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A phase separation-fortified bi-specific adaptor for conditional tumor killing

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Science China(life sciences) 2024年第7期67卷 1385-1397页

作者： Yuyan Liu Yuting Zhu Weifan Xu Pilong Li State Key Laboratory of Membrane Biology Frontier Research Center for Biological StructureTsinghua University-Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal *** the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor *** their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor *** development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal *** approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

关键词： phase separation therapeutic proteins receptor-ligand interactions DR5 tumor apoptosis

Interplant communication:an emerging battlefield in plant-aphid-virus interactions

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Science China(life sciences) 2024年第5期67卷 1069-1071页

作者： Yunjing Wang Qian Gong Yule Liu MOE Key Laboratory of Bioinformatics and center for Plant Biology School of Life SciencesTsinghua UniversityBeijing 100084China tsinghua-peking center for life sciences Beijing 100084China

Plants constantly face threats from various organisms,including pathogens and *** the pathogens,plant viruses are obligate intracellular parasites that infect plants and cause serious crop yield losses.

关键词： plant Plants communication

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A comparison of statistical learning of naturalistic textures between DCNNs and the human visual hierarchy

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Science China Technological sciences 2024年第8期67卷 2310-2318页

作者： LU XinCheng YUAN ZiQi ZHANG YiChi AI HaiLin CHENG SiYuan GE YiRan FANG Fang CHEN NiHong Department of Psychological and Cognitive sciences Tsinghua University Department of Computer Science and Technology Tsinghua University School of Psychological and Cognitive sciences and Beijing Key Laboratory of Behavior and Mental Health Peking University Key Laboratory of Machine Perception (Ministry of Education) Peking University peking-tsinghua center for life sciences Peking University IDG/McGovern Institute for Brain Research Peking University State Key Laboratory of Brain and Cognitive Science Institute of Psychology Chinese Academy of Sciences IDG/McGovern Institute for Brain Research Tsinghua University

The visual system continuously adapts to the statistical properties of the environment. Existing evidence shows a close resemblance between deep convolutional neural networks(CNNs) and primate visual stream in neural selectivity to naturalistic textures above the primary visual processing stage. This study delves into the mechanisms of perceptual learning in CNNs,focusing on how they assimilate the high-order statistics of natural textures. Our results show that a CNN model achieves a similar performance improvement as humans, as manifested in the learning pattern across different types of high-order image statistics. While L2 was the first stage exhibiting texture selectivity, we found that stages beyond L2 were critically involved in learning. The significant contribution of L4 to learning was manifested both in the modulations of texture-selective responses and in the consequences of training with frozen connection weights. Our findings highlight learning-dependent plasticity in the mid-to-high-level areas of the visual hierarchy. This research introduces an AI-inspired approach for studying learning-induced cortical plasticity, utilizing DCNNs as an experimental framework to formulate testable predictions for empirical brain studies.

关键词： CNN perceptual learning naturalistic texture psychophysics

A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance

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Journal of Genetics and Genomics 2024年第8期51卷 836-843页

作者： Shibo Hou Jingheng Chen Ruobing Feng Xuejiao Xu Nan Liang Jackson Champer center for Bioinformatics Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant *** operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a ***,resistance alleles formed by end-joining repair pose a significant *** address this,we create a homing drive targeting the essential hairy gene in Drosophila *** resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of *** drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the ***,the drive does not reach 100%due to the formation of functional resistance alleles despite using four *** alleles have a large deletion but likely utilize an alternate start ***,revised designs targeting more essential regions of a gene may be necessary to avoid such functional *** of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.

关键词： Genedrive Homing drive Rescueelement Population modification Multiplexed gRNAs Resistance alleles Cage study

Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 218-240页

作者： Feifei Li Chou Wu Gelin Wang School of Pharmaceutical sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyTsinghua UniversityBeijing 100084China tsinghua-peking Joint center for life sciences Tsinghua UniversityBeijing 100084China

As the aging population continues to grow rapidly, age-related diseases are becoming an increasing burden on the healthcare system and a major concern for the well-being of elderly individuals. While aging is an inevitable process for all humans, it can be slowed down and age-related diseases can be treated or alleviated. Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme or cofactor that plays a central role in metabolism and is involved in various cellular processes including the maintenance of metabolic homeostasis, post-translational protein modifications, DNA repair, and immune responses. As individuals age, their NAD levels decline, and this decrease has been suggested to be a contributing factor to the development of numerous age-related diseases, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. In pursuit of healthy aging, researchers have investigated approaches to boost or maintain NAD levels. Here, we provide an overview of NAD metabolism and the role of NAD in age-related diseases and summarize recent progress in the development of strategies that target NAD metabolism for the treatment of age-related diseases, particularly neurodegenerative diseases.

关键词： Ageing Neuroprotection NAD metabolism Therapeutic strategy Neurodegenerative diseases

Perspective on new cell-free DNA technologies for early cancer detection

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Cancer Biology & Medicine 2024年第2期21卷 139-143页

作者： Jie Li Xun Lan Department of Basic Medical sciences School of MedicineTsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Tsinghua UniversityBeijing 100084China tsinghua-peking Joint center for life sciences Tsinghua UniversityBeijing 100084China

High cancer heterogeneity and aggressiveness are major factors contributing to the poor prognosis of patients with advanced cancer~(1-5).Early detection of cancer can significantly improve the prognosis of patients with early-stage cancer after standard *** traditional cancer detection technologies,such as endoscopy for gastrointestinal cancer,mammography for breast cancer。

关键词： prognosis cancer patients

Long way up:rethink diseases in light of phase separation and phase transition

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Protein & Cell 2024年第7期15卷 475-492页

作者： Mingrui Ding Weifan Xu Gaofeng Pei Pilong Li State Key Laboratory of Membrane Biology&Frontier Research center for Biological Structure School of Life SciencesTsinghua UniversityBeijing 100084China tsinghua-peking center for life sciences Beijing 100084China NuPhase Therapeutics Beijing 100083China

Biomolecular condensation, driven by multivalency, serves as a fundamental mechanism within cells, facilitating the formation of distinct compartments, including membraneless organelles that play essential roles in various cellular processes. Perturbations in the delicate equilibrium of condensation, whether resulting in gain or loss of phase separation, have robustly been associated with cellular dysfunction and physiological disorders. As ongoing research endeavors wholeheartedly embrace this newly acknowledged principle, a transformative shift is occurring in our comprehension of disease. Consequently, significant strides have been made in unraveling the profound relevance and potential causal connections between abnormal phase separation and various diseases. This comprehensive review presents compelling recent evidence that highlight the intricate associations between aberrant phase separation and neurodegenerative diseases, cancers, and infectious diseases. Additionally, we provide a succinct summary of current efforts and propose innovative solutions for the development of potential therapeutics to combat the pathological consequences attributed to aberrant phase separation.

关键词： multivalency compartments aberant phase separation therapeutics gain or loss of phase separation diseases

Recent progress in MOFs-based nanozymes for biosensing

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Nano Research 2024年第1期17卷 39-64页

作者： Imamdin Chandio Yongjian Ai Lei Wu Qionglin Liang MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryLaboratory of Flexible Electronics TechnologyCenter for Synthetic and Systems BiologyTsinghua University-Peking University Joint Centre for Life SciencesTsinghua UniversityBeijing 100084China

Nanozymes are nanomaterials with enzyme-mimicking catalytic *** to natural enzymes,nanozymes show various properties such as easy to manufacture,stable,adjustable,and *** play key roles in biosensing,biocatalysis,and disease *** an important kind of nanozymes,metal-organic framework(MOF)-based nanozymes are receiving a lot of attention due to their structural properties and *** developing MOF with enzymes-like catalytic properties has opened new perspectives in *** review summarizes the up-to-date developments in synthesizing two-dimensional and three-dimensional MOF-based nanozymes and their applications in ***,classification of nanozymes obtained by MOFs is categorized,and different properties of MOF-based nanozymes are ***,the distinctive applications of MOF-based nanozymes in identifying various analytes are thoroughly ***,the recent challenges and progressive directions in this area are highlighted.

关键词： metal-organic frameworks nanozymes metal-organic framework (MOF)-based nanozymes biosensing analytes

Novel concept of nano-additive design:PTFE@silica Janus nanoparticles for water lubrication

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Friction 2024年第2期12卷 258-270页

作者： Yanfei LIU Hailing HE Meng YANG Ruize ZHANG Shengtao YU Tiantian YANG Wenzhong WANG Fuxin LIANG School of Mechanical Engineering Beijing Institute of TechnologyBeijing 100081China Institute of Polymer Science&Engineering Department of Chemical EngineeringTsinghua UniversityBeijing 100084China MOE Key Laboratory of Bioinformatics Center for Plant BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China tsinghua-peking center for life sciences Beijing 100084China College of Biological sciences China Agricultural UniversityBeijing 100193China

Polytetrafluoroethylene(PTFE)has been widely used as a lubrication additive for reducing friction and wear;however,the hydrophobic nature of PTFE restricts its application in eco-friendly water-based lubrication *** this study,for the first time,we designed novel PTFE@silica Janus nanoparticles(JNs)to meet the requirement for additives in water-based lubricants,which have excellent dispersion stability in water attributed to the unique amphiphilic *** introducing the lubrication of the aqueous dispersion of the JNs with a concentration of 0.5 wt%,the coefficient of friction(COF)and wear volume were reduced by 63.8%and 94.2%,respectively,comparing to those with the lubrication of pure ***,the JNs suspension also exhibits better lubrication and wear-resistance performances comparing to commercial silica and PTFE *** excellent tribological behaviors of PTFE@silica JNs as nano-additives could be attributed to the synergetic effect of the two components,where the PTFE provided lubrication through the formed tribofilms on the friction pairs,and the rigid silica further enhanced the wear-resistance *** importantly,the unique structure of JNs makes it possible to use PTFE as an additive in water-lubrication *** study shed light on the design and application of novel JNs nanomaterials as additives to meet the requirements of future industrial applications.

关键词： Janus nanoparticles(JNs) polytetrafluoroethylene(PTFE) nano-additives friction lubrication