Slc39a7/zip7 Plays a Critical Role in Development and Zinc Homeostasis in Zebrafish

Background: Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a) and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism. Principal Finding: Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf); at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO) gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF) showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects. Significance: Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish

Dust emission reduction enhanced gas-to-particle conversion of ammonia in the North China Plain

Liu et al. found that the formation rate of particulate ammonium is slower in the atmosphere than that observed in the laboratory, while it is sped up due to an increase in aerosol acidity driven by an emission reduction of dust in North China Plain.Ammonium salt is an important component of particulate matter with aerodynamic diameter less than 2.5 mu m (PM2.5) and has significant impacts on air quality, climate, and natural ecosystems. However, a fundamental understanding of the conversion kinetics from ammonia to ammonium in unique environments of high aerosol loading is lacking. Here, we report the uptake coefficient of ammonia (gamma(NH3)) on ambient PM2.5 varying from 2.2 x 10(-4) to 6.0 x 10(-4) in the North China Plain. It is significantly lower than those on the model particles under simple conditions reported in the literature. The probability-weighted gamma(NH3) increases obviously, which is well explained by the annual decrease in aerosol pH due to the significant decline in alkali and alkali earth metal contents from the emission source of dust. Our results elaborate on the complex interactions between primary emissions and the secondary formation of aerosols and the important role of dust in atmospheric chemistry.Peer reviewe

A New Type of Quartz Smog Chamber : Design and Characterization

Publisher Copyright: ©Since the 1960s, many indoor and outdoor smog chambers have been developed worldwide. However, most of them are made of Teflon films, which have relatively high background contaminations due to the wall effect. We developed the world's first medium-size quartz chamber (10 m(3)), which is jointed with 32 pieces of 5 mm thick polished quartz glasses and a stainless-steel frame. Characterizations show that this chamber exhibits excellent performance in terms of relative humidity (RH) (2-80%) and temperature (15-30 +/- 1 degrees C) control, mixing efficiency of the reactants (6-8 min), light transmittance (>90% above 290 nm), and wall loss of pollutants. The wall loss rates of the gas-phase pollutants are on the order of 10(-4) min(-1) at 298 K under dry conditions. It is 0.08 h(-1) for 100-500 nm particles, significantly lower than those of Teflon chambers. The photolysis rate of NO2 (J(NO2)) is automatically adjustable to simulate the diurnal variation of solar irradiation from 0 to 0.40 min(-1). The inner surface of the chamber can be repeatedly washed with deionized water, resulting in low background contaminations. Both experiments (toluene-NOx and alpha-pinene-ozone systems) and box model demonstrate that this new quartz chamber can provide high-quality data for investigating SOA and O-3 formation in the atmosphere.Peer reviewe

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal

The canonical Wnt/β-catenin signaling pathway governs diverse developmental, homeostatic and pathologic processes. Palmitoylated Wnt ligands engage cell surface Frizzled (Fzd) receptors and Lrp5/6 co-receptors enabling β-catenin nuclear translocation and Tcf/Lef-dependent gene transactivation1–3. Mutations in Wnt downstream signaling components have revealed diverse functions presumptively attributed to Wnt ligands themselves, although direct attribution remains elusive, as complicated by redundancy between 19 mammalian Wnts and 10 Fzds1 and Wnt hydrophobicity2,3. For example, individual Wnt ligand mutations have not revealed homeostatic phenotypes in the intestinal epithelium4, an archetypal canonical Wnt pathway-dependent rapidly self-renewing tissue whose regeneration is fueled by proliferative crypt Lgr5+ intestinal stem cells (ISCs)5–9. R-spondin ligands (Rspo1–4) engage distinct Lgr4-6 and Rnf43/Znrf3 receptor classes10–13, markedly potentiate canonical Wnt/β-catenin signaling and induce intestinal organoid growth in vitro and Lgr5+ ISCs in vivo8,14–17. However, the interchangeability, functional cooperation and relative contributions of Wnt versus Rspo ligands to in vivo canonical Wnt signaling and ISC biology remain unknown. Here, we deconstructed functional roles of Wnt versus Rspo ligands in the intestinal crypt stem cell niche. We demonstrate that the default fate of Lgr5+ ISCs is lineage commitment, escape from which requires both Rspo and Wnt ligands. However, gain-of-function studies using Rspo versus a novel non-lipidated Wnt analog reveal qualitatively distinct, non-interchangeable roles for these ligands in ISCs. Wnts are insufficient to induce Lgr5+ ISC self-renewal, but rather confer a basal competency by maintaining Rspo receptor expression that enables Rspo to actively drive and specify the extent of stem cell expansion. This functionally non-equivalent yet cooperative interplay between Wnt and Rspo ligands establishes a molecular precedent for regulation of mammalian stem cells by distinct priming and self-renewal factors, with broad implications for precision control of tissue regeneration

<p>Synthesis and characterization of form-stable carbonate/steel slag composite materials for thermal energy storage</p>

It is of practical importance to develop form stable composite phase change materials (FSPCMs) for high temperature thermal energy storage. Carbonates are promising candidates as the phase change material and steel slag is a promising economical skeleton material. However, the molten carbonates (Na2CO3 and K2CO3) react with steel slag (SS) at high temperature. Here, a two-step process was developed to overcome this problem. Firstly, the modified steel slag (MSS) was obtained by activation of the two carbonates, and secondly, FSPCMs were synthesized by mix-sintering method. The obtained K2CO3/KMSS FSPCMs kept better shape than that of Na2CO3/NMSS FSPCMs after the thermal cycles. Further test showed that K2CO3 had good chemical compatibility with KMSS and was uniformly distributed. With the increased K2CO3 & nbsp;content, the latent heat of K2CO3/ KMSS FSPCMs gradually increases, and the measured latent heat was consistent with the calculated values. With mass ratio 4:6 (40K(2)CO(3)/60KMSS), the developed FSPCM showed the best thermal stability, the latent heat attenuation was 7.08%, and the mass loss was 6.56% after 200 thermal cycles

<p>Synthesis and characterization of form-stable carbonate/steel slag composite materials for thermal energy storage</p>

It is of practical importance to develop form stable composite phase change materials (FSPCMs) for high temperature thermal energy storage. Carbonates are promising candidates as the phase change material and steel slag is a promising economical skeleton material. However, the molten carbonates (Na2CO3 and K2CO3) react with steel slag (SS) at high temperature. Here, a two-step process was developed to overcome this problem. Firstly, the modified steel slag (MSS) was obtained by activation of the two carbonates, and secondly, FSPCMs were synthesized by mix-sintering method. The obtained K2CO3/KMSS FSPCMs kept better shape than that of Na2CO3/NMSS FSPCMs after the thermal cycles. Further test showed that K2CO3 had good chemical compatibility with KMSS and was uniformly distributed. With the increased K2CO3 & nbsp;content, the latent heat of K2CO3/ KMSS FSPCMs gradually increases, and the measured latent heat was consistent with the calculated values. With mass ratio 4:6 (40K(2)CO(3)/60KMSS), the developed FSPCM showed the best thermal stability, the latent heat attenuation was 7.08%, and the mass loss was 6.56% after 200 thermal cycles

RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway

Association of body mass index with cause specific deaths in Chinese elderly hypertensive patients: Minhang community study.

BACKGROUND: Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population. METHODS: The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m(2)). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment. RESULTS: DURING FOLLOW UP (MEDIAN: 3.7 years), 561 deaths occurred. Underweight (BMI<18 kg/m(2)) was associated with significantly increased mortality from all cause mortality (OR: 2.00; 95% CI: 1.43-2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87-4.07), but not with cardiovascular mortality. For the cause specific analysis, the underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16-4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64-7.06). The results for total mortality and specific cause mortality were not influenced by sex, age and smoking status. CONCLUSION: Our study revealed an association between underweight and increased mortality from non-cardiovascular disorders in elderly hypertensive patients in Chinese community. Overweight and obesity were not associated with all cause or cause specific death

Geochronology, geochemistry, and tectonic implications of upper Silurian-Lower Devonian meta-sedimentary rocks from the Jiangyu Group in eastern Jilin Province, NE China

In this study, we present detrital zircon U-Pb ages and Hf isotopic data and whole-rock geochemical data from meta-sedimentary rocks of the Jiangyu Group in eastern Jilin Province (NE China) to constrain the late Silurian-Early Devonian tectonic evolution of the southeastern Xing’an-Mongolia Orogenic Belt. Two samples of the meta-sedimentary rocks from the Jiangyu Group yielded concordant ages ranging from 2926 Ma to 415 Ma, and the youngest zircon populations of the two samples yielded weighted mean ages of 427±3 Ma and 426±3 Ma, respectively. Combined with reliable published muscovite 40Ar-39Ar ages of 408 Ma from the overlying metamorphic ophiolitic mélange, these data indicate that the protoliths of the Jiangyu Group were deposited during the late Silurian-Early Devonian Era. A comparison of the U-Pb ages and Hf isotopic data for detrital zircons from northeastern Gondwana and the Jiangyu Group indicates a probable tectonic affinity. The whole-rock geochemical data indicate that the protoliths of the meta-sedimentary rocks from the Jiangyu Group were graywackes deposited in a continental arc setting. Based on the recognition of the early to middle Paleozoic subduction-accretion events along the eastern segment of the northern margin of the North China Craton (NCC), we infer that the subduction-accretion events may have occurred in the Yanbian area followed by one or more arc-continent collisions after the Early Devonian.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Multivariable adjusted hazard ratios for all causes mortality, cardiovascular mortality and non-cardiovascular mortality of body mass index (BMI) <18 kg/m² in subgroup analysis.

<p>The Cox regression model were adjusted for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment additionally. Subgroups of age were determined according to quintiles.</p>*<p>p<0.05,</p>§<p>p<0.01,</p>¶<p>p<0.001.</p