Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.

After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5pos basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5pos basal-like state. Activated murine Krt5pos LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2pos LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair

Extending the reliability and applicability of B3LYP

B3LYP is by far the most popular density functional in chemistry. Nevertheless, there is growing evidence, showing that B3LYP (1) degrades as the system becomes larger, (2) underestimates reaction barrier heights, (3) yields too low bond dissociation enthalpies, (4) gives improper isomer energy differences, and (5) fails to bind van der Waals systems, etc.NSFC [20525311, 20923004, 10774126, 20973138]; Ministry of Science and Technology [2007CB815206

EXTRACT OF PERILLA FRUTESCENS INHIBITS TUMOR PROLIFERATION OF HCC VIA PI3K/AKT SIGNAL PATHWAY

In this study, isoegomaketone(IK) was isolated from Perilla frutescens(L.), a Chinese herbal. The effects of IK were examined by cell viability assay, colony formation assay, xenograft tumor assay and western blotting in HCC cells. We found that IK inhibited cell viability, and its administration decreased tumor volume and weight profoundly. The presence of IK(10nmol/l) produced a dramatic decrease of pAkt, while total Akt level was not affected. The data suggested that IK from perilla suppressed HCC tumor growth via blocking PI3K/Akt signaling pathway

Impacts of the World Heritage List inscription: a case study of Kaiping Diaolou and Villages in China

This study aims to investigate the overall impacts of the World Heritage List (WHL) inscription in China from different socioeconomic aspects. Kaiping Diaolou and Villages was chosen as the case study because the long period of preparation for WHL inscription led to residents’ deep understanding of its heritage values. Results are as follows. (1) Cultural cognition, sense of belonging, community cohesion and infrastructure were positively improved by the WHL inscription, whereas damage to the community cultural environment slightly increased. (2) In the economic domain, the WHL inscription had generated positive (increase in tourism development and villagers’ income and employment and solution to the Diaolou property rights problem) and negative impacts (worse tourism development, unequal income and unsolved property rights problems). (3) The WHL inscription improved the ecological environment and people’s attention to environmental protection. Although it also caused environmental damage due to an increase in tourists. (4) The positive impacts on the political domain were reflected by government leadership, community participation and plan and legislation, whereas the negative impacts included limited community participation and insufficient planning. Innovations of this study include constructing a theoretical framework to evaluate the impacts of WHL inscription, analysing the present factors of WHL inscription’s impacts and providing development suggestions. First published online 22 October 201

Radioprotective Effect of Grape Seed Proanthocyanidins In Vitro and In Vivo

We have demonstrated that grape seed proanthocyanidins (GSPs) could effectively scavenge hydroxyl radical (•OH) in a dose-dependent manner. Since most of the ionizing radiation- (IR-) induced injuries were caused by •OH, this study was to investigate whether GSPs would mitigate IR-induced injuries in vitro and in vivo. We demonstrated that GSPs could significantly reduce IR-induced DNA strand breaks (DSBs) and apoptosis of human lymphocyte AHH-1 cells. This study also showed that GSPs could protect white blood cells (WBC) from IR-induced injuries, speed up the weight of mice back, and decrease plasma malondialdehyde (MDA), thus improving the survival rates of mice after ionizing radiation. It is suggested that GSPs have a potential as an effective and safe radioprotective agent

The Epigenetic Modifier PRDM5 Functions as a Tumor Suppressor through Modulating WNT/β-Catenin Signaling and Is Frequently Silenced in Multiple Tumors

BACKGROUND: PRDM (PRDI-BF1 and RIZ domain containing) proteins are zinc finger proteins involved in multiple cellular regulations by acting as epigenetic modifiers. We studied a recently identified PRDM member PRDM5 for its epigenetic abnormality and tumor suppressive functions in multiple tumorigeneses. METHODOLOGY/PRINCIPAL FINDINGS: Semi-quantitative RT-PCR showed that PRDM5 was broadly expressed in human normal tissues, but frequently silenced or downregulated in multiple carcinoma cell lines due to promoter CpG methylation, including 80% (4/5) nasopharyngeal, 44% (8/18) esophageal, 76% (13/17) gastric, 50% (2/4) cervical, and 25% (3/12) hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell lines. PRDM5 expression could be restored by 5-aza-2'-deoxycytidine demethylation treatment in silenced cell lines. PRDM5 methylation was frequently detected by methylation-specific PCR (MSP) in multiple primary tumors, including 93% (43/46) nasopharyngeal, 58% (25/43) esophageal, 88% (37/42) gastric and 63% (29/46) hepatocellular tumors. PRDM5 was further found a stress-responsive gene, but its response was impaired when the promoter was methylated. Ectopic PRDM5 expression significantly inhibited tumor cell clonogenicity, accompanied by the inhibition of TCF/β-catenin-dependent transcription and downregulation of CDK4, TWIST1 and MDM2 oncogenes, while knocking down of PRDM5 expression lead to increased cell proliferation. ChIP assay showed that PRDM5 bound to its target gene promoters and suppressed their transcription. An inverse correlation between the expression of PRDM5 and activated β-catenin was also observed in cell lines. CONCLUSIONS/SIGNIFICANCE: PRDM5 functions as a tumor suppressor at least partially through antagonizing aberrant WNT/β-catenin signaling and oncogene expression. Frequent epigenetic silencing of PRDM5 is involved in multiple tumorigeneses, which could serve as a tumor biomarker

Surface characterization, mechanical properties and corrosion behaviour of ternary based ZneZnOeSiO2composite coating of mild steel

Zinc coatings are obtained either from cyanide, non-cyanide alkaline or acid solutions. Because of the pollution and high cost associated with cyanide, deposition from other baths is gaining importance. In order to develop a bath with additive that could produce a quality coating is the motivation behind this present work which is surface modification of Zne8ZnOeSiO2 nano composite coating on mild steel surface by electrodeposition route. The influence of SiO2 on Zne8ZnO sulphate electrolyte on the properties and microstructure of the produced nano-coatings were investigated. The SiO2 was varied from 0 to 16wt%. The microstructure characteristics of these produced series composites coating were investigated using scanning electron microscopy couple with energy dispersive spectroscopy (SEM/EDS), X-ray diffraction and atomic force microscopy (AFM). The corrosion degradation properties in 3.65% NaCl medium were studied using potentiodynamic polarization technique and characterized by high resolution optical microscope (HR-OPM). The hardness and wear of the composite coating were measured with high diamond microhardness tester and dry abrasive MTR-300 testers respectively. The results showed that average hardness value of 142.5 and 251.2HV and corrosion rate of 0.13088 and 0.00122 mm/yr were obtained for the 0 and 16wt% SiO2 in Zne8ZnO. The work have established that upto 16% SiO2 in Zne8ZnO composite coating on mild steel can be used in improving the microhardness, wear loss and corrosion resistance of mild stee