the matrix, reducing the volume fraction of the nanoparticles.
A Reverse Phase Protein Array Based Phospho-antibody Characterization Approach and Its Applicability for Clinical Derived Tissue Specimens
Authors: Wang Nan , Zhang Li , Ying Qi , Song Zhentao , Lu Aiping , Treumann Achim , Liu Zhaojian , Sun Tao , Ding Zhiyong
Published: August 2021

Background: Systematic quantification of phosphoprotein within cell signaling networks in solid tissues remains challenging and precise quantification in large scale samples has great potential for biomarker identification and validation. Methods:We developed a reverse phase protein array (RPPA) based phosphor-antibody characterization workflow by taking advantage of the lysis buffer compatible with alkaline phosphatase (AP) treatment and here termed it as a bottom-up antibody screening that differs from the conventional RPPA antibody validation procedure and applied it onto fresh frozen and formalin-fixed and paraffin-embedded tissue (FFPE) to test its applicability.Results:We tested the feasibility of this method by screening 106 phospho-antibodies with RPPA first followed by western blots on a panel of cell lines and demonstrated that AP treatment could serve as an independent factor that can be adopted for rapid RPPA phospho-antibody selection. We also performed studies on different clinical materials. For fresh frozen (FF) samples, pre-selected highly-specific antibodies showed a desirable data reproducibility and antibody specificity based on AP treatment indicating a potential for fresh tissue-based phospho-protein RPPA profiling. Of further clinical significance, using the same approach, based on two sets of FFPE samples from 63 melanoma and 40 lung cancer patients, we showed great interexperimental reproducibility and significant correlation with pathological markers MelanA for melanoma as well as a panel of lung cancer biomarkers for subtyping (EGFR, Napsin A, p63/p40, TTF1 and CK7) generating meaningful data that match clinical features. Conclusions:Our findings establish a highly efficient approach for phospho-antibody characterization by taking advantage of RPPA whereby the same methodology can be applied for tissue-based proteomics and phosphoproteomics in clinical assay development and application.
Epimedin B Through Enhancing NLRP3 Inflammasome Activation To Induces Idiosyncratic Hepatotoxicity
Authors: Gao Yuan , Shi Wei , Tu Can , Zhao Guanyu , Xu Guang , Xiao Xiaohe , Bai Zhaofang
Published: August 2021

Background: The NLRP3 inflammasome plays a crucial role in the pathogenesis of various human diseases, also idiosyncratic drug-induced liver injury (IDILI). Epimedii Folium (EF) is commonly used for treating bone fractures, joint diseases and some chronic illness, but the EF also could induce IDILI. Several studies have confirmed that EF may induce liver injury by upregulating the activity of the NLRP3 inflammasome. However, the major active constituents of EF have not been well-studied. Results: In the present study, we showed that epimedin B, a major active ingredient of EF, induced the development of IDILI by promoting the activation of the NLRP3 inflammasome. Synergistic induction of mitochondrial reactive oxygen species was a crucial contributor to the promoting effect of epimedin B observed on nigericin- or ATP-induced NLRP3 inflammasome activation. Importantly, epimedin B induced liver injury in the LPS-mediated susceptibility mouse model of IDILI，while specifical NLRP3 inhibitor MCC950 pretreatment completely abrogated the Caspase-1 activation and IL-1β secretion then couldn't induce liver injury. Conclusions: Epimedin B specifically facilitated nigericin- or ATP-induced NLRP3 inflammasome activation and the development of IDILI, which is responsible for EF-induced liver injury. These findings suggest that epimedin B is one of the key constituents of liver injury caused by EF，the content of epimedin B in EF may be a risk factor for IDILI, especially in patients with diseases related to nigericin- or ATP-induced NLRP3 inflammasome activation.
An updated Simpson-Based Method for Chatter Stability Prediction in Milling
Authors: Yan Zhenghu , Zhang Changfu , Jia Jianli , Ma Baoji , Jiang Xinguang , Wang Dong , Wang Wei , Yang Chenxi
Published: August 2021

An updated Simpson-based method (USBM) is presented for milling stability analysis. Firstly, the delay differential equation (DDE) is employed to describe the milling process mathematically. Then, the tooth passing period is divided into two subintervals, i.e., the free and forced vibration intervals. Only the forced vibration interval is divided into many equal small-time intervals. Subsequently, the DDE in the state space is solved based on direct integration. By combining the two-step Simpson method and the semi-discretization method, the state transition matrix of the milling system is constructed. The comparison of convergence rate is conducted to validate the accuracy of the proposed method. The results show that the proposed method converges faster than the benchmark methods. The stability lobe diagrams for the one degree of freedom (one-DOF) and two degrees of freedom (two-DOF) milling systems are also obtained by different methods for further evaluation. Meanwhile, the computation time analysis is also carried out. It is revealed that the proposed USBM has advantages in both accuracy and efficiency. Besides, the proposed method can accurately and efficiently predict the stability of milling with both large and low immersion conditions.
Genistein Enhances the Promoting Effects of Exercise on Anti-Oxidant and Anti- Inflammation Balance and Cardiomyopathy in the Ovariectomized Diabetic Rat
Authors: Nazari-Serenjeh Farzaneh , Vafaie Seyyed Alireza , Khajvand-Abedini Maryam , Salehi Amir Mohammad , Mohammadi Mohammad , Habibi Parisa
Published: August 2021

Purpose: These experiments aimed to analyze the effects of genistein and/or exercise on the expression of miRNA-133, IGF-1, and Bcl-2, Bax plus oxidative stress and inflammation markers in the heart of diabetic ovariectomized rats. Methods: Animals were divided into seven groups (n=8): control, sham, ovariectomy (OVX), diabetic ovariectomized (OD), and diabetic ovariectomized with eight weeks of genistein administration (ODG) and with eight weeks of swimming training (ODS) and with eight weeks of both of them (ODGS). High-fat nutrition and low dose streptozotocin injection were used for induction of diabetes. The effect of those treatments was evaluated by measuring lipid profiles, miRNA-133 gene expression, and Bcl-2, Bax, and IGF-1 protein expression levels. Inflammation and oxidative stress markers levels were also measured.Results: ovariectomy down-regulated cardiac miRNA-133, IGF-1, and Bcl-2 expression levels and increased MDA, OSI, TOS, TNF- α, and NF-κB levels plus a reduction in TAC. Diabetes induced an additive effect on the above-measured factors. Genistein improved oxidative and inflammation conditions and up-regulated miRNA-133, Bcl-2, and IGF-1 expression in OD rats. Genistein also enhanced the positive effect of exercise on miRNA-133, Bcl-2, and IGF-1expression in the heart, along with a reduction in Bax. The combined intervention was associated with improvement in oxidative and inflammation conditions. Histological observation showed some abnormality in cardiac tissue, which was improved by genistein or/and exercise treatment.Conclusion: genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac complications within the heart of ovariectomized rats.