Epithelial–mesenchymal transition (EMT) is a critical event in metastasis of colorectal cancer (CRC). Rho/ROCKs signaling has a pivotal role in orchestrating actin cytoskeleton, leading to EMT and cancer invasion. However, the underlying mechanisms for ROCKs activation are not fully understood. Here, we identified FOXM1D, a novel isoform of Forkhead box M1 (FOXM1) that has a pivotal role in ROCKs activation by directly interacting with coiled-coil region of ROCK2. FOXM1D overexpression significantly polymerizes actin assembly and impairs E-cadherin expression, resulting in EMT and metastasis in xenograft mouse model and knockdown of FOXM1D has the opposite effect. Moreover, a high FOXM1D level correlates closely with clinical CRC metastasis. FOXM1D-induced ROCKs activation could be abrogated by the ROCKs inhibitors Y-27632 and fasudil. These observations indicate that the FOXM1D–ROCK2 interaction is crucial for Rho/ROCKs signaling and provide novel insight into actin cytoskeleton regulation and therapeutic potential for CRC metastasis.
Distinct clinical, dermatoscopic and histopathological features were found in SLE-associated alopecia regions, which were different from those of AA. Serological autoantibody tests are of value to confirm the differential diagnosis. Local angiotelectasis and vasculitis close to hair follicles may be involved in the pathogenesis of alopecia in SLE.
Dengue is a rapidly spreading mosquito-borne disease caused by the dengue virus (DENV) and has emerged as a severe public health problem around the world. Guangdong, one of the southern Chinese provinces, experienced a serious outbreak of dengue in 2014, which was believed to be the worst dengue epidemic in China over the last 20 years. To better understand the epidemic, we collected the epidemiological data of the outbreak and analyzed 14,594 clinically suspected dengue patients from 25 hospitals in Guangdong. Dengue cases were then laboratory-confirmed by the detection of DENV non-structural protein 1 (NS1) antigen and/or DENV RNA. Afterwards, clinical manifestations of dengue patients were analyzed and 93 laboratory-positive serum specimens were chosen for the DENV serotyping and molecular analysis. Our data showed that the 2014 dengue outbreak in Guangdong had spread to 20 cities and more than 45 thousand people suffered from dengue fever. Of 14,594 participants, 11,387 were definitively diagnosed. Most manifested with a typical non-severe clinical course, and 1.96 % developed to severe dengue. The strains isolated successfully from the serum samples were identified as DENV-1. Genetic analyses revealed that the strains were classified into genotypes I and V of DENV-1, and the dengue epidemic of Guangdong in 2014 was caused by indigenous cases and imported cases from the neighboring Southeast Asian countries of Malaysia and Singapore. Overall, our study is informative and significant to the 2014 dengue outbreak in Guangdong and will provide crucial implications for dengue prevention and control in China and elsewhere.
In this study, the effect of endotoxin tolerance on lipopolysaccharide (LPS)-initiated pulmonary inflammation, the local production of tumour necrosis factor-a (TNF-a) and the cytokine-induced neutrophil attractant (CINC), as well as the activation of nuclear factor-kB (NF-kB) and its subunit composition, were examined in vivo. Endotoxin tolerance was reproduced by four consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli 055:B5 LPS. Compared with control rats, endotoxin-tolerant rats failed to increase the permeability of pulmonary microvascular or recruit neutrophil to lung tissue upon restimulation with 6 mg/kg of LPSs. Pretreatment with LPSs inhibited the protein level of TNF-a in bronchoalveolar lavage fluid (BALF) and mRNA expression of CINC in lung tissue in response to subsequent LPS stimulation. These changes were accompanied by the suppression of activation of NF-kB, including the low level of total amount of DNA-binding activity and high percentage of non-transactive p50 homodimers. These data demonstrate that endotoxin tolerance can alleviate the LPS-induced acute neutrophilic pulmonary inflammation in rats and can inhibit the proinflammatory cytokines in lung and suggest that endotoxin tolerance might result from the unresponsiveness of NF-kB and persistent high percentage of p50 homodimers. Therefore, the phenomenon of endotoxin tolerance might be used as a strategy for the prevention or treatment of LPS-associated acute respiratory distress syndrome in which excessive or dysregulated inflammation leads to acute lung injury.
High-quality monofilamentary MgB2wires with Fe sheath were fabricated by the powder-in-tube (PIT) method at ambient pressure. The phase compositions, microstructure features and flux pinning properties are investigated by using x-ray diffractometer, SEM, TEM and a standard four-probe technique. It is found that MgB2 has no reaction with Fe. The results indicate that MgB2 wires are dense and only MgB2 and few MgO phases exist in the core area. MgB2/Fe wires exhibit very high transport critical current densities of 1.43 × 105 A cm−2 (4.2 K, 4 T), 2.8 × 104 A cm−2 (4.2 K, 6 T), 3.72 × 104 A cm−2 (15 K, 4 T) and 2.34 × 104 A cm−2 (25 K, 3 T). The maximum flux pinning force shows a peak at 4 T at 4.2 K, suggesting strong pinning at high fields. The reasons for the large Jc in the sample was also discussed.
A two-degree bipartite field was used to investigate the influence of pulse width on human luminous perception. The frequency of the pulsed light was 100 Hz and the duty ratio was set to 1, 2, 5, 10, 20, 30, 50 and 70%. The results show that pulsed light has a brightness enhancement effect and that the enhancement effect changes when the wavelength and duty ratio are different. The maximum enhancement effect appears at 430 nm and the minimum at 460 nm. Then, a theoretical spectral luminous function for pulsed light as a function of wavelength and duty ratio was calculated using cone fundamentals. The newly established luminous function can be used to calculate the real brightness perceived by human eyes when people are exposed to a space illuminated by pulse-width modulation dimming lamps.
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