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Biomedical subjects

Wei Luo

Publications and source records attributed to Wei Luo.

6 recordsLinked to original sources

Methylation-Associated Differentiation Features Define Biological and Prognostic Heterogeneity in CMS4 Colorectal Cancer.

Consensus molecular subtype 4 (CMS4) colorectal cancer (CRC) is associated with an aggressive clinical course and poor survival, yet the biological basis of heterogeneity within this subtype remains incompletely understood. DNA methylation is an epigenetic mechanism involved in transcriptional regulation, cellular differentiation, and colorectal tumorigenesis. Here, we integrated single-cell RNA sequencing (scRNA-seq), bulk data, and promoter DNA methylation data to characterize CMS4-associated cancer cell states and methylation-related features. Using the scAB algorithm, we integrated scRNA-seq with bulk CMS4 data and identified CMS4-related cells distributed across multiple patients. Single-cell analyses of cell-cell communication and transcriptional regulation revealed a CMS4-related cancer cell population characterized by macrophage migration inhibitory factor (MIF)-centered intercellular communication, enhanced caudal type homeobox 1 (CDX1) and Kruppel-like factor 5 (KLF5) regulon activity, and gene modules enriched in differentiation-related pathways. CytoTRACE analysis further stratified CMS4 cancer cells into poorly and well-differentiated states, yielding 802 differentially expressed genes (DEGs). Linking these differentiation-associated DEGs with bulk expression and promoter methylation data identified 218 methylation-associated DEGs showing significant inverse methylation expression correlations, suggesting a link between differentiation-related heterogeneity and promoter methylation. Univariable Cox regression followed by LASSO regression further prioritized eight genes for construction of the methylation and differentiation-related prognostic model (MeDiff-PM). MeDiff-PM consistently stratified overall survival in the TCGA CMS4 cohort and two independent validation cohorts, with cutoff-independent continuous Cox analyses further supporting its prognostic association across cohorts. And MeDiff-PM remained prognostically significant after adjustment for available clinical variables. High MeDiff-PM risk scores were associated with activation of P53, WNT, and ubiquitin-mediated proteolysis pathways and with consistent predicted drug response differences for compounds across three CMS4 cohorts. While individual in silico knockout analysis suggested links between MeDiff-PM genes and metallothionein-related and immune-associated transcriptional responses. Collectively, these findings indicate that methylation-associated differentiation features represent a molecular dimension of intra-CMS4 heterogeneity and provide a biologically informed framework for prognostic stratification within CMS4 CRC.

Humans

Unveiling microbial communities and biogeochemical cycles in Antarctic colored snow.

Snow cover, the extensive terrestrial habitat in Antarctica, sometimes exhibits vivid coloration, yet the structure and function of its microbial communities remain poorly characterized. Using metagenomic sequencing of red snow (RS) and green snow (GS) from the Fildes Peninsula, we found that bacterial, eukaryotic, and archaeal relative abundances were 85.82%, 13.52% and 0.16%, respectively. &#x3b2;-Diversity differed significantly between RS and GS across these three domains (P&#x2009;<&#x2009;0.05). Dominant bacterial phyla included Bacteroidota (RS: 62.61%; GS: 38.72%) and Pseudomonadota (RS: 32.80%; GS: 54.10%). Among eukaryotes, Chlorophyta (RS: 58.10%; GS: 52.98%) and Basidiomycota (RS: 14.80%; GS: 8.08%) were prevalent. Nanobdellota dominated archaea, with lower abundance in RS than GS. In the algal community, Sanguina, Gonium and Chloromonas were significantly enriched in red snow, while Chlorella and Micractinium were enriched in green snow (P&#x2009;<&#x2009;0.05). Marker genes associated with carbon (C), nitrogen (N), phosphorus (P) and sulfur (S) cycles were identified in green and red snow. Aerobic respiration and phosphate regulation were significantly enriched in red snow, while CO oxidation, fermentation, and denitrification were significantly enriched in green snow. Key microbial genera associated with these functional pathways also varied. In the denitrification of red snow, Stutzerimonas was the most abundant genus, while Janthinobacterium was abundant in green snow. Nitrification-related genes were detected only in red snow based on the present metagenomic data. The network of the red snow microbial community was potentially more complex and resistant based on topology, which not only benefited its own long-term survival but might also have potentially influenced the positive feedback effect of snowmelt by maintaining a low-albedo snow surface. This provided an ecological implication under climate warming: the expansion of red snow patches showed the potential to the increase nitrate runoff export, which would affect nitrogen nutrient levels in coastal Antarctic waters. Overall, this study used metagenomics to compare the multidomain (bacteria, archaea and eukaryotes) composition and diversity between red snow and green snow, and directly linked key microbial taxa with functional genes of biogeochemical cycles. This study provided new insights into the biological characteristics and functional potential of Antarctic colored snow.

Snow

A chromosome-level assembly of the alpine snow alga Chloromonas typhlos.

Chloromonas typhlos is a cosmopolitan alpine snow alga distributed across continents, and its blooming accelerates snow melting by decreasing the amount of snow albedo. To elucidate the genetic traits underlying the adaptation of C. typhlos to the alpine habitat, we combined PacBio sequencing and Hi-C to generate a high-quality chromosome-level genome assembly (contig N50: 1.29&#x2009;Mb; scaffold N50: 7.23&#x2009;Mb) with 31 chromosomes and a genome size of 200.86&#x2009;Mb. Repetitive elements constituted 11.05% of the genome, and 16,133 protein-coding genes were predicted, of which 82% were functionally annotated. This study provides a set of omics resources both for snow algae and the genus Chloromonas.

Snow

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16&#x2009;years [range, 9-41&#x2009;years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36&#x2009;months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors &#x2264; 10&#x2009;mm and > 10&#x2009;mm (p&#x2009;=&#x2009;.470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5&#x2009;months. The estimated OS rates at 12, 24 and 60&#x2009;months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent

Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-Response Relationships and Moderating Factors.

OBJECTIVE: This meta-analysis evaluated the efficacy of behavioral activation (BA) in adolescents with subthreshold depression (SD) or major depressive disorder (MDD), exploring dose-response relationships and moderating factors. METHOD: We searched PubMed, EMBASE, Web of Science, EBSCO, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) through December 31, 2024. Risk of bias was assessed using RoB-2, and evidence quality with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Analyses were performed with R, using standardized mean difference (SMD) for continuous variables and meta-regression for dose-response relationships. Subgroup analyses included symptom severity, intervention setting, delivery format, and parental involvement. The primary outcome was the reduction in depressive symptoms (PROSPERO: CRD42023444273). RESULTS: A total of 14 studies were included (11 RCTs meta-analyzed, comprising 572 participants). BA demonstrated a moderate effect size compared to treatment-as-usual (SMD = -0.42) and a large effect size compared to no-treatment controls (SMD = -0.87). BA was more effective for mild depressive symptoms (SMD = -0.93) than severe symptoms (SMD = -0.43), with significant efficacy in university settings (SMD = -0.94). Intervention without parental involvement exhibited significantly larger effects than those with parental participation (SMD = -0.94 vs -0.38; p < .0001), although this finding was likely confounded by age, symptom severity, and intervention setting. BA moderately improved both behavioral activation levels and functioning (SMD = 0.49). CONCLUSION: Short-term, school-based BA is significantly beneficial for older adolescents with mild depressive symptoms. Findings provide practical guidance for optimizing BA implementation and highlight directions for future research, including the need for larger sample sizes, standardized follow-up assessments, and more representative samples. PLAIN LANGUAGE SUMMARY: This meta-analysis evaluated the effectiveness of behavioral activation (BA), a therapeutic approach focused on improving positive activities, in adolescents with subthreshold depression or major depressive disorder. Based on 14 included studies and 572 participants, BA was found to be more effective for subthreshold compared to major depression. These findings suggest a promising role for BA as an early intervention tool in adolescent depression. STUDY REGISTRATION INFORMATION: Precision Optimization of Behavioral Activation for Major and Subthreshold Depression: A Meta-Analysis of Exploring Dose-response Relationships and Moderating Factors; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444273. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. Diverse cell lines and/or genomic datasets were not available. We actively worked to promote sex and gender balance in our author group.

Humans

CYFIP1 coordinate with RNMT to induce osteosarcoma cuproptosis via AURKAIP1 m7G modification.

Osteosarcoma (OS) presents challenges due to its genomic instability and complexity, necessitating investigation into its oncogenesis and progression mechanisms. Recent studies have implicated m7G, a post-transcriptional modification, in the development of various cancers. However, research on m7G modification in OS remains limited. This study aimed to explore the impact of m7G modification in OS, focusing on the role and mechanism of CYFIP1, a member of m7G cap binding complexes. Our findings demonstrated prominent anti-OS effects of CYFIP1 in vitro and vivo. Mechanistically, CYFIP1 collaborated with RNMT to induce the m7G methylation of AURKAIP1 mRNA, which resulted in the stability and the increasing translation of AURKAIP1 mRNA. AURKAIP1, a kind of mitochondrial small ribosomal subunit protein, exhibited increased expression, leading to the dysregulation of mitochondrial translation. This, in turn, caused an increase in the expression of FDX1, eventually triggering cuproptosis in OS cells and repressing OS occurrence and progression. In summary, our study identified the CYFIP1/RNMT/AURKAIP1/FDX1 axis as a potential therapeutic target for OS. These insights contribute to OS research and may guide the development of novel treatments for this challenging disease.

Humans