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CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes

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四川生理科学杂志 2024年第1期46卷 160-160页

作者： Alexis C Komor Department of Chemistry and Chemical Biology Harvard University Cambridge MA 02138 USA Howard Hughes Medical Institute Harvard University Cambridge MA 02138 USA Broad Institute of MIT and Harvard Cambridge MA 02141 USA. Department of Chemistry and Chemical Biology Harvard University Cambridge MA 02138 USA Howard Hughes Medical Institute Harvard University Cambridge MA 02138 USA Broad Institute of MIT and Harvard Cambridge MA 02141 USA. Electronic address: drliu@fas.harvard.edu.

The CRISPR-Cas9 RNA-guided DNA endonuclease has contributed to an explosion of advances in the life sciences that have grown from the ability to edit genomes within living *** this Review,we summarize CRISPR-based tec... 详细信息

关键词： CRISPR Cas9 Genome

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帝国的“蓝色公路”:《水经注》的空间想象

华东师范大学学报（哲学社会科学版） 2024年第1期56卷 38-56,176页

作者：田晓菲美国哈佛大学东亚语言与文明系美国波士顿02138

考察北魏郦道元(?—527)的《水经注》,可以从两个角度出发重构《水经注》的文本生态,以求阐明此巨著之意义与价值。其一将郦道元的作品置于经注传统的语境脉络中,一方面强调注经者所面临的局限,另一方面也指出注疏相对于原始文本的创造... 详细信息

考察北魏郦道元(?—527)的《水经注》,可以从两个角度出发重构《水经注》的文本生态,以求阐明此巨著之意义与价值。其一将郦道元的作品置于经注传统的语境脉络中,一方面强调注经者所面临的局限,另一方面也指出注疏相对于原始文本的创造潜力;其二,让郦道元的著作与同时代的南方山水写作进行对话,强调该著作在空间感知和空间表现方面的独特模式。由此提出,郦道元基于帝国想象,构建了一套由江河组成的基础设施体系,这套江河系统可以被视作以人工运河来佐助自然江河的中古隋唐政体的有力象征。

关键词：郦道元水经注帝国空间感知空间表现山水写作注疏

如何负责任地回应他人痛苦?——对中国缓和医疗的再思考

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协和医学杂志 2024年第1期15卷 7-11页

作者： Eric L.Krakauer 哈佛大学医学院美国马萨诸塞州波士顿MA02138 波士顿总医院缓和医疗与老年医学部美国马萨诸塞州波士顿MA02138

笛卡尔医学模式导致过度医疗已成为全球普遍现象。现代缓和医疗的兴起正是源于对笛卡尔医学模式的反思,其主要目的是缓解重病患者的痛苦,同时关注医学技术本身带来的不必要伤害。本文结合相关病例提出问题,围绕解除痛苦的历史溯源、笛... 详细信息

笛卡尔医学模式导致过度医疗已成为全球普遍现象。现代缓和医疗的兴起正是源于对笛卡尔医学模式的反思,其主要目的是缓解重病患者的痛苦,同时关注医学技术本身带来的不必要伤害。本文结合相关病例提出问题,围绕解除痛苦的历史溯源、笛卡尔医学模式的观点与弊端、维持生命技术的应用与善终等方面展开讨论,启发对中国缓和医疗发展的进一步思考与深刻理解。

关键词：笛卡尔医学模式过度医疗缓和医疗善终

Birth weight,ideal cardiovascular health metrics in adulthood,and incident cardiovascular disease

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Chinese Medical Journal 2024年第10期137卷 1160-1168页

作者： Ying Sun Bin Wang Yuefeng Yu Yuying Wang Xiao Tan Jihui Zhang Lu Qi Yingli Lu Ningjian Wang Department of Endocrinology and Metabolism Institute of Endocrinology and MetabolismShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China School of Public Health Zhejiang UniversityHangzhouZhejiang 310058China Department of Medical Sciences Uppsala UniversityUppsala 75105Sweden Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510370China Department of Epidemiology School of Public Health and Tropical MedicineTulane UniversityNew OrleansLA 70118USA Department of Nutrition Harvard T.H.Chan School of Public HealthBostonMA 02138USA Channing Division of Network Medicine Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02138USA

Background:Prenatal and postnatal factors may have joint effects on cardiovascular health,and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics(ICVHMs)prospectively in adulthood with incident cardiovascular disease(CVD).Methods:In the UK Biobank,227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were *** ICVHMs included smoking,body mass index,physical activity,diet information,total cholesterol,blood pressure,and hemoglobin *** Cox proportional hazards model was used to estimate the hazard ratios(HRs)and 95%confidence intervals(CIs)in men and ***:Over a median follow-up period of 13.0 years(2,831,236 person-years),we documented 17,477 patients with incident *** with participants with birth weights of 2.5-4.0 kg,the HRs(95%CIs)of CVD among those with low birth weights was 1.08(1.00-1.16)in men and 1.23(1.16-1.31)in *** association between having a birth weight<2.5 kg and CVD risk in men was more prominent for those aged<50 years than for those of older age(P for interaction=0.026).Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of *** with birth weights<2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD(HR[95%CI]:3.93[3.01-5.13]in men;4.24[3.33-5.40]in women).The joint effect(HR[95%CI]:1.36[1.17-1.58])could be decomposed into 24.7%(95%CI:15.0%-34.4%)for a lower birth weight,64.7%(95%CI:56.7%-72.6%)for a lower ICVHM score,and 10.6%(95%CI:2.7%-18.6%)for their additive interaction in ***:Birth weight and ICVHMs were jointly related to CVD *** a normal birth weight and ideal ICVHMs may reduce the risk of CVD,and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

关键词： Birth weight Health metrics Cardiovascular disease Adult Stroke Coronary heart disease

Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

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Nano-Micro Letters 2024年第6期16卷 439-457页

作者： Dandan Chu Mengyang Zhao Shisong Rong Wonho Jhe Xiaolu Cai Yi Xiao Wei Zhang Xingchen Geng Zhanrong Li Xingcai Zhang Jingguo Li Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhou 450003People’s Republic of China Department of Ophthalmology Mass Eye and EarMass General BrighamHarvard Medical SchoolBostonMA 02114USA School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA College of Chemistry Zhengzhou UniversityZhengzhou 450001People’s Republic of China

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual *** incidence of DED is gradually increasing with the highfrequency use of electronic *** inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from ***,current therapies merely targeting inflammation show the failure of DED ***,a novel dual-atom nanozymes(DAN)-based eye drops are *** antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic *** in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell ***,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious *** findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

关键词： Dry eye disease DAN Dual-atom nanozyme Vicious cycle NLRP3 inflammasome Nanomedicine

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基于图卷积神经网络的乳腺癌亚型分类研究

生物医学工程学杂志 2024年第1期41卷 121-128页

作者：安义帅刘晓军陈恒玲万桂宏中南民族大学生物医学工程学院武汉430074 哈佛大学麻省总医院皮肤科波士顿02138

恶性肿瘤分子亚型的准确识别是肿瘤患者个体化诊断、个性化治疗以及预后预测的重要支撑。综合性肿瘤基因组数据库的不断完善和深度学习技术的持续突破,推动了计算机辅助肿瘤分类技术的进一步发展。现有的基于基因表达数据的神经网络亚... 详细信息

恶性肿瘤分子亚型的准确识别是肿瘤患者个体化诊断、个性化治疗以及预后预测的重要支撑。综合性肿瘤基因组数据库的不断完善和深度学习技术的持续突破,推动了计算机辅助肿瘤分类技术的进一步发展。现有的基于基因表达数据的神经网络亚型分类方法虽然考虑了分子分型的复杂性,但仍然存在忽略基因内在关联性和协同性的问题。为了解决这一问题,本文提出了一种结合分层注意力机制的多层图卷积神经网络乳腺癌亚型分类模型。该模型基于先验的生物学知识构建乳腺癌患者的基因图表示数据集,训练出一种新的端到端的多分类模型,能够对乳腺癌分子亚型进行智能识别,并且在乳腺癌分子亚型的分类工作上表现出了很好的识别性能。相较于原始的图卷积神经网络以及两个主流的图神经网络分类算法,该模型在7分类任务中的准确率、加权F1分数、加权召回率、加权精确率分别达到了0.8517、0.8235、0.8517、0.7936,在4分类任务中则分别达到了0.9285、0.8949、0.9285、0.8650,具有明显的优势。此外,本文方法相较于最新的乳腺癌亚型分类算法,同样获得了最高的分类准确率。综上,本文所提模型或可作为一种辅助诊断技术为未来乳腺癌亚型的精确分类提供一个可信的选择,奠定计算机辅助肿瘤分类的理论基础。

关键词：乳腺癌深度学习图卷积神经网络亚型分类

Exploring the potential for improving material utilization efficiency to secure lithium supply for China's battery supply chain

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Fundamental Research 2024年第1期4卷 167-177页

作者： Xin Sun Han Hao Yong Geng Zongwei Liu Fuquan Zhao State Key Laboratory of Automotive Safety and Energy Tsinghua UniversityBeijing 100084China Belfer Center for Science and International Affairs Harvard UniversityCambridgeMA 02138United States Tsinghua-Rio Tinto Joint Research Center for Resources Energy and Sustainable Development Tsinghua UniversityBeijing 100084China School of International and Public Affairs Shanghai Jiao Tong UniversityShanghai 200240China

Lithium-ion battery(LIB)is the key technology for climate change *** sustainability of LIB supply chain has caused widespread concern since the material utilization efficiency of LIB supply chain has not been well *** study aims to fill this research gap by conducting a dynamic material flow analysis of lithium in China from 2015 to *** indicate that within the temporal boundary,lithium flow and in-use stock grew significantly in China due to the rapid development of the EV market,with lithium flow in domestic production of basic chemicals increasing by 614%to 100 kt,end-use consumption increasing by 160%to 35 kt,and in-use stock increasing by 62%to 195 *** has been a net importer of lithium,of which cumulative imports and exports were 343 kt and 169 kt,*** addition,103 kt of lithium was converted to inventories or was lost during the processing from 2015 to *** optimizing inventory and processing,developing substitutes for lithium for non-battery applications,and improving lithium recycling,China's net import dependency of lithium could be reduced from 27%-86%to 0%-16%.Our study demonstrates that it is urgent to improve material utilization efficiency so that the lithium resource supply can be secured.

关键词： Lithium Lithium-ion battery Critical material Supply chain Material flow analysis

Infanticide in golden snub-nosed monkeys with multilevel society

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Current Zoology 2024年第2期70卷 273-275页

作者： Wei Li Shixuan Dong Fei Niu Nianlong Li Ziyi Su Chengliang Wang Kang Huang Haitao Zhao Ruliang Pan Pei Zhang Baoguo Li Shaanxi Key Laboratory for Animal Conservation College of Life SciencesNorthwest UniversityXi'an 710069China Shaanxi Key Laboratory for Animal Conservation Shaanxi Institute of ZoologyXi'an 710032China School of Anatomy Physiology and Human BiologyThe University of Western AustraliaWestern Australia 6907Australia International Centre of Biodiversity and Primate Conservation Dali UniversityDali 671003China Division of ExpressiveTherapies.Lesley University.Cambridae.MA02138.USA

Infanticide,killing unweaned offspring in conspecifics,occurs widely among mammals,such as rodents,ungulates,and carnivores,especially in primates(Lukas and Huchard 2014).Such scenarios are often triggered by intruders that have replaced the former dominant males in nonhuman primates(Borries 1997).It has widely been viewed that infanticide is one of the solutions of sexually driven evolutionary selection:males kill infants to end lactational amenorrhea of the victim's mothers,forcing them to return to estrus and providing infanticidal males with the opportunities to sire their new offspring(Hrdy 1979).There is a broad spectrum regarding the patterns and mechanisms causing such events,referring to alternative breeding behaviors and mating systems-monogamy,polyandry,polygyny,and promiscuity(Qi et al.2020).

关键词： primates breeding mother

Planar matrices and arrays of Feynman diagrams:poles for higher k

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Communications in Theoretical Physics 2024年第4期76卷 1-13页

作者： Alfredo Guevara Yong Zhang Perimeter Institute for Theoretical Physics WaterlooON N2L 2Y5Canada Department of Physics&Astronomy University of WaterlooWaterlooON N2L 3G1Canada Society of Fellows Harvard UniversityCambridgeMA 02138United States of America CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesNo.19A Yuquan RoadBejing 100049China

Planar arrays of tree diagrams were introduced as a generalization of Feynman diagrams that enable the computation of biadjoint amplitudes m_(n)(^(k))for k>*** this follow-up work,we investigate the poles of m_(n)(^(k))from the perspective of such *** general k,we characterize the underlying polytope as a Flag Complex and propose a computation of the amplitude-based solely on the knowledge of the poles,whose number is drastically less than the number of the full *** an example,we first provide all the poles for the cases(k,n)=(3,7),(3,8),(3,9),(3,10),(4,8)and(4,9)in terms of their planar arrays of degenerate Feynman *** then implement simple compatibility criteria together with an addition operation between arrays and recover the full collections/arrays for such *** the way,we implement hard and soft kinematical limits,which provide a map between the poles in kinematic space and their combinatoric *** use the operation to give a proof of a previously conjectured combinatorial duality for arrays in(k,n)and(n-k,n).We also outline the relation to boundary maps of the hypersimplex Δ_(k,n) and rays in the tropical Grassmannian Tr(k,n).

关键词： Feynman diagrams biadjoint amplitudes poles