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Targeting oncogenic SOX2 in human cancer cells: therapeutic application

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Protein & Cell 2020年第2期11卷 82-84页

作者： Shizhen Zhang Yi Sun Division of Radiation and Cancer Biology Department of Radiation OncologyUniversity of MichiganAnn ArborMl 48109USA The Cancer Institute of the Second Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China

Sry-related high-mobility box 2(SOX2)is a critical transcription factor that plays an important role in various phases of embryonic development and maintenance of undifferentiated embryonic stem cells(ESCs)(Feng and Wen,2015).SOX2,as one of the Yamanaka factors,is involved in the conversion of mouse embryonic fibroblast cells(MEFs)into induced pluripotent stem cells(iPSCs)(Takahashi and Yamanaka,2006).Recently,SOX2 amplification,usually couples with aberrantly increased expression,were found in various human cancers,including breast,lung,esophagus,colon,prostate,ovarian among the others(Novak et al.,2019).SOX2 overexpression promotes cancer progression by accelerating cell proliferation,colony formation,migration,invasion,and sphere formation.Furthermore,SOX2 is causally related to the development of the resistance of cancer cells to chemotherapy.

关键词： SOX2 cancer invasion

Total Synthesis of Syringin and Its Natural Analogues via C—C Bond Activation of Aryl Ketones

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Chinese Journal of Chemistry 2023年第24期41卷 3587-3592页

作者： Zhen-Yu Wang Yi Sun Guo-Dong sun Hui Xu Hui-Xiong Dai School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjingJiangsu210023 China CAS Key Laboratory of Receptor Research State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203 China University of Chinese Academy of Sciences Beijing100049 China

Syringin is found in the root of Acanthopanax senticosus(Rupr.Maxim.)Harms and belongs to the lignin chemical compound with many biological activities.In this study,we employed commercially available starting materials and accomplished the total synthesis of syringin in 5 steps with an overall yield of 58%.Palladium-catalyzed C(O)–C bond activation and subsequent cross coupling reaction is the key to construct syringin and its natural analogues.

关键词： Syringin Total synthesis Cross-coupling C—C activation Syringin analogues

Buchstaber Invariants of Universal Complexes

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Chinese Annals of Mathematics,Series B 2017年第6期38卷 1335-1344页

作者： Yi Sun School of Mathematical Sciences Fudan UniversityShanghai 200433China.

Davis and Januszkiewicz introduced(real and complex) universal complexes to give an equivalent definition of characteristic maps of simple polytopes, which now can be seen as "colorings". The author derives an equivalent definition of Buchstaber invariants of a simplicial complex K, then interprets the difference of the real and complex Buchstaber invariants of K as the obstruction to liftings of nondegenerate simplicial maps from K to the real universal complex or the complex universal complex. It was proved by Ayzenberg that real universal complexes can not be nondegenerately mapped into complex universal complexes when dimension is 3. This paper presents that there is a nondegenerate map from 3-dimensional real universal complex to 4-dimensional complex universal complex.

关键词：建筑群通用戴维斯定义相等地图

A Survey of Voltage-Controlled-Oscillator-Based ?∑ ADCs

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Tsinghua Science and Technology 2022年第3期27卷 472-480页

作者： yi Zhong Nan sun Department of Electronic Engineering Tsinghua UniversityBeijing 100084China Department of Electrical and Computer Engineering The University of Texas at AustinAustinTX 78712USA

The benefits of technology scaling have fueled interest in realizing time-domain oversampling(?∑) of Analog-to-Digital Converters(ADCs). Voltage-Controlled Oscillators(VCO) are increasingly used to design ?∑ADCs because of their simplicity, high digitization, and low-voltage tolerance, making them a promising candidate to replace the classical Operational Transconductance Amplifier(OTA) in ?∑ ADC design. This work aims to provide a summary of the fully VCO-based ?∑ ADCs that are highly digital and scaling-friendly. This work presents a review of first-order and high-order VCO-based ?∑ ADCs with several techniques and architectures to mitigate the nonidealities introduced by VCO, achieving outstanding power efficiency. The contributions and drawbacks of these techniques and architectures are also discussed.

关键词： Voltage-Controlled Oscillator(VCO) Analog-to-Digital Converter(ADC) oversampling(?∑)ADC time-domain signal processing VCO-based?∑ADC

Emergent antisymmetric wrinkling patterns in films on ridged substrates

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Science China(Physics,Mechanics & Astronomy) 2023年第11期66卷 179-187页

作者： Jiahui Zhang Yi Sun Linghui He Yong Ni CAS Key Laboratory of Mechanical Behavior and Design of Materials Department of Modern MechanicsCAS Center for Excellence in Complex System MechanicsUniversity of Science and Technology of ChinaHefei230026China

We report the formation of antisymmetric wrinkling patterns in films on ridged substrates induced by the buckling instability of the substrates via finite element simulations and experiments.Our simulated results reveal that the uniaxial compression along the ridge can trigger both the wrinkling instability of the film and the lateral buckling instability of the ridge.The latter could change the wrinkles from a symmetric pattern to an antisymmetric pattern in a range of film-substrate modulus ratio and aspect ratio of the ridge profile,as validated by the experimental observations.A three-dimensional phase diagram with four buckling patterns,i.e.,sole ridge buckling pattern,antisymmetric wrinkling pattern with different wavelengths from ridge buckling,symmetric wrinkling pattern without ridge buckling,and antisymmetric wrinkling pattern with the same wavelength as ridge buckling,is built with respect to the uniaxial compression,modulus ratio,and aspect ratio.The results not only elucidate how and when the interplay between the wrinkling instability and the ridge instability results in the formation of the antisymmetric wrinkling pattern but also offer a way to generate controllable complex wrinkling patterns.

关键词： wrinkling pattern buckling instability ridged film-substrate system antisymmetric wrinkles

Anticancer drug discovery by targeting cullin neddylation

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Acta Pharmaceutica Sinica B 2020年第5期10卷 746-765页

作者： Qing Yu yihan Jiang Yi Sun Cancer Institute of the 2nd Affiliated Hospital Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Division of Radiation and Cancer Biology Department of Radiation OncologyUniversity of MichiganAnn ArborMI 48109.USA

Protein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade.The bestknown substrates of neddylation are cullin family proteins,which are the core component of Cullin-RING E3 ubiquitin ligases(CRLs).Given that cullin neddylation is required for CRL activity,and CRLs control the turn-over of a variety of key signal proteins and are often abnormally activated in cancers,targeting neddylation becomes a promising approach for discovery of novel anti-cancer therapeutics.In the past decade,we have witnessed significant progress in the field of protein neddylation from preclinical target validation,to drug screening,then to the clinical trials of neddylation inhibitors.In this review,we first briefly introduced the nature of protein neddylation and the regulation of neddylation cascade,followed by a summary of all reported chemical inhibitors of neddylation enzymes.We then discussed the structure-based targeting of protein-protein interaction in neddylation cascade,and finally the available approaches for the discovery of new neddylation inhibitors.This review will provide a focused,up-to-date and yet comprehensive overview on the discovery effort of neddylation inhibitors.

关键词： Neddylation Anticancer Drug discovery Ubiquitin-proteasome system Small molecule inhibitors Virtual screen High-throughput screening

DRRS-BC:Decentralized Routing Registration System Based on Blockchain

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IEEE/CAA Journal of Automatica Sinica 2021年第12期8卷 1868-1876页

作者： Huimin Lu Yu Tang Yi Sun College of Computer Science and Technology Qingdao UniversityQingdao 266071China School of Engineering Kyushu Institute of TechnologyKitakyushu 804-8550Japan School of Computer Science(National Pilot Software Engineering School) Beijing University of Posts and TelecommunicationsBeijing 100876China

The border gateway protocol(BGP)has become the indispensible infrastructure of the Internet as a typical inter-domain routing protocol.However,it is vulnerable to misconfigurations and malicious attacks since BGP does not provide enough authentication mechanism to the route advertisement.As a result,it has brought about many security incidents with huge economic losses.Exiting solutions to the routing security problem such as S-BGP,So-BGP,Ps-BGP,and RPKI,are based on the Public Key Infrastructure and face a high security risk from the centralized structure.In this paper,we propose the decentralized blockchain-based route registration framework-decentralized route registration system based on blockchain(DRRS-BC).In DRRS-BC,we produce a global transaction ledge by the information of address prefixes and autonomous system numbers between multiple organizations and ASs,which is maintained by all blockchain nodes and further used for authentication.By applying blockchain,DRRS-BC perfectly solves the problems of identity authentication,behavior authentication as well as the promotion and deployment problem rather than depending on the authentication center.Moreover,it resists to prefix and subprefix hijacking attacks and meets the performance and security requirements of route registration.

关键词： Blockchain decentralized routing protocol routing registration

Astrocyte polarization in glaucoma: a new opportunity

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Neural Regeneration Research 2022年第12期17卷 2582-2588页

作者： yi-Xin Liu Hao sun Wen-yi Guo Department of Ophthalmology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology ShanghaiChina

Astrocyte polarization is a new concept which is similar to microglia polarization and in which astrocytes are classified as A1(neurotoxic)and A2(neuroprotective).Several studies on astrocyte polarization have focused mainly on neurodegenerative diseases,trauma,and infections.However,the role of astrocyte polarization in glaucoma,a neurodegenerative disease,has not been fully explored.In this review,we first describe the characteristics of astrocyte astrogliosis in glaucoma,including morphological,molecular,proliferative and functional changes.We then summarize understanding of astrocyte polarization in other diseases,and show that A1 astrocytes are involved in the death of retinal ganglion cells in glaucoma,and that their neurotoxins kill only damaged retinal ganglion cells.Based on this,we propose new interesting conjecture on astrocyte polarization in glaucoma:(1)That the neurotoxin from A1 astrocytes is a product of the complement system(membrane-attacking complex),since this system is known to mediate synaptic elimination and the C3 expression is clearly increased in A1 astrocytes;(2)that reactive scar-forming astrocytes in the optic nerve head may be classified as A2 astrocytes since their ablation leads to a worse prognosis in glaucoma.Finally,current therapeutic research progress on astrocyte polarization in other diseases is also addressed.Regulation of astrocyte polarization can be achieved by extracellular microglia-related and intracellular pathways.Reduced A1 or increased A2 astrocytes can rescue the nerve.For example,glucagon-like peptide-1 receptor agonist rescues retinal ganglion cells by reducing A1 astrocytes via the extracellular microglia-related pathway in an ocular hypertension model,suggesting that regulation of astrocyte polarization as a therapeutic target in glaucoma is feasible.

关键词： astrocytes glaucoma heterogeneity microglia neurodegenerative disease neuroinflammation neuroprotection optic nerve retina therapy

Evaluation of water management on arsenic methylation and volatilization in arsenic-contaminated soils strengthened by bioaugmentation and biostimulation

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Journal of Environmental Sciences 2024年第3期137卷 515-526页

作者： Peng Chen yi Liu Guo-Xin sun State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Aquatic Botany and Watershed Ecology Wuhan Botanical GardenChinese Academy of SciencesWuhan 430074China University of Chinese Academy of Sciences Beijing 100049China

Arsenic(As) fate in paddy fields has been one of the most significant current issues due to the strong As accumulation potential of rice plants under fooded conditions. However,no attempt was done to explore As methylation and volatilization under non-fooded conditions. Herein, we investigated the effects of water management on As methylation and volatilization in three arsenic-contaminated soils enhanced by biostimulation with strawderived organic matter and bioaugmentation with genetic engineered Pseudomonas putida KT2440(GE P. putida). Under fooded conditions, the application of biochar(BC), rice straw(RS)and their combination(BC+RS) increased total As in porewater. However, these effects were greatly attenuated under non-fooded conditions. Compared with RS amendment alone, the combination of GE P. putida and RS further promoted the As methylation and volatilization,and the promotion percentage under non-fooded conditions were significantly higher than that under fooded conditions. The combined GE P. putida and RS showed the highest efficiency in As methylation(88 μg/L) and volatilization(415.4 μg/(kg·year)) in the non-fooded soil with moderate As contamination. Finally, stepwise multiple linear regression analysis presented that methylated As, DOC and p H in porewater were the most important factors contributing to As volatilization. Overall, our findings suggest that combination of bioaugmentation with GE P. putida and biostimulation with RS/BC+RS is a potential strategy for bioremediation of arsenic-contaminated soils by enhancing As methylation and volatilization under non-fooded conditions.

关键词： Arsenic methylation Arsenic volatilization Water management Straw incorporation Bioaugmentation