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Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

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Acta Pharmaceutica Sinica B 2024年第2期14卷 533-578页

作者： Xiaopeng peng Zhihao Hu Limei Zeng Meizhu Zhang Congcong Xu Benyan Lu Chengpeng Tao Weiming Chen Wen hou Kui Cheng Huichang Bi Wanyi Pan Jianjun Chen College of Pharmacy Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of EducationGannan Medical UniversityGanzhou 314000China College of Basic Medicine Gannan Medical UniversityGanzhou 314000China Guangdong Provincial Key Laboratory of New Drug Screening NMPA Key Laboratory for Research and Evaluation of Drug MetabolismSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators(e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges,including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result,the design of new epigenetic modulators(e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging(Hy T) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review,we aim to provide an in-depth illustration of new degrading strategies(2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

关键词： Epigenetic Degrader PROTAC Molecularglue Hydrophobic tagging

HiFAST:An HIdata calibration and imaging pipeline for FAST

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 182-199页

作者： Yingjie Jing Jie Wang Chen Xu Ziming Liu Qingze Chen Tiantian Liang Jinlong Xu Yixian Cao Jing Wang Huijie Hu Chuan-peng Zhang Qi Guo Liang Gao Mei Ai Hengqian Gan Xuyang Gao Jinlin Han Ligang hou Zhipeng hou peng Jiang Xu Kong Fujia Li Zerui Liu Li Shao Hengxing Pan Jun Pan Lei Qian Jinghai Sun Ningyu Tang Qingliang Yang Bo Zhang Zhiyu Zhang Ming Zhu National Astronomical Observatories Chinese Academy of SciencesBeijing 100012China Institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing 02206China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China Guizhou Radio Astronomical Observatory Guizhou UniversityGuiyang 55000China Max Planck Institute for Extraterrestrial Physics Garching 85748Germany Kavli Institute for Astronomy and Astrophysics Peking UniversityBeijing 100871China Institute of Computational Cosmology Department of PhysicsUniversity of DurhamDurham DHI 3LEUK CAS Key Laboratory of FAST National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Deep Space Exploration Laboratory/Department of Astronomy University of Science and Technology of ChinaHefei 230026China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China Astrophysics Department of PhysicsUniversity of OxfordOxford OX/3RHUK College of Earth Sciences Guilin University of TechnologyGuilin 541004China Department of Physics Anhui Normal UniversityWuhu 241002China School of Astronomy and Space Science Nanjing UniversityNanjing 210023China Key Laboratory of Modern Astronomy and Astrophysics Nanjing UniversityNanjing 20023China

The Five-hundred-meter Aperture Spherical radio Telescope(FAST)has the largest aperture and a 19-beam L-band receiver,making it powerful for investigating the neutral hydrogen atomic gas(HI)in the *** present HiFAST(https://***),a dedicated,modular,and self-contained calibration and imaging pipeline for processing the H?data of *** pipeline consists of frequency-dependent noise diode calibration,baseline fitting,standing wave removal using an FFT-based method,flux density calibration,stray radiation correction,and gridding to produce data *** modules can be combined as needed to process the data from most FAST observation modes:tracking,drift scanning,On-The-Fly mapping,and most of their *** HiFAST,the root-mean-square(RMS)noises of the calibrated spectra from all 19 beams were only slightly(~5%)higher than the theoretical *** results for the extended source M33 and the point sources are consistent with the results from *** moment maps(0,1 and 2)of M33 agree well with the results from the Arecibo Galaxy Environment Survey(AGES)with a fractional difference of less than 10%.For a common sample of 221 sources with signal-to-noise ratio S/N>10 from the Arecibo Legacy Fast ALFA(ALFALFA)survey,the mean value of fractional difference in the integrated flux density,Sint,between the two datasets is approximately 0.005%,with a dispersion of 15.4%.Further checks on the integrated flux density of 23 sources with seven observations indicate that the variance in the flux density of the source with luminous objects(Sint>2.5 Jy km s-1)is less than 5%.Our tests suggest that the FAST telescope,with the efficient,precise,and user-friendly pipeline HiFAST,will yield numerous significant scientific findings in the investigation of the H?in the universe.

关键词： fractional luminous correction

Rational design of a single-component mRNA vaccine against orthopoxvirus and SARS-CoV-2

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Science China(Life Sciences) 2024年第6期67卷 1311-1313页

作者： Yilong Yang Xiaofan Zhao Yu Li Xiaodong Zai Xinyi Wang Yue Zhang Xiaolin Wang peng Lv Jun Zhang Lihua hou Junjie Xu Wei Chen Laboratory of Advanced Biotechnology Beijing Institute of BiotechnologyAcademy of Military Medical SciencesBeijing 100071China

Dear Editor,In the era of COVID-19,the prevalence of viruses from other families poses new threats to *** the eradication of smallpox in 1980,the global outbreak of monkeypox in 2022(Lum et al.,2022;Nuzzo et al.,2022)alerted that the re-emerging orthopoxvirus(OPXV)remained a persistent threat to global *** includes a number of viruses with a broad host range,including variola virus(VARV),monkeypox virus(MPXV),vaccinia virus(VACV).

关键词： vaccine Rational

Vulnerable brain regions in adolescent major depressive disorder:A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis

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World Journal of Psychiatry 2024年第3期14卷 456-466页

作者： Hui Ding Qin Zhang Yan-Ping Shu Bin Tian Ji peng Yong-Zhe hou Gang Wu Li-Yun Lin Jia-Lin Li Department of Radiology The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Guizhou Provincial People’s HospitalGuiyang 550000Guizhou ProvinceChina Department of Psychiatry of Women and Children The Second People's Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Zhijin County People's HospitalBijie 552100Guizhou ProvinceChina Medical Humanities College Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in ***-state functional magnetic resonance imaging(rs-fMRI)offers unique insights into the neural mechanisms underlying this ***,despite previous research,the specific vulnerable brain regions affected in adolescent MDD patients have not been fully *** To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation(ALE)*** We performed a comprehensive literature search through July 12,2023,for studies investigating brain functional changes in adolescent MDD *** utilized regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and fractional ALFF(fALFF)*** compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls(HCs)using *** Ten studies(369 adolescent MDD patients and 313 HCs)were *** the ReHo and ALFF/fALFF data,the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs(voxel size:648 mm3,P<0.05),and no brain region exhibited increased *** on the ALFF data,we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients(voxel size:736 mm3,P<0.05),with no regions exhibiting increased *** Through ALE meta-analysis,we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients,increasing our understanding of the neuropathology of affected adolescents.

关键词： Major depressive disorder Resting-state functional magnetic resonance imaging Adolescent Activation likelihood estimation Meta-analysis

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain

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Science China(Life Sciences) 2024年第1期67卷 67-82页

作者： Chun-Kui Zhang Pan Wang Yuan-Yuan Ji Jian-Shuai Zhao Jun-xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li peng-Cheng Huang Yun-Qing Li Wu-Gang hou Jin-Lian Li Tao Chen Department of Anatomy and K.K.Leung Brain Research Centre Fourth Military Medical UniversityXi’an 710032China Beijing Institute of Basic Medical Sciences Beijing 100850China Key Laboratory of Ministry of Public Health for Forensic Science Xi’an Jiaotong UniversityXi’an 710061China Department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’an 710032China Department of Neurosurgery the Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China School of Biomedical Engineering Fourth Military Medical UniversityXi’an 710032China Affiliated Mental Health Centre and Hangzhou Seventh People’s Hospital Zhejiang University School of MedicineHangzhou 310013China The MOE Frontier Research Center of Brain&Brain-machine Integration Zhejiang University School of Brain Science and Brain MedicineHangzhou 310058China Department of Neurology The First Affiliated Hospital of Nanchang UniversityNanchang 330006China Department of Anatomy School of MedicineNorthwest UniversityXi’an 710069China

Chronic pain often develops severe mood changes such as ***,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely *** we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression *** determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA ***,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic *** of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic *** study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

关键词： chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility

Al-driven analysis establishes the single base substitution signatures as personalized prognostic predictors for five-year survival of gastric cancer

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Genes & Diseases 2024年第4期11卷 73-76页

作者： Zhenzhang Li Lingqing Xu Wen Luo Shaoan Zhangg Chunyu hou Xiaohong Xu ,Xubei peng E.Shiju Janak L.Pathak Shizhen Zhang Jiawei Liu Linhai Li Yang Li School of Biomedical Engineering The Sixth Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong 511436China College of Mathematics and Systems Science Guangdong Polytechnic Normal UniversityGuangzhouGuangdong 510665China The Second Affiliated Hospital Guangzhou Medical UniversityGuangzhouGuangdong 510260China Center for Learning Sciences and Technologies The Chinese University of Hong KongShatinNew Territories 999077China Affiliated Stomatology Hospital of Guangzhou Medical University Guangzhou Medical UniversityGuangzhouGuangdong 510182China International School of Photonics Cochin University of Science and TechnologyKochiKerala 682022India

Al-driven genetic engineering,as a burgeoning diagnostic tool,can offer predictive information on the five-year survival rate(FYSR)in the setup of a prognostic therapeutic *** approach provides the individuality and accuracy of prognosis for FYSR of gastric cancer(GC).Unlike traditional neoplasm staging criteria,our technique ensures accuracy and individuality without relying on statistical data and empirical study.

关键词： cancer gastric prognosis

Resource Allocation for Space-Air-Ground Integrated Networks:A Comprehensive Review

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Journal of Communications and Information Networks 2024年第1期9卷 1-23页

作者： Hui Liang Zhiqing Yang Guobin Zhang Hanxu hou School of Electrical Engineering and Intelligentization Dongguan University of TechnologyDongguan 523808China peng Cheng Laboratory Shenzhen 518055China School of Electronics and Information Engineering Shenzhen UniversityShenzhen 518061China School of Electrical Engineering and Intelligentization Dongguan University of TechonologyDongguan 523808China School of Information and Communication Engineering Guangzhou Maritime UniversityGuangzhou 510725China

The space-air-ground integrated networks (SAGIN) has emerged as a critical paradigm to address the growing demands for global connectivity and enhanced communication services. This paper gives a thorough review of the strategies and methodologies for resource allocation within SAGIN, focusing on the challenges and solutions within its complex structure. With the advent of technologies such as 6G, the dynamics of resource optimization have become increasingly complex, necessitating innovative approaches for efficient management. We examine the application of mathematical optimization, game theory, artificial intelligence (AI), and dynamic optimization techniques in SAGIN,offering insights into their effectiveness in ensuring optimal resource distribution, minimizing delays, and maximizing network throughput and stability. The survey highlights the significant advances in AI-based methods,particularly deep learning and reinforcement learning, in tackling the inherent challenges of SAGIN resource allocation. Through a critical review of existing literature, this paper categorizes various resource allocation strategies, identifies current research gaps, and discusses potential future directions. Our findings highlight the crucial role of integrated and intelligent resource allocation mechanisms in realizing the full potential of SAGIN for next-generation communication networks.

关键词： space-air-ground integrated networks resource allocation 6G optimization theory game theory artificial intelligence

Dynamic Non-Invasive Detection of NADH Based on Blood Flow-Mediated Skin Fluorescence (FMSF) Method

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Open Journal of Applied Sciences 2024年第6期14卷 1437-1453页

作者： peng Liu Tengfei Bi Gongzhi Du Long Yan Huayi hou Hubei Key Laboratory of Optical Information and Pattern Recognition Wuhan Institute of Technology Wuhan China

Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as a function of time in response to blocking and releasing of blood flow in a forearm are used as a measure of oxygen transport with blood to the tissue, which directly correlates with the skin microcirculation status. In this paper, a non-invasive dynamic monitoring system based on blood flow-mediated skin fluorescence (FMSF) technology is developed to monitor the NADH fluorescence intensity of skin tissue during the process of blocking reactive hyperemia. Simultaneously, laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) were used to observe blood flow, blood oxygen saturation (SOt2) and relative amount of hemoglobin (rHb) during the measurement process, which helped to explore NADH dynamics relevant physiological changes. A variety of parameters have been derived to describe NADH fluorescence curve based on the FMSF device. The experimental results are conducive to understanding the NADH measurement and the physiological processes related to it, which help FMSF to be a great avenue for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.

关键词： Reduced Nicotinamide Adenine Dinucleotide (NADH) Flow-Mediated Skin Fluorescence (FMSF) Laser Doppler Flowmetry (LDF) Blood Flow

Dynamic ocean inverse modeling based on differentiable rendering

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Computational Visual Media 2024年第2期10卷 279-294页

作者： Xueguang Xie Yang Gao Fei hou Aimin Hao Hong Qin State Key Lab of Virtual Reality Technology and Systems Beihang UniversityBeijing 100191China Qingdao Research Institute Beihang UniversityQingdao 266100Chinaand Peng Cheng LabShenzhen 518000China SKLCS Institute of SoftwareChinese Academy of SciencesBeijing 100190Chinaand University of Chinese Academy of SciencesBeijing 100049China Department of Computer Science Stony Brook University(SUNY at Stony Brook)Stony BrookNew York 11794-2424USA

Learning and inferring underlying motion patterns of captured 2D scenes and then re-creating dynamic evolution consistent with the real-world natural phenomena have high appeal for graphics and *** bridge the technical gap between virtual and real environments,we focus on the inverse modeling and reconstruction of visually consistent and property-verifiable oceans,taking advantage of deep learning and differentiable physics to learn geometry and constitute waves in a self-supervised ***,we infer hierarchical geometry using two networks,which are optimized via the differentiable *** extract wave components from the sequence of inferred geometry through a network equipped with a differentiable ocean ***,ocean dynamics can be evolved using the reconstructed wave *** extensive experiments,we verify that our new method yields satisfactory results for both geometry reconstruction and wave ***,the new framework has the inverse modeling potential to facilitate a host of graphics applications,such as the rapid production of physically accurate scene animation and editing guided by real ocean scenes.

关键词： inverse modeling surface reconstruction wave modeling ocean waves differentiable rendering(DR)