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miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer

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Journal of Molecular Cell Biology 2018年第4期10卷 302-315页

作者： Sanhong Liu Zifeng Wang Zukai Liu Shuo Shi Zhaoran Zhang Jiawei Zhang haifan lin Shanghai Institute of Advanced Immunochemical Studies ShanghaiTech University Shanghai China School of Life Science and Technology ShanghaiTech University Shanghai China The Yale Stem Cell Center and Department of Cell Biology Yale University School of Medicine New Haven CT USA

Triple-negative breast cancer （TNBC）, characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targeted therapies. Wnt/β-catenin signaling is hyperactivated in TNBC, which promotes the progression of TNBC. However, the molecular mechanism of Wnt/β-catenin activation in TNBC remains unknown. Here, we report the drastic overexpression of miR-221/222 in all of four TNBC cell lines and TNBC primary tumor samples from patients. Furthermore, we demonstrate by both ex vivo and xenograft experiments that inhibiting miR-221/222 expression in a TNBC cell line （MDA-MB-231） suppresses its proliferation, viability, epithelial-to-mesenchymal transition, and migration; whereas expressing miR-221/222 in a non-TNBC line （MCF7） promotes all of the above cancer properties. miR-221/222 achieve so by directly repressing multiple negative regulators of the Wnt/β-catenin signaling pathway, including WIF1, SFRP2, DKK2, and AXIN2, to activate the pathway. Notably, the level of miR-221/222 expression is inversely correlated whereas that of WIF1, DKK2, SFRP2, and AXIN2 expression is positively correlated with the patient survival. Last, we show that anti-miR-221/222 significantly increases apoptotic cells with tamoxifen/Wnt3a treatment but not with cyclophosphamide/Wnt3a treatment. These results demonstrate that miR-221/222 activate the Wnt/β-catenin signaling to promote the aggressiveness and TNBC properties of breast cancers, and thus reveal a new prospect for TNBC treatment.

关键词： miR-221/222 Wnt/β-catenin triple-negative breast cancer

The ever-expanding RNA world

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National Science Review 2014年第2期1卷 182-182页

作者： haifan lin Yale Stem Cell Center Yale University Guest Editor of Special Topic & Editorial Board Member of NSR

RNA is perhaps the most mystical molecule in *** a single molecule endowed with both informational and catalytic capacities,it was proposed by Alexander Rich 52 years ago to be the irst molecule that self-replicated at the origin of life,to be taken over by DNA only *** this‘RNA world’(vividly phrased by Walter Gilbert in 1986)remains an enticing yet unproven hypothesis,the crucial roles of messenger RNAs(m RNAs),transfer RNAs(t RNAs),and ribosomal RNAs(r RNAs)in transcribing and translating genetic information into proteins

关键词： RNA The ever-expanding RNA world

The role of the hedgehog/patched signaling pathway in epithelial stem cell proliferation: from fly to human

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Cell Research 1998年第1期8卷 15-21页

作者： PARISI MICHAEL J haifan lin (Depariment of Cell Biology, Box 3709, Duke University,Medical Center Durham, N.C. 27710, USA) Department of Cell Biology USA

The hedgehog-patched (hh-ptc) intercellular signaling pathway has recently been shown to control the proliferation of epithelial stem cells in both Drosophila and vertebrates. Mutant and ectopic expression analyses in Drosophila suggest that the HH protein diffuses from the signaling cells to promote the proliferation of nearby ovarian somatic stem cells by antagonizing the suppression of its receptor PTC towards the CI transcription factor in the stem cells. Consequently, the transcription of CIdependent genes leads to stem cell proliferation. This regulatory pathway appears to function also in vertebrates,where defects in ptc cause basal cell carcinoma, tumors of epidermal stem cell origin. Basal cell carcinoma can also be induced by ectopic expression of Sonic hedgehog (shh) or Glil, the vertebrate homolog of ci. These studies suggest the conservation of the hh signaling pathway in controlling epithelial stem cell divisions among different organisms.

关键词： Stem cell epithelia hedgehog patched Drosophila vertebrate

TC4钛合金激光拼焊接头显微组织及力学性能分析

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焊接学报 2009年第2期30卷 103-106页

作者：程东海黄继华林海凡张华北京科技大学材料科学与工程学院北京100083

文中系统分析了TC4钛合金激光拼焊接头的显微组织与力学性能.结果表明,TC4钛合金激光焊缝组织为粗大的柱状晶,晶粒内部是针状马氏体交织成的网篮状组织;热影响区组织为α+β+针状α′组织,且分布不均匀,靠近熔合线的区域晶粒更粗大,针... 详细信息

文中系统分析了TC4钛合金激光拼焊接头的显微组织与力学性能.结果表明,TC4钛合金激光焊缝组织为粗大的柱状晶,晶粒内部是针状马氏体交织成的网篮状组织;热影响区组织为α+β+针状α′组织,且分布不均匀,靠近熔合线的区域晶粒更粗大,针状马氏体数量更多分布更密集.0.8mm厚TC4钛合金薄板拼焊工艺参数为焊接功率1100～1300W,焊接速度1.5～3.0m/min.焊缝力学性能优良,拉伸试样均断裂于离焊缝中心较远的母材上,母材和焊缝断口形貌都显示韧窝断口特征,且焊缝断口韧窝相对更较小.

关键词： TC4钛合金激光焊接显微组织力学性能

从财经角度解读政府在基本公共卫生服务中的责任

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中国卫生法制 2016年第1期24卷 31-34页

作者：林海帆广西壮族自治区柳州市疾病预防控制中心广西柳州市545007

为城乡居民免费提供基本公共卫生服务,是我国政府"坚持以人为本、落实预防为主"卫生工作方针的具体体现,也是我国公共卫生领域的一项长期的、基础性的制度安排。政府作为基本公共卫生服务项目的管理者,正确履职是基本公共卫生服务成功... 详细信息

为城乡居民免费提供基本公共卫生服务,是我国政府"坚持以人为本、落实预防为主"卫生工作方针的具体体现,也是我国公共卫生领域的一项长期的、基础性的制度安排。政府作为基本公共卫生服务项目的管理者,正确履职是基本公共卫生服务成功贯彻实施的关键。本文解析了政府参与基本公共卫生服务项目管理的法律依据、经济依据,并尝试从财经的角度探讨政府在基本公共卫生服务领域中该如何正确履职。

关键词：基本公共卫生服务政府履职财经解读

TC4钛合金激光焊接接头高温热处理后的显微组织研究

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热加工工艺 2011年第1期40卷 154-156页

作者：林海凡李敬王盛胡忠文中国联合工程公司工业二院浙江杭州310022

研究了TC4钛合金激光焊接接头经高温热处理后的显微组织,结果表明:由于在TC4合金相变点附近温度进行热处理能极大提高其合金元素的扩散速率,激光焊接接头中的马氏体α′随热处理时间的延长而更粗大,且分布更杂乱;热处理前后焊缝截面显... 详细信息

研究了TC4钛合金激光焊接接头经高温热处理后的显微组织,结果表明:由于在TC4合金相变点附近温度进行热处理能极大提高其合金元素的扩散速率,激光焊接接头中的马氏体α′随热处理时间的延长而更粗大,且分布更杂乱;热处理前后焊缝截面显微硬度均自焊缝中心向热影响区逐渐降低,热影响区显微硬度低于母材。与原始接头显微硬度值相比,经历高温热处理后接头的显微硬度降低约60HV左右。

关键词：激光焊 TC4钛合金高温热处理

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PIWI/piRNA在癌症中的功能和机制

自然杂志 2021年第5期43卷 313-322页

作者：石硕王晨林海帆上海科技大学免疫化学研究所上海201210 耶鲁大学医学院干细胞中心和细胞生物学系纽黑文康涅狄格州06510美国

PIWI蛋白是PAZ/PIWI结构域家族亚家族之一的RNA结合蛋白。PIWI蛋白通常与称为"PIWI相互作用的小型非编码RNA"(piRNA)相结合形成功能复合体来发挥作用。PIWI-piRNA通路因其在抑制转座子和生殖系发育方面的重要作用而闻名。除了在生殖系... 详细信息

PIWI蛋白是PAZ/PIWI结构域家族亚家族之一的RNA结合蛋白。PIWI蛋白通常与称为"PIWI相互作用的小型非编码RNA"(piRNA)相结合形成功能复合体来发挥作用。PIWI-piRNA通路因其在抑制转座子和生殖系发育方面的重要作用而闻名。除了在生殖系中的卓越作用,PIWI蛋白也因其通常只在生殖细胞中表达而在正常体细胞组织中几乎不表达,但是PIWI蛋白在癌变的肿瘤组织里却异常表达,使其有望成为精准靶向治疗的绝佳靶点而在近年来备受关注。在这篇综述里,我们首先回顾PIWI蛋白如何与piRNA一起多面地调控生殖系中多种不同类型的RNA的表达,然后总结PIWI蛋白和piRNA在不同类型的癌症中的表达和功能,探讨近年来关于PIWI和piRNA在癌症研究中的局限性和可能存在的误区,并对最近冲击传统观念的PIWI在癌细胞中非piRNA依赖的生物学功能和调控机制展开深入的讨论。

关键词： PIWI piRNA 癌症

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乌司他丁治疗重症胰腺炎的效果观察

中国医药科学 2019年第2期9卷 50-52,67页

作者：林海帆叶美玲厦门市海沧医院消化内科福建厦门361000

目的探讨常规药物联合乌司他丁治疗重症胰腺炎的应用效果。方法回顾性分析2015年6月～2017年6月90例重症胰腺炎患者,根据随机数字表法分组。对照组给予单一常规药物治疗(34例),观察组则给予常规药物联合乌司他丁治疗(56例)。其中,根据... 详细信息

目的探讨常规药物联合乌司他丁治疗重症胰腺炎的应用效果。方法回顾性分析2015年6月～2017年6月90例重症胰腺炎患者,根据随机数字表法分组。对照组给予单一常规药物治疗(34例),观察组则给予常规药物联合乌司他丁治疗(56例)。其中,根据乌司他丁剂量分为两组,A组给予乌司他丁10万单位(30例),B组给予40万单位(26例)。比较两组重症胰腺炎控制率,腹痛消失时间、淀粉酶达标时间、总住院时间,干预前后患者血淀粉酶、炎症指标,药物不良反应率。结果观察组重症胰腺炎控制率高于对照组,且B组治疗效果高于A组,P 0.05;干预后观察组血淀粉酶、炎症指标优于对照组,P 0.05。结论常规药物联合乌司他丁治疗重症胰腺炎的应用效果确切,且大剂量乌司他丁可提高效果,可有效改善血气指标和降低炎症水平,改善临床症状,缩短疗程,且无严重不良反应,安全有效,值得推广应用。

关键词：常规药物乌司他汀重症胰腺炎不良反应

Channel pruning on frequency response

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Science China(Information Sciences) 2025年第1期68卷 159-170页

作者： Hang lin Yifan PENG lin BIE Chenggang YAN Xibin ZHAO Yue GAO School of Software Tsinghua University School of Automation Hangzhou Dianzi University

Network pruning has a significant role in reducing network parameters and accelerating the inference time of the network. Some existing methods prune the network based on the frequency of the data, and finally obtain a sub-network with high accuracy. However, according to our experimental analysis, different frequencies of information in the data contribute differently to the accuracy of the model, and using this information directly for pruning without making a selection will lead to incorrect results. We believe that pruning should retain the convolutional kernels in the network that process important information, while those kernels that process unimportant information should be removed. In this paper, we first investigate the meaning of each frequency band information in the spectrum and their contribution to the prediction accuracy of the network,and according to these results, we propose a new pruning method based on frequency response(PFR). Our PFR finds and removes the convolutional kernels in the network that specialize in processing unimportant information, resulting in a compact neural network model. PFR obtains significant experimental results on different datasets, for example, a 56.0% raduction of float points operations(FLOPs) on Res Net-50 and only 0.37% of Top-1 accuracy degradation on the Image Net dataset.

关键词： deep learning model compression filter pruning channel pruning frequency response

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