编译|冯维维

Science, VOLUME 385, ISSUE 6709, 9 AUG 2024

《科学》,第385卷，6709期，2024年8月9日

生命科学Life Science 

Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates

在非人类灵长类动物中，有条件地复制艾滋病病毒基因工程缺失以减少疾病

▲ 作者：FATHIMA N. NAGOOR PITCHAI, ELIZABETH J. TANNER, NEHA KHETAN, GUSTAVO VASEN, CLARA LEVREL, ARJUN J. KUMAR, SHILPI PANDEY, TRACY ORDONEZ, PHILIP BARNETTE, AND LEOR S. WEINBERGER

▲链接：

https://www.science.org/doi/10.1126/science.adn5866

▲摘要：

在复制过程中，RNA病毒经常产生有缺陷的颗粒，这些颗粒寄生并干扰完整病毒的复制和包装。这些有缺陷的颗粒也可能刺激宿主的免疫反应。Pitchai等人开发了一种连续培养方法，其中将缺失克隆到艾滋病病毒（HIV）中以产生治疗性干扰粒子（TIPs）。

首先，他们发现具有转导能力的病毒样颗粒是有条件地在完整的HIV和减少的HIV载量的转运中产生的。测序没有检测到随后的大缺失或重排。然后在捐赠的HIV感染的人类细胞、人源化小鼠和感染HIV的非人灵长类动物中注射一剂量的工程化TIPS进行测试。这些实验证实了血清转化、抑制HIV复制和TIP持续至少30周。

▲ Abstract：

During replication, RNA viruses frequently generate defective particles that parasitize and interfere with the replication and packaging of intact virus. Such defective particles may also stimulate host immune responses. Pitchai et al. developed a continuous culture method in which deletions were cloned into HIV to generate therapeutic interfering particles (TIPs). First, they showed that transduction-competent viral-like particles were produced conditionally in trans with intact HIV and reduced HIV load. Sequencing did not detect subsequent large deletions or rearrangements. Engineered TIPS were then tested with one injected dose in donated HIV-infected human cells, humanized mice, and nonhuman primates infected with HIV. These experiments verified seroconversion, suppression of HIV replication, and TIP persistence for at least 30 weeks.

Brain region–specific action of ketamine as a rapid antidepressant

氯胺酮作为快速抗抑郁药的脑区域特异性作用

▲ 作者：MIN CHEN, SHUANGSHUANG MA, HANXIAO LIU, YIYAN DONG, JINGXIANG TANG, ZHEYI NI, YI TAN, CHENCHI DUAN, HUI LI, AND HAILAN HU

▲链接：

https://www.science.org/doi/10.1126/science.ado7010

▲摘要：

氯胺酮抗抑郁作用的发现是心理健康治疗的重要进展。然而，其潜在机制仍未完全了解。Chen等人发现，在类似抑郁的动物中，氯胺酮选择性地抑制了侧缰核神经元的NMDA受体反应，但对海马锥体神经元没有作用。

研究者发现，与海马神经元相比，侧缰核神经元在抑郁状态下具有更高的内在活性，并且突触外的NMDA受体库要小得多。通过增加海马神经元的内在活性或降低外侧缰核神经元的活性，可以交换NMDA受体对氯胺酮阻断反应的敏感性。去除侧缰中强制性NMDA受体亚基NR1可阻止氯胺酮的抗抑郁作用。

▲ Abstract：

The discovery of the antidepressant effects of ketamine is an important advance in mental health therapy. However, the underlying mechanisms are still not fully understood. Chen et al. found that in depressive-like animals, ketamine selectively inhibited NMDA receptor responses in lateral habenula neurons, but not in hippocampal pyramidal neurons. Compared with hippocampal neurons, lateral habenula neurons have much higher intrinsic activity in the depressive state and a much smaller extrasynaptic reservoir pool of NMDA receptors. By increasing the intrinsic activity of hippocampal neurons or decreasing the activity of lateral habenula neurons, the sensitivity of their NMDA receptor responses to ketamine blockade could be swapped. Removal of the obligatory NMDA receptor subunit NR1 in the lateral habenula prevented ketamine’s antidepressant effects.

物理学Physics 

High-temperature quantum valley Hall effect with quantized resistance and a topological switch

具有量子化电阻和拓扑开关的高温量子谷霍尔效应

▲ 作者：KE HUANG, HAILONG FU, KENJI WATANABE, TAKASHI TANIGUCHI, AND JUN ZHU

▲链接：

https://www.science.org/doi/10.1126/science.adj3742

▲摘要：

在某些情况下，拓扑固态器件中的电子运动能以类似量子光学的方式进行控制。这个概念的核心是拓扑边缘状态，理想情况下，它应该没有后向散射，也不需要外加磁场。Huang等人观察到，在零磁场下，双层石墨烯中的一种称为扭结态的螺旋边缘态与电阻的非常精确的量化有关。

当温度增加到50K左右时，量子化仅表现出轻微的恶化，表明对后向散射的保护。研究者演示了拓扑控制开关的电气操作，其通/关比为200。这些结果证明了扭结态的鲁棒性和可调性，以及它在构建电子量子光学器件方面的前景。

▲ Abstract：

The motion of electrons in topological solid-state devices can be controlled in a manner analogous to quantum optics under certain circumstances. Central to this concept are topological edge states, which ideally should exhibit no backscattering and should not require an applied magnetic field. Huang et al. observed a very precise quantization of resistance associated with a type of helical edge states called kink states in bilayer graphene at zero magnetic field. The quantization exhibited only a slight deterioration as the temperature was increased to about 50 K, indicating protection against backscattering. 

Toward liquid cell quantum sensing: Ytterbium complexes with ultranarrow absorption

液体电池量子传感：具有超窄吸收的镱化合物

▲ 作者：ASHLEY J. SHIN, CHANGLING ZHAO, YI SHEN, CLAIRE E. DICKERSON, BARRY LI, HOOTAN ROSHANDEL, DANIEL BíM, TIMOTHY L. ATALLAH, PAUL H. OYALA, AND JUSTIN R. CARAM

▲链接：

https://www.science.org/doi/10.1126/science.adf7577

▲摘要：

蒸汽电池中的碱原子集合是检测电磁场最通用的系统之一，并用于制造最灵敏的磁力计。然而，这种原子蒸汽电池的低密度限制了它们的灵敏度。Shin等人提出了一种液体模拟物，可以提供更高的密度数和更高的化学可调性，从而有可能克服该技术的局限性。

作者报道了一种二茂铁负载的镱配合物，在室温下在溶液中表现出超窄的吸收线宽。该研究展示了定制分子在基于液体的精确量子传感中的潜力，这将有助于未来应用。

▲ Abstract：

Alkali atom ensembles in vapor cells are among the most versatile systems for detecting electromagnetic fields and are used to manufacture the most sensitive magnetometers. However, low number densities in such atomic vapor cells limit their sensitivity. Shin et al. proposed a liquid analog that can offer higher density numbers and higher chemical tunability, thus potentially overcoming the limitations of this technology. The authors reported a ferrocene-supported ytterbium complex that exhibits an ultranarrow absorption linewidth in solution at room temperature. Their work showcases the potential of tailor-designed molecules in liquid-based precision quantum sensing, which may spark future applications. 

地质学和材料学

Geology &Materials Science

A long section of serpentinized depleted mantle peridotite

一长段蛇纹石化的枯竭地幔橄榄岩

▲ 作者：C. JOHAN LISSENBERG, ANDREW M. MCCAIG, SUSAN Q. LANG, PETER BLUM, NATSUE ABE, WILLIAM J. BRAZELTON, RéMI COLTAT, JEREMY R. DEANS, KRISTIN L. DICKERSON, AND SARAH TREADWELL

▲链接：

https://www.science.org/doi/10.1126/science.adp1058

▲摘要：

地球的地幔很难取样，其大部分直接信息来自从海底挖出的岩石，或者来自以蛇绿岩的形式被推到地壳上的古代地幔。Lissenberg等人展示了国际海洋钻探项目远征399的船上观测结果，该项目在海底地幔下钻了1268米深。

岩石剖面是从大西洋中脊附近的热液活跃区恢复的，应该有助于我们更好地理解地幔岩石的化学成分，这些岩石是由附近岩浆提取过程形成的，形成了新的海洋地壳。

▲ Abstract：

The mantle of the Earth is hard to sample, with most of our direct information about it coming from rocks dredged off the ocean floor or from ancient mantle thrust up onto the crust in the form of ophiolites. Lissenberg et al. present the shipboard observations from the International Ocean Drilling Project Expedition 399, which drilled 1268 meters deep into the mantle under the seafloor. The rock section was recovered from a hydrothermally active region near the mid-Atlantic ridge and should help us better understand the chemistry of mantle rocks shaped by the nearby magma extraction process that forms new ocean crust. 

Strengthening gold with dispersed nanovoids

分散纳米孔洞强化金

▲ 作者：JIA-JI CHEN, HUI XIE, LING-ZHI LIU, HUAI GUAN, ZESHENG YOU, LIJIE ZOU, AND HAI-JUN JIN

▲链接：

https://www.science.org/doi/10.1126/science.abo7579

▲摘要：

材料在含有空隙的情况下，往往在载荷作用下过早或灾难性地失效，这对材料制造提出了挑战。Chen等人发现，当孔洞缩小到亚微米或纳米尺度时，含有高达10%球形孔洞的金不会在张力下过早断裂。相反，分散的纳米空隙增加了材料的强度和延展性，同时减轻了材料的重量。

除了抑制应力或应变集中外，这种结构提供了巨大的表面积，促进了表面位错的相互作用，从而实现了强化和额外的应变硬化，从而实现了增韧。将类似裂纹的有害缺陷中的空洞转化为有益的“成分”，为开发新型轻质高性能材料提供了一种廉价且环保的方法。

▲ Abstract：

Materials often fail prematurely or catastrophically under load while containing voids, posing a challenge to materials manufacturing. We found that a metal (gold) containing spherical voids with a fraction of up to 10% does not fracture prematurely in tension when the voids are shrunk to the submicron or nanometer scale. Instead, the dispersed nanovoids increase the strength and ductility of the material while simultaneously reducing its weight. Apart from the suppressed stress or strain concentration, such structure provides enormous surface area and promotes surface-dislocation interactions, which enable strengthening and additional strain hardening and thus toughening. Transforming voids from crack-like detrimental defects into a beneficial “ingredient” provides an inexpensive and environmentally friendly approach for the development of a new class of lightweight, high-performance materials.