科学（20220805出版）一周论文导读

　　编译 | 未玖
　　Science , 5 AUG 2022, VOL 377, ISSUE 6606
　　《科学》 2022年8月5日，第377卷，6606期
　　物理学 Physics
　　Observation of a continuous time crystal
　　连续时间晶体的首次观察
　　作者：：PHATTHAMON KONGKHAMBUT, JIM SKULTE, LUDWIG MATHEY, JAYSON G. COSME, ANDREAS HEMMERICH, AND HANS KESSLE
　　链接：
　　https://www.science.org/doi/10.1126/science.abo3382
　　摘要：
　　时间晶体分为离散时间晶体或连续时间晶体，这取决于其是否自发打破离散时间平移对称性或连续时间平移对称性。虽然离散时间晶体已在周期驱动系统中进行了广泛研究，但连续时间晶体的实验实现仍悬而未决。
　　研究组报道了在连续泵浦的耗散原子腔系统中观察到一个极限循环相位，其特征是内腔光子数中的涌现振荡。振荡相位对于不同的实现是随机的，因此，这种动态多体状态自发打破了连续时间平移对称性。
　　此外，观测到的极限循环对时间扰动具有鲁棒性，因此证明了连续时间晶体的实现。
　　Abstract：
　　Time crystals are classified as discrete or continuous depending on whether they spontaneously break discrete or continuous time translation symmetry. Although discrete time crystals have been extensively studied in periodically driven systems, the experimental realization of a continuous time crystal is still pending. We report the observation of a limit cycle phase in a continuously pumped dissipative atom-cavity system that is characterized by emergent oscillations in the intracavity photon number. The phase of the oscillation was found to be random for different realizations, and hence, this dynamical many-body state breaks continuous time translation symmetry spontaneously. Furthermore, the observed limit cycles are robust against temporal perturbations and therefore demonstrate the realization of a continuous time crystal.
　　材料科学 Materials Science
　　Synchronous assembly of chiral skeletal single-crystalline microvessels
　　手性骨架单晶微容器的同步组装
　　作者：OSAMU OKI, HIROSHI YAMAGISHI, YASUHIRO MORISAKI, RYO INOUE, KANA OGAWA, NANAMI MIKI, ET AL.
　　链接：
　　https://www.science.org/doi/10.1126/science.abm9596
　　摘要：
　　骨架或凹型多面体晶体在各种合成过程和自然环境中普遍存在。然而，由于它们具有高动力学生长特性，其形态、大小和取向很难控制。
　　研究组报道了一种从平面手性双层分子实现同步、单轴和分步生长微米尺度骨架单晶的方法。在将加热的乙醇溶液滴注到石英衬底上后，分子在衬底的宽广面积内单轴同步地自发组装成直立的容器形单晶，具有小尺寸的多分散性。
　　晶体边缘即使在消耗分子后仍然活跃，且通过连续分子增加恢复立体选择性生长。生成的形态可包装为多环芳烃类的微结构，并表现为一个微观容器。
　　Abstract：
　　Skeletal or concave polyhedral crystals appear in a variety of synthetic processes and natural environments. However, their morphology, size, and orientation are difficult to control because of their highly kinetic growth character. We report a methodology to achieve synchronous, uniaxial, and stepwise growth of micrometer-scale skeletal single crystals from planar-chiral double-decker molecules. Upon drop-casting of a heated ethanol solution onto a quartz substrate, the molecules spontaneously assemble into standing vessel-shaped single crystals uniaxially and synchronously over the wide area of the substrate, with small size polydispersity. The crystal edge is active even after consumption of the molecules and resumes stereoselective growth with successive feeding. The resultant morphology can be packed into polycyclic aromatic hydrocarbon–like microarchitectures and behaves as a microscopic container.
　　化学 Chemistry
　　Carbene reactivity from alkyl and aryl aldehydes
　　烷基和芳基醛的卡宾反应性
　　作者：LUMIN ZHANG, BETHANY M. DEMUYNCK, ALYSON N. PANEQUE, JOY E. RUTHERFORD, AND DAVID A. NAGIB
　　链接：
　　https://www.science.org/doi/10.1126/science.abo6443
　　摘要：
　　卡宾是高度赋能的活性中间体，有助于促进各种各样难以实现的化学反应，包括形成小环和插入到强σ键。为了获得这种有价值的反应性，通常使用具有高熵或高焓驱动力的试剂，包括爆炸性（重氮）或不稳定（偕二卤）化合物。
　　研究组报道了常见的醛很容易（通过稳定的α-酰氧基卤化物中间体）转化为电子多样性（供体或中性）卡宾，以促进>10种的反应类别。该策略使烷基、芳基和甲酰基醛的不稳定卡宾通过锌类卡宾发生安全反应。
　　地球上丰富的金属盐[氯化铁（II）（FeCl2）、氯化钴（II）（CoCl2）、氯化铜（I）（CuCl）]是这些化学选择性卡宾加成至σ和π键的有效催化剂。
　　Abstract：
　　Carbenes are highly enabling reactive intermediates that facilitate a perse range of otherwise inaccessible chemistry, including small-ring formation and insertion into strong σ bonds. To access such valuable reactivity, reagents with high entropic or enthalpic driving forces are often used, including explosive (diazo) or unstable (gem-dihalo) compounds. Here, we report that common aldehydes are readily converted (via stable α-acyloxy halide intermediates) to electronically perse (donor or neutral) carbenes to facilitate >10 reaction classes. This strategy enables safe reactivity of nonstabilized carbenes from alkyl, aryl, and formyl aldehydes via zinc carbenoids. Earth-abundant metal salts [iron(II) chloride (FeCl2), cobalt(II) chloride (CoCl2), copper(I) chloride (CuCl)] are effective catalysts for these chemoselective carbene additions to σ and π bonds.
　　地球科学 Earth Science
　　Changes in North Atlantic deep-water oxygenation across the Middle Pleistocene Transition
　　中更新世过渡期北大西洋深水氧合的变化
　　作者：NICOLA C. THOMAS, HAROLD J. BRADBURY, AND DAVID A. HODELL
　　链接：
　　https://www.science.org/doi/10.1126/science.abj7761
　　摘要：
　　海洋深水氧浓度和大气二氧化碳（pCO2）浓度通过有机碳再矿化和作为溶解无机碳储存在深海中而内在联系在一起。
　　研究组利用表栖和内栖底栖有孔虫物种之间的碳同位素梯度作为古氧的替代，对过去150万年来北大西洋深海氧浓度的相对变化进行了高分辨率重建。
　　他们报道了约96万至90万年前冰川大西洋深水氧合作用的显著减少（>40微摩尔/千克），这与大陆冰量增加和海洋温盐环流的重大变化相吻合。
　　古氧结果支持了一种假设，即在中更新世过渡期，深水氧浓度降低，呼吸碳储存增加，冰川pCO2减少。
　　Abstract：
　　The oxygen concentrations of oceanic deep-water and atmospheric carbon dioxide (pCO2) are intrinsically linked through organic carbon remineralization and storage as dissolved inorganic carbon in the deep sea. We present a high-resolution reconstruction of relative changes in oxygen concentration in the deep North Atlantic for the past 1.5 million years using the carbon isotope gradient between epifaunal and infaunal benthic foraminifera species as a proxy for paleo-oxygen. We report a significant (>40 micromole per kilogram) reduction in glacial Atlantic deep-water oxygenation at ~960 thousand to 900 thousand years ago that coincided with increased continental ice volume and a major change in ocean thermohaline circulation. Paleo-oxygen results support a scenario of decreasing deep-water oxygen concentrations, increased respired carbon storage, and a reduction in glacial pCO2 across the Middle Pleistocene Transition.
　　医学 Medicine
　　Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies
　　心肌病中致病性变异损害细胞组成和单细胞转录
　　作者：DANIEL REICHART, ERIC L. LINDBERG, HENRIKE MAATZ, ANTONIO M. A. MIRANDA, ANISSA VIVEIROS, NIKOLAY SHVETSOV, ET AL.
　　链接：
　　https://www.science.org/doi/10.1126/science.abo1984
　　摘要：
　　导致扩张型心肌病（DCM）和心律失常性心肌病（ACM）的致病基因变异通过未知机制引发心力衰竭发展的高风险。
　　使用单核RNA测序，研究组对18个对照和61个伴DCM和ACM基因致病性变异或特发性疾病的衰竭、非缺血性人类心脏的88万个核转录组进行了表征。他们对心室细胞谱系和转录状态进行了基因型分层分析。
　　获得的DCM和ACM心室细胞图谱显示了不同的右心室和左心室反应，突出了基因型相关通路、细胞间相互作用和单细胞分辨率下的差异基因表达。
　　总之，这些数据阐明了人类心力衰竭的共同和独特的细胞和分子结构，并提出了候选治疗靶点。
　　Abstract：
　　Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.
　　公共卫生 Public Health
　　Mosaic RBD nanoparticles protect against challenge by perse sarbecoviruses in animal models
　　马赛克RBD纳米颗粒可在动物模型中抵御多种沙贝病毒的攻击
　　作者：ALEXANDER A. COHEN, NEELTJE VAN DOREMALEN, ALLISON J. GREANEY, HANNE ANDERSEN, ANKUR SHARMA, TYLER N. STARR, ET AL.
　　链接：
　　https://www.science.org/doi/10.1126/science.abq0839
　　摘要：
　　为了对抗未来威胁全球健康的SARS-CoV-2变异株和SARS样β-冠状病毒（沙贝病毒）外溢，研究组设计了马赛克纳米颗粒，其呈现随机排列的沙贝病毒尖峰受体结合域（RBD），以诱导针对保守且相对封闭（而非可变、免疫显性和暴露）表位的抗体。
　　研究组比较了小鼠和猕猴中由马赛克-8（SARS-CoV-2和七种动物沙贝病毒）和同型（仅SARS-CoV-2）RBD纳米颗粒诱导的免疫反应，并观察到马赛克-8对错配（非纳米颗粒）毒株（包括SARS-CoV和动物沙贝病毒）诱导的反应更强。
　　马赛克-8免疫对SARS-CoV-2变异株（包括奥密克戎）具有同等的中和作用，并能抵御SARS-CoV-2和SARS-CoV攻击，而同型SARS-CoV-2免疫仅能抵御SARS-CoV-2攻击。表位图谱显示马赛克-8免疫后保守表位的靶向性增加。
　　总之，这些结果表明马赛克-8 RBD纳米颗粒可以防止SARS-CoV-2变异株和未来的沙贝病毒溢出。
　　Abstract：
　　To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.