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Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer

Asian Journal of Andrology 2016年第4期18卷 580-585页

作者： Jun Luo Department of Urology James Buchanan Brady Urological Institute Johns Hopkins University Baltimore MD USA.

Prostate cancer cells demonstrate a remarkable ＂addiction＂ to androgen receptor （AR） signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer （mCRPC）. In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 （AR-V7） has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.

关键词： androgen receptor androgen receptor splice variant-7 （AR-V7） castration-resistance prostate cancer circulating tumorcells treatment selection

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Pseudo-break imaging of carbon nanotubes for determining elastic bending energies

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Nano Research 2023年第5期16卷 7443-7451页

作者： Changfei Jing Yongji Qin Wengen Ouyang Jun Luo Institute for New Energy Materials and Low-Carbon Technologies and Tianjin Key Lab of Photoelectric Materials and Devices School of Materials Science and EngineeringTianjin University of TechnologyTianjin 300384China ShenSi Lab Shenzhen Institute for Advanced StudyUniversity of Electronic Science and Technology of ChinaShenzhen 518110China Department of Engineering Mechanics School of Civil EngineeringWuhan UniversityWuhan 430072China State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan UniversityWuhan 430072China

One-dimensional(1D)nanomaterials easily bend due to perturbations from their surroundings or their own behaviors.This phenomenon not only impacts the performances of various devices but has also been employed to develop a variety of new functional devices,in which the bending energies of the nanomaterials determine the device performances.However,measuring the energies of such nanomaterials is extremely difficult.Herein,pseudo-break imaging of 1D nanomaterials has been proposed and realized on individual carbon nanotubes(CNTs),in which a CNT appears to break and has a fracture but is actually intact.This imaging approach provides the values of the bending energies of the CNTs with an accuracy of 1–50 eV.Furthermore,this imaging approach can manipulate the bending shapes and energies of CNTs.This work presents a protocol for bending analysis and manipulation,which are vital to fundamental and applied studies of 1D nanomaterials.

关键词： pseudo-break imaging carbon nanotube electron microscopy elastic bending energy

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Effect of magnetic field on dislocation morphology and precipitation behaviour in ultrafine-grained 7075 aluminium alloy

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Journal of Materials Science & Technology 2021年第34期93卷 128-146页

作者： Jun Luo Hongyun luo Tianshu Zhao Runze Wang Key Laboratory of Aerospace Materials and Performance(Ministry of Education) School of Materials Science and EngineeringBeihang UniversityBeijing 100191China Beijing Key Laboratory of Advanced Nuclear Materials and Physics Beihang UniversityBeijing 100191China Beijing Advanced Innovation Centre for Biomedical Engineering Beihang UniversityBeijing 100191China

The influence of magnetic field(1 T)on dislocation morphology and precipitation behaviour of ultrafinegrained(UFG)Al 7075 alloy was investigated after ageing from 90 to 200℃ via wide angle X-ray scattering(WAXS),small angle X-ray scattering(SAXS),and transmission electron microscopy(TEM).Experimental results reveal that the improved precipitation kinetics of alloys in the thickness plane(denoted as sample II)as compared to those in the rolling plane(denoted as sample I),which arises due to a higher dislocation density(morphology of dislocation cells)of the thickness plane than that of the rolling plane(morphology of dislocations and dislocation tangles).Specifically,because of different dislocation morphologies,the magnetic field positively and negatively affects the dislocation activity in samples I and II,leading to enhanced and suppressed precipitation behaviors,respectively.Interestingly,nucleation of theηphase is facilitated in the UFG alloy at the critical temperature(140℃)because it affords a faster rate of atom diffusion and a higher dislocation density as compared to those exhibited by its coarse-grained alloy.This systematic and comprehensive study provides new insights into dislocation morphology and precipitation behaviour of the UFG 7075 Al alloy,while enabling the optimization of precipitation kinetics.

关键词： Ultrafine-grained Al alloy Precipitation behaviors Magnetic field Dislocation morphology Critical temperature

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Non-invasive actionable biomarkers for metastatic prostate cancer

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Asian Journal of Urology 2016年第4期3卷 170-176页

作者： Jun Luo Department of Urology and James Buchanan Brady Urological Institute Johns Hopkins UniversityBaltimoreMDUSA

In the current clinical setting,many disease management options are available for men diagnosed with prostate cancer.For metastatic prostate cancer,first-line therapies almost always involve agents designed to inhibit androgen receptor(AR)signaling.Castration-resistant prostate cancers(CRPCs)that arise following first-line androgen deprivation therapies(ADT)may continue to respond to additional lines of AR-targeting therapies(abiraterone and enzalutamide),chemotherapies(docetaxel and cabazitaxel),bonetargeting Radium-223 therapy,and immunotherapy sipuleucel-T.The rapidly expanding therapies for CRPC is expected to transform this lethal disease into one that can be managed for prolonged period of time.In the past 3 years,a number of promising biomarkers that may help to guide treatment decisions have been proposed and evaluated,including androgen receptor splice variant-7(AR-V7),a truncated AR lacking the ligand-binding domain(LBD)and mediate constitutively-active AR signaling.Putative treatment selection markers such as ARV7 may further improve survival benefit of existing therapies and help to accelerate development of new agents for metastatic prostate cancer.In the metastatic setting,it is important to consider compatibility between the putative biomarker with non-invasive sampling.In this review,biomarkers relevant to the setting of metastatic prostate cancer are discussed with respect to a number of key attributes critical for clinical development of non-invasive,actionable markers.It is envisioned that biomarkers for metastatic prostate cancer will continue to be discovered,developed,and refined to meet the unmet needs in both standard-of-care and clinical trial settings.

关键词： Prostate cancer Androgen receptor AR-V7 Biomarker CRPC

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Regulation of androgen receptor variants in prostate cancer

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Asian Journal of Urology 2020年第3期7卷 251-257页

作者： Yezi Zhu Jun Luo Department of Urology James Buchanan Brady Urological InstituteJohns Hopkins UniversityBaltimoreMDUSA LIVESTRONG Cancer Institutes The University of TexasAustinTXUSA

Aberrant activation of androgen receptor(AR)signaling occurs in patients treated with AR-targeted therapies,contributing to the development of castration-resistant prostate cancer(CRPC)and therapeutic resistance.Over the past decade,many AR variants(AR-Vs)have been identified in prostate cancer cell lines and clinical CRPC specimens.These AR-Vs lack the COOH-terminal ligand-binding domain(LBD),and may mediate constitutively active AR signaling acquired following AR-targeting therapies.AR splice variant-7(AR-V7),one of the most well characterized AR-Vs,can be reliably measured in tissue and liquid biopsy specimens,and blood-based detection of AR-V7 is a reliable indicator of poor outcome to relatively novel hormonal therapies(NHT)such as abiraterone and enzalutamide in men with metastatic CRPC(mCRPC).Given the important clinical implication of AR-Vs,this short review will focus on studies addressing how AR-Vs are regulated in prostate cancer.With regard to the molecular origin of AR-Vs,it is established that expression of AR-Vs is highly correlated with androgen deprivation and suppression of AR signaling.Therapeutic targeting of the AR axis may result in active transcription of the AR gene,elevated activities of certain components of the mRNA splicing machinery,as well as AR genomic alterations,all of which may explain the molecular origin of AR-Vs.Although a unified hypothesis is currently lacking,existing data suggest that elevated expression of AR-Vs,which in general occurs quite specifically in a cellular environment where the canonical AR signaling is suppressed,is driven by both genomic and epigenomic features acquired in the development of CRPC.

关键词： Androgen receptor Androgen receptor splice variant-7 Castration-resistant prostate cancer

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Active-site and interface engineering of cathode materials for aqueous Zn–gas batteries

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Nano Research 2023年第2期16卷 2325-2346页

作者： Wenxian Liu Jinxiu Feng Tianran Wei Qian Liu Shusheng Zhang Yang luo Jun Luo Xijun Liu College of Materials Science and Engineering Zhejiang University of TechnologyHangzhou 310014China Ministry of Education(MOE)Key Laboratory of New Processing Technology for Non-Ferrous Metals and Materials and Guangxi Key Laboratory of Processing for Non-Ferrous Metals and Featured MaterialsSchool of ResourceEnvironmentsand MaterialsGuangxi UniversityNanning 530004China Institute for Advanced Study Chengdu UniversityChengdu 610106China College of Chemistry Zhengzhou UniversityZhengzhou 450000China Empa Swiss Federal Laboratories for Materials Science and TechnologySwiss Federal Institute of Technology in Zurich(ETH)DomainDübendorf CH-8600Switzerland Hong Kong Productivity Council(HKPC) Hong Kong 999077China School of Materials Science and Engineering Tianjin University of TechnologyTianjin 300384China

Aqueous rechargeable Zn–gas batteries are regarded as promising energy storage and conversion devices due to their high safety and inherent environmental friendliness.However,the energy efficiency and power density of Zn–gas batteries are restricted by the kinetically sluggish cathode reactions,such as oxygen evolution reaction(OER)during charging and oxygen reduction reaction(ORR)/carbon dioxide reduction reaction(CO_(2)RR)/nitrogen reduction reaction(NRR)/nitric oxide reduction reaction(NORR)during discharge.In this review,battery configurations and fundamental reactions in Zn–gas batteries are first introduced,including Zn–air,Zn-CO_(2),Zn-N_(2),and Zn-NO batteries.Afterward,recent advances in active site engineering for enhancing the intrinsic catalytic activities of cathode catalysts are summarized.Subsequently,the structure and surface regulation strategies of cathode materials for optimizing the three-phase interface and improving the performance of Zn–gas batteries are discussed.Finally,some personal perspectives for the future development of Zn–gas batteries are presented.

关键词： Zn–gas batteries electrocatalysis single-atom catalysts chemical doping heterostructure interface

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A Simple Proof of ACC for Minimal Log Discrepancies for Surfaces

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Acta Mathematica Sinica,English Series 2024年第2期40卷 425-434页

作者： Jing jun HAN Yu Jie luo Shanghai Center for Mathematical Sciences Fudan UniversityJiangwan CampusShanghai 200438P.R.China Department of Mathematics Johns Hopkins UniversityBaltimoreMD 21218USA

Following Shokurov's idea,we give a simple proof of the ACC conjecture for minimal log discrepancies for surfaces.

关键词： Ascending chain condition minimal log discrepancies minimal model program surface

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Event-triggered adaptive finite-time control for nonlinear systems under asymmetric time-varying state constraints

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Frontiers of Information Technology & Electronic Engineering 2021年第12期22卷 1610-1624页

作者： Yan WEI Jun Luo Huaicheng YAN Yueying WANG School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai 200240China School of Mechatronic Engineering and Automation Shanghai UniversityShanghai 200444China School of Information Science and Engineering East China University of Science and TechnologyShanghai 200237China

This paper investigates the issue of event-triggered adaptive finite-time state-constrained control for multi-input multi-output uncertain nonlinear systems.To prevent asymmetric time-varying state constraints from being violated,a tan-type nonlinear mapping is established to transform the considered system into an equivalent“non-constrained”system.By employing a smooth switch function in the virtual control signals,the singularity in the traditional finite-time dynamic surface control can be avoided.Fuzzy logic systems are used to compensate for the unknown functions.A suitable event-triggering rule is introduced to determine when to transmit the control laws.Through Lyapunov analysis,the closed-loop system is proved to be semi-globally practical finite-time stable,and the state constraints are never violated.Simulations are provided to evaluate the effectiveness of the proposed approach.

关键词： Event-triggered control Nonlinear mapping Adaptive fuzzy control Finite-time State constraints

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Preparedness for a monkeypox outbreak

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Infectious Medicine 2022年第2期1卷 124-134页

作者： Qin luo jun Han State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention155 Changbai RdBeijing 102206China

In light of the ongoing COVID-19 pandemic,the unexpected outbreak and worldwide spread of monkeypox has gained global attention.As of june 22,2022,there were 3340 confirmed cases of monkeypox globally,which is the largest and most widespread monkeypox epidemic outside Africa.Monkeypox virus(MPXV)is transmitted from human-to-human through direct contact with infectious skin or mucosal skin lesions,respiratory droplets,or indirect contact with contaminated objects or materials,as well as mother-to-child vertical transmission.It is also possibly sexually transmitted through semen/vaginal fluid,and the possibility of community transmission cannot be ruled out.Monkeypox is a viral zoonotic disease caused by MPXV,which is an enveloped,linear,double-stranded DNA virus belonging to the Orthopoxvirus genus,of the Chordopoxvirinae subfamily,within the Poxviridae family.Monkeypox is usually a self-limiting infection,with symptoms lasting 2-4 weeks,and has a fatality rate that has historically fluctuated from 0%to 11%.Symptoms of monkeypox include intense headaches,fever,lesions,and lymphadenopathy.Although there is no specific treatment or vaccine for MPXV infection,antiviral drugs and vaccines for smallpox have been approved for use in several countries in response to the monkeypox outbreak.Before the virus can be allowed to establish efficient person-to-person transmission,rapid action must be taken to contain the local spread and,by extension,the multi-country outbreak of monkeypox.

关键词： Monkeypox virus Outbreak Infection Treatment

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Design and optimization of a gate-controlled dual direction electro-static discharge device for an industry-level fluorescent optical fiber temperature sensor

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Frontiers of Information Technology & Electronic Engineering 2022年第1期23卷 158-170页

作者： Yang WANG Xiangliang JIN Jian YANG Feng YAN Yujie LIU Yan PENG Jun Luo jun YANG School of Physics and Electronics Hunan Normal UniversityChangsha410081 China School of Mechatronic Engineering and Automation Shanghai UniversityShanghai200444 China Faculty of Engineering Western UniversityLondonONN6A 3K7Canada

The input/output(I/O)pins of an industry-level fluorescent optical fiber temperature sensor readout circuit need on-chip integrated high-performance electro-static discharge(ESD)protection devices.It is difficult for the failure level of basic N-type buried layer gate-controlled silicon controlled rectifier(NBL-GCSCR)manufactured by the 0.18µm standard bipolar-CMOS-DMOS(BCD)process to meet this need.Therefore,we propose an on-chip integrated novel deep N-well gate-controlled SCR(DNW-GCSCR)with a high failure level to effectively solve the problems based on the same semiconductor process.Technology computer-aided design(TCAD)simulation is used to analyze the device characteristics.SCRs are tested by transmission line pulses(TLP)to obtain accurate ESD parameters.The holding voltage(24.03 V)of NBL-GCSCR with the longitudinal bipolar junction transistor(BJT)path is significantly higher than the holding voltage(5.15 V)of DNW-GCSCR with the lateral SCR path of the same size.However,the failure current of the NBL-GCSCR device is 1.71 A,and the failure current of the DNW-GCSCR device is 20.99 A.When the gate size of DNW-GCSCR is increased from 2µm to 6µm,the holding voltage is increased from 3.50 V to 8.38 V.The optimized DNW-GCSCR(6µm)can be stably applied on target readout circuits for on-chip electrostatic discharge protection.

关键词： Electric breakdown Semiconductor device reliability CMOS technology

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