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The ongoing unprecedented severe acute respiratory syndrome caused by the SARS-CoV-2 outbreak worldwide has highlighted the need for understanding viral-host interactions involved in mechanisms of virulence. Here, we show that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, which is responsible for nuclear export of cellular mRNAs. Nsp1 prevents proper binding of NXF1 to mRNA export adaptors and NXF1 docking at the nuclear pore complex. As a result, a significant number of cellular mRNAs are retained in the nucleus during infection. Increased levels of NXF1 rescues the Nsp1-mediated mRNA export block and inhibits SARS-CoV-2 infection. Thus, antagonizing the Nsp1 inhibitory function on mRNA export may represent a strategy to restoring proper antiviral host gene expression in infected cells., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Cadmium sulfide nanoparticle (Nano-CdS) is a kind of important semiconductor material with special photochemistry property. With the Nano-CdS being widely used, the security problems it caused have been catching more and more attention. This study aims to explore the possible mechanism of liver injury induced by Nano-CdS and whether resveratrol can reduce the damage. In this study, male BALB/C mice were treated with Nano-CdS with a diameter of 20 to 30 nm and a length of 80 to 100 nm. It turned out that the mice liver inflammatory cells infiltrated, the liver tissue and the ultrastructure changed; The activities of T-AOC and GSH were suppressed (n = 6, P < 0.05) and the content of lipid peroxide (MDA) increased (n = 6, P < 0.05). Besides, Nano-CdS decreased the mRNA expression level of Sirt1 and FoxO1 genes in liver tissue (n = 3, P < 0.05). All the changes in the index were reversed by resveratrol. The mRNA expression level of FoxO3a showed no significant difference between the control group and the Nano-CdS group. But under the protection of resveratrol, the mRNA expression level of FoxO3a was higher than that in the control and Nano-CdS groups (n = 3, P < 0.05). Results suggest that Nano-CdS can cause oxidative damages to liver tissues in mice, in which process that the Sirt1 and FoxO1 genes may participate, and the damage can be reversed by resveratrol which may be a potential cure for oxidative damage to nanomaterials., (© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: To evaluate the expression of programmed death 1 ligand 1 (PD-L1) in the cancer tissues and tumor-adjacent normal tissues of patients with invasive ductal carcinoma of the breast and to analyze the relationship between the expression of PD-L1 and the clinicopathological features of patients., Materials and Methods: This study included 112 cases of patients with invasive ductal carcinoma of breast who received surgical treatment from March 2012 to February 2016 in Xuzhou Cancer Hospital. The clinical materials of included patients were retrospectively analyzed. The immunohistochemical assay and real-time polymerase chain reaction (PCR) assay were applied to examine the expression of mRNA and protein of PD-L1 in breast cancer specimens of 112 cases and paired tumor-adjacent tissue specimens of 57 cases. The relationship between PD-L1 protein expression and clinicopathological features of patients was analyzed., Results: PD-L1 protein was mainly expressed in the cytoplasm. The positive rate of PD-L1 expression in invasive ductal carcinoma was 19.6% (22/112), and the positive rate of PD-L1 expression of tumor-adjacent normal tissues was 3.5% (2/57), indicating that the positive rate of PD-L1 expression of cancerous tissues was significantly higher than that of in tumor-adjacent normal tissues (P < 0.05); the positive expression of PD-L1 was not related with the patients' age, menopause history, family history of breast cancer, tumor size, and location of the tumor (P > 0.05) while it was related with lymph node metastasis, the clinic staging, and histopathological grading (P < 0.05). Real-time PCR was applied to detect the mRNA expression of PD-L1 in breast-invasive ductal carcinoma with the mean ΔCt value of 7.79 ± 2.25. However, the mRNA expression of PD-L1 in normal tumor-adjacent tissues was of low expression with the mean ΔCt value of 12.37 ± 3.33. The difference was statistically significant (P< 0.05)., Conclusion: The expression of PD-L1 in breast-invasive ductal carcinoma was significantly increased, and it was related to histological grading, clinical staging, and lymph node metastasis of breast cancer. PD-L1 may be a significant marker for the prognosis of breast cancer patients., Competing Interests: There are no conflicts of interest.

Watermelon (Citrullus lanatus) as non‐climacteric fruit is domesticated from the ancestors with inedible fruits. We previously revealed that the abscisic acid (ABA) signaling pathway gene ClSnRK2.3 might influence watermelon fruit ripening. However, the molecular mechanisms are unclear. Here, we found that the selective variation of ClSnRK2.3 resulted in lower promoter activity and gene expression level in cultivated watermelons than ancestors, which indicated ClSnRK2.3 might be a negative regulator in fruit ripening. Overexpression (OE) of ClSnRK2.3 significantly delayed watermelon fruit ripening and suppressed the accumulation of sucrose, ABA and gibberellin GA4. Furthermore, we determined that the pyrophosphate‐dependent phosphofructokinase (ClPFP1) in sugar metabolism pathway and GA biosynthesis enzyme GA20 oxidase (ClGA20ox) could be phosphorylated by ClSnRK2.3 and thereby resulting in accelerated protein degradation in OE lines and finally led to low levels of sucrose and GA4. Besides that, ClSnRK2.3 phosphorylated homeodomain‐leucine zipper protein (ClHAT1) and protected it from degradation to suppress the expression of the ABA biosynthesis gene 9'‐cis‐epoxycarotenoid dioxygenase 3 (ClNCED3). These results indicated that ClSnRK2.3 negatively regulated watermelon fruit ripening by manipulating the biosynthesis of sucrose, ABA and GA4. Altogether, these findings revealed a novel regulatory mechanism in non‐climacteric fruit development and ripening. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA) is caused by repeated blockage of the upper respiratory airways during sleep. The traditional evaluation methods for OSA severity are yet limited. This study aimed to screen gene signatures to effectively evaluate OSA severity. Expression profiles of peripheral blood mononuclear cells in the different severities of OSA patients were accessed from Gene Expression Omnibus (GEO) database. A total of 446 differentially expressed genes (DEGs) were screened among the varying severities of OSA samples by analysis of variance (ANOVA) test. A total of 1,152 DEGs were screened between the pre- and post-treatment OSA samples by using t test. Overlap of the two groups of DEGs was selected (88 DEGs) for Metascape enrichment analysis. Afterwards, Mfuzz package was used to perform soft clustering analysis on these 88 genes, by which 6 clusters were obtained. It was observed that the gene expression condition of the cluster 3 was positively associated with OSA severity degree; also, the gene expression condition in cluster 4 was negatively correlated with OSA severity. A total of 10 gene markers related to OSA progression were selected from cluster 3 and cluster 4. Their expression levels and correlation were analyzed. The marker genes in cluster 3 and cluster 4 were examined, finding that most genes were significantly correlated with apnea hypopnea index (AHI). An accurate and objective assessment of the severity of OSA is of great significance for formulating follow-up treatment strategies for patients with OSA. In this paper, a set of marker genes that can detect the severity of OSA were screened by bioinformatics methods, which could be jointly used with the traditional OSA diagnostic index to achieve a more reliable OSA severity evaluation. [ABSTRACT FROM AUTHOR]

Grafting cultivation is implemented worldwide mainly to resist abiotic and biotic stresses and is an effective method to improve watermelon production. However, grafting may affect fruit development and quality. In our experiment, pumpkin-grafted (PG) watermelon fruits developed slower and the ripening period was extended compared to self-grafted (SG) fruits. We found that the concentrations of abscisic acid (ABA) among endogenous phytohormones were dramatically reduced by pumpkin grafting. In order to understand these changes at the gene expression level, we performed a comprehensive analysis of the fruit flesh transcriptomes between PG and SG during fruit development and ripening. A total of 1,675 and 4,102 differentially expressed genes (DEGs) were identified between PG and SG. Further functional enrichment analysis revealed that these DEGs were associated with carbohydrate biosynthesis, phytohormone signaling transmission, and cell wall metabolism categories. ABA centric phytohormone signaling and fruit quality-related genes including ABA receptor, PP2C proteins, AP2-EREBP transcription factors, sucrose transporter, and carotenoid isomerase were co-expressed with fruit ripening. These results provide the valuable resource for understanding the mechanism of pumpkin grafting effect on watermelon fruit ripening and quality development. [ABSTRACT FROM AUTHOR]

Nsp1 can stall mRNA translation and lead to accelerated degradation of cellular mRNA ([4]). First, upon the interaction between the Nsp1 and the 5' UTR of the SARS-CoV-2 genome, or the change of the Nsp1, ribosomal association with Nsp1 was inhibited. Keywords: SARS-CoV-2; mechanism; Nsp1; translational suppression; mRNA EN SARS-CoV-2 mechanism Nsp1 translational suppression mRNA 1 3 3 04/27/22 20220422 NES 220422 Highlights The relation between the structures of Nsp1 proteins and their function is further revealed. [Extracted from the article]

Export of mRNA from the nucleus to the cytoplasm is a critical process for all eukaryotic gene expression. As mRNA is synthesized, it is packaged with a myriad of RNA‐binding proteins to form ribonucleoprotein particles (mRNPs). For each step in the processes of maturation and export, mRNPs must have the correct complement of proteins. Much of the mRNA export pathway revolves around the heterodimeric export receptor yeast Mex67•Mtr2/human NXF1•NXT1, which is recruited to signal the completion of nuclear mRNP assembly, mediates mRNP targeting/translocation through the nuclear pore complex (NPC), and is displaced at the cytoplasmic side of the NPC to release the mRNP into the cytoplasm. Directionality of the transport is governed by at least two DEAD‐box ATPases, yeast Sub2/human UAP56 in the nucleus and yeast Dbp5/human DDX19 at the cytoplasmic side of the NPC, which respectively mediate the association and dissociation of Mex67•Mtr2/NXF1•NXT1 onto the mRNP. Here we review recent progress from structural studies of key constituents in different steps of nuclear mRNA export. These findings have laid the foundation for further studies to obtain a comprehensive mechanistic view of the mRNA export pathway. [ABSTRACT FROM AUTHOR]

Watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai) is a non-climacteric fruit. The modern sweet-dessert watermelon is the result of years of cultivation and selection for fruits with desirable qualities. To date, the mechanisms of watermelon fruit ripening, and the role of abscisic acid (ABA) in this process, has not been well understood. We quantified levels of free and conjugated ABA contents in the fruits of cultivated watermelon (97103; C. lanatus subsp. vulgaris), semi-wild germplasm (PI179878; C. lanatus subsp. mucosospermus), and wild germplasm (PI296341-FR; C. lanatus subsp. lanatus). Results showed that ABA content in the fruits of 97103 and PI179878 increased during fruit development and ripening, but maintained a low steady state in the center flesh of PI296341-FR fruits. ABA levels in fruits were highest in 97103 and lowest in PI296341-FR, but no obvious differences in ABA levels were observed in seeds of these lines. Examination of 31 representative watermelon accessions, including different C. lanatus subspecies and ancestral species, showed a correlation between soluble solids content (SSC) and ABA levels in ripening fruits. Furthermore, injection of exogenous ABA or nordihydroguaiaretic acid (NDGA) into 97103 fruits promoted or inhibited ripening, respectively. Transcriptomic analyses showed that the expression levels of several genes involved in ABA metabolism and signaling, including Cla009779 (NCED), Cla005404 (NCED), Cla020673 (CYP707A), Cla006655 (UGT) and Cla020180 (SnRK2), varied significantly in cultivated and wild watermelon center flesh. Three SNPs (-738, C/A; -1681, C/T; -1832, G/T) in the promoter region of Cla020673 (CYP707A) and one single SNP (-701, G/A) in the promoter of Cla020180 (SnRK2) exhibited a high level of correlation with SSC variation in the 100 tested accessions. Our results not only demonstrate for the first time that ABA is involved in the regulation of watermelon fruit ripening, but also provide insights into the evolutionary mechanisms of this phenomenon. [ABSTRACT FROM AUTHOR]

This study aims to find the difference of genomewide DNA methylation in Schwann cells (SCs) before and after peripheral nerve system (PNS) injury by Methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq) and seek meaningful differentially methylated genes related to repairment of injured PNS. SCs harvested from sciatic nerve were named as activated Schwann cells (ASCs), and the ones harvested from brachial plexus were named as normal Schwann cells (NSCs). Genomic DNA of ASCs and NSCs were isolated and MeDIP-Seq was conducted. Differentially methylated genes and regions were discovered and analyzed by bioinformatic methods. MeDIP-Seq analysis showed methylation differences were identified between ASCs and NSCs. The distribution of differentially methylated regions (DMRs) peaks in different components of genome was mainly located in distal intergenic regions. GO and KEGG analysis of these methylated genes were also conducted. The expression patterns of hypermethylated genes (Dgcr8, Zeb2, Dixdc1, Sox2, and Shh) and hypomethylated genes (Gpr126, Birc2) detected by qRT-PCR were opposite to the MeDIP analysis data with significance (p < 0.05), which proved MeDIP analysis data were real and believable. Our data serve as a basis for understanding the injury-induced epigenetic changes in SCs and the foundation for further studies on repair of PNS injury. [ABSTRACT FROM AUTHOR]

Fe deficiency is a widespread nutritional disorder in plants. The basic helix-loop-helix ( bHLH) transcription factors ( TFs), especially Ib subgroup bHLH TFs which are involved in iron uptake, have been identified. In this study, an IVc subgroup bHLH TF Mdb HLH104 was identified and characterized as a key component in the response to Fe deficiency in apple. The overexpression of the Mdb HLH104 gene noticeably increased the H+- ATPase activity under iron limitation conditions and the tolerance to Fe deficiency in transgenic apple plants and calli. Further investigation showed that Mdb HLH104 proteins bonded directly to the promoter of the Md AHA8 gene, thereby positively regulating its expression, the plasma membrane ( PM) H+- ATPase activity and Fe uptake. Similarly, Mdb HLH104 directly modulated the expression of three Fe-responsive bHLH genes, Mdb HLH38, Mdb HLH39 and Md PYE. In addition, Mdb HLH104 interacted with 5 other IVc subgroup bHLH proteins to coregulate the expression of the Md AHA8 gene, the activity of PM H+- ATPase and the content of Fe in apple calli. Therefore, Mdb HLH104 acts together with other apple bHLH TFs to regulate Fe uptake by modulating the expression of the Md AHA8 gene and the activity of PM H+- ATPase in apple. [ABSTRACT FROM AUTHOR]

Abstract: The fusellovirus SSV2 and the integrative plasmid pSSVi, which constitute a unique helper-satellite virus system, replicate in Sulfolobus solfataricus P2. In this study, we investigated the interplay among SSV2, pSSVi and their host by transcriptomic analysis. Following infection of S. solfataricus P2, SSV2 activated its promoters in a temporal and distributive fashion, starting from the transcription of ORF305. Expression of several host genes encoding DNA replication and transcription proteins was up-regulated, suggesting that SSV2 depended heavily on the host replication machinery for its replication. SSV2 gene expression appeared to follow a similar pattern in S. solfataricus P2 harboring pSSVi to that in S. solfataricus P2 lacking the plasmid. Several early genes of the virus were transcribed earlier and more efficiently in the presence of pSSVi than in its absence. These results provide valuable clues to the understanding of the three-way interactions among SSV2, pSSVi and the host. [Copyright &y& Elsevier]

The quantitative comparison of two or more microarrays can reveal, for example, the distinct patterns of gene expression that define different cellular phenotypes or the genes that are induced in the cellular response to certain stimulations. Normalization of the measured intensities is a prerequisite of such comparisons. However, a fundamental problem in cDNA microarray analysis is the lack of a common standard to compare the expression levels of different samples. Several normalization protocols have been proposed to overcome the variabilities inherent in this technology. We have developed a normalization procedure based on within-array replications via a semilinear in-slide model, which adjusts objectively experimental variations without making critical biological assumptions. The significant analysis of gene expressions is based on a weighted t statistic, which accounts for the heteroscedasticity of the observed log ratios of expressions, and a balanced sign permutation test. We illustrated the use of the techniques in a comparison of the expression profiles of neuroblastoma cells that were stimulated with a growth factor, macrophage migration inhibitory factor (MIF). The analysis of expression changes at mRNA levels showed that &ap;99 genes were up-regulated and 24 were reduced significantly (P <0.001) in MW-stimulated neuroblastoma cells. The regulated genes included several oncogenes, growth- related genes, tumor metastatic genes, and immuno-related genes. The findings provide clues as to the molecular mechanisms of MIF-mediated tumor progression and supply therapeutic targets for neuroblastoma treatment. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tear (RCT) is a common shoulder disorder in the elderly. Muscle atrophy, denervation and fatty infiltration exert secondary injuries on torn rotator cuff muscles. It has been reported that satellite cells (SCs) play roles in pathogenic process and regenerative capacity of human RCT via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) of SCs that regulated between the torn supraspinatus (SSP) samples and intact subscapularis (SSC) samples, identify their functions and molecular pathways. Methods: The gene expression profile GSE93661 was downloaded and bioinformatics analysis was made. Results: Five hundred fifty one DEGs totally were identified. Among them, 272 DEGs were overexpressed, and the remaining 279 DEGs were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene–gene interaction network analysis such as GNG13, GCG, NOTCH1, BCL2, NMUR2, PMCH, FFAR1, AVPR2, GNA14, and KALRN, that may contribute to the understanding of the molecular mechanisms of secondary injuries in RCT. We also discovered that GNG13/calcium signaling pathway is highly correlated with the denervation atrophy pathological process of RCT. Conclusion: These genes and pathways provide a new perspective for revealing the underlying pathological mechanisms and therapy strategy of RCT. [ABSTRACT FROM AUTHOR]

Background: Hyperleptinemia is a common feature of obese people, and leptin, an adipocyte-derived cytokine, is believed to be an important factor in the pathogenesis of cervical ossification of the posterior longitudinal ligament(C-OPLL). So this research was to identify the relation between the serum leptin and bone metabolic markers and how the leptin induced osteogenic effect in C-OPLL. Methods: Sixty-four samples were selected to determine the concentration of leptin, insulin, and alkaline phosphatase. And the association of leptin with these factors was also examined. We also evaluate the effect of leptin on the development of C-OPLL and further explored the possible underlying mechanism in vitro. Results: We found that serum leptin concentrations were higher in females than in males. Serum leptin and ALP concentrations were increased significantly in C-OPLL females compared to non-OPLL females. In OPLL subjects, the serum leptin concentration corrected for body mass index correlated negatively with the ALP concentrations. In C-OPLL cells, leptin treatment led to a significant increase in mRNA expressions of ALP and OCN and formation of mineralized nodule. Our experiments reported here that osteogenic effect of leptin in C-OPLL cells could be mediated via ERK1/2, p38 MAPK, and/or JNK signaling pathways. Conclusions: From this research, we got that leptin treatment led to a significant increase in mRNA expressions of ALP and OCN and formation of mineralized nodule. And the osteogenic effect of leptin in C-OPLL cells could be mediated via ERK1/2, p38 MAPK, and/or JNK signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Human osteosarcoma (OS) is one of the most common primary bone sarcoma, because of early metastasis and few treatment strategies. It has been reported that the tumorigenicity and self-renewal capacity of side population (SP) cells play roles in human OS via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) that regulated between the SP cells and the non-SP cells from primary human OS and identify their functions and molecular pathways associated with OS. Methods: The gene expression profile GSE63390 was downloaded, and bioinformatics analysis was made. Results: One hundred forty-one DEGs totally were identified. Among them, 72 DEGs (51.06%) were overexpressed, and the remaining 69 DEGs (48.94%) were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene–gene interaction network analysis such as EIF4E, FAU, HSPD1, IL-6, and KISS1, which may have a relationship with the development process of OS. We also discovered that EIF4E/mTOR signaling pathway could be a potential research target for therapy and tumorigenesis of OS. Conclusion: This analysis provides a comprehensive understanding of the roles of DEGs coming from SP cells in the development of OS. However, these predictions need further experimental validation in future studies. [ABSTRACT FROM AUTHOR]