日本科学家发现⻝欲暴增秘密；维⽣素A可促进肠道细胞适应性免疫

·⽣物技术（Biotechnology）

1.Nature⼦刊：“何时吃”⽐“吃得少”更重要

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice
美国威斯康⾟⼤学⻨迪逊分校在《Nature Metabolism》发⽂，研究指出想要健康⻓寿，仅靠卡路⾥摄⼊限制是不够的，还要注意饮⻝时间，“何时吃”⽐“吃得少”更重要。
研究⼈员测试⼩⿏各项代谢指标后发现，禁⻝时间最⻓的⼩⿏的胰岛素敏感性显着提升。此外，单纯的断⻝能改善⼩⿏的⾎糖和肝脏代谢变化。限⻝⼜断⻝的⼩⿏寿命⽐仅限⻝的⼩⿏⻓8个⽉，这对最⻓寿命3年的⼩⿏来说是个惊天数字。
这项研究表明，禁⻝与限⻝相结合，不仅可以提⾼⼩⿏身体素质，还能延⻓⼩⿏的寿命。未来将进⾏⼈体试验进⼀步验证该研究结论的真实性，为延⻓⼈类的寿命提供新思路。

Calorie restriction (CR) promotes healthy aging in diverse species.
Here we show that a prolonged fast is necessary for key metabolic, molecular and geroprotective effects of a CR diet. Using a series of feeding regimens, we dissect the effects of calories and fasting, and proceed to demonstrate that fasting alone recapitulates many of the physiological and molecular effects of CR.
Our results shed new light on how both when and how much we eat regulate metabolic health and longevity, and demonstrate that daily prolonged fasting, and not solely reduced caloric intake, is likely responsible for the metabolic and geroprotective benefits of a CR diet.
BY NATURE METABOLISM 10/2021

HTTPS://WWW.NATURE.COM/ARTICLES/S42255-021-00466-9

2.⾎液替代品有助应对全球⾎荒

A model of anemic tissue perfusion after blood transfusion shows critical role of endothelial response to shear stress stimuli
近⽇，美国斯坦福⼤学和加州⼤学圣迭⼽分校的研究⼈员设计的⼈体⽣化新模型表明，贫⾎或⾎液含氧量低的患者，可以输⼊更容易获得的⾎液替代品，获得有效治疗。
加州⼤学圣迭⼽分校教授指出，⼈们往往弄错了输⾎的最终⽬标 —— 恢复⾎液携氧和输送氧⽓的能⼒。预测结果显示，安全、低成本的⾎液替代品可以将输⾎的总成本降低⾄1/10，同时显著降低该过程的负⾯影响。

BY JOURNAL OF APPLIED PHYSIOLOGY
HTTPS://JOURNALS.PHYSIOLOGY.ORG/DOI/ABS/10.1152/ JAPPLPHYSIOL.00524.2021

3.瘦不下来？⽇本科学家发现⻝欲暴增的秘密

Neuronal XRN1 is required for maintenance of whole-body metabolic homeostasis
来⾃⽇本的最新研究指出，下丘脑区域表达的蛋⽩XRN1，能 整合来⾃身体各处的信号，调节⽣物体的进⻝⾏为和能量消耗。如果缺少XRN1，⼩⿏会⻝欲暴增，导致肥胖。

敲除XRN1蛋⽩后（右），⼩⿏肥胖
进⼀步研究发现，缺乏XRN1后，身体对瘦素和胰岛素没了反应，就会⼤吃特吃。吃下去的⻝物会升⾼⾎糖，顺便也提⾼了⾎液中的胰岛素⽔平。
另外，失去了XRN1的⼩⿏，⽆论是⽩天还是晚上，都主要使⽤碳⽔作为能量源，失去了燃烧脂肪的能⼒。团队还在探索具体的⽣物学机制，希望能提供减肥的新⽅法。

Control of mRNA stability and degradation is essential for appropriate gene expression, and its dysregulation causes various disorders, including cancer, neurodegenerative diseases, diabetes, and obesity.
The 5′–3′ exoribonuclease XRN1 executes the last step of RNA decay, but its physiological impact is not well understood. To address this, forebrain-
specific Xrn1 conditional knockout mice (Xrn1-cKO) were generated. Xrn1-cKO mice exhibited obesity with leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure.
Moreover, expression of mRNAs encoding proteins that regulate appetite and energy expenditure was dysregulated in the hypothalamus of Xrn1-cKO mice. Therefore, study proposes that XRN1 function in the hypothalamus is critical for maintenance of metabolic homeostasis.
BY ISCIENCE 10/2021
HTTPS://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/ S2589004221011196

4.合成⽣物学：利⽤⼯程菌移植来促进抗肿瘤免疫

Metabolic modulation of tumours with engineered bacteria for immunotherapy
精氨酸（L-arginine）对于T细胞的功能⼗分重要，科学家们在尝试通过提升肿瘤微环境中的 L-arginine 的⽔平来激活 T 细胞的抗肿瘤免疫。
来⾃瑞⼠提挈诺⼤学⽣物医学研究所在Nature上发表研究⽂章：利⽤合成⽣物学开发出⼀种⼯程菌，该菌株可以在肿瘤中定植并持续将肿瘤的代谢废物氨转化为精氨酸, 从⽽协同增强PD-L1抗体的免疫治疗效果。
研究发现，荷瘤⼩⿏在注射L-Arg菌株之后体内 T 细胞的肿瘤浸润是增加的。另外，L-Arg与PD-L1抗体联⽤可以显著抑制肿瘤的⽣⻓，⽽注射未经改造的⼤肠杆菌则不具备这种能⼒。此外，在肿瘤消退的90天后再去⽪下接种MC38细胞，肿瘤细胞则不能⽣⻓，说明经过联合治疗的⼩⿏已经形成⻓期的抗肿瘤免疫记忆。

The availability of L-arginine in tumors is a key determinant of an efficient anti-tumour T cell response.
Here we used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumours and continuously converts ammonia, a metabolic waste product that accumulates in tumors, to L- arginine. Colonization of tumors with these bacteria increased intratumoral L-arginine concentrations, increased the number of tumor-infiltrating T cells and had marked synergistic effects with PD-L1 blocking antibodies in the clearance of tumors. The anti-tumor effect of these bacteria was mediated by L-arginine and was dependent on T cells.
These results show that engineered microbial therapies enable metabolic modulation of the tumor microenvironment leading to enhanced efficacy of immunotherapies.
BY NATURE 10/2021

HTTPS://WWW.NATURE.COM/ARTICLES/S41586-021-04003-2

5.维⽣素A可促进肠道细胞适应性免疫

Serum Amyloid A Delivers Retinol to Intestinal Myeloid Cells to Promote Adaptive Immunity
维⽣素A可被肠上⽪细胞从饮⻝中吸收并转化为视⻩醇,视⻩醇指导B细胞和T细胞的发育，对调节肠道免疫功能⾄关重要。肠道⻣髓细胞可将视⻩醇转化为视⻩酸 ( RetinoicAcid )，然后将视⻩酸传递给发育中的B、T细胞。

本研究中，作者确定了⾎清淀粉样蛋⽩ A （SAA) 作为视⻩醇
结合蛋⽩所介导的肠道适应性免疫机制，证实了SAA和LRP1 蛋⽩与维⽣素A依赖性肠道免疫有关，可促进对肠道细菌感染的免疫。通过阐明维⽣素A 代谢物视⻩醇如何进⼊肠道免疫系统，该结果也证明，摄⼊充⾜的膳⻝维⽣素A可增强抵抗⼒和提⾼黏膜免疫应答功效。
BY SCIENCE 10/2021

HTTPS://WWW.SCIENCE.ORG/DOI/10.1126/SCIENCE.ABF9232

6.⻄班⽛科学家通过⼤脑植⼊电极技术让盲⼈成功识别⽂字和形状

根据⻄班⽛《国家报》报道，⼀项为盲⼈恢复部分视⼒的系统实验近⽇在⼀名57岁的⻄班⽛盲⼈妇⼥身上取得成效。通过在⼤脑负责视觉的区域植⼊电极，这名妇⼥能够识别物体形状和部分⽂字。
这项技术的关键在于将微型电极板植⼊盲⼈⼤脑负责视觉的区域，并通过⼈造视⽹膜将光对⼈眼的作⽤转化为电的作⽤，从⽽激活⼤脑中的视觉功能。该技术与利⽤光遗传学等现有的通过光技术恢复部分视⼒的⽅法有所不同，实验过程中盲⼈的眼中未接收到任何光亮。

BY SCIENCENET 10/2021

HTTP://NEWS.SCIENCENET.CN/HTMLNEWS/2021/10/467377.SHTM

·材料科学（Material Science）

7.碎裂⼿机屏⾃修复聚合物

Self-Healable Reprocessable Triboelectric Nanogenerators Fabricated with Vitrimeric Poly Networks
加拿⼤康考迪亚⼤学的研究者寻找了⼀种“⾃我修复”⼿机的⽅法，不损害⽹络的韧性，同时增加⾃修复损伤和划痕的动态能⼒。
该团队通过⾮常简单的合成路线创造了⾃愈聚合物⽹络，所开发的材料在室温下表现出良好的性能。“由于⾃愈合机制，这些材料可以快速修复损伤和裂缝。”， “这些材料节省了消费者的时间和⾦钱，同时也延⻓了材料的使⽤寿命，减少了环境负担。”在未来，研究将使⽤⾃愈聚合物⽹络来提⾼摩擦电纳⽶发电机的电池寿命。
This work demonstrated the integration of mechanically strong and self-healable poly (PHU) network in the fabrication of effective TENGs.
The designed PHU network is flexible but shows greater mechanical property of tensile strength as high as 1.7 MPa at break. The network is capable of self-healing quickly and repeatedly as well as being reprocessable under mild conditions, enabling the recovery of triboelectric performances after the complete healing of the damaged surfaces.
This work presents an avenue to the development of mechanical energy-harvesting devices and self-powered sensors with excellent stretchability, high recoverability, and good mechanical strength.
BY ACS NANO 08/2020

HTTPS://PUBS.ACS.ORG/DOI/10.1021/ACSNANO.0C03819

8.超硬⽊材能切⽜排，硬度提升23倍！

Hardened wood as a renewable alternative to steel and plastic
研究⼈员已开发出⼀种制造锋利⼑具的更可持续⽅法：使⽤硬化的⽊材。新⽅法将⽊材的硬度提⾼了23倍，⽤这种材料制成的⼑⽐不锈钢餐⼑锋利近3倍。
美国⻢⾥兰⼤学材料学家说：“这把⼑可以很容易地切开半熟⽜排，效果和餐⼑差不多。”硬化的⽊⼑也可以清洗和重复使⽤，它有望替代钢、陶瓷和⼀次性塑料⼑。
研究团队还展示了该新材料可⽤来制作像传统钢钉⼀样锋利的⽊钉。在未来，这种材料还可以⽤来制作更耐刮擦和磨损的⽊地板。
据悉，这种⽊材硬化过程⽐制备其他⼈造材料更节能，对环境的影响也更低。
Hard materials are in high demand in engineering applications. Here, we demonstrate a potential low-cost and sustainable hard material made from natural wood. Through a simple and effective approach, bulk natural wood can be processed into a hardened wood (HW) with a 23-fold increase in hardness.
We show that an HW table knife can be made nearly three times sharper than commercial table knives. An HW nail can be as functional as a steel nail with comparable performance but is immune from rusting, a key failure mechanism of steel nails. These encouraging applications suggest the promise of HW as a renewable and low-cost alternative for conventional hard materials with the potential to replace plastic table utensils and steel nails.
BY MATTER 09/2021

HTTPS://WWW.CELL.COM/MATTER/FULLTEXT/S2590-2385(21)00465-3

9.纳⽶机器⼈⽤于肿瘤细胞局部治疗

Environmentally Adaptive Shape- Morphing Microrobots for Localized Cancer Cell Treatment
来⾃合肥微尺度物质科学国家研究中⼼在《ACS NANO》发表最新研究成果，研究者们利⽤ pH 调控⽔凝胶膨胀程度， 制作了⼀种微型结构纳⽶机器⼈。这种微型结构被设计成⻥和螃蟹的形状，通过改变环境的pH可以控制⻥鳍的收缩和蟹钳的闭合。
另⼀⽅⾯，通过在⽔凝胶微型结构修饰磁性材料使其具有了磁感应性能，可以利⽤磁场来驱动⽔凝胶微型结构的位置变化。

⽔凝胶微型⻥、螃蟹结构
此外，研究者们还在⼈造⾎管的环境中验证了⽔凝胶微型⼩⻥的功能。使⽤光刻和PDMS模塑制作⼈造⾎管，并⽤磁驱微型⼩⻥对局部的HeLa细胞进⾏处理。与对照相⽐，微型⼩⻥局部的 DOX 浓度随时间越来越⾼，对Hela细胞的杀伤也越来越明显。
随环境变形的磁驱⽔凝胶微纳⽶机器⼈实现了微观上局部药物 (DOX) 包封和可控释放。不仅如此，它们还可以改造⽤以操作或者保护各种容易被破坏的药物分⼦和多肽药物等。因此，微纳⽶机器⼈技术在肿瘤治疗、⼲细胞移植、活体⽣物传感等⽅⾯有着巨⼤的研究潜⼒。
Microrobots have attracted considerable attention due to their extensive applications in microobject manipulation and targeted drug delivery.
Here, environmentally adaptive shape-morphing microrobots (SMMRs) have been developed by programmatically encoding different expansion rates in a pH-responsive hydrogel. Due to a combination with magnetic propulsion, a shape-morphing microcrab (SMMC) is able to perform targeted microparticle delivery, including gripping, transporting, and releasing by "opening-closing" of a claw.
Furthermore, localized HeLa cell treatment in an artificial vascular network is realized by "opening-closing" of the SMMF mouth. These magnetic SMMRs will provide ideal platforms for complex microcargo operations and on- demand drug release.

ACS NANO 10/2021

HTTPS://PUBS.ACS.ORG/DOI/10.1021/ACSNANO.1C06651

10.微⽣物催化⽣物陶瓷可⽤于⻣骼再⽣

Microbially Catalyzed Biomaterials for Bone Regeneration
近⽇，中国科学院上海硅酸盐研究所吴成铁团队提出微⽣物催化活性矿物诱导成⻣的思想，利⽤微⽣物催化作⽤构建⽣物陶瓷⽀架表⾯微纳⽶结构⽤于⻣组织再⽣。
研究团队利⽤产脲酶菌的代谢作⽤在陶瓷材料表⾯诱导出均匀的⽣物矿化层。纳⽶碳酸钙矿化层明显抑制了硅酸钙陶瓷的快速降解，并对⻣髓间充质⼲细胞的粘附、铺展、增殖、迁移和分化等细胞⽣物活性具有更好的促进作⽤。
并且，微⽣物催化的表⾯⽣物材料具有良好的⽣物相容性， 表现出促⻣组织再⽣的优良⽣物活性。
Bone is a complex mineralized tissue composed of various organic (proteins, cells) and inorganic (hydroxyapatite,
calcium carbonate) substances with micro/nanoscale structures. To improve interfacial bioactivity of bone- implanted biomaterials, extensive efforts are being made to fabricate favorable biointerface via surface modification.
Inspired by microbially catalyzed mineralization, a novel concept to biologically synthesize the micro/nanostructures on bioceramics, microbial-assisted catalysis, is presented.
The topographic and chemical cues of the grown micro/ nanostructures present excellent in vitro and in vivo bone- forming bioactivity.
The underlying mechanism is closely related to the activation of multiple biological processes associated with bone regeneration. The study offers a microbially catalytic concept and strategy of fabricating micro/nanostructured biomaterials for tissue regeneration.

BY ACS NANO 10/2021

HTTPS://PUBS.ACS.ORG/DOI/10.1021/ACSNANO.1C06651