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Particuology 2024年第5期88卷 282-289页

作者： Feng Li Yuan Yang Hua Yue Shuang Wang Xiao Zhang Wei Wei State Key Laboratory of Biochemical engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190China Key Laboratory of biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing100190China School of Chemical engineering University of Chinese Academy of SciencesBeijing100049China

Ferritin has emerged as a promising nanocarrier for delivering therapeutic agents to tumours.However,the limited drug loading and the off-target impacts after systemic administration remain challenges for cancer treatment with ferritin-based agents.Herein,we develop a microneedle patch loaded with ferritin-nanocaged doxorubicin(DoxFe@Fn/MN)for skin cancer treatment.Briefly,doxorubicin(Dox)is encapsulated in ferritin(Fn)using an iron core-assisted strategy,which results in a 3.4-fold increase in Dox loading compared to the direct loading method.Then,a polyvinyl alcohol-based microneedle(MN)patch is used for the transdermal delivery of DoxFe@Fn,enabling targeted tumour accumulation of DoxFe@Fn and preventing off-target impacts.The released DoxFe@Fn can bind to CD71 highly expressed on skin cancer cells,facilitating its uptake.As a result,the DoxFe@Fn/MN therapy presents a robust antitumour effect in a melanoma tumour model,showing its potential as a promising therapeutic modality for skin cancer treatment.

关键词： Ferritin Microneedle Skin cancer Drug delivery

Targeted therapeutic effects of oral magnetically driven pectin nanoparticles containing chlorogenic acid on colon cancer

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Particuology 2024年第1期84卷 53-59页

作者： Huatai Zhu Limei Zhang Fujia Kou Jingyang Zhao Jiandu Lei Jing He Beijing Key Laboratory of Lignocellulosic Chemistry Beijing Forestry UniversityBeijing100083China Institute of biopharmaceutical and Health engineering Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Oral colonic nano-drug delivery system has attracted growing attention in treating colon cancer for their excellent characteristics.However,the unique and complex structure of the gastrointestinal tract is still an obstacle to the safe delivery of drugs targeting sites in colon tumors.Here,we designed magnetically driven dual-targeted oral colonic nanoparticles loaded with chlorogenic acid using pectin and oleic acid-modified iron oxide(Fe3O4@OA).Specific degradation of pectin by pectinase produced by colonic flora and magnetic fields applied to the colon confers specific targeting of nanoparticles to the colon.In order to overcome the challenge of preparing magnetically driven nanoparticles with small and homogeneous particle sizes by a single conventional method,we developed the combined ultrasound-emulsification technique.The average particle size of the prepared nanoparticles was 81.04±1.02 nm,which showed good drug release in the simulated colonic environment.In vitro anticancer studies,the drug-loaded nanoparticles possess an obvious toxicity and apoptosis-inducing ability against cancer cells.Meanwhile,the hemolysis results demonstrated the safety of the nanoplatform(PET/CGA/Fe_(3)O_(4)@OA).This work holds broad prospects as a new treatment modality for colon cancer.

关键词： Pectin Chlorogenic acid Ultrasound-emulsion Magnetically driven Colon cancer Colon targeted

Base editor-mediated large-scale screening of functional mutations in bacteria for industrial phenotypes

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Science China(Life Sciences) 2024年第5期67卷 1051-1060页

作者： Yaomeng Yuan Xihao Liao Shuang Li Xin-Hui Xing Chong Zhang MOE Key Laboratory for Industrial Biocatalysis Institute of Biochemical EngineeringDepartment of Chemical EngineeringTsinghua UniversityBeijing 100084China Institute of biopharmaceutical and Health engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and engineering Shenzhen Bay LaboratoryShenzhen 440300China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China

Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.

关键词： base editor high-throughput large-scale screening Escherichia coli functional mutation

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Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

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Food Science and Human Wellness 2024年第4期13卷 1886-1905页

作者： Wei Li Haihong Chen Hongliang Chen Ziyin Li Wei Hu Qinxuan Zhou Bing Xu Yi Wang Xinhui Xing Institute of biopharmaceutical and Health engineering Tsinghua Shenzhen International Graduate SchoolShenzhen 518055China Institute of Biomedical Health Technology and engineering Shenzhen Bay LaboratoryShenzhen 440300China Key Laboratory for Industrial Biocatalysis Ministry of EducationInstitute of Biochemical EngineeringDepartment of Chemical EngineeringBeijing 100084China Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084China Affiliated Dongguan Hospital Southern Medical University(Dongguan People’s Hospital)Dongguan 523059China

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

关键词： Andrias davidianus bone peptides Hyperuricemia Uric acid Chronic kidney disease Gut microbiota

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Exogenous ketogenic supplements can mitigate the susceptibility to Alzheimer’s disease induced by chronic sleep deprivation:emerging role of Sirt1 in ferroptosis

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Food Science and Human Wellness 2024年

作者： Yueqi Yang Xueyan Wang Lu Chen Ning Zhang Shilei Ji Zhengping Wang Jun Han Yuming Wang Min Wen Pet Nutrition Rresearch and Development Center Gambol Pet Group Co. Ltd. Institute of biopharmaceutical Research Liaocheng University College of Food Science and engineering Ocean University of China

Emerging evidence supports that sleep disorders are the main risk factor for sporadic Alzheimer’s disease (AD)， and iron dysregulation may be the link between them. Our previous studies have confirmed that ketogenic diet (KD) can prevent chronic sleep deprivation-induced AD. However， it is uncertain whether exogenous ketones supplements (EKS)， as an alternative intervention， have the same effects as KD. Thus， we investigated the prophylactic efficiency of EKS on chronic sleep deprivation-induced AD and reveal the underlying mechanism focus on iron metabolism. We observed that the prophylactic efficacy of EKS against chronic sleep deprivation-induced AD was comparable to that of KD. Meanwhile， our results suggest that both EKS and KD inhibited iron metabolism disorder through regulation of iron metabolism-related proteins. Moreover， we found that both EKS and KD reduced hippocampal mitochondrial dysfunction and iron-mediated lipid peroxides. Furthermore， EX527 (Sirt1 inhibitor)， mostly abrogated these above protections of EKS， suggesting that the prophylactic effect of EKS on AD is partly dependent on Sirt1. Our findings provide novel evidence that EKS can be developed as functional foods to prevent or delay the development of AD， particularly in individuals with sleep disorders.

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Advances in advanced solution-synthesis-based structural materials for tactile sensors and their intelligent applications

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InfoMat 2024年第1期6卷 31-64页

作者： Hongsen Niu Ning Li Eun-Seoung Kim Young Kee Shin Nam-Young Kim Guozhen Shen Yang Li School of Information Science and engineering University of JinanJinanthe People's Republic of China RFIC Centre Department of Electronics EngineeringKwangwoon UniversitySeoulRepublic of Korea Department of Molecular Medicine and biopharmaceutical Sciences Seoul National UniversitySeoulRepublic of Korea School of Integrated Circuits and Electronics Beijing Institute of TechnologyBeijingthe People's Republic of China School of Microelectronics Shandong UniversityJinanthe People's Republic of China

Intelligent applications,with tactile sensors at their core,represent significant advancement in the field of artificial intelligence.However,achieving perception abilities in tactile sensors that match or exceed human skin remains a formidable challenge.Consequently,the design and implementation of hierarchical structural materials are considered the optimal solution to this challenge.In contrast to conventional methods,such as complicated lithography and three-dimensional printing,the cost-effective and scalable nature of advanced solution-synthesis methods makes them ideal for preparing diverse tactile sensors with hierarchical structural materials.However,the process and applicability of advanced solution synthesis methods have yet to form a seamless system.Accordingly,the development and intellectualization of tactile sensors based on advanced solution synthesis methods are still in their early stages,and require a comprehensive and systematic review to usher in progress.This study delves into the advantages and disadvantages of various advanced solution synthesis methods,providing detailed insights.Furthermore,the positive effects of hierarchical structural materials constructed using these methods in tactile sensors and their intelligent applications are also discussed in depth.Finally,the challenges and future opportunities faced by this emerging field are summarized.

关键词： aqueous phase reduction artificial intelligence hydrothermal growth in situ polymerization tactile sensor

Tailoring Classical Conditioning Behavior in TiO_(2) Nanowires:ZnO QDs-Based Optoelectronic Memristors for Neuromorphic Hardware

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Nano-Micro Letters 2024年第7期16卷 265-280页

作者： Wenxiao Wang Yaqi Wang Feifei Yin Hongsen Niu Young-Kee Shin Yang Li Eun-Seong Kim Nam-Young Kim School of Information Science and engineering University of JinanJinan 250022People’s Republic of China RFIC Centre NDAC CentreKwangwoon UniversityNowon-guSeoul 139-701South Korea Department of Electronics engineering Kwangwoon UniversityNowon-GuSeoul 139-701South Korea School of Microelectronics Shandong UniversityJinan 250101People’s Republic of China Department of Molecular Medicine and biopharmaceutical Sciences Seoul National UniversitySeoul 08826South Korea

Neuromorphic hardware equipped with associative learn-ing capabilities presents fascinating applications in the next generation of artificial intelligence.However,research into synaptic devices exhibiting complex associative learning behaviors is still nascent.Here,an optoelec-tronic memristor based on Ag/TiO_(2) Nanowires:ZnO Quantum dots/FTO was proposed and constructed to emulate the biological associative learning behaviors.Effective implementation of synaptic behaviors,including long and short-term plasticity,and learning-forgetting-relearning behaviors,were achieved in the device through the application of light and electrical stimuli.Leveraging the optoelectronic co-modulated characteristics,a simulation of neuromorphic computing was conducted,resulting in a handwriting digit recognition accuracy of 88.9%.Furthermore,a 3×7 memristor array was constructed,confirming its application in artificial visual memory.Most importantly,complex biological associative learning behaviors were emulated by mapping the light and electrical stimuli into conditioned and unconditioned stimuli,respectively.After training through associative pairs,reflexes could be triggered solely using light stimuli.Comprehen-sively,under specific optoelectronic signal applications,the four features of classical conditioning,namely acquisition,extinction,recovery,and generalization,were elegantly emulated.This work provides an optoelectronic memristor with associative behavior capabilities,offering a pathway for advancing brain-machine interfaces,autonomous robots,and machine self-learning in the future.

关键词： Artificial intelligence Classical conditioning Neuromorphic computing Artificial visual memory Optoelectronic memristors ZnO Quantum dots

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Constructing efficient bacterial cell factories to enable one-carbon utilization based on quantitative biology:A review

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Quantitative Biology 2024年第1期12卷 1-14页

作者： Yazhen Song Chenxi Feng Difei Zhou Zengxin Ma Lian He Cong Zhang Guihong Yu Yan Zhao Song Yang Xinhui Xing School of Life Sciences Shandong Province Key Laboratory of Applied Mycologyand Qingdao International Center on Microbes Utilizing BiogasQingdao AgriculturalUniversityQingdaoChina Department of Chemical engineering University of WashingtonSeattleWashingtonUSA Key Laboratory of Systems Bioengineering Ministry of EducationTianjin UniversityTianjinChina Key Laboratory of Industrial Biocatalysis Ministry of EducationDepartment of Chemical EngineeringTsinghua UniversityBeijingChina Center for Synthetic and Systems Biology Tsinghua UniversityBeijingChina Institute of biopharmaceutical and Health engineering Tsinghua Shenzhen International Graduate Schooland Insttute of Biomedical Health Technology and EngineeringShenzhen Bay LaboratoryShenzhenChina

Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic significance for building a carbon-neutral,sustainable economic and industrial system.With the rapid advancement of RNA sequencing technology and mass spectrometer analysis,researchers have used these quantitative microbiology methods extensively,especially isotope-based metabolic flux analysis,to study the metabolic processes initiating from C1 feedstocks in natural C1-utilizing bacteria and synthetic C1 bacteria.This paper reviews the use of advanced quantitative analysis in recent years to understand the metabolic network and basic principles in the metabolism of natural C1-utilizing bacteria grown on methane,methanol,or formate.The acquired knowledge serves as a guide to rewire the central methylotrophic metabolism of natural C1-utilizing bacteria to improve the carbon conversion efficiency,and to engineer non-C1-utilizing bacteria into synthetic strains that can use C1 feedstocks as the sole carbon and energy source.These progresses ultimately enhance the design and construction of highly efficient C1-based cell factories to synthesize diverse high value-added products.The integration of quantitative biology and synthetic biology will advance the iterative cycle of understand–design–build–testing–learning to enhance C1-based biomanufacturing in the future.

关键词： ^(13)C-metabolic flux analysis methylotrophic cell factories one-carbon feedstock quantitative biology

仿生酶固定化纳米反应器通过级联催化反应实现胆固醇的精确检测（英文）

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Science China Materials 2024年

作者：熊京商灵灵赵德偲王丹 State Key Laboratory of Biochemical engineering Key Laboratory of Biopharmaceutical Preparation and Delivery Institute of Process Engineering Chinese Academy of Sciences University of Chinese Academy of Sciences

基于酶的生化检测方法具有准确性高、检测速度快等优势,但生物酶的不稳定性限制了这一方法的应用.因此,开发一种活性高、稳定性强、反应效率高的酶包封体系是提高胆固醇生化检测的关键.为此,本研究发展了由二棕榈酸磷脂酰胆碱包覆中空...

基于酶的生化检测方法具有准确性高、检测速度快等优势,但生物酶的不稳定性限制了这一方法的应用.因此,开发一种活性高、稳定性强、反应效率高的酶包封体系是提高胆固醇生化检测的关键.为此,本研究发展了由二棕榈酸磷脂酰胆碱包覆中空多壳层结构的仿生人造细胞, HoMS的区室化结构和磷脂膜的选择透过性实现了酶的稳定包封和信号的高效传输.本研究通过信号的级联放大实现了胆固醇的快速准确检测.即利用负载胆固醇氧化酶的HoMS@DPPC引发胆固醇氧化反应,产生的中间产物H2O2作为信号分子,在负载辣根过氧化物酶的HoMS@DPPC催化作用下,促进荧光红染料生成试卤灵,再进行比色检测胆固醇的含量.由级联催化介导的胆固醇信号放大使得该系统可以应用于胆固醇检测,并且该方法表现出高的选择性和准确性,检测范围为0.05～0.3 mM,检测限可达4.9μM.该方法可用于动物血清中胆固醇的检测,回收率为90.8%～104.9%,检测值与商业检测方法的结果高度吻合.此外,该系统可与智能设备集成,构建智能比色平台,实现图像分析与胆固醇浓度检测的一体化,为准确、快速的生化检测开辟了新途径.

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Screening of Chinese giant salamander meat hydrolysates with DPP-IV inhibitory activity and systematic elucidation of their hypoglycemic functions in mouse model

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Food Science and Human Wellness 2024年

作者： Shucheng Li Changge Guan Yi Wang Haihong Chen Wei Li Songjun Wang Chong Zhang Xin-Hui Xing Key Laboratory for Industrial Biocatalysis Ministry of Education of China Department of Chemical engineering Tsinghua University School of Life Science and Technology Tokyo Institute of Technology Institute of biopharmaceutical and Health engineering Tsinghua Shenzhen International Graduate School Henan Giant Salamander Protection and Development Association Center for Synthetic and Systems Biology Tsinghua University Institute of Biomedical Health Technology and engineering Shenzhen Bay Laboratory

Type 2 diabetes (T2D) presents a significant health challenge， underscoring the need for functional foods and nutraceutical hypoglycemic bioactive peptides for its prevention. This study investigates the potential of proteolytic hydrolysate from artificially cultivated Chinese giant salamander (CGS) meat， a rich protein source， as a preventive strategy for T2D. We produced a CGS meat hydrolysate (CGSh) and demonstrated its ability to inhibit the T2D drug target DPP-IV through in vitro assays. We identified five peptides (WRPPDH， WAPPSKD， IPDSPF， IPEMIF， and VPIAVPT) with high DPP-IV inhibitory activity in CGSh， suggesting its potential antidiabetic effects. In vivo experiments showed that CGSh effectively reduced insulin resistance in mice induced with a high-fat diet， as evidenced by a slower increase in blood glucose levels and a decreased HOMA-IR index. 16S rRNA sequencing analysis revealed that CGSh improved gut microbial homeostasis， promoting beneficial microorganisms and reducing harmful bacteria. Metabolomic analyses identified an increase in valeric acid levels and highlighted nine potential biomarker metabolites. By inhibiting metabolic pathways such as AGE-RAGE， CGSh may also prevent diabetic complications and reduce inflammation. These findings suggest that CGSh has a promising hypoglycemic effect， making it a potential functional food ingredient for T2D prevention and treatment.

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