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The coronavirus disease 2019 (COVID-19) pandemic is a global public health event. Wuhan used to be the epicenter of China and finally controlled the outbreak through city lockdown and many other policies. However, the pandemic and the prevention strategies had a huge impact on the medical care procedures for breast cancer patients, leading to the delay or interruption of anticancer therapies. To better serve breast cancer patients under the premise of epidemic control, many strategies have been proposed and optimized in our center. One of the most important parts of these strategies is the promotion of telemedicine, including online consultation, online prescription, and drug mailing services. In keeping with the city and hospital policies, we have also introduced stricter ward management policies and more precise care. Here, we collected the diagnosis and treatment process of breast cancer patients in our center during the COVID-19 pandemic, which was found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, hoping to provide a reference for other cancer centers that may suffer from the similar situation. MicroAbstract The COVID-19 pandemic has a huge impact on the medical care procedures for breast cancer patients. Here we share our experience in the management of breast cancer patients during the pandemic in Wuhan, and it is found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, which may provide a reference for other centers.

Objective: To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Methods: SES (50, 100, and 200 mg kg−1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways. Results and conclusions: It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1β and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.

Acute liver injury can be caused by chemicals and can lead to liver failure. We investigated the protective effect of helicid (HEL) on acute liver injury caused by CCl4 in mice. We found that ALT and AST levels as well as hepatic pathological damage in mice treated with CCl4 was increased significantly, while the effects were decreased by HEL treatment. HEL treatment increased the activity of T-SOD, GSH and CAT and reduced the level of MDA in CCl4 treated mice. HEL improved the histopathology of liver caused by CCl4. HEL also reduced TNF-α, IL-1β and IL- 6 activity caused by CCl4. We investigated the phosphorylation of p65 and IκB protein and found that HEL can alleviate liver damage via the NF-κB signaling pathway. Our findings indicate that HEL protects against acute liver injury induced by CCl4. The protective effect of HEL appears to be due to its antioxidative and anti-inflammatory properties through the NF-κB signaling pathway.

Baicalin is a plant-derived flavonoid from Scutellaria baicalensis Georgi with multiple bioactivities and has a protective effect against avian pathogenic Escherichia coli (APEC) infection. However, the underlying mechanism of baicalin against APEC infection is still unknown. Therefore, we aimed to explore whether the protective effects and mechanisms of baicalin on APEC-induced lung inflammation were related to the regulation of gut microbiota. The results showed that baicalin significantly reduced APEC colonization and pro-inflammatory cytokines production, and additionally recovered air-blood barrier integrity in the lungs after APEC challenge. However, depletion of gut microbiota significantly weakened the protective effects of baicalin against APEC infection as mentioned above. Furthermore, baicalin markedly restored the dysbiosis of gut microbiota induced by APEC as well as increased the abundance of short chain fatty acid (SCFA)-producing bacteria and the production of SCFAs including acetic acid, propionic acid and butyric acid, especially acetic acid. In addition, the concentrations of acetic acid and its receptor free fatty acid receptor 2 (FFAR2) were significantly upregulated in the lung tissues after baicalin treatment. In conclusion, gut microbiota played a key role in the pharmacological action of baicalin against APEC-induced lung inflammation. Baicalin remodeled the dysbiosis of gut microbiota caused by APEC and increased the production of SCFAs, especially acetic acid in the gut, and then the increased acetate may circulate to the lungs to activate FFAR2 to defend APEC infection. Together, our study suggested that baicalin inhibited APEC infection through remodeling the gut microbiota dysbiosis and increasing the SCFA production. Furthermore, baicalin may serve as an alternative antibiotic and a novel therapeutic drug to prevent or treat APEC infection.

Background Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear. Methods In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL. Results The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4+CD8+ T cells. To explore the effect of immune response of lymphocytes to CDV, the mRNA expression of pro- and anti-inflammatory cytokines was examined. Interleukin (IL-6, IL-12B), and tumor necrosis factor (TNF)-α mRNA expression was significantly increased at 12–48 h after CDV infection. IL-10 mRNA expression was dramatically enhanced at 12–36 h after CDV infection. However, IL-4 and transforming growth factor (TGF-β) were not response to CDV infection. These results indicated that PBL differentiated intoCD4+CD8+ T cells and improved the inflammatory response to CDV infection. Conclusions After CDV infection, PBL differentiated into CD4+CD8+ T cells and initiated inflammatory response.

Avian pathogenic Escherichia coli (APEC), collectively known as causative agent of extraintestinal infections, is an important cause of morbidity and mortality in poultry. Currently, quorum sensing (QS), biofilm formation and virulence factors are considered as novel prospective targets for antimicrobial therapy to control APEC invasion. In addition, inflammatory responses are also served as the major pathological features of APEC invasion. This study was aimed to explore the effect of baicalin on APEC and APEC-induced inflammatory responses. After treatment with baicalin, we mainly examined the AI-2 secretion, biofilm formation, expression of virulence genes of APEC, and the levels of inflammatory cytokines, as well as the expression of NF-κB pathway. Our results showed that baicalin significantly inhibited the QS via decreasing the AI-2 secretion, biofilm formation, and the expression of virulence genes of APEC such as LsrB, LsrK, LuxS, pfs, H-NS, fimA, fimB, fyuA, csgA, csgB, and rpoS. Moreover, baicalin significantly attenuated the release of lactate dehydrogenase (LDH), and the adhesion of APEC to chicken type II pneumocytes to reduce cell damage. Furthermore, baicalin also inhibited the expression of pro-inflammatory cytokines and NF-κB activation. Thus, our data revealed that baicalin could interfere with the quorum sensing, biofilm formation and virulence genes expression to relieve the APEC pathogenicity. Additionally, baicalin decreased the inflammatory responses of chicken type II pneumocytes induced by APEC. Taken together, these data provide a novel potential pharmaco-therapeutic approach to chicken colibacillosis.

FOXA1 is a pioneer transcription factor which has been established as a carcinogenic factor and can regulate the expression of downstream target genes in breast cancer. We hypothesized that genetic variants modulating FOXA1 expression might play a role in the risk of breast cancer. Physical interaction predicted by PreSTIGE analysis and CHIA-PET data integration with cis-expression quantitative trait loci (cis-eQTL) based SNP-FOXA1 analysis were used to identify potentially regulatory variants modulating the expression of FOXA1. Then, we utilized a case–control study consisting of 855 new diagnosed breast cancer cases and 920 controls in the Chinese population to identify breast cancer associated variants. Biological assays were conducted in breast cancer cell lines to illustrate the effects of associated variants on breast cancer risk. We identified that rs7160774 G > A variant was associated with lower risk of breast cancer (OR = 0.77, 95% confidence interval = 0.62–0.96, P = 0.022). Biological experiments indicated that rs7160774[A] allele down-regulated the expression of FOXA1 compared to the G allele by influencing transcription factor binding affinity, thus playing an important role in the development of breast cancer. Our study suggested that the regulatory variant rs7160774 was associated with risk of breast cancer by long-range modulating FOXA1 expression and provided critical insights into pinpoint causal genetic variants.

Chicken colibacillosis is caused by avian pathogenic Escherichia coli (APEC), and results in huge economic losses to the poultry industry. With the investigation of the gut-lung axis, more studies have demonstrated the important role of gut microbiota in lung inflammation. The precise role of the gut microbiota in chickens-associated colibacillosis, however, is unknown. Thus, this study assessed the function of the gut microbiota in the chicken defense against APEC infection. Chicken gut microbiota was depleted by drinking water with a mixture of antibiotics (Abx), and subsequently, a model of colibacillosis was established by the intranasal perfusion of APEC. The results showed that gut microbiota protects the chicken challenge by APEC from aggravated lung histopathologic injury, up-regulated pro-inflammatory cytokine production, and increased bacterial load in lung tissues compared with controls. In addition, the air-blood barrier permeability was significantly increased in gut microbiota-depleted chickens compared to the control chickens after challenge with APEC. Furthermore, feeding acetate significantly inhibited the lung inflammatory response and the reduced air-blood permeability induced by APEC infection. The expression of free fatty acid receptor 2 (FFAR2), a receptor for acetate, was also increased in the lung after treatment with acetate. In conclusion, depletion of the gut microbiota resulted in increased susceptibility of chickens to APEC challenge, and gut microbiota derived acetate acted as a protective mediator during the APEC challenge. Novel therapeutic targets that focus on the gut microbiota may be effective in controlling colibacillosis in poultry.

Background: In recent years, the effective ingredients of some medicine play an anti-infection role in inhibiting the formation of bacterial virulence factors and biofilm without affecting the growth of bacteria, which can reduce the survival pressure of bacteria and is not easy to develop drug resistance. It is considered to be a better way to control the infection of pathogenic microorganisms. Bacteria can produce signal molecules called auto-inducers (AIs) which can sense the bacteria density change. When auto-inducers accumulate to the threshold, they will regulate the bacteria biological behavior to adapt the changes of environment, including the formation of biofilm, virulence factors and bioluminescence. This is quorum sensing (QS).4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) is a non-halogenated furanone found in strawberries, pineapples and other fruits and widely used as a safe food additive in beverages, ice cream and cigarettes. At present, there are lots of studies about furanone. Previous studies have shown that this kind of compound can compete with Acyl-homoserine lactone (AHL) in binding with its receptors, which inhibits the initiation of quorum sensing system. Results: In recent years, few studies about the transcriptome analysis of the furanone interacting with Enterotoxigenic Escherichia coli (ETEC) were reported. Therefore, we analyzed the effect of furanone on ETEC O139 transcriptome by RNA-seq. The result show that genes related to QS did not change after the interaction of 10μg/ml furanone and ETEC O139, while the expression of some genes related to the pathogenicity of ETEC O139 increased, such as flagellum assembly, biofilm formation and adhesion and so on.Conclusions: 10μg/ml furanone have no influence on QS system, but could contribute to adhesion, invasion, flagellum assembly and biofilm formation of ETEC O139.

Background Rap1GAP is a tumor suppressor and is downregulated in human malignancies including papillary thyroid cancer (PTC). The mechanism of its suppression in PTC remains unclear. Methods Bioinformatic analyses were carried out to evaluate clinical significance and to predict upstream miRNA bindings of Rap1GAP. Three PTC cell lines, TPC-1, B-CPAP, and K1, were employed for functional verification and further experiments. We used dual-luciferase reporter gene assay to confirm the miRNA binding prediction, Western blotting and quantitative polymerase chain reaction (qPCR) to explore miRNA and Rap1GAP regulation, Transwell and wound healing assays to compare cell migration and invasion after protein knockout or overexpression, and Cell Counting Kit-8 (CCK-8) assay to evaluate cell proliferation. Results Rap1GAP expression was suppressed in thyroid cancer compared to adjacent normal tissues and was a potential diagnostic marker of PTC. Rap1GAP suppression was correlated to younger age, advanced T stage, N stage, extrathyroidal extension, BRAF-like tumors, and higher risk of recurrence. Combined analysis of bioinformatic prediction and dual-luciferase assay revealed binding between miR-3121-3p with 3'UTR of Rap1GAP promoter. MiR-3121-3p promoted cell migration, invasion, and proliferation via inhibiting Rap1GAP and thus upregulating MAPK pathway. Overexpression and knockdown of Rap1GAP could counteract the influence on cell migration and invasion carried out by miR-3121-3p mimic and inhibitor, respectively. Rap1GAP partially impaired the effect of miR-3121-3p in cell growth in the CCK-8 assay. Conclusions Rap1GAP expression is suppressed in PTC and is a potential diagnostic marker. Its upstream regulator, miR-3121-3p, affects tumor metastasis and proliferation via regulating Rap1GAP expression. MAPK signaling pathway may be involved in this effect.

BACKGROUND AND PURPOSE Chicken colibacillosis, caused by avian Escherichia coli (APEC), results in huge economic losses to the poultry industry. Baicalin exerts protective effects during the development of colibacillosis. In this study, we mainly explored the mechanism of this protective effects with regard to gut microbiota. EXPERIMENTAL APPROACH The chicken colibacillosis model was established by intratracheal instillation of APEC. The gut microbiota-depleted chicken model was established with broad-spectrum antibiotics. Viscera index measurement and Haematoxylin and eosin stain were applied to assess histological changes of tissues. ELISA were used to measure the cytokines and Quantitative-PCR were used to evaluate the gene expression. The gut microbiota and its metabolite were detected by 16srDNA and ultrahigh-performance liquid chromatography (LC-MS). KEY RESULTS Depletion of gut microbiota exacerbated the tissue damage and weakened the protective effects of baicalin during APEC-induced chicken colibacillosis while pretreatment of baicalin reduced these changes and inflammatory response induced by APEC. Moreover, APEC infection led to dysbiosis of gut microbiota and its metabolites. However, the pretreatment of baicalin remodeled the gut microbiota featured with increased abundance of Intestinimonas and its associated with beneficial metabolites. CONCLUSIONS Gut microbiota played a protective role in the prevention of chicken colibacillosis and the pharmacological action of baicalin. The altered specific gut bacterial and/or metabolites may be served as indicators to predict the occurrence and prognosis of chicken colibacillosis. Our findings may provide a paradigm for the mechanistic studies of compounds and aid the exploration of the mechanisms and pathways underlying the function of herbal medicines.

Background: Thyroid cancer is one of the most prevalent endocrine cancers with a rising incidence rate over the past years. Papillary thyroid cancer (PTC) is the dominant historical type of thyroid cancer. Early lymph node metastasis happens frequently in PTC. However, some of the lymph node metastasis may be troublesome for detecting because of limited methods.Methods: Robust rank aggregation afforded us the shared differential expression genes among multiple datasets. Gene ontology analysis was performed to identify potential functions. Weighted gene co-expression network analysis was used to research the correlations between gene expression patterns with clinical characteristic. Protein-protein interaction network was performed to identify the hub genes. The least absolute shrinkage and selection operator and Logistic regression were performed to construct a prediction model.Results: We developed a three-gene signature prediction model for lymph node metastasis in PTC through transcriptomic analysis. After quality control, we collected 8 microarray datasets from GEO database and an RNA sequencing dataset from TCGA database. We found the transcriptome profiles were correlated with lymph node metastasis and 3 genes were verified to be independent prediction factors towards those statistic approach. Afterwards, we designed a predicable risk score system and effectively confirmed the model in two independent papillary thyroid cancer cohorts.Conclusions: We recommended a successful predicable model of lymph node metastasis in papillary thyroid cancer patients with moderate accuracy.

Madecassoside (MA), a crucial ingredient of Centella asiatica, has been reported to exhibit a variety of bioactivities, including antipulmonary fibrosis, and antiinflammatory effects. Here we aimed to elucidate the protective effects and underlying mechanisms of MA on LPS-induced acute lung injury (ALI). The mice were treated with MA for one week and then received intratracheal of LPS to establish the ALI model. Then we evaluated the pathological changes by haematoxylin and eosin staining and measured the levels of proinflammatory cytokines and myeloperoxidase (MPO) by ELISA, the transcriptional level of tight junction proteins by qRT-PCR, as well as the expression of Toll-like receptor4/Nuclear factor kappa-B (TLR4/NF-κB) pathway by Western blot. The results showed that MA significantly inhibited LPS-induced pathological damages, lung edema, MPO, and proinflammatory cytokines production. Furthermore, MA obviously repaired alveolar epithelium integrity showing by reduced secretion of total proteins in the BALF and enhanced mRNA expression of tight junction as Occludin and zonula occludens-1 (ZO-1) comparing to LPS. Further research showed that LPS stimulation activated the TLR4/NF-κB signaling pathway and the activation was inhibited by MA. In conclusion, these data indicated that MA had protective effects against LPS-induced ALI. The therapeutic mechanisms may be associated with reducing the alveolar epithelium permeability and inflammatory response via repressing the activation of TLR4/NF-κB pathway.

Background: Tumor microenvironment is essential for breast cancer progression and metastasis. Our study sets out to examine the genes affecting stromal and immune infiltration in breast cancer progression and prognosis. Materials and Methods: This work provides an approach for quantifying stromal and immune scores by using ESTIMATE algorithm based on gene expression matrix of breast cancer patients in TCGA database. We found differentially expressed genes (DEGs) through limma R package. Functional enrichments were accessed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Besides, we constructed a protein-protein network, identified several hub genes in Cytoscape, and discovered functionally similar genes in GeneMANIA. Hub genes were validated with prognostic data by Kaplan-Meier analysis both in The Cancer Genome Atlas (TCGA) database and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and a meta-analysis of hub genes prognosis data was utilized in multiple databases. Furthermore, their relationship with infiltrating immune cells was evaluated by Tumor IMmune Estimation Resource (TIMER) web tool. Cox regression was utilized for overall survival (OS) and recurrence-free survival (RFS) in TCGA database and OS in METABRIC database in order to evaluate the impact of stromal and immune scores on patients prognosis. Results: One thousand and eighty-five breast cancer patients were investigated and 480 differentiated expressed genes (DEGs) were found based on the analysis of mRNA expression profiles. Functional analysis of DEGs revealed their potential functions in immune response and extracellular interaction. Protein-protein interaction network gave evidence of 10 hub genes. Some of the hub genes could be used as predictive markers for patients prognosis. In this study, we found that tumor purity and specific immune cells infiltration varied in response to hub genes expression. The multivariate cox regression highlighted the fact that immune score played a detrimental role in overall survival (HR = 0.45, 95% CI: 0.27–0.74, p = 0.002) and recurrence-free survival (HR = 0.41, 95% CI: 0.22–0.77, p = 0.006) in TCGA database. These result was confirmed in METABRIC database that immune score was a protector of OS (HR = 0.88, 95% CI: 0.77–0.99, p = 0.039). Conclusions: Our findings promote a better understanding of the potential genes behind the regulation of tumor microenvironment and cells infiltration. Immune score should be considered as a prognostic factor for patients' survival.

Acute liver injury can be caused by chemicals and can lead to liver failure. We investigated the protective effect of helicid (HEL) on acute liver injury caused by CCl

Acute lung injury (ALI) is a common and complex inflammatory lung syndrome with higher morbidity and mortality rate. Piceatannol (PIC) has anti-inflammation and anti-oxidant properties. The study was designed to explore the effect and the action mechanisms of PIC on lipopolysaccharide (LPS)-induced ALI. Twenty-four hours after LPS challenge, mice from different treatment groups were euthanized, and the bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Then the degree of pulmonary edema, lung pathological changes, myeloperoxidase (MPO) activity, and the production of pro-inflammatory cytokines were detected. Additionally, the messenger RNA (mRNA) expressions associated with cell adhesion molecules and tight junction were analyzed through quantitative real-time (qRT)-PCR, and the TLR4/NF-κB activation was examined by western blot. The results showed that PIC significantly inhibited LPS-induced lung edema, histopathological damage, MPO activity, cell infiltration, and pro-inflammatory cytokines production. Moreover, PIC notably suppressed mRNA expressions associated with inflammation and cell adhesion molecules. Furthermore, PIC also alleviated LPS-induced damage of air-blood barrier through reducing the levels of total proteins in BALF and recovering the expression of occludin and ZO-1 in the lung tissues. We also found that PIC remarkably restrained the LPS-induced TLR4/NF-κB pathway activation in lung tissues. In conclusion, PIC may be potential to treat LPS-induced acute lung injury (ALI) via regulating air-blood barrier and TLR4/NF-κB signaling pathway activation.

Long non-coding RNA NBR2 is a transcript of the neighbor of BRCA1 gene 2 and can regulate tumor development. However, there is little information on the role of NBR2 in the progression of thyroid cancers (TC). Here, we show that NBR2 expression is down-regulated in TC tissues and associated with histologic subtypes of TC. NBR2 expression was variably reduced in different TC cells. While NBR2 silencing significantly enhanced the malignancy of BCPAP cells by increasing cell proliferation, clonogenicity, wound healing, and invasion as well as tumor growth in vivo, and decreasing spontaneous apoptosis, NBR2 over-expression had opposite effects in BHT101 cells. Furthermore, treatment with A-769662 (a specific AMPK activator), like NBR2 over-expression, significantly attenuated the malignancy of BHT101 cells while treatment with Compound C (a specific AMPK inhibitor) significantly rescued that NBR2-reduced malignancy of BHT101 cells. In comparison with non-tumor thyroid epithelial Nthy-ori 3-1 cells, obviously increased GLUT-1 expression, but decreased AMPK and ACC phosphorylation were detected in TC cells. While NBR2 silencing further enhanced GLUT-1 expression and reduced AMPK and ACC phosphorylation as well as the EMT process in BCPAP cells. NBR2 over-expression also had opposite effects in BHT101 cells. Similar patterns of GLUT-1 expression and AMPK and ACC phosphorylation were detected in the different types of xenograft TC tumors in vivo. Therefore, such data indicated that NBR2 acted as a tumor suppressor of thyroid cancers associated with enhancing the AMPK signaling and NBR2 may be a potential biomarker and therapeutic target for thyroid cancers.

Background Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer. Methods Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis. Results Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1. Conclusions In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.

Avian pathogenic Escherichia coli (APEC) is a kind of highly pathogenic parenteral bacteria, which adheres to chicken type II pneumocytes through pili, causing inflammatory damage of chicken type II pneumocytes. Without affecting the growth of bacteria, anti-adhesion to achieve anti-inflammatory effect is considered to be a new method for the treatment of multi-drug-resistant bacterial infections. In this study, the anti-APEC activity of schizandrin was studied in vitro. By establishing the model of chicken type II pneumocytes infected with APEC-O78, the adhesion number, the expression of virulence genes, the release of lactate dehydrogenase (LDH), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were detected. The results showed that schizandrin reduced the release of LDH and the adherence of APEC on chicken type II pneumocytes. Moreover, schizandrin markedly decreased the levels of IL-1β, IL-8, IL-6, and TNF-α, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings revealed that schizandrin could reduce the inflammatory injury of chicken type II pneumocytes by reducing the adhesion of APEC-O78 to chicken type II pneumocytes. The results indicate that schizandrin can be a potential agent to treat inflammation caused by avian colibacillosis.

Breast cancer is the most frequently diagnosed malignancy among women, and triple-negative breast cancer (TNBC) is a highly aggressive subtype. Increasing evidence has shown that lncRNAs are involved in tumor growth, cell-cycle, and apoptosis through interactions with miRNAs or mRNAs. However, there is still limited data on ceRNAs involved in the molecular mechanisms underlying TNBC. In this study, we applied the weighted gene co-expression network analysis to the existing microarray mRNA and lncRNA expression data obtained from the breast tissues of TNBC patients to find the hub genes and lncRNAs involved in TNBC. Functional enrichment was performed on the module that correlated with Ki-67 status the most (Turquoise module). The hub genes in the Turquoise module were found to be associated with DNA repair, cell proliferation, and the p53 signaling pathway. We performed co-expression analysis of the protein-coding and lncRNA hub genes in the Turquoise module. Analysis of the RNA-seq data obtained from The Cancer Genome Atlas database revealed that the protein-coding genes and lncRNAs that were co-expressed were also differentially expressed in the TNBC tissues compared with the normal mammary tissues. On the basis of establishing the ceRNA network, two mRNAs (RAD51AP1 and TYMS) were found to be correlated with overall survival in TNBC. These results suggest that TNBC-specific mRNA and lncRNAs may participate in a complex ceRNA network, which represents a potential therapeutic target for the treatment of TNBC.

Avian pathogenic Escherichia coli (APEC) causes great economic loss to the poultry industry worldwide. Chicken type II pneumocytes (CP II cells) secrete surfactants and modulate lung immunity to decrease the infection of the invading pathogen. Nevertheless, the pathogenesis of CP II cells to APEC infection remains poorly understood. Therefore, we conducted global gene expression profiling of CP II cells after APEC-O78 infection to explore the host-pathogen interaction. The differentially expressed genes of CP II cells to APEC infection were characterized by RNA-seq with EB-seq algorithm. In consequence, the mRNA of 18996 genes was identified, and CP II cells responded to APEC infection with marked changes in the expression of 1390 genes. Among them, there are 803 down-regulated mRNAs and 587 up-regulated mRNAs. The KEGG prediction and Gene Ontology terms analysis revealed that the major enriched pathways were related to NF-κB signaling pathway, apoptosis pathway, tight junction, and cytokine-cytokine receptor interaction and other pathways. We adopted qRT-PCR to verify the validity of the selected gene expression. The fold induction of qPCR was similar to the RNA-seq results. These results provide a better understanding of the pathogenesis of APEC, especially apoptosis pathway involved in APEC infection.

Bacterial pneumonia is a leading cause of death in the animal husbandry. Acute lung injury (ALI), most often seen as a part of systemic inflammatory process, characterized by progressive hypoxemia, edema, and neutrophil accumulation in the lung. Baicalin has been reported to inhibit inflammatory response, but its role in ALI remains unknown. The purpose of our study was to determine the protective effect and possible mechanism of baicalin against avian pathogenic Escherichia coli (APEC)-induced ALI in chicken. Chickens were conditioned with baicalin 1 week before intratracheally instilled with APEC. Then, chickens were sacrificed by CO2 inhalation 12 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of pro-inflammatory cytokines and activation of NF-κB signaling pathway. The results showed that pre-treatment of chickens with baicalin significantly alleviated the death rate, histopathological changes in lung tissues. The W/D ratio, MPO activity and production of cytokines, such as IL-1β, TNF-α, IL-6 of lung tissues were also decreased following treatment with baicalin. Furthermore, the mechanism responsible for these effects was attributed to the inhibitory effect of baicalin on nuclear factor-κB (NF-κB) signaling activation. These data thus support the application of baicalin as a potential medicine for the treatment of E. coli-induced ALI by regulating NF-κB signaling pathway.

Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear.In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL.The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4After CDV infection, PBL differentiated into CD4

Cinobufagin (CBG), one active ingredient isolated from Venenum Bufonis, has been demonstrated to have immunoregulatory effect. The aim of this study was to investigate whether CBG can enhance the protective efficacy of formalin-inactivated Salmonella typhimurium (FIST) in mice. ICR mice were immunized with FIST (106 CFU/mouse) alone or mixed with CBG (10, 20, and 40 μg) or alum (200 μg) on day 1 and day 15. Two weeks after the second immunization, serum and spleen were sampled for measuring FIST-specific antibody levels, cytokine levels, and splenocyte proliferation. The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNγ) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST. In vivo protection studies showed that CBG significantly decreased the bacterial burdens in the spleen and prolonged the survival time of FIST-immunized mice challenged with live Salmonella typhimurium. In vivo IFNγ neutralization led to a significant reduction in FIST-specific IgG2a and IFNγ levels, and in the protective efficacy in CBG/FIST-immunized mice. In conclusion, CBG enhances the protective efficacy of formalin-inactivated Salmonella typhimurium vaccine by promoting the Th1 immune response.

Avian pathogenic Escherichia coli (APEC) infections are responsible for great losses in the poultry industry. Quorum sensing (QS) acts as a global regulatory system that controls genes involved in bacterial pathogenesis, metabolism and protein biosynthesis. However, whether QS of APEC is related to cell damage has not been elucidated. In the present study, we explored the correlation between the damage of chicken type II pneumocytes induced by APEC and the autoinducer-2 (AI-2) activity of APEC. The results showed that when chicken type II pneumocytes were co-cultured with 108 CFU/ml of APEC-O78 for 6 h, the release of LDH reached the highest level (192.5 ± 13.4 U/L) (P

Avian pathogenic Escherichia coli (APEC) can cause serious pathological changes and inflammation in chickens. Schizandrin has anti-inflammatory activity and can prevent damage to various tissues and organs. The purpose of this study was to investigate the protective effect of schizandrin on APEC-induced lung lesions in chickens and explore the potential mechanism of schizandrin protection. The schizandrin (50, 100, and 200 mg/kg) was intragastrically administered for 3 days. APEC was administered using intraperitoneal (i.p.) injection to induce lung lesions. Then, chickens were sacrificed by CO2 inhalation 24 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings showed that schizandrin markedly inhibited pathological changes, pulmonary edema, MPO activity and MDA content. Moreover, schizandrin markedly reduced the levels of TNF-α, IL-1β, IL-6 and IL-8 in lung tissue. Importantly, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings reveal that schizandrin displays anti-oxidant and anti-inflammatory activity against APEC-induced lung lesions in chickens, paving the way for rational use of schizandrin as a protective agent against lung-related inflammatory disease.

Ideal potential vaccine adjuvants to stimulate a Th1 immune response are urgently needed to control intracellular infections in clinical applications. Telocinobufagin (TBG), an active component of Venenum bufonis, exhibits immunomodulatory activity. Therefore, we investigated whether TBG enhances the Th1 immune response to ovalbumin (OVA) and formalin-inactivated Salmonella typhimurium (FIST) in mice. TBG augmented serum OVA- and FIST-specific IgG and IgG2a and the production of IFNγ by antigen-restimulated splenocytes. TBG also dramatically enhanced splenocyte proliferative responses to concanavalin A, lipopolysaccharide, and OVA and substantially increased T-bet mRNA levels and the CD3(+)/CD3(+)CD4(+)/CD3(+)CD8(+) phenotype in splenocytes from OVA-immunized mice. In in vivo protection studies, TBG significantly decreased the bacterial burdens in the spleen and prolonged the survival time of FIST-immunized mice challenged with live S. typhimurium. In vivo neutralization of IFNγ with anti-IFNγ mAbs led to a significant reduction in FIST-specific IgG2a and IFNγ levels and in anti-Salmonella effect in TBG/FIST-immunized mice. In conclusion, these results suggest that TBG enhances a Th1 immune response to control intracellular infections.

Avian pathogenic Escherichia coli (APEC) induce septicemia in chickens by invading type II pneumocytes to breach the blood-air barrier. The virulence of APEC can be regulated by quorum sensing (QS). Andrographolide is a QS inhibitor of Pseudomonas aeruginosa (P. aeruginosa). Therefore, we investigate whether andrographolide inhibits the injury of chicken type II pneumocytes by avian pathogenic E. coli O78 (APEC-O78) by disrupting the bacterial QS system. The results showed that sub-MIC of andrographolide significantly reduced the release of lactate dehydrogenase (LDH), F-actin cytoskeleton polymerization, and the degree of the adherence to chicken type II pneumocytes induced by APEC-O78. Further, we found that andrographolide significantly decreased the autoinducer-2 (AI-2) activity and the expression of virulence factors of APEC-O78. These results suggest that andrographolide reduce the pathogenicity of APEC-O78 in chicken type II pneumocytes by interfering QS and decreasing virulence. These results provide new evidence for colibacillosis prevention methods in chickens.

Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 μg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3–57.0% and 37.2–38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59–86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection.

Climate change in Northwest China could lead to the change of the hydrological cycle and water resources. This paper assessed the influence of climate change on runoff in the Manas River basin as follows. First, the temporal trends and abrupt change points of runoff, precipitation, and mean, lowest and highest temperature in yearly scale during the period of 1961–2015 were analyzed using the Mann-Kendall (MK) test. Then the correlation between runoff and climatic variables was characterized in a monthly, seasonal and yearly scale using the partial correlation method. Furthermore, three global climate models (GCMs) from Coupled Model Inter-comparison Project Phase 5 (CMIP5) were bias-corrected using Equidistant Cumulative Distribution Functions (EDCDF) method to reveal the future climate change during the period from 2021 to 2060 compared with the baseline period of 1961–2000. The influence of climate change on runoff was studied by simulating the runoff with the GCMs using a modified TOPMODEL considering the future snowmelt during the period from 2021 to 2060. The results showed that the runoff, precipitation, and mean, lowest and highest temperature all presented an increasing trend in yearly scale during the period of 1961–2015, and their abrupt change points were at a similar time; the runoff series was more strongly related to temperature than to precipitation in the spring, autumn and yearly scales, and the opposite was true in winter. All GCMs projected precipitation and temperature, and the runoff simulated with these GCMs were predicted to increase in the period from 2021 to 2060 compared with the baseline period of 1961–2000. These findings provide valuable information for assessing the influence of climate change on water resources in the Manas River basin, and references for water management in such regions.

Avian pathogenic Escherichia coli (APEC) are extra-intestinal pathogenic E. coli, and usually cause avian septicemia through breaching the blood-gas barrier. Type II pneumocytes play an important role of maintaining the function of the blood-gas barrier. However, the mechanism of APEC injuring type II pneumocytes remains unclear. α-cyperone can inhibit lung cell injury induced by Staphylococcus aureus. In order to explore whether α-cyperone regulates the adherence and invasion of APEC-O78 to chicken type II pneumocytes, we successfully cultured chicken type II pneumocytes. The results showed that α-cyperone significantly decreased the adherence of APEC-O78 to chicken type II pneumocytes. In addition, α-cyperone inhibited actin cytoskeleton polymerization induced by APEC-O78 through down regulating the expression of Nck-2, Cdc42 and Rac1. These results provide new evidence for the prevention of colibacillosis in chicken.

This paper built a hybrid power system, including wind power, PV power and hydro power generation. It is presented mathematical model for the optional design of hybrid power system. The object of the model are to minimize the initial investment cost, power supply reliability and power complementation. The constraint condition are included system working, installed capacity and load balance, So the capacity matching model is established. A stand-alone photovoltaic of pasturing area is calculated by using the model. The result shows that the optional design model have an important sense, which improved power supply reliability, complementary characteristics of hybrid power and reduce the total cost of the system.

In this work, a magnetic polymer electrolyte composed by agarose as polymer matrix, NMP as solvent and NiO/TiO2mixed nanoparticles as modifier was investigated and employed in the solid-sate dye-sensitized solar cells (DSSCs). The influence of NiO/TiO2mixed nanoparticles on the morphology and ionic conductivity of the polymer electrolyte was studied by SEM and electrochemical impedance spectra. From SEM analysis, the mixing of NiO with TiO2nanoparticle in polymer electrolyte leads to smooth surface of the polymer electrolyte films. The polymer electrolyte modified by mixed nanoparticles with NiO: TiO2ratio of 1:4 shows the maximum ionic conductivity of 6.64×10-3S·cm-1. From photovoltaic performance study, the increase of NiO: TiO2ratio in polymer electrolyte leads to an improvement in light-to-electric conversion efficiency. The optimal photoelectric efficiency is achieved at NiO: TiO2ratio of 1: 4. Besides, after treatment under an external magnetic field, the DSSC modified with NiO: TiO2ratio of 1: 4 exhibits a better photovoltaic performance than that of DSSC without magnetic field treatment.

Ginsenoside Rh2, an active component of ginseng, exhibits immunoregulatory and anti-inflammatory properties. Rh2-B1, a sulfated derivative, was prepared to enhance its water solubility. We studied the effect of Rh2-B1 on CTLL-2, a CD8⁺ cytotoxic T cell line that was known for protecting against viral infection.We aimed to investigate the effect of Rh2-B1 on interferon (IFN)-γ production and cell proliferation and its possible mechanism.Enzyme-linked immunosorbent assay (ELISA) was employed to analyze the IFN-γ concentration of the whole blood and the supernatant of CTLL-2 cell culture. Cell proliferation assay was conducted using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Western blots were used to evaluate changes in signal transduction pathways in CTLL-2 cells.Rh2-B1 was able to enhance IFN-γ production from whole blood culture of Balb/c mice. We then evaluated the effect of Rh2-B1 on a cytotoxic T cell line, CTLL-2 for cell proliferation, IFN-γ production and its molecular mechanism. Rh2-B1 promoted cell proliferation and IFN-γ production of CTLL-2 cells. It also induced activation of p38 mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinases (ERK), but inhibited p56 Lck and transducer and activator of transcription 5 (STAT5) expression. The effect was blocked by the specific p38 MAPK inhibitor SB203580 and ERK inhibitor U0126.Rh2-B1 could stimulate cell proliferation and IFN-γ production by activating the p38 MAPK- and ERK-dependent signaling pathways in cytotoxic T cells. This may be a novel medicine for treatment of viral infections.

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor (ER), progesterone receptor (PR) and Her-2 status. The prevalence rate of each molecular subtype was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows: luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. However, in the age-specific groups, the age group of ≤35 years was more likely to get basal cell-like cancer (36.9%). Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node (LN) metastasis, tumor stage by American Joint Committee on Cancer (AJCC), radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis (≥1 positive LN) and incidence of high-volume LN metastasis (≥4 positive LN). The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopathological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese population.

A magnetic polymer electrolyte using agarose as polymer matrix, NMP as solvent and NiO nanoparticles as modifier was investigated and employed in the dye-sensitized solar cell (DSSC) in this paper. The influence of NiO nanoparticles content on magnetic polymer electrolyte was characterized by SEM and ionic conductivity test. The photovoltaic properties of the corresponding DSSCs were studied by photovoltaic performance tests. The results showed that the surface morphology of the polymer electrolyte with 1.0wt% NiO nanoparticles was smooth and this magnetic polymer electrolyte showed the maximum conductivity (2.43×10-3S•cm-1). The optimal photoelectric efficiency of 1.63% was achieved at the NiO nanoparticles content of 1.0wt%.