A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

The 5-methylcytosine (m5C) modification on an mRNA molecule is deposited by Nsun2 and its paralog Nsun6. While the physiological functions of Nsun2 have been carefully studied using gene knockout (KO) mice, the physiological functions of Nsun6 remain elusive. In this study, we generated an Nsun6-KO mouse strain, which exhibited no apparent phenotype in both the development and adult stages as compared to wild-type mice. Taking advantage of this mouse strain, we identified 80 high-confident Nsun6-dependent m5C sites by mRNA bisulfite sequencing in five different tissues and systematically analyzed the transcriptomic phenotypes of Nsun6-KO tissues by mRNA sequencing. Our data indicated that Nsun6 is not required for the homeostasis of these organs under laboratory housing conditions, but its loss may affect immune response in the spleen and oxidoreductive reaction in the liver under certain conditions. Additionally, we further investigated T-cell-dependent B cell activation in KO mice and found that Nsun6 is not essential for the germinal center B cell formation but is associated with the formation of antibody-secreting plasma cells. Finally, we found that Nsun6-mediated m5C modification does not have any evident influence on the stability of Nsun6 target mRNAs, suggesting that Nsun6-KO-induced phenotypes may be associated with other functions of the m5C modification or Nsun6 protein

Direct Impacts of Climate Change and Indirect Impacts of Non-Climate Change on Land Surface Phenology Variation across Northern China

Land surface phenology (LSP) is a sensitive indicator of climate change. Understanding the variation in LSP under various impacts can improve our knowledge on ecosystem dynamics and biosphere-atmosphere interactions. Over recent decades, LSP derived from remote sensing data and climate change-related variation of LSP have been widely reported at the regional and global scales. However, the smoothing methods of the vegetation index (i.e., NDVI) are diverse, and discrepancies among methods may result in different results. Additionally, LSP is affected by climate change and non-climate change simultaneously. However, few studies have focused on the isolated impacts of climate change and the impacts of non-climate change on LSP variation. In this study, four methods were applied to reconstruct the MODIS enhanced vegetation index (EVI) dataset to choose the best smoothing result to estimate LSP. Subsequently, the variation in the start of season (SOS) and end of season (EOS) under isolated impacts of climate change were analyzed. Furthermore, the indirect effects of isolated impacts of non-climate change were conducted based on the differences between the combined impact (the impacts of both climate change and non-climate change) and isolated impacts of climate change. Our results indicated that the Savitzky-Golay method is the best method of the four for smoothing EVI in Northern China. Additionally, SOS displayed an advanced trend under the impacts of both climate change and non-climate change (hereafter called the combined impact), isolated impacts of climate change, and isolated impacts of non-climate change, with mean values of −0.26, −0.07, and −0.17 days per year, respectively. Moreover, the trend of SOS continued after 2000, but the magnitudes of changes in SOS after 2000 were lower than those that were estimated over the last two decades of the twentieth century (previous studies). EOS showed a delayed trend under the combined impact and isolated impacts of non-climate change, with mean values of 0.41 and 0.43 days per year, respectively. However, EOS advanced with a mean value of −0.16 days per year under the isolated impacts of climate change. Furthermore, the absolute mean values of SOS and EOS trends under the isolated impacts of non-climate change were larger than that of the isolated impacts of climate change, indicating that the effect of non-climate change on LSP variation was larger than that of climate change. With regard to the relative contribution of climatic factors to the variation in SOS and EOS, the proportion of solar radiation was the largest for both SOS and EOS, followed by precipitation and temperature

RhoT1 and Smad4 are correlated with lymph node metastasis and overall survival in pancreatic cancer.

Cancer cell invasion and metastasis are the most important adverse prognostic factors for pancreatic cancer. Identification of biomarkers associated with outcome of pancreatic cancer may provide new approaches and targets for anticancer therapy. The aim of this study is to examine the relationship between the expression of RhoT1, Smad4 and p16 and metastasis and survival in patients with pancreatic cancer. The analysis showed that the high cytoplasmic expression levels of RhoT1, Smad4 and p16 in pancreatic cancer tissues had significantly negative correlation with lymph node metastasis (LNM) (P = 0.017, P = 0.032, P = 0.042, respectively). However, no significant association was observed between perineural invasion (PNI) and the expression of above three proteins (all P>0.05). Additionally, the survival analysis showed that the low expression levels of RhoT1 and Smad4 were significantly associated with worse survival (P = 0.034, P = 0.047, respectively). In conclusion, these results indicated that the low-expression levels of RhoT1 and Smad4 were significantly associated with LNM and shorter survival. RhoT1 may be considered as a potential novel marker for predicting the outcome in patients with pancreatic cancer

A Cross-Tissue Investigation of Molecular Targets and Physiological Functions of Nsun6 Using Knockout Mice

The 5-methylcytosine (m5C) modification on an mRNA molecule is deposited by Nsun2 and its paralog Nsun6. While the physiological functions of Nsun2 have been carefully studied using gene knockout (KO) mice, the physiological functions of Nsun6 remain elusive. In this study, we generated an Nsun6-KO mouse strain, which exhibited no apparent phenotype in both the development and adult stages as compared to wild-type mice. Taking advantage of this mouse strain, we identified 80 high-confident Nsun6-dependent m5C sites by mRNA bisulfite sequencing in five different tissues and systematically analyzed the transcriptomic phenotypes of Nsun6-KO tissues by mRNA sequencing. Our data indicated that Nsun6 is not required for the homeostasis of these organs under laboratory housing conditions, but its loss may affect immune response in the spleen and oxidoreductive reaction in the liver under certain conditions. Additionally, we further investigated T-cell-dependent B cell activation in KO mice and found that Nsun6 is not essential for the germinal center B cell formation but is associated with the formation of antibody-secreting plasma cells. Finally, we found that Nsun6-mediated m5C modification does not have any evident influence on the stability of Nsun6 target mRNAs, suggesting that Nsun6-KO-induced phenotypes may be associated with other functions of the m5C modification or Nsun6 protein

Dual Effects of Cellular Immunotherapy in Inhibition of Virus Replication and Prolongation of Survival in HCV-Positive Hepatocellular Carcinoma Patients

Immune cells play an important role in the development and progression of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). We conducted a retrospective study to evaluate the influence of adoptive cellular immunotherapy (CIT) on viral load and progression-free survival (PFS) for HCC patients infected with HCV. Patients (n=104) were divided into a control group (conventional therapy, n=73) and study group (combination of CIT and conventional therapy, n=31). Autologous mononuclear cells were induced into natural killer, γδT, and cytokine-induced killer cells and infused intravenously to study group patients. More patients had shown viral load decrease or were stable in study group (100% versus 75%) (p=0.014). The median PFS of the study group and control group was 16 and 10 months, respectively (p=0.0041), and only CIT was an independent prognostic factor for PFS (hazard ratio, 0.422; p=0.005). Three patients developed transient moderate fever after infusion, and there were no significant differences in alanine aminotransferase and aspartate aminotransferase levels before and after treatment in both groups. Our results show that CIT contributes to improvement of prognosis and inhibition of viral replication in HCV-related HCC patients, without impairment of liver function

Kaplan–Meier curves showing correlation between high or low expression of RhoT1, Smad4, p16 and overall survival in patients with pancreatic cancer (<i>n = </i>70).

<p>High expression levels of RhoT1 and Smad4 correlated with better survival (<i>P</i> = 0.034, <i>P = </i>0.047, respectively; log rank test), no significant association was observed between the expression level of p16 and overall survival (<i>P</i>>0.05).</p