Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.</p> <p>Methods</p> <p>From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.</p> <p>Results</p> <p>In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.</p> <p>Conclusions</p> <p>Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.</p

Advances in 3D Generation: A Survey

Generating 3D models lies at the core of computer graphics and has been the focus of decades of research. With the emergence of advanced neural representations and generative models, the field of 3D content generation is developing rapidly, enabling the creation of increasingly high-quality and diverse 3D models. The rapid growth of this field makes it difficult to stay abreast of all recent developments. In this survey, we aim to introduce the fundamental methodologies of 3D generation methods and establish a structured roadmap, encompassing 3D representation, generation methods, datasets, and corresponding applications. Specifically, we introduce the 3D representations that serve as the backbone for 3D generation. Furthermore, we provide a comprehensive overview of the rapidly growing literature on generation methods, categorized by the type of algorithmic paradigms, including feedforward generation, optimization-based generation, procedural generation, and generative novel view synthesis. Lastly, we discuss available datasets, applications, and open challenges. We hope this survey will help readers explore this exciting topic and foster further advancements in the field of 3D content generation.Comment: 33 pages, 12 figure

Pure curcumin decreases the expression of WT1 by upregulation of miR-15a and miR-16-1 in leukemic cells

<p>Abstract</p> <p>Background</p> <p>Pure curcumin has been reported to down-regulate the expression of WT1 in leukemic cells. However, the molecular mechanism underlying the down-regulation of WT1 by curcumin is not completely delineated. The purpose of this present study is to identify a new miRNA-mediated mechanism which plays an important role in the anti-proliferation effects of curcumin in leukemic cells.</p> <p>Methods</p> <p>K562 and HL-60 cells were treated with different concentrations of curcumin for 24 and 48 hours, the level of miR-15a/16-1 and WT1 were detected by qRT-PCR and Western blotting. WT1 expression and cell proliferation were detected by Western blotting and CCK-8, after curcumin treated-K562 and HL-60 cells were transfected with anti-miR-15a/16-1 oligonucleotides.</p> <p>Results</p> <p>We found that pure curcumin upregulated the expression of miR-15a/16-1 and downregulated the expression of WT1 in leukemic cells and primary acute myeloid leukemia (AML) cells. Overexpression of miR-15a/16-1 deduced the protein level of WT1 in leukemic cells, but downregulation of WT1 by siRNA-WT1 could not increase the expression of miR-15a/16-1 in leukemic cells. These results reveal that curcumin induced-upregulation of miR-15a/16-1 is an early event upstream to downregulation of WT1. Furthermore, anti-miR-15a/16-1 oligonucleotides (AMO) partly reversed the downregulation of WT1 induced by pure curcumin in leukemic cells and AMO promoted the growth of curcumin treated-K562 and HL-60 cells.</p> <p>Conclusion</p> <p>Thus, these data suggest for the first time that pure curcumin downregulated the expression of WT1 partly by upregulating the expression of miR-15a/16-1 in leukemic cells. miR-15a/16-1 mediated WT1 downregulation plays an important role in the anti-proliferation effect of curcumin in leukemic cells.</p

Lithospheric electrical structure across the Bangong-Nujiang Suture in northern tibet revealed by magnetotelluric

Competing hypotheses have been proposed to explain the subduction polarity of the Bangong-Nujiang Tethyan Ocean and the formation of the high-conductivity anomaly beneath the Qiangtang terrane. However, the lithospheric architecture of the northern Tibetan Plateau is still poorly understood due to inhospitable environments and topography. Therefore, in the winter of 2021, a 440 km long, SN-trending broadband magnetotelluric (MT) profile was recorded in northern Tibet to detect its regional lithospheric structure. The nonlinear conjugate gradients algorithm is conducted to invert the individual TM mode data. A reliable 2D electrical model was obtained by ablation processing and analysis of broadband magnetotelluric data to test the lithospheric electrical structure and dynamics between the northern Lhasa and Qiangtang terranes. The inversion results reveal the lithospheric structure at a depth of 100 km in northern Tibet, which synthesizes geological, geochemical and deep seismic reflection evidence and firmly identifies that the trace of the south-dipping conductor mainly resulted from the southward subduction of the Bangong-Nujiang Tethyan Ocean under the Lhasa terrane and the trace of the north-dipping conductor likely due to the northward subduction of the Bangong-Nujiang Tethyan Ocean under the Qiangtang terrane. In addition, the magnetotelluric profile also images a high-conductivity lithospheric-scale anticline beneath the central Qiangtang terrane, which may correspond to the upwelling of postcollisional magmatism triggered by northward subduction of the Bangong-Nujiang Tethyan Ocean under the Qiangtang terrane, aqueous fluid and/or partial melting

A point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity and reverses its transcriptional regulatory activity on the viral early promoter

<p>Abstract</p> <p>Background</p> <p>The human papillomavirus (HPV) E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa) substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells.</p> <p>Results</p> <p>CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA) showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2.</p> <p>Conclusions</p> <p>These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.</p

"To Chat-GPT or not to Chat-GPT":Navigating the paradoxes of generative AI in the advertising industry

Generative AI technology is evoking both excitement and fear about its potential impact across a host of industries—including advertising, where it is expected to have a significant disruptive effect. This article utilizes the paradox lens to explore the implications of text-to-text generative AI in the form of ChatGPT for the advertising industry. Drawing on 48 interviews with advertising professionals, we identify three operational paradoxes that are associated with conducting research, creativity, efficiency, and one psychological paradox related to work identity. To gain a competitive advantage, we urge practitioners to adopt a confrontation-based coping strategy to navigate these paradoxes. This can be mobilized via an ambidexterity or contingency paradox management approach. We outline specific tactics in this article.</p

Effect of Emodin on Preventing Postoperative Intra-Abdominal Adhesion Formation

Background. Postoperative intra-abdominal adhesions are a major complication after abdominal surgery. Although various methods have been used to prevent and treat adhesions, the effects have not been satisfactory. Emodin, a naturally occurring anthraquinone derivative and an active ingredient in traditional Chinese herbs, exhibits a variety of pharmacological effects. In our study, we demonstrated the effect of emodin treatment on preventing postoperative adhesion formation. Materials and Methods. A total of 48 rats were divided into six groups. Abdominal adhesions were created by abrasion of the cecum and its opposite abdominal wall. In the experimental groups, the rats were administered daily oral doses of emodin. On the seventh day after operation, the rats were euthanized, and blood and pathological specimens were collected. Abdominal adhesion formation was evaluated by necropsy, pathology, immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay analyses. Results. Abdominal adhesions were markedly reduced by emodin treatment. Compared with the control group, collagen deposition was reduced and the peritoneal mesothelial completeness rate was higher in the emodin-treated groups. Emodin had anti-inflammatory effects, reduced oxidative stress, and promoted the movement of the intestinal tract (P<0.05). Conclusion. Emodin significantly reduced intra-abdominal adhesion formation in a rat model