Strength-fracture toughness synergy strategy in ostrich tibia's compact bone: Hierarchical and gradient.

Ostriches are the fastest bipeds in the world, but their tibias are very thin. How the thin tibia can withstand the huge momentum impacts of the heavy body during running? The present work revealed that the combination of hierarchical and gradient design strategies was the main reason for their high strength and fracture toughness. The microstructure of ostrich's tibias compact bone was self-assembled into the 6-level hierarchical structure from the hydroxyapatite (HAP) crystals, collagen fiber (sub-nano), mineralized collagen fiber (nano-), mineralized collagen fiber bundle (sub-micro), lamellae (micro-) and osteon (macro-scales). The most distinctive design in the ostrich compact bone was that the HAP crystals were embedded in collagen fibers as well as wrapped in the outer layer of mineral collagen fibers (MCFs) in the form of HAP nanocrystals, thus achieving a high degree of soft and hard combination from the nanoscale. The bending strength was gradient-structure dependent and up to 787.2 ± 40.5 MPa, 4 times that of a human's compact bone. The fracture toughness (KJc) is 5.8 ± 0.1 MPa m1/2. Several toughening mechanisms, such as crack deflection/twist, bridging, HAP fibers pulling-out, and fracture of the MCF bundles were found in the compact bone.

Search for Light Weakly-Interacting-Massive-Particle Dark Matter by Annual Modulation Analysis with a Point-Contact Germanium Detector at the China Jinping Underground Laboratory.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.

Constraints on Spin-Independent Nucleus Scattering with sub-GeV Weakly Interacting Massive Particle Dark Matter from the CDEX-1B Experiment at the China Jinping Underground Laboratory.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m_{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m_{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ_{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35} cm^{2} for TI analysis at m_{χ}∼50-180 MeV/c^{2}, and 3×10^{-32}∼9×10^{-38} cm^{2} for AM analysis at m_{χ}∼75 MeV/c^{2}-3.0 GeV/c^{2}.

Limits on Light Weakly Interacting Massive Particles from the First 102.8 kg×day Data of the CDEX-10 Experiment.

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.

Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1 pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic kidney injury.

Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.

Myocyte enhancer factor 2C regulation of hepatocellular carcinoma via vascular endothelial growth factor and Wnt/ß-catenin signaling.

Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide. Myocyte enhancer factor 2C (MEF2C) was traditionally regarded as a development-associated factor and was recently reported to be an oncogene candidate. We have previously reported overexpression of MEF2C in HCC; however, the roles of MEF2C in HCC remain to be clarified. In this study, HCC cell lines and a xenograft mouse model were used to determine the functions of MEF2C in vitro and in vivo, respectively. Specific plasmids and small interfering RNA were used to upregulate and downregulate MEF2C expression, respectively. Functional assays were performed to assess the influence of MEF2C on cell proliferation, and VEGF-induced vasculogenic mimicry, migration/invasion as well as angiogenesis. Co-immunoprecipitation was conducted to identify the interaction of MEF2C and ß-catenin. Human HCC tissue microarrays were used to investigate correlations among MEF2C, ß-catenin and involved biomarkers. MEF2C was found to mediate VEGF-induced vasculogenic mimicry, angiogenesis and migration/invasion, with involvement of the p38 MAPK and PKC signaling pathways. However, MEF2C itself inhibited tumor growth in vitro and in vivo. MEF2C was upregulated by and directly interacted with ß-catenin. The nuclear translocation of ß-catenin blocked by MEF2C was responsible for MEF2C-mediated growth inhibition. The nuclear translocation of MEF2C was associated with intracellular calcium signaling induced by ß-catenin. HCC microarrays showed correlations of nuclear MEF2C with the angiogenesis-associated biomarker, CD31, and cytosolic MEF2C with the proliferation-associated biomarker, Ki-67. MEF2C showed double-edged activities in HCC, namely mediating VEGF-induced malignancy enhancement while inhibiting cancer proliferation via blockade of Wnt/ß-catenin signaling. The overall effect of MEF2C in HCC progression regulation was dictated by its subcellular distribution. This should be determined prior to any MEF2C-associated intervention in HCC.

National rates of Helicobacter pylori recurrence are significantly and inversely correlated with human development index.

BACKGROUND: Helicobacter pylori infection is a worldwide threat to human health with recurrence rates that vary widely. The precise correlation between H. pylori recurrence and socioeconomic development has not been determined. AIM: To determine H. pylori recurrence rates after successful eradication and their association with socioeconomic development metrics. METHODS: Bibliographical searches were performed in the MEDLINE database. We reviewed all results, filtered by inclusion criteria, extracted primary results to calculate H. pylori recurrence rates and calculated national Human Development Index (HDI) values for the periods during which the studies were conducted. RESULTS: One thousand two hundred and twenty six cases of H. pylori recurrence in 77 eligible studies were observed in 43 525.1 follow-up patient-years after successful eradication therapy, giving a recurrence rate of 2.82 ± 1.16% per patient-year (weighted mean ± 95% confidence interval). H. pylori recurrence rate was inversely correlated with national HDI on linear (r = -0.633) and weighted least square (r = -0.546) regression analysis. Countries with very high HDI had a mean recurrence rate significantly lower than that of high, medium and low HDI countries (P < 0.01, 0.001, and 0.001, respectively). CONCLUSIONS: Less-developed areas, as measured by HDI, are more likely to have high H. pylori recurrence rates. A different approach to follow-up after H. pylori eradication is needed in developing countries where reinfection is highly prevalent, paying special attention to sources of reinfection and high-risk groups.

The role of programmed cell death in streptozotocin-induced early diabetic nephropathy.

The mechanism of autophagy in diabetic nephropathy (DN) is still unclear. The study was performed on streptozotocin (STZ) rats to investigate whether programmed cell death contribute to the pathogenesis and progression of DN. STZ rats were induced by an single intravenous injection of STZ dissolved in citrate buffer, early DN (E-DN) for STZ rats was defined as the stage from modeling to the end of the 8th week according to previous studies. A total of 36 male Sprague-Dawley rats were randomly divided into two groups: an E-DN group and a control group. After the 1st, 4th, and 8th week, the rats were sacrificed. Beclin1 and microtubule associated protein 1 light chain 3 (LC3) were examined, apoptosis level in renal tissue was detected by Tunnel assay detected as the apoptotic index. An electron microscopic examination of kidney tissues was performed at end of the 4th and 8th week. Compared with the control group, Beclin1 expression increased since the 1st week after modeling in STZ rats kidney and peaked at the end of the 8th week in western blotting and immunohistochemical stain. Meanwhile the level of LC3-II in DN group was significantly lower from the end of the 1st to the 8th week. A small amount of autophagosomes were observed in both E-DN group and control group under electron microscopic examination, and there was no significant difference between the groups. These findings indicate that an abnormality on autophagy may play an important role in the pathogenesis of E-DN.

Axoglial interaction via the notch receptor in oligodendrocyte differentiation.

INTRODUCTION: Increasing evidence has revealed that the Notch signalling pathway is one of the pivotal systems that mediate oligodendrocyte development. The Notch receptor is a type I transmembrane molecule that represents a novel cellular signalling paradigm, namely, regulated intramembrane proteolysis (RIP). METHOD: The typical Notch ligands, such as Delta, Serrate/Jagged and Lag2 (DSL), promote the formation of oligodendocyte precursor cells (OPCs) and maintain them in an uncommitted stage, thus retarding oligodendrocyte appearance in the central nervous system (CNS). RESULTS: In contrast, our recent studies have revealed that F3/contactin, a GPI-linked neural adhesion molecule, interacts with Notch and speeds up the generation and maturation of oligodendrocytes. CONCLUSIONS: Considering the distinct, albeit somewhat overlapping expression patterns of F3 and DSL in the CNS, the Notch receptor appears to function ligand-dependently during oligodendrocyte development. This multipotentiality may well designate the Notch receptor as one of the therapeutic targets that one can manoeuvre to treat demyelinating diseases, such as multiple sclerosis, that is characterised by chronic myelin degeneration.

A human homolog of the yeast gene encoding tRNA 2'-phosphotransferase: cloning, characterization and complementation analysis.

The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2'-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiae

Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1.

We have identified LASS2, a previously unknown human homologue of the yeast longevity assurance gene LAG1. The LASS2 transcript is highly expressed in liver and kidney, which is very different from the expression of the previously identified human LAG1 homologue LAG1Hs-1. Radiation hybrid mapping studies indicated that LASS2 is located on chromosome 1q11. Yeast two-hybrid screening and glutathione S-transferase pull-down assays showed that the LASS2 protein interacts with several membrane-associated receptors or transporters. Furthermore, LASS2 protein was able to inhibit the colony formation of human hepatoma cells in vitro, which suggests that this gene may be involved in the regulation of cell growth.