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《Molecular therapy》2022,30(8):2856-2867
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By means of the ultrasonic surface impact (amplitude of 30 μm, strike number of 48,000 times/mm2), nanograins have been achieved in the surfaces of both Ti6Al4V(TC4) and Ti3Zr2Sn3Mo25Nb(TLM) titanium alloys, mainly because of the dislocation motion. Many mechanical properties are improved, such as hardness, residual stress, and roughness. The rotating–bending fatigue limits of TC4 and TLM subjected to ultrasonic impact are improved by 13.1% and 23.7%, separately. Because of the bending fatigue behavior, which is sensitive to the surface condition, cracks usually initiate from the surface defects under high stress amplitude. By means of an ultrasonic impact tip with the size of 8 mm, most of the inner cracks present at the zone with a depth range of 100~250 μm in the high life region. The inner crack core to TC4 usually appears as a deformed long and narrow α-phase, while the cracks in TLM specimens prefer to initiate at the triple grain boundary junctions. This zone crosses the grain refined layer and the deformed coarse grain layer. With the gradient change of elastic parameters, the model shows an increase of normal stress at this zone. Combined with the loss of plasticity and toughness, it is easy to understand these fatigue behaviors.  相似文献   
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The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti-apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra-terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti-apoptotic targets regulated by NF-kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro-apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I-BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3-only protein, BIM, and downregulated anti-apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT-199 or ABT-263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I-BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance.  相似文献   
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Body art has become common and mainstream. Tattoos and body piercings represent highly individual expressions of identity and personal values. Health care services are enhanced when clinicians understand the anatomy and physiology, common discomforts, and real but rare serious risks of body modification and are prepared to provide compassionate support for individuals’ choices. Special consideration must be given to the needs of childbearing women. By opening channels of communication, clinicians can engage with clients in shared decision making to help those who possess or desire body art take steps to reduce the risk of adverse effects and obtain prompt and effective medical care when problems arise. Through respectful discussion of existing body art, the therapeutic relationship is strengthened, and greater insight into an individual’s health needs may be achieved.  相似文献   
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家兔静注人血清白蛋白修饰的尿激酶(MUK)和天然尿激酶(NUK)40000IU后,MUK 的体内过程符合零级速率过程,NUK 则符合一级速率过程,血纤溶活性 MUK 持续100min,而 NUK 仅20~25min。在“功能性”去除肝肾的家兔,NUK 血浓度半衰期延长3~4倍,而 MUK 血浓度下降与正常家兔相似。MUK 及 NUK 在去除纤溶抑制物的优球蛋白成份中纤溶活性相似,但在血浆中 NUK 仅存24~35%的纤溶活性,MUK 则保留了64~85%的纤溶活性。提示肝肾的摄取、代谢和消除能力降低及对血浆纤溶抑制物抵抗力增强,是 MUK 血纤溶活性长时间维持高水平的主要原因。  相似文献   
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许多昆虫与寄生在昆虫体表或肠道细胞中的微生物建立了共生关系。臭虫、蚜虫、猎蝽等昆虫可以依靠非最佳食物为生,这一是由于其特殊的生存环境,还由于其体内的共生微生物可以帮助合成和补充其食物中所缺乏的必需营养物质。蚊虫也与其肠道中共生细菌有着密切的联系。成蚊喜产卵于富舍细菌的水体中,水体细菌成为蚊虫幼虫的重要食物来源。伊蚊和库蚊幼虫正常生长发育不可缺少细菌,在无菌条件下饲养,蚊虫或其他媒介昆虫不能正常发育至成熟或不能传播人畜疾病。该文对蚊虫与细菌的共生现象以及其在以下几方面的应用进行综述,(1)蚊虫共生细菌的分离与鉴定,(2)共生细菌的形成与传代,(3)共生细菌在昆虫中的分布,并讨论了经过遗传改造的蚊虫共生细菌对蚊虫防治及控制疟疾等由昆虫传播的疾病的应用前景。  相似文献   
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