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Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1624-1643页

作者： Can Cheng Hanhui Yao Heng Li Jingwen Liu Zhengyi Liu Yang wu liang Zhu Hejie Hu Zhengdong Fang liang wu Department of General Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Comprehensive Surgery Anhui Provincial Cancer HospitalWest District of the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Provincial Hospital Health Management Center the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Breast Surgery Henan Provincial People's HospitalPeople's Hospital of Zhengzhou UniversityPeople's Hospital of Henan UniversityZhengzhou 450003China

HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

关键词： Colorectal cancer Invasion and metastasis Post-translational modification Ubiquitination SUMOylation USP48 HMGA2 Specific inhibitors

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Research on Credit Default Swaps Pricing Considering Moral Hazard Incentive under Reduce-Form Model

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Journal of Systems Science and Systems Engineering 2024年第3期33卷 311-329页

作者： liang wu Kangjie He Zhe Guo School of Mathematical Science Henan Institute of Science and TechnologyXinxiang453003China Public Front Office Department Industrial and Commercial Bank of ChinaZhengzhou450000China

Equilibrium pricing of credit default swaps(CDS)promotes efficient identification of credit risk in the market,which in turn leads to efficient allocation of resources.However,even when CDS have been priced in equilibrium,i.e.,when premiums are equal to anticipated payments,the moral hazard incentives of CDS buyers increase with CDS transactions.Consequentially,it becomes an interesting research direction to study the impact of moral hazard incentives on the trading mechanism or pricing of derivatives(CDS).Most of the existing literature on the impact of moral hazard incentives in CDS pricing on derivatives trading mechanisms takes a macro perspective and focuses on the agreement risk effect.The literature exploring the analysis of the impact of moral hazard on the probability of agreement default from a micro perspective is not yet available.With this in mind,this paper focuses on the mechanisms by which“fraud”,an extreme manifestation of micro-moral hazard incentives,affects the probability of default.This paper introduces for the first time the concept of“claiming fraud”by credit protection buyers,which is different from the macro perspective of moral hazard incentives,and thus defines a specific extreme form of moral hazard incentives.Meanwhile,to address the intrinsic feature of the lack of economic explanatory power of the reduce-form model,this paper introduces a moral hazard incentive factor into the reduce-form model,and proposes a moral hazard state variable as a function of the asset value of the reference entity,which gives the reduce-form model strong economic explanatory power,and the default predictability is reduced by the description of the reduce-form model.In terms of the object of study,this paper considers the issue of moral hazard incentives in the presence of claiming fraud in two reference entities to further explore the impact of moral hazard incentives on default protection at the micro level in terms of cyclic default.Finally,based on the analysis of the results of the numerical simulat

关键词： Financial engineering moral hazard incentive claiming fraud reduce-form model probability of default calculation CDS pricing

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Modified electronic structure and enhanced hydroxyl adsorption make quaternary Pt-based nanosheets efficient anode electrocatalysts for formic acid-/alcohol-air fuel cells

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Journal of Energy Chemistry 2024年第5期92卷 142-150页

作者： Fengling Zhao Qiang Yuan Siyang Nie liang wu Xun Wang State-Local Joint Laboratory for Comprehensive Utilization of Biomass Center for R&D of Fine ChemicalsCollege of Chemistry and Chemical EngineeringGuizhou UniversityGuiyang 550025GuizhouChina Key Lab of Organic Optoelectronics&Molecular Engineering Tsinghua UniversityBeijing 100084China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Surface/interface engineering of a multimetallic nanostructure with diverse electrocatalytic properties for direct liquid fuel cells is desirable yet challenging.Herein,using visible light,a class of quaternary Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)ultrathin nanosheets is fabricated and used as high-performance anode electrocatalysts for formic acid-/alcohol-air fuel cells.The modified electronic structure of Pt,enhanced hydroxyl adsorption,and abundant exterior defects afford Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C high intrinsic anodic electrocatalytic activity to boost the power densities of direct formic acid-/methanol-/ethanol-/ethylene glycol-/glycerol-air fuel cells,and the corresponding peak power density of Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C is respectively 129.7,142.3,105.4,124.3,and 128.0 mW cm^(-2),considerably outperforming Pt/C.Operando in situ Fourier transform infrared reflection spectroscopy reveals that formic acid oxidation on Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)/C occurs via a CO_(2)-free direct pathway.Density functional theory calculations show that the presence of Ag,Bi,and Te in Pt_(1)Ag_(0.1)Bi_(0.16)Te_(0.29)suppresses CO^(*)formation while optimizing dehydrogenation steps and synergistic effect and modified Pt effectively enhance H_(2)O dissociation to improve electrocatalytic performance.This synthesis strategy can be extended to 43 other types of ultrathin multimetallic nanosheets(from ternary to octonary nanosheets),and efficiently capture precious metals(i.e.,Pd,Pt,Rh,Ru,Au,and Ag)from different water sources.

关键词： Pt-based nanosheets Modifiedelectronic structure Enhanced hydroxyl adsorption Formicacidand alcohol oxidation Direct liquid fuel cells

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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

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Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding liang wu Jie Chen Ping He Yan Cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor prognosis.Despite that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired resistance.Therefore,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing necessity.Here,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive BC.We determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice models.This may be attributed to enhanced autophagy induced by endoplasmic reticulum stress.Furthermore,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of BC.Mechanistically,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with ZBTB16.Inhibition of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive BC.Together,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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Proteomics for early prenatal screening of gestational diabetes mellitus

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World Journal of Clinical Cases 2024年第26期12卷 5850-5853页

作者： liang wu Xiu-Ping Wang Yun-Xia Zhu Yan-Ping Tan Chun-Ming Li Department of Dermatology The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Dermatology Jiangxi Provincial Maternal and Child Health HospitalNanchang 330000Jiangxi ProvinceChina

In this editorial,we comment on the article by Cao et al.Through applying isobaric tags for relative and absolute quantification technology coupled with liquid chromatography-tandem mass spectrometry,the researchers observed significant differential expression of 47 proteins when comparing serum samples from pregnant women with gestational diabetes mellitus(GDM)to the healthy ones.GDM symptoms may involve abnormalities in inflammatory response,complement system,coagulation cascade activation,and lipid metabolism.Retinol binding protein 4 and angiopoietin like 8 are potential early indicators of GDM.GDM stands out as one of the most prevalent metabolic complications during pregnancy and is linked to severe maternal and fetal outcomes like pre-eclampsia and stillbirth.Nevertheless,none of the biomarkers discovered so far have demonstrated effectiveness in predicting GDM.Our topic was designed to foster insights into advances in the application of proteomics for early prenatal screening of GDM.

关键词： Gestational diabetes mellitus Proteomics Biomarker Blood Placenta

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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.wu Shawn N.Whitehead Department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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Synchronization of second-order Kuramoto networks from the perspective of edge dynamics

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Control Theory and Technology 2023年第4期21卷 580-590页

作者： liang wu Jiuming Zhong Haoyong Chen School of Physics and Electronic Engineering Hainan Normal UniversityHaikou571158HainanChina School of Electric Power South China University of TechnologyGuangzhou510640GuangdongChina

This paper presents new synchronization conditions for second-order phase-coupled Kuramoto oscillators in terms of edge dynamics.Two types of network-underlying graphs are studied,the positively weighted and signed graphs,respectively.We apply an edge Laplacian matrix for a positively weighted network to represent the edge connections.The properties of the edge Laplacian matrix are analyzed and incorporated into the proposed conditions.These conditions take account of the dynamics of edge-connected oscillators instead of all oscillator pairs in conventional studies.For a network with positive and negative weights,we represent the network by its spanning tree dynamics,and derive conditions to evaluate the synchronization state of this network.These conditions show that if all edge weights in the spanning tree are positive,and the tree-induced dynamics are in a dominant position over the negative edge dynamics,then this network achieves synchronization.The theoretical findings are validated by numerical examples.

关键词： Kuramoto oscillator Signed graph Synchronization Edge Laplacian matrix Spanning tree

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Hybrid Adaptive Event‑Triggered Platoon Control with Package Dropout

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Automotive Innovation 2022年第4期5卷 347-358页

作者： Jiawei Wang Fangwu Ma liang wu Guanpu wu The State Key Laboratory of Automotive Simulation and Control Jilin University5988 Renmin StreetChangchun 130022China

A novel hybrid adaptive event-triggered platoon control strategy is proposed to achieve the balanced coordination between communication resource utilization and vehicle-following performance considering the effect of package dropout.To deal with the disturbance caused by the event-triggered scheme,the parameter space approach is adopted to derive the feasible region from which cooperative adaptive cruise control controller satisfies internal stability,distance accuracy,and string stability.Subsequently,the Bernoulli random distribution process is employed to depict the phenomenon of package drop-out,and the hybrid coefficient is proposed to realize the allocation between the adaptive trigger threshold strategy and the adaptive headway strategy.The simulation of a six-vehicle platoon is carried out to verify the effectiveness of the designed control strategy.Results show that about 78.76%of communication resources have been saved by applying the event-triggered scheme,while guaranteeing the desired vehicle-following performance.And in the non-ideal communication environment with frequent package dropouts,the hybrid adaptive strategy achieves the coordination among communication resource utilization,string stability margin,distance accuracy,and traffic efficiency.

关键词： Cooperative adaptive cruise control Event-triggered scheme Hybrid adaptive strategy Package dropout Parameter space approach

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An all-silicon design of a high-efficiency broadband transmissive terahertz polarization convertor

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Frontiers of Optoelectronics 2023年第4期16卷 91-99页

作者： Xiaohua Xing Die Zou Xin Ding Jianquan Yao liang wu College of Precision Instrument and Optoelectronics Engineering Key Laboratory of Optoelectronics Information and Technology(Ministry of Education)Tianjin UniversityTianjin 300072China

Polarization,a fundamental behavior of electromagnetic waves,holds immense potential across diverse domains such as environmental monitoring,biomedicine,and ocean exploration.However,achieving efcient modulation of terahertz waves with wide operational bandwidth poses signifcant challenges.Here,we introduce an all-silicon polarization converter designed specifcally to operate in the terahertz range of the electromagnetic spectrum.Simulation results demonstrate that the average conversion efciency of cross-linear waves exceeds 80%across a wide frequency range spanning from 1.00 to 2.32 THz,with the highest conversion efciency peaking at an impressive 99.97%.Additionally,our proposed structure facilitates linear-to-circular polarization conversion with an ellipticity of 1 at 0.85 THz.Furthermore,by rotating the crossshaped microstructure,active control over arbitrary polarization states can be achieved.To summarize,the proposed structure ofers remarkable fexibility and ease of integration,providing a reliable and practical solution for achieving broadband and efcient polarization conversion of terahertz waves.

关键词： Broadband High efficiency Polarization conversion All-silicon

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Enthalpy-change driven synthesis of high-entropy perovskite nanoparticles

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Nano Research 2022年第6期15卷 4867-4872页

作者： Siyang Nie liang wu Lingci Zhao Pengfei Zhang School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Due to their diverse and tunable composition,distorted lattice and excellent stability,high-entropy ceramics(HECs)hold great promise for catalysis,especially when they present as nanoparticles(NPs).However,current HECs are typically limited to bulky materials with none or fewer defects,because high synthetic temperature(e.g.,1,000–1,200°C)is usually required to highlight the entropic contribution(TΔS)inΔG=ΔH−TΔS.Being different with previous strategies,a negative Gibbs free energy for HECs crystallization is obtained by dramatically decreasing the mixing enthalpy(ΔH).Guided by this principle,single-phase highentropy La(Ni_(0.2)Mn_(0.2)Cu_(0.2)Fe_(0.2)Co_(0.2))O_(3−δ)perovskite(HE-LMO)NPs were prepared at a relatively low temperature(≤500°C).Interestingly,abundant oxygen vacancies were directly created within HE-LMO NPs,which exhibited good activity in catalytic oxidation.Meanwhile,the high-entropy structure endows as-made HE-LMO with robust stability even with 5 vol.%water in feeding gas.Density functional theory(DFT)calculations revealed that the defective sites in HE-LMO NPs facilitated the charge transfer from HE-LMO to CO,thus activating the adsorbed CO gas.The current work may inspire future design and synthesis of HECs NPs.

关键词： enthalpy-change high-entropy ceramics mechanochemical synthesis perovskite CO oxidation

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