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Genes & Diseases 2024年第3期11卷 39-42页

作者： Haoyu Ruan Zhe Wang Xuemei Tang Qiong zhan Kun Chen Lu gao Ming Guan Department of Laboratory Medicine Huashan HospitalFudan UniversityShanghai 200040China Department of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Physiology Naval Medical UniversityShanghai 200433China Department of Oncology Huashan HospitalFudan UniversityShanghai 200040China

Cancer of unknown primary(CUP)is a rare disease characterized by metastases in which the primary tumor is of unknown origin.The cerebrospinal fluid(CSF)tumor microenvironment of CUP is still unknown.A Chinese male was diagnosed with leptomeningeal metastases from CUP(CUP-LM)based on the following medical examination results:partial leptomeningeal enhancement by brain magnetic resonance imaging,few malignant cells of diverse morphology in CSF,and no abnormalities or lymphadenopathy by systemic examination.

关键词： metastases cerebrospinal fluid

Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei zhan Thomas L.Gallagher Guangping gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues.Recombinant AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various diseases.However,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing methods.Seven rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and neurotoxicity.In this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies.We discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as cancers.We outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these reactions.We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

Coherence phase spectrum analyzer for a randomly fluctuated fractional vortex beam

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Photonics Research 2024年第1期12卷 33-39页

作者： ZHUOYI WANG XINGYUAN LU JIANBO gao XUECHUN ZHAO QIWEN zhan YANGJIAN CAI CHENGLIANG ZHAO School of Physical Science and Technology Soochow UniversitySuzhou 215006China School of Optical-Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai 200093China Shandong Provincial Engineering and Technical Center of Light Manipulations&Shandong Provincial Key Laboratory of Optics and Photonic Device School of Physics and ElectronicsShandong Normal UniversityJinan 250358China Shandong Joint Research Center of Light Manipulation Science and Photonics Integrated Chip of East China Normal University and Shandong Normal University East China Normal UniversityShanghai 200241China

Fractional vortex beams exhibit a higher degree of modulation dimensions than conventional vortices,thus inheriting superior anti-turbulent transmission properties through the incorporation of additional coherence modulation.However,aliasing the mixed modes induced by coherence degradation makes the quantitative measurement of the topological charge in fractional vortex beams challenging.In this study,a coherence phase spectrum was introduced,and experimental demonstrations to quantitatively determine the fractional topological charge of partially coherent fractional vortex beams were performed.By leveraging the four-dimensional measurement of a partially coherent light field,the source coherence function was inversely reconstructed,and fractional topological charges were determined with high precision by extracting the phase spectrum of the coherence function.Laguerre–Gaussian,elliptical Gaussian,and plane-wave-fraction vortex beams with various degrees of coherence were used to demonstrate measurement precision.The proposed method is applicable to X-rays and electron vortices.It has potential applications in optical encryption,high-capacity optical communication,and quantum entanglement.

关键词： function fractional vortex

Single-shot phase retrieval for randomly fluctuated and obstructed vortex beams

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Science China(Physics,Mechanics & Astronomy) 2024年第4期67卷 72-80页

作者： Hao zhang Jun’an Zhu Xingyuan Lu Zhiquan Hu Jianbo gao Kun Liu Qiwen zhan Yangjian Cai Chengliang Zhao School of Physical Science and Technology Soochow UniversitySuzhou 215006China School of Optical-Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai 200093China Shandong Provincial Engineering and Technical Center of Light Manipulations Shandong Provincial Key Laboratory of Optics and Photonic DeviceSchool of Physics and ElectronicsShandong Normal UniversityJinan 250358China Joint Research Center of Light Manipulation Science and Photonic Integrated Chip of East China Normal University and Shandong Normal University East China Normal UniversityShanghai 200241China

Vortex beams with orbital angular momentum play a crucial role in increasing the information capacity in optical communications.The magnitude of orbital angular momentum determines the ability of information encoding.In practice,a vortex beam can encounter random objects or turbulence during free-space propagation,resulting in information damage.Therefore,accurately measuring the orbital angular momentum of a randomly fluctuated and obstructed vortex beam is a considerable challenge.Herein,we propose a single-shot method for the phase retrieval of a randomly fluctuated and obstructed vortex beam by combining the phase-shift theorem and self-reference holography.Experimental results reveal that the sign and magnitude of the initial orbital angular momentum can be simultaneously determined based on their quantitative relation with the number of coherence singularities on the observation plane,thus addressing the effects of random occlusion and atmospheric turbulence.The proposed method considerably improved the accurate decoding of orbital angular momentum information in nonideal freespace optical communications.

关键词： optical vortex phase retrieve orbital angular momentum measurement antiturbulence antidisturbance

Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng zhang Zhen gao Zihao Sang Erik De Clercq Christophe Pannecouque Dongwei Kang Peng zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase inhibitors.To fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design strategy.Most of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar levels.Among them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/L.Especially,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and etravirine.Besides,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and etravirine.The binding target of 23h was further confirmed to be HIV-1 reverse transcriptase.Molecular modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization campaign.Furthermore,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for 23h.Most importantly,23h was characterized by good pharmacokinetic properties and excellent safety in vivo.Collectively,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

Renewable synthetic fuel:turning carbon dioxide back into fuel

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Frontiers in Energy 2022年第2期16卷 145-149页

作者： Zhen HUANG Lei ZHU Ang LI zhan gao Key Laboratory for Power Machinery and Engineering of the Ministry of Education Shanghai Jiao Tong UniversityShanghai 200240China China Research Institute of Carbon Neutrality Shanghai Jiao Tong UniversityShanghai 200240China

Climate change has emerged as one of the major challenges worldwide.Since the First Industrial Revolution,the discovery and utilization of fossil energy has promoted the great prosperity and development of human society.Meanwhile,serious issues of environmental and climate change have arisen.In May 2021,CO_(2) concentration in the atmosphere reached 419.13 ppm,observed by the National Oceanic and Atmospheric Administration(NOAA)of US,which arrives at the highest value in human history[1].The CO_(2)-based greenhouse gas emissions lead to global warming,which causes a serious threat to the survival of human being as well as sustainable development of society.In September 2020,it was announced that China would scale up its nationally determined contributions and adopt more vigorous policies and activities to peak carbon dioxide emissions before 2030 and achieve carbon neutrality before 2060.

关键词： turning dioxide carbon

An assessment of surrogate fuel using Bayesian multiple kernel learning model in sight of sooting tendency

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Frontiers in Energy 2022年第2期16卷 277-291页

作者： Lei ZHU zhan gao Xiaogang CHENG Fei REN Zhen HUANG Key Laboratory for Power Machinery and Engineering of the Ministry of Education Shanghai Jiao Tong UniversityShanghai 200030China

An integrated and systematic database of sooting tendency with more than 190 kinds of fuels was obtained through a series of experimental investigations. The laser-induced incandescence (LII) method was used to acquire the 2D distribution of soot volume fraction, and an apparatus-independent yield sooting index (YSI) was experimentally obtained. Based on the database, a novel predicting model of YSI values for surrogate fuels was proposed with the application of a machine learning method, named the Bayesian multiple kernel learning (BMKL) model. A high correlation coefficient (0.986) between measured YSIs and predicted values with the BMKL model was obtained, indicating that the BMKL model had a reliable and accurate predictive capacity for YSI values of surrogate fuels. The BMKL model provides an accurate and low-cost approach to assess surrogate performances of diesel, jet fuel, and biodiesel in terms of sooting tendency. Particularly, this model is one of the first attempts to predict the sooting tendencies of surrogate fuels that concurrently contain hydrocarbon and oxygenated components and shows a satisfying matching level. During surrogate formulation, the BMKL model can be used to shrink the surrogate candidate list in terms of sooting tendency and ensure the optimal surrogate has a satisfying matching level of soot behaviors. Due to the high accuracy and resolution of YSI prediction, the BMKL model is also capable of providing distinguishing information of sooting tendency for surrogate design.

关键词： sooting tendency yield sooting index Bayesian multiple kernel learning surrogate assessment surrogate formulation

Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease:a cohort study

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Journal of Geriatric Cardiology 2023年第12期20卷 845-854页

作者： Tian-Yu LI Pei ZHU Ying SONG Xiao-Fang TANG zhan gao Run-Lin gao Jin-Qing YUAN National Clinical Research Center for Cardiovascular Diseases National Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

BACKGROUND The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease(CAD)at residual cardiovascular risk remain controversial.This study aimed to compare the predictive powers of apolipoprotein B(apoB),non-high-density lipoprotein cholesterol(non-HDL-C),low-density lipoprotein cholesterol(LDL-C),apoB/apolipoprotein A-1(apoA-1)and non-HDL-C/HDL-C for myocardial infarction(MI)in CAD patients treated with statins in the setting of secondary prevention.METHODS The study included 9191 statin-treated CAD patients with a five-year median follow-up.All measures were anal-yzed as continuous variables and concordance/discordance groups by medians.The hazard ratio(HR)with 95%CI was estimated by Cox proportional hazards regression.Patients were classified by the clinical presentation of CAD for further analysis.RESULTS The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40(95%CI:1.04–1.88)and 1.51(95%CI:1.07–2.13)for MI,respectively,whereas discordant high LDL-C with low apoB or non-HDL-C was not associa-ted with the risk of MI.No association of MI with discordant apoB versus non-HDL-C,apoB/apoA-1 versus apoB,non-HDL-C/HDL-C versus non-HDL-C,or apoB/apoA-1 versus non-HDL-C/HDL-C was observed.Similar patterns were found in patients with acute coronary syndrome.In contrast,no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome.CONCLUSIONS ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C,especially in patients with acute coronary syndrome.ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predict-ing MI.

关键词： patients coronary infarction

Applications of ambient electric arc ionization mass spectrometry in saline samples

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Chinese Chemical Letters 2022年第5期33卷 2708-2710页

作者： Yuan Li Yuanji gao Binpeng zhan Weiwei Chen Fengjian Chu Hongru Feng zhan gao Zihan Ma Yuanjiang Pan Department of Chemistry Zhejiang UniversityHangzhou 310027China College of Chemistry and Materials Science Sichuan Normal UniversityChengdu 610068China

Salinity tolerance of ambient electric arc ionization(AEAI)was evaluated by comparing electrospray ionization for various samples at NaCl concentrations from 0 to 1000 mmol/L.AEAI-mass spectrometry(AEAI-MS)exhibited an excellent signal intensity even at NaCl concentrations of 1000 mmol/L,while the ESI-MS had no signal because high salinity has a strong inhibitory effect on analytes.The sodium adduct was verified using LiCl instead of NaCl.AEAI-MS successfully quantified saline samples with an excellent quantitative ability(R^(2)≥0.998).We also achieved some analytical samples in the buffer solution at a very high concentration and even in a saturated salt solution.Overall,AEAI-MS has protonated ions for most target analytes.In addition,the relationship between auxiliary temperature and the distance from the sample to the arc was investigated,and the results indicated that thermal desorption plays an important role in AEAI source.

关键词： Electric arc Ion source Salinity tolerance Mass spectrometry Ambient electric arc ionization

Recent advances in Fe-N-C-and Co-N-C-based materials as bifunctional electrocatalysts for oxygen reduction and oxygen evolution

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Science China Chemistry 2024年第4期67卷 1137-1160页

作者： Hui-Min Xu Hong-Rui Zhu Chen-Jin Huang Zhi-Jie zhang Ting-Yu Shuai Qi-Ni zhan gao-Ren Li College of Materials Science and Engineering Sichuan UniversityChengdu 610065China

Fe-nitrogen-carbon(Fe-N-C)-and Co-nitrogen-carbon(Co-N-C)-based electrocatalysts have been widely concerned because of their high OER/ORR activity,low metal cost,and simple preparation.The exploration of Fe-N-C and Co-N-C single atombased catalysts with high activity and stability to overcome the slow kinetics of oxygen reduction and oxygen evolution reactions is also the key to the development of efficient electrolytic water,fuel cells,and rechargeable metal-air batteries.Fe-N-C and Co-N-C single atom-based electrocatalysts have the advantages of a high utilization rate of metal atoms and high electrocatalytic activity,and are ideal catalysts for promoting electrochemical energy conversion and storage.The general principles of designing Fe-N-C and Co-N-C single atom-based electrocatalysts are reviewed in this paper.Then,the strategies to improve the bifunctional catalytic activity and stability are proposed.Finally,the challenges and prospects of Fe-N-C and Co-N-C single atom-based catalysts are well summarized.This review will provide a reference for the directed optimization of Fe-N-C and Co-N-C single atom-based catalysts.

关键词： Fe-N-C Co-N-C single atom bifunctional oxygen electrocatalysts