Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple.

Fusarium pathogens cause two major diseases in cereals, Fusarium crown rot (FCR) and head blight (FHB). A large-effect locus conferring resistance to FCR disease was previously located to chromosome arm 3BL (designated as Qcrs-3B) and several independent sets of near isogenic lines (NILs) have been developed for this locus. In this study, five sets of the NILs were used to examine transcriptional changes associated with the Qcrs-3B locus and to identify genes linked to the resistance locus as a step towards the isolation of the causative gene(s). Of the differentially expressed genes (DEGs) detected between the NILs, 12.7% was located on the single chromosome 3B. Of the expressed genes containing SNP (SNP-EGs) detected, 23.5% was mapped to this chromosome. Several of the DEGs and SNP-EGs are known to be involved in host-pathogen interactions, and a large number of the DEGs were among those detected for FHB in previous studies. Of the DEGs detected, 22 were mapped in the Qcrs-3B interval and they included eight which were detected in the resistant isolines only. The enrichment of DEG, and not necessarily those containing SNPs between the resistant and susceptible isolines, around the Qcrs-3B locus is suggestive of local regulation of this region by the resistance allele. Functions for 13 of these DEGs are known. Of the SNP-EGs, 28 were mapped in the Qcrs-3B interval and biological functions for 16 of them are known. These results provide insights into responses regulated by the 3BL locus and identify a tractable number of target genes for fine mapping and functional testing to identify the causative gene(s) at this QTL.

Fatty liver disease is one of the leading causes of chronic damage in western countries. Approximately 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease (NAFLD). Little is known about the prevalence and genetic background of NAFLD or the factors that determine its development. In this study, we used the Gene-Cloud of Biotechnology Information bioinformatics platform to carry out a comprehensive bioinformatics analysis identifying differentially expressed genes (DEGs), key biological processes and intersecting pathways. We imported 3 Gene Expression Omnibus datasets (GSE31803, GSE49541, and GSE63067). Then, we assessed the expression of the DEGs in clinical samples. We found that CD24 was the only gene co-expressed in all 3 datasets. "Glycolysis/gluconeogenesis", "p53 signaling pathway" and "glycine, serine and threonine metabolism" were 3 common pathways related to the fatty liver process. In NAFLD tissues, CD24, COL1A1, LUM, THBS2 and EPHA3 were upregulated, and PZP was downregulated. CD24 is a core gene among these DEGs and have not yet been studied of its impact on NAFLD. Co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in NAFLD progression. Further studies are needed to elucidate the mechanism of these potential genes and pathways in NAFLD.

As a cleavage enzyme of precursor TNF-α, the high expression level of ADAM17 in endothelial cells is an important factor in atherosclerosis. In this study, we demonstrate that ADAM17 is the target of miR-152. We found that miR-152 could reduce TNF precursor cleavage and inhibit cell proliferation and migration by targeting ADAM17 in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression pattern of miR-152 and corresponding target ADAM17 was opposite in HUVECs under hypoxic conditions. The levels of circulating miR-152 in AS patient sera were lower than those detected in the sera of normal individuals. Our results indicate that miR-152 may be involved in the development of human atherosclerosis and could be used as diagnostic biomarker or therapeutic target in atherosclerosis.

MicroRNAs (miRNAs) are a class of non-coding small RNAs that consist of ≈ 22 nt and are involved in several biological processes by regulating target gene expression. MiR-138 has many biological functions and is often downregulated in cancers. Our results showed that overexpression of miR-138 downregulated target RMND5A (required for meiotic nuclear division 5 homolog A) and reduced Exportin-5 stability, which results in decreased levels of pre-miRNA nuclear export in HeLa cells. We also found that miR-138 could significantly inhibit HeLa cell migration by targeting RMND5A. Our study therefore identifies miR-138-RMND5A-Exportin-5 as a previously unknown miRNA processing regulatory pathway in HeLa cells.

Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3'-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.

Mapping chromosome regions responsible for quantitative phenotypic variation in recombinant populations provides an effective means to characterize the genetic basis of complex traits. We conducted a quantitative trait loci (QTL) analysis of 150 rice recombinant inbred lines (RILs) derived from a cross between two cultivars, Oryza sativa ssp. indica cv. 93-11 and Oryza sativa ssp. japonica cv. Nipponbare. The RILs were genotyped through next-generation sequencing, which accurately determined the recombination breakpoints and provided a new type of genetic markers, recombination bins, for QTL analysis. We detected 49 QTL with phenotypic effect ranging from 3.2 to 46.0% for 14 agronomics traits. Five QTL of relatively large effect (14.6-46.0%) were located on small genomic regions, where strong candidate genes were found. The analysis using sequencing-based genotyping thus offers a powerful solution to map QTL with high resolution. Moreover, the RILs developed in this study serve as an excellent system for mapping and studying genetic basis of agricultural and biological traits of rice.

Thrombin-binding aptamer (TBA) is a DNA 15-mer of sequence 5'-GGT TGG TGT GGT TGG-3' that folds into a G-quadruplex structure linked by two T-T loops located on one side and a T-G-T loop on the other. These loops are critical for post-SELEX modification to improve TBA target affinity. With this goal in mind we synthesized a T analog, 5-(indolyl-3-acetyl-3-amino-1-propenyl)-2'-deoxyuridine (W) to substitute one T or a pair of Ts. Subsequently, the affinity for each analog was determined by biolayer interferometry. An aptamer with W at position 4 exhibited about 3-fold increased binding affinity, and replacing both T4 and T12 with W afforded an almost 10-fold enhancement compared to native TBA. To better understand the role of the substituent's aromatic moiety, an aptamer with 5-(methyl-3-acetyl-3-amino-1-propenyl)-2'-deoxyuridine (K; W without the indole moiety) in place of T4 was also synthesized. This K4 aptamer was found to improve affinity 7-fold relative to native TBA. Crystal structures of aptamers with T4 replaced by either W or K bound to thrombin provide insight into the origins of the increased affinities. Our work demonstrates that facile chemical modification of a simple DNA aptamer can be used to significantly improve its binding affinity for a well-established pharmacological target protein.

Neuroblastomas (NBs) exhibit heterogeneity and show clinically significant prognosis classified by genetic alterations. Among prognostic genes or genome factors, MYCN amplification (MNA) is the most established genomic marker of poor prognosis in patients with NB. However, the prognostic classification of more than 60% of patients without MNA has yet to be clarified. In this study, the application of target next-generation sequencing (NGS) was extended on the basis of a comprehensive panel of regions where copy number variations (CNVs) or point mutations occurred to improve the prognostic evaluation of these patients and obtain the sequence of 33 patients without MNA. A mean coverage depth of 887× was determined in the target regions in all of the samples, and the mapped read percentage was more than 99%. Somatic mutations in patients without MNA could be precisely defined on the basis of these findings, and 17 unique somatic aberrations, including 14 genes, were identified in 11 patients. Among these variations, most were CNVs with a number of 13. The 3-year event-free survival (EFS) of CNV(-) patients was 60.0% compared with the EFS (16.7%) of CNV(+) patients (P = 0.015, HR = 0.1344, 95%, CI = 0.027 to 0.678). CNVs were also associated with unfavorable histological characteristics (P = 0.003) and likely to occur in stage 4 (P = 0.041). These results might further indicate the role of CNVs in NB chemotherapy resistance (P = 0.059) and show CNVs as a therapeutic target. In multivariate analysis, the presence of CNVs was a clinically negative prognostic marker that impaired the outcome of patients without MNA and associated with poor prognosis in this tumor subset. Comprehensive genetic/genomic profiling instead of focusing on single genetic marker should be performed through in-depth NGS that could reveal prognostic information, improve NB target therapy, and provide a basis for investigations on NB pathogenesis.

NAC transcription factors play important roles in the regulation of plant growth, development, abiotic and biotic stress responses. The transcriptional level of MdNACs in different tissues and under various biotic and abiotic stress treatments was determined to provide a solid foundation for studying the function of MdNACs.

During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease.

Escherichia coli is an opportunistic bacterial pathogen that causes a wide range of nosocomial infections. The emergence of multidrug resistance in E. coli poses a severe threat to global health. Phage therapies are an alternative method to control multidrug-resistant pathogens, which have been attracting increasing attention. Owing to their ability to lyse bacteria specifically and efficiently, bacteriophages are considered novel antimicrobial agents. In this study, we used multidrug-resistant E. coli as an indicator and isolated, characterized, and compared two new phages of the Siphoviridae family referred to as vB_EcoS_XF and vB_EcoS_XY2. These phages were able to infect several pathogenic multidrug-resistant E. coli strains. A short latent period and large burst size ensured their rapidly reproduction in host cells. Their tolerance of high temperatures and high pH levels meant that remained stable when used to control pathogenic E. coli strains. No obvious cytotoxicity was observed when either HEK293 T or A549 cells were incubated with these two phages. Mass spectrometry analysis allowed us to identify several phage-encoded proteins. Genomic analysis revealed that no toxic proteins or antibiotic proteins were encoded. Genome comparison and phylogenetic analysis indicated that the phages identified show high similarity with E. coli phages of the genus Kagunavirus. The desirable characteristics of the novel phages identified make them good potential therapeutic candidates, and components of phage cocktails to treat multidrug-resistant E. coli in the future.

Tumor microenvironment is a complex and dynamic community, which plays a crucial role in tumor progression via the co-evolution of cancer cells and tumor stroma. Among them, tumor-associated macrophages (TAMs) and tumor neo-vessels are two key components in the tumor microenvironment during cancer invasion. In addition, programmed cell death ligand 1/programmed cell death ligand 1 (PD-1/PD-L1) also plays an important role in tumorigenesis and development, and the clinical strategies to block PD-1/PD-L1 pathway could have great benefits for cancer patients. This study was aimed at analyzing the quantitative expression and prognostic significance of TAMs, tumor neo-vessels and PD-L1 in tumor microenvironment and exploring the relations between the expression of above components with the patients' prognosis of non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death worldwide. The family of glutathione peroxidase (GPX), an important antioxidant enzyme in human tissues, has been discovered to play a key role in the development of cancers. GPX8 is the most promising molecule of the family in a therapeutic strategy against a variety of cancers. The main purpose of this study was to examine and analyze the function and clinical value of GPX8 in NSCLC.

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

In this study, aimed at valorization of industrial xylan-rich hemicelluloses (a by-product of dissolving pulp process), water-soluble hemicelluloses were fabricated with mild acetylation in 1-ethyl-3-methylimidazolium acetate ionic liquid (EmimAc) and dichloroacetyl chloride (Cl2AcCl) system by a facile and novel method. The structure of the acetylated hemicelluloses was characterized by FT-IR and NMR spectra. The resultant modified products could fully dissolve in water with the degree of substitution (DS) valued between 0.17 and 0.37. Structural characterization indicated that the modified hemicelluloses were chiefly composed of the (1 → 4)-linked β-D-Xylp backbone with hydroxyl or -COCH3 linked to O-2 and O-3 of the Xylp units. Moreover, the mild acetylation was achieved by one-pot method, in which the hemicelluloses reacted with mixed anhydride produced between EmimAc and Cl2AcCl rather than Cl2AcCl. Rheological behavior measurements revealed that acetylated hemicelluloses solutions showed shear-thinning behavior and indicated lower viscosity compared with those of the referenced hemicelluloses. The excellent water-solubility of industrial hemicelluloses would widen its application field and be easier for its conversion into desired chemicals.

Background: Latent membrane protein 1 (LMP1) is known as an oncogenic protein encoded by the EBV genome. The purpose of this study was to investigate the mechanism of LMP1-induced cell epithelial-mesenchymal transition (EMT). Methods: The NP69 cell line of nasopharyngeal epithelial cells with high expression of LMP1 was established to observe the effect of high expression of LMP1 on cell growth, proliferation, cycle, apoptosis, migration and invasion. We used proteomics to screen and identify differentially expressed proteins related to LMP1-mediated epithelial cell transformation. Then, we analyzed the expression and significance of differentially expressed calreticulin (CRT) in nasopharyngeal carcinoma (NPC), and observed the effect of CRT expression on EMT in CNE2 cells of NPC. Finally, the expression of neuropilin-1 (NRP1), which is a protein downstream of the EMT-related signaling pathway TGF-β (transforming growth factor β), was detected. Results: LMP1 promoted NP69 cells proliferation, inhibited apoptosis and induced EMT. We identified 22 differentially expressed proteins associated with LMP1-induced EMT. Among them, CRT expression level was significantly increased in NPC compared with adjacent tissues, and was interrelated with TNM staging and lymph node metastasis of NPC. After knockdown of CRT expression, the phenomenon of cell EMT was reduced and the ability of cell migration and invasion was weakened. CRT regulated NRP1 expression by affecting SMAD3 phosphorylation. Conclusion: LMP1 induced cell EMT via TGF-β/Smad3/NRP1 pathway, which promoted migration and invasion of NPC cells.

Developing high-efficient afterglow from metal-free organic molecules remains a formidable challenge due to the intrinsically spin-forbidden phosphorescence emission nature of organic afterglow, and only a few examples exhibit afterglow efficiency over 10%. Here, we demonstrate that the organic afterglow can be enhanced dramatically by thermally activated processes to release the excitons on the stabilized triplet state (T1*) to the lowest triplet state (T1) and to the singlet excited state (S1) for spin-allowed emission. Designed in a twisted donor-acceptor architecture with small singlet-triplet splitting energy and shallow exciton trapping depth, the thermally activated organic afterglow shows an efficiency up to 45%. This afterglow is an extraordinary tri-mode emission at room temperature from the radiative decays of S1, T1, and T1*. With the highest afterglow efficiency reported so far, the tri-mode afterglow represents an important concept advance in designing high-efficient organic afterglow materials through facilitating thermally activated release of stabilized triplet excitons.

Drought stress often limits plant growth and global crop yields. Catalase (CAT)-mediated hydrogen peroxide (H2 O2 ) scavenging plays an important role in the adaptation of plant stress responses, but the transcriptional regulation of the CAT gene in response to drought stress is not well understood. Here, we isolated an APETALA2/ETHYLENE-RESPONSIVE FACTOR (AP2/ERF) domain-containing transcription factor (TF), NtERF172, which was strongly induced by drought, abscisic acid (ABA) and H2 O2 , from tobacco (Nicotiana tabacum) by yeast one-hybrid screening. NtERF172 localized to the nucleus and acted as a transcriptional activator. Chromatin immunoprecipitation, yeast one-hybrid assays, electrophoretic mobility shift assays and transient expression analysis assays showed that NtERF172 directly bound to the promoter region of the NtCAT gene and positively regulated its expression. Transgenic plants overexpressing NtERF172 displayed enhanced tolerance to drought stress, whereas suppression of NtERF172 decreased drought tolerance. Under drought stress conditions, the NtERF172-overexpressed lines showed higher catalase activity and lower accumulation of H2 O2 compared with wild-type (WT) plants, while the NtERF172-silenced plants showed the inverse correlation. Exogenous application of amino-1,2,4-triazole (3-AT), an irreversible CAT inhibitor, to the NtERF172-overexpression lines showed decreased catalase activity and drought tolerance, and increased levels of cellular H2 O2 . Knockdown of NtCAT in the NtERF172-overexpression lines displayed a more drought stress-sensitive phenotype than NtERF172-overexpression lines. We propose that NtERF172 acts as a positive factor in drought stress tolerance, at least in part through the regulation of CAT-mediated H2 O2 homeostasis.

As one of the most malicious cancers, pancreatic cancer is difficult to treat due to the lack of effective early diagnosis. Therefore, it is urgent to find reliable diagnostic and predictive markers for the early detection of pancreatic cancer. In recent years, the detection of circulating cell-free DNA (cfDNA) methylation in plasma has attracted global attention for non-invasive and early cancer diagnosis. Here, we carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 0.0001). Then, 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. After performing the least absolute shrinkage and selection operator (LASSO) method, a total of eight markers were found to fairly distinguish PDAC patients from healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977, and LOC100130148. In conclusion, this work identified a set of eight differentially methylated markers that may be potentially applied in non-invasive diagnosis of pancreatic cancer.