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PICOTEES:a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts

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Journal of Genetics and Genomics 2024年第2期51卷 243-251页

作者： Xinran Dong Yulan Lu Lanting Guo chuan Li qi Ni Bingbing Wu Huijun Wang Lin Yang Songyang Wu qi Sun Hao zheng Wenhao Zhou Shuang Wang Center for Molecular Medicine Children's Hospital of Fudan UniversityShanghai 201102China Key Laboratory of Birth Defects Children's Hospital of Fudan UniversityShanghai 201102China Department of Bioinformatics Hangzhou Nuowei Information Technology Co.LtdHangzhouZhejiang 310000China The Third Research Institute of the Ministry of Public Security Shanghai 200031China Xiamen Campus of Children's Hospital of Fudan University XiamenFujian 361006China Institutes for Systems Genetics West China HospitalChengduSichuan 610041China Shanghai Putuo People's Hospital Tongji UniversityShanghai 200060China

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://***:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

关键词： Privacy protecti on Rare diseases in children Genetic testing Web system Trusted executi on envir onment

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A Fibonacci View on the Galois NFSR Used in Trivium

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Journal of Systems Science & Complexity 2024年第3期37卷 1326-1350页

作者： WANG Hongyu zheng Qunxiong qi Wenfeng PLA Strategic Support Force Information Engineering University Zhengzhou 450001China

Trivium is an international standard of lightweight stream ciphers(ISO/IEC 29192-3:2012).In this paper,the Trivium-like NFSRs,a class of Galois NFSRs generalized from the Galois NFSR of Trivium,are studied from the perspective of Fibonacci NFSRs.It is shown that an n-stage Trivium-like NFSR cannot be equivalent to an n-stage Fibonacci NFSR,which is proved by showing the existence of“collision initial states”.As an intermediate conclusion,a necessary and sufficient condition for a kind of linear degeneracy of a Trivium-like NFSR is obtained from the persepective of interleaved sequences.Moreover,the smallest stage number of a Fibonacci NFSR that can generate all the output sequences of an n-stage Trivium-like NFSR is shown to be greater than n-7 and this value is no less than 371=287+min{93,84,111}specifically for the 288-stage Galois NFSR used in Trivium.These results contradict the existence of a equivalent Fibonacci model of Trivium NFSR of small stage,which implies that Trivium algorithm possesses a fair degree of immunity against“structure attack”.

关键词： Fibonacci NFSR galois NFSR interleaved sequence linear degeneracy trivium

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Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

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World Journal of Stem Cells 2024年第5期16卷 499-511页

作者： Shuai Zhang chuan Lu Sheng zheng Guang Hong Division for International Collaborative and Innovative Dentistry Tohoku University Graduate School of DentistrySendai 980-8575MiyagiJapan School of Stomatology Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina

BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

关键词： Hydrogel Bone marrow mesenchymal stem cells Macrophage polarization Angiogenesis Bone regeneration

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Dual-assisted high-precision tracking technique for wideband multiplexed signals in new generation GNSS

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Satellite Navigation 2024年第1期5卷 52-73页

作者： Yunhan qi zheng Yao Mingquan Lu Department of Electronic Engineering Tsinghua UniversityBeijing100084China Beijing National Research Center for Information Science and Technology Beijing100084China

With the evolution of Global Navigation Satellite System(GNSS),new generation GNSS signals have adopted the dual-frequency multiplexing modulation techniques,which jointly modulate multiple signals located on multiple sub-frequencies into a Wideband Multiplexed Signal(WMS).Although WMSs were proposed initially to reduce the complexity of satellite transmitters and improve the transmission efficiency of signals,their multi-component structures and wide root mean square bandwidths introduced by high-frequency subcarriers also provide the possibility to improve the GNSS ranging precision.Therefore,this paper proposes a Dual-assisted Multi-component Tracking(DMT)technique,which can not only fully use high-frequency subcarriers in WMSs,but also effectively track carrier,subcarrier,and code by jointly utilizing all components in WMS.In this paper,the tracking and ranging performances of DMT are comprehensively analyzed theoretically and by simulation and real experiments.The results show that compared with existing WMS tracking methods,DMT can achieve tracking results with lower tracking jitters and ranging results with higher precision,providing a highly advantageous solution for new generation GNSS signal processing.

关键词： Wideband multiplexed signal Dual-assisted Multi-component High precision tracking

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π-conjugated chromophore functionalized high-nuclearity titanium-oxo clusters containing structural unit of anatase for photocatalytic selective oxidation of sulfides

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Rare Metals 2024年第4期43卷 1736-1746页

作者： Ling-Rong Liao Dong-Chun zheng Pin-Xi Ou qi-Xin Zhao Wei-Min Xuan qi zheng State Key Laboratory for Modification of Chemical Fibers and Polymer Materials & College of Materials Science and Engineering Donghua University State Key Laboratory for Modification of Chemical Fibers and Polymer Materials and College of Chemistry and Chemical Engineering Donghua University

N-doping has significant influence in manipulating the properties of TiO2,and this has stimulated the development of N-donor-functionalized titanium-oxo clusters（TOCs） as molecular models to study the structure-property relationship.However,the structural type and photoresponsive application are still limited for such TOCs,especially regarding the high-nuclearity TOCs that contain structure unit of TiO2for photocatalysis.Herein,we showed the synthesis of a series of high-nuclearity TOCs 1-3 compounds using π-conjugated 1,10-phenanthroline（phen） as chromophore and N-donor functional ligand.Compound 1 features cocrystal structure composed of one [Ti26]2+and half [Ti22]2+,which renders it as the first cocrystallized TOC containing two positively charged species and phen-functionalized TOC showing the highest nuclearity up to 37 Ti centers.By adjusting the synthetic conditions,the individual {Ti22} and {Ti26} clusters can also be isolated as Compounds 2 and 3,respectively.The core structure of {Ti22} is mainly constructed from four lacunary {Ti4} derived from pentagonal {Ti（Ti）5} unit,while {Ti26} is built from four complete {Ti（Ti）5} unit.Notably,a {Ti8O14} structure unit of anatase TiO2can be identified in {Ti26}.Based on the unique structural features and proper photophysical and photochemical properties of Compounds 1-3,they are applied for photocatalytic sulfoxidation.Owing to the presence of anatase structure unit in {Ti26} and the synergistic effect from {Ti22} and {Ti26},the catalytic performance presents in the order of Compound 1> Compound 3> Compound 2.This work provides excellent models to understand the structureproperty relationship from the perspective of cocrystallization and Ti-O binding model and will further promote the application of TOCs as functional catalysts for organic transformation.

关键词： Titanium-oxo cluster Molecular model of anatase TiO 2 High nuclearity π-conjugated chromophore Photocatalytic sulfoxidation

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Boundary points, minimal L^(2) integrals and concavity property Ⅱ: Weakly pseudoconvex Kähler manifolds

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Science China Mathematics 2024年第7期67卷 1665-1718页

作者： qi’an Guan Zhitong Mi zheng Yuan School of Mathematical Sciences Peking UniversityBeijing100871China School of Mathematics and Statistics Beijing Jiaotong UniversityBeijing100044China Institute of Mathematics Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing100190China

In this paper, we consider minimal L^(2) integrals on the sublevel sets of plurisubharmonic functions on weakly pseudoconvex K?hler manifolds with Lebesgue measurable gain related to modules at boundary points of the sublevel sets, and establish a concavity property of the minimal L^(2) integrals. As applications, we present a necessary condition for the concavity degenerating to linearity, a concavity property related to modules at inner points of the sublevel sets, an optimal support function related to modules, a strong openness property of modules and a twisted version, and an effectiveness result of the strong openness property of modules.

关键词： minimal L^(2)integrals plurisubharmonic functions boundary points weakly pseudoconvex K?hler manifold

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Multi-electron reaction and fast Al ion diffusion of δ-MnO_(2) cathode materials in rechargeable aluminum batteries via first-principle calculations

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Chinese Chemical Letters 2024年第4期35卷 248-254页

作者： Lumin zheng Ying Bai chuan Wu School of Materials Science&Engineering Beijing Institute of TechnologyBeijing 100081China Yangtze Delta Region Academy of Beijing Institute of Technology Jiaxing 314019China

Rechargeable aluminum batteries with multi-electron reaction have a high theoretical capacity for next generation of energy storage devices. However, the diffusion mechanism and intrinsic property of Al insertion into MnO_(2) are not clear. Hence, based on the first-principles calculations, key influencing factors of slow Al-ions diffusion are narrow pathways, unstable Al-O bonds and Mn^(3+) type polaron have been identified by investigating four types of δ-MnO_(2)(O3, O'3, P2 and T1). Although Al insert into δ-MnO_(2) leads to a decrease in the spacing of the Mn-Mn layer, P2 type MnO_(2) keeps the long(spacious pathways)and stable(2.007–2.030 A) Al-O bonds resulting in the lower energy barrier of Al diffusion of 0.56 e V. By eliminated the influence of Mn^(3+)(low concentration of Al insertion), the energy barrier of Al migration achieves 0.19 e V in P2 type, confirming the obviously effect of Mn^(3+) polaron. On the contrary, although the T1 type MnO_(2) has the sluggish of Al-ions diffusion, the larger interlayer spacing of Mn-Mn layer,causing by H_(2)O could assist Al-ions diffusion. Furthermore, it is worth to notice that the multilayer δ-MnO_(2) achieves multi-electron reaction of 3|e|. Considering the requirement of high energy density, the average voltage of P2(1.76 V) is not an obstacle for application as cathode in RABs. These discover suggest that layered MnO_(2) should keep more P2-type structure in the synthesis of materials and increase the interlayer spacing of Mn-Mn layer for providing technical support of RABs in large-scale energy storage.

关键词： Rechargeable aluminum batteries δ-MnO_(2) First-principles calculations Multi-electron reaction Diffusion mechanism

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Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1009-1029页

作者： Runping Liu Yajing Li qi zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102400China School of Life Sciences Beijing University of Chinese MedicineBeijing 102400China Department of Microbiology and Immunology Virginia Commonwealth UniversityRichmondVA 22460USA

Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

关键词： Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development

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DGS1 improves rice disease resistance by elevating pathogenassociated molecular pattern-triggered immunity

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aBIOTECH 2024年第1期5卷 46-51页

作者： Yu Wang chuan zheng You-liang Peng qian Chen MOA Key Lab of Pest Monitoring and Green Management and Frontiers Science Center for Molecular Design Breeding China Agricultural UniversityBeijing 100193China

Rice yield and disease resistance are two crucial factors in determining the suitability of a gene for agricultural breeding.Decreased grain size1(DGS1),encoding an RING-type E3 ligase,has been found to have a positive effect on rice yield by regulating rice grain number and 1000-grain weight.However,the role of DGS1 in rice blast resistance is still unknown.In this study,we report that DGS1 enhances disease resistance by improving PTI responses,including stronger ROS burst and MAPK activation,and also increased expression of defense-related genes.Furthermore,DGS1 works in conjunction with ubiquitin conjugating enzyme OsUBC45 as an E2-E3 pair to facilitate the ubiquitin-dependent degradation of OsGSK3 and OsPIP2;1,thereby influencing rice yield and immunity,respectively.Therefore,the DGS1-OsUBC45 module has the potential in facilitating rice agricultural breeding.

关键词： Rice blast PTI ERAD E2-E3 pair Ubiquitination

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DEM analysis of the influence of stirrer design on die filling with forced powder feeding

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Particuology 2024年第5期88卷 107-115页

作者： Chao zheng Edward Yost Ariel R.Muliadi Nicolin Govender Ling Zhang chuan-Yu Wu School of Chemistry and Chemical Engineering University of SurreyGuildfordGU2 7XHUnited Kingdom Small Molecule Pharmaceutics GenentechInc.One DNA WaySouth San FranciscoCA94080USA

Die filling is a critical stage during powder compaction,which can significantly affect the product quality and efficiency.In this paper,a forced feeder is introduced attempting to improve the filling performance of a lab-scale die filling system.The die filling process is analysed with a graphics processing units(GPU)enhanced discrete element method(DEM).Various stirrer designs are assessed for a wide range of process settings(i.e.,stirrer speed,filling speed)to explore their influence on the die filling performance of free-flowing powder.Numerical results show that die filing with the novel helical-ribbon(i.e.,type D)stirrer design exhibits the highest filling ratio,implying that it is the most robust stirrer design for the feeder configuration considered.Furthermore,die filling performance with the type D stirrer design is a function of the stirrer speed and the filling speed.A positive variation of filling ratio(ηf>0%)can be ensured over the whole range of filling speed by adjusting the stirrer speed(i.e.,increasing the stirrer speed).The approach used in this study can not only help understand how the stirrer design affects the die filling performance but also guide the optimization of feeder system and process settings.

关键词： Discrete element method Die filling Forced feeding Stirrer design GPU computing

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