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Eukaryotic RNA polymerase I (Pol I) products play fundamental roles in ribosomal assembly, protein synthesis, metabolism and cell growth. Abnormal expression of both Pol I transcription-related factors and Pol I products causes a range of diseases, including ribosomopathies and cancers. However, the factors and mechanisms governing Pol I-dependent transcription remain to be elucidated. Here, we report that transcription factor IIB-related factor 1 (BRF1), a subunit of transcription factor IIIB required for RNA polymerase III (Pol III)-mediated transcription, is a nucleolar protein and modulates Pol I-mediated transcription. We showed that BRF1 can be localized to the nucleolus in several human cell types. BRF1 expression correlates positively with Pol I product levels and tumour cell growth in vitro and in vivo. Pol III transcription inhibition assays confirmed that BRF1 modulates Pol I-directed transcription in an independent manner rather than through a Pol III product-to-45S pre-rRNA feedback mode. Mechanistically, BRF1 binds to the Pol I transcription machinery components and can be recruited to the rDNA promoter along with them. Additionally, alteration of BRF1 expression affects the recruitment of Pol I transcription machinery components to the rDNA promoter and the expression of TBP and TAF1A. These findings indicate that BRF1 modulates Pol I-directed transcription by controlling the expression of selective factor 1 subunits. In summary, we identified a novel role of BRF1 in Pol I-directed transcription, suggesting that BRF1 can independently regulate both Pol I- and Pol III-mediated transcription and act as a key coordinator of Pol I and Pol III.

Salmonella entericais a leading cause of foodborne illness in the United States. In this study, 3S. enterica strains (serovars Cerro, Montevideo, and Typhimurium) were isolated from a beef processing plant with a history of Salmonella recurrence. Floor drains of the hotbox area and storage cooler of the same plant were sampled for environmental microorganisms. Biofilm formation on stainless steel (SS) by the microorganisms recovered from the drains and surface colonization by the isolated S. enterica strains were assessed. Pathogen survival and community compositions after sanitization (quaternary ammonium compound [QAC]) were examined. Alone the Cerro strain exhibited greater (P

This study aimed to investigate the role and regulatory mechanisms of Ezrin in synovial vessels in rheumatoid arthritis (RA). Synovial tissues were obtained from people with osteoarthritis people and patients with RA patients. We also used an antigen‐induced arthritis (AIA) mice model by using Freund's adjuvant injections. Ezrin expression was analysed by immunofluorescence and immunohistochemical staining in synovial vessels of patients with RA and AIA mice. We investigated the role of Ezrin on vascular endothelial cells and its regulatory mechanism in vivo and in vitro by adenoviral transfection technology. Our results suggest a role for the Ezrin protein in proliferation, migration and angiogenesis of vascular endothelial cells in RA. We also demonstrate that Ezrin plays an important role in vascular endothelial cell migration and tube formation through regulation of the Hippo‐yes‐associated protein 1 (YAP) pathway. YAP, as a key protein, can further regulate the activity of PI3K/Akt signalling pathway in vascular endothelial cells. In AIA mice experiments, we observed that the inhibition of Ezrin or of its downstream YAP pathway can affect synovial angiogenesis and may lead to progression of RA. In conclusion, Ezrin plays an important role in angiogenesis in the RA synovium by regulating YAP nuclear translocation and interacting with the PI3K/Akt signalling pathway.

RNA polymerase I (Pol I) is responsible for the synthesis of the majority of ribosomal RNA molecules in eukaryotes. Pol I subunit 12 (RPA12) is involved in the transcriptional termination and lipid metabolism in yeast. However, its role in human cells hasn't been investigated so far. Here, we show that RPA12 is present in the nucleolus and nucleoplasm of HeLa cells. RPA12 can act as a positive factor to regulate Pol I-mediated transcription and the proliferation of 293T and HeLa cells. Unexpectedly, RPA12 can repress HeLa cell migration, indicating that RPA12 plays opposite roles in cell proliferation and migration. This study provides a novel insight into the role of RPA12 in human cells.

Cystic hygroma is one type of the benign malformations and typically located in the neck, clavicle, and others, in children under the age of 5 years. However, the incidence of giant cervicomediastinal giant cystic hygroma is very rare, especially in adulthood. Such a location and age make its diagnosis difficult because they are usually asymptomatic. Complete surgical resection seems impossible while multiple sites are involved. Herein, we present a case of giant cervicomediastinal cystic hygroma, describing the clinical presentation, radiographic features, and OK-432 sclerotherapy. In conclusion, repeated OK-432 sclerotherapy may be an effective treatment option in giant cervicomediastinal cystic hygroma. Pay close attention to patient's symptoms and vital signs, adjusting the OK-432 dose throughout the process.

Varying degrees of bone destruction and bone loss occur in the development of rheumatoid arthritis (RA). Nevertheless, the mechanism underlying osteoporosis in the development of RA is not completely elucidated. Recent evidence indicates that mitophagy may play a vital role in regulating the differentiation and function of preosteoblast. Parkin is associated with mitophagy and various inflammatory diseases, but the precise role of Parkin in the treatment of osteoporosis in RA is unclear. In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. In this study, we found that Parkin was upregulated, and the mitochondrion was damaged in tumor necrosis factor alpha (TNF-α) stimulated preosteoblasts. Rapamycin (RAPA, an mTORC1 pathway blocker) upregulation of Parkin-mediated mitophagy tends to attenuate mitochondrial impairment caused by TNF-α in preosteoblasts. Theexperimentinvivo demonstrated that the combination therapy with TNF-α neutralizing antibody and RAPA significantly reduced osteoporosis in AIA mice. Drug inhibition of this pathway can be a potential treatment for osteoporosis in patients with RA.

Inhibition of the immune microenvironment is the main cause of tumor recurrence after surgery in patients with gastric cancer (GC). In this study, immunohistochemistry and multiple immunofluorescence staining were used to evaluate immunosuppressive indicators and immune biomarkers in 825 patients with gastric cancer from three centers. We constructed an immunosuppressive recurrence score (IRS) using LASSO Cox regression based on the expression of six immunosuppressive indicators and found that the IRS and IRS-based nomogram were significantly accurate and reliable in predicting recurrence. Moreover, an elevated IRS was associated with locoregional recurrence and postoperative adjuvant chemotherapy failure. Furthermore, an increase in IRS indicated inhibition of the antitumor effect of CD8(+) tumor-infiltrating lymphocytes in the invasive margin. Thus, we propose that the IRS can predict the recurrence outcome of patients with GC by distinguishing the immunosuppressive status, which is helpful in the selection of individualized adjuvant treatment plans.

BACKGROUND Proximal contact loss (PCL) is very common between implant-fixed prostheses (IFPs) and adjacent teeth and leads to a high incidence of food impaction. Our aim was to determine if the mesio-distal adjustable (MDA) crown prostheses introduced in this study could easily establish new contacts intraorally without the intervention of prostheses retrieval. MATERIAL AND METHODS The MDA crown requires casting in the inlay framework at the proximal contact area. If PCL occurred, the resin in the inlay framework could be easily removed and refilled chairside. This single-center prospective study aimed to investigate the use of a resin inlay dental implant-fixed prosthesis for the closing proximal contact loss in 93 patients who were recruited from April 2017 to December 2017. Four patients dropped out during the 3-year follow-up; therefore, 89 patients were included. The effect of this technique was assessed by the implant mucosal status and follow-up investigations of food impaction. RESULTS PCL occurred in 29.21% (26 prostheses) of the IFPs. The PCL rate at the mesial contact surfaces (n=24, 26.97%) was significantly higher than that at the distal contact surfaces (n=5, 8.33%) (P0.01); however, the incidence of PCL was greater at adjacent teeth with significant bone resorption (P=0.00). After readjusting the resin inlay and closing the clearance, implant mucosal status and food impaction were significantly reduced (P0.01). CONCLUSIONS The findings of this study showed that use of the MDA crown for closing PCL was time-saving and effective with satisfactory results at 3-year follow-up.

We suggest the possibility to build graphene analogue with the planar hexacoordinate wheel-type Fe@B6H6 cluster as the building block through studying theoretically the geometry, stability, and electron structure of its dimer and trimer as well as the dimerization of the two trimers. Employing the dehydrogenation route to polymerization, we can obtain the hexagonal boron sheet that are partly and uniformly filled by Fe atoms in the center of the holes, achieving uniform chemical doping and a very large hexagonal-hole density. Thus, we may offer a novel cluster-assembled material for experimental chemists to construct graphene analogue.

We suggest the possibility to build graphene analogue with the planar hexacoordinate wheel-type Fe@B

RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription.

BACKGROUND Proximal contact loss (PCL) is very common between implant-fixed prostheses (IFPs) and adjacent teeth and leads to a high incidence of food impaction. Our aim was to determine if the mesio-distal adjustable (MDA) crown prostheses introduced in this study could easily establish new contacts intraorally without the intervention of prostheses retrieval. MATERIAL AND METHODS The MDA crown requires casting in the inlay framework at the proximal contact area. If PCL occurred, the resin in the inlay framework could be easily removed and refilled chairside. This single-center prospective study aimed to investigate the use of a resin inlay dental implant-fixed prosthesis for the closing proximal contact loss in 93 patients who were recruited from April 2017 to December 2017. Four patients dropped out during the 3-year follow-up; therefore, 89 patients were included. The effect of this technique was assessed by the implant mucosal status and follow-up investigations of food impaction. RESULTS PCL occurred in 29.21% (26 prostheses) of the IFPs. The PCL rate at the mesial contact surfaces (n=24, 26.97%) was significantly higher than that at the distal contact surfaces (n=5, 8.33%) (P

In this report, a series of novel four-arm star-shaped polymethyl methacrylate with core of phthalocyanine indium polymers (InPc-(PMMAx)4) were achieved with different molecular weights through Activator ReGenerated by Electron Transfer Atom Transfer Radical Polymerization, using the synthesized phthalocyanine indium (InPc-Br) as initiator. The InPc-(PMMAx)4 polymers were characterized by NMR, FT-IR, GPC, UV–Vis and PL spectroscopy. The nonlinear optical (NLO) properties of InPc-(PMMAx)4 polymers were investigated by the Z-scan technique and it revealed that InPc-(PMMA16)4 obtained satisfactory NLO properties with imaginary third order susceptibility (Im[χ(3)]) of 16.4 × 10−12 esu. Furthermore, reacting polymer InPc-(PMMA16)4 with NaN3 and 1-(4-nitrophenyl)-2-(4-(prop-2-yn-1-yloxy) phenyl) diazene (Azo-yne) through click reaction, a novel InPc polymer InPc-(PMMA16-b-Azo)4 was successfully synthesized. InPc-(PMMA16-b-Azo)4 displayed a weak fluorescence at 707 nm compared to InPc-(PMMA16)4, demonstrating the energy transfer (ET) process between Azo and InPc, which could be proved by density functional theory. Because of the ET process, InPc-(PMMA16-b-Azo)4 exhibited a better NLO performance than InPc-(PMMA16)4, with Im[χ(3)] of 20.7 × 10−12 esu. In addition, the InPc-(PMMA16-b-Azo)4/PMMA complexes were prepared for the convenience of practical application, and it exhibited an excellent Im[χ(3)] value of 30.2 × 10−12 esu and a satisfactory limiting threshold of 0.04 J/cm2. The significantly enhanced NLO properties of InPc-(PMMA16-b-Azo)4/PMMA complexes demonstrate a weaker aggregation effect in polymethyl methacrylate matrix than in methyl methacrylate solution. Our study provides a promising design strategy to synthesize high performance NLO materials for practical applications.

Zinc oxide nanoparticles (ZnO-NPs) have been extensively applied in our daily life. Humans are at high risk of being exposed to ZnO-NPs, which induce potentially adverse health effects. Although a growing number of studies have investigated the toxic effects of ZnO-NPs, the available data concerning ZnO-NP interactions with the blood-milk barrier (BMB) remain highly limited. Herein, we systematically investigated the damage to BMB integrity induced by ZnO-NPs and the mechanisms involved. ZnO-NPs that were intravenously injected into lactating dams accumulated in the mammary gland and entered into the breast milk, inducing disruption to BMB integrity and changes in the tight junction (TJ) and adherens junction (AJ) components. Furthermore, using an in vitro BMB model composed of EpH4-Ev cells, we verified that ZnO-NP-triggered ROS generation and the activation of MKK4 and JNK are the main mechanism of cell-cell junction damage. More interestingly, JNK activation played different roles in inducing changes in the TJ and AJ complex, and these effects did not need to activate the downstream c-Jun. These data provide more information for understanding ZnO-NP interactions with the BMB and raise concern for the daily use and the intravenous use of ZnO-NPs by lactating mothers.

To explore the prognostic assessment value of preoperative blood platelet-lymphocyte ratio (PLR) in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) treated with radical surgery.Clinical and pathological data of 84 gMANEC patients who underwent radical resection from 2006 to 2016 in Department of Gastric Surgery, Fujian Medical University Union Hospital were analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PLR for predicting prognosis. The Cox proportional hazards regression model was used to identify prognostic factors of gMANEC.All the patients underwent D2 lymph node dissection, including 26 cases of distal subtotal gastrectomy and 58 cases of total gastrectomy. The postoperative pathological TNM stage system(pTNM) demonstrated that the patients of stage I(, II(, and III( were 9(10.7%), 14(16.7%), and 61(72.6%) cases, respectively. The median follow-up time was 40(3 to 96) months. The recurrence rate was 41.7%(35/84). The median time to recurrence was 10 (1 to 40) months, and 82.9%(29/35) patients experienced recurrence within the first 2 years after operation. The median overall survival time was 27(3 to 39) month, and the median recurrence-free survival time was 21 (1 to 96) months. The 1-, 3-, and 5-year overall survival(OS) rates were 87.6%, 56.6%, and 47.4%, respectively, and the 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 70.5%, 50.7%, and 44.9%, respectively. The best cutoff value of the PLR for predicting prognosis was 133 through ROC curve, which categorized all the patients into low PLR group (≤133) comprising 28 patients and high PLR group (133) comprising 56 patients. The tumor recurrence rate was significantly higher in high PLR group (50.0%, 28/56) than that in low PLR group(25.0%, 7/28)(P=0.028). The live metastasis rate was significantly higher in high PLR group(35.7%, 20/56) than that in low PLR group(10.7%, 3/28)(P=0.015). Cox regression analysis showed that only pTNM stage (P=0.003) was independent prognostic factors of OS, while both pTNM stage (P=0.000) and blood PLR (P=0.015) were independent prognostic factors of RFS.gMANEC patients with high preoperative PLR tend to present recurrence and metastasis, especially to present live metastasis, so they should be kept under surveillance more frequently after surgery.

To investigate the efficacy of laparoscopic surgery in the treatment of gastrointestinal stromal tumors (GIST) in different anatomical locations.Clinical data of 133 patients with primary gastric GIST undergoing laparoscopic resection at our department from January 2006 to December 2014 were retrospectively analyzed. These patients were divided into favorable site group (F group, 90 cases), including gastric fundus, anterior wall and greater curvature of gastric body, and unfavorable site group (UF group, 43 cases),including gastroesophageal junction, posterior wall and lesser curvature of gastric body,antrum and pylorus, according to the 2014 version National Comprehensive Cancer Network Clinical Guidelines. Short-term and long-term efficacy between the two groups was compared.There were no significant differences between the two groups in the general clinicopathological parameters (all P0.05). The operation time of F group and UF group was (107.3±52.3) min and (119±53.4) min respectively (P=0.21). The blood loss in F group and UF group was (35.2±34.2) ml and (35.2±31.2) ml respectively (P=1.00). In addition, there were no significant differences in time to first fluid diet, time to first flatus, postoperative hospital stay and hospitalization expenses between the two groups(all P0.05). In F group and UF group, morbidity of postoperative complication was 6.7%(6/90) and 4.7%(2/43) respectively (P=0.72), morbidity of category I(-II( complication was 4.4%(4/90) and 2.3%(1/43) respectively (P=0.66),and morbidity of category III(-IIII( complication was 2.2%(2/90) and 2.3% (1/43) respectively (P=1.00). Median follow-up time of all the cases was 36(1 to 84) months. The 5-year overall survival rates of F group and UF group were 93.8% and 95.2% respectively, and 5-year relapse-free survival rates were 81.1% and 89.4% respectively, without significant differences(both P0.05).Laparoscopic operation for gastric GIST in unfavorable sites can yield similar short- and long-term outcomes compared with those in favorable sites.

To explore the feasibility and efficacy of laparoscopic D2 radical gastrectomy in patients with gastric neuroendocrine carcinoma (GNEC).Clinical data of 84 patients with GNEC undergoing laparoscopic D2 radical gastrectomy in Union Hospital from January 2006 to December 2012 were analyzed respectively. Among these patients, 44 cases underwent laparoscopic D2 gastrectomy (LAG group) and 40 cases underwent open gastrectomy (OG group). The short- and long-term outcomes, 3-year survival and recurrence-free survival were compared between two groups.The LAG group and OG group did not differ significantly in terms of clinicopathologic characteristics. All the patients completed operations successfully and no patients in the LAG group ware converted to laparotomy. The operative time was similar (P0.05). As compared to OG group, LAG group had less intra-operative blood loss [(85±21) ml vs. (192±89) ml, P=0.003], lower ratio of transfusion [2.3%(1/44) vs. 15.0%(6/40), P=0.048], shorter time to ambulation after surgery [(2.5±1.1) days vs. (3.5±1.1) days, P=0.001], faster postoperative gastrointestinal function recovery [(2.9±1.1) days vs. (5.1±1.0) days, P=0.001], shorter time to resume soft diet [(4.1±1.2) days vs. (5.7±1.3) days, P=0.001] and shorter postoperative hospital stay [(12.0±3.4) days vs. (15.0±5.5) days, P=0.002]. No significant difference was observed in average dissected lymph node number between LAG and OG group (35.0±16.4 vs. 31.6±12.1, P=0.204). Morbidity of postoperative complication of LAG group and OG group was 11.4%(5/44) and 17.5%(7/40) respectively (P=0.422). The overall 3-year survival rate was 54.0% for all the patients, while 3-year survival rate was 56.3% in LAG group and 51.4 % in OG group (P=0.478). In addition, there was no significant difference in recurrence-free survival between the two group (33.0 months vs. 31.5 months, P=0.703).Compared with open gastrectomy, laparoscopic D2 radical gastrectomy has the advantages of faster recovery and less blood loss, and similar short-term and long-term outcomes in treatment of patients with GNEC, thus it is a safe and feasible treatment for GNEC.

Typically, the main form of Chinese medicine is based on interrogation of the patient's condition and artificial judgement by asking related patient symptom information; which is strongly subjective and prone to errors of judgment, leading to the wrong treatment outcome. The development in computer greatly improved the level of research in medicine, and also allowed the gradually objective and systematic improvement of experience knowledge. By analyzing TCM inquiry chronic gastritis data, the Relieff & Rough Set feature selection method was presented by combining different classification algorithms with experiments and analysis; the experimental results showed that efficient feature selection method can greatly enhance the effect of the classification; therefore, Relieff & Rough Set can be used as an efficient tool for feature selection and applied in the syndrome classification of TCM.