From mandatory icebreaker guiding to a permission regime: changes to the new Russian legislation of the Northern Sea Route

This article focuses on two issues. The first concerns definitions of the Northern Sea Route (NSR) in old and new Russian legislation, and the second relates to Russian rules on icebreaker guiding. Based on a comprehensive comparative analysis of relevant Russian legal provisions enacted in 2013 and previous laws in this area, we offer the following conclusions. (1) Our legal analysis indicates that Russia’s view of the NSR as a historical national transportation route has not changed. However, the new law redefines the scope and coverage of the NSR, which now comprises the internal waters, territorial sea, adjacent zone, and the exclusive economic zone of the Russian Federation. In fact, the new law resolves previous ambiguity regarding extension of the NSR boundary to the high seas. (2) Based on an analysis of the new rules on icebreaker guiding, the article concludes that NSR is transitioning from a mandatory icebreaker guiding regime into a permit regime. This is particularly evident in its provision of a concrete, practical, and predictable clause on permissible or impermissible conditions relating to independent navigation. According to the new rules, it is possible for foreign ships to undertake independent navigation in the NSR. The Russian NSR policy, therefore, appears to have changed significantly, and has future potential for opening the NSR up to the international community

Exploratory Factor Analysis for Validating Traditional Chinese Syndrome Patterns of Chronic Atrophic Gastritis

Background. Traditional Chinese medicine (TCM) has long been used to treat chronic atrophic gastritis (CAG). The aim of the present study was to evaluate the TCM syndrome characteristics of CAG and its core pathogenesis so as to promote optimization of treatment strategies. Methods. This study was based on a participant survey conducted in 4 hospitals in China. Patients diagnosed with CAG were recruited by simple random sampling. Exploratory factor analysis (EFA) was conducted on syndrome extraction. Results. Common factors extracted were assigned to six syndrome patterns: qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, and yang deficiency. Distribution frequency of all syndrome patterns showed that qi deficiency, qi stagnation, blood stasis, phlegm turbidity, and heat excess were higher (76.7%–84.2%) compared with yang deficiency (42.5%). Distribution of main syndrome patterns showed that frequencies of qi deficiency, qi stagnation, phlegm turbidity, heat, and yang deficiency were higher (15.8%–20.8%) compared with blood stasis (8.3%). Conclusions. The core pathogenesis of CAG is combination of qi deficiency, qi stagnation, blood stasis, phlegm turbidity, heat, and yang deficiency. Therefore, treatment strategy of herbal prescriptions for CAG should include herbs that regulate qi, activate blood, resolve turbidity, clear heat, remove toxin, and warm yang

CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.Peer reviewe

Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability

<p>Abstract</p> <p>Background</p> <p>Amplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene <it>eIF-5A2 </it>within the 3q26 region. Functional study has demonstrated the oncogenic role of <it>eIF-5A2 </it>in the initiation and progression of human cancers. In the present study, we aim to investigate the physiological and pathological effect of <it>eIF-5A2 </it>in an <it>eIF-5A2 </it>transgenic mouse model.</p> <p>Methods</p> <p>An <it>eIF-5A2 </it>transgenic mouse model was generated using human <it>eIF-5A2 </it>cDNA. The <it>eIF-5A2 </it>transgenic mice were characterized by histological and immunohistochemistry analyses. The aging phenotypes were further characterized by wound healing, bone X-ray imaging and calcification analysis. Mouse embryo fibroblasts (MEF) were isolated to further investigate molecular mechanism of <it>eIF-5A2 </it>in aging.</p> <p>Results</p> <p>Instead of resulting in spontaneous tumor formation, overexpression of eIF-5A2 accelerated the aging process in adult transgenic mice. This included decreased growth rate and body weight, shortened life span, kyphosis, osteoporosis, delay of wound healing and ossification. Investigation of the correlation between cellular senescence and aging showed that cellular senescence is not required for the aging phenotypes in <it>eIF-5A2 </it>mice. Interestingly, we found that activation of <it>eIF-5A2 </it>repressed p19 level and therefore destabilized p53 in transgenic mouse embryo fibroblast (MEF) cells. This subsequently allowed for the accumulation of chromosomal instability, such as errors in cell dividing during metaphase and anaphase. Additionally, a significantly increase in number of aneuploidy cells (<it>p </it>< 0.05) resulted from an increase in the incidences of misaligned and lagging chromosomal materials, anaphase bridges, and micronuclei in the transgenic mice.</p> <p>Conclusion</p> <p>These observations suggest that <it>eIF-5A2 </it>mouse models could accelerate organismal aging by increasing chromosome instability.</p

Integrated Bioinformatic Analysis of a Competing Endogenous RNA Network Reveals a Prognostic Signature in Endometrial Cancer

In endometrial carcinoma, the clinical outcome directly correlates with the TNM stage, but the lack of sufficient information prevents accurate prediction. The molecular mechanism underlying the competing endogenous RNA (ceRNA) hypothesis has not been investigated in endometrial cancer. Multi-bioinformatic analyses, including differentially expressed gene analysis, ceRNA network construction, Cox regression analysis, function enrichment analysis, and protein-protein network analysis, were performed on the sequence data acquired from The Cancer Genome Atlas (TCGA) data bank. A ceRNA network comprising 366 mRNAs, 27 microRNAs (miRNAs), and 66 long non-coding RNAs (lncRNAs) was established. Survival analysis performed with the univariate Cox regression analysis revealed nine lncRNAs with prognostic power in endometrial carcinoma. In multivariate Cox regression analysis, a signature comprising LINC00491, LINC00483, ADARB2-AS1, and C8orf49 showed remarkable prognostic power. Risk score and neoplasm status, but not TNM stage, were independent prognostic factors of endometrial carcinoma. A ceRNA network comprising differentially expressed mRNAs, miRNAs, and lncRNAs may reveal the molecular events involved in the progression of endometrial carcinoma. In addition, the signature with prognostic value may discriminate patients with increased risk for poor outcome, which may allow physicians to take accurate decisions

Vitamin B12 Enhances Nerve Repair and Improves Functional Recovery After Traumatic Brain Injury by Inhibiting ER Stress-Induced Neuron Injury

Traumatic brain injury (TBI) is one of the most common causes of neurological damage in young human populations. Vitamin B12 has been reported to promote axon growth of neuronal cells after peripheral nerve injury, which is currently used for the treatment of peripheral nerve damage in the clinical trial. Thus, we hypothesized that TBI can be attenuated by vitaminB12 treatment through its beneficial role on axon regeneration after nerve injury. To confirm it, the biological function of vitaminB12 was characterized using hematoxylin and eosin (H&amp;E) staining, Luxol fast blue (LFB) staining, western blot analysis, and immunohistochemistry staining. The results showed that the neurological functional recovery was improved in the VitaminB12-treated group after TBI, which may be due to downregulation of the endoplasmic reticulum stress-related apoptosis signaling pathway. Moreover, the microtubule stabilization, remyelination and myelin reparation were rescued by vitamin B12, which was consistent with the treatment of 4-phenylbutyric acid (4-PBA), an endoplasmic reticulum stress inhibitor. The study suggests that vitamin B12 may be useful as a novel neuroprotective drug for TBI

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

Influence of O2 on the erosion-corrosion performance of 3cr steels in CO2 containing environment

2020 by the authors. With the introduction of O2 during oil and gas production, the erosion-corrosion rate of tubing steels increases; the objective of this report is to explore the reason for this. Erosion-corrosion experiments were performed in environments of CO2 and CO2-O2, respectively. Macrographs, microstructures, and the compositions of erosion-corrosion scales were investigated using a digital camera, scanning electron microscope (SEM), Kevex-SuperDry energy spectrometer (EDS) and Xray diffraction (XRD). The results show that the erosion-corrosion products are composed of large FeCO3 particles and some amorphous product in the CO2 environment, while they are made up of FeCO3, Fe2O3, Fe3O4, and bits of amorphous product in the CO2-O2 environment. The interface between erosion-corrosion scales and the substrate of 3Cr steel is smooth, and Cr enrichment obviously exists in the erosion-corrosion products in the CO2 condition. However, the erosioncorrosion scale is loose and porous with little Cr enrichment in the CO2-O2 environment, which makes the protectiveness of the erosion-corrosion scale weak, and pitting corrosion occurs. The addition of O2 may destroy the protective FeCO3 scale and Cr enrichment in the erosion-corrosion scale, which may be the main reason for the decline in the level of protectiveness of the erosioncorrosion scale, making it weak in terms of preventing the corrosive medium from diffusing to the substrate