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Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

Protein & Cell 2024年第1期15卷 6-20页

作者： Ning Wu Ling Wei Zhipeng Zhu Qiang Liu Kailong Li Fengbiao Mao Jie Qiao Xiaolu Zhao State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China National Clinical Research center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking university) Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Institute of Medical Innovation and Research Peking University Third HospitalBeijing 100191China Cancer center Peking University Third HospitalBeijing 100191China Department of Biochemistry and Biophysics Beijing Key Laboratory of Protein Posttranslational Modifications and Cell FunctionSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Beijing Advanced Innovation center for Genomics Beijing 100191China Peking-Tsinghua center for Life Sciences Peking UniversityBeijing 100191China

Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular eukaryotes.Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are available.Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research hotspot.Several mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification models.Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health.The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites.The present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction.We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic tumors.This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

关键词： extrachromosomal circular DNAs gynecologic tumors reproduction liquid biopsy non-invasive prena-tal testing

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Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani Nicholas W.Markin Kim F.Duncan Michael J.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation.Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based interventions.Important considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical practice.We present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical research.Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation.It is imperative to minimize animal loss during procedures that are surgically complex.We present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

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Layer Hall effect induced by hidden Berry curvature in antiferromagnetic insulators

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National Science Review 2024年第2期11卷 15-23页

作者： Rui Chen Hai-Peng Sun Mingqiang Gu Chun-Bo Hua Qihang Liu Hai-Zhou Lu X.C.Xie Shenzhen Institute for Quantum Science and Engineering and Department of Physics Southern University of Science and Technology(SUSTech) International Quantum Academy Institute for Theoretical Physics and Astrophysics University of Würzburg School of Electronic and Information Engineering Hubei University of Science and Technology Guangdong Provincial Key Laboratory of Computational Science and Material Design Southern University of Science and Technology Shenzhen Key Laboratory of Quantum Science and Engineering International center for Quantum Materials School of PhysicsPeking University Collaborative Innovation center of Quantum Matter CAS center for Excellence in Topological Quantum Computation University of Chinese Academy of Sciences

The layer Hall effect describes electrons spontaneously deflected to opposite sides at different layers, which has been experimentally reported in the MnBi2Te4thin films under perpendicular electric fields. Here, we reveal a universal origin of the layer Hall effect in terms of the so-called hidden Berry curvature, as well as material design principles. Hence, it gives rise to zero Berry curvature in momentum space but non-zero layer-locked hidden Berry curvature in real space. We show that, compared to that of a trivial insulator, the layer Hall effect is significantly enhanced in antiferromagnetic topological insulators. Our universal picture provides a paradigm for revealing the hidden physics as a result of the interplay between the global and local symmetries, and can be generalized in various scenarios.

关键词： layerHall effect hidden Berry curvature antiferromagnetic insulator axion insulator, quantum transport

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Geometry characteristics and wide temperature behavior of silicon-based GaN surface acoustic wave resonators with ultrahigh quality factor

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Science China(Information Sciences) 2024年第2期67卷 267-278页

作者： Guofang YU Renrong LIANG Haiming ZHAO Lei XIAO Jie CUI Yue ZHAO Wenpu CUI Jing WANG Jun XU Jun FU Tianling REN School of Integrated Circuits Tsinghua University Beijing National Research center for Information Science Technology Tsinghua University

Surface acoustic wave(SAW) resonators with an ultrahigh Q-factor are designed and fabricated on silicon-based gallium nitride(GaN/Si). The temperature-dependent performance is characterized over a wide range, from 10 to 500 K. Finite element analysis is employed to guide the design of the SAW resonator from indications of the Rayleigh mode and weak propagation direction dependence of SAW in the c-plane of GaN/Si. The SAW resonator with 100 pairs of interdigital transducers(IDT), 100 pairs of grating reflectors(GR) for each side, aperture size of 80 μm, metallization ratio of 0.5, and electrode width of 500 nm resonates at 1.9133 GHz accordingly with an ultrahigh Q-factor of 7622 at room temperature, which contributes the fr× Qr, up to 14.583×1012Hz. A resonator operating over 10 to 500 K indicates an approximately linear decreasing temperature dependence above 280 K while being approximately constant below 40 K. The fitting to resonator characteristics using the modified Butterworth Van Dyke(m BVD) model reveals a reduction in both the electrode and mechanical losses while worsening the dielectric loss with cooling down.

关键词： GaN/Si SAW resonator ultrahigh Q-factor temperature-dependent performance mBVD losses

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Progress in electrocatalytic nitrate reduction for green energy: Catalyst engineering, mechanisms, and techno-economic feasibility

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Journal of Energy Chemistry 2024年第8期95卷 380-406页

作者： Hafiz Muhammad Adeel Sharif Hafiz Muhammad Farooq Khan Sadeeq Ullah Yuwei Wang Muhammad Ahmad Bo Yang Changping Li Muhammad Bilal Asif Research center for Eco-Environmental Engineering Dongguan University of Technology College of Chemistry and Engineering Shenzhen University FMH College of Medicine and Dentistry School of Environment and Civil Engineering Research Center for Eco-Environment Engineering Dongguan University of Technology Advanced Membranes and Porous Materials center (AMPMC) Physical Sciences and Engineering (PSE) King Abdullah University of Science and Technology (KAUST)

Ammonia（NH3） is an irreplaceable chemical that has been widely demanded to keep the sustainable development of modern society.However,its industrial production consumes a huge amount of energy and releases extraordinary greenhouse gases（GHGs）,leading to various environmental issues.Achieving the green production of ammonia is a great challenge,which has been extensively pursued in the last decade.In this review,the most promising strategy,electrochemical nitrate reduction reaction（e-NO3RR）,is comprehensively investigated to give a complete understanding of its development and mechanism and provide guidance for future directions.However,owing to the complex reactions and limited selectivity,a comprehensive understanding of the mechanisms is crucial to further development and commercialization.Moreover,NO3-RR is a promising strategy for simultaneous water treatment and NH3production.A detailed overview of the recent progress in NO3-RR for NH3production with nontransition and transition metal based electrocatalysts is summarized.In addition,critical advanced techniques,future challenges,and prospects are discussed to guide future research on transition metal-based catalysts for commercial NH3synthesis by NO3-reduction.

关键词： Ammonia synthesis Electrolysis Green energy Nitrate reduction Pollution to solution Transition metal catalysts

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Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

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Cellular & Molecular Immunology 2024年第3期21卷 275-291页

作者： Zhi-Dong Zhang Chang-Rui Shi Fang-Xu Li Hu Gan Yanhong Wei Qianhui Zhang Xin Shuai Min Chen Yu-Lin Lin Tian-Chen Xiong Xiaoqi Chen Bo Zhong Dandan Lin Department of Gastrointestinal Surgery Medical Research InstituteFrontier Science Center of Immunology and MetabolismZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan430071China Department of Virology College of Life SciencesWuhan UniversityWuhan430072China TaiKang center for Life and Medical Sciences Wuhan UniversityWuhan430071China Wuhan Research center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan430071China Department of Rheumatology and Immunology Zhongnan Hospital of Wuhan UniversityWuhan430071China Cancer center Renmin Hospital of Wuhan UniversityWuhan430060China

STING(also known as MITA)is an adaptor protein that mediates cytoplasmic DNA-triggered signaling,and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation.Here,we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram(DSF).Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1^(–/–)mice and STING^(N153S/WT) bone marrow chimeric mice.In addition,knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α,IFN-γand proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus(SLE)who exhibit high concentrations of dsDNA in peripheral blood.Mechanistically,knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1^(–/–)mice.Interestingly,knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts.Taken together,these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

关键词： STING/MITA Disulfiram RNF115 SLE Autoimmunity

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Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao Zhu Xiaoxia Chen Kwok-Fai So Anding Xu Lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University Department of Neurology and Stroke center The First Affiliated HospitalJinan University Department of Psychiatry The First Affiliated HospitalJinan University Co-innovation center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

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CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Journal of Genetics and Genomics 2024年第5期51卷 531-542页

作者： Danhui Ruan Jiancheng Xu Yang Liu Juan Luo Xuyang Zhao Yuhua Li Guangxi Wang Jiawen Feng Hui Liang Yue Yin Jianyuan Luo Yuxin Yin Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University International Cancer InstitutePeking-Tsinghua Center of Life SciencesPeking University Health Science CenterBeijing 100191China Institute of Precision Medicine Peking University Shenzhen HospitalShenzhenGuangdong 518036China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Medical Genetics Center for Medical GeneticsSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Soochow university Cancer Institute SuzhouJiangsu 215127China

Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

关键词： Circular RNA LRPPRC Mitochondrial energy metabolism mtDNApost-transcriptional regulation

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The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

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Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss Christine Heuer Marina Herwerth Institute of Pharmacology and Toxicology University of Zurich Neuroscience center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders purinergic system P2 receptor inhibitors suramin

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang Laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical Science Wenzhou Medical University Institute of Life Sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

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