Lingxiao Wang

As a highly heterogeneous and complex disease, the identification of cancer’s molecular subtypes is crucial for accurate diagnosis and personalized treatment. The integration of multi-omics data enables a comprehensive interpretation of the molecular characteristics of cancer at various biological levels. In recent years, an increasing number of multi-omics clustering algorithms for cancer molecular subtyping have been proposed. However, the absence of a definitive gold standard makes it challenging to evaluate and compare these methods effectively. In this study, we developed a general framework for the comprehensive evaluation of multi-omics clustering algorithms and introduced an innovative metric, the accuracy-weighted average index, which simultaneously considers both clustering performance and clinical relevance. Using this framework, we performed a thorough evaluation and comparison of 11 state-of-the-art multi-omics clustering algorithms, including deep learning-based methods. By integrating the accuracy-weighted average index with computational efficiency, our analysis reveals that PIntMF demonstrates the best overall performance, making it a promising tool for molecular subtyping across a wide range of cancers.

Pygopus (Pygo) has been identified as a specific nuclear co-activator of the canonical Wingless (Wg)/Wnt signaling pathway in Drosophila melanogaster. Pygo proteins consist of two conserved domains: an N-terminal homologous domain (NHD) and a C-terminal plant homologous domain (PHD). The PHD’s ability to bind to di- and trimethylated lysine 4 of histone H3 (H3K4me2/3) appears to be independent of Wnt signaling. There is ongoing debate regarding the significance of Pygo’s histone-binding capacity. Drosophila Pygo orthologs have a tryptophan (W) > phenylalanine (F) substitution in their histone pocket-divider compared to vertebrates, leading to reduced histone affinity. In this research, we utilized CRISPR/Cas9 technology to introduce the Pygo-F773W point mutation in Drosophila, successfully establishing a viable homozygous Pygo mutant line for the first time. Adult mutant flies displayed noticeable abnormalities in reproduction, locomotion, heart function, and lifespan. RNA-seq and cluster analysis indicated that the mutation primarily affected pathways related to immunity, metabolism, and posttranslational modification in adult flies rather than the Wnt signaling pathway. Additionally, a reduction in H3K9 acetylation levels during the embryonic stage was observed in the mutant strains. These findings support the notion that Pygo plays a wider role in chromatin remodeling, with its involvement in Wnt signaling representing only a specific aspect of its chromatin-related functions.

Aging of the brain usually leads to the decline of neurological processes and is a major risk factor for various neurodegenerative diseases, including sleep disturbances and cognitive decline. Adipose tissue exosomes, as adipocyte-derived vesicles, may mediate the regulatory processes of adipose tissue on other organs, including the brain; however, the regulatory mechanisms remain unclear. We analyzed the sleep-wake behavior of young (10 days) and old (40 days) Drosophila and found that older Drosophila showed increased sleep fragmentation, which is similar to mammalian aging characteristics. To investigate the cross-tissue regulatory mechanisms of adiposity on brain aging, we extracted 10-day and 40-day Drosophila adipose tissue exosomes and identified circRNAs with age-dependent expression differences by RNA-seq and differential analysis. Furthermore, by combining data from 3 datasets of the GEO database (GSE130158, GSE24992, and GSE184559), circ_sxc that was significantly downregulated with age was finally screened out. Moreover, dme-miR-87-3p, a conserved target of circ_sxc, accumulates in the brain with age and exhibits inhibitory effects in predicted binding relationships with neuroreceptor ligand genes. In summary, the current study showed that the Drosophila brain could obtain circ_sxc by uptake of adipose tissue exosomes which crossed the blood-brain barrier. And circ_sxc suppressed brain miR-87-3p expression through sponge adsorption, which in turn regulated the expression of neurological receptor ligand proteins (5-HT1B, GABA-B-R1, Rdl, Rh7, qvr, NaCP60E) and ensured brain neuronal synaptic signaling normal function of synaptic signaling. However, with aging, this regulatory mechanism is dysregulated by the downregulation of the adipose exosome circ_sxc, which contributes to the brain exhibiting sleep disturbances and other “aging” features.

Sleep–wake stability is imbalanced with natural aging, and microRNAs (miRNAs) play important roles in cell proliferation, apoptosis, and aging; however, the biological functions of miRNAs in regulating aging-related sleep–wake behavior remain unexplored. This study varied the expression pattern of dmiR-283 in Drosophila and the result showed that the aging decline in sleep–wake behavior was caused by the accumulation of brain dmiR-283 expression, whereas the core clock genes cwo and Notch signaling pathway might be suppressed, which regulate the aging process. In addition, to identify exercise intervention programs of Drosophila that promote healthy aging, mir-283^SP/+ and Pdf > mir-283^SP flies were driven to perform endurance exercise for a duration of 3 weeks starting at 10 and 30 days, respectively. The results showed that exercise starting in youth leads to an enhanced amplitude of sleep–wake rhythms, stable periods, increased activity frequency upon awakening, and the suppression of aging brain dmiR-283 expression in mir-283^SP/+ middle-aged flies. Conversely, exercise performed when the brain dmiR-283 reached a certain accumulation level showed ineffective or negative effects. In conclusion, the accumulation of dmiR-283 expression in the brain induced an age-dependent decline in sleep–wake behavior. Endurance exercise commencing in youth counteracts the increase in dmiR-283 in the aging brain, which ameliorates the deterioration of sleep–wake behavior during aging.

(1) Background: There are few diagnostic and therapeutic targets for myocardial remodeling in the salvageable non-infarcted myocardium. (2) Methods: Hub genes were identified through comprehensive bioinformatics analysis (GSE775, GSE19322, and GSE110209 from the gene expression omnibus (GEO) database) and the biological functions of hub genes were examined by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, the differential expression of hub genes in various cell populations between the acute myocardial infarction (AMI) and sham-operation groups was analyzed by processing scRNA data (E-MTAB-7376 from the ArrayExpress database) and RNA-seq data (GSE183168). (3) Results: Ten strongly interlinked hub genes (Timp1, Sparc, Spp1, Tgfb1, Decr1, Vim, Serpine1, Serpina3n, Thbs2, and Vcan) were identified by the construction of a protein–protein interaction network from 135 differentially expressed genes identified through comprehensive bioinformatics analysis and their reliability was verified using GSE119857. In addition, the 10 hub genes were found to influence the ventricular remodeling of non-infarcted tissue by modulating the extracellular matrix (ECM)-mediated myocardial fibrosis, macrophage-driven inflammation, and fatty acid metabolism. (4) Conclusions: Ten hub genes were identified, which may provide novel potential targets for the improvement and treatment of AMI and its complications.