Image_1_Bibliometric analysis of rheumatic immune related adverse events associated with immune checkpoint inhibitors.pdf

BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to “monoclonal antibody,” “anti-CLTA4 antibody,” and “melanoma”. This was followed by a rise in interest related to “sarcoidosis,” “safety,” “inflammatory arthritis,” and “preexisting autoimmune.”ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.</p

Image_2_Bibliometric analysis of rheumatic immune related adverse events associated with immune checkpoint inhibitors.pdf

BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to “monoclonal antibody,” “anti-CLTA4 antibody,” and “melanoma”. This was followed by a rise in interest related to “sarcoidosis,” “safety,” “inflammatory arthritis,” and “preexisting autoimmune.”ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.</p

Image_3_Bibliometric analysis of rheumatic immune related adverse events associated with immune checkpoint inhibitors.pdf

BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to “monoclonal antibody,” “anti-CLTA4 antibody,” and “melanoma”. This was followed by a rise in interest related to “sarcoidosis,” “safety,” “inflammatory arthritis,” and “preexisting autoimmune.”ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.</p

Image_4_Bibliometric analysis of rheumatic immune related adverse events associated with immune checkpoint inhibitors.pdf

BackgroundImmune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.MethodsThe Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.ResultsIn This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to “monoclonal antibody,” “anti-CLTA4 antibody,” and “melanoma”. This was followed by a rise in interest related to “sarcoidosis,” “safety,” “inflammatory arthritis,” and “preexisting autoimmune.”ConclusionThis study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.</p

Role of Reelin in cell migration.

<p><b>A</b>: RT-PCR analysis showing RELN mRNA level in RELN and scramble siRNAs transfected cells, and GAPDH was used as an internal control. <b>B</b>: Transwell assay showing that RELN knockdown increased cell migration. Cells were stained with crystal violet (<i>left</i>). The bar graph shows the relative number of migrated cells from three independent experiments (mean+SE, <i>right</i>). *, p<0.05. <b>C</b>: RT-PCR analysis showing RELN mRNA level in RELN shRNA and scramble clones. <b>D</b>: Transwell assay showing cell migration of the RELN shRNA and scramble clones. Cells were stained with crystal violet (<i>top</i>). The bar graph shows the relative number of migrated cells from three independent experiments (mean+SE, <i>bottom</i>). *, <i>p</i><0.05. <b>E</b>: RT-qPCR showing the mRNA expression of some EMT markers in RELN shRNA and scramble clones. Data represent the mean ± SD of triplicate experiments.</p

A Single Hot Event Stimulates Adult Performance but Reduces Egg Survival in the Oriental Fruit Moth, <i>Grapholitha molesta</i>

<div><p>Climate warming is expected to increase the exposure of insects to hot events (involving a few hours at extreme high temperatures). These events are unlikely to cause widespread mortality but may modify population dynamics via impacting life history traits such as adult fecundity and egg hatching. These effects and their potential impact on population predictions are still largely unknown. In this study, we simulated a single hot event (maximum of 38°C lasting for 4 h) of a magnitude increasingly found under field conditions and examined its effect in the oriental fruit moth, <i>Grapholitha molesta</i>. This hot event had no impact on the survival of <i>G. molesta</i> adults, copulation periods or male longevity. However, the event increased female lifespan and the length of the oviposition period, leading to a potential increase in lifetime fecundity and suggesting hormesis. In contrast, exposure of males to this event markedly reduced the net reproductive value. Male heat treatment delayed the onset of oviposition in the females they mated with, as well as causing a decrease in the duration of oviposition period and lifetime fecundity. Both male and female stress also reduced egg hatch. Our findings of hormetic effects on female performance but concurrent detrimental effects on egg hatch suggest that hot events have unpredictable consequences on the population dynamics of this pest species with implications for likely effects associated with climate warming.</p></div

Kinetic Mechanism of Thioflavin T Binding onto the Amyloid Fibril of Hen Egg White Lysozyme

Thioflavin T (ThT) is widely used as a fluorescent probe for amyloid fibril detection. Yet the exact kinetic mechanism of ThT binding onto amyloid fibril remains elusive. Previously reported kinetic studies using ThT-fluorescence-detected kinetic design suggested two completely different ThT-binding mechanisms. In one study, a multistep sequential binding mechanism onto a single ThT-binding site was suggested. In another study, a one-step parallel binding mechanism onto multiple ThT-binding sites was suggested. The discrepancy is likely due to the incapability of ThT-fluorescence-detected kinetic design to differentiate the two above-mentioned mechanisms. Considering the weakness of the ThT-fluorescence-detected approach, we investigated the ThT-binding mechanism onto the amyloid fibril of hen egg white lysozyme (HEWL) using a new approach, ThT-absorbance-detected kinetic design. Our new results suggest that ThT binds to HEWL fibril through the one-step parallel binding mechanism. We hope our work can offer some new insights into the interactions between dye molecules and amyloid fibrils

TGF-β1 suppressed RELN expression and transient transfection of Reelin blocked TGF-β1-induced cell migration.

<p><b>A</b>: RT-PCR analysis showing RELN mRNA expression in eight ESCC cell lines, GAPDH was used as an internal control. <b>B</b>: Reelin protein was localized in cytoplasm in KYSE-510 cells by immunostaining. Mouse IgG was used as isotype negative control. <i>Scale bar</i>: 20 µm. <b>C</b>: KYSE-510 cells were treated with 5 ng/ml TGF-β1, RELN mRNA expression was examined by RT-PCR, and GAPDH was used as an internal control. <b>D</b>: Western blot for Reelin protein using whole cell extract at 48 hours after reelin (pCrl) transfection in KYSE-30 cells. β-actin served as the loading control. <b>E</b>: 5 ng/ml TGF-β1 was added in media for 24 hours after pCrl transfection and Transwell assay was performed at 48 hours after transfection (<i>left</i>). The bar graph shows the relative number of migrated cells from three independent experiments (<i>right</i>). Data represent the mean ± SD of triplicate experiments. *, <i>p</i><0.05.</p

Snail regulates RELN expression in ESCC cells.

<p><b>A&B</b>: Snail protein was increased (<b>A</b>) and RELN mRNA was decreased (<b>B</b>) in a time-dependent manner after 5 ng/ml TGF-β1 treatment in KYSE-510 cells. β-actin served as the loading control in Western blot. <b>C</b>: RT-qPCR analysis showing that Snail down-regulates RELN mRNA expression in KYSE30 and KYSE-510 cells. Data represent the mean ± SD of triplicate experiments. *, <i>p</i><0.05. <b>D</b>: Snail down-regulates RELN promoter activity in KYSE-30 and KYSE510 cells in a dose-dependent manner. Data represent the mean ± SD of triplicate experiments. <b>E</b>: Snail binds to the RELN promoter after TGF-β1 treatment in KYSE-510 cells. Schematic representation of RELN promoter region, +1 = transcription start site (<i>left</i>). ChIP assay was carried out by using a rabbit anti-Snail antibody or the rabbit IgG as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031802#s4" target="_blank"><i>Materials and Methods</i></a>. The presence of sequences corresponding to RELN promoters and β-actin were analyzed, and β-actin served as the negative control (<i>right</i>).</p

TGF-β1 treatment decreased RELN transcriptional activity, but did not affect RELN mRNA stability.

<p><b>A</b>: TGF-β1 down-regulated the RELN promoter activity. KYSE-510 cells were transiently transfected with pGL3-basic and the RELN promoter-luciferase construct, and simultaneously treated by 5 ng/ml TGF-β1 at 24 hours after transfection. Data represent the mean ± SD of triplicate experiments. *, <i>p</i><0.05. B. KYSE-510 cells were treated with or without 5 ng/ml TGF-β1 for 1 hour followed by actinomycin D (<i>Act D</i>; 5 µg/ml) treatment for the indicated time. RELN mRNA level was measured by RT-qPCR (<i>left</i>) and plotted on a logarithmic scale to calculate the time required for each mRNA to reach one-half of its initial abundance (<i>right</i>). Dotted line represents RELN mRNA expression after TGF-β1 treatment and straight line represents RELN mRNA expression of untreated control.</p