Zearalenone Promotes Cell Proliferation or Causes Cell Death?

Citation: Zheng, W.; Wang, B.; Li, X.; Wang, T.; Zou, H.; Gu, J.; Yuan, Y.; Liu, X.; Bai, J.; Bian, J.; Liu, Z. Zearalenone Promotes Cell Proliferation or Causes Cell Death? Toxins 2018, 10, 184.Zearalenone (ZEA), one of the mycotoxins, exerts different mechanisms of toxicity in different cell types at different doses. It can not only stimulate cell proliferation but also inhibit cell viability, induce cell apoptosis, and cause cell death. Thus, the objective of this review is to summarize the available mechanisms and current evidence of what is known about the cell proliferation or cell death induced by ZEA. An increasing number of studies have suggested that ZEA promoted cell proliferation attributing to its estrogen-like effects and carcinogenic properties. What’s more, many studies have indicated that ZEA caused cell death via affecting the distribution of the cell cycle, stimulating oxidative stress and inducing apoptosis. In addition, several studies have revealed that autophagy and some antioxidants can reverse the damage or cell death induced by ZEA. This review thoroughly summarized the metabolic process of ZEA and the molecular mechanisms of ZEA stimulating cell proliferation and cell death. It concluded that a low dose of ZEA can exert estrogen-like effects and carcinogenic properties, which can stimulate the proliferation of cells. While, in addition, a high dose of ZEA can cause cell death through inducing cell cycle arrest, oxidative stress, DNA damage, mitochondrial damage, and apoptosis

Oxymatrine and Cisplatin Synergistically Enhance Anti-tumor Immunity of CD8+ T Cells in Non-small Cell Lung Cancer

Oxymatrine (OMT) has shown broad antitumor activities for the treatment of several types of cancers. However, little is known about its effect on anti-tumor immunity. Combination therapy is a potentially promising strategy of cancer to enhance anticancer activity, overcome drug resistance, and lower treatment failure rate. In the present study, we demonstrated that the combination of OMT with cisplatin (DDP) synergistically inhibited non-small cell lung cancer (NSCLC) cells growth when co-cultured with peripheral blood mononuclear cells in vitro. Furthermore, the combination of OMT with DDP significantly inhibited the growth of Lewis lung cancer (LLC) mouse xenograft tumors. Flow cytometry analysis revealed that OMT and DDP synergistically increase the CD8+/ regulatory T cells ratio and enhanced more CD8+ T cells secreted cytokines of IFN-γ, TNF-α, and IL-2 in vivo. Mechanistically, upregulation of miR-155 and downregulation of suppressor of cytokine signaling-1 (SOCS1) were confirmed as a target signaling pathway to positively regulate the anti-tumor response of CD8+ T cells. Overall, OMT in combination with DDP showed outstanding synergistic anti-tumor immunity, suggesting that this beneficial combination may offer a potential immunotherapy for NSCLC patients

The Euscaphis japonica genome and the evolution of malvids

Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the c event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.DATA AVAILABILITY STATEMENT : All sequences described in this manuscript have been submitted to the National Genomics Data Center (NGDC). The raw whole-genome data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005268/CRA004271, and the assembly and annotation data have been deposited at BioProject/GWH (https://bigd.big.ac.cn/gwh) under the accession codes PRJCA005268/GWHBCHS00000000. The raw transcriptomes data of E. japonica have been deposited in BioProject/GSA (https://bigd.big.ac.cn/gsa.) under the accession codes PRJCA005298/CRA004272.SUPPLEMENTARY MATERIAL 1: Supplementary Note 1. Chromosome number assessment. Supplementary Note 2. Whole-genome duplication identification and dating. Supplementary Note 3. Observation of E. japonica seed dispersal. Supplementary Note 4. Determination of pentacyclic triterpene substances. Figure S1. Cytogenetic analysis of E. japonica. Figure S2. Genome size and heterozygosity of E. japonica estimation using 17 k-mer distribution. Figure S3. Interchromosomal of Hi-C chromosome contact map of E. japonica genome. Figure S4. Gene structure prediction results of E. japonica and other species. Figure S5. Venn diagram shows gene families of malvids. Figure S6. Phylogenetic tree constructed by chloroplast genomes from 17 species. Figure S7. Concatenated- and ASTRAL-based phylogenetic trees. Figure S8. Ks distribution in E. japonica. Figure S9. Distributions of synonymous substitutions per synonymous site (Ks) of one-to-one orthologs identified between E. japonica and P. trichocarpa and V. vinifera. Figure S10. Population structure plot. Figure S11. Fixation index (FST) heat map among E. japonica populations. Figure S12. Phylogenetic analysis of MADS-box genes from O. sativa, A. thaliana, E. japonica, and T. cacao. Figure S13. Observation the fruit development. Figure S14. Animal seed dispersal. Figure S15. Anthocyanin biosynthesis in E. japonica fruits. Figure S16. Carotenoid accumulation and the chlorophyll degradation in E. japonica fruits. Figure S17. Expression profile of fruit dehiscence-related genes. Figure S18. Phylogenetic tree of DELLA genes obtained from six malvids species. Figure S19. Phylogenetic tree of CAD genes obtained from seven malvids species. Figure S20. Expression pattern of fruit abscission-related genes. Figure S21. Structure of pentacyclic triterpene compounds separated from Euscaphis. Figure S22. Phylogenetic tree of HMGR gene in plants. Figure S23. Phylogenetic tree of P450s gene family obtained from A. thaliana and E. japonica.SUPPLEMENTARY MATERIAL 2: Table S1. Assembled statistics of E. japonica genome. Table S2. Evaluation of E. japonica genome assembly. Table S3. Chromosome length of E. japonica. Table S4. Prediction of gene structures of the E. japonica genome. Table S5. Statistics on the function annotation of the E. japonica genome. Table S6. Non-coding RNA annotation results of E. japonica genome. Table S7. BUSCO assessment of the E. japonica annotated genome. Table S8. Statistic of repeat sequence in E. japonica genome. Table S9. Gene-clustering statistics for 17 species. Table S10. KEGG enrichment result of unique genes families of E. japonica. Table S11. Gene Ontology (GO) and KEGG enrichment result of significant shared by malvids species gene families. Table S12. Gene Ontology (GO) and KEGG enrichment result of significant expansion of E. japonica gene families. Table S13. Gene Ontology (GO) enrichment result of significant contraction of E. japonica gene families. Table S14. Statistical sampling population information. Table S15. Statistics population resequencing information. Table S16. Statistical nucleotide polymorphisms in the populations. Table S17. Candidate positive selection genes (PSGs) in the evergreen population. Table S18. Candidate positive selection genes (PSGs) in the deciduous population. Table S19. Gene Ontology (GO) enrichment result of significant PSGs in the evergreen population. Table S20. List of MADS-box genes identified in E. japonica. Table S21. Genes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and chlorophyll degradation. Table S22. Identification fruit dehiscence-related genes in E. japonica. Table S23. Genes related to lignin synthesis that are highly expressed during pericarp dehiscence. Table S24. Gene expression levels (FPKMs) of fruit abscission-related genes in pericarp. Table S25. Triterpene compounds separated from Euscaphis. Table S26. Number of putative pentacyclic triterpene-related genes in the malvids species. Table S27. Identified pentacyclic triterpene synthesis-related genes in E. japonica genome. Table S28. Statistical simple sequence repeat.Fund for Excellent Doctoral Dissertation of Fujian Agriculture and Forestry University, China; Fujian Provincial Department of Science E. japonica Evolution and Selection of Ornamental Medicinal Resources, China; the Project of Forestry Peak Discipline at Fujian Agriculture and Forestry University, China; the Collection, Development and Utilization of Eascaphis konlshli Germplasm Resources; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program and from Ghent University.https://onlinelibrary.wiley.com/journal/1365313xam2022BiochemistryGeneticsMicrobiology and Plant Patholog

Associations of long-term visit-to-visit blood pressure variability with subclinical kidney damage and albuminuria in adulthood: a 30-year prospective cohort study

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood. Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g. Results: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP, ARVMAP, and ARVPP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up. Conclusions: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve