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G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang Ting chen Xun Lu Xiaobing lan Ziqiang chen Shaoyong Lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

Link Prediction Method Fusion with Local Structural Entropy for Directed Network

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Chinese Journal of Electronics 2024年第1期33卷 204-216页

作者： Shuxin LIU Hongchang chen lan WU Kai WANG Xing LI People’s Liberation Army Strategic Support Force Information Engineering University

Link prediction utilizes accessible network information to complement or predict the network links.Similarity is an important prerequisite for link prediction which means links more likely occurs between two similar nodes. Existing methods utilize the similarity of nodes but neglect of network structure. However the link direction leads to a far more complex structure and contains more information useful than the undirected networks. Most classic methods are difficult to depict the distribution of the network structure with incidental direction so the similarity characteristics of the network structure itself are lost. In this respect, a new method of local structure entropy is proposed to depict the directed structural distribution characteristics, which can be used to evaluate the degree of local structural similarity of nodes and then applied to link prediction methods. Experimental results on 8 real directed networks show that this method is effective for both area under the receiver operating characteristic curve(AUC)and ranking-score measures, and improved predictive capacity of the baseline methodology.

关键词： Local structural entropy Structural complexity Similar nodes Link prediction

Monothetic and conductive network and mechanical stress releasing layer on micron-silicon anode enabling high-energy solid-state battery

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Rare Metals 2024年第3期43卷 1017-1029页

作者： Xiang Han Min Xu lan-Hui Gu Chao-Fei lan Min-Feng chen Jun-Jie Lu Bi-Fu Sheng Peng Wang Song-Yan chen Ji-Zhang chen College of Materials Science and Engineering Co-Innovation Center of Efficient Processing and Utilization of Forestry ResourcesNanjing Forestry UniversityNanjing210037China Department of Physics Xiamen UniversityXiamen361005China Western Digital Corporation MilpitasCA95035USA

Silicon has ultrahigh capacity,dendrite-free alloy lithiation mechanism and low cost and has been regarded as a promising anode candidate for solid-state battery.Owing to the low infiltration of solid-state electrolyte(SSE),not the unstable solid-electrolyte interphase(SEI),but the huge stress during lithiation-and delithiation-induced particle fracture and conductivity lost tend to be the main issues.In this study,starting with micron-Si,a novel monothetic carbon conductive framework and a MgO coating layer are designed,which serve as electron pathway across the whole electrode and stress releasing layer,respectively.In addition,the in situ reaction between Si and SSE helps to form a LiF-rich and mechanically stable SEI layer.As a result,the mechanical stability and charge transfer kinetics of the uniquely designed Si anode are significantly improved.Consequently,high initial Coulombic efficiency,high capacity and durable cycling stability can be achieved by applying the Si@MgO@C anode in SSB.For example,high specific capacity of 3224.6 mAh·g^(-1)and long cycling durability of 200 cycles are achieved.This work provides a new concept for designing alloy-type anode that combines surface coating on particle and electrode structure design.

关键词： Lithium-ion battery(LIB) Solid-state electrolyte(SSE) Silicon anode Stress relief Coating

Construction and properties of venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres

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Particuology 2024年第3期86卷 205-210页

作者： chenjing Liang Lingling Shi Zhengguo chen lan Zhou Zhaoxia Zhang Guoqing Zhang School of Materials Science and Engineering Zhejiang Sci-tech UniversityHangzhouChina College of Textile Science and Engineering Zhejiang Sci-tech UniversityHangzhouChina Zhejiang Provincial Innovation Center of Advanced Textile Technology ShaoxingChina

The aim of this work is to develop a venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres(HMSMs).HMSMs were innovatively prepared with tetraethyl silicate(TEOS)as the precursor and volatile n-heptane as a soft template.The obtained HMSMs show a well-defined hollow structure with an average size of 967 nm and pore volume of 0.85 cm^(3)/g,implying it is a potential drug carrier.Subsequently,venlafaxine hydrochloride(VF)was absorbed in the HMSMs with a content of 37.67% or so.The sustained release effect is further measured by the dissolution in-strument at 37℃ and 50 rpm in ultrapure water.The results showed that the HMSMs/VF system shows good sustained release properties compared with sustained release tablets with hydroxypropyl meth-ylcellulose as the main component.This HMSMs sustained release system appears to be a promising candidate for a sustained drug release.

关键词： Hollowmesoporous silica microspheres(HMSMs) Venlafaxine hydrochloride Drug loading Sustained release

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2024年第3期19卷 619-628页

作者： Jun Chang Yujiao Li Xiaoqian Shan Xi chen Xuhe Yan Jianwei Liu lan Zhao First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina Tianjin University of Traditional Chinese Medicine TianjinChina

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

关键词： Alzheimer’s disease amyloid-β cell therapy extracellular vesicle neural stem cell synaptic plasticity tau

Safety and efficacy of omalizumab for antihistamine-resistant chronic urticaria in children:a case series and literature review

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World Journal of Pediatrics 2024年第3期20卷 294-298页

作者： Wei-Fang Zhu chen Wang Jian-Jun Qiao lan-Juan Li Department of Dermatology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Chronic urticaria(CU)is a common skin disease characterized by the occurrence of wheals,with or without angioedema,lasting more than 6 weeks.The prevalence of CU is about 0.7%[1],but higher in children,with an incidence of 1.38%[1].The occurrence of severe pruritus and unpredictable wheals may severely impact patients'quality of life,cause psychological problems,including sleep disorders and depression,and lead to economic burden due to limitation on daily life and work[2,3].

关键词： edema prevalence children

Sustained remission of Cronkhite-Canada syndrome after corticosteroid and mesalazine treatment: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2431-2437页

作者： Ya-lan chen Rui-Yao Wang Ling Mei Ran Duan Department of Gastroenterology The Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina Department of Thoracic Surgery The Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina Department of Medical Imageology The Affiliated Hospital of Hebei UniversityBaoding 071000Hebei ProvinceChina

BACKGROUND Cronkhite-Canada syndrome(CCS)is a rare disease of unknown etiology.The optimal treatment for CCS remains unknown.Treatment with corticosteroids is considered the mainstay treatment because of its high efficacy,but the therapeutic strategy for steroid-resistant CCS is not yet established.CASE SUMMARY This is the case of an 81-year-old woman who was diagnosed with CCS.Given her severe diarrhea,nausea,vomiting,and hypoproteinemia,hormone therapy(40 mg/d)was administered,and the symptoms improved within 1 wk.After 3 mo,the patient had no obvious symptoms.The polyps were significantly reduced on review gastroscopy and colonoscopy,thus hormone reduction gradually began.The hormone level was maintained at 10 mg/d after 6 mo.Despite the age of the patient and the side effects of hormones,the patient had no obvious discomfort.However,hormone drugs were discontinued,and mesalazine was administered orally at 3 g/d.The patient's symptoms continued to improve after a follow-up of 5 years.CONCLUSION Corticosteroids and mesalazine are potential treatment options for CCS.

关键词： Cronkhite-Canada syndrome Corticosteroids Mesalazine Gastrointestinal polyposis Case report

Multiscale Study on Low Temperature Crack Resistance Mechanism of Steel Slag Asphalt Mixture

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 705-715页

作者：白雪峰王岚 chen Xiunan School of Science Inner Mongolia University of TechnologyHohhot 010051China School of Civil Engineering Key Laboratory of Civil Engineering Structure and MechanicsInner Mongolia University of TechnologyHohhot 010051China Inner Mongolia Traffic De-sign Institute Co.LTD Hohhot 010050China

The objective of this paper was to study low temperature crack resistance mechanism of steel slag asphalt mixture(SAM).Thermal stress restrained specimen test(TSRST)and three-point bending test were carried out to evaluate the low-temperature crack resistance of SAM and basalt asphalt mixture(BAM).Based on the digital image correlation technique(DIC),the strain field distribution and crack propagation of SAM were analyzed from the microscopic point of view,and a new index,crack length factor(C),was proposed to evaluate the crack resistance of the asphalt mixture.The crystal phase composition and microstructure of steel slag aggregate(SA)and basalt aggregate(BA)were studied by X-ray diffraction(XRD)and scanning electron microscopy(SEM)to explore the low-temperature crack resistance mechanism of SAM.Results show that the low-temperature crack resistance of SAM is better than that of BAM;SAM has good integrity and persistent elastic deformation,and its bending failure mode is a hysteretic quasi-brittle failure;The SA surface is evenly distributed with pores and has surface roughness.SA has the composition phase of alkaline aggregate-calcite(CaCO3),so it has good adhesion to asphalt,which reveals the mechanism of excellent low-temperature crack resistance of SAM.

关键词： steel slag asphalt mixture ·low-temperature crack resistance ·strain energy density ·XRD SEM

Anchoring heterometallic cluster on P-doped carbon nitride for efficient photocatalytic nitrogen fixation in water and air ambient

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Chinese Chemical Letters 2024年第4期35卷 176-180页

作者： Chao-Long chen Rong chen La-Sheng Long lan-Sun Zheng Xiang-Jian Kong Collaborative Innovation Center of Chemistry for Energy Materials State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of ChemistryCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China

Light-driven nitrogen fixation to produce ammonia is a green and economical technology of nitrogen reduction but is still quite challenging, especially in an air atmosphere without any sacrificial reagents.Herein, we demonstrate efficient photocatalytic nitrogen fixation using water and air directly by loading lanthanide–transition metal(4f–3d) cluster NdCo_(3) on two-dimensional P-doped graphitic carbon nitrides(PCN) material surface. Benefiting from the increase in the number of nitrogen vacancies(NVs) and highly matched band gap structure and excellent hole trapping ability of clusters, the NdCo_(3)/PCN photocatalyst exhibits efficient nitrogen reduction activity with 371(in air) and 825 μmol h^(-1)g^(-1)(in pure nitrogen)without any sacrificial reagents. The introduction of potassium sulfate inhibits hydrogen production and promotes nitrogen reduction activation. This work suggests that anchoring precisely structured clusters on 2D materials may enhance photocatalytic nitrogen reduction under normal temperature and pressure.

关键词： Photocatalytic Nitrogen fixation 4f-3d Cluster Air atmosphere