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Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

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Current Medical Science 2023年第2期43卷 246-254页

作者： Xun li You-jian LI Meng-jie WANG Ke-peng OU Ya-qi CHEN GI Cancer Research Institute Tongji HospitalHuazhong University of Science and TechnologyWuhan430030China College of Pharmacy National&Local Joint Engineering Research Center of Targeted and Innovative TherapeuticsChongqing Key Laboratory of Kinase Modulators as Innovative MedicineChongqing University of Arts and SciencesChongqing402160China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China College of Pharmaceutical Sciences and Chinese Medicine Southwest UniversityChongqing400715China

Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as EliSA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.

关键词： cyclin F kidney renal clear cell carcinoma clinical outcome cyclin-dependent kinase 1 senescence

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HOXA11-AS aggravates microglia-induced neuroinflammation after traumatic brain injury

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Neural Regeneration Research 2022年第5期17卷 1096-1105页

作者： Xiang-Long li Bin Wang Fu-Bing Yang li-Gang Chen jian you Department of Neurosurgery the Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Neurosurgical Clinical Research Center and Academician(Expert)Workstation of Sichuan Province LuzhouSichuan ProvinceChina Laboratory of Neurological Diseases and Brain Functions the Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina

Long noncoding RNAs(lnc RNAs)participate in many pathophysiological processes after traumatic brain injury by mediating neuroinflammation and apoptosis.Homeobox A11 antisense RNA(HOXA11-AS)is a member of the lnc RNA family that has been reported to participate in many inflammatory reactions;however,its role in traumatic brain injury remains unclear.In this study,we established rat models of traumatic brain injury using a weight-drop hitting device and injected LV-HOXA11-AS into the right lateral ventricle 2 weeks before modeling.The results revealed that overexpression of HOXA11-AS aggravated neurological deficits in traumatic brain injury rats,increased brain edema and apoptosis,promoted the secretion of proinflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factorα,and promoted the activation of astrocytes and microglia.Microglia were treated with 100 ng/m L lipopolysaccharide for 24 hours to establish in vitro cell models,and then transfected with pc DNA-HOXA11-AS,mi R-124-3 p mimic,or sh-MDK.The results revealed that HOXA11-AS inhibited mi R-124-3 p expression and boosted MDK expression and TLR4-nuclear factor-κB pathway activation.Furthermore,lipopolysaccharide enhanced potent microglia-induced inflammatory responses in astrocytes.Forced overexpression of mi R-124-3 p or downregulating MDK repressed microglial activation and the inflammatory response of astrocytes.However,the mi R-124-3 p-mediated anti-inflammatory effects were reversed by HOXA11-AS.These findings suggest that HOXA11-AS can aggravate neuroinflammation after traumatic brain injury by modulating the mi R-124-3 p-MDK axis.This study was approved by the Animal Protection and Use Committee of Southwest Medical University(approval No.SMU-2019-042)on February 4,2019.

关键词： astrocyte competitive endogenous RNA HOXA11-AS microglia midkine miR-124-3p neuroinflammation traumatic brain injury

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Neoantigen cancer vaccines:a new star on the horizon

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Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling li jian you liping Hong Weijiang liu Peng Guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University Cancer Institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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Squeezing microwaves by magnetostriction

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National Science Review 2023年第5期10卷 208-214页

作者： Jie li Yi-Pu Wang jian-Qiang you Shi-Yao Zhu Interdisciplinary Center of Quantum Information Zhejiang Province Key Laboratory of Quantum Technology and Deviceand State Key Laboratory of Modern Optical InstrumentationSchool of PhysicsZhejiang University

Squeezed light finds many important applications in quantum information science and quantum metrology,and has been produced in a variety of physical systems involving optical non-linear processes.Here,we show how a non-linear magnetostrictive interaction in a ferrimagnet in cavity magnomechanics can be used to reduce quantum noise of the electromagnetic field.We show optimal parameter regimes where a substantial and stationary squeezing of the microwave output field can be achieved.Realization of the scheme is within reach of current technology in cavity electromagnonics and magnomechanics.Our work provides a new and practicable approach for producing s queezed vacuum states of electromagnetic fields,and may find promising applications in quantum information processing and quantum metrology.

关键词： squeezing of quantum noise cavity magnonics magnomechanics

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An in-depth mechanistic insight into the redox reaction and degradation of aqueous Zn-MnO_(2) batteries

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Chinese Chemical Letters 2023年第4期34卷 531-536页

作者： Zongyuan you Wei Hua Na li Huanyan liu jian-Gan Wang State Key Laboratory of Solidication Processing Center for Nano Energy MaterialsSchool of Materials Science and EngineeringNorthwestern Polytechnical UniversityShaanxi Joint Lab of Graphene(NPU)Xi’an 710072China

Rechargeable aqueous Zn/MnO_(2)batteries raise massive research activities in recent years. However, both the working principle and the degradation mechanism of this battery chemistry are still under debate. Herein, we provide an in-depth electrochemical and structural investigation on this controversial issue based on α-MnO_(2)crystalline nanowires. Mechanistic analysis substantiates a two-electron reaction pathway of Mn2+/Mn4+redox couple from part of MnO_(2)accompanying with a reversible precipitation/dissolution of flaky zinc sulfate hydroxide(ZSH) during the discharge/charge processes. The formation of the ZSH layer is double-edged, which passivates the deep dissolution of MnO_(2)upon discharging,but promotes the electrochemical deposition kinetics of active MnO_(2)upon charging. The cell degradation originates primarily from the corrosion failure of metallic zinc anode and the accumulation of irreversible ZnMn2O_(4)phases on the cathode. The addition of MnSO_(4)to the electrolyte could afford supplementary capacity contribution via electro-oxidation of Mn2+. However, a high MnSO_(4)concentration will expedite the cell failure by corroding the metallic zinc anodes. The present study will shed a fundamental insight on developing new strategies toward practically viable Zn/MnO_(2)batteries.

关键词： Zinc-ion battery MnO_(2)cathode Working mechanism Degradation mechanism Zinc anode

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Exploring the Cation Regulation Mechanism for Interfacial Water Involved in the Hydrogen Evolution Reaction by In Situ Raman Spectroscopy

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Nano-Micro Letters 2024年第3期16卷 303-312页

作者： Xueqiu you Dongao Zhang Xia‑Guang Zhang Xiangyu li Jing‑Hua Tian Yao‑Hui Wang jian‑Feng li School of Ocean Information Engineering Fujian Provincial Key Laboratory of Oceanic Information Perception and Intelligent ProcessingJimei UniversityXiamen 361021People’s Republic of China State Key Laboratory of Physical Chemistry of Solid Surfaces MOE Key Laboratory of Spectrochemical Analysis and InstrumentationiChEMCollege of Chemistry and Chemical EngineeringCollege of MaterialsCollege of EnergyXiamen UniversityXiamen 361005People’s Republic of China Key Laboratory of Green Chemical Media and Reactions Ministry of EducationCollaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsCollege of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007People’s Republic of China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005People’s Republic of China

Interfacial water molecules are the most important participants in the hydrogen evolution reaction(HER).Hence,understanding the behavior and role that interfacial water plays will ultimately reveal the HER mechanism.Unfortunately,investigating interfacial water is extremely challenging owing to the interference caused by bulk water molecules and complexity of the interfacial environment.Here,the behaviors of interfacial water in different cationic electrolytes on Pd surfaces were investigated by the electrochemistry,in situ core-shell nanostructure enhanced Raman spectroscopy and theoretical simulation techniques.Direct spectral evidence reveals a red shift in the frequency and a decrease in the intensity of interfacial water as the potential is shifted in the positively direction.When comparing the different cation electrolyte systems at a given potential,the frequency of the interfacial water peak increases in the specified order:li+

关键词： In situ Raman Interfacial water Hydrogen evolution reaction Cations

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Recent progress in ultraviolet and deep-ultraviolet nonlinear optical aluminoborates

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Chinese Journal of Structural Chemistry 2023年第3期42卷 47-55页

作者： Qing-Fen li Wei-Feng Chen you-Zhao Lan jian-Wen Cheng Key Laboratory of the Ministry of Education for Advanced Catalysis Materials Institute of Physical ChemistryZhejiang Normal UniversityJinhuaZhejiang321004China

Aluminoborates(ABOs)show wide ultraviolet(UV)transmittance,and are one of the important types of UV and deep-UV nonlinear optical(NLO)materials.In recent years,the combination of AlO_(n)(n=4,5,6)polyhedra or their fluorinated analogues with different polyborate anions leads to a rich variety of crystalline ABOs.In this review,we summarize the recent developments of UV and deep-UV NLO inorganic ABOs.These ABOs can be grouped into three types in terms of their compositions:(i)aluminum oxyborates,(ii)alkali/alkaline earth metal aluminoborates,and(iii)alkali/alkaline earth metal aluminoborate fluorides and fluoroaluminoborates.We discuss the synthesis,structural features,NLO properties,as well as related structure-performance relationships of these non-centrosymmetric ABOs.Finally,the future perspectives in this field are discussed.

关键词： Aluminum borate Nonlinear optical Ultraviolet Deep-ultraviolet

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Reconfigurable physical unclonable cryptographic primitives based on current-induced nanomagnets switching

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Science China(Information Sciences) 2022年第2期65卷 188-196页

作者： Shuai ZHANG jian ZHANG Shihao li Yaoyuan WANG Zhenjiang CHEN Jeongmin HONG Long you Wuhan National Laboratory for Optoelectronics and School of Optical and Electronic Information Huazhong University of Science and Technology

Hardware security primitives that preserve secrets are playing a crucial role in the Internet-ofThings(Io T) era. Existing physical unclonable function(PUF) instantiations, exploiting static randomness,generate challenge-response pairings(CRPs) to produce unique security keys that can be used to authenticate devices linked to the Io T. Reconfigurable PUFs(RPUFs) with dynamically refreshable CRPs can enhance the security and robustness of conventional PUFs. The in-plane current-driven perpendicular polarized nanomagnet switching via spin-orbit torque(SOT) possesses great potential for application to memory and logic, as the write-current path is separate from the read-current path, which naturally resolves the write-read interference. However, the stochastic switching of perpendicular magnetization, without an additional symmetry-breaking field, would significantly hinder the technological viability of commercial implementations. Here, we report an initialization-free physical RPUF implemented by SOT-induced stochastic switching of perpendicularly magnetized Ta/Co Fe B/Mg O nanodevices. Using a 15×15 nanomagnet array, we experimentally demonstrate a security primitive that offers a near-ideal 50% uniqueness over 100 reconfiguration cycles, as well as a low correlation coefficient between every two reconfiguration cycles. Our results show that current-induced nanomagnets switching paves the way for developing highly reliable and energy-efficient reconfigurable cryptographic primitives with a smaller footprint.

关键词： reconfigurable physical unclonable function spin-orbit torque cryptographic primitive spintronics nanomagnet

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Improving the damage potential of W-Zr reactive structure material under extreme loading condition

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Defence Technology（防务技术） 2021年第2期17卷 467-477页

作者： Lu-yao Wang jian-wei jiang Mei li jian-bing Men Shu-you Wang State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing 100081PR China

Projectiles made of reactive structure materials(RSM)can damage the target with not only kinetic but also chemical energy,but the enhanced damage potential of RSM may become compromised if extreme loading condition disintegrates the projectile before the target is reached.In this work,a ductile coating of Ni was introduced to a tungsten-zirconium(W-Zr)alloy,a typical brittle RSM,to preserve the damage potential of the projectile.Detonation driving tests were carried out with X-ray photography and gunpowder deflagration driving tests were carried out with high-speed photography for the coated and uncoated RSM samples,respectively.The craters on the witness target were analyzed by scanning electron microscopy and X-ray diffraction.The Ni coating was found to effectively preserve the damage potential of the W-Zr alloy under extreme loading conditions,whereas the uncoated sample fractured and ignited before impacting the target in both detonation and deflagration driving.The crack propagation between the reactively brittle core and the ductile coating was analyzed based on the crack arrest theory to mechanistically demonstrate how the coating improves the structural integrity and preserves the damage potential of the projectile.Specifically,the Ni coating envelops theW-Zr core until the coated sphere penetrates the target,and the coating is then eroded and worn to release the reactive core for the projectile to damage the target more intensively.

关键词： Reactive structure material Extreme loading Structural integrity Damage potential

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The E3 ubiquitin ligase SINA1 and the protein kinase BIN2 cooperatively regulate PHR1 in apple anthocyanin biosynthesis

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植物学报:英文版 2023年第9期65卷 2175-2193页

作者： jian‐Ping An Hong‐liang li Zhi‐Ying liu Da‐Ru Wang Chun‐Xiang you Yuepeng Han CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenHubei Hongshan LaboratoryThe Innovative Academy of Seed Design of Chinese Academy of SciencesWuhan 430074China College of Horticulture Science and Engineering Shandong Agricultural UniversityTai‐An 271018China

PHR1(PHOSPHATE STARVATION RESPONSE1)plays key roles in the inorganic phosphate(Pi)starvation response and in Pi deficiency-induced anthocyanin biosynthesis in plants. However, the post-translational regulation of PHR1 is unclear,and the molecular basis of PHR1-mediated anthocyanin biosynthesis remains elusive. In this study, we determined that MdPHR1 was essential for Pi deficiency-induced anthocyanin accumulation in apple(Malus × domestica). MdPHR1 interacted with MdWRKY75, a positive regulator of anthocyanin biosynthesis, to enhance the MdWRKY75-activated transcription of MdMYB1,leading to anthocyanin accumulation. In addition,the E3 ubiquitin ligase SEVEN IN ABSENTIA1(MdSINA1) negatively regulated MdPHR1-promoted anthocyanin biosynthesis via the ubiquitination-mediated degradation of MdPHR1.Moreover, the protein kinase apple BRASSINOSTEROID INSENSITIVE2(MdBIN2) phosphorylated MdPHR1 and positively regulated MdPHR1-mediated anthocyanin accumulation by attenuating the MdSINA1-mediated ubiquitination degradation of MdPHR1. Taken together,these findings not only demonstrate the regulatory role of MdPHR1 in Pi starvation induced anthocyanin accumulation, but also provide an insight into the post-translational regulation of PHR1.

关键词： anthocyanin biosynthesis apple phosphate starvation response phosphorylation PHR1 ubiquitination

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