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Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan zhiqiang wei Jianqiang Yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice.Unfortunately,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions.As G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum.Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects.This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this treatment.We will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased agonists.It is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

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pH-sensitive KHA/CMC-Fe^(3+)@CS hydrogel loading and the drug release properties of riboflavin

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Particuology 2024年第3期86卷 13-23页

作者： Jie Song Xi Li Yuhua Niu Lijun Chen zhiqiang wei Yidan Li Youqian Wang Shaanxi University of Science&Technology Xi'an710021China

To improve drug utilization,reduce the drug administration frequency,increase the release time,and reduce the drug side effects in the human body,we prepared(KHA/CMC-Fe^(3+))@CS hydrogel spheres using green and natural potassium humate(KHA),carboxymethyl cellulose(CMC),and chitosan(CS)as raw materials and Fe3+as a crosslinking agent,and loaded them with riboflavin for drug sustainedrelease study using the drop ball method.The tests with FTIR,SEM,TG,and X-ray diffractometer showed that the coordination among KHA,CMC,and Fe^(3+)formed a three-dimensional network structure,where cs was encapsulated on the surface of the hydrogel spheres via noncovalent bonding,resulting in good thermal stability.The stability,drug loading,swelling,and in vitro release of the(KHA/CMC-Fe^(3+))@CS hydrogel spheres were investigated.The results showed that the hydrogel spheres were significantly pH-sensitive,with 11.16 g/g higher swelling in an alkaline environment(pH=7.4)than that in an acidic environment(pH=1.2).The swelling and drug release process of the hydrogel spheres were analyzed using mathematical models,concluding that the hydrogel swelling follows Schott second-order swelling kinetics,and the drug release mechanism was Fickian delivery mode.

关键词： Potassium humate Hydrogel spheres pH-sensitive Drugsustained-release Drug release model

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Switching from 2-pyridination to difluoromethylation:ligand-enabled nickel-catalyzed reductive difluoromethylation of aryl iodides with difluoromethyl 2-pyridyl sulfone

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中国科学:化学英文版 2023年第10期66卷 2785-2790页

作者： wei Du Qinyu Luo zhiqiang wei Xiu Wang Chuanfa Ni Jinbo Hu Key Laboratory of Organofluorine Chemistry Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China

The divergent reductive cross-coupling with an ambident electrophile is rare.Previously,we demonstrated a nickel-catalyzed reductive 2-pyridination of aryl iodides with difluoromethyl 2-pyridyl sulfone(2-Py SO_(2)CF_(2)H)via selective C(sp^(2))-S bond cleavage of the sulfone by using a phosphine ligand.In this communication,we report a novel nickel-catalyzed reductive coupling of aryl iodides and 2-Py SO_(2)CF_(2)H reagent,which constitutes a new method for aromatic difluoromethylation.The use of a tridentate terpyridine ligand is pivotal for the selective C(sp^(3))-S bond cleavage of the sulfone.This method employs readily available nickel catalyst and 2-Py SO_(2)CF_(2)H as the difluoromethylation reagent,providing a facile access to difluoromethylarenes under mild reaction conditions without pre-generation of arylmetal reagents.

关键词： nickel catalysis difluoromethylation 2-PySO_(2)CF_(2)H reductive cross-coupling

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Collecting and analyzing key-value data under shuffled differential privacy

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Frontiers of Computer Science 2023年第2期17卷 241-243页

作者： Ning WANG wei ZHENG Zhigang WANG zhiqiang wei Yu GU Peng TANG Ge YU Faculty of Information Science and Engineering Ocean University of ChinaQingdao 266100China School of Computer Science and Engineering Northeastern UniversityShenyang 110819China Key Lab of Cryptologic Technology and Information Security Ministry of EducationShandong UniversityQingdao 266200China School of Cyber Science and Technology Shandong UniversityQingdao 266200China

1 Introduction Key-value data,as NoSQL data widely used in recent years,has been frequently collected and used for analysis in major websites and mobile apps.The frequency distribution estimation on the key domain,as well as the mean estimation of values associated with the same key,are crucial and worth billion dollars in the business.However,in real applications,the key-value records are submitted by terminal devices of different users.Directly collecting the information from users may pose serious risks on personal privacy.On the other hand,the emerging shuffled differential privacy(SDP)model[1]is proposed to collect sensitive data from users.

关键词： NoSQL app value

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New Delay Doppler Communication Paradigm in 6G Era:A Survey of Orthogonal Time Frequency Space(OTFS)

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China Communications 2023年第6期20卷 1-25页

作者： weijie Yuan Shuangyang Li zhiqiang wei Yuanhao Cui Jiamo Jiang Haijun Zhang Pingzhi Fan Department of Electronic and Electrical Engineering Southern University of Science and TechnologyShenzhenChina Faculty of Electrical Engineering and Computer Science Technical University of BerlinBerlinGermany School of Mathematics and Statistics Xi’an Jiaotong UniversityXi’anChina Department of Communication Engineering Beijing University of Posts and TelecommunicationsBeijingChina China Academy of Information and Communications Technology BeijingChina School of Computer and Communication Engineering University of Science and Technology BeijingBeijingChina School of Information Science and Technology Southwest Jiaotong UniversityChengduChina

In the 6G era,Space-Air-Ground Integrated Network(SAGIN)are anticipated to deliver global coverage,necessitating support for a diverse array of emerging applications in high-mobility,hostile environments.Under such conditions,conventional orthogonal frequency division multiplexing(OFDM)modulation,widely employed in cellular and Wi-Fi communication systems,experiences performance degradation due to significant Doppler shifts.To overcome this obstacle,a novel twodimensional(2D)modulation approach,namely orthogonal time frequency space(OTFS),has emerged as a key enabler for future high-mobility use cases.Distinctively,OTFS modulates information within the delay-Doppler(DD)domain,as opposed to the timefrequency(TF)domain utilized by OFDM.This offers advantages such as Doppler and delay resilience,reduced signaling latency,a lower peak-to-average ratio(PAPR),and a reduced-complexity implementation.Recent studies further indicate that the direct interplay between information and the physical world in the DD domain positions OTFS as a promising waveform for achieving integrated sensing and communications(ISAC).In this article,we present an in-depth review of OTFS technology in the context of the 6G era,encompassing fundamentals,recent advancements,and future directions.Our objective is to provide a helpful resource for researchers engaged in the field of OTFS.

关键词： OTFS 6G delay-Doppler(DD)domain

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Example-based large-scale marine scene authoring using Wang Cubes

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Visual Informatics 2022年第3期6卷 23-34页

作者： Siyuan Zhu Xinjie Wang Ming Wang Yucheng Wang zhiqiang wei Bo Yin Xiaogang Jin Ocean University of China Shandong266100China Pilot National Laboratory for Marine Science and Technology(Qingdao) Shandong266237China Zhejiang University Zhejiang310058China

Virtual marine scene authoring plays an important role in generating large-scale 3D scenes and it has a wide range of applications in computer animation and simulation.Existing marine scene authoring methods either produce periodic patterns or generate unnatural group distributions when tiling marine entities such as schools of fish and groups of reefs.To this end,we propose a new large-scale marine scene authoring method based on real examples in order to create more natural and realistic results.Our method first extracts the distribution of multiple marine entities from real images to create Octahedral Blocks,and then we use a modified Wang Cubes algorithm to quickly tile the 3D marine scene.As a result,our method is able to generate aperiodic tiling results with diverse distributions of density and orientation of entities.We validate the effectiveness of our method through intensive comparative experiments.User study results show that our method can generate satisfactory results which are in accord with human preferences.

关键词： Wang Cubes Marine scene authoring Virtual environments

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A lock-free approach to parallelizing personalized PageRank computations on GPU

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Frontiers of Computer Science 2023年第1期17卷 219-220页

作者： Zhigang WANG Ning WANG Jie NIE zhiqiang wei Yu GU Ge YU Faculty of Information Science&Engineering Ocean University of ChinaQingdao 266100China School of Computer Science and Engineering Northeastern UniversityShenyang 110819China

1 Introduction Personalized PageRank(PPR)is a classic topology-based proximity measure and it is most widely computed by Forward Push.That is,given a starting vertex in graph,it iteratively computes the importance score of any vertex in with respect to,and then broadcasts the new score as messages to’s neighboring vertices.The process converges until all scores hold stable.Recently,Graphical Processing Units(GPU)with massive threads has been extensively used to parallelize such compute-intensive process.It yields performance improvement but also involves two atomic locks for correctness.Such locks are practically inefficient and become a new performance bottleneck.This paper proposes a separation technique to partially eliminate atomic protections,termed as Lightweight Forward Push.A Forward Pull solution is further devised to support lock-free PPR computations but also causes useless reads.For best performance,a new Hybrid Framework is then designed to adaptively balance locking costs and reading costs.

关键词： PageRank GPU Push

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城市空中交通无人机群尾流危险区域评估方法

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飞行力学 2024年第2期42卷 42-48页

作者：魏志强王晶中国民航大学空中交通管理学院天津300300

为了避免在城市空中交通无人机群造成的尾流危险遭遇事件的发生,对无人机群产生的复杂尾涡场危害区域进行评估。首先,以单架无人机为基础,建立了适用于无人机群的尾流环量和诱导速度模型。其次,通过计算滚转力矩系数评估后机飞行安全区... 详细信息

为了避免在城市空中交通无人机群造成的尾流危险遭遇事件的发生,对无人机群产生的复杂尾涡场危害区域进行评估。首先,以单架无人机为基础,建立了适用于无人机群的尾流环量和诱导速度模型。其次,通过计算滚转力矩系数评估后机飞行安全区域。最后,对后机的飞行速度、机翼展长和机翼面积对危险区域的影响进行探究。结果表明:后机在大于旋翼机飞行路径宽度的4.5倍和大于固定翼无人机飞行路径宽度的2.33倍处区域飞行,更能保障飞行安全;后机飞行速度变为原来的3倍时,危险区域覆盖面积减小为原先的1/3;后机翼展变为原来3倍时,危险区域覆盖面积减小为原来的1/3;机翼面积不影响危险区域大小。该模型能更好地预测后机在复杂尾流场下的安全位置,为无人机提供航行指导。

关键词：城市空中交通无人机群复杂尾涡场尾涡遭遇安全评估

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激光雷达探测中基于贝叶斯网络的飞机尾流反演

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激光与光电子学进展 2024年第4期61卷 394-405页

作者：谷润平鹿彤魏志强中国民航大学空中交通管理学院天津300300

尾流是飞机飞行时的必然产物,对航空安全有重大威胁,还限制着航空效率和容量的提升,飞机尾流涡核的精准辨识是动态缩减尾流间隔的前提,目前晴空尾涡探测的主要工具是相干多普勒激光雷达(CDL)。针对使用激光雷达进行飞机尾流探测中受限... 详细信息

尾流是飞机飞行时的必然产物,对航空安全有重大威胁,还限制着航空效率和容量的提升,飞机尾流涡核的精准辨识是动态缩减尾流间隔的前提,目前晴空尾涡探测的主要工具是相干多普勒激光雷达(CDL)。针对使用激光雷达进行飞机尾流探测中受限于雷达时空分辨率和背景风场的影响导致的识别和反演尾流关键参数误差较大这一问题,提出一种在激光雷达探测数据基础上基于贝叶斯网络(BN)和均方误差(MSE)构建的尾涡参数反演模型。搭建大气背景风和湍流环境,并将其叠加到模拟的尾涡速度场上,得到用于训练模型的仿真数据集。实验结果表明:所提算法能够得到误差较小的参数反演结果(仿真算例中涡核位置偏差在2 m以内,环量偏差在5%以内);在实际算例中,所提算法与传统算法相比,反演速度场均方误差显著降低(平均超过50%)。本研究可用于机场实时尾涡监测,对尾涡间隔标准制定有重要意义。

关键词：激光雷达航空安全飞机尾涡贝叶斯网络尾涡特征参数反演模型

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mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

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Virologica Sinica 2021年第6期36卷 1303-1314页

作者： Xueyu Wang zhiqiang wei Yongfang Jiang Zhongji Meng Mengji Lu Department of Infectious Diseases The Second Xiangya HospitalCentral South UniversityChangsha 410011China Institute of Virology University Hospital EssenUniversity of Duisburg-Essen45122 EssenGermany Institute of Biomedical Research Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver CancerTaihe HospitalHubei University of MedicineShiyan 442000China Department of Infectious Diseases Taihe HospitalHubei University of MedicineShiyan 442000China

Mammalian target of rapamycin(m TOR) is a conserved Ser/Thr kinase that includes m TOR complex(m TORC) 1 and m TORC2. The m TOR pathway is activated in viral hepatitis, including hepatitis B virus(HBV) infection-induced hepatitis.Currently, chronic HBV infection remains one of the most serious public health issues worldwide. The unavailability of effective therapeutic strategies for HBV suggests that clarification of the pathogenesis of HBV infection is urgently required. Increasing evidence has shown that HBV infection can activate the m TOR pathway, indicating that HBV utilizes or hijacks the m TOR pathway to benefit its own replication. Therefore, the m TOR signaling pathway might be a crucial target for controlling HBV infection. Here, we summarize and discuss the latest findings from model biology research regarding the interaction between the m TOR signaling pathway and HBV replication.

关键词： Mammalian target of rapamycin(mTOR) Hepatitis B virus(HBV) Metabolism Autophagy

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