《科學》（20240809出版）一周論文導讀

編譯|馮維維

Science, VOLUME 385, ISSUE 6709, 9 AUG 2024

《科學》,第385卷，6709期，2024年8月9日

生命科學Life Science 

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

在非人類靈長類動物中，有條件地復制艾滋病病毒基因工程缺失以減少疾病

▲ 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

▲鏈接：

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

▲摘要：

在復制過程中，RNA病毒經常產生有缺陷的顆粒，這些顆粒寄生并干擾完整病毒的復制和包裝。這些有缺陷的顆粒也可能刺激宿主的免疫反應。Pitchai等人開發了一種連續培養方法，其中將缺失克隆到艾滋病病毒（HIV）中以產生治療性干擾粒子（TIPs）。

首先，他們發現具有轉導能力的病毒樣顆粒是有條件地在完整的HIV和減少的HIV載量的轉運中產生的。測序沒有檢測到隨后的大缺失或重排。然后在捐贈的HIV感染的人類細胞、人源化小鼠和感染HIV的非人靈長類動物中注射一劑量的工程化TIPS進行測試。這些實驗證實了血清轉化、抑制HIV復制和TIP持續至少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

氯胺酮作為快速抗抑郁藥的腦區域特異性作用

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

▲鏈接：

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

▲摘要：

氯胺酮抗抑郁作用的發現是心理健康治療的重要進展。然而，其潛在機制仍未完全了解。Chen等人發現，在類似抑郁的動物中，氯胺酮選擇性地抑制了側韁核神經元的NMDA受體反應，但對海馬錐體神經元沒有作用。

研究者發現，與海馬神經元相比，側韁核神經元在抑郁狀態下具有更高的內在活性，并且突觸外的NMDA受體庫要小得多。通過增加海馬神經元的內在活性或降低外側韁核神經元的活性，可以交換NMDA受體對氯胺酮阻斷反應的敏感性。去除側韁中強制性NMDA受體亞基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.

物理學Physics 

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

具有量子化電阻和拓撲開關的高溫量子谷霍爾效應

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

▲鏈接：

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

▲摘要：

在某些情況下，拓撲固態器件中的電子運動能以類似量子光學的方式進行控制。這個概念的核心是拓撲邊緣狀態，理想情況下，它應該沒有后向散射，也不需要外加磁場。Huang等人觀察到，在零磁場下，雙層石墨烯中的一種稱為扭結態的螺旋邊緣態與電阻的非常精確的量化有關。

當溫度增加到50K左右時，量子化僅表現出輕微的惡化，表明對后向散射的保護。研究者演示了拓撲控制開關的電氣操作，其通/關比為200。這些結果證明了扭結態的魯棒性和可調性，以及它在構建電子量子光學器件方面的前景。

▲ 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

液體電池量子傳感：具有超窄吸收的鐿化合物

▲ 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

▲鏈接：

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

▲摘要：

蒸汽電池中的堿原子集合是檢測電磁場最通用的系統之一，并用于制造最靈敏的磁力計。然而，這種原子蒸汽電池的低密度限制了它們的靈敏度。Shin等人提出了一種液體模擬物，可以提供更高的密度數和更高的化學可調性，從而有可能克服該技術的局限性。

作者報道了一種二茂鐵負載的鐿配合物，在室溫下在溶液中表現出超窄的吸收線寬。該研究展示了定制分子在基于液體的精確量子傳感中的潛力，這將有助于未來應用。

▲ 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. 

地質學和材料學

Geology &Materials Science

A long section of serpentinized depleted mantle peridotite

一長段蛇紋石化的枯竭地幔橄欖巖

▲ 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

▲鏈接：

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

▲摘要：

地球的地幔很難取樣，其大部分直接信息來自從海底挖出的巖石，或者來自以蛇綠巖的形式被推到地殼上的古代地幔。Lissenberg等人展示了國際海洋鉆探項目遠征399的船上觀測結果，該項目在海底地幔下鉆了1268米深。

巖石剖面是從大西洋中脊附近的熱液活躍區恢復的，應該有助于我們更好地理解地幔巖石的化學成分，這些巖石是由附近巖漿提取過程形成的，形成了新的海洋地殼。

▲ 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

分散納米孔洞強化金

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

▲鏈接：

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

▲摘要：

材料在含有空隙的情況下，往往在載荷作用下過早或災難性地失效，這對材料制造提出了挑戰。Chen等人發現，當孔洞縮小到亞微米或納米尺度時，含有高達10%球形孔洞的金不會在張力下過早斷裂。相反，分散的納米空隙增加了材料的強度和延展性，同時減輕了材料的重量。

除了抑制應力或應變集中外，這種結構提供了巨大的表面積，促進了表面位錯的相互作用，從而實現了強化和額外的應變硬化，從而實現了增韌。將類似裂紋的有害缺陷中的空洞轉化為有益的“成分”，為開發新型輕質高性能材料提供了一種廉價且環保的方法。

▲ 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.