Improved Duncan-Chang model for reconstituted hydrate-bearing clayey silt from the South China Sea

The experimental testing and analysis of strength and deformation characteristics of hydrate reservoirs is an integral part of natural gas hydrate exploitation. However, studies so far have failed to deeply explore samples from the South China Sea. Especially, there is a lack of a simple and applicable method to estimate their mechanical behaviors. Thus, based on test data, an improved Duncan-Chang model is established in this paper to characterize the strength and deformation of reconstituted samples with various hydrate saturation and stress states from this area. This model can accurately describe the strain-hardening characteristics, and failure strength is estimated by the improved Drucker-Prager criterion with high fitting accuracy. The initial elastic modulus and failure ratio are given by the proposed empirical models, which are obtained from experimental data and fitting methods. Generally, this model has several advantages including simple structure, favorable performances, and a limited number of model parameters. Therefore, it could be widely used in strength and deformation analysis. This study can support the prevention and control of geological risks during natural gas hydrate exploitation in the South China Sea.Cited as: Dong, L., Wu, N., Zhang, Y., Liao, H., Hu, G. Li, Y. Improved Duncan-Chang model for reconstituted hydrate-bearing clayey silt from the South China Sea. Advances in Geo-Energy Research, 2023, 8(2): 136-140. https://doi.org/10.46690/ager.2023.05.0

Spontaneously immortalised bovine mammary epithelial cells exhibit a distinct gene expression pattern from the breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Spontaneous immortalisation of cultured mammary epithelial cells (MECs) is an extremely rare event, and the molecular mechanism behind spontaneous immortalisation of MECs is unclear. Here, we report the establishment of a spontaneously immortalised bovine mammary epithelial cell line (BME65Cs) and the changes in gene expression associated with BME65Cs cells.</p> <p>Results</p> <p>BME65Cs cells maintain the general characteristics of normal mammary epithelial cells in morphology, karyotype and immunohistochemistry, and are accompanied by the activation of endogenous <it>bTERT </it>(bovine Telomerase Reverse Transcriptase) and stabilisation of the telomere. Currently, BME65Cs cells have been passed for more than 220 generations, and these cells exhibit non-malignant transformation. The expression of multiple genes was investigated in BME65Cs cells, senescent BMECs (bovine MECs) cells, early passage BMECs cells and MCF-7 cells (a human breast cancer cell line). In comparison with early passage BMECs cells, the expression of senescence-relevant apoptosis-related gene were significantly changed in BME65Cs cells. P16^INK4awas downregulated, p53 was low expressed and Bax/Bcl-2 ratio was reversed. Moreover, a slight upregulation of the oncogene <it>c-Myc</it>, along with an undetectable level of breast tumor-related gene <it>Bag-1 </it>and <it>TRPS-1</it>, was observed in BME65Cs cells while these genes are all highly expressed in MCF-7. In addition, <it>DNMT1 </it>is upregulated in BME65Cs. These results suggest that the inhibition of both senescence and mitochondrial apoptosis signalling pathways contribute to the immortality of BME65Cs cells. The expression of <it>p53 </it>and <it>p16</it>^{<it>INK4a </it>}in BME65Cs was altered in the pattern of down-regulation but not "loss", suggesting that this spontaneous immortalization is possibly initiated by other mechanism rather than gene mutation of <it>p53 </it>or <it>p16</it>^{<it>INK4a</it>}.</p> <p>Conclusions</p> <p>Spontaneously immortalised BME65Cs cells maintain many characteristics of normal BMEC cells and exhibit non-malignant transformation. Although this cell line displays altered patterns of gene expression, it is clearly distinct from malignant breast cancer cell line. It showed that co-inhibition of cellular senescence and mitochondrial apoptosis pathways coordinates BME65Cs cells immortalisation. Additionally, mechanisms other than gene mutation are likely to be involved in regulation of cellular functions. This study provides an insight into the relationship between cell senescence and immortalisation. BME65Cs cells will be useful in future studies of cellular senescence and tumorigenesis.</p

Clinical features and prognosis of lung cancer in patients with connective tissue diseases: a retrospective cohort study

BackgroundStudies have demonstrated a close association between connective tissue diseases (CTDs) and lung cancer (LC). Evidence supports that poor survival may be associated with the presence of CTDs in patients with LC.MethodsThis retrospective cohort study investigated 29 patients with LC with CTDs, and 116 patients with LC without CTDs were enrolled as case-matched control cohorts. Medical records, therapeutic efficacy of cancer, and outcomes were analyzed.ResultsThe median duration from the diagnosis of CTDs to LC was 17 years. The Eastern Cooperative Oncology Group (ECOG) performance score for LC-CTD patients was worse than that for matched non-CTD LC patients. The median progression-free survival (mPFS) and overall survival (mOS) of first-line chemotherapy did not differ between patients with lung adenocarcinoma (AC) with and without CTDs. A significant difference was observed in mPFS [4 months vs. 17 months; hazard ratio (HR), 9.987; p = 0.004] and mOS (6 months vs. 35 months; HR, 26.009; p &lt; 0.001) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment between patients with AC with and without CTDs. The presence of CTD, sex, ECOG performance status, and tumor-node-metastasis clinical stage were the independent prognostic factors in all patients with non–small cell LC (NSCLC). ECOG performance status was determined to be an independent prognostic factor in patients with LC-CTD. In patients with NSCLC with CTD (n = 26), sex (male) and worse ECOG score were the independent poor prognostic factors.ConclusionsCTDs were associated with poor survival in patients with LC. The therapeutic efficacy of first-line EGFR-TKI therapy was significantly worse in patients with lung AC with CTDs than in those without CTDs. ECOG performance status was determined as an independent prognostic factor for patients with LC and CTDs

A multicenter, randomized controlled, non-inferiority trial, comparing nasal continuous positive airway pressure with nasal intermittent positive pressure ventilation as primary support before minimally invasive surfactant administration for preterm infants with respiratory distress syndrome (the NIV-MISA-RDS trial): Study protocol

BackgroundNon-invasive ventilation (NIV) treatment has been developed to minimize lung damage and to avoid invasive mechanical ventilation (IMV) in preterm infants, especially in those with a gestational age of &lt;30 weeks. Our hypothesis is that for preterm infants &lt;30 weeks with potential to develop respiratory distress syndrome (RDS), nasal continuous positive airway pressure (NCPAP) is non-inferior to the nasal intermittent positive pressure ventilation (NIPPV) as primary respiratory support before minimal invasive surfactant administration (MISA).Methods and designThe NIV-MISA-RDS trial is planned as an unblinded, multicenter, randomized, non-inferiority trial at 14 tertiary neonatal intensive care units (NICUs) in China. Eligible infants are preterm infants of 24–29+6 weeks of gestational age who have spontaneous breaths at birth and require primary NIV support for RDS. Infants are randomized 1:1 to treatment with either NCPAP or NIPPV once admitted into NICUs. If an infant presents progressively aggravated respiratory distress and is clinically diagnosed as having RDS, pulmonary surfactant will be supplemented by MISA in the first 2 h of life. The primary outcome is NIV treatment failure within 72 h after birth. With a specified non-inferiority margin of 10%, using a two-sided 95% CI and 80% power, the study requires 480 infants per group (in total 960 infants).DiscussionCurrent evidence shows that NIV and MISA may be the most effective strategy for minimizing IMV in preterm infants with RDS. However, there are few large randomized controlled trials to compare the effectiveness of NCPAP and NIPPV as the primary respiratory support after birth and before surfactant administration. We will conduct this trial to test the hypothesis that NCPAP is not inferior to NIPPV as the initial respiratory support in reducing the use of IMV in premature infants who have spontaneous breaths after birth and who do not require intubation in the first 2 h after birth. The study will provide clinical data for the selection of the initial non-invasive ventilation mode in preterm infants with a gestational age of &lt;30 weeks with spontaneous breaths after birth.Clinical trial registrationhttps://register.clinicaltrials.gov, identifier: NCT05137340

Dub3 Inhibition Suppresses Breast Cancer Invasion and Metastasis by Promoting Snail1 Degradation

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. Our study reveals a critical Dub3–Snail1 signalling axis in EMT and metastasis, and provides an effective therapeutic approach against breast cancer

Clinical Implications of Unmasking Dormant Conduction After Circumferential Pulmonary Vein Isolation in Atrial Fibrillation Using Adenosine: A Systematic Review and Meta-Analysis

Purpose: Circumferential pulmonary vein isolation (CPVI) is a routine ablation strategy of atrial fibrillation (AF). The adenosine test can be used to unmask dormant conduction (DC) of pulmonary veins after CPVI, thereby demonstrating possible pulmonary vein re-connection and the need for further ablation. However, whether adenosine test could help improve the long term successful rate of CPVI is still controversial. This systemic review and meta-analysis was to determine the clinical utility of the adenosine test.Methods: PubMed, EMBASE, Web of Science and Cochrane Library database were searched through July 2016 to identify relevant studies using the keywords “dormant pulmonary vein conduction,” “adenosine test,” “circumferential pulmonary vein isolation,” and “atrial fibrillation.” A random-effects model was used to compare pooled outcomes and tested for heterogeneity.Results: A total of 17 studies including 5,169 participants were included in the final meta-analysis. Two groups of comparisons were classified: (1) Long-term successful rate in those AF patients underwent CPVI with and without adenosine test [Group A (+) and Group A (−)]; (2) Long-term successful rate in those patients who had adenosine test with and without dormant conduction [Group DC (+) and Group DC (−)]. The overall meta-analysis showed that no significant difference can be observed between Group A (+) and Group A (−) (RR 1.08; 95% CI 0.97–1.19; P = 0.16; I2 = 66%) and between Group DC (+) and Group DC (−) (RR 1.01; 95% CI 0.91–1.12; P = 0.88; I2 = 60%).Conclusion: Pooled meta-analysis suggested adenosine test may not improve long-term successful rate in AF patients underwent CPVI. Furthermore, AF recurrence may not be decreased by eliminating DC provoked by adenosine, even though adenosine test was applied after CPVI

Decline in plankton diversity and carbon flux with reduced sea ice extent along the Western Antarctic Peninsula

Since the middle of the past century, the Western Antarctic Peninsula has warmed rapidly with a significant loss of sea ice but the impacts on plankton biodiversity and carbon cycling remain an open question. Here, using a 5-year dataset of eukaryotic plankton DNA metabarcoding, we assess changes in biodiversity and net community production in this region. Our results show that sea-ice extent is a dominant factor influencing eukaryotic plankton community composition, biodiversity, and net community production. Species richness and evenness decline with an increase in sea surface temperature (SST). In regions with low SST and shallow mixed layers, the community was dominated by a diverse assemblage of diatoms and dinoflagellates. Conversely, less diverse plankton assemblages were observed in waters with higher SST and/or deep mixed layers when sea ice extent was lower. A genetic programming machine-learning model explained up to 80% of the net community production variability at the Western Antarctic Peninsula. Among the biological explanatory variables, the sea-ice environment associated plankton assemblage is the best predictor of net community production. We conclude that eukaryotic plankton diversity and carbon cycling at the Western Antarctic Peninsula are strongly linked to sea-ice conditions