导 读

Review of scientific breakthroughs in 2023, from neuromodulation and brain-machine interfaces to AI, superconductivity, and space exploration by The Innovation's editorial team (Figure 1).

2023年科技创新的焦点有哪些？从神经调控和脑机接口到人工智能、从超导材料到太空探索……The Innovation编辑团队回顾了2023年的科学突破。

图1 藏在图片中的十大创新焦点

1

Neuromodulation leads to breakthroughs

神经调控带来突破

Neuromodulation aims to modulate the activity of specific neurons through physical, chemical, or biological means, thereby modifying related perception, action, or even reversing disease states. Among the currently available neuromodulation techniques, chemogenetics has emerged as a rising star in recent years, offering advantages such as cell-type and pathway specificity, less invasiveness, and increased flexibility. Through the use of this promising technique, researchers worldwide have achieved significant breakthroughs in 2023. One notable example is the world's first cell-level hypothermia experiment on primates conducted by Drs. Dai & Wang, which successfully induced a drop in body temperature and triggered a strong defensive response against the cold by activating specific neurons in the monkeys' brains. This represents a significant advancement in understanding human torpor and its potential applications in medicine and space exploration. Another breakthrough is developing a gene therapy strategy by Dr. Lu and collaborators, aimed at selectively manipulating the circuitry affected by Parkinson's disease and attenuating its core motor symptoms in rodent and nonhuman primate animals. This strategy brings new hope for the treatment of Parkinson's disease.

神经调控旨在通过物理、化学或生物学手段调节特定神经元的活动，从而改变相关的感知、动作，甚至逆转疾病状态。目前的神经调控技术中，化学遗传学已成为近年来一颗冉冉升起的新星，它具有细胞类型和通路特异性、侵入性更小和灵活性更高的优势。利用这种前沿技术，世界各地的研究人员在 2023 年取得了很多令人瞩目的突破。一个值得注意的例子是，中国科学家开展了世界上第一个在灵长类动物上的低体温诱导实验，成功地通过激活猴子大脑中的特定神经元诱导了体温下降，并引发了对失温的强烈防御反应。该研究是理解人类休眠及其在医学和太空探索中的潜在应用的重大进步。另一项突破是中国科学家开发了一种神经调控治疗策略，该策略通过选择性地操纵受帕金森病影响的神经回路，减轻了帕金森鼠和猴模型的核心运动症状。这一策略为帕金森病的治疗带来了新的希望。

2

Functional ultrasound brain-machine interface

功能超声脑机接口

Non-implanted brain-machine interfaces (BMI) have the potential for various applications such as biomedicine, consumer electronics, and smart manufacturing. A team of scientists has made important progress in decoding motor plans using a non-implanted and closed-loop online functional ultrasound brain–machine interface (fUS-BMI). They used a miniaturized 15.6 MHz ultrasound transducer to record the neural activities during the ultrafast pulse-echo fUS neuroimaging. The experiments performed on the posterior parietal cortex of two trained monkeys achieved real-time control of up to 8 motion directions and stable decoding for over a month. The technological breakthrough established the feasibility of fUS-BMI and paved a way for the less invasive and portable human BMI, which is high-resolution, stable across time, and scalable to sense activities from larger and deeper brain regions. To make fUS-BMI for humans a reality in the future, several cutting-edge technological innovations should be embarked upon, especially new techniques to overcome ultrasound signal attenuation in non-craniotomy mode.

非植入式脑机接口在生物医学、消费电子、智能制造等广受关注的领域具有更多应用潜力。加州理工学院的科学家与其合作者完成了通过非植入式、在线、闭环功能超声脑机接口（fUS-BMI）读取大脑运动规划并实施驱动控制的重要进展。使用基于15.6 MHz微小型超声换能器的超快脉冲回波的功能超声神经成像技术记录神经活动，实验中读取了两只恒河猴后顶叶皮层的大脑活动，通过训练后实现了对8个径向方向实时运动控制、跨度超过一个月的稳定解码能力。该技术进展确立了超声脑机接口技术的可行性，为实现低侵入性、便携式、高分辨率、长时间稳定性、能够感知人类大脑的更大区域和更深层次的脑机接口技术铺平了道路。该技术成为现实之前仍要协同实现多项令人期待的前沿技术创新，尤其是新的经颅超声神经成像技术，从而克服目前因超声波信号被骨严重衰减而需要在颅部开孔的问题。

科学家眼中的2023科技热词：脑机接口

3

OvaRePred: redefing ovarian aging

卵巢储备

The ovarian reserve, indicative of the number of primordial follicles in the ovarian cortex that can mature into oocytes, is a vital fertility marker in women. This reserve varies dramatically, spanning from thousands to millions at birth. Traditionally, ovarian reserve assessment relies on clinicians' personal experiences. OvaRePred, utilizing advanced algorithms and big data, offers insights into current ovarian health and predicts key fertility milestones, such as the onset age of diminished ovarian reserve and perimenopause. Its capability to evaluate and forecast ovarian reserve status paves the way for individualized care, informed decision-making, and an enhanced quality of life. OvaRePred is currently being routinely implemented in several hospitals and physical examination centers in China. As its application becomes more widespread, it promises to deepen our understanding of fertility and perimenopause, culminating in improved health management for individuals globally. This tool represents not just a significant milestone in medical technology; it also signals the onset of a revolutionary era in precision reproductive health management.

卵巢储备，即卵巢皮质内有潜力发育为成熟卵母细胞的原始卵泡的数量，是衡量女性生育力的重要指标。卵巢储备个体差异巨大，出生时原始卵泡就可达到数万至数百万不等。传统上，卵巢储备的评估主要依赖于医生的个人经验。OvaRePred运用先进的算法和大数据，不仅可评估女性当前的卵巢储备，还能预测如卵巢储备下降（DOR）和围绝经期等关键生育里程碑事件的发生年龄，使女性能够更个性化地规划自己的生育计划和围绝经期健康管理。OvaRePred目前已在中国的多家医院和体检中心常规使用。随着其应用范围的扩大，它有望加深全社会对女性生育力和围绝经期的理解，从而在全球范围内改善女性的健康管理效率。OvaRePred不仅代表了医学技术的重大进步，同时也开启了精准生殖健康管理的新时代。

科学家眼中的2023科技热词：生殖健康

4

Beyond LLM, AI is moving to multimodal foundation models

面向多模态基础模型的AI

Just one month after the emergence of ChatGPT, Innovation Focus 2022 accurately predicted the profound impact that large models would have on the development of human technology. Indeed, these AI technologies have made their way into the progress lists of Nature and Science this year. In 2023, large models have transcended confines of natural language processing and have successively emerged as foundation models for multimodal data and various artificial intelligence tasks. Huawei's Pangu-Weather and Google DeepMind's GraphCast utilized AI foundation model techniques and achieved a breakthrough in more accurate weather forecasting. OpenAI’s GPT-4 Turbo showcased outstanding capabilities in processing image, text and speech. Google’s Gemini achieved results that surpass human capabilities in multiple tasks. The continuous advancement of large foundation models is pushing the boundaries of artificial intelligence capabilities and gradually transforming the way people interact with the world.

在ChatGPT问世仅一个月后，The Innovation期刊就在2022年十大年度进展准确预测了大模型将对人类科技发展产生深远影响。果然，在2023年大模型发展迅速、受到全球学术界和工业界的高度关注和参与，多种人工智能成果也进入了Nature和Science的年度重要进展列表中。2023年，大模型不再局限于自然语言处理领域，面向多模态数据的大模型被相继提出，并成为各个人工智能任务的基础模型。华为的“盘古天气模型”和谷歌DeepMind的“GraphCast”模型利用了人工智能基础模型技术，在更准确的天气预测方面取得了突破。除此之外，OpenAI的GPT-4 Turbo展示了在处理图像、文本和语音方面的卓越能力，谷歌的Gemini也在多个任务中取得了超越人类的结果。多模态大模型不断刷新着人工智能的能力边界，也将逐步改变人类与世界的交互方式。

5

Analyzing samples from asteroids RYUGU and BENNU

分析小行星RYUGU和BENNU的样品

Organic compounds in exogenous materials are thought to have significantly contributed to prebiotic chemistry on Earth. Japan's Hayabusa 2 mission and the United States' OSIRIS-Rex mission collected samples from carbonaceous asteroids Ryugu and Bennu and delivered them to Earth. Analyzing these samples in the laboratory revealed approximately 20,000 organic molecular species with molecular weights of up to 700 Daltons in the Ryugu sample, including indigenous amino acids, nucleobase, vitamer, monocarboxylic acids, alkylamines, and polycyclic aromatic hydrocarbons. Ryugu sample's organic species distribution is as diverse as that in carbonaceous meteorites, probably representing the real distribution of organics in the Solar System. The analysis of the Bennu sample also shows high carbon and water content. These findings will help advance our understanding of the early history of our solar system and the origin of life.

地外物质中的有机化合物被认为对地球生命诞生前的化学具有重要影响。日本的Hayabusa 2任务和美国的OSIRIS-Rex任务分别从碳质小行星Ryugu和Bennu收集了样品，并将它们运送到地球。在实验室中分析这些样品后，发现Ryugu样品中含有大约2万多种有机分子，分子量可高达700道尔顿，包括氨基酸、核碱基、维生素、单羧酸、烷基胺和多环芳烃。Ryugu样品的有机物种类与碳质陨石一样多样化，可能代表了太阳系有机物的真实分布。此外，对Bennu样品的分析也显示其包含高碳和水。这些发现将有助于促进我们对太阳系早期历史和生命起源的理解。

6

Deciphering the most violent dynamics of the universe

解密宇宙中最剧烈的天体现象

The observation of gamma-ray bursts (GRBs) and extremely energetic cosmic rays can offer valuable insights into the formation and evolution of stars and galaxies. The Large High Altitude Air Shower Observatory (LHAASO) achieved a groundbreaking observation of tera-electron volt afterglow onset and decay phases of an exceptionally bright GRB 221009A. GRBs with such brightness are extremely rare, being expected to occur only once every ten thousand years. This observation led to the finding of a jet break of the GRB that explains its brightness nature and the first-ever discovery of a rapid rise to a peak in the afterglow's light curve, which is still a mystery. Another notable discovery reported this year is that the Telescope Array experiment's surface detector array detected a cosmic ray with an energy level of around 200 exa-electron volts on May 27, 2021. Scientists are actively researching the origins of these energetic cosmic rays and the mechanisms responsible for accelerating them to such extraordinary energies. Overall, both the observations of GRBs and extremely energetic cosmic rays provide valuable data to expand our understanding of the universe.

对伽马射线暴(GRB)和极端高能宇宙射线的观测可以提供关于恒星和星系形成与演化的宝贵资料。大型高海拔宇宙线观测站（LHAASO）首次精确地记录了极亮伽马射线暴GRB 221009A万亿电子伏特余辉射线流量增强和衰减的整个过程。如此高亮度的伽马射线暴极为罕见，预计每一万年才会扫过地球一次。这次观测发现了伽马射线暴的喷流截断，正好能解释GRB 221009A为什么这么亮。观测还首次发现了余辉光变曲线的快速上升行为，其成因仍是一个谜。今年另一个值得注意的报道是，望远镜阵列实验在2021年5月27日探测到一个能量约为200百亿亿电子伏特的宇宙线粒子。虽然目前这些高能宇宙射线的起源以及产生如此高能量的机制并不清楚，这类伽马射线暴和极高能宇宙射线的观测为我们理解宇宙的未知奥秘提供了宝贵的数据。

7

Decoding the Y chromosome

揭秘Y染色体

When the preliminary human genome sequence was assembled over two decades ago, gaps riddled the maps of all chromosomes. However, unlike tiny scattered gaps in other chromosomes, over half of the Y chromosome's sequence remained a mystery, with its highly repetitive DNA impervious to decoding. For the last 22 years, scientists have struggled to interpret the Y chromosome's genetic information. To tackle the most repetitive regions of the genome, the T2T Consortium leveraged new DNA sequencing approaches, sequence assembly methodology, and knowledge from generating the first complete sequences of the other 23 human chromosomes. In August, researchers at NIST and partner institutions integrated a comprehensive picture of the Y chromosome, uncovering 42 novel genes and establishing a solid basis for analyzing chromosomal structure and function. Sequencing revealed unexpected uniformity within the Y chromosome, with nearly half composed of alternating blocks of two specific repeating satellite DNA sequences in an orderly, quilt-like pattern. Additionally, deciphering repetitive regions involved in sperm production and containing variable gene copies allows for a more accurate assessment of DNA deletions and connections between genomic variation, fertility, disease, and health.

二十多年前，当初步的人类基因组序列被组装起来时，所有染色体的图谱中都布满了缺失信息（缺口）。然而，与其他染色体中零星分布的小缺口不同，Y染色体序列的一半以上仍是一个谜，其高度重复的DNA部分始终无法被破译。多年来科学家们一直在努力尝试解读Y染色体的遗传信息。为了解决基因组中最重复的区域问题，T2T联盟的NIST及其合作机构的研究人员，利用新的DNA测序方法，序列组装技术，以及早前其他23条人类染色体完整序列中所获得的知识，综合分析出Y染色体的所有序列，发现了Y染色体上42个新基因，并为分析染色体结构和功能奠定了坚实的基础。测序揭示了Y染色体内部出人意料的统一性，近半部分由两种特定重复卫星DNA序列的交替块组成，呈现出有序的图案。此外，研究人员破译了涉及精子生产并包含可变基因拷贝的重复区域，使得人们可以更准确地评估DNA缺失，系统理解Y染色体重复区域的功能将有助于人类更好的理解基因组变异、生育力、疾病和健康之间的联系。

8

Recent decline in global water availability

南半球可用水量呈下降趋势

Water availability across the globe plays a crucial role in shaping livelihoods, socioeconomic development, and ecosystems. However, it is anticipated that this availability will undergo substantial transformations in the next few decades due to the combined effects of climate change and socioeconomic growth. A group of scientists found that the Southern Hemisphere was responsible for the declining trend in global water availability in the early 21st century (from 2001 to 2020), with significant decreases occurring specifically in South America, southwestern Africa, and northwestern Australia. In contrast, the Northern Hemisphere displayed complex regional trends that offset each other, leading to a negligible overall trend. The Southern Hemisphere's water availability trends were predominantly driven by precipitation associated with climate modes, particularly the El Niño-Southern Oscillation, emphasizing their critical role in regulating global water availability.

水资源对于维持国民生计和保障社会经济发展至关重要。但近年来，全球水资源的可用性发生了重大变化，成为备受关注和争议的焦点。近期，由中国科学家开展的一项研究表明，在过去20年中，全球陆地水资源的可用性发生了显著变化，但南北半球变化差异明显。南半球经历了显著的水资源可用性下降，其中在南美洲、西南非洲和澳大利亚西北部等地尤为明显。北半球的水资源可用性整体变化趋势微弱，但区域差异显著，有增有减。在中国南部、北美东部和亚洲东北部地区的水资源可用性上升，而东南亚、欧洲东部和西伯利亚等地区则经历了可用性的下降。这些变化主要决定于气候模态，特别是厄尔尼诺-南方涛动引起的降水变化是主控因素。

9

Rising nickel age of superconductivity

冉冉升起的镍基超导新时代

Superconductivity is a macroscopic quantum phenomenonwithzero resistance and full diamagnetism states at low temperatures. Over the past 36 years, the copper oxides, have been the only unconventional superconductors that exhibit bulk superconductivity with T_c above 77 K, a threshold for practical applications. Since 2019, superconductivity has been discovered in a thin nickelate film NdNiO₂ with T_c up to 15 K.A great breakthrough was made by Sun et al. this year, revealing superconductivity up to 80 K in its cousin compound La₃Ni₂O₇ at pressures between 14.0 GPa and 43.5 GPa. Transition-metal oxides have been intensively explored for many years to search for unconventional superconductivity. Now, a new chapter of the nickel age of superconductivity is finally opened, not only in the 112-type and 327-type of nickelates but also in many related compounds named Ruddlesden-Popper phases with a formula La_n+1Ni_nO_3n+1 (n=1, 2, 3, …, ∞). Indeed, they show many aspects of similarity to cuprates, as well as the iron-based superconductors, such as competing magnetic and charge orders, sign reversal pairing symmetry, and hybridized orbitals, where strong magnetic fluctuations may play as the pairing glue of superconducting electrons.

超导是低温下同时具有零电阻和完全抗磁性的一种宏观量子现象。在过去的 36 年里，铜氧化物是唯一具有临界温度突破实用化门槛77 K之上的非常规超导材料。2019年，人们在镍氧化物NdNiO₂中发现了15 K的超导电性，中国科学家在今年再次取得重大突破，在另一镍氧化物La₃Ni₂O₇中发现高达80 K的超导电性，压力范围为14.0 GPa-43.5 GPa。多年来，人们一直在各种过渡金属氧化物中探索非常规超导电性，如今，镍基超导时代开启了新篇章。不仅在112型和327型的镍酸盐中具有超导电性，而且在众多Ruddlesden-Popper相的相关化合物中同样发现了超导电性，其通用分子式为La_n+1Ni_nO_3n+1（n=1,2,3，...，∞）。此外，镍氧化物显示出与铜氧化物乃至铁基超导体许多相似的特性，例如磁性或电荷竞争序、符号反转的超导配对对称性和轨道杂化效应等，其中强烈的磁性涨落可能是非常规超导电子配对的“胶水”。

镍基超导新时代

10

What's next for space exploration

太空探索的未来计划

SpaceX’s Starship spacecraft and Super Heavy rocket (Starship) represent a fully reusable transportation system designed to carry both crew and cargo to Earth orbit, the Moon, Mars, and beyond. SpaceX also has crewed spaceflights with private passengers aboard Starship planned for later this decade. In 2021, Isaacman flew on Inspiration-4, SpaceX’s first all-civilian Crew Dragon flight, and will also lead the first Polaris flight aboard a SpaceX Dragon early next year. Although a second test flight of SpaceX's Starship was failed on November 12, 2023, the spacecraft could potentially transport astronauts and private passengers to the moon within the next several years, and possibly to Mars later on. China also conducted three commercial rocket launches in December, 2023. The solid carrier rocket Gui Shen Xing-1, developed by Galaxy Power, successfully completed the first orbital launch mission by a private rocket company, covering the period from dawn to dusk. Additionally, Zhuque-2 is the world's first liquid oxygen-methane carrier rocket to achieve consecutive successful launches, marking China's commercial space exploration entering the fast lane globally. In the future of space exploration, commercialization is an inevitable trend.

SpaceX的星际飞船和超重型火箭（统称为星际飞船）代表了一种完全可重复使用的运输系统，旨在将机组人员和货物运送到地球轨道、月球、火星等地。SpaceX计划近10年内实现乘坐星际飞船进行私人太空飞行。2021年，Inspiration4成功实现首飞，并将在2024年初实现SpaceX Dragon的发射。尽管SpaceX星际飞船的第二次试飞于2023年11月12日发射升空以失败告终，但是该航天器有可能在未来几年内将宇航员和私人乘客运送到月球，并可能在以后运送到火星。中国2023年12月商业火箭“捷龙三号”的成功发射，标志着其顺利进入商业发射交付的新阶段。银河动力研制的固体运载火箭桂神星一号成功执行了第一家民营火箭公司的黎明至黄昏轨道发射任务，以及朱雀二号是世界上首枚实现连续发射成功的液氧-甲烷运载火箭，标志着中国商业太空探索进入了世界快车道。未来太空探索，商业化是必然趋势。

原文信息

本文内容来自Cell Press合作期刊The Innovation第五卷第一期以Editorial发表的“Innovation Focus in 2023” (投稿: 2023-12-21；接收: 2023-12-24；在线刊出: 2024-01-02)。

DOI: https://doi.org/10.1016/j.xinn.2023.100560

原文链接：https://www.cell.com/the-innovation/fulltext/S2666-6758(23)00188-1

引用格式：The Innovation Editorial Team. (2024). Innovation Focus in 2023. The Innovation. 5(1),100560.

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