Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders ...the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.
Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders ...the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.
Flavonoids are the most common phytochemicals in vegetables and herbal products. The beneficial functions of flavonoids in the brain and erythropoietic system have been proposed. Erythropoietin (EPO) ...is a potent protective agent in the brain; but which has difficulty to cross the blood brain barrier (BBB). Here, about 60 flavonoids were screened for their potential activation on the transcription of EPO mRNA in the neuronal embryonic stem cell lines, NT2/D1 and PC12. Amongst the screened flavonoids, formononetin, calycosin, ononin, chrysin, baicalein and apigenin showed robust up regulation of EPO production via enhancement of hypoxia response element (HRE) activity in cultured embryonic stem cells. In addition, the flavonoids showed activation of HRE activity by having increased accumulation of HIF-1α, but not on level of HIF-1β, in the cultures. The accumulation of HIF-1α was attributed to up regulation of HIF-1α mRNA and blockade of HIF-1α degradation upon treatment of the flavonoids. These results suggested a promising trend of developing commercial products of flavonoids as food supplements tailored for brain health.
•Flavonoids are identified to activate the transcription of EPO mRNA via enhancement of hypoxia response element activity.•The activation of hypoxia response element by flavonoids are mediated by increased accumulation of HIF-1α, but not HIF-1β.•The accumulation of HIF-1α protein is caused by up regulation of HIF-1α mRNA and blockade of HIF-1α protein degradation.
Traditional Chinese medicines (TCMs) have been demonstrated as an important source for potential drug discovery. Flavonoids are regarded as the most common active components in TCMs because of their ...beneficial functions in the brain and erythropoietic system. Erythropoietin (EPO), a glycoprotein hormone, has been well‐studied for its neuroprotective function. The blood circulating EPO is not able to cross the blood brain barrier, and thus there is mounting demand to search for compounds that can induce endogenous cerebral EPO. Here, tectorigenin, an active compound in the rhizome of Belamcanda chinensis (L.) DC., significantly induced the expression of EPO mRNA via accumulation of hypoxia‐inducible factor (HIF)‐1α in cultured neuron‐like NT2/D1 cells and rat cortical neurons. Furthermore, tectorigenin induced transcription of HIF‐1α and reduced degradation of HIF‐1α‐OH, a hydroxylated form of HIF‐1α, in the culture. Thus, the upregulation of HIF‐1α was assumed to play a significant role in regulating EPO during the treatment of tectorigenin in cultured neurons. Hence, we reported the neuroprotective function of tectorigenin through upregulation of EPO in neurons, which could be a good candidate in developing drugs or food supplements for the treatment of brain disorders.
The cultivation of professionals and the fostering of awareness and literacy surrounding blockchain technology are indispensable because of its unprecedented impact on daily lives. However, the ...existing blockchain Teaching and Learning (T&L) approaches for secondary students are inadequate. In this study, we designed a tailored workshop for secondary students and examined the effectiveness of introducing blockchain concepts in the context of metaverse by implementation. The workshop integrated four educational theories, including Transfer of Learning, Interest Theory, Situated Learning, and Experiential Learning. The synthesis of typical theories gives rise to an innovative education strategy aimed at facilitating a transfer of awareness and interest from the metaverse domain to the blockchain domain, which is also the workshop’s ultimate goal. The workshop was designed considering the developmental status of secondary school students and its alignment with the Hong Kong secondary curriculum framework to accomplish the learning objective of enhancing their knowledge, skill, awareness and interest in blockchain technology. 225 secondary students joined the workshop, and the findings demonstrated that our approach is effective and the adoption of the transfer from the metaverse domain to the blockchain domain is feasible. The results of this paper may serve as a successful example of blockchain education for secondary students.
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