Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice.

Background The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. Material/Methods The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes were also measured. Regulation of MTA1 on HIF-1α was determined in vitro. Results MTA1 deficiency reduced the number of pulmonary alveolar capillaries compared to the wild-type mice. MTA1-KO mice exhibited a decreased expression of HIF-1α and VEGF in the lungs. The retarded growth of the MTA1-KO mice was also noticed during the first week after birth. Accordingly, MTA1 deficiency resulted in increased infant mortality. In surviving adult mice, MTA1 deficiency induced myocardial hypertrophy, highlighted by an increased heart weight/body weight ratio and larger cardiomyocytes. In cultured cells, HIF-1α and VEGF levels were significantly upregulated upon MTA1 overexpression, suggesting a close relationship between all 3 molecules. Conclusions MTA1 participates in the formation of pulmonary capillaries via stabilization of HIF-1α. This finding sheds new light on the function of MTA1 in lung development, opening new avenues for the diagnosis/treatment of related pulmonary diseases

Efficient and chemoselective alkylation of amines/amino acids using alcohols as alkylating reagents under mild conditions

We report a mild and environmentally benign method for the synthesis of tertiary amines using alcohols as the alkylating reagents. Not only secondary amines such as piperazines but also amino acids and amino alcohols can be N-alkylated selectively. For N,O-benzyl protected amino alcohols, both N,O-de-benzylation and N-methylation were achieved in one-pot.NSF of China [20832005]; National Basic Research Program (973 Program) of China [2010CB833200

A CsI hodoscope on CSHINE for Bremsstrahlung {\gamma}-rays in Heavy Ion Reactions

Bremsstrahlung $\gamma$ production in heavy ion reactions at Fermi energies carries important physical information including the nuclear symmetry energy at supra-saturation densities. In order to detect the high energy Bremsstrahlung $\gamma$ rays, a hodoscope consisting of 15 CsI(Tl) crystal read out by photo multiplier tubes has been built, tested and operated in experiment. The resolution, efficiency and linear response of the units to $\gamma$ rays have been studied using radioactive source and $({\rm p},\gamma)$ reactions. The inherent energy resolution of $1.6\%+2\%/E_{\gamma}^{1/2}$ is obtained. Reconstruction method has been established through Geant 4 simulations, reproducing the experimental results where comparison can be made. Using the reconstruction method developed, the whole efficiency of the hodoscope is about $2.6\times 10^{-4}$ against the $4\pi$ emissions at the target position, exhibiting insignificant dependence on the energy of incident $\gamma$ rays above 20 MeV. The hodoscope is operated in the experiment of $^{86}$Kr + $^{124}$Sn at 25 MeV/u, and a full $\gamma$ energy spectrum up to 80 MeV has been obtained.Comment: 9 pages, 19 figure

An immunogenic cell death-related classification predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma

IntroductionImmunogenic cell death (ICD) is a form of regulated cell death that activates an adaptive immune response in an immunocompetent host and is particularly sensitive to antigens from tumor cells. Kidney clear cell carcinoma (KIRC) is an immunogenic tumor with extensive tumor heterogeneity. However, no reliable predictive biomarkers have been identified to reflect the immune microenvironment and therapeutic response of KIRC.MethodsTherefore, we used the CIBERSORT and ESTIMATE algorithms to define three ICD clusters based on the expression of ICD-related genes in 661 KIRC patients. Subsequently, we identified three different ICD gene clusters based on the overlap of differentially expressed genes (DEGs) within the ICD clusters. In addition, principal component analysis (PCA) was performed to calculate the ICD scores.ResultsThe results showed that patients with reduced ICD scores had a poorer prognosis and reduced transcript levels of immune checkpoint genes regulated with T cell differentiation. Furthermore, the ICD score was negatively correlated with the tumor mutation burden (TMB) value of KICD. patients with higher ICD scores showed clinical benefits and advantages of immunotherapy, indicating that the ICD score is an accurate and valid predictor to assess the effect of immunotherapy.DiscussionOverall, our study presents a comprehensive KICD immune-related ICD landscape that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about the patient’s disease and treatment modalities, and can guide current research on immunotherapy strategies for KICD

A novel reporter system for neutralizing and enhancing antibody assay against dengue virus

10.1186/1471-2180-14-44BMC Microbiology1414

Probing high-momentum component in nucleon momentum distribution by neutron-proton bremsstrahlung {\gamma}-rays in heavy ion reactions

The high momentum tail (HMT) of nucleons, as a signature of the short-range correlations in nuclei, has been investigated by the high-energy bremsstrahlung $\gamma$ rays produced in $^{86}$Kr + $^{124}$Sn at 25 MeV/u. The energetic photons are measured by a CsI(Tl) hodoscope mounted on the spectrometer CSHINE. The energy spectrum above 30 MeV can be reproduced by the IBUU model calculations incorporating the photon production channel from $np$ process in which the HMTs of nucleons is considered. A non-zero HMT ratio of about $15\%$ is favored by the data. The effect of the capture channel $np \to d\gamma$ is demonstrated

Revisit to the yield ratio of triton and 3^3He as an indicator of neutron-rich neck emission

The neutron rich neck zone created in heavy ion reaction is experimentally probed by the production of the $A=3$ isobars. The energy spectra and angular distributions of triton and $^3$He are measured with the CSHINE detector in $^{86}$Kr +$^{208}$Pb reactions at 25 MeV/u. While the energy spectrum of $^{3}$He is harder than that of triton, known as "$^{3}$He-puzzle", the yield ratio $R({\rm t/^3He})$ presents a robust rising trend with the polar angle in laboratory. Using the fission fragments to reconstruct the fission plane, the enhancement of out-plane $R({\rm t/^3He})$ is confirmed in comparison to the in-plane ratios. Transport model simulations reproduce qualitatively the experimental trends, but the quantitative agreement is not achieved. The results demonstrate that a neutron rich neck zone is formed in the reactions. Further studies are called for to understand the clustering and the isospin dynamics related to neck formation

Functional Promoter -31G>C Variant in Survivin Gene Is Associated with Risk and Progression of Renal Cell Cancer in a Chinese Population

BACKGROUND: Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (-31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population. METHODS: We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC. RESULTS: Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [P = 0.006, adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76]. The polymorphism was associated with risk of developing advanced stage (OR = 2.02, 95%CI = 1.34-3.07) and moderately differentiated (OR = 1.75; 95%CI = 1.20-2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (P(trend) = 0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC. CONCLUSIONS: Our results suggest that the functional -31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings