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DK Eyewitness Top 10 Mallorca

為了解決Discovery Plus的問題，作者Dk Eyewitness 這樣論述：

Mallorca has it all: a spectacular coastline and gorgeous beaches, a proliferation of ancient sites and castles, a stylish capital, and an arresting mountainous interior peppered with picturesque villages, hiking trails and abundant wildlife.Make the most of your trip to this beautiful island wit

h DK Eyewitness Top 10. Planning is a breeze with our simple lists of ten, covering the very best that Mallorca has to offer and ensuring that you don’t miss a thing. Best of all, the pocket-friendly format is light and easily portable; the perfect companion while out and about. Our updated 2022 tra

vel guide brings Mallorca to life. DK Eyewitness Top 10 Mallorca is your ticket to the trip of a lifetime. Inside DK Eyewitness Mallorca you will find: - Up-to-date information with insider tips and advice for staying safe- Top 10 lists of Mallorca’s must-sees, including detailed descriptions of La

Seu, Castell de Bellver, Fundació Pilar i Joan Miró, La Granja, Valldemossa, Sóller Valley, Monestir de Nostra Senyora de Lluc, Península de Formentor, Alcúdia and Coves del Drac- Mallorca’s most interesting areas, with the best places for shopping, going out, andsightseeing- Inspiration for differ

ent things to enjoy during your trip - including walks and drives, children’s activities and things to do for free- Seven easy-to-follow itineraries, perfect for a day-trip, a weekend, or a week- A laminated pull-out map of Mallorca, plus five color area maps About DK Eyewitness: At DK Eyewitness,

we believe in the power of discovery. We make it easy for you to explore your dream destinations. DK Eyewitness travel guides have been helping travellers to make the most of their breaks since 1993. Filled with expert advice, striking photography and detailed illustrations, our highly visual DK Eye

witness guides will get you closer to your next adventure. We publish guides to more than 200 destinations, from pocket-sized city guides to comprehensive country guides. Named Top Guidebook Series at the 2020 Wanderlust Reader Travel Awards, we know that wherever you go next, your DK Eyewitness tra

vel guides are the perfect companion.

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透過基於基因本體之整合性分析識別卵巢上皮性腫瘤發病機轉的失調基因功能體

為了解決Discovery Plus的問題，作者蘇國銘 這樣論述：

上皮性卵巢癌（EOCs）在晚期或復發的婦科惡性腫瘤中常是致命的和頑固的，其中漿液性佔絕大多數而卵巢清亮細胞癌（OCCC）是僅次於漿液性上皮性卵巢癌的第二常見的上皮性卵巢癌。即便經過腫瘤減積手術後加上化學藥物治療後仍有不少的患者有著較差的預後或是復發，故整體而言，對於卵巢癌的治療仍是一個相當大的挑戰。此外，邊緣性卵巢腫瘤(BOT)，包括漿液性 BOT與黏液性BOT，是屬於介於良性與惡性之間的卵巢疾病，雖然大部分的預後不差但是也有與卵巢癌不同的組織病理學特性。本研究使用以基因本體(GO)為基礎加上機器學習輔助運算的綜合分析去探討卵巢清亮細胞癌以及漿液性卵巢腫瘤包含漿液性邊緣性卵巢腫瘤與漿液性卵巢

癌的GEO資料庫中失調的基因體、功能途徑，藉以去識別重要的差異表達基因(DEG)。首先在卵巢清亮細胞癌的整合性分析中，發現無論是早期抑或是晚期，與免疫功能相關尤其是活化補體系統的替代途徑的功能失調在腫瘤發生佔有相當重要的關聯性，而補體C3與補體C5也影響了疾病無惡化存活期(Progression-free survival, PFS)和整體存活率(Overall survival, OS)且免疫染色結果是有意義的。而在漿液性卵巢腫瘤的分析中發現，SRC基因和功能失調的芳烴受體(AHR)結合路徑(Binding pathway)確實影響PFS和OS，而且與上皮細胞間質轉化(Epithelial-

mesenchymal transition, EMT)相關的鋅指蛋白SNAI2在腫瘤發生過程中有重要角色，並顯示出從漿液性 BOT 到卵巢癌有著逐漸上升的影響趨勢。未來，標靶治療可以專注於這些有意義的生物標誌並結合精確監測，以提高治療效果和患者存活率。

DK Eyewitness Top 10 San Diego

為了解決Discovery Plus的問題，作者Dk Eyewitness 這樣論述：

Home to the lively Gaslamp Quarter, world-famous Balboa Park, and an eclectic collection of art galleries and museums, San Diego is jam-packed with must-visit spots and surrounded by natural beauty.Make the most of your trip to this laid-back city with DK Eyewitness Top 10. Planning is a breeze w

ith our simple lists of ten, covering the very best that San Diego has to offer and ensuring that you don’t miss a thing. Best of all, the pocket-friendly format is light and easily portable; the perfect companion while out and about. DK Eyewitness Top 10 San Diego is your ticket to the trip of a li

fetime. Inside DK Eyewitness Top 10 San Diego you will find: - Top 10 lists of San Diego’s must-sees, including the Gaslamp Quarter, Balboa Park, Coronado, and La Jolla- San Diego’s most interesting areas, with the best places for sightseeing, food and drink, and shopping- Themed lists, including

the best museums and art galleries, beaches, nightlife, performing arts venues, and much more- Easy-to-follow itineraries, perfect for a day trip, a weekend, or a week- A laminated pull-out map of San Diego, plus four full-color area maps Looking to explore more of California? Try our DK Eyewitnes

s California.About DK Eyewitness: At DK Eyewitness, we believe in the power of discovery. We make it easy for you to explore your dream destinations. DK Eyewitness travel guides have been helping travellers to make the most of their breaks since 1993. DK Eyewitness travel guides have been helping tr

avelers to make the most of their breaks since 1993. Filled with expert advice, striking photography and detailed illustrations, our highly visual DK Eyewitness guides will get you closer to your next adventure. We publish guides to more than 200 destinations, from pocket-sized city guides to compre

hensive country guides. Named Top Guidebook Series at the 2020 Wanderlust Reader Travel Awards, we know that wherever you go next, your DK Eyewitness travel guides are the perfect companion.

Pharmacoinformatic analysis and preclinical evaluation of a novel first-in class onco-immunotherapeutic small molecule for the treatment of non-small-cell lung cancer (NSCLC)

為了解決Discovery Plus的問題，作者Bashir Lawal 這樣論述：

Lung cancer poses a serious threat to human health and has recently been tagged the most common malignant disease with the highest incidence and mortality rate. Although epidermal growth factor (EGFR)-tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of advanced non-small

cell lung cancer (NSCLC) patients with EGFR mutations often develop resistance to these drugs. There is therefore a need to identify new drug candidates with multitarget potential for treating NSCLC. We hereby provide preclinical evidence of the therapeutic efficacy of NLOC-015A a multitarget first-

in class small-molecule inhibitor of EGFR/mitogen-activated protein (MAP) kinase kinase 1 (MAP2K1)/mammalian target of rapamycin (mTOR)/yes-associated protein 1 (YAP1) for the treatment NSCLC. Our multi-omics analysis of clinical data from cohorts of NSCLC revealed that dysregulation of EGFR/MEK1/mT

OR/YAP1 signaling pathways was associated with the progression, therapeutic resistance, immune-invasive phenotypes, and worse prognoses of NSCLC patients. Analysis of single-cell RNA sequencing datasets revealed that MAP2K1, mTOR, YAP1 and EGFR were predominantly located on monocytes/macrophages, Tr

eg and exhaustive CD8 T cell, and are involved in M2 polarization within the TME of patients with primary and metastatic NSCLC which further implied gene’s role in remodeling the tumor immune microenvironment. A molecular-docking analysis revealed that NLOC-015A bound to YAP1, EGFR, MEK1, and mTOR w

ith strong binding efficacies ranging –8.4 to –9.50 kcal/mol. Interestingly, compared to osimertinib, NLOC-015 bound with higher efficacy to the tyrosine kinase (TK) domains of both T790M and T790M/C797S mutant-bearing EGFR. Our in vitro studies revealed that NLOC-015A inhibited the proliferation an

d oncogenic properties of NSCLC with concomitant downregulation of EGFR/MAP2K1/mTOR/YAP1 signaling networks. In addition, the stemness inhibitory effect of NLOC0-15A was accompanied by decreased expression levels of aldehyde dehydrogenase (ALDH), c-Myc, and SOX2 in both H1975 and H1299 cell lines. F

urthermore, NLOC-015A suppressed the tumor burden and increased the body weight and survival of H1975 xenograft-bearing mice. Interestingly, NLOC-015A synergistically enhanced the anti-NSCLC activities of osimertinib both in vitro and in vivo models. We, therefore, suggest that NLOC-015A might repre

sent a new candidate for treating NSCLC via acting as a multitarget inhibitor of EGFR, mTOR/NF-κB, YAP1, MEK1 in NSCLC.