A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density.

Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, Pfdr = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (Pcombined = 2.43 × 10(-5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (Padj = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery

Axin downregulates TCF-4 transcription via β-catenin, but not p53, and inhibits the proliferation and invasion of lung cancer cells

<p>Abstract</p> <p>Background</p> <p>We previously reported that overexpression of Axin downregulates T cell factor-4 (TCF-4) transcription. However, the mechanism(s) by which Axin downregulates the transcription and expression of TCF-4 is not clear. It has been reported that β-catenin promotes and p53 inhibits TCF-4 transcription, respectively. The aim of this study was to investigate whether β-catenin and/or p53 is required for Axin-mediated downregulation of TCF-4.</p> <p>Results</p> <p>Axin mutants that lack p53/HIPK2 and/or β-catenin binding domains were expressed in lung cancer cells, BE1 (mutant p53) and A549 (wild type p53). Expression of Axin or AxinΔp53 downregulates β-catenin and TCF-4, and knock-down of β-catenin upregulates TCF-4 in BE1 cells. However, expression of AxinΔβ-ca into BE1 cells did not downregulate TCF-4 expression. These results indicate that Axin downregulates TCF-4 transcription via β-catenin. Although overexpression of wild-type p53 also downregulates TCF-4 in BE1 cells, cotransfection of p53 and AxinΔβ-ca did not downregulate TCF-4 further. These results suggest that Axin does not promote p53-mediated downregulation of TCF-4. Axin, AxinΔp53, and AxinΔβ-ca all downregulated β-catenin and TCF-4 in A549 cells. Knock-down of p53 upregulated β-catenin and TCF-4, but cotransfection of AxinΔβ-ca and p53 siRNA resulted in downregulation of β-catenin and TCF-4. These results indicate that p53 is not required for Axin-mediated downregulation of TCF-4. Knock-down or inhibition of GSK-3β prevented Axin-mediated downregulation of TCF-4. Furthermore, expression of Axin and AxinΔp53, prevented the proliferative and invasive ability of BE1 and A549, expression of AxinΔβ-ca could only prevented the proliferative and invasive ability effectively.</p> <p>Conclusions</p> <p>Axin downregulates TCF-4 transcription via β-catenin and independently of p53. Axin may also inhibits the proliferation and invasion of lung cancer cells via β-catenin and p53.</p

Surgical treatment strategy for multiple injury patients in ICU

AbstractObjectiveTo investigate the surgical treatment for patients with multiple injuries in ICU.MethodsClinical data of 163 multiple injury patients admitted to ICU of our hospital from January 2006 to January 2009 were retrospectively studied, including 118 males and 45 females, with the mean age of 36.2 years (range, 5-67 years). The injury regions included head and neck (29 cases), face (32 cases), chest (89 cases), abdomen (77 cases), pelvis and limbs (91 cases) and body surface (83 cases). There were 57 cases combined with shock. ISS values varied from 10 to 54, 18.42 on average. Patients received surgical treatments in ICU within respectively 24 hours (10 cases), 24-48 hours (8 cases), 3-7 days (7 cases) and 8-14 days (23 cases).ResultsFor the 163 patients, the duration of ICU stay ranged from 2 to 29 days, with the average value of 7.56 days. Among them, 143 were cured (87.73%), 11 died in the hospital (6.75%) due to severe hemorrhagic shock (6 cases), craniocerebral injury (3 cases) and multiple organ failure (2 cases), and 9 died after voluntarily discharging from hospital (5.52%). The total mortality rate was 12.27%.ConclusionsThe damage control principle should be followed when multiple injury patients are resuscitated in ICU. Surgical treatment strategies include actively controlling hemorrhage, treating the previously missed injuries and related wounds or surgical complications and performing planned staging operations

Hierarchical TiO2/C nanocomposite monoliths with a robust scaffolding architecture, mesopore-macropore network and TiO2-C heterostructure for high-performance lithium ion batteries.

Engineering hierarchical structures of electrode materials is a powerful strategy for optimizing the electrochemical performance of an anode material for lithium-ion batteries (LIBs). Herein, we report the fabrication of hierarchical TiO2/C nanocomposite monoliths by mediated mineralization and carbonization using bacterial cellulose (BC) as a scaffolding template as well as a carbon source. TiO2/C has a robust scaffolding architecture, a mesopore-macropore network and TiO2-C heterostructure. TiO2/C-500, obtained by calcination at 500 °C in nitrogen, contains an anatase TiO2-C heterostructure with a specific surface area of 66.5 m(2) g(-1). When evaluated as an anode material at 0.5 C, TiO2/C-500 exhibits a high and reversible lithium storage capacity of 188 mA h g(-1), an excellent initial capacity of 283 mA h g(-1), a long cycle life with a 94% coulombic efficiency preserved after 200 cycles, and a very low charge transfer resistance. The superior electrochemical performance of TiO2/C-500 is attributed to the synergistic effect of high electrical conductivity, anatase TiO2-C heterostructure, mesopore-macropore network and robust scaffolding architecture. The current material strategy affords a general approach for the design of complex inorganic nanocomposites with structural stability, and tunable and interconnected hierarchical porosity that may lead to the next generation of electrochemical supercapacitors with high energy efficiency and superior power density.Sincere gratitude goes to funding agencies for financially support: Y. Xu to NNSF China (2117 1067, 21373100), Jilin Provincial Talent Fund (802110000412) and Tang Aoqing Professor Fund of Jilin University (450091105161). T. Hasan to the Royal Academy of Engineering Research Fellowship. B.L. Su to the Thousand Talents Program of China (“Expert of the State” position), Clare Hall Life Membership at the Clare Hall College and the financial support of the Department of Chemistry, University of Cambridge, L.H. Chen and Y. Li to the Department of Education of Hubei Province for “Chutian Scholar” program, NNSF China (21301133), Hubei Natural Science Foundation (2014CFB1 60, 2015CFB428) and the financial support of SRF for ROCS (SEM [2015]311).This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via https://doi.org/10.1039/C5NR09149

Anti-Vibrio Indole-Diterpenoids and C-25 Epimeric Steroids From the Marine-Derived Fungus Penicillium janthinellum

A systematic chemical exploration of the marine-derived fungus Penicillium janthinellum led to the isolation of four indole-diterpenoid derivatives (1–4), including new penijanthines C and D (1 and 2), and a pair of new steroidal epimers, penijanthoids A and B (5 and 6). The calculated ECD spectra and Snatzke's method for the new compound 1 were carried out to determine its absolute configuration. The absolute configuration of 3 was established by X-ray diffraction and calculated ECD methods for the first time. DP4plus approach was used to elucidate the absolute configurations of the C-25 epimeric steroids 5 and 6. 25-Epimeric 5 and 6 represent the first examples of steroids forming a five-membered lactone between C-23 and C-27 from marine fungi. Compounds 1, 2, 5, and 6 displayed significant anti-Vibrio activity (Minimum inhibitory concentration, MIC values ranging from 3.1 to 50.0 μM) against three pathogenic Vibrio spp