This study aimed to investigate the polymorphism of porcine-origin Ral guanine nucleotide dissociation stimulator (RalGDS) in LLC-PK1 cells using RT-PCR and sequencing. Our results revealed seven polymorphisms in the RalGDS gene, including insertions, deletions, and frameshift mutations. These variations may significantly alter the protein structure and function of RalGDS, potentially influencing its role in Ral GTPase-mediated signaling pathways. This work provides foundational insights into the genetic diversity of porcine RalGDS and its implications for pig physiology and economically important traits.
Individuals carrying mutations at both ataxia telangiectasia mutated (ATM) gene alleles reportedly have increased plasma cholesterol and triglyceride levels. Previous studies have demonstrated that defective ATM function promotes atherosclerosis. We previously demonstrated that ATM facilitates the clearance of plasma apolipoprotein (Apo)E-deficient, ApoB48-containing (E-/B48) lipoproteins in ApoE-deficient mice (ApoE-/- mice). However, to date there is no exact explanation available as to the mechanism(s) through which ATM is involved in the removal of E-/B48 lipoprotein in ApoE-/- mice. In this study, to our knowledge, we demonstrate for the first time that heterozygous ATM mutation reduces the hepatocyte uptake of E-/B48 lipoproteins in ApoE-/- mice; however, heterozygous ATM mutation did not affect hepatocyte binding to E-/B48 lipoproteins. Moreover, our results revealed that ATM proteins were localized in the nucleus, early endosomes and late endosomes, but not in the plasma membrane in the hepatocytes of ApoE-/- mice. In addition, following treatment with the ATM activator, chloroquine, and E-/B48 lipoproteins, ATM interacted with class III phosphatidylinositol-3-kinases (PI3Ks) and the activated ATM protein enhanced class III PI3K activity. Furthermore, treatment with a class III PI3K inhibitor (LY290042 and 3-MA) attenuated the intracellular total cholesterol accumulation induced by ATM activation. These results provide insight into the mechanisms behind the involvment of ATM in the process of endocytosis of E-/B48 lipoprotein in ApoE-/- mice, demonstrating the role of class III PI3K protein.
Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been reported to be involved in the progression, metastasis and recurrence of malignancies. However, the potential role of LPCAT1 in NSCLC remains poorly understood. This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression.We used integrative genomic analysis to identify genes involved in lung adenocarcinomas. LPCAT1 expression was evaluated in tumor tissues from LUAD patients and LUAD cell lines. The role of LPCAT1 was subsequently investigated both in vitro and in vivo. The mechanism underlying the involvement of LPCAT1 in LUAD progression was explored with the activator of PI3K/AKT pathway. RNA sequencing was performed to confirm the involvement of LPCAT1 and associated pathway in LUAD brain metastasis.LPCAT1 was up-regulated in LUAD tissues and cell lines. shRNA-mediated depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth and brain metastases in vivo. Notably, LPCAT1 at least partially influenced LUAD progression through PI3K/AKT signal pathway by targeting MYC transcription. Moreover, expression of LPCAT1 was higher in tissues of LUAD patients with BM than those without BM as revealed by IHC staining, RNA-Sequencing and qPCR analysis. Finally, elevated LPCAT1 expression in patients with lung adenocarcinomas was associated with a poor clinical outcome.This study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma.
Cigarettes are divided into five price categories in China.A survey of cigarette consumers in Inner Mongolia was questionnaired,and the main factors affecting the consumption of cigarettes in each category were studied.The results showed that the main factors affecting cigarette consumption differed between the categories,particularly between Categories Ⅰ and Ⅴ;cigarette price and family income affected the consumption of cigarettes in all the 5 categories.
Abstract Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection (ARI) with the most severe disease in the young and elderly 1,2 . Non-pharmaceutical interventions (NPIs) and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent 3–6 . However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated states of Australia, Western Australia (WA) and New South Wales (NSW) including the Australian Capital Territory (ACT). Genome sequencing revealed a significant reduction in RSV genetic diversity following COVID-19 emergence except for two genetically distinct RSV-A clades. These clades circulated cryptically, likely localized for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria (VIC) and caused extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic as mitigation measures introduced may result in unusual seasonality, along with larger or more severe outbreaks in the future.
Subsequently to the publication of the above article, a concerned reader drew to our attention that the data panel shown in Fig. 7A for the 400 μM isoquercitrin experiment had previously appeared in Fig. 4A in another article published in the journal International Journal of Oncology [Tang B, Li Y, Yuan S, Tomlinson S and He S: Upregulation of the δ opioid receptor in liver cancer promotes liver cancer progression both in vitro and in vivo. Int J Oncol 43: 1281‑1290, 2013], indicating that results that were purported to have been obtained under different experimental conditions had been derived from the same original source. Furthermore, concerns were also raised regarding the originality of some of the other data belonging to this figure. Given the errors that were identified in the compilation of Fig. 7 in this article, the Editor of Oncology Reports has decided that this article should be retracted from the publication owing to a lack of overall confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience that might result from the retraction of this article. [Oncology Reports 31: 2377‑2384, 2014; DOI: 10.3892/or.2014.3099].
Our starting point is colour and the notion that colour makes a difference. We studied colour science and colour geography in order to research the architecture facades in Karlskrona. The first part of the paper introduces the significance of our study, background, research objective and methodology, along with the definitions of some concepts，and urban colourscape situation of foreign counties and China. The second part of the paper expounds problems of urban colourscape and discusses principles, significance and function of urban colourscape planning. The third part of the paper analyses the colourscape planning of Copenhagen in order to demonstrate the significance and process of colourscape planning. It also investigates geography, history and culture of Karlskrona. The fourth part of the paper has the results of our research--a colour program of Karlskrona's architecture. The fifth part of the paper summarize the whole thesis.
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