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Objectives To characterize the oxazolidinone resistance gene poxtA in a Lactobacillus salivarius isolate of pig origin. Methods L. salivarius isolate BNS11 was investigated for the presence of mobile oxazolidinone resistance genes by PCR. Antimicrobial susceptibility testing was performed by broth microdilution. Transfer experiments were conducted to assess horizontal transferability of the gene poxtA. WGS was carried out using a combination of Oxford Nanopore MinION/Illumina HiSeq platforms. The presence of translocatable units (TUs) carrying resistance genes was studied by PCR assays and subsequent sequence analysis. Results L. salivarius isolate BNS11 was positive for poxtA. WGS showed that it harboured two gene copies each of the poxtA and the fexB genes, which were located on the broad-host-range Inc18 plasmid pBNS11-37kb and in the chromosomal DNA, respectively. The plasmid-borne poxtA gene together with the genes fexB, vat(E) and erm(C) were located in an MDR region on plasmid pBNS11-37kb. Analysis of the genetic context showed that an approx. 11 kb poxtA-fexB fragment was integrated into the chromosomal DNA and two novel IS elements ISLasa1 and ISLasa2 were identified in this inserted fragment. PCR assays revealed that five different IS1216E-based TUs carrying the resistance genes poxtA, fexB, vat(E) or erm(C) were formed. Conclusions To the best of our knowledge, this is the first report of the transferable oxazolidinone resistance gene poxtA in the genus Lactobacillus. In addition, the presence of IS1216E-based TUs will contribute to the persistence and accelerate the dissemination of resistance genes, including poxtA.

Nonlinear ultrasonic guided waves have attracted increasing attention in the field of structural health monitoring due to their high sensitivity and long detection distance. In practical applications, the temperature of the tested structure will inevitably change, so it is essential to evaluate the effects of temperature on nonlinear ultrasonic guided waves. In this paper, an analytical approach is proposed to obtain the response law of nonlinear guided waves to temperature based on the semi-analytical finite element (SAFE) method. The plate structure is investigated as a demonstration example, and the corresponding simulation analysis and experimental verification are carried out. The results show that the variation trends of different cumulative second harmonic modes with temperature are distinct, and their amplitudes monotonically increase or decrease with the continuously rising temperature. Therefore, in the applications with nonlinear ultrasonic guided waves, it is necessary to predict the changing trend of selected cumulative second harmonics under the action of temperature and compensate the result for the influence of temperature. The methods and conclusions presented in this paper are also applicable to other types of structures and have general practicality.

Aim at the actual engineering requirements of wind power operation and maintenance under complex sea conditions, a control method of the active wave compensation system for maintenance ships based on the Stewart platform is presented. The kinematics of the platform is analyzed, and the coordinate transformation, pose, and inverse solutions are analyzed and calculated. The multi-body dynamics simulation model is established by using MATLAB. For the problem of the load nonlinearity and strong coupling of the nonlinear Stewart platform, an active wave compensation active disturbance rejection control (ADRC) is built to attain the high-precision control of the six-degree-of-freedom (6-DOF) Stewart platform. The numerical simulation shows that the proposed control scheme has good tracking accuracy and strong anti-interference ability.

Acute myocardial infarction is a common cardiovascular disease with high mortality. Myocardial reperfusion injury can counteract the beneficial effects of heart reflow and induce secondary myocardial injury. A simple and reproducible model of myocardial infarction and myocardial ischemia-reperfusion injury is a good tool for researchers. Here, a customizable method to create a myocardial infarction (MI) model and MIRI by precision ligation of the left anterior descending coronary artery (LAD) through micromanipulation is described. Accurate and reproducible ligature positioning of the LAD helps obtain consistent results for heart injury. ST-segment changes can help to identify model accuracy. The serum level of cardiac troponin T (cTnT) is used to assess the myocardial injury, cardiac ultrasound is employed to evaluate the myocardial systolic function, and Evans-Blue/triphenyl tetrazolium chloride staining is used to measure infarct size. In general, this protocol reduces procedure duration, ensures controllable infarct size, and improves mouse survival.

Psoriasis is considered as an inflammatory disease driven by T cells, and its pathogenesis is closely related to the imbalance of intestinal bacteria flora. It has been reported that Bacteroides fragilis could play an anti-inflammatory role by regulating the expression of cytokines in T cells. To date, there is no report using B. fragilis to treat psoriasis. In this study, we explored the therapeutic effect of B. fragilis BF839 on psoriasis. We selected 27 psoriasis patients who were treated in the Second Affiliated Hospital of Guangzhou Medical University from April to October 2019. The patients were given B. fragilis BF839 orally for 12 weeks while maintaining the original treatment. The psoriasis area and severity index (PASI) score was evaluated before and after the treatment. The rate of drug withdrawal and reduction after 12 weeks of treatment were calculated. Our results showed that the rate of 12-week trial completion was 96.3% (26/27). We used PASIN to define the proportion of people whose PASI score decreased more than or equal to N% after treatment. At 12 weeks, PASI30, PASI50, and PASI75 were 65.4%, 42.3%, and 19.2%, respectively. The PASI score was 9.1±5.9 and 5.8±4.9 before and after 12 weeks of treatment respectively, and the difference was statistically significant (P0.01). The effective rate of the visual analog scale (VAS) score was 42.3% at 12 weeks, and the VAS score was 2.9±2.2 and 2.3±2.1 before and after 12 weeks of treatment, respectively, which had no statistically significant difference (P0.05). The adverse reaction rate of patients was 3.8% (1/26) within 12 weeks of treatment, including 1 case of constipation, and the rate of drug withdrawal and reduction was 60.0%. The above results suggest that B. fragilis BF839 may be functional on the treatment of psoriasis by reducing the PASI score and the drug usage rate with few side effect, which deserves further study.

The occurrence and dissemination of linezolid-resistant Gram-positive bacteria among food-producing animals poses severe threats to public health. To date, information about the emergence of the oxazolidinone resistance gene optrA in isolates from goats is scare. In this study, the optrA-positive multiresistant E. faecalis strain SY-1 was isolated from a goat in China. E. faecalis strain SY-1 displayed a multidrug resistance profile for most of antimicrobial agents tested, including linezolid and tedizolid. MLST analysis showed that E. faecalis strain SY-1 belonged to the high-risk clone ST16. Whole genome sequencing analysis revealed that the optrA gene together with several other resistance genes was located on a novel RepA_N-family plasmid pSY-1-optrA. Detailed sequence analysis indicated that pSY-1-optrA exhibited a mosaic structure that may be the result of recombination events. In addition, a mobile bacitracin resistance operon bcrABDR was identified on plasmid pSY-1-optrA. In conclusion, this is, to our knowledge, the first report of the optrA gene in the high-risk clone E. faecalis ST16 of goat origin. Active surveillance of optrA-positive E. faecalis high-risk clones in food-producing animals is urgently warranted.

Objectives To investigate the genetic context and transferability of the oxazolidinone resistance genes cfr(D) and optrA in a porcine Vagococcus lutrae isolate. Methods V. lutrae isolate BN31 was screened for the presence of known oxazolidinone resistance genes via PCR assays. Conjugation experiments were carried out to assess horizontal transferability of resistance genes. WGS was performed using a combination of Nanopore MinION and Illumina HiSeq platforms. Detection of a translocatable unit (TU) was conducted by PCR. Results V. lutrae isolate BN31 harboured the oxazolidinone resistance genes cfr(D) and optrA. The optrA gene, together with the phenicol resistance gene fexA, was located on a novel pseudo-compound transposon, designated Tn7363. Tn7363 was bounded by two copies of the new insertion sequence ISVlu1, which represented a new member of the ISL3 family. A TU, comprising one copy of ISVlu1 and the segment between the two IS elements including the optrA gene, was detected. The cfr(D) gene and an erm(B) gene were identified on the broad-host-range Inc18 plasmid pBN31-cfrD, a pAMβ1-like plasmid. Similar to plasmid pAMβ1, plasmid pBN31-cfrD was conjugative. Conclusions To the best of our knowledge, we report the first identification of the cfr(D) and optrA in Vagococcus. Two novel oxazolidinone resistance gene-carrying mobile genetic elements, Tn7363 and pBN31-cfrD, were identified in V. lutrae BN31. Considering their transmission potential, attention should be paid to the risk of transfer of the optrA and cfr(D) genes from V. lutrae to clinically more important bacterial pathogens.

Tetracyclines are the broad-spectrum agents used in veterinary medicine and food animal production. Known mechanisms of tetracycline resistance include ribosome protection, active efflux and enzymatic inactivation. However, the presence of two different tet genes conferring different resistance mechanisms on the same plasmid has rarely been reported. In this study, we identified the tandem tetracycline resistance genes tet(61)-tet(58) on the novel plasmid pT4303. These tet genes were identified for the first time in Aerococcus urinaeequi. Reduced susceptibility to doxycycline was observed in S. aureus RN4220 harboring tet(61) when an extra tet(58) was expressed. Plasmid pT4303 was electrotransformed into S. aureus RN4220, E. faecalis JH2-2, S. suis BAA and E. coli DH5α and conferred tetracycline resistance (MIC ≥ 16) in both Gram-positive and Gram-negative bacteria, assuming that it might serve as a vehicle for the dissemination of the tetracycline resistance genes tet(61) and tet(58).

Netherton syndrome (NS) is a rare, autosomal recessive hereditary skin disease caused by mutations in SPINK5 gene, characterized with severe skin barrier damage. A human induced pluripotent stem cell (iPSC) line has been established with electroporation method from urine-derived cells of a NS patient carrying a compound heterozygous mutation c.2260A > T (p.K754X) and c.2423C > T(p.T808I) in SPINK5 gene. This iPSC line may serve as a valuable model for the research of pathogenesis of NS, and the mechanisms and therapeutics for skin barrier damage.

BACKGROUND SETDB1, an H3K9-specific histone methyltransferase, plays important roles in the progression of various human cancers. However, the expression patterns and its clinical roles of SETDB1 remain elusive in breast cancer (BC). MATERIAL AND METHODS The transcriptional level of SETDB1 and survival data in BC were analyzed through UALCAN, ONCOMINE, and Pan Cancer Prognostics Database. SETDB1 protein expression was assessed by immunohistochemistry (IHC) in 159 BC tissue samples. The associations between SETDB1 expression and clinical pathological characteristics of patients were analyzed. The GEO dataset GSE108656 was downloaded and analyzed to identify the differentially expressed genes (DEGs) between control and BC cells targeting interference with SETDB. The DEGs were further integrated by bioinformatics analysis to decipher the key signaling pathways and hub genes that are regulated by SETDB. RESULTS The public databases showed the level of SETDB1 mRNA was significantly upregulated in BC. Our IHC results demonstrated the level of SETDB1 protein was associated with tumor size (P=0.028), histopathological grading (P=0.012), lymph node metastasis (P

Hepatocellular carcinoma-related protein 1 (HCRP1), also known as human vacuolar protein sorting 37 homologue A (hVps37A), has not been detected or is significantly downregulated in hepatocellular carcinoma (HCC) tissues. However, information on the regulatory mechanisms of HCRP1 in HCC remains unclear. Here we found that the downregulation of HCRP1 in HepG2 cells (with low invasion capacity) significantly enhanced migration and invasion, whereas HCRP1 upregulation in SMMC-7721 cells (with high invasion capacity) generated the opposite result. Interestingly, the morphology of HepG2 cells significantly changed from an epithelial to mesenchymal phenotype after HCRP1 knockdown. Moreover, we observed a decrease in the expression of epithelial cell markers E-cadherin and β-catenin, and an increase in the expression of mesenchymal cell markers N-cadherin and vimentin. We also observed that the downregulation of HCRP1 induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β pathway. Together, our findings define a novel function for HCRP1 from the perspective of EMT, which is closely associated with the migration and invasion of HCC cells.

SET domain bifurcated 1 (SETDB1) is a histone H3 lysine 9 methyltransferase that is highly expressed in various tumor types, including breast cancer. However, how SETDB1 functions in breast cancer is unclear. In the present study, proliferation, migration and invasion assays were performed to explore the role of SETDB1 in breast cancer cells. SETDB1 downregulation in BT549 and MDA‑MB‑231 cells reduced cell proliferation, whereas upregulation in MCF7 and T47D cells enhanced proliferation. Depletion of SETDB1 suppressed cell migration and invasion in vitro and reduced lung metastasis in vivo. By contrast, SETDB1 overexpression enhanced cell migration and invasiveness. Notably, SETDB1 overexpression appeared to induce epithelial‑mesenchymal transition (EMT) in MCF7 cells. Mechanistic investigations indicated that SETDB1 acts as an EMT inducer by binding directly to the promoter of the transcription factor Snail. Thus, SETDB1 is involved in breast cancer metastasis and may be a therapeutic target for treating patients with breast cancer.

Breast cancers bear overexpression of neurokinin-1 (NK-1). The aim of this study was to investigate the relationship between NK-1 and EGFR in triple negative breast cancers (TNBCs). Immunohistochemistry was performed to investigate NK-1 and EGFR expressions in TNBCs. [Sar(9), \Met(O2)(11)] substance P (SMSP) was used to activate NK-1 in two TNBC cell lines, MDA-MB-231 and MDA-MB-468. L-733060 and siRNA against NK-1 were used to inhibit NK-1. The in vitro regulatory effect of NK-1 was determined using CCK-8 proliferation assay. The effects of NK-1 activation and inhibition on EGFR and its downstreaming pathway were analyzed using western blot and real-time quantitative PCR. We found that the proportion of EGFR positive cases was increased with the increasement of NK-1 levels. SMSP could promote the proliferation of TNBC cells, while L-733060 and siRNA could inhibit cell proliferation and induce apoptosis. Moreover, SMSP could enhance expressions of phosphorylation (p)-EGFR and EGFR, and activate p-Akt and p-Erk. NK1-siRNA could decrease p-EGFR, p-Akt and p-Erk. In the presence of cetuximab (0.2mg/mL), SMSP still could stimulate cell proliferation, and activate p-EGFR. However, in the presence of erlotinib (10μM), SMSP could not stimulate cell proliferation and could not activate p-EGFR. Our study showed the interaction between NK-1 and EGFR in TNBCs. These results suggested that NK-1 may regulate TNBC proliferation through EGFR phosphorylation, and the curative effect of EGFR monoclonal antibodies may be affected by NK-1 activation.

Previous study showed that hepatocellular carcinoma related protein 1 (HCRP1) is decreased in breast cancer. HCRP1 expression is inversely related to epithelial growth factor receptor (EGFR) in breast cancer tissues, and patients with breast cancer expressing lower HCRP1 tended to suffer a shorter life expectancy. However, the detailed biological functions of HCRP1 in breast cancer as well as the interaction between HCRP1 and EGFR remain unexplored. In this study, we examined HCRP1 expression in breast cancer tissues and cell lines by western blot. Thereafter, we performed transwell migration and matrigel invasion assays after siRNA interference and lentiviral vector of HCRP1 infection. To further investigate the interaction between HCRP1 downregulation and EGFR signaling pathway, we evaluated the phosphorylation status of EGFR, Erk1/2 and Akt by western blot following HCRP1-siRNA transfection. Moreover, we investigated the in vivo functions of HCRP1 using a breast cancer xenograft model. We found that HCRP1 depletion significantly promoted breast cancer migration and invasion while HCRP1 overexpression produced an opposite effect. In addition, HCRP1 depletion decreased EGFR degradation and enhanced phosphorylation of EGFR. Interestingly, HCRP1 depletion also led to insensitivity to EGFR inhibitors treatment. The in vivo experiment confirmed the metastasis inhibition function of HCRP1. The present data indicate that HCRP1 inhibits breast cancer metastasis through downregulating EGFR phosphorylation.

Environmental contamination due to uncontrolled e-waste recycling is an emerging global problem. The aim of this study is to test the applicability of magnetic methods for detecting the metal pollutants emitted from e-waste recycling activities. Dust samples collected from a typical e-waste recycling region in Guiyu, Guangdong Province, China, were investigated using magnetic, geochemical, micro-morphological and mineralogical analysis. The values of mass-specific susceptibility (χ) and saturation isothermal remanent magnetization (SIRM) in dusts from e-waste recycling impacted areas ranged from 101 to 636×10(-8) m(3) kg(-1) and from 10.5 to 85.2×10(-3) Am(2) kg(-1), respectively. There was a significant correlation between SIRM and χ (r(2)=0.747, p

Lead (Pb) concentration, speciation and bioaccessibility were measured in 122 household dust samples collected in rural areas of eight provinces of China. The mean Pb concentration in the household dust was 208 mg kg−1, of which samples from sites in Hunan (538 mg kg−1) and Yunnan (280 mg kg−1) provinces exhibited the highest Pb concentrations while those from Shaanxi (96 mg kg−1) and Fujian (80 mg kg−1) provinces had a relatively low Pb content. The major fraction of Pb in the household dust samples was found to be strongly bound to Fe–Mn oxide phases (37%) while Pb present in minor fractions individually making up between 14 and 18% was characterized in falling orders as residual, carbonate, organic/sulphide, and exchangeable fractions by the sequential extraction method applied. Bioaccessible Pb making up an average proportion of 53% in the household dusts was significantly correlated to the Fe–Mn oxide phases of Pb. According to the Hazard Quotient (HQ), the ingestion of dust particles pose the highest risk to children in Chinese rural areas, followed by dermal contact and inhalation. Hazard Index (HI) values for most samples were lower than 1, indicating that the domestic Pb exposure in rural areas of China were relatively safe for children when they exposure to the household dust. However, dust Pb in 4.1% of the studied families having HI values higher than 1 may pose adverse health effect to the children.

Erythropoietin-producing hepatocellular A6 (EphA6) is a member of the Eph receptor tyrosine kinase family, which has been implicated in tumorigenesis. However, little is known about the expression and function of EphA6 in breast cancer. The aim of the present study was to investigate the expression of EphA6 and the possible association between EphA6 and clinicopathological characteristics in breast cancer. In the present study, EphA6 mRNA expression was measured in 26 paired breast cancer tissues and adjacent non-cancerous tissues by reverse transcription-quantitative polymerase chain reaction. Additionally, the protein expression of EphA6 in breast cancer tissues from 116 patients was examined by immunohistochemistry, and the prognostic value for patients with breast cancer was evaluated. The results of the present study indicated that EphA6 mRNA and protein expression in breast cancer was significantly higher than that in adjacent non-cancerous tissues (P

// Juan Yu 1, * , Ji-Gang Wang 1, 2, * , Lei Zhang 1 , Hai-Ping Yang 3 , Lei Wang 1 , Di Ding 1 , Qi Chen 1 , Wen-Lin Yang 1 , Ke-Han Ren 1 , Dan-Mei Zhou 1 , Qiang Zou 4 , Yi-Ting Jin 4 , Xiu-Ping Liu 1, 5 1 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 2 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China 3 Department of Pathology, People’s Hospital, Linzi District, Zibo 255400, China 4 Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China 5 Department of Pathology, The Fifth People’s Hospital, Fudan University, Shanghai 200240, China * These authors contributed equally to this work and are co-first authors Correspondence to: Xiu-Ping Liu, email: xpliu1228@fudan.edu.cn Yi-Ting Jin, email: clara_raky@aliyun.com Keywords: miR-320a, MTDH, metastasis, breast cancer Received: September 05, 2015 Accepted: May 01, 2016 Published: May 24, 2016 ABSTRACT Dysregulated microRNAs play important pathological roles in carcinogenesis that are yet to be fully elucidated. This study was performed to investigate the biological functions of microRNA-320a (miR-320a) in breast cancer and the underlying mechanisms. Function analyses for cell proliferation, cell cycle, and cell invasion/migration, were conducted after miR-320a silencing and overexpression. The specific target genes of miR-320a were predicted by TargetScan algorithm and then determined by dual luciferase reporter assay and rescue experiment. The relationship between miR-320a and its target genes was explored in human breast cancer tissues. We found that miR-320a overexpression could inhibit breast cancer invasion and migration abilities in vitro , while miR-320a silencing could enhance that. In addition, miR-320a could suppress activity of 3′-untranslated region luciferase of metadherin ( MTDH ), a potent oncogene. The rescue experiment revealed that MTDH was a functional target of miR-320a. Moreover, we found that MTDH was negatively correlated with miR-320a expression, and it was related to clinical outcomes of breast cancer. Further xenograft experiment also showed that miR-320a could inhibit breast cancer metastasis in vivo . Our findings clearly demonstrate that miR-320a suppresses breast cancer metastasis by directly inhibiting MTDH expression. The present study provides a new insight into anti-oncogenic roles of miR-320a and suggests that miR-320a/MTDH pathway is a putative therapeutic target in breast cancer.

House dust has been recognized as an important contributor to Pb exposure of children. Here we conducted a comprehensive study to investigate geographical variation of Pb in Chinese villager house dust. The influences of outdoor soil Pb concentrations, dates of construction, house decoration materials, heating types, and site specific pollution on Pb concentrations in house dust were evaluated. The concentrations of Pb in 477 house dust samples collected from twenty eight areas throughout China varied from 12 to 2510 mg/kg, with a median concentration of 42 mg/kg. The median Pb concentrations in different geographical areas ranged from 16 (Zhangjiakou, Hebei) to 195 mg/kg (Loudi, Hunan). No correlations were found between the house dust Pb concentrations and the age of houses, as well as house decoration materials. Whereas outdoor soil, coal combustion, and site specific pollution may be potential Pb sources. Principal component analysis (PCA) confirmed that elemental compositions of the house dust were controlled by both anthropogenic and geogenic sources. Using scanning electron microscopy (SEM), the Pb bearing particles in the house dust were also studied.

Environmental contamination due to uncontrolled e-waste recycling is an emerging global issue. Antimony (Sb) is a toxic element used in semiconductor components and flame retardants for circuit board within electronic equipment. When e-waste is recycled, Sb is released and contaminates the surrounding environment; however, few studies have characterized the extent of this problem. In this study, we investigated Sb and arsenic (As) distributions in indoor dust from 13 e-waste recycling villages in Guiyu, Guangdong Province, southeastern China. Results revealed significantly elevated concentrations of Sb (6.1–232 mg/kg) in dust within all villages, which were 3.9–147 times higher than those from the non e-waste sites, indicating e-waste recycling was an important source of Sb pollution. On the contrary, As concentrations (5.4–17.7 mg/kg) in e-waste dusts were similar to reference values from the control sites. Therefore, dusts emitted from e-waste recycling may be characterized by high Sb/As ratios, which may help identify the contamination due to the e-waste recycling activities.

Proliferating trichilemmal tumor (PTT) is a rare but morphologically distinctive tumor. It usually occurs on the scalp of elderly women, characterized by frequent local recurrence. Some authors have recently proposed to classify PTT among the squamous cell carcinomas. We present the case of a 47-year-old yellow man with a 20-year history of multiple benign tumors in a number of anatomic areas. Based on their histological features, the tumors were diagnosed as PPTs. The case is unusual for the sex and age of the patient and the tumor locations. Moreover, this report illustrates a rare tumor which can be diagnostically challenging. The differentiation between a benign or malignant process in these lesions can sometimes be difficult. Careful clinical and histological assessment is necessary for an accurate diagnosis.