Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer.

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway analysis were employed to explore the potential regulatory relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues was higher than that of normal tissues (p<0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (p<0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW 1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (p<0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW 1990 cells and PANC-1 cells (p<0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (p<0.05). The colony formation was notably inhibited in the shCDCA3 group relative to the shCtrl group in SW 1990 cells (p<0.05). Moreover, the tumor growth was evidently suppressed in the shCDCA3 group compared with the shCtrl group in vivo (p<0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

The earliest human occupation of the high-altitude Tibetan Plateau 40 thousand to 30 thousand years ago.

The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.

A Multiple-Cell Microenvironment in a 3-Dimensional System Enhances Direct Cellular Reprogramming Into Hepatic Organoids.

OBJECTIVES: The difficulty in proliferation and availability and the rapid loss functions of primary human hepatocytes highlight the need to develop an alternative, preferably renewable source of human induced hepatocytes in regenerative medicine. Liver organoids generated on a multiple-cell microenvironment in a 3-dimensional (3D) system can provide a highly efficient solution to this issue. METHODS: Human hepatocytes were induced from fibroblasts by the lentiviral expression of FOXA3, HNF1A, and HNF4A. Together with these induced hepatocytes, human umbilical vein endothelial cells and mesenchymal stem cells in a 3D system were used to produce liver organoids. Liver-related gene and protein expression of liver organoids and induced hepatocytes were tested using a 2-dimensional (2D) system. RESULTS: Liver organoids notably increased the expression of hepatic transcription factors, marker genes, transporter genes, and liver metabolism enzyme genes, while it decreased the specific gene expression of fibroblasts. Liver organoids expressed comparable liver-specific proteins, such as ALB, AAT, and HNF4A in the 3D system. CONCLUSION: Direct reprogramming in multiple-cell microenvironments in 3D systems is more controllable and efficient than cell reprogramming in 2D systems. Liver organoids have the potential for use in disease modeling, pharmaceutical applications, and cellular transplantation.

Effect of irrigation on surface roughness and fatigue resistance of controlled memory wire nickel-titanium instruments.

AIM: To investigate the effect of irrigation on the surface roughness and fatigue resistance of HyFlex and M3 controlled memory (CM) wire nickel-titanium instruments. METHODOLOGY: Two new files of each brand were analysed by atomic force microscopy (AFM). Then, the instruments were dynamically immersed in either 5.25% sodium hypochlorite (NaOCl) or 17% ethylene diamine tetraacetic acid (EDTA) solution for 10 min, followed by AFM analysis. The roughness average (Ra) and root mean square (RMS) values were analysed statistically using an independent sample t-test. Then, 36 files of each brand were randomly assigned to three groups (n = 12). Group 1 (the control group) was composed of new instruments. Groups 2 and 3 were dynamically immersed in 5.25% NaOCl and 17% EDTA solutions for 10 min, respectively. The number of rotations to failure for various groups was analysed using the one-way analysis of variance software. RESULTS: For M3 files, the Ra and RMS values significantly increased (P < 0.05) after the immersion. For the HyFlex file, the Ra and RMS values significantly increased (P < 0.05) only in EDTA, but not (P > 0.05) NaOCl. The resistance to cyclic fatigue of both HyFlex and M3 files did not significantly decrease (P > 0.05) by immersing in 5.25% NaOCl and 17% EDTA solutions. CONCLUSIONS: Except the HyFlex files immersed in NaOCl, the surface roughness of other files exposed to irrigants increased. However, a change in the surface tomography of CM wire instruments caused by contact with irrigants for 10 min did not trigger a decrease in cyclic fatigue resistance.

Multiple idiopathic cervical root resorption: a case report.

AIM: To report a severe and rare case of multiple idiopathic cervical root resorption (MICRR) in an adult female. SUMMARY: A healthy 27-year-old Chinese female, with no significant associated factors, presented with MICRR. Resorption progressed quickly and lesions varied in severity, involving 29 teeth and leading to the loss of 23 teeth over a period of only 3 years. The inner surface of the crown showed extensive areas with worm-eaten lacunar resorption, and the resorptive lesions had abundant lysosomes throughout their cytoplasm. Further, heavy deposits of reaction products were shown in variously sized lysosomes.

First measurement of the form factors in the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e).

The beauty to up quark coupling constant |V(ub)| can be extracted from B → ρ e+ ν(e) combined with the form factors for D → K* e+ ν(e) and B → V ℓ+ ℓ- and D → ρ e+ ν(e). Using the entire CLEO-c ψ(3770) → DD event sample, corresponding to an integrated luminosity of 818 pb(-1) and approximately 5.4×10(6) DD events, we measure the form factors for the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e) for the first time and the branching fractions with improved precision. A four-dimensional unbinned maximum likelihood fit determines the form factor ratios to be V(0)/A1(0)=1.48±0.15±0.05 and A2(0)/A1(0)=0.83±0.11±0.04. Assuming Cabibbo-Kobayashi-Maskawa unitarity, the known D meson lifetimes, and our measured branching fractions we obtain the form factor normalizations A1(0), A2(0), and V(0). We also present a measurement of the branching fraction for D+ → ω e+ ν(e) with improved precision.

Localisation and role of activin receptor-interacting protein 1 in mouse brain.

Activin A, a stimulator of follicle-stimulating hormone secretion from the pituitary, acts as a neurotrophic and neuroprotective factor in the central nervous system. Activin receptor-interacting protein 1 (ARIP1) has been identified as a cytoplasmic protein that interacts with the type II receptor of activin (ActRII). However, the distribution pattern and function of ARIP1 are not well characterised in the brain. In the present study, we confirmed the existence of mRNA and protein of ARIP1 in the mouse brain, and found that ARIP1 was mainly localised at the hippocampus and hypothalamus in the cerebrum, granular layers in the cerebellum (especially in Purkinje cells of the cerebellum) and choroid epithelial cells by immunohistochemical staining. Furthermore, in contrast to the significant increase of activin A mRNA, ARIP1 mRNA and protein expression decreased in the mechanically lesioned brain of the mouse. Using neuroblastoma-derived Neuro-2a cells to investigate the function of ARIP1, we found that overexpression of ARIP1 down-regulated the activin A-induced signal transduction and significantly decreased the voltage-gated Na(+) current (I(Na) ). These data indicate that ARIP1 is a key molecule for the regulation of the action of activin in neurones, and also that decreased ARIP1 expression in the lesioned brain may be beneficial to the neurotrophic and neuroprotective roles of activin A in recovery after brain injury.

Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.

Using 586 pb(-1) of e+ e- collision data at E(c.m.) = 4170 MeV, produced at the Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we observe the process e+ e- → π+ π- h(c)(1P). We measure its cross section to be 15.6±2.3±1.9±3.0 pb, where the third error is due to the external uncertainty on the branching fraction of ψ(2S) → π0 h(c)(1P), which we use for normalization. We also find evidence for e+ e- → ηh(c)(1P) at 4170 MeV at the 3σ level and see hints of a rise in the e+ e- → π+ π- h(c)(1P) cross section at 4260 MeV.

J/psi and psi(2S) Radiative Transitions to eta_{c}.

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

Observation of chicJ radiative decays to light vector mesons.

Using a total of 2.74 x 10(7) decays of the psi(2S) collected with the CLEO-c detector, we present a study of chi(cJ)-->gammaV, where V=rho(0), omega, phi. The transitions chi(c1)-->gammarho(0 and chi(c1)-->gammaomega are observed with B(chi(c1)-->gammarho(0))=(2.43+/-0.19+/-0.22) x 10(-4) and B(chi(c1)-->gammaomega)=(8.3+/-1.5+/-1.2) x 10(-5). In the chi(c1)-->gammarho(0) transition, the final state meson is dominantly longitudinally polarized. Upper limits on the branching fractions of other chi(cJ) states to light vector mesons are presented.

Search for very light CP-odd Higgs Boson in radiative decays of Upsilon(1S).

We search for a non-SM-like CP-odd Higgs boson (a(1)(0)) decaying to tau(+)tau(-) or mu(+)mu(-) in radiative decays of the Upsilon(1S). No significant signal is found, and upper limits on the product branching ratios are set. Our tau(+)tau(-) results are almost 2 orders of magnitude more stringent than previous upper limits. Our data provide no evidence for a Higgs state with a mass of 214 MeV decaying to mu(+)mu(-), previously proposed as an explanation for 3 Sigma(+)-->pmu(+)mu(-) events observed by the HyperCP experiment. Our results constrain NMSSM models.

Measurement of the eta'-meson mass using J/psi-->gammaeta'.

We measure the mass of the eta;{'} meson using psi(2S)-->pi;{+}pi;{-}J/psi, J/psi-->gammaeta;{'} events acquired with the CLEO-c detector operating at the CESR e;{+}e;{-} collider. Using three decay modes, eta;{'}-->rho;{0}gamma, eta;{'}-->pi;{+}pi;{-}eta with eta-->gammagamma, and eta;{'}-->pi;{+}pi;{-}eta with eta-->pi;{+}pi;{-}pi;{0}, we find M_{eta;{'}}=957.793+/-0.054+/-0.036 MeV, in which the uncertainties are statistical and systematic, respectively. This result is consistent with but substantially more precise than the current world average.

Precision measurement of the mass of the hc(1P1) state of charmonium.

A precision measurement of the mass of the h_{c}(1P1) state of charmonium has been made using a sample of 24.5x10;{6} psi(2S) events produced in e;{+}e;{-} annihilation at the Cornell Electron Storage Ring (CESR). The reaction used was psi(2S)-->pi;{0}h_{c}, pi;{0}-->gammagamma, h_{c}-->gammaeta_{c}, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_{c} decays are reconstructed in 15 hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_{c})=3525.28+/-0.19(stat.)+/-0.12(syst.) MeV, and B(psi(2S)-->pi;{0}h_{c})xB(h_{c}-->gammaeta_{c})=(4.19+/-0.32+/-0.45)x10;{-4}. Using the ;{3}P_{J} centroid mass, DeltaM_{hf}(1P) identical withM(chi_{cJ})-M(h_{c})=+0.02+/-0.19+/-0.13 MeV.

Measurement of the absolute branching fraction of Ds+ --> tau+ nutau decay.

Using a sample of tagged D(s)(+) decays collected near the D(s)(*+/-)D(s)(-/+) peak production energy in e(+)e(-) collisions with the CLEO-c detector, we study the leptonic decay D(s)(+)-->tau(+)nu(tau) via the decay channel tau(+)-->e(+)nu(e)nu(tau). We measure B(D(s)(+)-->tau(+)nu(tau))=(6.17+/-0.71+/-0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of D(s)(+)-->mu(+)nu(mu) and D(s)(+)-->tau(+)nu(tau) (via tau(+)-->pi(+)nu(tau)), we determine f(D(s))=(274+/-10+/-5) MeV.

First observation of the decay Ds+-->pn.

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

Measurement of prominent eta-decay branching fractions.

The decay psi(2S) --> etaJ/psi is used to measure, for the first time, all prominent eta-meson branching fractions with the same experiment in the same dataset, thereby providing a consistent treatment of systematics across branching fractions. We present results for eta decays to gamma gamma, pi(+)pi(-)pi(0), 3pi(0), pi(+)pi(-)gamma and e(+)e(-)gamma, accounting for 99.9% of all eta decays. The precision of several of the branching fractions and their ratios is improved. Two channels, pi(+)pi(-)gamma and e(+)e(-)gamma, show results that differ at the level of three standard deviations from those previously determined.

Measurement of the eta-meson mass using psi(2S) --> etaJ/psi.

We measure the mass of the eta meson using psi(2S) --> etaJ/psi events acquired with the CLEO-c detector operating at the CESR e(+)e(-) collider. Using the four decay modes eta --> gamma gamma, 3pi(0), pi(+)pi(-)pi(0), and pi(+)pi(-)gamma, we find M(eta) = 547.785 +/- 0.017 +/- 0.057 MeV, in which the first uncertainty is statistical and the second systematic. This result has an uncertainty comparable to the two most precise previous measurements and is consistent with that of NA48, but is inconsistent at the level of 6.5 sigma with the much smaller mass obtained by GEM.