{"id":3592,"date":"2024-08-02T15:24:12","date_gmt":"2024-08-02T15:24:12","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=3592"},"modified":"2024-08-02T15:24:12","modified_gmt":"2024-08-02T15:24:12","slug":"uplc-q-tof-ms-extraction-of-fructus-psorale","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/es\/uplc-q-tof-ms-extraction-of-fructus-psorale\/","title":{"rendered":"An\u00e1lisis de la composici\u00f3n qu\u00edmica y exploraci\u00f3n preliminar del mecanismo de promoci\u00f3n de la producci\u00f3n de melanina en el extracto alcoh\u00f3lico de Fructus Psorale mediante UPLC-Q-TOF-MS"},"content":{"rendered":"<p>An\u00e1lisis de la composici\u00f3n qu\u00edmica y exploraci\u00f3n preliminar del mecanismo de promoci\u00f3n de la producci\u00f3n de melanina en el extracto alcoh\u00f3lico de Fructus Psorale mediante UPLC-Q-TOF-MS<br \/>\nEl vit\u00edligo es una enfermedad cl\u00ednica localizada y com\u00fan de la piel que provoca despigmentaci\u00f3n, con una tasa de prevalencia de aproximadamente 0,5%~2% en todo el mundo. Es f\u00e1cil de diagnosticar y dif\u00edcil de tratar, con una elevada tasa de incidencia y un largo curso de la enfermedad, lo que repercute negativamente en la salud f\u00edsica y mental de los pacientes. La psoralea es un fruto seco y maduro de la planta leguminosa Psoralea corylifolia L. Se utiliza principalmente en la medicina tradicional china para tratar la disfunci\u00f3n er\u00e9ctil, las emisiones nocturnas, el dolor lumbar y de rodilla, y las sibilancias causadas por la deficiencia de yang renal. Tambi\u00e9n puede utilizarse por v\u00eda t\u00f3pica para tratar el vit\u00edligo y la alopecia areata. No s\u00f3lo en nuestro pa\u00eds hay antecedentes de su uso para tratar el vit\u00edligo, sino que tambi\u00e9n hay registros en pa\u00edses del sudeste asi\u00e1tico como Jap\u00f3n, Corea del Sur, India, etc. (conocido como \"semillas de Babchi\", \"polvo de Bakuchi\", \"Bakuchiol\", etc.). Tambi\u00e9n existen diversas formas de dosificaci\u00f3n para el tratamiento del vit\u00edligo con psoraleno, como decocciones, tinturas e inyecciones (Norma M\u00e9dica Nacional Z41022361). Aunque existen muchos registros bibliogr\u00e1ficos sobre el tratamiento del vit\u00edligo con psoraleno, su mecanismo de acci\u00f3n y la base material para el tratamiento del vit\u00edligo no se conocen por completo. Por lo tanto, este art\u00edculo utiliza la tecnolog\u00eda de espectrometr\u00eda de masas de tiempo de vuelo cuadrupolar de cromatograf\u00eda l\u00edquida de ultra alto rendimiento (UPLC-Q-TOF-MS) para estudiar la composici\u00f3n qu\u00edmica del extracto alcoh\u00f3lico de Psoraleae Fructus (PFE); Mediante la realizaci\u00f3n de experimentos en peces cebra para promover la producci\u00f3n de melanina, se investig\u00f3 el efecto del PFE en la producci\u00f3n de melanina. Se utiliz\u00f3 la reacci\u00f3n en cadena de la polimerasa cuantitativa con fluorescencia en tiempo real (qRT PCR) para detectar los niveles de expresi\u00f3n del ARNm de la tirosinasa (Tyr), la prote\u00edna 1 relacionada con la tirosinasa (Tyrp1) y la prote\u00edna 2 relacionada con la tirosinasa (Tyrp2) en c\u00e9lulas de melanoma de rat\u00f3n B16-F10 tratadas con PFE, psoraleno (PSO) e isosoraleno (IPSO). El objetivo de este estudio es seguir explorando los posibles efectos terap\u00e9uticos del PFE en las c\u00e9lulas de melanoma blanco. Los compuestos activos y las dianas del vit\u00edligo sientan las bases.<\/p>\n<p>El vit\u00edligo es una mancha blanca localizada en la piel causada por el da\u00f1o de los melanocitos, que est\u00e1 ampliamente reconocida como una enfermedad dif\u00edcil y obstinada. Hasta ahora, su etiolog\u00eda y patog\u00e9nesis no se han comprendido del todo. La investigaci\u00f3n ha demostrado que la pigmentaci\u00f3n de la piel est\u00e1 estrechamente relacionada con los tres principales procesos metab\u00f3licos de los melanocitos en la epidermis, incluida la proliferaci\u00f3n de melanocitos, la s\u00edntesis y activaci\u00f3n de TYR y la s\u00edntesis de melanina, as\u00ed como la v\u00eda de transferencia de melanina de los melanosomas a los queratinocitos. La s\u00edntesis de melanina es una reacci\u00f3n compleja que se produce en los melanocitos y est\u00e1 regulada por m\u00faltiples factores. TYR es la enzima limitante de la s\u00edntesis de melanina, y su actividad est\u00e1 regulada por TYRP1 y TYRP2, lo que la convierte en un factor regulador clave en la s\u00edntesis de melanina.<br \/>\nBas\u00e1ndose en la patog\u00e9nesis y las manifestaciones cl\u00ednicas del vit\u00edligo, los investigadores han desarrollado una serie de modelos animales en los \u00faltimos a\u00f1os, como la inducci\u00f3n de agentes despigmentantes qu\u00edmicos, la inducci\u00f3n de estr\u00e9s melanoc\u00edtico, la inducci\u00f3n inmunol\u00f3gica, la inducci\u00f3n de c\u00e9lulas T ex\u00f3genas, la inducci\u00f3n transg\u00e9nica, la inducci\u00f3n de desprendimiento de melanocitos, etc. Los ratones son la principal elecci\u00f3n como animales. Seg\u00fan las investigaciones, 71,4% de los genes humanos codificantes de prote\u00ednas y 82% de los genes pat\u00f3genos son directamente hom\u00f3logos al pez cebra, incluidos muchos genes relacionados con enfermedades cut\u00e1neas humanas. Las larvas de pez cebra son transparentes, y la estructura global y celular de su piel es similar a la de la piel de los mam\u00edferos. Tienen melanocitos y melanosomas similares a los humanos, y los melanocitos se observan f\u00e1cilmente durante el desarrollo individual. Esto convierte al pez cebra en un modelo animal muy utilizado para la investigaci\u00f3n de la pigmentaci\u00f3n, incluidas enfermedades como el vit\u00edligo y el melanoma. Sin embargo, dado que el vit\u00edligo es una enfermedad multifactorial compleja, actualmente no existe ning\u00fan modelo animal que pueda simular completamente la aparici\u00f3n y el proceso de desarrollo del vit\u00edligo humano. Por lo tanto, los modelos animales de vit\u00edligo todav\u00eda necesitan ser explorados m\u00e1s a fondo.<br \/>\nPTU es un inhibidor de TYR, ampliamente utilizado para bloquear la pigmentaci\u00f3n y mejorar la transparencia \u00f3ptica en embriones de pez cebra. Los estudios han demostrado que el uso de soluci\u00f3n de PTU en lugar de agua de peces despu\u00e9s de la embriog\u00e9nesis intestinal del pez cebra (5,5 hpf) puede inhibir eficazmente la producci\u00f3n de melanina y mantener la transparencia del pez cebra. Los resultados de este experimento indican que tras tratar al pez cebra con PFE durante 18 horas despu\u00e9s del modelado con PTU, en comparaci\u00f3n con el grupo tratado con medio de cultivo embrionario, el PFE puede acelerar la regeneraci\u00f3n de melanina en los ojos, el abdomen, la columna vertebral y la cola de los alevines de pez cebra, lo que concuerda con la aplicaci\u00f3n cl\u00ednica del psoraleno en el tratamiento del vit\u00edligo.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3593\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231931.png\" alt=\"\" width=\"540\" height=\"302\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3594\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231938.png\" alt=\"\" width=\"1070\" height=\"384\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231938.png 1070w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231938-768x276.png 768w\" sizes=\"(max-width: 1070px) 100vw, 1070px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3595\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231941.png\" alt=\"\" width=\"1072\" height=\"652\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231941.png 1072w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231941-768x467.png 768w\" sizes=\"(max-width: 1072px) 100vw, 1072px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3596\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231944.png\" alt=\"\" width=\"1076\" height=\"734\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231944.png 1076w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231944-768x524.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231944-1055x720.png 1055w\" sizes=\"(max-width: 1076px) 100vw, 1076px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3597\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231948.png\" alt=\"\" width=\"1096\" height=\"1228\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231948.png 1096w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231948-768x860.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231948-643x720.png 643w\" sizes=\"(max-width: 1096px) 100vw, 1096px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3598\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231951.png\" alt=\"\" width=\"1082\" height=\"1240\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231951.png 1082w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231951-768x880.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231951-628x720.png 628w\" sizes=\"(max-width: 1082px) 100vw, 1082px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3599\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231954.png\" alt=\"\" width=\"1086\" height=\"1246\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231954.png 1086w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231954-768x881.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231954-628x720.png 628w\" sizes=\"(max-width: 1086px) 100vw, 1086px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3600\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231957.png\" alt=\"\" width=\"1080\" height=\"1248\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231957.png 1080w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231957-768x887.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802231957-623x720.png 623w\" sizes=\"(max-width: 1080px) 100vw, 1080px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3601\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232000.png\" alt=\"\" width=\"1090\" height=\"1272\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232000.png 1090w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232000-768x896.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232000-617x720.png 617w\" sizes=\"(max-width: 1090px) 100vw, 1090px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3602\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232003.png\" alt=\"\" width=\"1064\" height=\"922\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232003.png 1064w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232003-768x666.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232003-831x720.png 831w\" sizes=\"(max-width: 1064px) 100vw, 1064px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3603\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232007.png\" alt=\"\" width=\"1048\" height=\"1034\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232007.png 1048w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232007-768x758.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232007-730x720.png 730w\" sizes=\"(max-width: 1048px) 100vw, 1048px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3604\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232010.png\" alt=\"\" width=\"1048\" height=\"450\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232010.png 1048w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232010-768x330.png 768w\" sizes=\"(max-width: 1048px) 100vw, 1048px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3605\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232013.png\" alt=\"\" width=\"1036\" height=\"500\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232013.png 1036w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232013-768x371.png 768w\" sizes=\"(max-width: 1036px) 100vw, 1036px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3606\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232017.png\" alt=\"\" width=\"1046\" height=\"824\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232017.png 1046w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232017-768x605.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232017-914x720.png 914w\" sizes=\"(max-width: 1046px) 100vw, 1046px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3607\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/\u5fae\u4fe1\u56fe\u7247_20240802232019.png\" alt=\"\" width=\"554\" height=\"460\" \/>Seg\u00fan la farmacopea china y los libros de fitoterapia antiguos y modernos, el Fructus Psorale es un medicamento tradicional chino de eficacia probada en el tratamiento del vit\u00edligo. La mayor\u00eda de las instituciones m\u00e9dicas utilizan Fructus Psorale en tinturas, con concentraciones de etanol que oscilan entre 30% y 100%. Por lo tanto, bas\u00e1ndose en la literatura y las aplicaciones pr\u00e1cticas, este estudio seleccion\u00f3 etanol 65% como reactivo de extracci\u00f3n. Este estudio utiliz\u00f3 la tecnolog\u00eda UPLC-Q-TOF-MS para identificar los componentes qu\u00edmicos en el PFE. Se identificaron un total de 47 componentes qu\u00edmicos, principalmente flavonoides (27) y cumarinas (10). Los componentes qu\u00edmicos cumar\u00ednicos identificados PSO e IPSO pueden ser los principales componentes qu\u00edmicos eficaces para el tratamiento del vit\u00edligo. Los benzofuranos (como el psoraleno y el isopsoraleno) tambi\u00e9n pueden convertirse en PSO e IPSO en el organismo para ejercer sus efectos. El PSO y el IPSO son tambi\u00e9n componentes de control de calidad para los materiales medicinales de grasa \u00f3sea especificados en la Farmacopea China. Por lo tanto, se seleccionaron PFE y estos dos componentes qu\u00edmicos para los experimentos celulares. La exploraci\u00f3n preliminar del mecanismo de acci\u00f3n mostr\u00f3 que los resultados de la PCR qRT mostraron que, en comparaci\u00f3n con el grupo de control, el PFE aumentaba significativamente la expresi\u00f3n de ARNm de Tyr y Tyrp2 en c\u00e9lulas B16-F10, mientras que otros grupos de tratamiento pod\u00edan aumentar la expresi\u00f3n de ARNm de Tyr, Tyrp1 y Tyrp2 en diversos grados, con diferencias estad\u00edsticas, lo que indica que el PSO, el IPSO y otros compuestos potencialmente desconocidos del Fructus Psorale pueden ejercer efectos terap\u00e9uticos sobre el vit\u00edligo aumentando el contenido de tirosinasa. Sin embargo, tambi\u00e9n hay informes en la literatura que indican que PSO act\u00faa sobre la l\u00ednea celular de melanoma humano A375, inhibiendo la actividad del promotor de la tirosinasa; la disminuci\u00f3n de los niveles de expresi\u00f3n de ARNm de Tyr, Tyrp1 y Tyrp2 y la inhibici\u00f3n de la producci\u00f3n de melanina, contrariamente a los resultados de este experimento, pueden deberse a diferentes sujetos de investigaci\u00f3n o a la regulaci\u00f3n bidireccional de la producci\u00f3n de melanina por PSO en diferentes rangos de concentraci\u00f3n. Se necesitan m\u00e1s investigaciones para extraer conclusiones m\u00e1s rigurosas y precisas. Para el tratamiento del vit\u00edligo con psoraleno, la PSO y la IPSO son los principales principios activos, que pueden utilizarse como indicadores de control de calidad de este f\u00e1rmaco o de las formulaciones que contienen esta medicina tradicional china.<\/p>","protected":false},"excerpt":{"rendered":"<p>Chemical composition analysis and preliminary exploration of the mechanism of promoting melanin production in the alcohol extract of Fructus Psorale by UPLC-Q-TOF-MS Vitiligo is a common clinical localized depigmentation skin disease, with a prevalence rate of about 0.5%~2% worldwide. It is easy to diagnose and difficult to treat, with a high incidence rate and a [&hellip;]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Chemical composition analysis and preliminary exploration of the mechanism of promoting melanin production in the alcohol extract of Fructus Psorale by UPLC-Q-TOF-MS - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/es\/uplc-q-tof-ms-extraction-of-fructus-psorale\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Chemical composition analysis and preliminary exploration of the mechanism of promoting melanin production in the alcohol extract of Fructus Psorale by UPLC-Q-TOF-MS - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Chemical composition analysis and preliminary exploration of the mechanism of promoting melanin production in the alcohol extract of Fructus Psorale by UPLC-Q-TOF-MS Vitiligo is a common clinical localized depigmentation skin disease, with a prevalence rate of about 0.5%~2% worldwide. 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