bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tolerance of repeated toxic injuries of murine livers is associated with steatosis and inflammation
Authors: Hammad Seddik , Ogris Christoph , Othman Amnah , Erdoesi Pia , Schmidt-Heck Wolfgang , Biermayer Ina , Helm Barbara , Piorońska Weronika , Gao Yan , D'Alessandro Lorenza , Theis Fabian , Ebert Matthias , Klingmüller Ursula , Hengstler Jan , Dooley Steven , Mueller Nikola 
Published: September 2022

Abstract
The human liver has a remarkable capacity to regenerate and thus compensate over decades for fibrosis caused by toxic chemicals, drugs, alcohol, or malnutrition. To date, no protective mechanisms have been identified that help the liver tolerate these repeated injuries. In this study, we revealed dysregulation of lipid metabolism and mild inflammation as protective mechanisms by studying longitudinal multi-omic measurements of liver fibrosis-induced by repeated CCl4 injections in mice (n = 45). Based on comprehensive proteomics, transcriptomics, blood- and tissue-level profiling, we uncovered three phases of early disease development - Initiation, Progression, and Tolerance. Using a novel multi-omic network analysis, we identified multi-level mechanisms that are significantly dysregulated in the injury-tolerant response. A public data analysis and shows that these profiles are altered in human liver diseases, including fibrosis and early cirrhosis stages. Our findings mark the beginning of the Tolerance phase as the critical switching point in liver response to repetitive toxic doses. After fostering extracellular matrix accumulation as an acute response, we observe a deposition of tiny lipid droplets in hepatocytes only in the Tolerant phase. Our comprehensive study shows that lipid metabolism and mild inflammation may serve as biomarkers and are putative functional requirements to resist further disease progression.
Determination of 5-Fluorouracil and Doxorubicin Concentrations Required for Effective Induction of Cytotoxicity and Morphological Responses in 3D Tumor Spheroids
Authors: Mutahar Adel Zaid I. , SALIMATH BHARATHI P 
Published: September 2022

Abstract
Introduction:
2-dimensional (2D) cell culture is commonly used for the evaluation of anticancer drugs, which is incapable of simulating the three dimensions (3D) microenvironment of the original tumors, therefore, a new pre-clinical platform for drug screening is urgently needed.
Material and Methods
MDA-MB231 cells were grown either as 2D- monolayers or 3-dimensional (3D) spheroids and treated with 5-FU or doxorubicin. Cytotoxicity assays were performed using trypan blue exclusion dye for 2D- monolayers and 3D spheroids. We have evaluated the efficacy of 5-fluorouracil (5-FU) and doxorubicin at different concentrations on the growth, size of the spheroids, induction of cytotoxicity and cell death over 10 days. Shapiro-Wilk test was used for normal distribution and two-way ANOVA for multiple group comparisons.
Results
2D- and 3D cultures responded with significant sensitivity toward the cytotoxic effect of 5-FU and doxorubicin. However, 3D spheroids were less sensitive to either of these drugs. The 3D spheroids exhibited significant variations in morphometric parameters in response to either 5-FU or doxorubicin treatment. The efficacy of doxorubicin was 1000-fold more effective than 5-FU over 10 days growth period of tumor spheroids. When compared to control spheroids both 5-FU and doxorubicin showed the presence of dead cells in the core of the spheroids as measured by live/dead assay.
Discussion and Conclusion:
Results indicated that 3D spheroid culture recapitulates in vivo tumor microenvironment and reflects the concentration of chemotherapeutic drugs required for effective treatment in cancer patients. Spheroid analysis using AnaSP/ReViSP could be further upgraded to include fluorescent stains within the workflow.
Intrahost variation in early monkeypox virus cases introduced to Finland, 2022
Authors: Vauhkonen Hanna , Kallio-Kokko Hannimari , Hiltunen-Back Eija , Lönnqvist Lasse , Leppäaho-Lakka Jaana , Mannonen Laura , Kant Ravi , Sironen Tarja , Kurkela Satu , Lappalainen Maija , Zorec Tomaž Mark , Zakotnik Samo , Vlaj Doroteja , Korva Miša , Avšič-Županc Tatjana , Poljak Mario , Smura Teemu , Vapalahti Olli 
Published: September 2022

Abstract
We report early importations of monkeypox virus to Finland during late May - early June 2022. Intrahost viral genome variation in one sample comprised a major variant with three lineage B.1.3-specific mutations and a minor variant with ancestral B.1 nucleotides, suggesting either ongoing APOBEC3-mediated evolution or coinfection.
Genetic Diversity and Runs of homozygosity analysis of Hetian Sheep Populations Revealed by Illumina OvineSNP50 BeadChip
Authors: Han Zhipeng , Zhou Wen , Zhang Lulu , Wang Ruotong , Liu Chunjie , Bai Xinyu , Liu Shudong 
Published: September 2022

Abstract
Background
Hetian sheep have a long history, a wide production area and rich genetic resources. Due to the different growing environment and feeding methods, wool, body shape and other traits also have some differences. Hetian sheep can be roughly divided into three groups, but the classification at the genome level is not clear.
Results
We randomly selected 84 healthy, adult ewes were randomly selected from three different ecological regions in Hetian area of Xinjiang, China. DNA was extracted from Ear tissues using phenol chloroform method to produce Illumina OvineSNP50 BeadChip. The SNP chip data were analyzed by Principal component analysis (PCA), neighbor-joining (NJ) phylogenetic and admixture for the population genetic structure of Hetian sheep, and the degree of population linkage was analyzed based on linkage disequilibrium (LD). Finally, the genetic region selection of Hetian sheep genetic germplasm resource populations in three different ecological environments was obtained by runs of homozygosity (ROH) analysis. The obtained candidate genes were annotated with Oar_v4.0 and enriched by GO and KEGG for analysis.Main screened 31 candidate genes adapting to high altitude environment were obtained in the Mountain type. Among them, Genes related to bone cell generation, differentiation and maintenance of bone homeostasis WNT6, WNT10A, CHSY1, etc. Genes related to tooth and tongue development LEF1, TP63, PRDM16, etc. Hearing and vision-related genes RBP4, ATF6, JAG1, etc. Main screened 22 candidate genes related to economic traits were obtained in the Grass type. Among them, Reproduction-related genes PLA2G4F, ACVR1, ADCY2, etc. Growth-related genes CAPN3, YAP1, FGF9, etc.
Conclusions
Hetian sheep can be classified into three subtypes at the genomic level: Mountain, Mountain-Grass and Grass types. The Grass type evolved from the Mountain type, and some of the Grass type further evolved into the Mountain-Grass type, and the genetic relationship between the Mountain-Grass type and Grass type was closest. Genetic structure and ROH analysis of Hetian sheep based on genomic microarray technology revealed the Mountain-Grass type strain. We enriched the genetic diversity of Hetian sheep germplasm resources, provided directions for Hetian sheep breed conservation, and found that genes related to multiparous trait exist in Mountain-Grass and Grass types Hetian sheep, which provides ideas for the selection and breeding of multiparous Hetian sheep.
The Causal Relationship Between Rheumatoid Arthritis and Pneumonia: A Mendelian Randomization Study
Authors: Luo Pan , Hou Weikun , Xu Ke , Liu Lin , Xu Peng 
Published: September 2022

Abstract
Background
At present, it is not clear whether there is a causal relationship between rheumatoid arthritis (RA) and pneumonia.
Method
Single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study (GWAS) of RA, were used as instrumental variables. Inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode and weighted mode methods were used to investigate causal effects. We applied MR-PRESSO methods and MR–Egger methods to investigate sensitivity. The heterogeneity of individual genetic variants was evaluated by Cochran's Q test and a leave-one-out analysis.
Results
Forty-two SNPs were selected as instrumental variables. The results of the IVW method were very significant (OR, 1.056 for pneumonia per log-odds increment in RA risk, 95% CI 1.034–1.077; p = 1.87E-07), and other methods were also statistically significant. The results of the IVW method showed a causal effect of genetically determined RA on pneumonia (critical care) (OR, 1.053, 95% CI 1.001–1.106; p = 0.044) but no causal effect of genetically determined RA on pneumonia (death) or pneumonia (28-day death in critical care)
Conclusions
The study showed that RA was associated with an increased risk of pneumonia, but it did not cause death or a need for critical care.
Subtype Classification based on Ferroptosis-related Genes and Signature for Predicting Outcomes in Cervical Cancer
Authors: Li Xinrong , Gong Han , Wang Pan , He Ling , Wang Jingjing , Feng Yeqian , Liu Jing , Zou Wen 
Published: September 2022

Abstract
BACKGROUND: Cervical cancer (CC) mainly relies on tumor stage to determine patient prognosis and guide treatment, but the prognosis of patients with the same stage still varies greatly. Ferroptosis, a novel iron-dependent programmed cell death, has been reported in a variety of tumors, but its impact on CC prognosis is currently uncertain. Herein, the express situation and prognostic value of ferroptosis-related genes (FRGs) in CC are explored by collecting public database and constructing a corresponding prognostic signature.
METHODS: Molecular data and corresponding clinicopathological data from the Cancer Genome Atlas-Cervical squamous cell carcinoma and endocervical adenocarcinoma (TCGA-CESC) cohort and the corresponding 10 Normal tissue samples of cervical canal from the Genotype-Tissue Expression (GTEx) database were collected. Applying univariate logistic regression analysis to identify prognostic FRGs. Subsequently, genes were further screened using differentially expressed genes (DEGs) and a prognostic model was constructed using the least absolute shrinkage and selection operator (LASSO)-COX stepwise regression. Finally, Validation of the risk model is achieved by using the corresponding data in the Gene Expression Omnibus (GEO) database of CC patients and clinical specimens from CC patients were collected for Quantitative reverse transcription PCR (qRT-PCR) validation.
RESULTS: Stepwise regression analysis identified five FRG features used to predict outcomes in patients with CC, and further divided patients into two subgroups. KM survival analysis showed that the prognosis of the two subgroups of patients was significantly different, and the Receiver operating characteristic (ROC) curve analysis verified the good specificity and accuracy of the signature. The model was externally validated with the GEO44001 cohort, and the results show that the model has good prognostic power. Finally, detection of clinical specimens by qRT-PCR demonstrated that five FRGs were significantly highly expressed in tumor samples than in normal samples.
CONCLUSION: A risk signature based on five FRGs validated to have excellent prognostic ability for CC patients. Our signature predicting outcomes in CC patients can contribute to targeted and personalized therapy for CC patients.
Vigna Legumes: Exploring Some Biochemical Constituents of the Wild Species for Potential Neo-Domestication Candidates
Authors: Harouna Difo Voukang , Ndakidemi Patrick Alois , Venkataramana Pavithravani B. , Matemu Athanasia O. 
Published: September 2022

Abstract
Due to the foresight of food system collapse, the search for alternative food and feed sources for human and animal nutrition becomes a daunting task. In addition, achieving Zero Hunger target by the year 2030 as set by the FAO is challenging. Re-exploring the less explored foods, coupled to refining less refined traits, cultivating the uncultivated, and popularizing the unpopular food crops are steps to achieve the domestication of wild plants for food and nutrition security. In that line of thought, this study explored the proximate composition of 87 accessions of four wild unexplored Vigna species in order to reveal information leading to their future domestication and utilization. Standard procedures and methods approved by AOAC were used in carrying out the proximate composition of the wild Vigna legumes. The study revealed that the wild Vigna species possess a large variation range of nutrient characteristics which could be exploited in the improvement of domesticated species or guide their domestication. It was also found that some individual wild accessions have higher nutrient, content as compared with domesticated ones which could be advantageous for bio-fortification or domestication. Indications relating to the candidate accessions favorable for domestication, based on the nutrient characteristics were revealed.
Ensifer meliloti denitrification is involved in infection effectiveness and N2O emissions by alfalfa root nodules
Authors: DELGADO Maria Jesus , Pacheco Pedro J , Bedmar Eulogio J , Mesa Socorro , Torosa German 
Published: September 2022

Abstract
Purpose: Ensifer meliloti, the endosymbiont of alfalfa, contains all the denitrification genes but the capacity of alfalfa root nodules to produce N2O is not known. In this work, N2O emissions as well as the influence of bacteroidal denitrification on nodulation competitiveness and N2O release from alfalfa nodules has been investigated.
Methods: Medicago sativa cv. Victoria plants were inoculated with E. meliloti 1021 and napA-, nap+ and nosZ- mutants. Plants were grown in the presence of different nitrate and copper treatments and subjected to flooding during one week before harvesting. MV+-NR and MV+-NIR enzymatic activities were measured in isolated bacteroids by analysing the capacity of the cells to produce or consume nitrite, respectively. Bacteroidal nitrous reductase (N2OR) activity was determined by measuring N2O consumption capacity. N2O was analysed by using a gas cromatograph.
Results: Alfalfa root nodules are able to produce N2O in response to nitrate and flooding. Overexpression of the periplasmic nitrate reductase (Nap) improved nodulation competitiveness and induced N2O emissions. The addition of Cu to the plant nutrient is required for an effective symbiosis as well as triggered a reduction of N2O production by alfalfa nodules due to the induction of the N2OR and a reduction of NIR activities in the bacteroids.
Conclusion: Alfalfa root nodules emit N2O. Nap is involved in nodulation competitiveness and in N2O emissions by the nodules. Bacteroidal N2OR and NIR activities are modulated by Cu and may be considered as effective targets for the mitigation strategies of N2O emissions derived from alfalfa crops.
Abnormal variations in expression of LRP5, β-catenin, OPG, RANKL and LGR4 in postmenopausal osteoporotic fractures
Authors: Wang Bin , Mai Caiyuan , Pan Lei 
Published: September 2022

Abstract
Background: The various osteogenesis and osteoclastogenesis factors including LRP5, β-catenin, OPG, RANKL and LGR4 have been associated with osteoporotic incidence, and can be regulated via the activation of diverse signaling pathways including Wnt/β-catenin, OPG/RANKL and LGR4/RANKL/RANK. This study aimed to analyze the expressions of the factors associated with these three pathways in postmenopausal osteoporotic fracture (PMOPF).
Methods: Patientswith proximal tibial fractures were first divided into control group and PMOPF group. Bone samples were obtained from them during surgery and the expressions of RNAs and proteins derived from the bone tissues were analyzed using RT-qPCR and Western Blot. It was observed that as the time of the collected peripheral serum changed, PMOPF group turned into groups A-F, whereas control group were also converted into groups A0-F0. The expression of the selected serum factors was analyzed using ELISA. We then analyzed significant differences in the expression of the factors between groups A-F and groups A0-F0. LRP5, β-catenin, OPG, and LGR4 were found to be underexpressed in PMOPF group, relative to control group, and they were underexpressed in groups A-F, relative to groups A0-F0 respectively. In contrast, RANKL was overexpressed in PMOPF group, and it was overexpressed in groups A-F, relative to groups A0-F0 respectively.
Results:LRP5 was expressed as the lowest level in group B (the third day after racture), whereas β-catenin was expressed as the lowest in group C (the seventh day after racture), on the contrary, RANKL was expressed as the highest level in group C and finally, OPG and LGR4 were expressed as the lowest in group E (the twenty-eighth day after fracture).
Conclusions:The Wnt/β-catenin, OPG/RANKL and LGR4/RANKL/RANK signaling pathways have been reported to be closely associated with the fracture development or repair in PMOPF. The factors changed at different time intervals in PMOPF patients, which could be potentially associated with the bone repair process in osteoporotic fractures.
Comprehensive Analysis of Circular RNAs in Porcine Small Intestine Epithelial Cells Associated with Susceptibility to Escherichia coli F4ac Diarrhea
Authors: Zhao Qingyao , Xu Qinlei , Serafino MA. , Zhang Qin , Wang Chuduan , Yu Ying 
Published: September 2022

Abstract
Background: Diarrhea is one of the most common diseases in pig industry, which seriously threatens the health of piglets and causes huge economic losses. Enterotoxigenic Escherichia coli (ETEC) F4 is regarded as the most important cause of diarrhea in piglets. Some pigs are naturally resistant to those diarrheas caused by ETEC-F4, because they have no F4 receptors (F4R) on their small intestine epithelial cells that allow F4 fimbriae adhesion. Circular RNA (circRNA) plays an important regulatory role in the pathogenesis of disease. However, the mechanism of circRNAs regulating Enterotoxigenic Escherichia coli F4 fimbriae (ETEC-F4ac) adhesion phenotype in small intestine epithelial cells of Large White piglets is still unclear. Hence, the present study assessed the circRNA expression profiling in small intestine epithelial cells of eight male piglets with different ETEC-F4 adhesion phenotypes and ITGB5genotypes to unravel their regulatory function in susceptibility to ETEC-F4ac diarrhea. Piglets were divided into two groups: non-adhesive group (n= 4) with CC genotype and adhesive group (n = 4) with TT genotype.
Results: The RNA-seq data analysis identified 13,199 circRNAs from eight samples, most of which were exon-derived. In the small intestine epithelial cells, 305 were differentially expressed (DE) circRNAs between the adhesive and non-adhesive groups; of which 46 circRNAs were upregulated, and 259 were downregulated. Gene ontology and KEGG enrichment analysis revealed that most significantly enriched DE circRNAs’ host genes were linked to cytoskeletal components, protein phosphorylation, cell adhesion, ion transport and pathways associated with ETEC diarrhea. The circRNA-miRNA-mRNA interaction network was also constructed to elucidate their underlying regulatory relationships. Our results identified several candidate circRNAs that affects susceptibility to ETEC diarrhea. Among them, circ-SORBS1 can adsorb ssc-miR-345-3p to regulate the expression of its host gene SORBS1, thus improving cell adhesion.
Conclusion: Our results provided insights into the regulation function of circRNAs in susceptibility to ETEC diarrhea of piglets, and enhanced our understanding of the role of circRNAs in regulating ETEC diarrhea, and reveal the great potential of circRNA as a diagnostic marker for susceptibility of ETEC diarrhea in piglets.
Localization-enhanced moiré exciton in twisted transition metal dichalcogenide heterotrilayer superlattices
Authors: LIU Yanping , Zheng Haihong , Wu Biao , Li Shaofei , Ding Junnan , He Jun , Liu Zongwen , Wang Chang-Tian , Wang Jian-Tao , Pan Anlian 
Published: September 2022

Abstract
Moiré superlattice created by the stacking of twisted 2D layered materials have become a new platform for the study of quantum optics. The strong coupling of moiré superlattices can generate flat minibands that enhance electronic interactions and produce a variety of fascinating strongly correlated states such as non-conventional superconductivity, Mott insulating states and moiré excitons. However, the influence between the adjustment and localization of moiré excitons in Van der Waals heterostructures has not been the subject of experimental investigations. Here we report experimental evidence of the localization-enhanced moiré excitons in the twisted WSe2/WS2/WSe2 heterotrilayer with type-II band alignments. At low temperature, we observed multiple excitons splitting phenomena in the twisted WSe2/WS2/WSe2 heterotrilayer, manifesting as multiple sharp emission lines, contrasting strongly with the moiré excitonic behavior of the twisted WSe2/WS2 heterobilayer (the linewidth is 4 times narrower). This is primarily because the enhancement of the two moiré potentials in the twisted heterotrilayer enables the moiré excitons at the highly localized interface. Furthermore, the changes in temperature, laser power and valley polarization further demonstrate the confinement effect of moiré potential on moiré excitons. Our findings provide a new way for the localization of moiré excitons in twist-angle heterostructures, facilitating the development of coherent quantum light emitters.
The Structural Analysis of Driving Forces to Adaptive Capacity with Climate Change in Ahvaz City. Iran
Authors: dehcheshmeh mostafa mohammadi , Ghaedi Sohrab , Shanbehpour Fereshteh 
Published: September 2022

Abstract

Climate change is an increasing concern for national and local governments around the world. The severity of the natural disasters affected by these changes has led to negative impacts on various economic, social and environmental dimensions in cities. One of the important global strategies in responding to the adverse effects of climate change is the adaptation strategy. The aim of this study is to identification and structural modeling of driving forces for adaptation to climate change according to the special geography of Ahvaz city as a strategic city in southwest of Iran. After identifying the factors and indicators through the study of records and a survey of the elite group, analysis and stratification was done using the combined ISM-DEMATEL model and finally the main driving forces of adapting to climate change in Ahvaz were identified by Mic-Mac Structural Model. The research findings have shown: among the five economic, social, institutional, physical and technological factors, the economy has known as the most effective factor in adapting to climate change in Ahvaz. Also, among the 44 selected indicators, 10 important driving forces were selected that 6 driving forces, have the economic and social background. Based on cross-impact analysis by Mic-Mac; the financial support for vulnerable groups, business improvement, alleviation poverty measures, diversification of economic activities, social cohesion and social trust to government were recognized as the main drivers of Ahvaz city's adaptation to climate change.