Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Difference in Thermotolerance Between Green and Red Color Variants of the Japanese Sea Cucumber, Apostichopus japonicus Selenka: Hsp70 and Heat-Hardening Effect

We studied thermal tolerance limits, heat-hardening, and Hsp70 to elucidate the difference in thermotolerance between two color variants of the sea Cucumber Apostichopus japonicus. Green and Red variants Occupy different habitats and have different aestivation responses to high temperature in summer. In the absence of heat-hardening the variants showed no difference in the temperature at which 50% of the individuals died: Green 31.49 degrees C; Red, 31.39 degrees C. However. Green specimens acquired higher thermotolerance than Red after a prior Sublethal heat exposure. After 72 h of recovery from a heat-hardening treatment (30 degrees C for 2 h) the survival of Green variants was more than 50% and that of Red wits less than 5% when they were treated at 33 degrees C for 2 h. Levels of mRNA and protein for Hsp70 were significantly higher in Green than Red after the heat shock of 30 degrees C, and the stability of hsp70 mRNA of Green was significantly higher than that of Red. Our findings suggest that within the same species, different variants that have similar thermal limits in the absence of heat-hardening can acquire different thermotolerances after a prior sublethal heat shock. The difference in induced thermotolerance between Green and Red is closely related to the expression pattern of Hsp70, which was partly governed by the stability of hsp70 mRNA

Mediastinal Lymph Node Metastases in Thyroid Cancer: Characteristics, Predictive Factors, and Prognosis

Background. Mediastinal lymph node metastases (MLNM) have not been extensively studied. The aim of this study is to investigate the characteristics, predictive factors, and prognosis of MLNM in thyroid cancer. Methods. This is a retrospective study based on the thyroid cancer patients with MLNM at our institution from 2008 to 2015. Results. In total, 73 thyroid cancer patients with positive MLNM were included in this study. It contained sixty patients (82.2%) with papillary thyroid carcinoma (PTC), twelve (16.4%) with medullary thyroid carcinoma, and one (1.4%) with anaplastic thyroid carcinoma. Forty-eight patients had the surgery as initial treatment. Fifty-three (72.6%) patients remained disease-free, and fifteen (20.5%) developed a regional recurrence. Distant metastases occurred in four (5.5%) patients and five (6.8%) patients died. Five-year overall survival rate and disease-free survival (DFS) rate of the PTC patients for initial treatment are 95.4% and 77.2%, respectively. Extrathyroidal extension and multiple lymph nodes involved were associated with DFS in PTC patients. Conclusions. Initial therapeutic control is very important for the thyroid cancer patients. Extrathyroidal extension and multiple mediastinal lymph nodes involved were the influence factors of prognosis in the thyroid cancer patients with MLNM

circRNA-SMO upregulates CEP85 to promote proliferation and migration of glioblastoma via sponging miR-326

Circular RNAs (circRNAs) play an important role in cancer development by sponging microRNAs (miRNAs) to regulate the signaling axis. However, more comprehensive mechanisms of circRNAs in glioblastoma need to be elucidated. RT-qPCR was used to detect the expression levels of circRNA-SMO and miR-326. Dual-luciferase reporter assays were conducted to verify the interaction among circRNA-SMO, miR-326, and CEP85. Flow cytometric analysis was performed to detect apoptosis. Western blotting was used to determine the protein levels of the different molecules. Animal xenograft experiments were performed to evaluate the role of circRNA-SMO in vivo. CircRNA-SMO was upregulated in glioblastoma tissues and glioblastoma cells. CircRNA-SMO downregulation inhibited the viability and colonyforming ability of the glioblastoma cells. In addition, miR-326 was downregulated in glioblastoma cells, which was verified to sponge circRNA-SMO and interact with CEP85. Moreover, circRNA-SMO inhibition induced the elevation of miR-326 and apoptosis, accompanied by a decrease in CEP85. CircRNA-SMO knockdown-mediated tumor inhibition was prevented by an miR-326 inhibitor. Furthermore, circRNA-SMO inhibition inhibited tumor growth in vivo, accompanied by an increase in miR-326 and a decline in CEP85 in tumor tissues. Conclusions. CircRNA-SMO sponges miR-326 to promote glioblastoma proliferation and migration by upregulating CEP85 expression. This study clarified the role of circRNA-SMO in the development of glioblastoma, providing novel insights for its treatment

Behaviour of Sr, Ca, and Mg isotopes under variable hydrological conditions in high-relief large river systems

To assess how chemical weathering processes in large high-relief river systems respond to climatic variability, we studied seasonal changes in radiogenic strontium (87Sr/86Sr) and stable calcium (δ44/40Ca) and magnesium (δ26Mg) isotopes in the Jinsha and Yalong rivers, which drain the southeastern Tibetan Plateau. During the low-runoff season, with discharge (Q) 4000 m3/s), storms generate rapid overland flow, which transfers large volumes of soil into the rivers, such that soil weathering plays an important role in regulating riverine chemical compositions. At these times, the riverine Ca and Sr isotope evolution is influenced by secondary mineral dissolution and sediment–water cation exchange. Overall, this study highlights the potential of combining multiple isotope systems (Sr, Ca, Mg) to trace the dynamics of water–rock interaction under variable hydrological conditions

3,6,8-Tribromo-7-ethyl­amino-4-methyl-2H-chromen-2-one

In the title mol­ecule, C12H10Br3NO2, the 2H-chromen ring is essentially planar (r.m.s. deviation = 0.022 Å) with the ethyl­amino group oriented at 13.9 (5)° with respect to the ring. The mol­ecular structure is stabilized by intra­molecular N—H⋯Br and C—H⋯Br interactions