An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report

Systemic chemotherapies are the primary treatment options for patients with unresectable and metastatic intrahepatic cholangiocarcinoma (ICC), but the effectiveness of current systemic therapies is limited. The development of targeted-therapy has changed the treatment landscape of ICC, and comprehensive genome sequencing of advanced cholangiocarcinoma patients could be beneficial to identify potential targets to guide individualized treatment. Herein, we reported an unresectable and metastatic ICC patient who detected EML4-ALK rearrangement in peripheral blood, which was later confirmed on tissue-based testing, and achieved partial response (PR) after first-line treatment with ensartinib. This case suggests that the liquid biopsy is of clinical value for unresectable or metastatic ICC, and the discovery of rare molecular targets provides new therapeutically approaches for advanced ICC patients

Long Non-coding RNAs Contribute to the Inhibition of Proliferation and EMT by Pterostilbene in Human Breast Cancer

Background: There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the process of carcinogenesis and treatment using chemotherapy. Pterostilbene, a phytochemical agent with natural antioxidant and anti-inflammatory properties, has been shown to modulate oncogenic processes in many cancers. However, there has been limited research on the association between pterostilbene and the expression of lncRNAs.Methods: MCF7 breast cancer cells were treated with various concentrations of pterostilbene and their gene expression profile was analyzed by quantitative real-time PCR, Western blotting and immunofluorescence.Results: Treatment with pterostilbene inhibited cell proliferation and epithelial-to-mesenchymal transition (EMT), and increased cell apoptosis, autophagy and ER stress. The Akt/mTOR pathway was downregulated, but p38 MAPK/Erk signaling was activated in cells following treatment with pterostilbene. Pterostilbene increased the expression of the lncRNAs MEG3, TUG1, H19, and DICER1-AS1 whereas the expression of LINC01121, PTTG3P, and HOTAIR declined. Knockdown of lncRNA H19 resulted in a reduction of the cell invasion, with the cells becoming more sensitive to pterostilbene therapy.Conclusions: These results suggest that efficient optimum disruption of lncRNA expression might possibly improve the anti-tumor effects of phytochemical agents, thus serving as a potential therapy for breast cancer

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2

Background/Aims: B-cell receptor-associated protein 31 (Bap31) is an evolutionarily conserved, ubiquitously expressed, polytopic integral membrane protein in the endoplasmic reticulum (ER) that is involved in the regulation of apoptosis, protein transport and degradation. Patients with Bap31 mutations exhibit symptoms similar to those exhibited by patients with central nervous system (CNS) diseases, such as deafness, dystonia, and intellectual disability. The present study aimed to investigate the function of Bap31 in CNS diseases by identifying a CNS disease-related gene regulated by Bap31 and exploring the underlying molecular mechanism. Methods: ShRNA-Bap31 and siRNA-Bap31 were used to knockdown Bap31 in N2a cells, and real-time PCR was performed to detect the mRNA levels of genes involved in CNS diseases. Western blot analyses were used to examine the protein levels of the candidate gene (valosin-containing protein, VCP) both in vivo and in vitro. The functions of Bap31 and VCP in mediating the degradation of the hyper-unstable mutant of cystic fibrosis trans-membrane conductance regulator (CFTRΔF508) were studied. Moreover, real-time PCR, Western blot and dual luciferase reporter analyses were conducted to investigate the molecular mechanism by which Bap31 regulates the expression levels of VCP. Results: VCP was identified as a candidate gene based on its differential expression in N2a cells following both shRNA- and siRNA-mediated knockdown of Bap31. Both the mRNA and protein levels of VCP were regulated by Bap31 in vivo and in vitro. In the ER-associated degradation (ERAD) pathway, Bap31 also regulated VCP expression and caused differences in the binding quantities of CFTRΔF508 and VCP. Furthermore, a transcription factor of VCP (E74-like factor 2, Elf2) was regulated by Bap31, and Elf2 mediated the changes in VCP transcription and expression in cells with altered Bap31 expression. Conclusion: These results indicate that Bap31 regulates the expression of VCP possibly via Elf2 and support the potential molecular function of Bap31 in CNS diseases

SketchMate: Deep Hashing for Million-Scale Human Sketch Retrieval

We propose a deep hashing framework for sketch retrieval that, for the first time, works on a multi-million scale human sketch dataset. Leveraging on this large dataset, we explore a few sketch-specific traits that were otherwise under-studied in prior literature. Instead of following the conventional sketch recognition task, we introduce the novel problem of sketch hashing retrieval which is not only more challenging, but also offers a better testbed for large-scale sketch analysis, since: (i) more fine-grained sketch feature learning is required to accommodate the large variations in style and abstraction, and (ii) a compact binary code needs to be learned at the same time to enable efficient retrieval. Key to our network design is the embedding of unique characteristics of human sketch, where (i) a two-branch CNN-RNN architecture is adapted to explore the temporal ordering of strokes, and (ii) a novel hashing loss is specifically designed to accommodate both the temporal and abstract traits of sketches. By working with a 3.8M sketch dataset, we show that state-of-the-art hashing models specifically engineered for static images fail to perform well on temporal sketch data. Our network on the other hand not only offers the best retrieval performance on various code sizes, but also yields the best generalization performance under a zero-shot setting and when re-purposed for sketch recognition. Such superior performances effectively demonstrate the benefit of our sketch-specific design.Comment: Accepted by CVPR201

Aggregation-Induced Emission (AIE), Life and Health

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health

Factors influencing foreign students’ choice of studying in Finland

With the globalization and internationalization of higher education, the flow of global students has become frequently, people's demand for higher education has increased, and the importance of the education industry has also enhanced. Nowadays, Finland is recognized as one of the countries with the most complete education system in the world and has attracted many foreign students to study in Finland. The objective of the research is to understand what factors influence foreign students to choose college in Finland. In-depth research can not only design strategies for attracting foreign students for Finnish higher education institutions, but also provide foreign students with factors to consider when choosing a college as a reference. Based on Hossler et al.’s (1999) combined model as the theoretical framework, qualitative research methods are used. In the research process, the author organized the semi-structured interviews with four international students who are studying at JAMK University of Applied Sciences (JAMK) to obtain the primary data. In addition, the author uses some existing data collected early by the survey agency or organization as secondary data. And then the author uses the coding method to analyze the primary data and through the data triangulation method, combined with secondary data for in-depth analysis. The research results of this thesis are helpful to analyze the factors that influence foreign students to choose Finnish higher education and can also provide reference for the recruitment of international students in Finnish higher education institutions and guide foreign students to make the right choice of college