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Transient receptor potential (TRP) channels are the vanguard of sensory systems in response to temperature, touch, pain, osmolarity, pheromones, taste, and other stimuli. TRP is expressed at the end of a specific sensory element in the skin.[1,2] After the skin is stimulated by cold and heat, it activates the TRP protein family. TRPV3 is a subtype protein that senses heat, and TRPM8 is a “cold sense” protein.[3] Since it was reported in 2005, TRP has attracted considerable interest, and in light of recent events in the Nobel Prize in Physiology or Medicine, more people have followed TRP. Recent evidence suggests that David Julius exploited cryoelectron microscopy (cryo-EM) to visualize conformational transitions of the capsaicin receptor, TRPV1. It describes the conformational transition of TRPV1 and reveals the ion passage of this capsaicin receptor upon stimulation.[4] Research on TRP involves important diseases in many departments and accounts for the majority of tumor research. In the future, TRP will become a breakthrough for people to overcome various diseases. However, few writers have been able to draw on any systematic research into TRP. This study systematically reviews the data for TRP, and the knowledge was mapped from the extracted bibliographic records using CiteSpace to analyze the TRP research status, aiming to provide research directions in this field and prospects for future research hotspots. This is the first study to undertake a longitudinal analysis of TRP. The reader should bear in mind that the study is based on Bibliometrics Visualization Analysis.
2. MethodsLiterature was extracted from the Web of Science Core Collection, and the search and download process were carried out on October 6, 2021, to eliminate substantial errors caused by daily database updates. The search terms were as follows: TS = (“Transient Receptor Potential” OR “TRP”) and invalid documents were eliminated. The search period ranged from June 5, 2001 to June 5, 2021, resulting in 19,862 records fetched. The retrieved papers were exported and saved as plain text files and stored in download_txt format. Given that the data were directly downloaded from the database, ethical approval was not required, and Microsoft Office Excel 2019 and CiteSpace were used to analyze the articles. Analyze the distribution of countries visually, authors and co-cited authors, co-cited references, keyword cluster analysis, and timelines.
3. Results 3.1. Publication outputsIn total, 19,862 articles were examined in the present study. Figure 1 shows the chronological distribution of the publications from 2000 to 2021. As shown in the diagram, the number of articles steadily increased. The histogram represents the number of articles published per year, and the red dotted line represents the cumulative number of articles published. The were of articles in 2020 has reached 1037. As of the search date, there are already 747 articles in 2021, and it is expected that the number of articles published this year will exceed 1500.
Figure 1.: The number of articles published annually of annual articles related to TRP have been steadily increasing from 2000 to 2021. TRP = transient receptor potential.
3.2. Funding agencyTo a certain extent, funding agencies can reflect the hotspots in this field. The more funding there is, the more important is the research field. As shown in Table 1, the top 10 funding agencies include six in the United States and two in Japan, one from the European Union, and one from China. The top two institutions are from the United States, namely the United States Department of Health Human Services (5260, 26.483%) and National Institutes of Health NIH USA (5243, 26.397%). The third is an institution from China, the National Natural Science Foundation of China NSFC (1482, 7.461%).
Table 1 - Funding agency of relevant papers on TRP published from 1990 to 2021. No. Funding agency Record % of 19,862 1 United States Department of Health Human Services 5260 26.483 2 National Institutes of Health NIH USA 5243 26.397 3 National Natural Science Foundation of China NSFC 1482 7.461 4 European Commission 1398 7.039 5 NIH National Heart Lung Blood Institute NHLBI 1255 6.319 6 NIH National Institute of Neurological Disorders Stroke NINDS 1222 6.152 7 Ministry of Education Culture Sports Science And Technology Japan MEXT 969 4.879 8 NIH National Institute of Diabetes Digestive Kidney Diseases NIDDK 804 4.048 9 Japan Society for the Promotion Of Science 789 3.972 10 NIH National Institute of General Medical Sciences NIGMS 719 3.62TRP = transient receptor potential.
In total, 14,44 author were chosen/selected from 19,862 publications. The top 10 most productive authors contributed 619 articles (3.12%) to the TRP research (Table 2). MAKOTO TOMINAGA contributed the most articles (113 articles), followed by YASUO MORI and LUTZ BIRNBAUMER with 38 and 37 publications, respectively (Table 3). Their centrality scores were low, with only one researcher reaching above 0.05. The co-citation network map of the authors contained 1741 links, and there was active collaboration among the productive authors (Fig. 2).
Table 2 - Top 10 authors in the number of papers published. No. Freq Degree Centrality Author Year Half-life 1 113 25 0.03 MAKOTO TOMINAGA 2006 8.5 2 78 27 0.04 YASUO MORI 2006 8.5 3 77 16 0.06 LUTZ BIRNBAUMER 2007 6.5 4 63 13 0.02 VINCENZO DI MARZO 2007 5.5 5 60 10 0.02 INSUK SO 2007 5.5 6 59 20 0.04 BERND NILIUS 2007 2.5 7 53 13 0.03 THOMAS VOETS 2007 6.5 8 39 6 0 LUCIANO DE PETROCELLIS 2007 5.5 9 39 9 0.04 WOLFGANG LIEDTKE 2007 3.5 10 38 15 0.03 THOMAS GUDERMANN 2008 6.5
Figure 2.: Map of authors’ collaborations related to TRP research. TRP = transient receptor potential.
3.4. Distribution of countries/regions and institutionsFrom 415 countries and 841 units, 19,862 papers were published. As shown in Table 3, the most significant number of publications came from the USA (6386, 32.15%), which is far more than 3 times higher than that of China (2165, 10.90%). Other countries that published more than 1000 articles included Japan (1377, 6.93%) and Germany (1150, 5.79%). Among the top 3 institutions, 2 of institutions are found to be in the USA: Harvard University and Johns Hopkins University. The second-ranked institution is Seoul National University of South Korea, as indicated by the purple circles in Figures 3 and 4. Each circle in the figure represents a country, and the size of the circle indicates the country’s publication output. The lines between the circles denote cooperation between countries; the wider the lines, the closer the cooperation.
Figure 3.: Distribution of publications from different countries/regions.
Figure 4.: Distribution of publications from different institutions.
3.5. Co-occurrence of keywords and analysis of research hotspotsKeywords were extracted from titles and abstracts of all 19,862 publications. Figure 5 shows the keywords mentioned most frequently in publications; there were 1126 nodes and 7864 links in the network map. In terms of frequency, these terms “activation”(2973 times), “expression”(2518 times), “receptor”(1962 times), “channel”(1702 times), “ion channel”(1264 times), “rat”(1237 times), “mechanism”(1192 times), “cell”(1189 times), “pain”(1094 times), “protein”(976 times) appeared most. The top 20 keywords in terms of their frequency of use are listed in Table 4. By analyzing the evolution trend of keywords over time, one can better understand the dynamic trend of the TRP research field. For the documents selected in the WOS database, keywords were used to analyze the years. Documents with a node of 1126 and a line of 7864 were drawn as keyword co-occurrence time zone diagrams, as shown in Figure 6. We found that the initial research focused on channels, activation, acetylcholine, etc. The keywords that appeared in the second stage were cgrp and hypertrophy.
Table 4 - Top 20 keywords related to TRP. No. Freq Degree Centrality Keyword No. Freq Degree Centrality Keyword 1 2973 43 0.02 activation 11 969 32 0.01 capsaicin receptor 2 2518 36 0.02 expression 12 795 45 0.02 inhibition 3 1962 33 0.01 receptor 13 785 37 0.01 neuron 4 1702 41 0.01 channel 14 767 53 0.03 calcium 5 1264 33 0.01 ion channel 15 689 34 0.01 cation channel 6 1237 52 0.03 rat 16 630 41 0.02 mice 7 1192 42 0.01 mechanism 17 622 30 0.01 in vitro 8 1189 30 0.01 cell 18 567 36 0.01 release 9 1094 26 0 pain 19 566 43 0.02 sensory neuron 10 976 37 0.01 protein 20 532 38 0.02 identificationTRP = transient receptor potential.
Figure 5.: Map of co-occurring keywords related to TRP research. TRP = transient receptor potential.
Figure 6.: Timeline viewer related to TRP. TRP = transient receptor potential.
A clustering analysis of the keywords was performed. The results are presented in Figure 7 and Table 5. There were 8 clusters of keywords, which are #0“breast cancer cell,” #1“ventricular myocyte,” #2“sensory neuron,” #3“store-operated channel,” #4“hippocampal slice,” #5“cerebral ischemia-reperfusion cell,” #6“design syntnesis,” #7“adrenergic receptor”.
Table 5 - Top 8 subjects of cluster analysis. Cluster ID Size Year Cluster label (LLR) #0 210 2004 transient receptor; calcium-sensing receptor; risk factors; interleukin-1 receptor antagonist; cxcl12 expression; proliferation; ion channel; cancer; pathway #1 184 1997 transient receptor; potential channels; heart failure; trpc channels; potential canonical channels activation; channel; mechanism; in vivo; involvement #2 184 2008 transient receptor; potential vanilloid type; chemokine receptor; renal injury; deoxycorticosterone acetate-salt pain; expression; neuron; thermosensation; nociceptor #3 184 2003 transient receptor; endothelial barrier dysfunction; tumor necrosis factor-alpha; store-operated calcium ion; growth protein; expression; domain; cloning; period #4 180 1999 transient receptor; potential ankyrin; neuron differentiation; social preference; anxiolytic-like behavior long term; ischemic penumbra; animal models; uveal melanoma; superior colliculus #5 151 2012 transient receptor; potential canonical channel; myocardial infarction; neurotrophic factor; tooth development oxidative stress; dopamine d-4 receptor; soce; adp-ribose; ip3r #6 22 2008 identification; expression; inflammation; capsaicin receptor; primary afferent neuron transient receptor; potential canonical; non-selective cation channel; artemisia annua; membrane-delimited activator #7 9 1998 secretion gene therapy; adeno-associated virus; ocular neovascularization; vascular endothelial growth factor; feline ions sodium; ions calcium; opioid morphine; transgenic mouse; myocardial contractility
Figure 7.: The term co-occurrence network in TRP research. TRP = transient receptor potential.
Keywords with strong burst strength are another important indicator to reflect research hotspots, frontiers, and emerging trends over time. There are 553 hot keywords from 1990 to 2021 (附件 S1). For the focus and hotspot of research in this field, we display the keywords in 3 parts. As shown in Table 6, The top 10 keywords with the longest research time in the past 30 years are displayed. As shown in Table 7, The top 15 keywords from 2015 to 2021 are displayed. Table 8 displays 25 keywords from 2019 to 2021. Most notably, 25 keywords have continued to 2021, and the bursts are still ongoing, indicating that these research directions have received great attention in recent years and have the potential to become new research hotspots in the future.
Table 6 - Top 10 keywords with the strongest citation bursts from 1990 to 2021. Keywords Year Strength Begin End 1990–2021 depolarization 1990 9.53 1991 2009 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂ messenger rna 1990 38.23 1991 2007 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂ calcium current 1990 12.85 1992 2008 ▂▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂ dentate gyrus 1990 7.45 1993 2009 ▂▂▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂ cloning 1990 34.91 1991 2006 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂ transient outward current 1990 27.75 1991 2006 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂ d aspartate receptor 1990 15.3 1991 2006 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂ transient 1990 15.09 1991 2006 ▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂▂ potassium current 1990 10.67 1992 2007 ▂▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂ transient forebrain ischemia 1990 9.33 1992 2007 ▂▂▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▃▂▂▂▂▂▂▂▂▂▂▂▂▂▂
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