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The impact of variable valence A-sites on the redox property and reactivity of Ln2Ce2O7 compounds in soot particulate combustion has been investigated. It was observed that Yb2Ce2O7, Y2Ce2O7, and Gd2Ce2O7 formed a rare earth C-type phase, while Tb2Ce2O7 formed a solid solution phase. Both Tb2Ce2O7 and Yb2Ce2O7 possess dual valence state A-sites, resulting in significantly more surface vacancies. Additionally, the advantageous solid solution phase structure of Tb2Ce2O7 leads to even more surface vacancies than Yb2Ce2O7, which is crucial to generate active oxygen sites. Moreover, the introduction of NO into the reaction feed enhances combustion activity by producing active surface monodentate nitrates. A catalyst with higher numbers of surface vacancies exhibits improved NO oxidation ability and better NO2 utilization efficiency. Consequently, the Tb2Ce2O7 compound demonstrates not only the best soot combustion activity, but also an optimal NOx-assistance effect. Therefore, it is concluded that variable valence A-site is the intrinsic factor to improve the reactivity of Ln2Ce2O7 catalysts.
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The quantity of surface oxygen vacancies/defects is critical to promote the reactivity of metal oxide catalysts. Therefore, for the controlled engineering of Bi2Zr2O7 with rich surface defects for soot combustion, four different methods have been adopted. Bi2Zr2O7 compounds with a defective fluorite phase but with varied surface vacancy concentrations have been successfully synthesized by various methods. The best catalyst (Bi2Zr2O7-CP) was fabricated by a facile co-precipitation method. Both O2- and O22- were the active surface sites whose number positively correlated to the number of surface oxygen vacancies and determined the activity. Moreover, a sample with more surface vacancies usually had weaker Zr-O bonds, which could be the intrinsic factor to enhance the activity. In addition, a novel and simple method has been developed to accurately titrate the absolute amount of soot reactive oxygen sites and calculate the TOF values. In conclusion, by optimizing the preparation methods, Bi2Zr2O7 catalysts with rich surface defects can be tuned, which may help in designing more applicable soot oxidation catalysts.
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OBJECTIVE: The clinical characteristics and mechanisms of stroke caused by anterior circulation atherosclerotic plaques (ACAPs) and posterior circulation atherosclerotic plaques (PCAPs) are distinct. We aimed to compare the differences in vulnerability, morphology, and distribution between ACAPs and PCAPs based on hign-resolution magnetic resonance imaging (HR-MRI). MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang database were retrieved from inception through May 2023. Meta-analysis was performed by R 4.2.1 software. The quality of the literature was assessed by the Agency for Healthcare Research and Quality (AHRQ). Subgroup analysis was conducted to explore the heterogeneity of the pooled results. RESULTS: There were a total of 13 articles, including 1194 ACAPs and 1037 PCAPs. The pooled estimates demonstrated that the incidence of intraplaque hemorrhage in the PCAPs was higher (OR 1.72, 95%CI 1.35-2.18). The plaque length (SMD 0.23, 95%CI 0.06-0.39) and remodeling index (SMD 0.29, 95%CI 0.14-0.44) of PCAPs were larger than those in ACAPs. However, there were no evident differences in significant enhancement or stenosis degree between the two groups. CONCLUSION: There were more unstable features in PCAPs, highlighting an elevated risk of recurrent ischemic stroke in the posterior circulation. Furthermore, PCAPs were prone to developing penetrating artery disease due to their wider distribution. Nevertheless, posterior circulation arteries exhibited a greater propensity for outward remodeling, which may lead treatment team to miss the optimal intervention stage by being overlooked on angiographic detection.
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Circulação Cerebrovascular , Arteriosclerose Intracraniana , Imageamento por Ressonância Magnética , Placa Aterosclerótica , Valor Preditivo dos Testes , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Fatores de Risco , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Medição de Risco , Ruptura Espontânea , Prognóstico , Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior/fisiopatologia , Artéria Cerebral Anterior/diagnóstico por imagem , Artéria Cerebral Anterior/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) has become a global public health problem. The prevalence of IBD in China increased annually in past two decades. METHODS: This study was to translate and validate the rating form of IBD patients' concerns (RFIPC), and to describe disease-related worries and concerns of patients with IBD. The simplified Chinese version of the RFIPC was developed according to translation and back-translation procedure. Patients with IBD were consecutively enrolled from the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The participants were assessed using the RFIPC and the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Internal consistency, test-retest reliability, measurement error, confirmatory factor analysis (CFA) and correlation of the RFIPC with the SIBDQ were performed to evaluate the psychometric characteristics of the RFIPC. RESULTS: A total of 116 patients with IBD, 73 with ulcerative colitis (UC) and 43 with Crohn's disease (CD), were enrolled in this study. Thirty-seven of them recompleted the questionnaires for the second time between 7 and 14 days after the first interview. The results of CFA indicated the original structure of the RFIPC was reasonable. Cronbach's alpha value of the RFIPC were 0.97. The intraclass correlation coefficients of four domains ranged from 0.85 to 0.92. The standard error of measurement was 7.10. The correlation coefficients between total score of the RFIPC and the SIBDQ score ranged from - 0.54 to - 0.70. Median total score of the RFIPC was 39.4 (IQR 24.0-59.3). Patients with severe symptoms reported higher scores of the RFIPC. The uncertain nature of disease, having surgery, having an ostomy bag, developing cancer, feeling out of control, being a burden on others and financial difficulties were highest concerns of patients with IBD. Comparing with patients with UC, patients with CD had more concerns of the ability to have children and being treated as different (P < 0.05). CONCLUSIONS: The simplified Chinese version of RFIPC is a valid and reliable tool. It could be used for assessing disease-related worries and concerns of patients with IBD in China. Specific concerns of patients with UC and CD are different, therefore, health workers should consider the specific needs of UC and CD patients.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Criança , China , Doença Crônica , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Humanos , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , TraduçõesRESUMO
With the target of developing efficient base metal oxide catalysts for soot particulate combustion, Nb2O5 catalysts promoted using different alkali metal nitrates have been prepared via an impregnation method. The activity of all the modified catalysts is better than that of the pure Nb2O5, and follows the sequence of CsNb1-9 > KNb1-9 > NaNb1-9 > LiNb1-9 > Nb2O5. It has been discovered that the original LiNO3 and NaNO3 precursors were decomposed into inert Li2O and Na2O on LiNb1-9 and NaNb1-9 during the calcination process. However, the KNO3 and CsNO3 precursors were intact on KNb1-9 and CsNb1-9 due to the strong stabilization effect of the K+ and Cs+ cations. As confirmed using different means, surface nitrates are the predominant active centers that contribute to the soot oxidation activity, through the redox cycles between nitrate (NO3-) and nitrite (NO2-) groups. Due to the existence of a large quantity of active surface NO3- groups, KNb1-9 and CsNb1-9 thus exhibit a much better reaction performance than LiNb1-9 and NaNb1-9.
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Nanoscale zero-valent iron particles (NZVI) are widely used in a variety of industries owing to their advantageous mechanical, physical, and chemical properties. These particles can be released into environmental media, including water, soil, and air, through several pathways. NZVI in the ecosystem can be taken up, excreted and distributed within organisms, which is harmful to plants, animals and humans. Plants play a significant role as producers in the ecological circle and can both positively and negatively affect the ecological behavior of NZVI. Therefore, understanding the relationship between plants and NZVI is likely to be of great value for the assessment of NZVI-associated risks and future research directions. In this review, we summarize the current knowledge on the uptake, distribution, and accumulation of NZVI in plants; the phytotoxicity triggered by NZVI exposure at the physiological, biochemical, and molecular levels; and the defense mechanism used by plants to defend against NZVI-induced insults. We further discuss the toxic effects of NZVI on soil animals and microorganisms as well as the risk posed by the presence of NZVI in the food chain.
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Recuperação e Remediação Ambiental , Nanopartículas Metálicas , Nanopartículas , Poluentes do Solo , Animais , Ecossistema , Humanos , Ferro/química , Ferro/toxicidade , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Nanopartículas/química , Solo/química , Poluentes do Solo/análiseRESUMO
Enhancing the built-in electric field to promote charge dynamitic process is of great significance to boost the performance of the non-fullerene organic solar cells (OSCs), which has rarely been concerned. In this work, we introduced a cheap ferroelectric polymer as an additive into the active layers of non-fullerene OSCs to improve the device performance. An additional and permanent electrical field was produced by the polarization of the ferroelectric dipoles, which can substantially enhance the built-in electric field. The promoted exciton separation, significantly accelerated charge transport, reduced the charge recombination, as well as the optimized film morphology were observed in the device, leading to a significantly improved performance of the PVDF-modified OSCs with various active layers, such as PM6 : Y6, PM6 : BTP-eC9, PM6 : IT-4F and PTB7-Th : Y6. Especially, a record efficiency of 17.72 % for PM6 : Y6-based OSC and an outstanding efficiency of 18.17 % for PM6 : BTP-eC9-based OSC were achieved.
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We demonstrate a composite multiscale entropy (CMSE) method of terahertz (THz) signal complexity analysis to distinguish different biological tissues. The THz signals reflected from fresh porcine skin and muscle tissues were measured and analyzed. The statistically significant difference and separation of the two tissues based on several parameters were analyzed and compared for THz spectroscopy and imaging, which verified the better performance of the CMSE method and further enhancement of the contrast among THz signals that interact with different tissues. This process provides a better analysis and discrimination method for THz spectroscopy and imaging in biomedical applications.
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Espectroscopia Terahertz/métodos , Animais , Entropia , Músculos , SuínosRESUMO
In the widely studied two-color laser scheme for terahertz (THz) radiation from a gas, the frequency ratio of the two lasers is usually fixed at ω_{2}/ω_{1}=1:2. We investigate THz generation with uncommon frequency ratios. Our experiments show, for the first time, efficient THz generation with new ratios of ω_{2}/ω_{1}=1:4 and 2â¶3. We observe that the THz polarization can be adjusted by rotating the longer-wavelength laser polarization and the polarization adjustment becomes inefficient by rotating the other laser polarization; the THz energy shows similar scaling laws with different frequency ratios. These observations are inconsistent with multiwave mixing theory, but support the gas-ionization or plasma-current model. This study pushes the development of the two-color scheme and provides a new dimension to explore the long-standing problem of the THz generation mechanism.
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The recent progresses on chemical components and pharmacological activities of the genus Valerianawere summarized.Besides-essential oil, the chemical composition of Valerianais mainly focused on monoterpenoids,sesquiterpenoids,lignans, flavonoids, alkaloids, etc. Iridoids are the main chemical components ofmonoterpenoids. There are two types ofiridoidson the basis of the cyclopentane open or not. The Valerianahas been drawmuch attention for their significant sedation,spasmolysis,antidepression,antitumor, against adenosine A1 receptors and cytotoxicityactivity,and had certain function for cardiovascular disease treatment. Given to the fact of the lack of systematic review and summary of studies on the Valeriana, we summarized and analyze the study literatures on the pharmacological activity of Valerianain recent years, and providedsome basisfor further study.
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Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Valeriana/química , Humanos , Iridoides/análiseRESUMO
Miniature resonant piezoelectric robots have the advantages of compact structure, fast response, high speed, and easy control, which have attracted the interest of many scholars in recent years. However, piezoelectric robots usually suffer from the problem of poor adaptability due to the micron-level amplitude at the feet. Inspired by the fact that earthworms have actuation trajectories all around their bodies to move flexibly under the ground, a miniature piezoelectric robot with circumferentially arranged driving feet to improve adaptability is proposed. Notably, a longitudinal-vibration-compound actuation principle with multilegged collaboration is designed to achieve the actuation trajectories around the robot, similar to the earthworms. The structure and operating principle are simulated by the finite element method, and the prototype is fabricated. The robot weighs 22.7 g and has dimensions of 35.5 × 36.5 × 47 mm3. The robot is tethered to an ultrasonic power supply, and the experimental results show that the speed reaches 179.35 mm s-1 under an exciting signal with a frequency of 58.5 kHz and a voltage of 200 Vp-p. High adaptability is achieved by the proposed robot, it can move on flat, fold, concave, and convex surfaces, and even in an inclined or rotating tube.
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Modular reconfigurable robots exhibit prominent advantages in the reconnaissance and exploration tasks within unstructured environments for their characteristics of high adaptability and high robustness. However, due to the limitations in locomotion mechanism and integration requirements, the modular design of miniature robots in the aquatic environment encounters significant challenges. Here, a modular strategy based on the synthetic jet principle is proposed, and a modular reconfigurable robot system is developed. Specialized bottom and side jet actuators are designed with vibration motors as excitation sources, and a motion module is developed incorporating the jet actuators to realize three-dimensional agile motion. Its linear, rotational, and ascending motion speeds reach 70.7 mm s-1, 3.3 rad s-1, and 28.7 mm s-1, respectively. The module integrates the power supply, communication, and control system with a small size of 48 mm × 38 mm × 38 mm, which ensures a wireless controllable motion. Then, various configurations of the multi-module robot system are established with corresponding motion schemes, and the experiments with replaceable intermediate modules are further conducted to verify the transportation and image-capturing functions. This work demonstrates the effectiveness of synthetic jet propulsion for aquatic modular reconfigurable robot systems, and it exhibits profound potential in future underwater applications.
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Vibration is a common strategy for aquatic organisms to achieve their life activities, especially at the air-water interface. For the locomotion of small creatures, the organs with plate features are often used on water surfaces, which inspires relevant studies about using thin plates for robot propulsions. However, the influence of the general deformations of thin plates on the generated flow fields has not been considered. Here, a comprehensive investigation is conducted about the flow fields that arose by vibrations of thin plates and the potential as locomotion strategies are explored. It is discovered that as thin plates are subjected to vibration excitations on the water surface, the produced flow fields are mainly determined by the vibration shapes, and the influence rules of plate deformations on the flow fields are identified. The main factors producing asymmetric flow fields are analyzed to realize the morphology control of the flow fields. Then, to determine effective locomotion strategies on the water surface, the flow fields stimulated by integrated vibration exciters are explored, and 2 water surface robots are developed consequentially, which exhibit superior motion performance. This work reveals the basic rules of the vibration-induced-flow mechanism by thin plates and establishes new locomotion strategies for aquatic robots.
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Ciliates in the subclass Hypotrichia have long been difficult to classify as they are one of the most polymorphic and highly differentiated groups, leading to their systematics remaining unresolved. Phylogenetic relationships within the hypotrich family Strongylidiidae have been ambiguous due to discordance between the morphological and genetic data. In this study, a new strongylidiid genus Heterouroleptus is established, mainly based on the novel mode of origin of the ventral cirral rows: left ventral cirral row (LVR) originates from frontal-ventral-transverse cirral anlagen (FVTA) III (anterior portion), IV (middle portion), and V (rear portion); right ventral cirral row comes from the entire FVTA VI. A new species, Heterouroleptus weishanensis gen. nov., sp. nov., is investigated along with the morphometric and molecular data from a population of Strongylidium wuhanense. Eight new sequences and nuclear gene markers (single-gene and multi-gene) are provided to analyze the phylogenetic relationships of strongylidiids, with the COI gene utilized to uncover further genetic information at species level and below. The results reveal that: (1) Strongylidiidae is monophyletic and has a close relationship with Dorsomarginalia; (2) Heterouroleptus gen. nov. forms a clade that is sister to all the other strongylidiids; (3) Hemiamphisiella Foissner, 1988 and Pseudouroleptus Hemberger, 1985 should not be synonyms, and both genera should be subdivided due to their variable morphological characteristics; (4) LVR originating from three anlagen is a plesiomorphy of Strongylidiidae. The discovery of the origin of the LVR not only contributes to the establishment of the genus Heterouroleptus, but also helps to improve the diagnosis of the family Strongylidiidae. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00243-z.
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BACKGROUND: Translational medical research literature has increased rapidly in the last few decades and played a more and more important role during the development of medicine science. The main aim of this study is to evaluate the global performance of translational medical research during the past few decades. METHODS: Bibliometric, social network analysis, and visualization technologies were used for analyzing translational medical research performance from the aspects of subject categories, journals, countries, institutes, keywords, and MeSH terms. Meanwhile, the co-author, co-words and cluster analysis methods were also used to trace popular topics in translational medical research related work. RESULTS: Research output suggested a solid development in translational medical research, in terms of increasing scientific production and research collaboration. We identified the core journals, mainstream subject categories, leading countries, and institutions in translational medical research. There was an uneven distribution of publications at authorial, institutional, and national levels. The most commonly used keywords that appeared in the articles were "translational research", "translational medicine", "biomarkers", "stroke", "inflammation", "cancer", and "breast cancer". CONCLUSIONS: The subject categories of "Research & Experimental Medicine", "Medical Laboratory Technology", and "General & Internal Medicine" play a key role in translational medical research both in production and in its networks. Translational medical research and CTS, etc. are core journals of translational research. G7 countries are the leading nations for translational medical research. Some developing countries, such as P.R China, also play an important role in the communication of translational research. The USA and its institutions play a dominant role in the production, collaboration, citations and high quality articles. The research trends in translational medical research involve drug design and development, pathogenesis and treatment of disease, disease model research, evidence-based research, and stem and progenitor cells.
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Bibliometria , Pesquisa Translacional Biomédica/normas , Feminino , Humanos , Comportamento de Busca de Informação , Rede Social , Integração de Sistemas , Pesquisa Translacional Biomédica/estatística & dados numéricos , Pesquisa Translacional Biomédica/tendênciasRESUMO
Piezoelectric ultrasonic-assisted precision machining (PUAPM) technology is considered to be an efficient and environmentally friendly machining strategy by virtue of cutting force reduction, ductile cutting promotion, tool wear and machining noise reduction. Piezoelectric ultrasonic transducer (PUT) provides ultrasonic energy for PUAPM system, which is the core component to ensure the normal operation of the system. PUTs for PUAPM devices have emerged endlessly in recent decades and have been successfully applied in many fields, such as MEMS, biomedicine, optoelectronics, aerospace, etc. However, there is no comprehensive classification and analysis of the basic configurations, excitation principles, typical structures, performance analyses and control strategies for PUT. This work gives a critical review of research on PUT in recent years, especially the structural optimization, application expansion and ultrasonic energy stabilization in PUAPM. The influence mechanism of excitation mode, modal type, modal combination, horn structure and ceramic arrangement on the optimization of PUT structure is summarized. The improvement effect and mechanism of PUT vibration dimension, amplitude, frequency and structural characteristics on surface roughness, surface texture and cutting force are discussed. In addition, the causes of PUT amplitude fluctuation, and the influence of sensing and control methods on PUT amplitude regulation and system integration are analyzed. This review will help in understanding the current development and diversified applications of PUT and will promote the application of ultrasonic technology in more fields.
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Miniature robots have been widely studied and applied in the fields of search and rescue, reconnaissance, micromanipulation, and even the interior of the human body benefiting from their highlight features of small size, light weight, and agile movement. With the development of new smart materials, many functional actuating elements have been proposed to construct miniature robots. Compared with other actuating elements, piezoelectric actuating elements have the advantages of compact structure, high power density, fast response, high resolution, and no electromagnetic interference, which make them greatly suitable for actuating miniature robots, and capture the attentions and favor of numerous scholars. In this paper, a comprehensive review of recent developments in miniature piezoelectric robots (MPRs) is provided. The MPRs are classified and summarized in detail from three aspects of operating environment, structure of piezoelectric actuating element, and working principle. In addition, new manufacturing methods and piezoelectric materials in MPRs, as well as the application situations, are sorted out and outlined. Finally, the challenges and future trends of MPRs are evaluated and discussed. It is hoped that this review will be of great assistance for determining appropriate designs and guiding future developments of MPRs, and provide a destination board to the researchers interested in MPRs.
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Multiple degrees of freedom (DOFs) motion manipulation of various objects is a crucial skill for robotic systems, which relies on various robotic hands. However, traditional robotic hands suffer from problems of low manipulation accuracy, poor electromagnetic compatibility and complex system due to limitations in structures, principles and transmissions. Here we present a direct-drive rigid piezo robotic hand (PRH) constructed on functional piezoelectric ceramic. Our PRH holds four piezo fingers and twelve motion DOFs. It achieves high adaptability motion manipulation of ten objects employing pre-planned functionalized hand gestures, manipulating plates to achieve 2L (linear) and 1R (rotary) motions, cylindrical objects to generate 1L and 1R motions and spherical objects to produce 3R motions. It holds promising prospects in constructing multi-DOF ultra-precision manipulation devices, and an integrated system of our PRH is developed to implement several applications. This work provides a new direction to develop robotic hand for multi-DOF motion manipulation from micro scale to macro scale.
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PURPOSE: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma originating in the skin. Studies are needed to determine the mechanisms of immune escape in patients with MCC, and malignant cell conditions that promote immune evasion. METHODS: We used Single-cell RNA sequencing (scRNA-seq) to determine cellular features associated with MCC disease trajectory. A longitudinal multi-omics study was performed using scRNA-seq data of peripheral blood harvested from four-time points. Six major cell types and fifteen cell subgroups were identified and confirmed their presence by expression of characteristic markers. The expression patterns and specific changes of different cells at different time points were investigated. Subsequently, bulk RNA data was used to validate key findings. RESULTS: The dynamic characteristics of the cells were identified during the critical period between benign improvement and acquisition of resistance. Combined with the results of the validation cohort, the resistance program expressed in the relapse stage is mainly associated with T cell exhaustion and immune cell crosstalk disorder. Coinciding with immune escape, we also identified a decrease non-classical monocytes and an expansion of classical monocytes with features of high inflammation and immune deficiency. CONCLUSION: Changes in cellular status, such as depletion of T cells and dysregulation of B cell proliferation and differentiation, may lead to drug resistance in MCC patients. Meanwhile, the widespread decreased antigen presentation ability and immune disorders caused by deletion of MHC class II gene expression should not be ignored.
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Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/patologia , Linfócitos T , Neoplasias Cutâneas/patologia , Monócitos/patologia , Imunoterapia/métodosRESUMO
BACKGROUND & OBJECTIVES: Artemisinin was first extracted from the herb Artemisia annua which has been used for many centuries in Chinese traditional medicine as a treatment for fever and malaria. It has been given the 2011 Lasker-DeBakey clinical medical research award. In this paper, knowledge map of artemisinin research was drawn to provide some information for global researchers interested in artemisinin and its relevant references. METHODS: In this work, bibliometric analysis and knowledge visualization technology were applied to evaluate global scientific production and developing trend of artemisinin research through Science Citation Index (SCI) papers and Medline papers with online version published as following aspects: publication outputs, subject categories, journals, countries, international collaboration, citations, authorship and co-authorship, author key words and co-words analysis. The Thomson Data Analyzer (TDA), Netdraw and Aureka software were employed to analyze the SCI as well as Medline papers data for knowledge mapping. RESULTS: Global literature of artemisinin research has increased rapidly over the past 30 years and has boosted in recent years. Seen from the statistical study in many aspects, Pharmacology & Pharmacy, and Chemistry are still the main subjects of artemisinin research with parasitology and tropical medicine increasing quickly. Malaria Journal and American Journal of Tropical Medicine are top productive journals both in SCI and Medline databases. Quantity and quality of papers in US are in a leading position, although papers quantity and active degree in developing countries such as P.R. China, Thailand and India are relatively high, the quality of papers from these countries needs to be improved. New emerging key words and co-words remind us that mechanism of action, pharmacokinetics, artemisinin-based alternatives, etc. are the future trends of artemisinin research. CONCLUSION: Through bibliometric analysis the development trends of artemisinin research are predicted. With further development of artemisinin research, it is presumed that scientists might concentrate mainly on the synthesis of new compounds with activity, action mechanism, new artemisinin-based combination therapy regimens, etc.