Io Nam Wong

Objective: This study aimed to investigate the expression pattern, clinical significance, immune association and biological function of general control nonderepressible 1 (GCN1) in colorectal cancer (CRC). Methods: Gene expression and clinical data from 1603 CRC patients were obtained from TCGA and E‐MTAB‐12862 datasets, with external validation using GEO cohorts. Tumour immune cell proportions were estimated using the CIBERSORT and ESTIMATE algorithms. Predicted drug responses were assessed using the oncoPredict package based on the GDSC database. In vitro functional experiments, including MTT proliferation assays and transwell migration and invasion assays, were conducted in HCT116 and HT29 cell lines following GCN1 knockdown. Results: GCN1 was significantly upregulated in CRC tissues compared with normal tissues. Higher GCN1 expression was associated with improved overall survival in early‐stage CRC and lower tumour stage. Immune microenvironment analysis revealed that tumours with high GCN1 expression showed computationally inferred enrichment of antitumor immune cell populations and reduced immunosuppressive components, along with lower TIDE scores. Functional enrichment analyses indicated that GCN1 was involved in pathways related to cell cycle regulation, DNA replication and epithelial–mesenchymal transition (EMT). Knockdown of GCN1 significantly inhibited CRC cell proliferation, migration and invasion while modulating EMT and cell cycle‐related proteins. Drug sensitivity prediction further indicated that tumours with high GCN1 expression exhibited lower computationally inferred IC50 values for several commonly used chemotherapeutic agents, including 5‐fluorouracil, oxaliplatin, paclitaxel and docetaxel. Conclusion: Our findings suggest that GCN1 may exhibit context‐dependent associations in CRC. While in vitro experiments support a tumour cell‐intrinsic role of GCN1 in regulating malignant phenotypes through EMT‐ and cell cycle‐related processes, higher GCN1 expression at the tissue level was also associated with favourable clinical and immune‐related features. These observations suggest that GCN1 may serve as a potential prognostic indicator and warrant further mechanistic investigation.

Algal polysaccharides are an essential active substance in food nutrition and even pharmaceutical activity research due to wide sources, low toxicity, and no side effects. In our previous research, we identified the chemical structure and studied the immunomodulatory mechanism of the polysaccharide CRVP from edible green algae Caulerpa racemosa var. peltata. In this study, we further investigated the cytotoxicity and potential mechanism of CRVP against Hepa1-6 cells. Metabolomics analysis showed that CRVP might affect glutathione metabolism-related pathways. CRVP significantly up-regulated oxidized glutathione (GSSG) and down-regulated reduced glutathione (GSH) in Hepa1-6 cells, increasing the ratio of GSSG to GSH and intracellular reactive oxygen species. The potential anti-liver cancer mechanism is that CRVP may affect redox homeostasis and lead to apoptosis by inhibiting glutathione reductase or System Xc^-. Based on the known immunomodulatory mechanism of CRVP, this study can provide a material basis for adjuvant therapeutic nutritional agents with immune-enhancing anti-cancer activity.

Algal polysaccharides (APs) have attracted increasing interest in recent years as adjunctive agents in cancer therapy due to their abundance, low toxicity, and diverse bioactivity. This review explores the pharmacological effects and mechanisms of APs in combination with chemotherapy, radiotherapy, and immunotherapy, as well as their potential as a nano medicine delivery system. It highlights a wide range of biological activities exhibited by APs in combination therapy, including enhanced tumor cell killing, modulation of the tumor immune microenvironment, and protection of healthy tissues from treatment-related toxicity. Furthermore, the review summarizes the advancements in the pharmacodynamics, pharmacokinetics, and safety profiles of APs, emphasizing the need for standardized raw materials, combined strengths analysis, and clinical validation as key future directions.

Aging research has primarily focused on adult aging clocks, leaving a critical gap in understanding a biological clock across the full life cycle, particularly during infancy and childhood. Here we introduce LifeClock, a biological clock model that predicts biological age across all life stages using routine electronic health records and laboratory test data. To enhance individualized predictions, we integrated virtual patient representations from 24,633,025 heterogeneous longitudinal clinical visits across 9,680,764 individuals and projected them into a latent space. Our approach leverages EHRFormer, a time-series transformer-based model, to analyze developmental and aging dynamics with high precision and develop accurate biological age clocks spanning infancy to old age. Our findings reveal distinct biological clock patterns across different life stages. The pediatric clock is strongly associated with children’s development and accurately predicts current and future risks of major pediatric diseases, including malnutrition, growth and developmental abnormalities. The adult clock is strongly associated with aging and accurately predicts current and future risks of major age-related diseases, such as diabetes, renal failure, stroke and cardiovascular diseases. This work therefore distinguishes pediatric development from adult aging, establishing a novel framework to advance precision health by leveraging routine clinical data across the entire lifespan.

Introduction: Medical education standards influence the academic performance and clinical competencies of medical students as career practitioners. With the rising demand for teaching innovation and technological advancement in medical education, clinical teaching in China has faced many challenges, which necessitate a re-evaluation of traditional educational approaches. To overcome these challenges, the tertiary hospital in Guangzhou and the medical school in Macau have initiated the reform of clinical teaching in an undergraduate teaching program with a specific project for Macau medical students to perform clinical placement in anaesthesia at the tertiary hospital in Guangzhou. The project was co-led and co-chaired by both institutions and coordinated by the Anaesthetic Department, International Office, and Medical Education Department at the tertiary hospital in Guangzhou. This project aimed to analyse students’ anaesthetic placement experiences to illustrate the effectiveness of collaborative teaching and the development of a student-co-designed curriculum. Methods: The participating medical students attended the anaesthetic placement at the tertiary hospital in Guangzhou, which is scheduled to spend one day in operating theatres, recovery rooms, and central theatre pharmacies under supervision. All participating students provided post-placement feedback by answering a pre-designed enquiry questionnaire to develop a co-designed curriculum. Post-placement feedback, including written reflections in response to the enquiry questionnaires, was collected and semantically analysed. Results: Post-placement feedback in response to the enquiry questionnaires was presented as themes, which formed the core elements of the student-co-designedanaesthetic placement curriculum. Conclusion: This study demonstrates the effective implementation of collaborative teaching and curriculum co-designed in anaesthesia education at a tertiary hospital in the “Greater Bay Innovative Zones of China”. This curricular design model facilitates the development of a student-centred anaesthetic curriculum for better clinical teaching and learning.

DDX27, a member of the DEAD-box RNA helicase family, plays a pivotal role in RNA metabolism and is essential for diverse cellular processes, including transcription, pre-mRNA splicing, translation, and ribosome biogenesis. Recent findings have implicated DDX27 as a substantial contributor to tumorigenesis and cancer progression across various malignancies, establishing its significance as a molecular hub that interacts with key oncogenic partners such as major vault protein (MVP) and nucleophosmin 1 (NPM1). We conducted systematic search in the following comprehensive academic databases: PubMed, MEDLINE or Web of Science. The keywords such as DDX27, DEAD-box protein 27, RNA helicase DDX27 and cancer, tumor or carcinoma were used for searching. This review consolidates the existing literature on DDX27, examining its structural features and biological functions within the context of tumorigenesis. We systematically explore the molecular mechanisms by which DDX27 influences tumor development and progression, focusing particularly on its roles across different cancer types, including colorectal cancer (CRC), gastric cancer (GC), breast cancer (BC), hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC). Key molecular mechanisms such as NF-κB activation and ERK1/2 phosphorylation involved in DDX27-related pathways are discussed. Our comprehensive summary elucidates the context-dependent roles of DDX27 across various cancers, highlighting its associations with advanced disease stages, metastasis, and therapeutic resistance. We also assess the potential of DDX27 as a diagnostic and prognostic biomarker, correlating its expression levels with negative clinical outcomes. Novel therapeutic strategies targeting DDX27 are proposed, including RNA interference techniques (siRNA and shRNA), miRNA-based therapies (miR-617 mimics), pathway modulation, and synthetic lethality approaches. Furthermore, we identify notable limitations in current research surrounding DDX27 and offer potential avenues for future investigation. These innovative strategies present significant promise for the development of precision cancer therapies aimed at improving treatment outcomes for patients.

Background: Activating the ubiquitin-proteasome system to dismantle disease- related proteins such as tau, β-amyloid, APP, and α-synuclein is an important focus in the research of neurodegenerative proteinopathy. By analyzing the serum RNA extracted from wild-type and Alzheimer’s disease (AD) transgenic mice at different ages (4, 8, and 12 months), this study revealed a new protective role of FBXL16 in AD, primarily through facilitating the degradation of disease-related proteins via the ubiquitin proteasome system. Methods: Proteomic analysis were conducted using protein lysates from HEK293 cells overexpressing FBXL16 to identify potential interacting proteins that interact with FBXL16. Subsequent experiments demonstrated that FBXL16 promotes the proteasomal degradation of the APP protein, as evidenced by co-immunoprecipitation with MG132 and cycloheximide (CHX), immunohistochemistry (IHC) and immunocytochemistry (ICC). Memory and cognitive improvements were observed in 3×Tg AD mice through the use of a lentivirus-mediated approach to generate a brain-specific AD mouse model overexpressing FBXL16 via stereotaxic injection. Furthermore, a brain-specific conditional knockout (cko) FBXL16 mouse model was generated and employed to further confirm the functional role of FBXL 16 in AD via various behavioral tests including Morris water maze and Y-maze. Results: The level of FBXL16 in the brains of transgenic APP/PSEN mice with AD decreased with age. Accelerated degradation of APP was observed when FBXL16 was overexpressed in the hippocampi of these AD mice via a lentivirus. This process led to notable improvements in cognitive impairments and reductions in neuroinflammation. Further studies using proteomics and bioinformatics techniques identified transcription factors and binding proteins associated with FBXL16, providing deeper insights into the potential role of FBXL16 in the regulation of AD. Finally, the in vivo effects of FBXL16 deficiency were further substantiated in cko mice, which overexpress Aβ but specifically lack FBXL16 in the brain region. Conclusions: These findings suggest that FBXL16 could be a new regulator of AD. These findings provide a foundation for further research into drug development and potential therapeutic strategies to combat other related neurodegenerative proteinopathies.

Introduction: The rising demand for knowledge updates and technological innovations in China has made clinical placement teaching challenging. Reforms for innovative teaching models through pilot classes have shown to improve students’ academic performance. This novel integration led to the announcement of healthcare collaboration in the Guangdong-Hong-Kong-Macao Greater Bay Area for projects within China’s “Global-Innovation-Hub” zones. First Affiliated Hospital (FAH) of Sun Yat-sen University (SYSU) in Guangzhou and the Faculty of Medicine (FMD) of Macau University of Science & Technology (MUST) in Macau have developed an inaugural project for FMD/MUST medical students to perform pre-internships at FAH-SYSU. This study aimed to reflect on students’ experiences with collaborative teaching and learning through medical curricular integration in the “Global-Innovation-Hub” zones designed by both institutions for developing integrated curriculum. Methods: FMD/MUST students attended medical clerkships at FAH-SYSU using a system-integrated curriculum in China’s “Global-Innovation-Hub” zones, allowing different education systems at different locations. Post-clerkship surveys ranked teaching models in conjunction with written reflections in response to post-clerkship questionnaires for all participating students. The teaching models were defined by the way supervisors’ interaction with students, and written reflections in response to the post-clerkship questionnaire were descriptively and semantically analysed. Results: The top-ranked teaching models include first “Student-led consultation under supervision in observers’ chair with discussion”, second “Observe consultation and discuss with the teacher in-between patients in observers’ chair” and third “Student-led consultation under supervision in consultants’ chair with discussion”. The post-clerkship questionnaires showed positive outcomes. Conclusion: This study demonstrates the successful delivery of collaborative teaching and learning through medical curricular integration in China’s “Global-Innovation-Hub” zones. This integration enables the development of a consistent and student-preferred teaching model being introduced into clinical placement curriculum. The unique location of China’s “Global-Innovation-Hub” zones in the Guangdong-Hong-Kong-Macao Greater Bay Area allows this integration to significantly improve students’ clinical reasoning learning.