bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential drug delivery to tumor cells than normal cells using a tunable niosome–chitosan double package nanodelivery system: a novel in vitro model
Authors: Wiranowska Marzenna , Singh Rupin , Falahat Rana , Williams Eva , Johnson Joseph O. , Alcantar Norma 
Published: March 2020

Abstract
Background
We previously described the properties of a targeted drug delivery system (DDS) in a cell-free system. Here, in this comparative cell-based study (normal and tumor cells), we provide a quantitative analysis of the extracellular diffusion and intracellular localization of this DDS. This DDS consists of fluorescence-labeled paclitaxel encapsulated in non-ionic surfactant vesicles/niosomes embedded in a thermo-sensitive cross-linked chitosan hydrogel with an affinity for the MUC1 mucin surface antigen overexpressed on tumor cells, and designed for a sustained and controlled, localized delivery of embedded drugs. We evaluated DDS in our novel in vitro model using MatTek’ glass-bottom culture plates and compared human cancer cell lines (OV2008 epithelial origin carcinoma and U373 glioma, both overexpressing MUC1) with human normal epithelial control cell lines (IMMC3 and IOSE-121 using differential contrast and confocal microscopy.

Results
Tumor cells incubated in the presence of chitosan alone or DDS-containing chitosan–niosome–paclitaxel–BODIPY 564/570, showed a prominent granular accumulation on their surface when compared to the normal cells. Quantitation of gray value light intensity of the extracellular region of chitosan alone treated OV2008 and IOSE-121 controls done by analysis of multiple radial line segments, 4 µm each, using ImageJ software showed 2 times higher intensity around the OV2008 than around normal IOSE-121 controls (p < 0.05). In the DDS-treated OV2008 cells, extracellular fluorescence intensity measured at different diffusion distances outside of the cells, in three different zones showed the difference in means of fluorescence intensity in these zones (p < 0.05) with the highest level of fluorescence near the cell surface indicating a concentration gradient, most likely driven by the high affinity of chitosan to the MUC1 receptor. Also, as chitosan alone accumulated two times more along the edge of tumor cells compared to normal cells, we found intracellular fluorescence intensity quantified at time intervals to be also 2 times higher in OV2008 than in normal IMCC3 cells (p < 0.05).

Conclusion
Based on the observation of the DDS preferentially targeting tumor cells, there is a potential implication for the localized delivery of therapeutic drug doses to solid tumors or post-surgical solid tumors cavities containing residual tumor cells.
LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503
Authors: Zheng Hongyu , Wang Tingting , Li Xiangmin , He Wei , Gong Zhiqiang , Lou Zhenkai , Wang Bing , Li Xingguo 
Published: March 2020

AbstractBackgroundIntervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects.ResultsWe validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro,overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo,MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment.ConclusionOur data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.
The effect of antibiotics on the gut microbiome: a metagenomics analysis of microbial shift and gut antibiotic resistance in antibiotic treated mice
Authors: Xu Lei , Surathu Anil , Raplee Isaac , Chockalingam Ashok , Stewart Sharron , Walker Lacey , Sacks Leonard , Patel Vikram , Li Zhihua , Rouse Rodney 
Published: March 2020

Abstract
Background
Emergence of antibiotic resistance is a global public health concern. The relationships between antibiotic use, the gut community composition, normal physiology and metabolism, and individual and public health are still being defined. Shifts in composition of bacteria, antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) after antibiotic treatment are not well-understood.

Methods
This project used next-generation sequencing, custom-built metagenomics pipeline and differential abundance analysis to study the effect of antibiotic monotherapy on resistome and taxonomic composition in the gut of Balb/c mice infected with E. coli via transurethral catheterization to investigate the evolution and emergence of antibiotic resistance.

Results
There is a longitudinal decrease of gut microbiota diversity after antibiotic treatment. Various ARGs are enriched within the gut microbiota despite an overall reduction of the diversity and total amount of bacteria after antibiotic treatment. Sometimes treatment with a specific class of antibiotics selected for ARGs that resist antibiotics of a completely different class (e.g. treatment of ciprofloxacin or fosfomycin selected for cepA that resists ampicillin). Relative abundance of some MGEs increased substantially after antibiotic treatment (e.g. transposases in the ciprofloxacin group).

Conclusions
Antibiotic treatment caused a remarkable reduction in diversity of gut bacterial microbiota but enrichment of certain types of ARGs and MGEs. These results demonstrate an emergence of cross-resistance as well as a profound change in the gut resistome following oral treatment of antibiotics.
The genome-wide landscape of C:G > T:A polymorphism at the CpG contexts in the human population
Authors: Youk Jeonghwan , An Yohan , Park Seongyeol , Lee June-Koo , Ju Young Seok 
Published: March 2020

Abstract
Background
The C:G > T:A substitution at the CpG dinucleotide contexts is the most frequent substitution type in genome evolution. The mutational process is obviously ongoing in the human germline; however, its impact on common and rare genomic polymorphisms has not been comprehensively investigated yet. Here we observed the landscape and dynamics of C:G > T:A substitutions from population-scale human genome sequencing datasets including ~ 4300 whole-genomes from the 1000 Genomes and the pan-cancer analysis of whole genomes (PCAWG) Project and ~ 60,000 whole-exomes from the Exome Aggregation Consortium (ExAC) database.

Results
Of the 28,084,558 CpG sites in the human reference genome, 26.0% show C:G > T:A substitution in the dataset. Remarkably, CpGs in CpG islands (CGIs) have a much lower frequency of such mutations (5.6%). Interestingly, the mutation frequency of CGIs is not uniform with a significantly higher C:G > T:A substitution rate for intragenic CGIs compared to other types. For non-CGI CpGs, the mutation rate was positively correlated with the distance from the nearest CGI up to 2 kb. Finally, we found the impact of negative selection for coding CpG mutations resulting in amino acid change.

Conclusions
This study provides the first unbiased rate of C:G > T:A substitution at the CpG dinucleotide contexts, using population-scale human genome sequencing data. Our findings provide insights into the dynamics of the mutation acquisition in the human genome.
Identification, evolution and expression analyses of whole genome-wide TLP gene family in Brassica napus
Authors: Wang Tong , Hu Jingjing , Ma Xiao , Li Chunjin , Yang Qihang , Feng Shuyan , Li Miaomiao , Li Nan , Song Xiaoming 
Published: March 2020

AbstractBackgroundBrassicais a very important genus of Brassicaceae, including many important oils, vegetables, forage crops, and ornamental horticultural plants.TLPfamily genes play important regulatory roles in the growth and development of plants. Therefore, this study used a bioinformatics approach to conduct the systematic comparative genomics analysis ofTLPgene family inB. napusand other three important Brassicaceae crops.ResultsHere, we identified a total of 29TLPgenes fromB. napusgenome, and they distributed on 16 chromosomes ofB. napus.The evolutionary relationship showed that these genes could be divided into six groups from Group A to F. We found that the gene corresponding toArabidopsis thaliana AT1G43640was completely lost inB. rapa,B. oleraceaandB. napusafter whole genome triplication. The gene corresponding toAT1G25280was retained in all the three species we analysed, belonging to 1:3:6 ratios. Our analyses suggested that there was a selective loss of some genes that might be redundant after genome duplication. This study proposed that theTLPgenes inB. napusdid not directly expansion compared with its diploid parentsB. rapa, andB. oleracea. Instead, an indirect expansion ofTLPgene family occurred in its two diploid parents. In addition, the study further utilized RNA-seq to detect the expression pattern ofTLPgenes between different tissues and two subgenomes.ConclusionsThis study systematically conducted the comparative analyses ofTLPgene family inB. napus, discussed the loss and expansion of genes after genome duplication. It provided rich gene resources for exploring the molecular mechanism ofTLPgene family. Meanwhile, it provided guidance and reference for the research of other gene families inB. napus.
Characterising the mechanisms underlying genetic resistance to amoebic gill disease in Atlantic salmon using RNA sequencing
Authors: Robledo Diego , Hamilton Alastair , Gutiérrez Alejandro P. , Bron James E. , Houston Ross D. 
Published: March 2020

AbstractBackgroundGill health is one of the main concerns for Atlantic salmon aquaculture, and Amoebic Gill Disease (AGD), attributable to infection by the amoebaNeoparamoeba perurans,is a frequent cause of morbidity. In the absence of preventive measures, increasing genetic resistance of salmon to AGD via selective breeding can reduce the incidence of the disease and mitigate gill damage. Understanding the mechanisms leading to AGD resistance and the underlying causative genomic features can aid in this effort, while also providing critical information for the development of other control strategies. AGD resistance is considered to be moderately heritable, and several putative QTL have been identified. The aim of the current study was to improve understanding of the mechanisms underlying AGD resistance, and to identify putative causative genomic factors underlying the QTL. To achieve this, RNA was extracted from the gill and head kidney of AGD resistant and susceptible animals following a challenge withN. perurans, and sequenced.ResultsComparison between resistant and susceptible animals primarily highlighted differences mainly in the local immune response in the gill, involving red blood cell genes and genes related to immune function and cell adhesion. Differentially expressed immune genes pointed to a contrast in Th2 and Th17 responses, which is consistent with the increased heritability observed after successive challenges with the amoeba. Five QTL-region candidate genes showed differential expression, including a gene connected to interferon responses (GVINP1), a gene involved in systemic inflammation (MAP4K4), and a positive regulator of apoptosis (TRIM39). Analyses of allele-specific expression highlighted a gene in the QTL region on chromosome 17, cellular repressor of E1A-stimulated genes 1 (CREG1), showing allelic differential expression suggestive of a cis-acting regulatory variant.ConclusionsIn summary, this study provides new insights into the mechanisms of resistance to AGD in Atlantic salmon, and highlights candidate genes for further functional studies that can further elucidate the genomic mechanisms leading to resistance and contribute to enhancing salmon health via improved genomic selection.
The stringent response regulator (p) ppGpp mediates virulence gene expression and survival in Erwinia amylovora
Authors: Yang Ho-wen , Yu Menghao , Lee Jae Hoon , Chatnaparat Tiyakhon , Zhao Youfu 
Published: March 2020

Abstract
Background
The nucleotide second messengers, i.e., guanosine tetraphosphate and pentaphosphate [collectively referred to as (p) ppGpp], trigger the stringent response under nutrient starvation conditions and play an essential role in virulence in the fire blight pathogen Erwinia amylovora. Here, we present transcriptomic analyses to uncover the overall effect of (p) ppGpp-mediated stringent response in E. amylovora in the hrp-inducing minimal medium (HMM).

Results
In this study, we investigated the transcriptomic changes of the (p) ppGpp0 mutant under the type III secretion system (T3SS)-inducing condition using RNA-seq. A total of 1314 differentially expressed genes (DEGs) was uncovered, representing more than one third (36.8%) of all genes in the E. amylovora genome. Compared to the wild-type, the (p) ppGpp0 mutant showed down-regulation of genes involved in peptide ATP-binding cassette (ABC) transporters and virulence-related processes, including type III secretion system (T3SS), biofilm, and motility. Interestingly, in contrast to previous reports, the (p) ppGpp0 mutant showed up-regulation of amino acid biosynthesis genes, suggesting that it might be due to that these amino acid biosynthesis genes are indirectly regulated by (p) ppGpp in E. amylovora or represent specific culturing condition used. Furthermore, the (p) ppGpp0 mutant exhibited up-regulation of genes involved in translation, SOS response, DNA replication, chromosome segregation, as well as biosynthesis of nucleotide, fatty acid and lipid.

Conclusion
These findings suggested that in HMM environment, E. amylovora might use (p) ppGpp as a signal to activate virulence gene expression, and simultaneously mediate the balance between virulence and survival by negatively regulating DNA replication, translation, cell division, as well as biosynthesis of nucleotide, amino acid, fatty acid, and lipid. Therefore, (p) ppGpp could be a promising target for developing novel control measures to fight against this devastating disease of apples and pears.
Clinical and microbiological characteristics of Cryptococcus gattii isolated from 7 hospitals in China
Authors: Jin Liang , Cao Jing-Rong , Xue Xin-Ying , Wu Hua , Wang Li-Feng , Guo Ling , Shen Ding-Xia 
Published: March 2020

Abstract
Background
Infection, even outbreak, caused by Cryptococcus gattii (C. gattii) has been reported in Canada and the United States, but there were sparsely-reported cases of C. gattii in China. Our interest in occurrence, clinical manifestation, laboratory identification and molecular characterization of Chinese C. gattii strains leads us to this research.

Results
Out of 254 clinical isolates, initially identified as Cryptococcus neoformans (C. neoformans), eight strains were re-identified as C. gattii. Multi-locus sequence typing (MLST) showed genotype VGI accounted for the most (6 / 8), the other two strains were genotype VGII (VGIIa and VGIIb respectively) with 3 specific spectra of molecular weight about 4342, 8686, 9611 Da by MALDI-TOF MS. The minimal inhibitory concentrations (MICs) of Fluconazole with Yeast one was 2~4 times higher than that with ATB fungus 3 and MICs of antifungal agents against VGII strains were higher than against VGI strains. Comparative proteome analysis showed that 329 and 180 proteins were highly expressed by C. gattii VGI and VGII respectively. The enrichment of differentially expressed proteins was directed to Golgi complex.

Conclusions
Infection by C. gattii in China occurred sparsely. Genotype VGI was predominant but VGII was more resistant to antifungal agents. There was significant difference in protein expression profile between isolates of VGI and VGII C. gattii.
Identification and evolution of C4 photosynthetic pathway genes in plants
Authors: Shi Weiping , Yue Linqi , Guo Jiahui , Wang Jianming , Yuan Xiangyang , Dong Shuqi , Guo Jie , Guo Pingyi 
Published: March 2020

Abstract
Background
NADP-malic enzyme (NAPD-ME), and pyruvate orthophosphate dikinase (PPDK) are important enzymes that participate in C4 photosynthesis. However, the evolutionary history and forces driving evolution of these genes in C4 plants are not completely understood.

Results
We identified 162 NADP-ME and 35 PPDK genes in 25 species and constructed respective phylogenetic trees. We classified NADP-ME genes into four branches, A1, A2, B1 and B2, whereas PPDK was classified into two branches in which monocots were in branch I and dicots were in branch II. Analyses of selective pressure on the NAPD-ME and PPDK gene families identified four positively selected sites, including 94H and 196H in the a5 branch of NADP-ME, and 95A and 559E in the e branch of PPDK at posterior probability thresholds of 95%. The positively selected sites were located in the helix and sheet regions. Quantitative RT-PCR (qRT-PCR) analyses revealed that expression levels of 6 NADP-ME and 2 PPDK genes from foxtail millet were up-regulated after exposure to light.

Conclusion
This study revealed that positively selected sites of NADP-ME and PPDK evolution in C4 plants. It provides information on the classification and positive selection of plant NADP-ME and PPDK genes, and the results should be useful in further research on the evolutionary history of C4 plants.
Effect of arsenic stress on 5-methylcytosine, photosynthetic parameters and nutrient content in arsenic hyperaccumulator Pteris cretica (L.) var. Albo-lineata
Authors: Zemanová Veronika , Popov Marek , Pavlíková Daniela , Kotrba Pavel , Hnilička František , Česká Jana , Pavlík Milan 
Published: March 2020

Abstract
Background
Arsenic toxicity induces a range of metabolic responses in plants, including DNA methylation. The focus of this paper was on the relationship between As-induced stress and plant senescence in the hyperaccumulator Pteris cretica var. Albo-lineata (Pc-Al). We assume difference in physiological parameters and level of DNA methylation in young and old fronds as symptoms of As toxicity.

Results
The As accumulation of Pc-Al fronds, grown in pots of haplic chernozem contaminated with 100 mg As kg− 1 for 122 days, decreased with age. Content of As was higher in young than old fronds for variants with 100 mg As kg− 1 (2800 and 2000 mg As kg− 1 dry matter, respectively). The highest As content was determined in old fronds of Pc-Al grown in pots with 250 mg As kg− 1. The increase with age was confirmed for determined nutrients – Cu, Mg, Mn, S and Zn. A significant elevation of all analysed nutrients was showed in old fronds. Arsenic accumulation affected DNA methylation status in fronds, but content of 5-methylcytosine (5mC) decreased only in old fronds of Pc-Al (from 25 to 12%). Determined photosynthetic processes showed a decrease of fluorescence, photosynthetic rate and chlorophylls of As treatments in young and old fronds. Water potential was decreased by As in both fronds. Thinning of the sclerenchymatous inner cortex and a reduction in average tracheid metaxylem in the vascular cylinder was showed in roots of As treatment. Irrespective to fronds age, physiological parameters positively correlated with a 5mC while negatively with direct As toxicity. Opposite results were found for contents of Cu, Mg, Mn, S and Zn.

Conclusions
The results of this paper point to changes in the metabolism of the hyperaccumulator plant Pc-Al, upon low and high exposure to As contamination. The significant impact of As on DNA methylation was found in old fronds. Irrespective to fronds age, significant correlations were confirmed for 5mC and As toxicity. Our analysis of the very low water potential values and lignification of cell walls in roots showed that transports of assimilated metabolites and water between roots and fronds were reduced. As was showed by our results, epigenetic changes could affect studied parameters of the As hyperaccumulator plant Pc-Al, especially in old fronds.
Diffused hepatic angiosarcoma with Kasabach-Merritt syndrome-case report and literature review
Authors: Zhang Xing-mao , Tong Yao , Li Qing , He Qiang 
Published: March 2020

Abstract
Background
Hepatic angiosarcoma is a rare malignant tumor featured by highly aggressive behavior and poor prognosis. There are few reports about diffused hepatic angiosarcoma with Kasabach-Merritt syndrome till now.

Case presentation
A male patient with the chief complain of hepatic space-occupying lesion accompanied by disturbance of consciousness and jaundice. Hyperbilirubinemia, anemia, thrombocytopenia, prolonged prothrombin time, hypofibrinogenemia, decreased prothrombin activity, and increased fibrinogen degradation product and D-dimer were confirmed by blood analysis; multiple focal hypodense lesions in liver was detected by abdominal computed tomography. Liver failure and Kasabach-Merritt syndrome induced by hepatic hemangioma was diagnosed before operation and liver transplantation was performed. Hepatic angiosarcoma was finally proven by postoperative pathology. This patient died of tumor metastasis 2 months after operation.

Conclusions
Hepatic angiosarcoma which can generate Kasabach-Merritt syndrome and even liver failure has an extremely poor prognosis; liver transplantation option should not be considered in hepatic angiosarcoma regardless of the reason.