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Stem canker and black scurf of potatoes, caused by Rhizoctonia solani, are economically important diseases. Although the field application of sodium silicate has been shown to improve potato's resistance against R. solani, the underlying mechanism remains unclear. In this study, we examined this resistance using transcriptomic analysis. Potato stems inoculated with R. solani were treated with sodium silicate, while a control group received no sodium silicate treatment. The plants were grown under natural environmental conditions at the farm of Inner Mongolia Agricultural University. Potato stems were sampled 4, 8, and 12 days after treatment. Total RNA was extracted using the TRIzol reagent and transformed into cDNA. The cDNA was sequenced, the reads were aligned, and the expression levels of genes were quantified and compared between the treated and control groups. A total of 1491 genes were identified as differentially expressed genes (DEGs). Furthermore, these DEGs were found to be involved in hydrolase activity, plant–pathogen interactions, hormone signal transduction, and the phenylpropanoid biosynthesis pathway. To confirm the up- and down-regulation of DEGs, quantitative real-time polymerase chain reaction (qRT-PCR) was performed on randomly selected genes. The results showed that the application of sodium silicate induces a complex defense network in potato plants involving physical barriers, innate immunity, phytohormone signaling, and various phenylpropanoid compounds to combat R. solani infection. This study provides valuable insights into the molecular mechanisms underlying sodium-silicate-induced resistance and its potential for reducing stem canker and black scurf in potato crops. [ABSTRACT FROM AUTHOR]

Background: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. Methods: We obtained obesity‐related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high‐fat diet model (maternal high‐fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high‐fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co‐expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity‐associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. Results: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD‐induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor–miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid‐stimulated microglial inflammation model. Conclusion: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity‐associated risks in the offspring of obese mothers. [ABSTRACT FROM AUTHOR]

Sweet clover (Melilotus albus) is a high-quality leguminous forage grass with salinity tolerance, drought tolerance, and cold hardiness. We selected four varieties of sweet clover with different sensitivities (061898, 061930, No. 55 white flower, and Ningxia white flower) and analyzed the effects of different concentrations of three sodium salts (Na2CO3, NaHCO3, and NaCl) on their physiology and biochemistry responses. Growth and development indexes (such as germination rate, root length, shoot length), chlorophyll content, osmotic regulators (proline, soluble sugar), malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were determined under saline–alkali stress. Seed germination and seedling growth of all four clover species were significantly inhibited under saline–alkali stress. During germination, seed germination rate, root length, and shoot length decreased with increasing saline and alkaline concentration. Under saline–alkali stress, chlorophyll content tended to increase and then decrease, cell damage and death increased, and malondialdehyde, soluble sugar, and proline content tended to increase and then decrease. Moreover, the activities of SOD, POD, and CAT all increased and then decreased. Under Na2CO3 stress, the decrease in chlorophyll content of the resistant variety 061898 was less than in the sensitive Ningxia white flower variety. As the concentrations of Na2CO3, NaHCO3, and NaCl increased, the maximum photochemical efficiency of PSII was significantly affected. The resistant 061898 is capable of maintaining higher photosynthetic efficiency. Furthermore, under treatments with the three kinds of saline–alkali solutions, cell damage and death for Ningxia white flower were greater than in 061898. For 061898, the increases in soluble sugar and proline content were greater and the increase in malondialdehyde content was less, while the antioxidant enzyme activities were higher than those in Ningxia white flower. All four sweet clover varieties had higher stress resistance with neutral than with alkaline salts. When stressed by medium to high saline–alkali concentrations, sweet clover seedlings had increased osmotic substance content, enhanced antioxidant enzyme activity, and regulated physiological metabolism. Additionally, sweet clovers regulated the expression of WRKY33, GH3, CYCD3, OXI1, MKK2, MYC2, JAZ, COI1, PYL, PP2C, TGA, and MPK3 to adapt to the saline–alkali environment and improve saline–alkali tolerance. Our analysis of the sweet clover salinity tolerance mechanism contributes to its further use and is of significant importance for addressing land salinization and promoting sustainable agricultural and pastoral practices in China. [ABSTRACT FROM AUTHOR]

Weeds seriously affect the yield and quality of crops. Because manual weeding is time-consuming and laborious, the use of herbicides becomes an effective way to solve the harm caused by weeds in fields. Both 5-enolpyruvyl shikimate-3-phosphate synthetase (EPSPS) and acetyltransferase genes (bialaphos resistance, BAR) are widely used to improve crop resistance to herbicides. However, cotton, as the most important natural fiber crop, is not tolerant to herbicides in China, and the EPSPS and BAR family genes have not yet been characterized in cotton. Therefore, we explore the genes of these two families to provide candidate genes for the study of herbicide resistance mechanisms. In this study, 8, 8, 4, and 5 EPSPS genes and 6, 6, 5, and 5 BAR genes were identified in allotetraploid Gossypium hirsutum and Gossypium barbadense, diploid Gossypium arboreum and Gossypium raimondii, respectively. Members of the EPSPS and BAR families were classified into three subgroups based on the distribution of phylogenetic trees, conserved motifs, and gene structures. In addition, the promoter sequences of EPSPS and BAR family members included growth and development, stress, and hormone-related cis-elements. Based on the expression analysis, the family members showed tissue-specific expression and differed significantly in response to abiotic stresses. Finally, qRT-PCR analysis revealed that the expression levels of GhEPSPS3, GhEPSPS4, and GhBAR1 were significantly upregulated after exogenous spraying of herbicides. Overall, we characterized the EPSPS and BAR gene families of cotton at the genome-wide level, which will provide a basis for further studying the functions of EPSPS and BAR genes during growth and development and herbicide stress. [ABSTRACT FROM AUTHOR]

BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y 6 (P2RY6, P2Y 6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS: P2RY6 expression was elevated in LUAD and correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Cotton has tremendous economic value worldwide; however, its allopolyploid nature and time-consuming transformation methods have hampered the development of cotton functional genomics. The protoplast system has proven to be an important and versatile tool for functional genomics, tissue-specific marker gene identification, tracking developmental trajectories, and genome editing in plants. Nevertheless, the isolation of abundant viable protoplasts suitable for single-cell RNA sequencing (scRNA-seq) and genome editing remains a challenge in cotton. Results: We established an efficient transient gene expression system using protoplasts isolated from cotton taproots. The system enables the isolation of large numbers of viable protoplasts and uses an optimized PEG-mediated transfection protocol. The highest yield (3.55 × 105/g) and viability (93.3%) of protoplasts were obtained from cotton roots grown in hydroponics for 72 h. The protoplasts isolated were suitable for scRNA-seq. The highest transfection efficiency (80%) was achieved when protoplasts were isolated as described above and transfected with 20 μg of plasmid for 20 min in a solution containing 200 mM Ca2+. Our protoplast-based transient expression system is suitable for various applications, including validation the efficiency of CRISPR vectors, protein subcellular localization analysis, and protein–protein interaction studies. Conclusions: The protoplast isolation and transfection protocol developed in this study is stable, versatile, and time-saving. It will accelerate functional genomics and molecular breeding in cotton. [ABSTRACT FROM AUTHOR]

Background: Norwogonin is a natural flavone with three phenolic hydroxyl groups in skeletal structure and has excellent antioxidant activity. However, the neuroprotective effect of norwogonin remains unclear. Here, we investigated the protective capacity of norwogonin against oxidative damage elicited by hypoxia in PC12 cells. Methods: The cell viability and apoptosis were examined by MTT assay and Annexin V-FITC/PI staining, respectively. Reactive oxygen species (ROS) content was measured using DCFH-DA assay. Lactate dehydrogenase (LDH), malondialdehyde (MDA) and antioxidant enzyme levels were determined using commercial kits. The expression of related genes and proteins was measured by real-time quantitative PCR and Western blotting, respectively. Results: We found that norwogonin alleviated hypoxia-induced injury in PC12 cells by increasing the cell viability, reducing LDH release, and ameliorating the changes of cell morphology. Norwogonin also acted as an antioxidant by scavenging ROS, reducing MDA production, maintaining the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and decreasing the expression levels of HIF-1α and VEGF. In addition, norwogonin prevented cell apoptosis via inhibiting the expression levels of caspase-3, cytochrome c and Bax, while increasing the expression levels of Bcl-2 and the ratio of Bcl-2/Bax. Conclusions: Norwogonin attenuates hypoxia-induced injury in PC12 cells by quenching ROS, maintaining the activities of antioxidant enzymes, and inhibiting mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer involves thyroid follicular carcinoma (FTC) and papillary thyroid carcinoma (PTC). Patients with FTC have a worse prognosis than those with PTC for early metastasis through blood of FTC. However, the mechanism of poor prognosis of FTC is still unclear. Here, we aim to evaluate the role of DUSP5 in the prognostic evaluation of FTC. Method: We searched the Gene Expression Omnibus (GEO) database for the differentially expressed genes (DEGs) between FTC and PTC, and then combined with survival analysis of cBioPortal database to locate the gene significantly related to prognosis. Tissue microarrays and clinical tissues were used to examine DUSP5 expression by immunohistochemical (IHC) staining between FTC and PTC tissues. In vitro experiment, proliferation, migration and invasion of FTC were observed after regulation of DUSP5 by transfection of siRNA and plasmids, respectively. Results: After searching the GEO database, 26 DEGs were found. DUSP5 was significantly associated with prognosis of FTC in combination with survival analysis. Data of IHC staining showed lower expression of DUSP5 in FTC compared to PTC tissues. Furthermore, overexpression of DUSP5 inhibited the proliferation, migration and invasion accompanied with low level of MMP9 and Vimentin and high level of E‐cadherin. Nevertheless, inhibition of DUSP5 ameliorated above damaging effect on the proliferation, migration and invasion. Conclusion: DUSP5 was differentially expressed in FTC and PTC tissues. Low level of DUSP5 in FTC participates in the high frequency of metastasis, and further contributes to poor prognosis of FTC. DUSP5 could be served as a novel therapeutic target for FTC. [ABSTRACT FROM AUTHOR]

Background. A large number of proinflammatory/anti-inflammatory cytokines are produced in the extracellular matrix (ECM) after myocardial infarction (MI), and the inflammatory pathways activated by these inflammatory stimuli are involved in the regulation of lesions with excessive accumulation of ECM. Wenxin granules can play a protective role against MI, but the mechanism of its effect on the inflammatory pathway and ECM collagen expression is still unclear. Objective. To verify the effect of Wenxin granules on the inflammatory pathway and collagen expression after MI. Method. The proximal left anterior descending coronary artery in rats was ligated to induce acute MI. Then, animals were randomly assigned to the model group, the Carvedilol group, and the Wenxin Granules group. In addition, sham operation rats were used as the control group. 10 rats were allocated in each group. Gavage was given once a day for 4 weeks. The changes of cardiac hemodynamics were detected by the catheter method, morphological changes were observed by HE staining, and myocardial tissue collagen volume was counted by Immunohistochemistry combined with Masson staining, and the expression of inflammatory TGFβ-p38/JNK MAPK signal pathway markers was detected by Western blot. Results. Wenxin granules could significantly improve the hemodynamics, so that the fibrosis scar was relatively dense and uniform, and the residual myocardium was relatively neat, while Collagen type I and III volume and TGFβ expression levels were lessened. Although there were no differences in the expression of CTGF, p38, and JNK proteins, their phosphorylation levels showed significant differences. Conclusion. Wenxin granules can affect the inflammation-related TGFβ-p38/JNK MAPK signaling pathway and change the structural properties of myocardium and scar after MI by attenuated collagen deposition in the left ventricular myocardial tissue to improve cardiac function. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to detect pyroptosis in macrophages stimulated with Porphyromonas gingivalis and elucidate the mechanism by which P. gingivalis induces pyroptosis in macrophages. Methods: The immortalized human monocyte cell line U937 was stimulated with P. gingivalis W83. Flow cytometry was carried out to detect pyroptosis in macrophages. The expression of miR‐155 was detected by real‐time PCR and inhibited using RNAi. Suppressor of cytokine signaling (SOCS) 1, cleaved GSDMD, caspase (CAS)‐1, caspase‐11, apoptosis‐associated speck‐like protein (ASC), and NOD‐like receptor protein 3 (NLRP3) were detected by Western blotting, and IL‐1β and IL‐18 were detected by ELISA. Results: The rate of pyroptosis in macrophages and the expression of miR‐155 increased upon stimulation with P. gingivalis and pyroptosis rate decreased when miR‐155 was silenced. GSDMD‐NT, CAS‐11, CAS‐1, ASC, NLRP3, IL‐1β, and IL‐18 levels increased, but SOCS1 decreased in U937 cells after stimulated with P. gingivalis. These changes were weakened in P. gingivalis‐stimulated U937 macrophages transfected with lentiviruses carrying miR‐155 shRNA compared to those transfected with non‐targeting control sequence. However, there was no significant difference in ASC expression between P. gingivalis‐stimulated shCont and shMiR‐155 cells. Conclusions: Porphyromonas gingivalis promotes pyroptosis in macrophages during early infection. miR‐155 is involved in this process through regulating the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common glomerular disease. The major pathological changes associated with it affect cell proliferation, fibrosis, apoptosis, inflammation and extracellular matrix (ECM) organization. However, the molecular events underlying IgAN remain to be fully elucidated. In the present study, an integrated bioinformatics analysis was applied to further explore novel potential gene targets for IgAN. The mRNA expression profile datasets GSE93798 and GSE37460 were downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) enrichment analysis of DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were built with the STRING online search tool and visualized by using Cytoscape, and hub genes were identified through the degree of connectivity in the PPI. The hub genes were subjected to Kyoto Encyclopedia of Genes and Genomes pathway analysis, and co-expression analysis was performed. A total of 298 DEGs between IgAN and control groups were identified, and 148 and 150 of these DEGs were upregulated and downregulated, respectively. The DEGs were enriched in distinct GO terms for Biological Process, including cell growth, epithelial cell proliferation, ERK1 and ERK2 cascades, regulation of apoptotic signaling pathway and ECM organization. The top 10 hub genes were then screened from the PPI network by Cytoscape. As novel hub genes, Fos proto-oncogene, AP-1 transcription factor subunit and early growth response 1 were determined to be closely associated with apoptosis and cell proliferation in IgAN. Tumor protein 53, integrin subunit β2 and fibronectin 1 may also be involved in the occurrence and development of IgAN. Co-expression analysis suggested that these hub genes were closely linked with each other. In conclusion, the present integrated bioinformatics analysis provided novel insight into the molecular events and novel candidate gene targets of IgAN. [ABSTRACT FROM AUTHOR]

Qiliqiangxin capsule (QLC), a natural herb recipe with therapeutic effect from China, has been widely used in clinical practice for attenuating cardiac remodeling induced by myocardial infarction (MI). However, the pharmacological mechanism of QLC on cardiac remodeling after MI is not entirely clear. The present study aims to investigate the effectiveness and mechanisms of QLC on cardiac remodeling induced by MI in rats. The animal model was established by permanently ligating the left anterior descending coronary artery in rats. Subsequently, rats with successful ligation were randomly divided into model group, captopril group, and QLC group. And the control group was operated upon in parallel except ligation, namely, the sham group. All rats were treated through the intragastric administration once a day for 4 weeks. Cardiac hemodynamics was measured after treatment. Then, the left ventricular mass index (LVMI) was examined. The pathological changes were observed by HE staining. The collagen volume fraction (CVF) was detected by Masson trichrome staining. The apoptosis index was obtained by TUNEL fluorescent staining. The miR-133a and mRNA of TGF-β1, CTGF, Caspase9, and Caspase3 were examined by real-time PCR. The protein expressions of TGF-β1, CTGF, Caspase9, Caspase3, and cleaved-Caspase3 were tested by Western blot. Compared with the model group, QLC partially improved cardiac hemodynamics and decreased LVMI. miR-133a was significantly increased in QLC group. In addition, QLC declined CVF by downregulating TGF-β1 rather than CTGF. Meanwhile, QLC decreased the apoptosis index by attenuating Caspase9, Caspase3, and cleaved-Caspase3. This study suggested that QLC could improve cardiac function and partially attenuate cardiac remodeling by attenuating fibrosis and decreasing apoptosis, which might be partially related to miR-133a, TGF-β1, Caspase9, and Caspase3. [ABSTRACT FROM AUTHOR]

Recent investigations revealed the relationship between chronic periodontitis, Porphyromonas gingivalis and cancer. However, host genes that change in response to chronic infection with P. gingivalis and may contribute to oral cancer have remained largely unknown. In the present study, we aimed to comprehensively analyze microarray data obtained from the chronic infection model of immortalized oral epithelial cells that were persistently exposed to P. gingivalis for 15 weeks. Using protein-protein interaction (PPI) networks and Ingenuity Pathway Analysis (IPA), we identified hub genes, major biological processes, upstream regulators and genes potentially involved in tumor initiation and progression. We also validated gene expression and demonstrated genetic alteration of hub genes from clinical samples of head and neck cancer. Overall, we utilized bioinformatical methods to identify IL6, STAT1, LYN, BDNF, C3, CD274, PDCD1LG2 , and CXCL10 as potential candidate genes that might facilitate the prevention and treatment of oral squamous cell carcinoma (OSCC), the most common type of head and neck squamous cell carcinoma (HNSCC). [ABSTRACT FROM AUTHOR]

Background: Rapidly progressive glomerulonephritis (RPGN) is caused by various diseases process, thereby resulting in extensive crescent formation, which could lead to a rapid loss of kidney function. The molecular pathogenesis of RPGN remains largely unknown and requires clarification. The weighted gene co-expression network analysis (WGCNA) is a powerful bioinformatics tool to identify meaningful molecules in diseases.Methods: The dataset of GSE104948, which contains 22 RPGN and 18 normal samples, was obtained from Gene Expression Omnibus database. After data pre-processing, the WGCNA was performed to successfully cluster several significant modules. The most significant module was selected for further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Visualization of network and screening of hub genes were performed by using Cytoscape software.Results: A total of 11 modules were clustered by WGCNA, and the most significant module-turquoise module was selected. As discovered via GO enrichment and KEGG pathway analysis, the turquoise module was mainly associated with neutrophil activation and degranulation. After visualization and calculation for the network, the PYCARD gene has higher relationship score in 2 clusters, namely, neutrophil activation and degranulation. In accordance with the literature review, the hub gene could be closely related to the inflammation response and could act as the potential therapeutic targets in RPGN.Conclusions: WGCNA in RPGN expression profiling was used for the first time in this paper. A novel hub gene closely associated with RPGN was screened out, thereby providing the brand-new molecular candidate for RPGN. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the correlations of magnetic resonance imaging (MRI) manifestations with survivin gene expression in primary hepatocellular carcinoma (HCC). METHODS: A total of 84 HCC patients receiving partial hepatectomy in the Surgery Department and Oncology Department in our hospital from April 2011 to May 2014 were recruited. At 1 week before operation, MRI was used to examine the imaging features of liver, a certain size of area was defined and the signal value of each sequence was recorded. HCC and para-carcinoma tissues were collected after operation, and the expression levels of survivin were detected via immunohistochemistry (IHC). All patients were followed up for 30 months after operation, and the Kaplan-Meier survival curve was drawn. The correlations of survivin expression with MRI features and signal parameters of each sequence were analyzed. RESULTS: There was no expression of survivin in normal liver tissues. In HCC and para-carcinoma tissues, the nuclei of positive cells showed brown yellow. The positive expression rate of survivin in HCC tissues was 76.19% (64/84), which was significantly higher than that in para-carcinoma tissues (20.81%, 20/84) (p < 0.05). The overall survival (OS) of patients with high expression of survivin was 12.5 months, which was significantly shorter than that of patients with low expression of survivin (17.6 months) (p < 0.05). Results of chi-square test showed that the survivin level had no correlations with the MRI scan shape and edge in the tumor area (p > 0.05), but it was significantly correlated with tumor diameter, MRI enhancement features and lymphatic metastasis (p < 0.05). Pearson correlation analyses revealed that the survivin IHC score was not correlated with in-phase T1-weighted gradient-recalled echo (GRE), hepatic arterial-phase T1-weighted GRE, portal venous-phase T1-weighted GRE and equilibrium-phase T1-weighted GRE signals (p > 0.05). Besides, the survivin IHC score was negatively correlated with opposed-phase T1-weighted GRE (r = - 0.46, p = 0.038), but positively correlated with T2-weighted fast spin echo signal (r = - 0.49, p = 0.025). CONCLUSION: Survivin is significantly up-regulated in HCC tissues and associated with tumor growth and lymph node metastasis. Clinical detection of survivin level combined with MRI examination might be beneficial for clinical diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]

The type 2 immune response is the central mechanism of disease progression in schistosomiasis, but the signals that induce it after infection remain elusive. Aberrant microRNA (miRNA) expression is a hallmark of human diseases including schistosomiasis, and targeting the deregulated miRNA can mitigate disease outcomes. Here, we demonstrate that efficient and sustained elevation of miR-203-3p in liver tissues, using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), protects mice against lethal schistosome infection by alleviating hepatic fibrosis. We show that miR-203-3p targets interleukin-33 (IL-33), an inducer of type 2 immunity, in hepatic stellate cells to regulate the expansion and IL-13 production of hepatic group 2 innate lymphoid cells during infection. Our study highlights the potential of rAAV8-mediated miR-203-3p elevation as a therapeutic intervention for fibrotic diseases. [ABSTRACT FROM AUTHOR]

LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells. [ABSTRACT FROM AUTHOR]

Cotton is sensitive to waterlogging stress, which usually results in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in cotton remain elusive. Cotton was grown in a rain-shelter and subjected to 0 (control)-, 10-, 15- and 20-d waterlogging at flowering stage. The fourth-leaves on the main-stem from the top were sampled and immediately frozen in liquid nitrogen for physiological measurement. Global gene transcription in the leaves of 15-d waterlogged plants was analyzed by RNA-Seq. Seven hundred and ninety four genes were up-regulated and 1018 genes were down-regulated in waterlogged cotton leaves compared with non-waterlogged control. The differentially expressed genes were mainly related to photosynthesis, nitrogen metabolism, starch and sucrose metabolism, glycolysis and plant hormone signal transduction. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis indicated that most genes related to flavonoid biosynthesis, oxidative phosphorylation, amino acid metabolism and biosynthesis as well as circadian rhythm pathways were differently expressed. Waterlogging increased the expression of anaerobic fermentation related genes, such as alcohol dehydrogenase (ADH), but decreased the leaf chlorophyll concentration and photosynthesis by down-regulating the expression of photosynthesis related genes. Many genes related to plant hormones and transcription factors were differently expressed under waterlogging stress. Most of the ethylene related genes and ethylene-responsive factor-type transcription factors were up-regulated under water-logging stress, suggesting that ethylene may play key roles in the survival of cotton under waterlogging stress. [ABSTRACT FROM AUTHOR]

Ring finger protein 1 (RING1) is a RING domain characterized protein belonging to the RING finger family. It is an E3 ubiquitin-protein ligase that mediated monoubiquitination of histone H2A and the core component of PRC1 complex, which is the repressive multiprotein complex of Polycomb group (PcG). Previous studies showed the important tumorigenic role of RING1 via promoting cell proliferation and the crucial function in maintaining transcriptional program stability during development. However, its mechanism for spinal cord injury (SCI) is still unknown. In our research, we established an acute SCI model in adult rats and studied the expression and function profiles of RING1. RING1 protein level detected by western blot peaked at day 3 after trauma and then decreased gradually. Immunohistochemistry showed the increase of RING1 expression displayed in the white matter more obviously than in the gray matter. Furthermore, increased co-expression of RING1 and GFAP confirmed activated astrocytes in injured spinal cord via double immunofluorescence staining. Meanwhile, we also found the co-localization of PCNA, a famous marker of proliferative cells, with RING1 and GFAP, which indicated RING1 might play a role in astrocyte proliferation after SCI. In vitro studies, RING1 protein level in C6 cells increased after LPS challenge and RING1 was required for astrocyte proliferation and activation induced by LPS. In summary, we took a new insight into the function of RING1 in the cellular and molecular mechanism underlying the pathophysiology of SCI. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a multisystem disorder unique to Homo sapiens that is known to cause maternal and perinatal mortality and morbidity. Between 5–7% of all pregnancies are affected by PE and it is responsible for approximately 50,000 maternal deaths annually. The pathogenesis of PE remains poorly understood. However, the results of this study indicated that insufficient decidualization plays a significant role. NR5A1 and NR5A2 are orphan members of the Ftz-F1 subfamily of nuclear receptors and are involved in mammal follicular development, female reproduction, steroidogenesis, and decidualization. The expression of NR5A1 and NR5A2 in the human decidua and their functions during decidualization were investigated using in vitro cultured cells by real-time PCR, immunohistochemistry, western blotting, and siRNA techniques. The results demonstrated that the levels of NR5A2 mRNA and protein in the decidual tissues of women with PE were lower than those of normal pregnant women. However, the levels of NR5A1 mRNA and protein did not significantly differ between groups. The expression of NR5A2 was upregulated after in vitro decidualization, but the expression of NR5A1 remained low and showed no difference compared with that of the control cells. Knocking down of NR5A2 in human endometrial stromal cells (hESC) resulted in a significant reduction in their expression of decidualization markers (IGFBP1 and PRL) and signaling pathway molecules (WNT4 and BMP2) (P < 0.05). From these data, we concluded that NR5A2 is pivotal for the decidualization of decidual tissues and cultured human endometrial stromal cells. Disorders of the endometrium in decidual tissues may be associated with the abnormal decidualization thought to cause PE. [ABSTRACT FROM AUTHOR]

Cellulose, which can be converted into numerous industrial products, has important impacts on the global economy. It has long been known that cellulose synthesis in plants is tightly regulated by various phytohormones. However, the underlying mechanism of cellulose synthesis regulation remains elusive. Here, we show that in rice (Oryza sativa), gibberellin (GA) signals promote cellulose synthesis by relieving the interaction between SLENDER RICE1 (SLR1), a DELLA repressor of GA signaling, and NACs, the top-layer transcription factors for secondary wall formation. Mutations in GA -related genes and physiological treatments altered the transcription of CELLULOSE SYNTHASE genes (CESA s) and the cellulose level. Multiple experiments demonstrated that transcription factors NAC29/31 and MYB61 are CESA regulators in rice; NAC29/31 directly regulates MYB61 , which in turn activates CESA expression. This hierarchical regulation pathway is blocked by SLR1-NAC29/31 interactions. Based on the results of anatomical analysis and GA content examination in developing rice internodes, this signaling cascade was found to be modulated by varied endogenous GA levels and to be required for internode development. Genetic and gene expression analyses were further performed in Arabidopsis thaliana   GA -related mutants. Altogether, our findings reveal a conserved mechanism by which GA regulates secondary wall cellulose synthesis in land plants and provide a strategy for manipulating cellulose production and plant growth. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, inflammatory skin disease involving both environmental and genetic factors. According to genome-wide association studies (GWAS), the TNIP1 gene, which encodes the TNF-α–induced protein 3-interacting protein 1 (TNIP1), is strongly linked to the susceptibility of psoriasis. TNIP1 is a widely expressed ubiquitin sensor that binds to the ubiquitin-editing protein A20 and restricts TNF- and TLR-induced signals. In our study, TNIP1 expression decreased in specimens of epidermis affected by psoriasis. Based on previous studies suggesting a role for TNIP1 in modulating cancer cell growth, we investigated its role in keratinocyte proliferation, which is clearly abnormal in psoriasis. To mimic the downregulation or upregulation of TNIP1 in HaCaT cells and primary human keratinocytes (PHKs), we used a TNIP1 specific small interfering hairpin RNA (TNIP1 shRNA) lentiviral vector or a recombinant TNIP1 (rTNIP1) lentiviral vector, respectively. Blocking TNIP1 expression increased keratinocyte proliferation, while overexpression of TNIP1 decreased keratinocyte proliferation. Furthermore, we showed that TNIP1 signaling might involve extracellular signal-regulated kinase1/2 (Erk1/2) and CCAAT/enhancer-binding protein β (C/EBPβ) activity. Intradermal injection of TNIP1 shRNA in BALB/c mice led to exaggerated psoriatic conditions in imiquimod (IMQ)-induced psoriasis-like dermatitis. These findings indicate that TNIP1 has a protective role in psoriasis and therefore could be a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Abstract: The glycinamide ribonucleotide transformylase (GART) gene, a trifunctional polypeptide, has phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, and phosphoribosylaminoimidazole synthetase activity, and is required for de novo purine biosynthesis. GART is highly conserved in vertebrates. Alternative splicing of GART results in two transcript variants encoding different isoforms. However, the expression and function of GART in the central nervous system lesion are still unclear. In this study, we used a traumatic spinal cord injury (SCI) model in adult Sprague-Dawley rats and investigated the dynamic changes of GART protein expression in the spinal cord. Western blot analysis revealed that GART was present in sham-operated spinal cord. It gradually increased, reached a peak at day 3 after SCI, and then declined during the following days. Double immunofluorescence staining revealed a widespread of GART, and the majority of GARTs are detected in astrocytes. After injury, GART expression was increased predominantly in astrocytes, positively correlated with the highly expressed proliferating cell nuclear antigen (PCNA). Knockdown of GART expression in cultured primary astrocytes by siRNA revealed that expression of GART in astrocytes plays a role in the LPS-induced release of pro-inflammatory factors, such as TNF-α and IL-6. These results showed that GART may participate in the pathophysiology of SCI, and more research is needed to have a good understanding of its function and mechanism. [Copyright &y& Elsevier]

Abstract: Aims: Nod like receptor pyrin domain containing 3 (NLRP3) is the best characterized member of nod like receptor family. Recent studies suggest that NLRP3 plays a crucial role in the pathogenesis of type-2 diabetes (T2DM), and variants in NLRP3 affect its mRNA stability and expression. Therefore, we hypothesize that the variants in NLRP3 gene may contribute to T2DM susceptibility. The aim of this study is to evaluate the association of NLRP3 SNPs with T2DM in Chinese Han patients. Methods: Two common variants in NLRP3 gene, rs10754558 and rs4612666, were detected using the polymerase chain reaction–restriction fragment length polymorphism procedure in 952 unrelated T2DM patients and 871 healthy controls. All participants were unrelated Chinese Hans. Results: The GG genotype and G allele frequencies of rs10754558 were significantly higher in T2DM patients than those in controls (for GG genotype, 19.6% vs. 14.5%, p =0.019; for G allele, 43.9% vs. 39.8%, p =0.013). The GG genotype of rs10754558 was significantly associated with higher LDL-C levels and more prone to insulin resistance, as evaluated by HOMA-IR or QUICK indexes. Conclusions: The variant (rs10754558) in NLRP3 is related to insulin resistance and increased risk of T2DM in Chinese Han population. [Copyright &y& Elsevier]

Adhesion molecules expressed on the uterine endometrium are potential receptive markers in embryo implantation. RL95-2 and HEC-1A cell lines represent the high- and low-receptive endometrial epithelium respectively. LeY (Lewis Y) is a difucosylated oligosaccharide highly expressed in the endometrium of some species during implantation. α1, 3 fucosylation of LeY is catalysed by FUT4 (fucosyltransferase IV), the key synthesis enzyme for LeY. We investigated whether the difference in receptivity between the 2 cell lines was related to different expressions of LeY and FUT4. RL95-2 cells expressed a higher level of LeY and FUT4 than HEC-1A cells, as shown by immunofluorescent staining, RT-PCR (reverse transcription-PCR) or Western blotting. FUT4-siRNA (small interfering RNA) transfection down-regulated FUT4 and LeY in RL95-2 cells, and inhibited the adhesion of the embryonic cells (JAR) to RL95-2 cell monolayer. FUT4-cDNA, however, increased the expression of FUT4 and LeY in HEC-1A cells, and increased the adhesion of embryonic cells to HEC-1A cell monolayer. Alterations of LeY level by up- or down-regulation of FUT4 also mediated EGFR (epidermal growth factor receptor)/MAPK (mitogen-activated protein kinase) signalling pathway. To conclude, the expression of LeY and FUT4 correlates with endometrial receptivity, making them potential new markers for the evaluation of endometrial receptivity. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is involved in the regulation of Purkinje cell development and motor learning, neural stem cell differentiation and reproductive-related plasticity. It is widely distributed in the adult brain, but the aging-related changes in the brain remain unclear. In this study age-related alterations of SRC-1 expression in female brain were examined. The results showed that striking age-related decreases of SRC-1 were noticed in those regions related to central regulation of motor (substantia nigra, pontine nuclei, lateral reticular nucleus and Purkinje cells, etc.), learning and memory (olfactory bulb, hippocampus, Purkinje cells, etc.), and neural stem cell (olfactory, dentate gyrus, cerebral cortex, etc.). Surprisingly, although SRC-1 immunopositive materials were predominantly detected in the cell nuclei, they were also detected in the extra-nuclear components predominantly in these motor-regulation sub-regions. The above results showing age-related decrease of SRC-1 in specific motor, learning and memory nuclei suggested its potential roles in neurodegenerative disorders, which may be one of the underlying mechanisms of the vulnerability of the aged brain. [Copyright &y& Elsevier]

Fiber quality is a major breeding goal in cotton, but phenotypically direct selection is often hindered. In this study, we identified fiber quality and yield related loci using GWAS based on 2.97 million SNPs obtained from 10.65× resequencing data of 1081 accessions. The results showed that 585 novel fiber loci, including two novel stable SNP peaks associated with fiber length on chromosomes At12 and Dt05 and one novel genome regions linked with fiber strength on chromosome Dt12 were identified. Furthermore, by means of gene expression analysis, GhM_A12G0090 , GhM_D05G1692 , GhM_D12G3135 were identified and GhM_D11G2208 function was identified in Arabidopsis. Additionally, 14 consistent and stable superior haplotypes were identified, and 25 accessions were detected as possessing these 14 superior haplotype in breeding. This study providing fundamental insight relevant to identification of genes associated with fiber quality and yield will enhance future efforts toward improvement of upland cotton. • A total of 909 novel fiber and yield loci were detected via WGRS with 10.65× coverage depth in 1,081 cotton accessions. • Three novel stable SNP peaks associated with FL and FS were found. • GhM_D11G2208 can promote cell elongation based up leaf trichome and dark-grown hypocotyls in Arabidopsis. • 14 consistent and stable superior haplotypes were detected based on 915 SNPs in Dt11 region. [ABSTRACT FROM AUTHOR]

Summary In a genome-wide survey on somatic copy-number alterations (SCNAs) of long noncoding RNA (lncRNA) in 2,394 tumor specimens from 12 cancer types, we found that about 21.8% of lncRNA genes were located in regions with focal SCNAs. By integrating bioinformatics analyses of lncRNA SCNAs and expression with functional screening assays, we identified an oncogene, f ocally a mplified l ncRNA on chromosome 1 ( FAL1 ), whose copy number and expression are correlated with outcomes in ovarian cancer. FAL1 associates with the epigenetic repressor BMI1 and regulates its stability in order to modulate the transcription of a number of genes including CDKN1A . The oncogenic activity of FAL1 is partially attributable to its repression of p21. FAL1 -specific siRNAs significantly inhibit tumor growth in vivo. [ABSTRACT FROM AUTHOR]

The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. AS models were established by subjecting ApoE-/-mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaque was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the Cytokine-cytokine receptor interaction pathway and Chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12 , Ccl22 , Cx3cr1 , Ccr7 , Ccr2 , Tnfrsf25 , and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, in cell models, the mRNA expressions of Ccl12 , Ccl22 , and Ccr2 were significantly upregulated (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12 , Ccl22 , Cx3cr1 , Ccr7 and Ccr2 (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the Cytokine-cytokine receptor interaction and Chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies. [Display omitted] • XFZY reduced lipid deposition and macrophage infiltration, increased collagen of plaques. • Cytokine-cytokine receptor interaction and Chemokine signaling pathways were enriched in AS. • XFZY downregulated CX3CL1 and CX3CR1, and upregulated GDF5. [ABSTRACT FROM AUTHOR]

Banxia Xiexin Decoction (BXD) is a traditional Chinese medical formula applied to gastrointestinal (GI) motility disorders. Previous studies showed that miR-451-5p was down-regulated in rats with GI motility disorders induced by gastric electrical dysrhythmia. Interstitial cells of Cajal (ICCs) are pacemakers for GI motility, while loss of ICCs is responsible for GI motility disturbance. Thus, the underlying interaction mechanisms for BXD regulating ICCs apoptosis via miR-451-5p remain to be explored. In this work, the main objectives were to examine the efficacy of BXD on ICCs via miR-451-5p both in GI motility disorders rats model and in vitro, as well as the potential contributions of SCF/c-kit signaling. Rats with gastric electrical dysrhythmia were established in male SD rats by using a single-day diet and a double fasting method (drinking diluted hydrochloric acid water during the period) for 4 weeks. The gastric slow wave (GSW) recording, RT-qPCR, and western blot were performed to examine the effects of BXD on ICCs apoptosis in rats with GED and miR-451-5p expression. In vitro assays included CCK-8, flow cytometry analysis, RT-qPCR, and western blot were applied to investigate the potential molecular mechanism of BXD on ICCs apoptosis via miR-451-5p. BXD promoted gastric motility, reduced ICCs apoptosis, and elevated miR-451-5p in GED rats. In addition, miR-451-5p was significantly up-regulated in ICCs after BXD treatment compared with that in ICCs with miR-451-5p inhibitor transfection. Meanwhile, high miR-451-5p expression with either BXD treatment or miRNA mimics enhanced ICCs proliferation and inhibit apoptosis. Moreover, overexpression of miR-451-5p can reverse G0/G1 arrest in ICCs by BXD treatment. Further, SCF and c-kit protein levels were detected to demonstrate that modulation of miR-451-5p by BXD treatment was involved in this signaling. Through this study, we demonstrated that BXD could promote ICCs proliferation and inhibit apoptosis via miR-451-5p and may involve the modulations of SCF/c-kit signaling, thus suggesting a new therapy basis for GI motility dysfunction from the perspective of modulation of ICCs apoptosis by targeting miR-451-5p. [Display omitted] • Banxia Xiexin Decoction improves gastric motility. • Inhibition of miR-451-5p expression induces interstitial cells of Cajal apoptosis. • Banxia Xiexin Decoction increases miR-451-5p expression. • The protective mechanism involves in SCF/c-kit signaling pathway. [ABSTRACT FROM AUTHOR]

Summary The discovery of long non-coding RNA (lncRNA) has dramatically altered our understanding of cancer. Here, we describe a comprehensive analysis of lncRNA alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across 13 cancer types from The Cancer Genome Atlas. Our results suggest that the expression and dysregulation of lncRNAs are highly cancer type specific compared with protein-coding genes. Using the integrative data generated by this analysis, we present a clinically guided small interfering RNA screening strategy and a co-expression analysis approach to identify cancer driver lncRNAs and predict their functions. This provides a resource for investigating lncRNAs in cancer and lays the groundwork for the development of new diagnostics and treatments. [ABSTRACT FROM AUTHOR]

Objective Karyopherin alpha 2 (KPNA2) is a member of the importin α family, which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic nuclear localization signal (NLS) of the cargo protein, and which has been reported as being involved in the pathogenesis of many diseases. This study was undertaken to determine the expression and possible functions of KPNA2 in osteoarthritis (OA). Methods KPNA2 expression in cartilage tissues of OA patients and normal controls was detected by RT-PCR and immunohistochemistry. SW1353 cells were stimulated with IL-1β to establish the chondrocyte injury model in vitro. The expression of KPNA2 and catabolic genes in IL-1β-treated SW1353 cells were determined by Western blot. The interaction between KPNA2 and P65 was analyzed by co-immunoprecipitation, the subcellular distribution and transportation of P65 were detected by the subcellular fractionation followed by immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference to analyze the role of KPNA2 in IL-1β-induced P65 nuclear importation and MMP13, ADAMTS-5 expression in SW1353 cells. Results Cartilage expression of KPNA2 was higher in patients with OA compared with normal controls and mainly locating in chondrocytes. In IL-1β-treated SW1353 cells, up-regulation of KPNA2 was accompanied by the elevated expression of the catabolic marker protein levels, including MMP13 and ADAMTS-5, and increased NF-κB P65 nuclear importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein levels in IL-1β-treated SW1353 cells. KPNA2 interacted with p65, and loss of KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-κB complex. Conclusions These findings suggested that KPNA2 may promote NF-κB activation via facilitating P65 nuclear transportation, and thus subsequently accelerate the catabolic events of osteoarthritis. [ABSTRACT FROM AUTHOR]

• Foliar spray of exogenous nitric oxide increased its concentration in waterlogged cotton. • Increased nitric oxide concentration triggered a series of physiological and molecular events. • Foliar spray of nitric oxide ultimately reduced yield loss under waterlogging. Waterlogging is a major abiotic stress that reduces crop growth and productivity. Nitric oxide (NO) is an essential signaling molecule involved in abiotic stress responses in many plant species. However, it is unclear if and how NO mitigates waterlogging stress in field-grown cotton. In this study, the NO donor sodium nitroprusside (SNP) or its scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl -imidazoline-1-1-oxyl-3-oxide (cPTIO) was foliar-applied to waterlogged and non-waterlogged cotton plants. The NO concentrations in different plant parts, plant growth, yield and yield components, as well as related physiological and molecular events, were examined over three consecutive years under field conditions. Foliar application of SNP increased NO concentration in leaves by 83.6 and roots by 80.2 % under waterlogging, while cPTIO decreased the NO concentration by 18.9 and 5.3 %, respectively. Biomass and lint yield were reduced by 17.2 and 36.0 % under waterlogging without the application of SNP or cPTIO, but the reductions were 8.8 and 28.4 % following SNP application and 29.5 and 43.4 % respectively, following cPTIO application. Foliar applied SNP increased biomass by 10.2 % and lint yield by 12.0 % under waterlogging, whereas cPTIO caused 5.0 and 11.5 % reductions in biomass and lint yield. Quantitative real-time PCR analysis showed that the SNP up-regulated the NO synthesis gene (Gh NIR), but down-regulated the genes involved in glycolysis and fermentation (Gh ADH 2 and Gh PDC), ethylene production (Gh ACO and Gh ACS 8), and abscisic acid (ABA) synthesis (Gh NCED 2). It also reduced hydrogen peroxide (H 2 O 2) production and malonaldehyde (MDA) content in the leaves, but increased the leaf chlorophyll content and photosynthetic rate. The levels of auxin (IAA) and gibberellic acid (GA) were increased by SNP but those of ABA and ethylene contents as well as the activities of alcohol dehydrogenase (ADH) and pyruvate decarboxylase (PDC) in leaves were decreased. The cPTIO showed an opposite effect to SNP in almost all physiological and molecular responses to waterlogging. The overall results indicated that increasing the concentrations of NO in plant tissues via the foliar application of SNP mitigates waterlogging stress through a series of physiological and molecular events, ultimately reducing biological and lint yield loss under waterlogging. Therefore, increasing the concentration of NO in plant tissues by genetic breeding or agronomic measures might be a potential strategy for improving waterlogging tolerance and reducing yield loss in cotton. [ABSTRACT FROM AUTHOR]