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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Chen, Zhipeng, et al.
(författare)
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Design, Synthesis, and Structure-Activity Relationship of N-Aryl-N'-(thiophen-2-yl) thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
- 2021
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Ingår i: Journal of Medicinal Chemistry. - Washington, DC : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:11, s. 7371-7389
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Tidskriftsartikel (refereegranskat)abstract
- The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl) urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells. © 2021 American Chemical Society
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| 3. |
- Zhang, Sulin, et al.
(författare)
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SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC
- 2020
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Ingår i: Autophagy. - Philadelphia : Taylor & Francis. - 1554-8627 .- 1554-8635. ; 16:4, s. 735-749
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Tidskriftsartikel (refereegranskat)abstract
- The non-receptor tyrosine kinase SRC is a key mediator of cellular protumorigenic signals. SRC is aberrantly over-expressed and activated in more than 80% of colorectal cancer (CRC) patients, therefore regulation of its stability and activity is essential. Here, we report a significant down regulation of SNX10 (sorting nexin 10) in human CRC tissues, which is closely related to tumor differentiation, TNM stage, lymph node metastasis and survival period. SNX10 deficiency in normal and neoplastic colorectal epithelial cells promotes initiation and progression of CRC in mice. SNX10 controls SRC levels by mediating autophagosome-lysosome fusion and SRC recruitment for autophagic degradation. These mechanisms ensure proper controlling of the activities of SRC-STAT3 and SRC-CTNNB1 signaling pathways by up-regulating SNX10 expression under stress conditions. These findings suggest that SNX10 acts as a tumor suppressor in CRC and it could be a potential therapeutic target for future development.Abbreviations: ACTB: actin beta; ATG5: autophagy related 5; ATG12: autophagy related 12; CQ: chloroquine; CRC: colorectal cancer; CTNNB1: catenin beta 1; EBSS: Earle's balanced salt solution; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane protein 2; MAP1LC3: microtubule associated protein 1 light chain 3; MKI67: marker of proliferation Ki-67; mRNA: messenger RNA; PX: phox homology; RT-qPCR: real time quantitative polymerase chain reaction; siRNA: small interfering RNA; SNX10: sorting nexin 10; SQSTM1: sequestosome 1; SRC: SRC proto-oncogene, non-receptor tyrosine kinase; STAT3: signal transducer and activator of transcription 3; WT: wild type. © 2019 Informa UK Limited, trading as Taylor & Francis Group
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| 4. |
- Zhang, Yazhou, et al.
(författare)
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A Multimodal Coupled Graph Attention Network for Joint Traffic Event Detection and Sentiment Classification
- 2023
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Ingår i: IEEE transactions on intelligent transportation systems (Print). - Piscataway, NJ : IEEE. - 1524-9050 .- 1558-0016. ; 24:8, s. 8542-8554
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Tidskriftsartikel (refereegranskat)abstract
- Traffic events are one of the main causes of traffic accidents, leading to traffic event detection being a challenging research problem in traffic management and intelligent transportation systems (ITSs). The main gap in this task lies in how to extract and represent the valuable information from various kinds of traffic data. Considering the important role that social networks play in traffic data analysis, we argue that sentiment classification and traffic event detection are two closely related tasks in ITSs, where event and sentiment can reveal both explicit and implicit traffic accidents, respectively. Unfortunately, none of the recent approaches in traffic event detection have taken sentiment knowledge into view. This paper proposes a multimodal coupled graph attention network (MCGAT). It aims to construct a multimodal multitask interactive graphical structure where terms (sucha as words, and pixels) are treated as nodes, and their contextual and cross-modal correlations are formalized as edges. The key components are cross-modal and cross-task graph connection layers. The cross-modal graph connection layer captures the multimodal representation, where each node in one modality connects all nodes in another modality. The cross-task graph connection layer is designed by connecting the multimodal node in one task to two single nodes in another task. Empirical evaluation of two benchmarking datasets, such as MGTES and Twitter, shows the effectiveness of the proposed model over state-of-the-art baselines in terms of F1 and accuracy, with significant improvements of 2.4%, 2.4%, 2.7%, and 2.7%. © 2022 IEEE.
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| 5. |
- Zhang, Yazhou, et al.
(författare)
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A Multitask learning model for multimodal sarcasm, sentiment and emotion recognition in conversations
- 2023
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Ingår i: Information Fusion. - Amsterdam : Elsevier. - 1566-2535 .- 1872-6305. ; 93, s. 282-301
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Tidskriftsartikel (refereegranskat)abstract
- Sarcasm, sentiment and emotion are tightly coupled with each other in that one helps the understanding of another, which makes the joint recognition of sarcasm, sentiment and emotion in conversation a focus in the research in artificial intelligence (AI) and affective computing. Three main challenges exist: Context dependency, multimodal fusion and multitask interaction. However, most of the existing works fail to explicitly leverage and model the relationships among related tasks. In this paper, we aim to generically address the three problems with a multimodal joint framework. We thus propose a multimodal multitask learning model based on the encoder–decoder architecture, termed M2Seq2Seq. At the heart of the encoder module are two attention mechanisms, i.e., intramodal (Ia) attention and intermodal (Ie) attention. Ia attention is designed to capture the contextual dependency between adjacent utterances, while Ie attention is designed to model multimodal interactions. In contrast, we design two kinds of multitask learning (MTL) decoders, i.e., single-level and multilevel decoders, to explore their potential. More specifically, the core of a single-level decoder is a masked outer-modal (Or) self-attention mechanism. The main motivation of Or attention is to explicitly model the interdependence among the tasks of sarcasm, sentiment and emotion recognition. The core of the multilevel decoder contains the shared gating and task-specific gating networks. Comprehensive experiments on four bench datasets, MUStARD, Memotion, CMU-MOSEI and MELD, prove the effectiveness of M2Seq2Seq over state-of-the-art baselines (e.g., CM-GCN, A-MTL) with significant improvements of 1.9%, 2.0%, 5.0%, 0.8%, 4.3%, 3.1%, 2.8%, 1.0%, 1.7% and 2.8% in terms of Micro F1. © 2023 Elsevier B.V.
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| 6. |
- Zhang, Zheng, et al.
(författare)
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Our way(s) to action research : Doctoral students’ international and interdisciplinary collective memory work
- 2014
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Ingår i: Action Research. - London, UK : SAGE Publications. - 1476-7503 .- 1741-2617 .- 0264-5122. ; 12:3, s. 293-314
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Tidskriftsartikel (refereegranskat)abstract
- This study involved six Swedish and Canadian doctoral students who shared interests in using action research in professional education in different disciplines. We employed Noffke’s three dimensions of action research as a theoretical framework (i.e., the Professional, the Personal, and the Political). Using collective biography as a methodology, we cooperatively examined how our personal and professional agendas and macro-level structures have been shaping our intentions to conduct action research projects in our respective disciplines. The key findings of this international and interdisciplinary collective biography relate our growing awareness of the intimacy between research and life in vari- ous professional and geographic contexts. Collectively addressing our shared frustrations, we celebrated action research as a methodology that attends to the dynamic and concrete lived experiences of our participants in various spatio-temporalities. Reflecting upon the hybridity of our own researcher identities, we were also able to see the intimate relation between ourselves as active citizens and critical action researchers who are determined to take up the challenges and engage in critically oriented action research that could nurture more ‘‘caring,’’ ‘‘empowering,’’ and ‘‘transforming’’ public spheres.
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| 7. |
- Zheng, Lu, et al.
(författare)
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Potential treatment methods targeting 2019-nCoV infection
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 205
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Forskningsöversikt (refereegranskat)abstract
- The novel coronavirus, 2019-nCoV, has quickly spread across the world and pose serious threat to public health because it can infect people very easily. The major clinical symptoms of 2019-nCoV infection include fever, dry cough, myalgia, fatigue, and diarrhea. The 2019-nCoV belongs to the betacoronavirus family, and gene sequencing results demonstrate that it is a single-stranded RNA virus, closely related to Severe Acute Respiratory Syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). It has been observed that the virus invades human body mainly through binding to angiotensin-converting enzyme 2 (ACE2) receptors similar to SARS-CoV and the main protease (Mpro) acts as a critical protease for digesting the polyprotein into functional polypeptides during the replication and transcription process of 2019-nCoV. In this review, we summarized the real-time information of 2019-nCoV treatment methods and mainly focused on the chemical drugs including lopinavir/ritonavir, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir and other potential innovative active molecules. Their potential targets, activity, clinical status and side effects are described. In addition, Traditional Chinese Medicine (TCM), Convalescent plasma therapy (CPT) and biological reagents available, as well as the promising vaccine candidates against 2019-nCoV are also discussed.
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