The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the “stem-like” immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.     

Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis

Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.     

The Effect of Sodium-Dependent Glucose Cotransporter 2 Inhibitor Tofogliflozin on Neurovascular Coupling in the Retina in Type 2 Diabetic Mice

We investigated the effect of tofogliflozin, a sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i), on retinal blood flow dysregulation, neural retinal dysfunction, and the impaired neurovascular coupling in type 2 diabetic mice. Tofogliflozin was added to mouse chow to deliver 5 mg/kg/day and 6-week-old mice were fed for 8 weeks. The longitudinal changes in the retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice that received tofogliflozin (n =6) or placebo (n = 6) from 8 to 14 weeks of age. We also evaluated glial activation and vascular endothelial growth factor (VEGF) expression by immunofluorescence. Tofogliflozin treatment caused a sustained decrease in blood glucose in db/db mice from 8 weeks of the treatment. In tofogliflozin-treated db/db mice, both responses improved from 8 to 14 weeks of age, compared with vehicle-treated diabetic mice. Subsequently, the electroretinography implicit time for the oscillatory potential was significantly improved in SGLT2i-treated db/db mice. The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence. Our results suggest that glycemic control with tofogliflozin significantly improved the impaired retinal neurovascular coupling in type 2 diabetic mice with the inhibition of retinal glial activation.     

Reduction and Sintering of a Nickel–Dispersed-Alumina Composite and Its Properties

High-density nickel–dispersed-alumina (Al₂O₃/nickel) composites with superior mechanical properties were obtained by the hydrogen reduction and the hot pressing of alumina–nickel oxide (Al₂O₃/NiO) mixed powders. The mixtures were prepared by using NiO or nickel nitrate (Ni(NO₃)₂· n H₂O) as a dispersion source of nickel metal. Microstructural investigations of the composite fabricated using nitrate powder revealed that fine nickel particles, } 100 nm in diameter, dispersed homogeneously at the matrix grain boundaries, forming the intergranular nanocomposite. High strength (.1 GPa) and high-temperature hardness were registered for the composite that contained a small amount of nickel dispersion. The ferromagnetic properties of nickel, such as high coercive force, were observed, because of the fine magnetic dispersions, which indicates a functional value of structural composites.     

A green and facile one-pot synthesis of Ag–ZnO/RGO nanocomposite with effective photocatalytic activity for removal of organic pollutants

In this study, Ag–ZnO/reduced graphene oxide (Ag–ZnO/RGO) composite was synthesized by a green and facile one-step hydrothermal process. Aqueous suspension containing Ag and ZnO precursors with graphene oxide (GO) sheets was heated at 140 °C for 2 h. The morphology and structure of as-synthesized particles were characterized by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and Photoluminescence (PL) spectroscopy which revealed the formation of composite of metal, metal oxide and RGO. It was observed that the presence of Ag precursor and GO sheets in the hydrothermal solution could sufficiently decrease the size of ZnO flowers. The hybrid nanostructure, with unique morphology, obtained from this convenient method (low temperature, less time, and less number of reagents) was found to have good photocatalytic and antibacterial activity. The perfect recovery of catalyst after reaction and its unchanged efficiency for cyclic use showed that it will be an economically and environmentally friendly photocatalyst.     

Determination of acrylamide in processed foods by LC/MS using column switching

An LC/MS method was developed for the determination of acrylamide (AA) in processed or cooked foods. AA was extracted with a mixture of water and acetone from homogenized food samples after the addition of 13C-labeled acrylamide (AA-1-(13)C) as an internal standard. The extract was concentrated, washed with dichloromethane for defatting, and cleaned up on Bond Elut C18, PSA and ACCUCAT cartridge-columns, and then AA was determined by LC/MS in the selected ion recording (SIR) mode. For the LC/MS analysis, four LC columns were connected in-line and the flow of the mobile phase was switched according to a time-program. Monitoring ions for AA were m/z 72 and 55, and those for AA-1-(13)C were m/z 73 and 56. AA and AA-1-(13)C were determined without interference from the matrices in all samples. The recoveries of AA from potato chips, corn snack, pretzel and roasted tea spiked at the level of 500 ng/g of AA were 99.5-101.0% with standard deviations (SD) in the range from 0.3 to 1.6%. The limits of detection and quantification of the developed method were 9 and 30 ng/g for AA in samples, respectively. The method was applied to the analysis of AA in various processed or cooked food samples purchased from retail markets. High levels of AA were found in potato chips and French-fried potato (467-3,544 ng/g). Fried and sugar-coated dough cakes (karinto) contained 374 and 1,895 ng/g. Corn snacks contained 117-535 ng/g of AA. Roasted foods (such as roasted sesame seed, roasted barley (mugi-cha), roasted tea (hoji-cha), coffee beans and curry powder) contained 116-567 ng/g of AA. Foods made from fish, egg and meat contained lower levels of AA than the plant-based foods. Foods containing much water showed a tendency to have low levels of AA compared with dry foods. The proposed method was applicable to the analysis of AA in variety of processed foods.     

Stoichiometry Control for the Tuning of Grain Passivation and Domain Distribution in Green Quasi‐2D Metal Halide Perovskite Films and Light‐Emitting Diodes

Quasi‐2D metal halide perovskite films are promising for efficient light‐emitting diodes (LEDs), because of their efficient radiative recombination and suppressed trap‐assisted quenching compared with pure 3D perovskites. However, because of the multidomain polycrystalline nature of solution‐processed quasi‐2D perovskite films, the composition engineering always impacts the emitting properties with complicated mechanisms. Here, defect passivation and domain distribution of quasi‐2D perovskite films prepared with various precursor compositions are systematically studied. As a result, in perovskite films prepared from stoichiometric quasi‐2D precursor compositions, large organic ammonium cations function well as passivators. In comparison, precursor compositions of simply adding large organic halide salt into a 3D perovskite precursor ensure not only the defect passivation but also the effective formation of quasi‐2D perovskite domains, avoiding unfavorable appearance of low‐order domains. Quasi‐2D perovskite films fabricated with a well‐designed precursor composition achieve a high photoluminescence quantum yield of 95.3% and an external quantum efficiency of 14.7% in LEDs.     

In Situ Formation of Copper‐Based Hosts Embedded within 3D N‐Doped Hierarchically Porous Carbon Networks for Ultralong Cycle Lithium–Sulfur Batteries

Lithium–sulfur (Li–S) batteries are promising energy storage systems due to their large theoretical energy density of 2600 Wh kg^?1 and cost effectiveness. However, the severe shuttle effect of soluble lithium polysulfide intermediates (LiPSs) and sluggish redox kinetics during the cycling process cause low sulfur utilization, rapid capacity fading, and a low coulombic efficiency. Here, a 3D copper, nitrogen co‐doped hierarchically porous graphitic carbon network developed through a freeze‐drying method (denoted as 3D Cu@NC‐F) is prepared, and it possesses strong chemical absorption and electrocatalytic conversion activity for LiPSs as highly efficient sulfur host materials in Li–S batteries. The porous carbon network consisting of 2D cross‐linked ultrathin carbon nanosheets provides void space to accommodate volumetric expansion upon lithiation, while the Cu, N‐doping effect plays a critical role for the confinement of polysulfides through chemical bonding. In addition, after sulfuration of Cu@NC‐F network, the in situ grown copper sulfide (Cu_xS) embedded within Cu_xS@NC/S‐F composite catalyzes LiPSs conversion during reversible cycling, resulting in low polarization and fast redox reaction kinetics. At a current density of 0.1 C, the Cu_xS@NC/S‐F composites' electrode exhibits an initial capacity of 1432 mAh g^?1 and maintains 1169 mAh g^?1 after 120 cycles, with a coulombic efficiency of nearly 100%.     

Thermoelectric Properties of Multifilled Skutterudites with La as the Main Filler

Bulk multifilled n- and p-type skutterudites with La as the main filler were fabricated using the spark plasma sintering (SPS) method. The thermoelectric properties and thermal stability of these skutterudites were investigated. It was found that the interactions among the filling atoms also play a vital role in reducing the lattice thermal conductivity of the multifilled skutterudites. ZT = 0.76 for p-type La_0.8Ba_0.01Ga_0.1Ti_0.1Fe₃CoSb₁₂ and ZT = 1.0 for n-type La_0.3Ca_0.1Al_0.1Ga_0.1In_0.2Co_3.75Fe_0.25Sb₁₂ skutterudites have been achieved. Furthermore, the differential scanning calorimetry (DSC) results show that there is no skutterudite phase decomposition till 750°C for the La_0.8Ba_0.01Ga_0.1Ti_0.1Fe₃CoSb₁₂ sample. The thermal stability of the La_0.8Ba_0.01Ga_0.1Ti_0.1Fe₃CoSb₁₂ skutterudite is greatly improved. Using the developed multifilled skutterudites, the fabricated module with size of 50 mm × 50 mm × 7.6 mm possesses maximum output power of 32 W under the condition of hot/cold sides = 600°C/50°C.     

Molecular evidence for maternal inheritance of the chloroplast genome in tea,Camellia sinensis (L.) O. Kuntze

BACKGROUND: Tea is the most consumed beverage worldwide after water. Yet very little is known about the genetics of tea in comparison with other crop species. Here we have taken advantage of the polymorphic nature of microsatellite DNA to investigate the mode of chloroplast inheritance in tea, Camellia sinensis (L.) O. Kuntze. This is important for the correct interpretation of phylogeny and introgression data as well as assessing the suitability of chloroplast transformation as a means for transgene containment in tea. RESULTS: The study was based on six Japanese tea cultivars, namely Aj2, CK23, Hatsumomiji, Nka05, Yamanoibuki and Kanayamidori used to generate four informative families. The parental pairs in the crosses differed at a single chlroroplast locus with respect to an imperfect microsatellite repeat of 16 nucleotide bases. In agreement with earlier cytological studies, all 61 progeny displayed a cpDNA profile that was consistent with the maternal inheritance of chloroplasts in tea. CONCLUSIONS: The data generated here provide the first molecular evidence of the plastid inheritance in tea. However, we suggest that additional families and polymorphic markers be screened for increasing the confidence in the observed maternal inheritance of chloroplasts in this important crop species. Copyright © 2011 Society of Chemical Industry