Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of Macrophage Migration Inhibitory Factor Reduces Susceptibility to Ventricular Arrhythmias During the Acute Phase of Myocardial Infarction

Background Macrophages are involved in inflammatory responses and play a crucial role in aggravating ventricular arrhythmias (VAs) after myocardial infarction (MI). Macrophage migration inhibitory factor (MIF) participates in inflammatory responses during acute MI. In the present study, we hypothesized that knockout (KO) of MIF may prevent VAs during the acute phase of MI by inhibiting macrophage-derived pro-inflammatory mediators. Methods and Results We demonstrated that MIF-KO mice in a mouse model of MI exhibited a significant decrease in susceptibility to VAs both in vivo (84.6% vs 40.7%, P < 0.05) and ex vivo (86.7% vs 40.0%, P < 0.05) at day 3 after MI compared with that in wild-type (WT) mice. Both WT and MIF-KO mice presented similar left ventricular contractility, peri-infarct myocardial fibrosis and sympathetic reinnervation, and circulating and local norepinephrine levels during the acute phase of MI. Meanwhile, MIF-KO mice had inhibited macrophage aggregation, alleviated connexin 43 (Cx43) redistribution, and reduced level of pro-inflammatory mediators, including tumor necrosis factor-α and interleukin-1β (P < 0.05) at day 3 after MI. The differences in susceptibility to VAs, expression of pro-inflammatory mediators, and Cx43 redistribution after MI between WT and MIF-KO mice disappeared by macrophage depletion with clodronate liposomes in both groups. Furthermore, the pro-inflammatory activity of cultured peritoneal macrophages was inhibited by MIF deficiency and recovered with replenishment of exogenous MIF in vitro. Conclusion In conclusion, we found that lack of MIF reduced the susceptibility to VAs in mouse heart during the acute phase of MI by inhibiting pro-inflammatory activity of macrophages and improving gap-junction and electrical remodeling.
Genome-wide identification and expression pattern of SnRK gene family under several hormone treatments and its role in floral scent emission in Hedychium coronarium

The SnRK (Snf1-Related protein Kinase) gene family plays crucial roles in various plant signaling pathways and stress-adaptive responses including biotic and abiotic stresses via activating protein phosphorylation pathways. However, there is no information available on the role of the SnRK gene family in Hedychium coronarium. H. coronarium is an important crop widely cultivated as an ornamental plant, herb, spice, or condiment. In this study, 60 HcSnRK genes were identified from the H. coronarium genomic and transcriptome data. Phylogenetic and gene structure analysis showed that the HcSnRK genes were divided into three groups (HcSnRK1, HcSnRK2 and HcSnRK3) and among them HcSnRK3 subfamily was further subdivided into two clades according to the number of introns. Chromosome localization analysis showed that HcSnRK genes were unevenly mapped onto all chromosomes, and the Ka/Ks ratio of 24 paralogues includes four tandems and 20 segmental duplications indicated that the HcSnRK gene family underwent a purifying selection. Cis-regulatory elements analysis suggested that the HcSnRK genes respond to multiple hormones and other stresses. The responsiveness of HcSnRK genes to several hormones was analyzed by quantitative real-time PCR. Based on the different transcriptome data, two candidates HcSnRK genes (HcSnRK2.2 and HcSnRK2.9) were screened out for further characterization . The subcellular localization experiment revealed that both genes were located in the nucleus and cytoplasm. Moreover, virus-induced gene silencing (VIGS) of HcSnRK2.2 and HcSnRK2.9 significantly reduced the floral volatile contents by suppressing the expression of terpene synthase genes (HcTPS1, HcTPS3, and HcTPS5), indicating that HcSnRK2.2 and HcSnRK2.9 genes play an important role in the regulatory mechanism of floral aroma. These results will provide novel insights into the functional dissection of H. coronarium SnRK gene family.
Complete chloroplast genome sequence of a Chinese traditional cultivar in Chrysanthemum, Chrysanthemum morifolium ‘Anhuishiliuye’

Abstract The complete plastid genome of Chrysanthemum morifolium ‘Anhuishiliuye’, a Chinese traditional cultivar, was determined and analyzed in this work. It had a circular-mapping molecular with the length of 151,059 bp.The LSC and SSC of 82,857 bp and 18,294 bp were separated by two IRs of 24,954 bp. The chloroplast genome of C. morifolium ‘Anhuishiliuye’ contains 125 genes, including 83 protein-coding genes, 34 ribosomal RNA genes and 8 transfer RNA genes. Phylogenetic analysis showed that C. morifolium ‘Anhuishiliuye’ clustered together with other Chrysanthemum species. The data provided would be useful for elucidation of phylogenetics and evolution in Chrysanthemum cultivars.
RNA Interference-Mediated Aurora Kinase A Gene Silencing Inhibits Human Glioma Cells Proliferation and Tumor Growth in Mice

Objective: This study aims to explore the roles of Aurora Kinase A (Aurora A) in human glioma progression and relevant molecular mechanisms involved. Methods: RNA interference (RNAi) technology was performed to silence the Aurora A gene in human glioma cell line U251 and U87. Western blot and real-time PCR were used to determine the protein and mRNA expression levels of Aurora A. Flow cytometry was performed to analyze the cell cycle distribution and MTT was used to examine the cell viability. Annexin V/FITC double staining and Hoechst 33258 staining were carried out to examine cell apoptosis. Xenograft tumor model was established to examine the effect of Aurora A siRNA on tumor growth in vivo. Results: RNAi-mediated Aurora A gene silencing with specific short interfering RNA (siRNA) significantly decreased Aurora A protein and mRNA expression levels in human glioma cell line U251 and U87. Aurora A knockdown in glioma cells with siRNA strongly inhibited cell proliferation, along with the accumulation of cells in the G1, G2/M phase and decrease in S phase. Furthermore, the enhancement of cell apoptosis in vitro and the suppression of xenograft tumor growth in vivo were also observed after Aurora A silencing in U251 cell. In addition, Aurora A knockdown resulted in decreased expression of anti-apoptotic protein Bcl-2 and cell cycle protein Cyclin D1, while increased expression of pro-apoptotic factor caspase-3. Conclusion: Aurora A can be used as a candidate targeting gene and inhibition of Aurora A is a potentially promising therapy for glioblastoma.
Physiologically-based pharmacokinetic model for clozapine in Korean patients with schizophrenia

Clozapine has been used as a treatment of schizophrenia. Despite its large interindividual variability, few reports addressed the physiologically-based pharmacokinetic modeling and simulation (PBPK M&S) of clozapine in patients. This study aimed to develop a PBPK M&S of clozapine in Korean patients with schizophrenia. PBPK modeling for clozapine was constructed using a population-based PBPK platform, the SimCYP® Simulator (V19; Certara, Sheffield, UK). The PBPK model was developed by optimizing the physiological parameters of the built-in population and compound libraries in the SimCYP® Simulator. The model verification was performed with the predicted/observed ratio for pharmacokinetic parameters and visual predictive checks (VPCs) plot. Simulations were performed to predict toxicities according to dosing regimens. From published data, 230 virtual trials were simulated for each dosing regimen. The predicted/observed ratio for the area under the curve and peak plasma concentration was calculated to be from 0.78 to 1.34. The observation profiles were within the 5th and 95th percentile range with no serious model misspecification through the VPC plot. A significant impact on age and gender was found for clozapine clearance. The simulation results suggested that 150 mg twice a day and 150 mg three times a day of clozapine have toxicity concerns. In conclusion, a PBPK model was developed and reasonable parameters were made from the data of Korean patients with schizophrenia. The provided model might be used to predict the pharmacokinetics of clozapine and assist dose adjustment in clinical settings.
Evaluation of Corneal Epithelial Thickness and Dry Eye Disease Tests in Thalassemic Adolescents

Purpose To assess dry eye disease (DED) in thalassemic adolescents by evaluating corneal epithelial thickness (CET) and various dry eye clinical tests and correlate them to tissue iron overload. Methods The study included 120 Beta-thalassemia patients (11 to 18 years) and 120 matched controls. CET maps were captured using anterior segment optical coherence tomography. OSDI questionnaire was completed. Dry eye tests included Schirmer test, tear film breakup time ‎‎ (TBUT), and ocular surface staining (OSS) with fluorescein and lissamine green. We recorded serum ferritin ‎level, and liver iron concentration (LIC) measured by magnetic resonance imaging. Results Superior and inferior CET was thinner, while map standard deviation (MSD) was higher in thalassemics compared to controls (all P‎<0.001‎). Thalassemic group also showed higher OSDI scores‎ (P‎<0.001), shorter TBUT ‎‎(P‎<0.001‎), and higher OSS grades (P‎<0.001‎). Both superior and inferior CET was correlated positively with TBUT, and negatively with OSS (all P < 0.001). Serum ferritin and LIC showed negative correlations with CET (superior and inferior, both P< 0.001), positive correlations with MSD, P< 0.001, as well as with TBUT (P< 0.001), OSS ‎(P< 0.001), and OSDI scores (P< 0.001). Conclusion Thalassemic adolescents had thinner CET with higher thickness’ variability, shorter TBUT and more marked OSS‎ than controls. Correlation of higher serum ferritin and hepatic iron overload with irregular epithelial thinning and more affected dry eye tests results supports our hypothesis that high tissue iron levels could play a pivotal role in DED pathogenesis in thalassemic patients.
Predictors of adherence to option B+ approach for the prevention of mother to child transmission of human immunodeficiency virus in Abuja, 2017

Introduction option B+ ART is a lifelong regimen of ART using a combination of 3 ARVs and adherence to this regimen can reduce risk of MTCT to 1-2% as against 15-40% without treatment. To achieve an undetectable viral load and prevent the development of drug resistance, a person on ARV drugs need to take at least 95% of prescribed doses on time. This study assessed the level of adherence to Option B+ PMTCT program and its predictors among HIV+ Pregnant women accessing antenatal care in health facilities Abuja. Methods we enrolled 284 HIV positive pregnant women and lactating mothers in a hospital-based cross-sectional study. We sampled respondents using two-staged sampling technique. We collected data on socio-demographic characteristics, level of adherence, patients and healthcare related factors affecting adherence, knowledge of clients on HIV, ART and MTCT. Focused group discussion guide, data abstraction form and key informant interview guide were used for PMTCT focal persons. We conducted bivariate analysis and logistic regression using Epi-Info version 7 at 5% level of significance. Results the mean age of respondents was 30.12 years (SD±4.86) with mean knowledge score of 16.7 and 75.5%% of them had good knowledge. The level of good adherence was 83.3%. Independent factors associated with non-adherence to ART included: Forgetfulness (OR 20.02; 95% CI 6.42-62.48), having side effects (OR 39.6; 95% C.I: 4.46-352.32), lack of food (OR 34.76; 95% C.I: 2.37-509.33), disclosure of HIV status (OR 2.51; 95% CI 1.22-5.15), being too busy (OR 13.96; 95% CI 3.89-49.98). Encountering challenge in ART initiation (OR 2.05; 95% CI 1.01-4.72) and level of Knowledge (OR 2.12; 95% CI 1.06-5.42). Conclusion the level of adherence would improve study if the Public health department of Federal Ministry of Health (FMOH), Federal Capital Development Authority (FCDA) and National Agency for the Control of AIDS (NACA) sponsors public enlightenment on HIV/AIDS through the media which may help reduce stigma and encourage voluntary HIV status disclosure. Reminders should be used by patients to help them overcome forgetfulness.
Association of Endocrine Therapy and Dementia in Women with Breast Cancer

Purpose Prior studies have reported differing results regarding the association between endocrine therapy (ET) in the treatment of breast cancer and dementia risk. However, existing findings may be limited by common sources of bias and confounding. Here we investigate the association of ET utilized in the definitive setting to treat non-metastatic breast cancer with dementia risk accounting for multiple potential sources of bias and confounding. Patients and Methods We conducted a retrospective study in SEER-Medicare of women aged ≥ 66 years with non-metastatic breast cancer. We examined the risk of all-cause dementia among ET users versus non-ET users using multivariable regression models, accounting for the competing risk of death, and using a start of the follow-up period as 12-months following breast cancer diagnosis for both groups to avoid immortal time bias. Results Among 25,777 individuals there were 2,869 incident dementia cases. We found a statistically significantly decreased risk of any dementia among ET users in unadjusted and adjusted models that completely attenuated when accounting for the competing risk of death (hazard ratio, 0.98; 95% confidence interval, 0.90–1.07). Conclusion When accounting for common sources of bias and confounding we did not find evidence to support an association between ET in the definitive treatment of non-metastatic breast cancer and dementia risk. These results suggest that ET may not be associated with dementia risk.
Human papillomavirus, gene mutation and estrogen and progesterone receptors in breast cancer: a cross-sectional study

Introduction recent studies show a good relationship between breast cancer (BC) and human papillomaviruses (HPV) wich is responsible for about 18% of BC cases. This study aimed to assess the relationship between different genotypes of HPV and the expression of P53 and retinoblastoma (RB) genes and estrogen and progesterone receptors in BC among Sudanese women. Methods one hundred and fifty tissue blocks were obtained from females diagnosed with BC. Positive samples were used to determine genotypes with an applied biosystem (ABI 3730XL) genetic analyzer for sequencing and immunohistochemistry. Results 13/150 samples showed HPV DNA. High-risk HPV-16 was detected in 5 cases, high-risk-HPV-58 was found in four cases, and HPV-18 was detected in three cases. Low-risk-HPV-11 was detected in a single invasive lobular carcinoma (ILC) case. P53 and RB gene mutations were detected in 35 and 30 BC cases, respectively. P53 gene mutation was frequently identified in grade (III) BC while RB gene mutation was positive in grade (II). Grade (II) BC had a higher incidence of HPV-16 and 58. On the other hand, HPV-18 had a higher incidence in grade (III). Estrogen and progesterone receptors were expressed in 94 and 79 HPV cases among the study group, respectively. Conclusion this study elucidates the associations between HPV genotypes and BC. A statistically significant association was observed among p53 and RB gene mutations and different BC histological types. On the other hand, there was a statistically insignificant association between HPV genotyping and different BC gradings, BC histological types, P53 and RB genes mutations, and estrogen and progesterone receptor expression. Also, there was a statistically insignificant association among estrogen and progesterone receptors expression and BC grading. RB gene mutation was significantly associated with different BC grades. On the other hand, there was a statistically insignificant association between progesterone receptor expression and BC.
CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma

Objective To explore the immune cell therapy for T cell lymphoma, we developed CD4-specific chimeric antigen receptor- (CAR-) engineered T cells (CD4CART), and the cytotoxic effects of CD4CART cells were determined in vitro and in vivo. Methods CD4CART cells were obtained by transduction of lentiviral vector encoding a single-chain antibody fragment (scFv) specific for CD4 antigen, costimulatory factor CD28 fragment, and intracellular signal transduction domain of CD3 fragments. Control T cells were obtained by transduction of reporter lentiviral vector. The cytotoxicity, tumor growth, and survival rate of mice with T cell lymphoma were analyzed after adoptive T cell transfer in vivo. Results CD4CART cells had potent cytotoxic activity against CD4+ T1301 tumor T cells in a concentration-dependent manner. In addition, adoptive CD4CART cell transfer significantly suppressed tumor growth and improved animal survival with T cell lymphoma, compared to the mice who received control T cells and PBS. Conclusion CD4CART cells have potent cytotoxic effects on T cell lymphoma. The study provided an experimental basis for CD4CART-mediated therapy of T cell lymphoma.
Downregulation of RIPK4 Expression Inhibits Epithelial-Mesenchymal Transition in Ovarian Cancer through IL-6

RIPK4 has been implicated in multiple cancer types, but its role in ovarian cancer (OC) has not been clearly elucidated. Our data from Gene Expression Profiling Interactive Analysis, RT-PCR, and immunohistochemical analysis showed that RIPK4 was expressed at higher levels in OC tissues and cells than in normal ovarian tissues and cells. Increased RIPK4 expression in OC markedly correlated with a worse overall survival than lower RIPK4 expression levels (hazard rate (HR) 1.5 (1.45–1.87); P = 0.001). In functional experiments, RIPK4 downregulation significantly inhibited metastatic behaviours in OC cells. Subsequently, based on data from 593 OC patients in the TCGA database, gene set enrichment analysis revealed that RIPK4 was involved in epithelial-mesenchymal transition (EMT) in OC. At the molecular level, silencing RIPK4 significantly downregulated vimentin, N-cadherin, and Twist expression but induced an increase in the protein level of E-cadherin and inhibited the IL-6 and STAT3 levels. Moreover, IL-6 levels were significantly decreased in RIPK4-silenced OC cells (P < 0.05). The addition of IL-6 to OC cells rescued the suppressive effect of RIPK4 knockdown on EMT. Thus, our data illustrate that downregulation of RIPK4 expression can restrain EMT in OC by inhibiting IL-6. This finding may provide a novel diagnostic and therapeutic target for improving the poor prognoses of OC patients.
Settling taxonomic and nomenclatural problems in brine shrimps, Artemia (Crustacea: Branchiopoda: Anostraca), by integrating mitogenomics, marker discordances and nomenclature rules

High morphological plasticity in populations of brine shrimp subjected to different environmental conditions, mainly salinity, hindered for centuries the identification of the taxonomic entities encompassed within Artemia. In addition, the mismatch between molecular and morphological evolution rates complicates the characterization of evolutionary lineages, generating taxonomic problems. Here, we propose a phylogenetic hypothesis for Artemia based on two new complete mitogenomes, and determine levels of congruence in the definition of evolutionary units using nuclear and mtDNA data. We used a fossil of Artemia to calibrate the molecular clock and discuss divergence times within the genus. The hypothesis proposed herein suggests a more recent time frame for lineage splitting than previously considered. Phylogeographic analyses were performed using GenBank available mitochondrial and nuclear markers. Evidence of gen e flow, identified through discordances between nuclear and mtDNA markers, was used to reconsider the specific status of some taxa. As a result, we consider Artemia to be represented by five evolutionary units: Southern Cone, Mediterranean—South African, New World, Western Asian, and Eastern Asian Lineages. After an exhaustive bibliographical revision, unavailable names for nomenclatural purposes were discarded. The remaining available names have been assigned to their respective evolutionary lineage. The proper names for the evolutionary units in which brine shrimps are structured remain as follows: Artemia persimilis Piccinelli & Prosdocimi, 1968 for the Southern Cone Lineage, Artemia salina (Linnaeus, 1758) for the Mediterranean-SouthAfrican Lineage, Artemia urmiana Günther, 1899 for the Western Asian Lineage, and Artemia sinica Cai, 1989 for the Eastern Asian Lineage. The name Artemia monica Verrill, 1869 has nomenclatural priority over A. franciscana Kellogg, 1906 for naming the New World Lineage. New synonymies are proposed for A. salina (= C. dybowskii Grochowski, 1896 n. syn., and A. tunisiana Bowen & Sterling, 1978 n. syn.), A. monica (= A. franciscana Kellogg, 1906 n. syn., and A. salina var. pacifica Sars, 1904 n. syn.); A. urmiana (= B. milhausenii Fischer de Waldheim, 1834 n. syn., A. koeppeniana Fischer, 1851 n. syn., A. proxima King, 1855 n. syn., A. s. var. biloba Entz, 1886 n. syn., A. s. var. furcata Entz, 1886 n. syn., A. asiatica Walter, 1887 n. syn., A. parthenogenetica Bowen & Sterling, 1978 n. syn., A. ebinurica Qian & Wang, 1992 n. syn., A. murae Naganawa, 2017 n. syn., and A. frameshifta Naganawa & Mura, 2017 n. syn.). Internal deep nuclear structuring within the A. monica and A. salina clades, might suggest the existence of additional evolutionary units within these taxa.
Drug-Target Interaction Prediction via Dual Laplacian Graph Regularized Logistic Matrix Factorization

Drug-target interactions provide useful information for biomedical drug discovery as well as drug development. However, it is costly and time consuming to find drug-target interactions by experimental methods. As a result, developing computational approaches for this task is necessary and has practical significance. In this study, we establish a novel dual Laplacian graph regularized logistic matrix factorization model for drug-target interaction prediction, referred to as DLGrLMF briefly. Specifically, DLGrLMF regards the task of drug-target interaction prediction as a weighted logistic matrix factorization problem, in which the experimentally validated interactions are allocated with larger weights. Meanwhile, by considering that drugs with similar chemical structure should have interactions with similar targets and targets with similar genomic sequence similarity should in turn have interactions with similar drugs, the drug pairwise chemical structure similarities as well as the target pairwise genomic sequence similarities are fully exploited to serve the matrix factorization problem by using a dual Laplacian graph regularization term. In addition, we design a gradient descent algorithm to solve the resultant optimization problem. Finally, the efficacy of DLGrLMF is validated on various benchmark datasets and the experimental results demonstrate that DLGrLMF performs better than other state-of-the-art methods. Case studies are also conducted to validate that DLGrLMF can successfully predict most of the experimental validated drug-target interactions.