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Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics

  • Hanqi Liu , Yanqing Huang , Shanshan Lu , Didi Yuan and Junwen Liu EMAIL logo
Published/Copyright: March 23, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

N6-methyladenosine (m6A) is a representative of RNA methylation modification, which plays a critical role in the epigenetic modification process of regulating human diseases. As a key protein for m6A, methyltransferase 3 (METTL3) had been identified to be associated with a variety of diseases. The publications related to METTL3 were searched in the Web of Science Core Collection from the earliest mention to July 1st, 2022. Being screened by the retrieval strategy, a total of 1,738 articles related to METTL3 were retrieved. Much of our work focused on collecting the data of annual publication outputs, high-yielding countries/regions/authors, keywords, citations, and journals frequently published for qualitative and quantitative analysis. We found that diseases with high correlations to METTL3 not only included various known cancers but also obesity and atherosclerosis. In addition to m6A-related enzyme molecules, the most frequent key molecules were MYC proto-oncogene (C-MYC), Enhancer of zeste homolog 2 (EZH2), and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN). METTL3 and methyltransferase 14 (METTL14) may function through opposite regulatory pathways in the same disease. “Leukemia,” “Liver Cancer,” and “Glioblastoma” were speculated to be potential hotspots in METTL3 related study. The number of publications had significantly surged year by year, demonstrating the growing importance of the research on epigenetic modification in the pathology of various diseases.

Keywords: METTL3; publications; bibliometrics; RNA methylation; epigenetics

1 Introduction

As an emblematic type of RNA methylation, N6-methyladenosine (m6A) had been found to function by changing RNA structure or recruiting specific m6A binding proteins [1]. In 1994, Bokar et al. first purified a protein complex which can catalyze the formation of m6A, then scientists referred to the enzymes as m6A “writer” proteins [2]. Subsequently, the methylase system was gradually revealed, which consists of writers (catalyzation), erasers (removal), and readers (recognition). Summary of the m6A methylation modification mechanism is shown in Figure 1. These proteins regulate the methylation level of RNA in cells [3], and then affect the process of RNA nuclear export, degradation and translation. Writers perform indispensable functions in regulating the fate of mRNA in the first stage of methylation modification. Methyltransferase 3-methyltransferase 14 (METTL3-METTL14) is a vital heterodimer of multicomponent m6A methyltransferase complex (MTC), in which METTL3 constitutes the catalytic core [4].

Figure 1 m6A methylation modification mechanism. Note: Writers, erasers, and readers are represented in different colors (green, blue, and purple, respectively). The structure of the membrane represented the nuclear membrane. For readers, the solid arrows indicate that the proteins directly interact with the substrate m6A-mRNA, and the dashed one indicate that the proteins did not directly bind to the m6A site, but mediate methylation modification by recognizing and binding to m6A-dependent structures.
Figure 1

m6A methylation modification mechanism. Note: Writers, erasers, and readers are represented in different colors (green, blue, and purple, respectively). The structure of the membrane represented the nuclear membrane. For readers, the solid arrows indicate that the proteins directly interact with the substrate m6A-mRNA, and the dashed one indicate that the proteins did not directly bind to the m6A site, but mediate methylation modification by recognizing and binding to m6A-dependent structures.

METTL3 encodes the 70 kDa subunit of N6-adenosine-methyltransferase. In eukaryotic mRNAs, METTL3 plays a regulatory role through forming m6A to adjust the post-transcriptional methylation level of internal adenosine residues. Its related pathways include chromatin regulation/acetylation and processing of capped intron-containing pre-mRNA [2]. Existing studies show diseases associated with METTL3 mainly involved in oncology [5,6].

Bibliometric analysis is broadly used to visually calculate the academic impact of achievements in various disciplines [7]. Although it has several methodological limitations, it is still an effective tool for the assessment of scientific relevance in a specific field. It usually obtains and processes quantitative data from existing publications and then assesses the current research performance. Bibliometric analysis of publications can help to understand the research progress of METTL3, summarize and evaluate the current existing research results, as well as inspire researchers to explore more consequential treatment in the direction of epigenetics [8,9].

Although there had already been many publications on basic research in METTL3, we found that the bibliometric studies on METTL3 lack an overall and global analysis of the research progress and a systematic description. We tried to search for “METTL3 OR methyltransferase-like protein 3 OR methyltransferase like 3 protein” and “Bibliometric OR Bibliometrics” in the Web of Science Core Collection (WoSCC), but no relevant literature was retrieved. In view of the limitations of retrieval [10], there may exist some bibliometric publications on METTL3 not utilizing the words like “bibliometric(s)” in titles or abstracts, leading to their not being retrieved, but our research results still demonstrated that there were only few bibliometric studies on METTL3.

In this study, we had conducted our analysis on annual publication outputs, output contributors, journals, keywords, and citations to better assist researchers in selecting appropriate collaborators and research directions. The hotspots and frontiers of METTL3 were then mapped using VOSviewer, CiteSpace, and a bibliometric website. In this way, we expect our analysis to reveal the research pattern, highlight trending topics, and provide new inspiration for epigenetic researchers.

2 Materials and methods

2.1 Data source and search strategy

Relevant subject terms for METTL3 were first searched at NCBI (https://www.ncbi.nlm.nih.gov/mesh) to minimize misses. Then, literature retrieval was performed online through the WoSCC (https://www.webofscience.com) on July 1st, 2022. To avoid possible bias on account of daily database updation, we performed all searches within the same day. The research terms were as follows: TS = (METTL3 OR methyl-transferase-like protein 3 OR methyltransferase like 3 protein) refined by WEB OF SCIENCE INDEX (Web of Science Core Collection. SCI) AND DOCUMENT TYPES (ARTICLE OR REVIEW) AND LANGUAGES (ENGLISH), and the timespan was 1999–2022. The involved publications included the “early access.” We then utilized CiteSpace to remove duplicate literature from the retrieved results. The screening and analyzing process is illustrated in Figure 2.

Figure 2 Flow diagram of search strategy in the screening of publications.
Figure 2

Flow diagram of search strategy in the screening of publications.

2.2 Data collection

Raw data from the WoSCC were initially downloaded and verified. Then, the data were imported into Microsoft Excel, Bibliometric online analysis platform (https://bibliometric.com), VOSviewer (Version 1.6.18; https://www.vosviewer.com), and CiteSpace VI (Version 6.1.R2; https://CiteSpace.podia.com) and systematically analyzed.

2.3 Statistical methods

We performed analysis on publications included by publication years, countries, institutions, authors, journals, keywords, and citations, and tried to abstract their characteristics to get descriptive results. The figure of mechanism was created with BioRender.com. (www.biorender.com) CiteSpace VI was then utilized for constructing a correlation map in countries’ cooperation, and VOSviewer software for network visualizations in some cases such as institutions, co-authors, keywords, and citations. Besides, CiteSpace VI was also used to apply burst detection to investigate research directions and institutions with great research potential.

3 Results

3.1 Annual publication outputs

We counted the number of publications each year in the core journals of WoS. Overall, a total of 1,738 literature were included in our analysis. The number of publications in each year are shown in Table 1. Here the results illustrated that the number of publications from 1999 to 2011 was less than 30. However, since 2012, the publications began to surge, showing a sharp upward trend. To account for the law of publication trend, as shown in Figure 3a, exponential and polynomial fitting were both performed with the acquired data of annual outputs in the recent 10 years (2012–2021). The fitting equation of the exponential curve was y = 2 × 10−237e0.2724 x (with a correlation coefficient of 0.9132), and the polynomial curve fitting equation was y = 1.6078x 3 − 9716.8x 2 + 2 × 1007 x − 1 × 1010 (with a correlation coefficient of 0.9972).

Table 1

Number of publications in each year

Year Documents Year Documents Year Documents Year Documents
1999 10 2005 16 2011 21 2017 69
2000 8 2006 21 2012 39 2018 90
2001 7 2007 27 2013 41 2019 158
2002 12 2008 18 2014 41 2020 288
2003 16 2009 21 2015 44 2021 455
2004 16 2010 30 2016 51 2022* 239

*Result statistics as of July 1st, 2022.

Figure 3 (a) Annual publication outputs of publications on METTL3. Note: The number of publications quickly surge year by year from 2012 to 2021, and since 2019, publications had an explosion of growth. Polynomial adjustment (a): y = 1.6078x 3 − 9716.8x 2 + 2 × 107 x − 1 × 1010, R 2 = 0.9972. Exponential adjustment (b): y = 2 × 10−237e0.2724 x, R 2 = 0.9132). (b) The proportion of articles published by countries each year from 1999 to 2021. Note: Different colors represent publications number of different countries.
Figure 3

(a) Annual publication outputs of publications on METTL3. Note: The number of publications quickly surge year by year from 2012 to 2021, and since 2019, publications had an explosion of growth. Polynomial adjustment (a): y = 1.6078x 3 − 9716.8x 2 + 2 × 107 x − 1 × 1010, R 2 = 0.9972. Exponential adjustment (b): y = 2 × 10−237e0.2724 x, R 2 = 0.9132). (b) The proportion of articles published by countries each year from 1999 to 2021. Note: Different colors represent publications number of different countries.

It could be observed that since 2019, the number of METTL3 publications had an explosion of growth, and the number of literature in 2020 was nearly twice that in 2019. Polynomial curve fitting was more consistent with METTL3 publication trend. By July 1st, 2022, the number of literature had reached 239 in 2022. Given that the publications were consistent with the results of polynomial fitting, total number of publications in 2022 was expected to reach 675 and 980 in 2023. In aggregate, the publication number had increased rapidly in the past 10 years, which suggested METTL3 had become a research hotspot year by year, showing self-evident importance.

The top 10 countries by the number of publications each year are shown in Figure 3b in different colors, which presents the evidence that China and USA contributed the most to the total publications. From 2011, China began to emerge, and the number of publications showed a steady upward trend. After 2019, publications number in China steadily accounted for more than half of the total number. The rapid growth of publications in China was the main reason for the noticeable increase in the total number of literature, which indicated that compared with other countries all over the world, China may have a larger population base for scientific research in this field. According to the bar chart, USA had begun to study on METTL3 since 1999, and the number of publications in the past 2 years had also increased.

3.2 Countries and regions

The 1,738 publications on WoSCC were contributed by 58 countries/regions. The top 10 countries by citation counts are shown in Table 2. Our major evaluation indicators were citation counts, centrality, total link strength, bursts, and sigma. Sigma is constructed by combining centrality with bursts, which represents the nodes’ novelty. The top ranked item by citation counts were China (n = 1,023, 46.8%), pursued by USA (n = 424, 19.4%), and Germany (n = 88, 4.0%). Extensive collaboration between countries/regions are shown in Figure 4a. The purple circles around nodes represent centrality indicating the pivotal role in cooperative relationships among countries/regions. Node with high mediating centrality is often a key hub connecting two different domains. The country with the highest centrality is Spain (0.44), followed by Japan (0.43) and Italy (0.42). Citation counts of China was almost half the number; however, its centrality was very low. While only a few documents were published by Spain and Italy, the two countries were still important hubs in the network of study on METTL3.

Table 2

Top 10 countries by citation counts

RANK Country Occurrence Centrality Burst Sigma
1 China 1,023 0 0 1
2 USA 424 0.26 8.08 6.61
3 Germany 88 0.21 7.22 4.06
4 Japan 79 0.43 11.85 70.35
5 England 53 0.18 4.27 2.02
6 Canada 46 0.14 7.21 2.62
7 France 37 0.28 4.46 2.98
8 Italy 36 0.42 0 1
9 India 35 0.11 0 1
10 Spain 29 0.44 4.14 4.53
Figure 4 (a) Analysis of cooperation among the top 10 countries/regions with the highest documents. Note: The size of each node presents its number of documents, and the proportion of the outermost ring means its centrality. Central red circles illustrate nodes’ temporal importance. (b) Top ten countries/regions with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.
Figure 4

(a) Analysis of cooperation among the top 10 countries/regions with the highest documents. Note: The size of each node presents its number of documents, and the proportion of the outermost ring means its centrality. Central red circles illustrate nodes’ temporal importance. (b) Top ten countries/regions with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.

We also analyzed the bursts of each country’s publications, which showed in the form of central red circles in Figure 4a. Bursts indicate the temporal importance of nodes. Detailed information of top 10 countries with strongest citation bursts are shown in Figure 4b. Japan (11.85), USA (8.08), and Germany (7.22) are in the top three. Among them, Japan had the largest burst length, which lasted from 1999 to 2016, and was in the first group of countries that began study on METTL3. Thus, combined with the above data, Japan indeed had strong centrality in the publications network. Remarkably, the shortest burst length that lasted for only 3 years from 2014 to 2017 belongs to USA, but its publications were the second prolific, which elucidated that METTL3 related research in USA was rapid and concentrated.

3.3 Institutions

Over 1,703 institutions had contributed to the publications on WoSCC. The institutions, documents, citations, and centrality are shown in Table 3. In relation to institutions with the highest number of publications, Sun Yat-Sen University (93), Zhejiang University (74), and Chinese Academy of Sciences (69) are in the top three. Among them, document citations of Chinese Academy of Sciences far exceeded other institutions, reaching 6,588. The top 10 institutions with publications number are distributed in China (n = 9) and USA (n = 1). Although the publications were only 38, the University of Chicago’s citations were far higher than any other institution, with 7,195.

Table 3

Institutions ranked by documents

Rank Institutions Country Documents Citations Centrality
1 Sun Yat-Sen University China 93 2,987 0.03
2 Zhejiang University China 74 4,962 0.04
3 Chinese Academy of Sciences China 69 6,588 0.12
4 Nanjing Medical University China 63 2,507 0.03
5 Shanghai Jiao Tong University China 60 2,027 0.02
6 Central South University China 45 777 0.01
7 University of Chinese Academy of Sciences China 45 3,896 0.05
8 Fudan University China 40 1,887 0.03
9 The University of Chicago USA 38 7,195 0.07
10 Zhengzhou University China 35 908 0.02

We then utilized VOSviewer to construct a relationship network between institutions, which reflect the cooperative relationships between organizations. The institutions are classified into three groups in Figure 5a, represented by three colors (red, blue, and green). Node size indicates the number of articles published by institutions. Lines between nodes represent the cooperative relationships among organizations, and the line thickness showed the link strength between two nodes and evaluated the degree of cooperation among organizations. Chinese Academy of Sciences had the highest centrality (0.12), and it can also be observed in Figure 5a that it played a pivotal role in the central position. Comparing the centrality of countries in Table 2 with that of institutions in Table 3, it showed that the centrality of country is generally higher, which indicated that cooperation between institutions was less.

Figure 5 (a) Visualization graphs of correlation between institutions. Note: The main institutions were classified into three clusters, presented by three colors (red, blue, and green). Node size indicates number of publications by institutions. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength. (b) Top five institutions with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.
Figure 5

(a) Visualization graphs of correlation between institutions. Note: The main institutions were classified into three clusters, presented by three colors (red, blue, and green). Node size indicates number of publications by institutions. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength. (b) Top five institutions with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.

Top five institutions with strongest citation bursts are shown in Figure 5b, among which Central South University has shown high enthusiasm in the research during the past 2 years (2020–2022). The outbreak of Harvard University lasted for 13 years (2002–2015), indicating that in the early stage of METTL3 research, Harvard University showed a strong research interest and may have had a deep foundation now.

3.4 Co-author

More than 10,999 authors contributed to the writing of 7,038 documents. Taking 5 as the minimum number of the documents of an author, 104 authors meet the threshold. A total of 91 authors were used to construct the author correlation network, excluding authors who were not directly related to other authors. The correlation diagram in Figure 6a consists of 91 items, 262 links, and 4 clusters (red, blue, green, and yellow), and there were 2 main cooperative groups. The core of blue group was He Chuan’s team, which also served as the core in the whole research network and linked main cooperative groups. The cores in red were Yang Ying’s team and Lin Shuibin’s team. Remarkably, there was no direct connection between the two teams, which shed light on that the two teams may have studied relatively independent important topics. Yang Ying’s team mainly focused on the methyltransferase centered with METTL3. Among their research results, “Mammalian WT1 Associated Protein (WTAP) is a regulatory subunit of the RNA m6A methyltransferase [11]” has been cited up to 1,285 times, which illustrated that the RNA-binding capacity of METTL3 is strongly reduced in the absence of WTAP, revealing key factors that may influence METTL3 function. However, Lin Shuibin’s team concentrated more on how METTL3-mediated m6A RNA methylation regulates bone marrow mesenchymal stem cells’ fate and osteoporosis directions [12]. Further exploration on these topics may have potential research prospects. As to the time network diagram in Figure 6b, we found essential publications mainly concentrated in 2019. Plenty of autonomous groups had started to emerge in the last 2 years, indicating that more investigators were joining the METTL3 research cohort.

Figure 6 Visualization graphs of co-authorship analysis of authors. (a) Network visualization of authors involved in studies on METTL3. Note: Total number authors were classified into four clusters with different colors (red, blue, green, and yellow) to show different major cooperative groups. Node size indicates publications number. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength. (b) Overlay visualization of authors involved in studies on METTL3. Note: Different colors showed different period of publications for each node.
Figure 6

Visualization graphs of co-authorship analysis of authors. (a) Network visualization of authors involved in studies on METTL3. Note: Total number authors were classified into four clusters with different colors (red, blue, green, and yellow) to show different major cooperative groups. Node size indicates publications number. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength. (b) Overlay visualization of authors involved in studies on METTL3. Note: Different colors showed different period of publications for each node.

Then, we further analyzed the detailed information of the top ten authors by citations. The main authors and their affiliations, Hirsch index (H-index), documents, citations, and total link strength are shown in Table 4. Among these indices, H-index helps to understand the importance and impact of a researcher’s cumulative research contribution. Total link strength indicates how many links are connected to that node (including the number of repetitions), demonstrating the level of correlation between researchers of that node and other. According to affiliations, most of the authors belong to China (n = 7), and the rest were from USA (n = 1) and Norway (n = 1). Among these authors, He Chuan (116), Liu Jianzhao (54), and Yang Yungui [39] had the top three H-index, playing important roles in the network, and this result was also consistent with data of total link strength.

Table 4

Pivotal authors of documents

RANK Author Affiliation Country H-index Documents Citations Total link strength
1 He, Chuan University of Chicago USA 116 25 4,700 44
2 Lu, Zhike Westlake University China 47 7 3,294 18
3 Liu, Jianzhao Zhejiang University China 54 10 2,904 36
4 Yang, Ying Wuhan University China 16 20 2,675 43
5 Yue, Yanan Zhejiang University China 16 5 2,235 19
6 Yang, Yungui China Natl Ctr Bioinformation China 39 13 2,202 36
7 Wang, Yang Hospital of Harbin Medical University China 20 6 1,823 7
8 Wang, Xiao Nankai University China 8 8 1,786 7
9 Lin, Shuibin Sun Yat-Sen University China 22 12 1,637 20
10 Zhao, Xu National Hospital Norway Norway 7 5 1,506 15

3.5 Journals

METTL3 related publications had been published in 617 journals from 1999 to 2022 (by July 1st). Information of the top ten journals by number of publications are listed in Table 5. Impact factor (IF) was utilized to evaluate the significance of a journal (https://clarivate.com/webofsciencegroup/essays/impact-factor/). According to the Journal Citation Reports (JCR) 2021 standards, IF of journals in Table 5 range from 3.75 to 69.50, with an average of 18.39. Among the top ten journals, Nature had the highest IF of 66.85 in 2021, followed by Molecular Cancer (41.44) and Nucleic Acids Research (19.16), which showed more authority in this field and indicated that METTL3 had high research value and prospects. The top three journals in which the articles were published were Journal of Biological Chemistry (40, 2.30%), Frontiers in Cell and Developmental Biology (40, 2.30%), and Frontiers in Oncology (35, 2.01%), respectively. As such, it was more likely to find the valuable references we need in these mentioned journals.

Table 5

Top ten journals with the largest number of documents

Rank Journal 2021 IF Count % of 1,738
1 Journal of Biological Chemistry 5.49 40 2.30
2 Frontiers in Cell and Developmental Biology 6.08 40 2.30
3 Frontiers in Oncology 5.74 35 2.01
4 Nucleic Acids Research 19.16 27 1.55
5 Cell Death & Disease 9.71 26 1.50
6 Molecular Cancer 41.44 25 1.44
7 Nature Communications 17.69 24 1.38
8 Nature 69.50 22 1.27
9 Journal of Cellular and Molecular Medicine 5.30 22 1.27
10 PLOS ONE 3.75 22 1.27

3.6 Keywords

To present the knowledge map of keywords for METTL3 research, a total of 7,089 keywords were extracted from titles and abstracts. Taking 10 as the minimum number of occurrences of a keyword, of the 7,089 keywords, 237 met the threshold. VOSviewer was utilized to construct a relationship network between keywords, which can reflect hot topics visually and show how research hotspots change over time. Theme words were classified into three clusters, as shown in Figure 7a represented by three colors (red, blue, and green). Depending on the keywords network was clustered by years, as shown in Figure 7b, the research focus had gradually shifted from cell-level research like “Stem cell” to disease research such as “fat mass” and “cancer” over time. Table 6 shows the top ten diseases, key molecules, and states among the filtered keywords, which indicated mainstream topics and frontiers in METTL3 related research.

Figure 7 Visualization graphs of keywords. (a) Network visualization of keywords in METTL3. Note: Total number of authors were classified into 3 clusters with different colors (red, blue, and green) to show different research theme. Node size shows the frequency of keywords. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength). (b) Overlay visualization of keywords in METTL3. Note: Different colors showed different periods of publications for each node.
Figure 7

Visualization graphs of keywords. (a) Network visualization of keywords in METTL3. Note: Total number of authors were classified into 3 clusters with different colors (red, blue, and green) to show different research theme. Node size shows the frequency of keywords. Lines between nodes showed cooperative relationships among organizations, and thicker lines between two nodes indicate stronger link strength). (b) Overlay visualization of keywords in METTL3. Note: Different colors showed different periods of publications for each node.

Table 6

Top ten diseases, key molecules, and states in studies on METTL3

Rank Disease Occurrence Molecule Occurrence State Occurrence
1 Hepatocellular carcinoma 90 FTO 72 Proliferation 154
2 Breast cancer 85 ALKBH5 69 Differentiation 107
3 Colorectal cancer 57 METTL14 35 Progression 90
4 Leukemia 38 C-MYC 21 Apoptosis 81
5 Prostate cancer 25 WTAP 21 Metastasis 63
6 Glioblastoma 22 Histone H3 19 EMT 45
7 Obesity 22 EZH2 17 Invasion 39
8 Gastric cancer 19 YTHDF1 15 Inflammation 34
9 Lung cancer 18 YTHDF2 15 Tumorigenesis 33
10 Atherosclerosis 14 PTEN 10 Autophagy 30

It can be found that the METTL3 related studies were mainly concentrated in cancer. The top three diseases were “Hepatocellular Carcinoma,” “Breast Cancer,” and “Colorectal Cancer.” Therefore, we could put more effort on in-depth research of these areas. The molecules most closely related to METTL3 were “Fat Mass and Obesity Associated (FTO),” “AlkB Homolog 5 (ALKBH5),” and “METTL14.” Similarly, the top three states were “Proliferation,” “Differentiation,” and “Progression.”

CiteSpace was utilized to detect burst keywords, which represented words that had been cited frequently over a period and indicated research frontier topics. By analyzing extracted keywords, we found 37 entries that suggested outbreak trends, as shown in Figure 8. Among them, DNA methylation (2008–2016), Histone methylation (histone methyltransferase) (2011–2018), and m6A (2018–2019) articulated that study on METTL3 shifted from DNA to histones, and the current research focus is m6A methylation on RNA. Arabidopsis Thaliana (2005–2017, 10.33), Histone H3 (2007–2015, 5.01), and FTO (2015–2018, 3.89) appeared to be an increasing trend in corresponding time periods. Research on Embryonic Stem Cells (2004–2019) had lasted for 15 years, and now more attention is devoted to leukemia (2018–2020). In addition, research from 2017 to 2019 suggested that METTL3 may also be involved in sex determination.

Figure 8 Top 37 keywords with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.
Figure 8

Top 37 keywords with the strongest citation bursts. Note: The strongest citation burst means that a variable changes greatly in a short period. Red bars illustrate the duration of the burst.

3.7 Citations

Table 7 shows the details of top ten articles with highest citations including title, journal, first Author, year, citations, and links. Higher the value of link, more nodes are connected with others (excluding the number of duplicates), indicating the correlation between publications. Themes of highly cited literature were mainly concentrated in the fields of stem cells, cancer cells, and germ cells, illustrating MTTTL3 plays a part mainly in the processes of cell division, differentiation, and transcription. Ranked first, “Auxin: Regulation, action, and interaction [13]” was published by Annals of Botany in 2005 and was cited 1,434 times in total. The second and third articles in turn were “A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation [4]” and “Mammalian WTAP is a regulatory subunit of the RNA m6A methyltransferase [11],” both had been published in 2014. Throughout the journals published literature with high citations, “Nature” and “Cell research” appeared more frequently, indicating METTL3-related articles published in these journals were more favored by scholars.

Table 7

Top ten highly cited publications related to METTL3

Rank Title Journal First author Year Citations Links
1 Auxin: Regulation, action, and interaction. Annals of Botany Woodward, AW 2005 1,434 1
2 A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation Nature Chemical Biology Liu, JZ 2014 1,384 186
3 Mammalian WTAP is a regulatory subunit of the RNA N-6-methyladenosine methyltransferase Cell Research Ping, XL 2014 1,026 153
4 Extensive translation of circular RNAs driven by N-6-methyladenosine Cell Research Yang, Y 2017 886 20
5 m(6)A mRNA methylation facilitates resolution of naive pluripotency toward differentiation Science Geula, S 2015 859 135
6 Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L Nature Bourc’his, D 2004 805 8
7 The m(6)A methyltransferase METTL3 promotes translation in human cancer cells Molecular Cell Lin, SB 2016 757 148
8 N-6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells Nature Cell Biology Wang, Y 2014 741 115
9 m(6)A RNA methylation promotes XIST-mediated transcriptional repression Nature Patil, DP 2016 722 78
10 Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites Cell Reports Schwartz, S 2014 660 103

We also constructed temporal and density networks of cited articles with VOSviewer, data on this topic over the past years are shown in Figure 9a. Further, in Figure 9b, each item represents a literature, and the more frequently a literature is cited, the color of the point closer to yellow. On the contrary, the less frequently the literature is cited, the color of the point closer to blue. It can be observed that the article published by Liu et al. in 2014 occupies a central position in the correlation network. In the first half of 2022, their article had been cited more than 1,384 times and it had a high link strength of 186 with other literature, linking the individual publications. The METTL3 research network was heavily influenced by articles that came out around 2014, indicating additional fresh discoveries were urgently needed to strengthen and expand the research network.

Figure 9 Visualization graphs of citations analysis. (a) Overlay visualization of citations involved in studies on METTL3. Note: Different colors show different periods of publications for each node. (b) Further, in Figure 9b, each item represents a literature, and the more frequently a literature is cited, the color of the point closer to yellow. On the contrary, the less frequently the literature is cited, the color of the point closer to blue.
Figure 9

Visualization graphs of citations analysis. (a) Overlay visualization of citations involved in studies on METTL3. Note: Different colors show different periods of publications for each node. (b) Further, in Figure 9b, each item represents a literature, and the more frequently a literature is cited, the color of the point closer to yellow. On the contrary, the less frequently the literature is cited, the color of the point closer to blue.

Co-citation can reveal the potential topics of a research field by analyzing the clusters of highly cited topics. As shown in Table 8, we statistically analyzed title, journal, first author, years, and frequency. The top five co-citations were all cancer-related, including leukemia (n = 2), liver cancer (n = 1), and glioblastoma (n = 1), indicating that these could all be potential topics with research prospects. In the existing research, there are few studies of METTL3 related to the diseases like glioblastoma. The article entitled “m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells [14]” published by Cui et al. in the Cell Reports has been repeatedly cited as a reference by METTL3 related articles, indicating that the research results of this article have played an important role in explaining how METTL3 functions in diseases. The role of METTL3 in glioblastoma could be a new research direction, and it is more likely to find new research results for scientists.

Table 8

Top five highly co-citation of cited references on METTL3

Rank Title Journal First author Year Freq.
1 The m(6)A methyltransferase METTL3 promotes translation in human cancer cells Molecular Cell Lin, SB 2016 316
2 RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2 Hepatology Chen, MN 2018 282
3 The N-6-methyladenosine (m(6)A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells Nature Medicine Vu, LP 2017 254
4 m(6)A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma Stem Cells Cell Reports Cui, Q 2017 229
5 Promoter-bound METTL3 maintains myeloid leukemia by m(6)A-dependent translation control Nature Barbieri, I 2017 213

4 Discussion

Bibliometric analysis is progressively being utilized as an essential tool for analyzing existing publications and assessing the trends in various research fields. m6A methylation modification plays a critical role in the research of epigenetic modification and attracts attention of more and more scientific research communities. As a leading molecule in the study of m6A methylation modification study, METTL3 had been put into great interests and research enthusiasm by lots of scientists. However, to date, there has been no bibliometric analysis of METTL3-related studies. This study used bibliometric methods to comprehensively analyze the current perspectives and trending topics of METTL3 research from 1999 to 2022 (up to July 1st, 2022). Based on inclusion and exclusion criteria, we adjusted the original results of 1,807 METTL3-related papers published in WoSCC, and finally screened 1,738 articles for inclusion in our analysis.

In 2012, methylated RNA immunoprecipitation sequencing (MeRIP-seq), an m6A antibody enrichment technique combined with high-throughput sequencing, first revealed the m6A modification profile in the entire human transcriptome [15]. This reversible eukaryotic post-transcriptional regulation opens up new areas for studying physiological and pathological processes, and also provides a technical tool for scientists’ research [16]. Likewise in this year, the number of METTL3-related publications have steadily increased. According to our fitting analysis of publications in the past 10 years from 2012 to 2021, starting from 2019, publications number had even far exceeded the exponential growth and entered a period of rapid surge. In this case, based on our polynomial fitting results, the total number of publications in 2022 is expected to reach 675 and 980 in 2023. China and USA occupied main position in the number of publications. Publications in each country increased significantly in the last 2 years, illustrating that the research on METTL3 had entered an active phase worldwide. It is well-known that there are many diseases regulated by METTL3, but its detailed molecular mechanism and how to target METTL3 to regulate m6A modification related diseases need more intensive research. The increase in the number of literature indicated that it was more likely to obtain new findings from the existing huge research data to promote the research process.

As to publications output contributors in global landscapes, China had a large number of publications but with a low centrality. On the contrary, even though a few articles had been published by Spain and Italy, the centrality of which were still high. Japan was one of the first group of countries that started to study METTL3, and the research in USA was rapid and centralized. Analyzing from the institutional level, Chinese institutions were firmly in the top of the world in terms of publications number, but the University of Chicago had high citations, which may be largely related to He Chuan’s team affiliated with the University of Chicago. The number of publications and the institutions devoted to research in China were relatively high, but articles published by western countries had a greater impact in this field. In addition, out of 10,999 authors, He Chuan’s team was at the core of the research network, with a high number of publications and H-index, and his team was also a pioneer team in epigenetic research. The paper “A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation [4],” with He Chuan as the corresponding author, proposed that METTL14 and WTAP act together as a complex of METTL3, which was a breakthrough milestone in METTL3-related research and had an important impact in the epigenetic field.

Further, keywords analysis indicated that METTL3 played a significant role in oncology. “Hepatocellular carcinoma” appeared as the most frequent keyword, followed by “Breast cancer” and “Colorectal cancer.” Overexpression of METTL3 was pertinent with tumorigenicity [17]. Research showed that METTL3 substantially overexpressed in HCC patients and has been identified as an adverse prognostic factor [18]. As to hepatocellular carcinoma, Pan et al. explicitly narrated the METTL3-related mechanism in HCC, which revealed the potential research prospects of METTL3. METTL3 targets Suppressor of Cytokine Signaling 2 (SOCS2), RAD52 Motif-containing 1 (RDM1), SNAI1, Hypoxia-Inducible Factor 1α (HIF-1α), LINC00958 and Forkhead box O3 (FOXO3) in HCC, and has a significant impact on the occurrence and development of the disease [19]. Therefore, further exploration on METTL3 combined with the abovementioned downstream target RNA may be an important potential research direction in HCC. In addition, as the most lethal cancer in women worldwide, 2.1 million females globally are presently afflicted by breast cancer, the epigenetic mechanism of which has received more and more attention [20]. The positive feedback loop of HBXIP/let-7g/METTL3/HBXIP was proposed to accelerate proliferation of breast cancer cells and then aggravate the process of HCC [21]. BCL-2 was also the target of METTL3, which regulated breast cancer’s proliferation and apoptosis in a m6A modification pathway [22]. The latest study related to colorectal cancer published in 2023 showed that METTL3 influenced the proliferation, migration, and invasion of colorectal cancer cells through regulating Notch1 and Hsa_circ_0000390 [23]. From our results, “FTO” and “ALKBH5” usually work together with METTL3 to regulate disease progression through epigenetic pathways. Above analysis elucidates the critical role of epigenetic mechanisms in oncology. In the latest literature published in 2023, breast cancer [24] and colorectal cancer [25] accounted for a significant proportion of publications, illustrating that these diseases were still the main research areas where METTL3 plays a regulatory role. By combining the proven upstream and downstream molecules of METTL3 in these diseases, we can further explore the role of METTL3 or directly research on how METTL3 affected the occurrence and development of these diseases through m6A modification pathways, which were both extremely promising research directions.

Apart from tumor-related diseases, “Obesity” and “Atherosclerosis” also appeared frequently in our results, suggesting that METTL3 may influence multiple pathways in other diseases. As a highly conserved single-standard and non-coding small RNAs with a length of 19–24nt, miRNAs play significant roles in development, differentiation, and fat deposition [26]. 67% of 3′-UTR regions containing m6A sites had at least one miRNA binding site [26]. On the one hand, as a major part of methyltransferase, METTL3 regulated the methylation level on mRNAs and affected the binding of miRNAs to target genes. On the other hand, METTL3 promoted the transformation of pri-miRNA into mature miRNA. It can also regulate adipocyte differentiation by directly modifying key genes [27]. The abovementioned ways allowed METTL3 influence adipocyte fate in a variety of ways. Some other studies revealed that METTL3-centered MTC positively controlled adipogenesis by promoting cell cycle transition during adipogenesis [28]. Therefore, it is reasonable to speculate that METTL3 may have a substantial regulatory function in diseases related to lipid metabolism. It is of great significance to explore METTL3’s role in lipid metabolism related diseases such as “obesity” and “atherosclerosis.”

Intriguingly, a recent study conducted a multi-omics analysis of METTL3 and METTL14 in HCC, illustrating that the two enzymes influenced stability or translation efficiency of mRNAs in an m6A dependent manner, then jointly regulate multiple signaling pathways and biological processes [29]. As core components of MTC, METTL3 and METTL14 are crucial in the process of methylation modification. In some other independent studies on the same cancer, METTL3 and METTL14 also have an opposite effect on tumor process [17,30]. We had found that “leukemia” showed an outbreak trend from 2018 to 2020, which is also why the keyword appears frequently, indicating a potential research direction. Martin and Park published “Follow-up with METTLs in Normal and Leukemia Stem Cells” in 2018 [31], which summarized three independent studies that identified METTL3 and METTL14 as vital regulators of differentiation in acute myelocytic leukemia pathogenesis, elucidating the important regulatory role of METTL3 in the pathogenesis of leukemia and further exploration may help to reveal the epigenetic mechanism in the pathogenesis of leukemia. Additionally, simultaneous research on METTL4 may further reveal opposite epigenetic pathways regulating the disease.

In addition to m6A-related enzyme molecules, the most frequent key molecules were C-MYC, EZH2, and PTEN. C-MYC is a kind of immortalized gene, which makes cells to proliferate indefinitely. As a master transcriptional factor, it regulates approximately 10–15% of genes in the genome and has been identified to be closely related to tumorigenesis [32]. METTL3 along with C-MYC regulatory pathways have been verified in oral squamous cell carcinoma [33], lung cancer [34], bladder cancer [35], etc. EZH2 encodes a histone lysine N-methyltransferase. This gene has a strong relationship with DNA methylation, and inhibit transcription of other genes [36]. It had already been verified that it was connected to nasopharyngeal carcinoma [37], breast cancer [38], and lung cancer [39], which were all identified to be regulated by epigenetic pathways via the METTL3-EZH2 pathway. A well-known tumor suppressor gene PTEN can inhibit tumor growth by antagonizing phosphorylases like tyrosine kinase from activating [40]. According to existing studies, diabetic nephropathy [41], diabetic retinopathy [42], ovarian cancer [43], hypoxic pulmonary hypertension [44], prostate enlargement [45], and some other diseases were associated with METTL3-PTEN pathway. Deeper study on these molecules can be more likely to quickly find diseases regulated by METTL3 and reveal their molecular pathways in pathogenesis of the specific disease.

Co-citations analysis present the evidence that “Leukemia,” “Liver Cancer,” and “Glioblastoma” were the major themes in the high frequency co-cited literature. Therefore, we reasonably speculate that research focused on these diseases would become potential hotspots in METTL3 related study. Focusing in these areas might more likely provide some valuable new discoveries. Among these diseases, there are few studies on the direct regulation of METTL3 on the occurrence and development of glioblastoma. The existing studies suggest that METTL3 can promote the development of glioblastoma stem cells in the m6A modification pathway. As mentioned above, the highly cited literature expounded overexpression of METTL3 gene suppresses glioblastoma stem cells growth and self-renewal [14]. Shi et al. recently focused on the role of METTL3 in glioma drug resistance [46]. Tassinari et al. demonstrated that METTL3 upregulation increases ADAR1 mRNA methylation modification and its protein level leading to a pro-tumorigenic [47]. Targeting the promoting effect of METTL3 on glioblastoma or further exploring the influence of downstream molecules such as ADAR1 on the disease perhaps could open up a new field of epigenetics in glioblastoma.

Though we had followed certain bibliographic principles and comprehensive analysis strategies, it is inevitable to lose some articles. During our retrieval, some articles may not have been involved because of not having keywords in their title or abstract. In addition, for the reason that some recently published high-quality articles had not appeared for a long time, the citation frequency cannot accurately evaluate their scientific value. Despite such limitations, given the lengthy publication retrieval timespan and sufficient number of publications, our analysis enables us to build a comprehensive picture of research trends and provide an instructive perspective for METTL3 research. Researchers should also pay more attention to the latest publications and keep up with the frontier research, which is more likely to discover potential significant research directions.

5 Conclusion

Rapid growth trend of publications on METTL3 proves its great research prospects. As far as we were concerned, this article has published the first bibliometric analysis of trends in METTL3 research. Our results show that China, USA and Germany were the top three countries contributing to METTL3 studies. Active cooperation was observed between developed countries. Sun Yat-Sen university was the institution with the largest number of publications, which might be an ideal candidate for academic collaboration. He Chuan, from the University of Chicago, had been influential in METTL3 research. Apart from cancers such as hepatocellular carcinoma, lipid diseases like obesity and atherosclerosis also showed high correlations with METTL3. In addition to m6A-related enzyme molecules, the key molecules with the highest frequency were C-MYC, EZH2, and PTEN, indicating that METTL3 is closely related to these molecules in human body. The abovementioned diseases and molecules were the frontiers of current research. METTL3 and METTL14 may function through opposite regulatory pathways in the same disease. “Leukemia,” “Liver Cancer,” and “Glioblastoma” may be potential research topics, and researchers should follow closely relevant studies to find more new findings in the coming years.

Acknowledgments

We thank Xueying Huang (Department of Histology and Embryology, Xiangya School of Medicine, Central South University) and Zhenyu Huang (Big Data Institute, Central South University) for inspiration and advice.

  1. Funding information: This research was funded by grants from Hunan Province Natural Science Foundation, No. 2022JJ30780 and Hunan Provincial Innovation Foundation for Postgraduate, CX20220360.

  2. Author contributions: H.L. and J.L. contributed to conception and design of the study. H.L. and Y.H. collected and analyzed the experimental data. H.L. and S.L. performed the statistical analysis. H.L. wrote the article. H.L. and D.Y. prepared the figures and tables. J.L. revised the article for intellectual content. J.L. was responsible for fundraising, provided administrative and material support, and supervised the study. The authors applied the SDC approach for the sequence of authors. All authors contributed to manuscript revision and read and approved the submitted version.

  3. Conflict of interest: Authors state no conflicts of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. The datasets analyzed during the current study are available from the Web of Science repository (https://www.webofscience.com).

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Received: 2022-11-25
Revised: 2023-01-26
Accepted: 2023-02-21
Published Online: 2023-03-23

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0586
Keywords for this article
METTL3; publications; bibliometrics; RNA methylation; epigenetics
Creative Commons
BY 4.0

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  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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