Subtype-WGME enables whole-genome-wide multi-omics cancer subtyping.

We present an innovative strategy for integrating whole-genome-wide multi-omics data, which facilitates adaptive amalgamation by leveraging hidden layer features derived from high-dimensional omics data through a multi-task encoder. Empirical evaluations on eight benchmark cancer datasets substantiated that our proposed framework outstripped the comparative algorithms in cancer subtyping, delivering superior subtyping outcomes. Building upon these subtyping results, we establish a robust pipeline for identifying whole-genome-wide biomarkers, unearthing 195 significant biomarkers. Furthermore, we conduct an exhaustive analysis to assess the importance of each omic and non-coding region features at the whole-genome-wide level during cancer subtyping. Our investigation shows that both omics and non-coding region features substantially impact cancer development and survival prognosis. This study emphasizes the potential and practical implications of integrating genome-wide data in cancer research, demonstrating the potency of comprehensive genomic characterization. Additionally, our findings offer insightful perspectives for multi-omics analysis employing deep learning methodologies.

Analysis of global research hotspots and trends in immune cells in intervertebral disc degeneration: A bibliometric study.

Intervertebral disc degeneration is an important pathological basis for spinal degenerative diseases. The imbalance of the immune microenvironment and the involvement of immune cells has been shown to lead to nucleus pulposus cells death. This article presents a bibliometric analysis of studies on immune cells in IDD in order to clarify the current status and hotspots. We searched the WOSCC, Scopus and PubMed databases from 01/01/2001 to 08/03/2023. We analyzed and visualized the content using software such as Citespace, Vosviewer and the bibliometrix. This study found that the number of annual publications is increasing year on year. The journal study found that Spine had the highest number of articles and citations. The country/regions analysis showed that China had the highest number of publications, the USA had the highest number of citations and total link strength. The institutional analysis found that Shanghai Jiao Tong University and Huazhong University of Science Technology had the highest number of publications, Tokai University had the highest citations, and the University of Bern had the highest total link strength. Sakai D and Risbud MV had the highest number of publications. Sakai D had the highest total link strength, and Risbud MV had the highest number of citations. The results of the keyword analysis suggested that the current research hotspots and future directions continue to be the study of the mechanisms of immune cells in IDD, the therapeutic role of immune cells in IDD and the role of immune cells in tissue engineering for IDD.

Current status and trends in quantitative MRI study of intervertebral disc degeneration: a bibliometric and clinical study analysis.

Background: Quantitative magnetic resonance imaging (MRI) has the function of noninvasive quantitative evaluation, providing unique advantages in intervertebral disc degeneration (IDD) assessment. Although studies exploring the field for domestic and international scholars are increasingly being published, there is a lack of systematic scientific measurement and clinical analysis of the literature in this field. Methods: Articles published from the respective database establishment to September 30, 2022, were obtained from the Web of Science core collection (WOSCC), PubMed database, and ClinicalTrials.gov. The scientometric software (VOSviewer 1.6.18, CiteSpace 6.1.R3, Scimago Graphica, and R software) were used for bibliometric and knowledge graph visualization analysis. Results: We included 651 articles from the WOSCC database and 3 clinical studies from ClinicalTrials.gov for literature analysis. With the passage of time, the number of articles in this field gradually increased. The United States and China were the top 2 countries in terms of the number of publications and citations, and Chinese publications lacked international cooperation and exchange. The author with the most publications was Schleich C, while the author with the most citations was Borthakur A, who have both made important contributions to research in this field. The journal publishing the most relevant articles was Spine, and the journal with the most mean times cited per study was Radiology, both of which are the authoritative journals in this field. Keyword co-occurrence, clustering, timeline view, and emergent analysis revealed that recent studies in this field have focused on quantifying the biochemical components of the degenerated intervertebral disc (IVD). There were few available clinical studies. The more recent clinical studies mainly used molecular imaging technology to explore the relationship between different quantitative MRI sequence values and the IVD biomechanical environment and biochemical components content. Conclusions: The study provided a knowledge map of quantitative MRI for IDD research in terms of countries, authors, journals, cited literature, and keywords through bibliometric analysis, and systematically sorted the current status, hotspots, and clinical research features in the field to provide a reference for future research.

Research hotspots and trends of microRNAs in intervertebral disc degeneration: a comprehensive bibliometric analysis.

BACKGROUND: MicroRNAs (miRNAs) are involved in various pathological processes, such as proliferation, growth, and apoptosis, of intervertebral disc (IVD) cells and play an important role in the development of intervertebral disc degeneration (IDD). Although some studies have reported the role of miRNAs in IDD, scientific econometric analysis in this field is not available. OBJECTIVES: We designed this study to describe the current research trends and potential mechanisms associated with the role of miRNAs in IDD and to provide new ideas for future research in this field. METHODS: We conducted a bibliometric analysis of the publications on the role of miRNAs in IDD included in the Web of Science core collection database to elucidate the current research trends in this field. The potential mechanisms were constructed using the Arrowsmith project. RESULTS: We found that the number of miRNAs and IDD-related publications increased over the years. China was the most important contributor to research in this field. The top three institutions in terms of number of articles published were Huazhong University of Science and Technology, Shanghai Jiao Tong University, and Xi'an Jiao Tong University. Shanghai Jiao Tong University had the highest number of citations. Experimental and thermal medicine had the maximum number of documents, and Cell promotion had the most citations. The journal with the most mean times cited per study was Annals of the Rheumatic Diseases. The author Wang K had the highest number of publications, and Wang HQ had the highest number of citations. These two authors made important contributions to the research in this field. The keyword analysis showed that recent studies have focused on miRNAs regulating nucleus pulposus cell apoptosis and proliferation. Moreover, we revealed the potential mechanisms of miRNAs associated with IDD, including miRNAs regulating the extracellular matrix (ECM) degradation, mediating cartilage endplate (CEP) degeneration, and participating in inflammatory responses. CONCLUSION: We demonstrated the knowledge map of miRNAs and IDD-related research through bibliometric analysis and elucidated the current research status and hotspots in this field. The mechanisms by which miRNAs regulate the apoptosis and proliferation of degenerated IVDs, promote ECM degradation, mediate CEP degeneration, and participate in inflammatory responses should be explored in further studies.

Comprehensive analysis of potential ceRNA network and immune cell infiltration in intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) has become a serious public health problem, the mechanism of which is complex and still unclear. We aimed to construct a ceRNA network related to IDD to explore its pathogenesis. METHODS: We downloaded the GSE67566, GSE63492, GSE116726 and GSE124272 datasets from GEO database, and obtained the differentially expressed RNAs. Then, we constructed a ceRNA network and the KEGG and GO enrichment analysis were performed. Finally, we performed immune cell infiltration analysis on the GSE124272 dataset and analysed the correlation between immune cell abundance and hub genes expression levels. RESULTS: The ceRNA network included three down-regulated circRNAs: hsa_circ_0074817, hsa_circ_0002702, hsa_circ_0003600, three up-regulated miRNAs: hsa-miR-4741, hsa-miR-3158-5p, hsa-miR-508-5p, and 57 down-regulated mRNAs, including six hub genes: IGF1, CHEK1, CCNB1, OIP5, BIRC5, AR. GO and KEGG analysis revealed that the network is involved in various biological functions. Immune infiltration analysis showed that IDD was closely related to immune cell infiltration, and hub genes could further affect the development of IDD by affecting immune cell infiltration. CONCLUSION: This study identified the hsa_circ_0074817-hsa-miR-508-5p-IGF1/CHEK1/CCNB1, the hsa_circ_0003600-hsa-miR-4741-BIRC5/OIP5/AR and the hsa_circ_0002702-hsa-miR-3158-5p-IGF1/AR as important regulatory axis of IDD, which will help us gain further insight into the pathogenesis of IDD and determine potential therapeutic targets.

Global research status and hot trends in stem cells therapy for Intervertebral disc degeneration: A bibliometric and clinical study analysis.

Background: Stem cells (SCs) therapy for intervertebral disc degeneration (IDD) has been studied for nearly 20 years and it is an important part of regenerative medicine and tissue engineering research, as well as a current research hotspot and challenge. Although the volume of literature has shown an annual growth trend, there is no literature available for bibliometric and clinical analysis of the content of multiple databases in this field. Methods: The articles were obtained from the WOSCC, Scopus, Pubmed, and ClinicalTrials on 27 December 2021. Three scientometric software (VOSviewer 1.6.17, CiteSpace 5.8.R.1 and Scimago Graphica) were used to perform bibliometric and knowledge-map analysis. Results: We included 867 articles from WOSCC, 716 articles from Scopus and 6 clinical studies from ClinicalTrials for literature analysis. Our results showed that China was the country with the highest number of publications, with the United States (US) being the leader in terms of international collaborations and the number of citations. Sakai D, Grad S and Hoyland JA had made outstanding contributions for their high productivity and the quality articles. Spine was the most published and most cited journal, in addition to Spine Journal and Biomaterials, which were also more authoritative journals and had received high citations. All of them had received high citations. Keyword co-occurrence studies suggested that the current hotspots were in mechanistic studies, including inflammation, apoptosis, exosome, autophagy, and others. Some studies had also investigated tissue-engineered scaffolds of SCs to better repair degenerated discs. Clinical studies were relatively scarce. Direct injection of Mesenchymal Stem Cells (MSCs) into degenerated discs for the treatment of Degenerative disc disease (DDD) was the current direction of research. Conclusion: This study demonstrates the global research hotspots, trends and clinical use of SCs in the treatment of IDD. It can help scholars to quickly understand the current status and hotspots of research in this field, and also provide some guidance and reference for those who are currently researching in this area.

Identification of SMIM1 and SEZ6L2 as Potential Biomarkers for Genes Associated with Intervertebral Disc Degeneration in Pyroptosis.

Background: Inflammatory reactions and pyroptosis play an important role in the pathology of intervertebral disc degeneration (IDD). The aim of the present study was to investigate pyroptosis in the nucleus pulposus cells (NPCs) of inflammatory induced IDD by bioinformatic methods and to search for possible diagnostic biomarkers. Methods: Gene expression profiles related to IDD were downloaded from the GEO database to identify differentially expressed genes (DEGs) between inflammation-induced IDD and non-inflammatory intervention samples. Pyroptosis genes were then searched for, and their expression in IDD was analyzed. Weighted gene co-expression network analysis (WGCNA) was then used to search for modules of IDD genes associated with pyroptosis and intersected with DEGs to discover candidate genes that would be diagnostically valuable. A LASSO model was developed to screen for genes that met the requirements, and ROC curves were created to clarify the diagnostic value of the genetic markers. Ultimately, the screened genes were further validated, and their diagnostic value assessed by selecting gene sets from the GEO database. RT-PCR was used to assess the mRNA expression of diagnostic markers in the nucleus pulposus (NP). Pan-cancer analysis was applied to demonstrate the expression and prognostic value of the screened genes in various tumors. Results: A total of 733 DEGs were identified in GSE41883 and GSE27494, which were mainly enriched in transmembrane receptor protein serine/threonine, kinase signaling pathway, response to lipopolysaccharide, and other biological processes, and they were mainly related to TGF beta signaling pathway, toll-like receptor signaling pathway, and TNF signaling pathway. A total of 81 genes related to pyroptosis were identified in the literature, and eight genes related to IDD were identified in the Veen diagram, namely, IL1A, IL1B, NOD2, GBP1, IL6, AK1, EEF2K, and PYCARD. Eleven candidate genes were obtained after locating the intersection of pyroptosis-related module genes and DEGs according to WGCNA analysis. A total of six valid genes were obtained after constructing a machine learning model, and five key genes were finally identified after correlation analysis. GSE23132 and GSE56081 validated the candidate genes, and the final IDD-related diagnostic markers were obtained as SMIM1 and SEZ6L2. RT-PCR results indicated that the mRNA expression of both was significantly elevated in IDD. The pan-cancer analysis demonstrated that SMIM1 and SEZ6L2 have important roles in the expression and prognosis of various tumors. Conclusion: In conclusion, this research identifies SMIM1 and SEZ6L2 as important biomarkers of IDD associated with pyroptosis, which will help to unravel the development and pathogenesis of IDD and determine potential therapeutic targets.

Disc measurement and nucleus calibration in a smoothened lumbar model increases the accuracy and efficiency of in-silico study.

BACKGROUNDS: Finite element analysis (FEA) is an important tool during the spinal biomechanical study. Irregular surfaces in FEA models directly reconstructed based on imaging data may increase the computational burden and decrease the computational credibility. Definitions of the relative nucleus position and its cross-sectional area ratio do not conform to a uniform standard in FEA. METHODS: To increase the accuracy and efficiency of FEA, nucleus position and cross-sectional area ratio were measured from imaging data. A FEA model with smoothened surfaces was constructed using measured values. Nucleus position was calibrated by estimating the differences in the range of motion (RoM) between the FEA model and that of an in-vitro study. Then, the differences were re-estimated by comparing the RoM, the intradiscal pressure, the facet contact force, and the disc compression to validate the measured and calibrated indicators. The computational time in different models was also recorded to evaluate the efficiency. RESULTS: Computational results indicated that 99% of accuracy was attained when measured and calibrated indicators were set in the FEA model, with a model validation of greater than 90% attained under almost all of the loading conditions. Computational time decreased by around 70% in the fitted model with smoothened surfaces compared with that of the reconstructed model. CONCLUSIONS: The computational accuracy and efficiency of in-silico study can be improved in the lumbar FEA model constructed using smoothened surfaces with measured and calibrated relative nucleus position and its cross-sectional area ratio.

Corrigendum: Dislocation Strengthening without Ductility Trade-off in Metastable Austenitic Steels.

This corrects the article DOI: 10.1038/srep35345.

Dislocation Strengthening without Ductility Trade-off in Metastable Austenitic Steels.

Strength and ductility are mutually exclusive if they are manifested as consequence of the coupling between strengthening and toughening mechanisms. One notable example is dislocation strengthening in metals, which invariably leads to reduced ductility. However, this trend is averted in metastable austenitic steels. A one-step thermal mechanical treatment (TMT), i.e. hot rolling, can effectively enhance the yielding strength of the metastable austenitic steel from 322 ± 18 MPa to 675 ± 15 MPa, while retaining both the formability and hardenability. It is noted that no boundaries are introduced in the optimized TMT process and all strengthening effect originates from dislocations with inherited thermal stability. The success of this method relies on the decoupled strengthening and toughening mechanisms in metastable austenitic steels, in which yield strength is controlled by initial dislocation density while ductility is retained by the capability to nucleate new dislocations to carry plastic deformation. Especially, the simplicity in processing enables scaling and industrial applications to meet the challenging requirements of emissions reduction. On the other hand, the complexity in the underlying mechanism of dislocation strengthening in this case may shed light on a different route of material strengthening by stimulating dislocation activities, rather than impeding motion of dislocations.

[The historical condition in the spread of Sanqi (Panax notoginseng) in the Ming Dynasty].

A well-known and extensively applied Chinese herbs for promoting blood circulation and resolving blood stasis, San qi (Pana Notoginseng) is one of the medicinal plants first applied by the minority ethnic groups in southwestern China originally grown in Wenshan of Yunnan and Baise of Guangxi, China. The doctors in inland China began to know and apply it in the Ming Dynasty, indicating that the spread of medicine is restricted and influenced not only by geographical positions but also by social environments. The author suggests that it was the appropriate social environment, medical improvement inherited from previous generations and Li Shizhen's contributions that led to the spread of Sanqi (Panax notoginseng) in the Ming Dynasty.