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Substance P promotes epidural fibrosis via induction of type 2 macrophages

Neural Regeneration Research 2023年第10期18卷 2252-2259页

作者： Feng Hua Hao-Ran Wang Yun-Feng Bai jin-peng sun Wei-Shun Wang Ying Xu Ming-Shun Zhang Jun Liu Department of Orthopedics The Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Orthopedics Sir Run Run HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Intensive Care Unit Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina NHC Key Laboratory of Antibody Technique Jiangsu Province Engineering Research Center of Antibody DrugDepartment of ImmunologyNanjing Medical UniversityNanjingJiangsu ProvinceChina

In response to spinal surgery,neurons secrete a large amount of substance P into the epidural *** P is involved in macrophage differentiation and fibrotic ***,the specific roles and mechanisms of substance P in epidural fibrosis remain *** this study,we established a mouse model of L1–L3 laminectomy and found that dorsal root ganglion neurons and the macrophages infiltrating into the wound area released *** vitro experiments revealed that type 1 macrophages secreted substance P,which promoted differentiation of type 1 macrophages towards a type 2 ***-throughput mRNA-seq analysis revealed that the sphingolipid metabolic pathway may be involved in the regulation of type 2 macrophages by substance ***,sphingomyelin synthase 2,a component of the sphingolipid metabolic pathway,promoted M2 differentiation in substance P-treated macrophages,while treating the macrophages with LY93,a sphingomyelin synthase 2 inhibitor,suppressed M2 *** addition,substance P promoted the formation of neutrophil extracellular traps,which further boosted M2 *** substance P with the neurokinin receptor 1 inhibitor RP67580 decreased the number of M2 macrophages in the wound area after spinal surgery and alleviated epidural fibrosis,as evidenced by decreased fibronectin,α-smooth muscle actin,and collagen I in the scar *** results demonstrated that substance P promotes M2 macrophage differentiation in epidural fibrosis via sphingomyelin synthase 2 and neutrophil extracellular *** findings provide a novel strategy for the treatment of epidural fibrosis.

关键词： dorsal root ganglion epidural fibrosis laminectomy macrophage mitochondria neurokinin receptor 1 neutrophil extracellular traps sphingomyelin synthase 2 substance P

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Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

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Acta Pharmaceutica Sinica B 2024年第1期14卷 87-109页

作者： Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi jin-peng sun Luis Menéndez-Arias Johan Neyts Xinyong Liu peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen Research Institute of Shandong University Shenzhen 518057China The Key Laboratory of Infection and Immunity of Shandong Province Department of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a Molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous University of Madrid) Madrid 28049Spain KU Leuven Department of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life *** covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic *** antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable *** non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available *** viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

关键词： COVID-19 SARS-CoV-2 Main protease Non-covalent inhibitors Medicinal chemistry strategies

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Arrestin mediated GPCR biased signaling and its application in new drug discovery

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中国药理学与毒理学杂志 2017年第10期31卷 944-945页

作者： jin-peng sun Department of Biochemistry and Molecular Biology Shandong University Jinan 250012 China

G protein coupled receptors (GPCR) are important transmembrane proteins which account for more than 30% of direct clinical drug targets. Two main signaling pathways, either mediated by different G protein subtype or arrestins, underlies most of 800 GPCR functions in human genome. Selective ligands targeting to one of the G protein or arrestin signaling through specific receptor, which is also called biased ligands, may have beneficial effects and delete the unwanted side effects compared with traditional full agonists or antagonists. However, the mechanism governing the arrestin mediated GPCR biased signaling is still unclear. In recent years, our research group have combined animal models, cell biology and biophysical approaches to address the arrestin mediated GPCR function and its underlying mechanism, which is a key issue for GPCR targeted drug discovery. We have identified that downstream of β2 adrenergic receptor, arrestin mediated signaling plays critical roles in maintaining the pancreatic islet homeostasis and promotes the learning and memory through regulation of astrocyte-neuron lactate transportation cycle. Targeting β- arrestin- 1 signaling rather than Gq signaling down?stream of CCK1R receptor may provide a better therapy for diabetes. Although arrestin mediated signaling was traditionally recognized as the second wave of GPCR signaling, our recent results indicated that β-arrestin-1 was able to induce the first wave signaling in to regulate the catecholamine secretion from adrenal gland, by directly mediating AT1R/TRPC3 coupling. This result provided new mode for the connection of GPCR to activation of ion channels. Moreover, all above arrestin mediated signaling are regulated by receptor phosphorylation barcode, a hypothesis brought up by Prof. Lefkowitz and Prof. Andrew Tobin. Using biophysical and cellular approaches, we have identified that the 10 distinct phosphorylation interacting sites along the N-terminal of arrestin is the ″phospho-code

关键词： G protein coupled receptors arrestin phosphorylation interacting sites

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Gradient age-precipitation behavior induced by gradient nano-grain in Mg-Gd-Ag-Zr alloy

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Journal of Iron and Steel Research International 2025年第1期32卷 19-24页

作者： Bang-jun Li Jia-peng sun jing Han Guo-song Wu College of Materials Science and Engineering Hohai UniversityNanjing 210024JiangsuChina School of Mechanical and Electrical Engineering China University of Mining and TechnologyXuzhou 221116JiangsuChina

Gradient nano-grained structure is frequently engineered into metallic materials,including Mg alloys,to achieve superior combination of strength and ***,the influence of this microstructural feature on aging precipitation behavior remains inadequately *** this study,the age-precipitation behavior of a gradient nano-grained Mg-Gd-Ag-Zr alloy prepared via ultrasonic severe surface rolling was *** result indicates that the aging precipitation behavior exhibits a depth-dependent variation within this *** the nano-grained surface layer,hierarchicalβnano-precipitates are predominant,while at greater depths,the precipitates consist ofβnanoparticles located at grain boundaries,along with intragranularβ′andγ″*** formation ofβnano-precipitates deviates from the conventional precipitation behavior observed in Mg-Gd-Ag alloys,and is attributed to the high density of defects induced by the surface nano-grained *** finding advances our understanding of the precipitation behavior in the alloys with heterogeneous microstructure.

关键词： Mg alloy Gradient Precipitation Aging behavior Microstructure

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Folding encapsulation toward Lindqvist polyoxometalates within adaptive coordination cages for catalysis

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Science China Chemistry 2025年第2期68卷 561-569页

作者： Ying-Mei Zhong jin-jin Xuan Xujie Qin Han Xiao Zi-Jun Xia Li-peng Zhou Xiao-Qing Guo Yu-Hang Hu Lu Zhang Chunsen Li Li-Xuan Cai Qing-Fu sun State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China University of Chinese Academy of Sciences Beijing 100049China College of Chemistry and Materials Science Fujian Normal UniversityFuzhou 350007China

In nature,enzymes at specific folded conformations exhibit high substrate complementarity,enabling them to efficiently and selectively catalyze biochemical *** by enzymes,coordination cages with conformational dynamics have been designed and are receiving increasing attention due to their versatile applications in allosteric guest binding and *** present here two enzyme-mimicking adaptive macrocycle-based coordination cages,Pd_(2)L_(2)^(1) and Pd_(2)L_(2)^(2),from macrocycle-based ligands(L^(1) and L^(2))and the encapsulation and stabilization of Lindqvist polyoxometalates anions M6O192−(M=W or Mo)in neutral aqueous solution.X-ray crystallographic studies have verified the formation of 1:1 host-guest complexes of two Pd_(2)L_(2) cages and the W6O192−anion,via an induced-fit folding *** with the free host,Pd_(2)L_(2)^(1) exhibited an induced-fit semi-folded conformation in the inclusion complex,while Pd_(2)L_(2)^(2) adopted an induced-fit fully-folded ***,the Mo_(6)O_(19)⊂Pd_(2)L_(2) host-guest complexes demonstrate high yield and selectivity in the oxidative decontamination reaction of the sulfur mustard simulant,2-chloroethyl ethyl *** work not only sheds light on the importance of conformational adaptability in enzyme-like systems but also paves the way for protecting labile POM clusters via host-guest encapsulation toward enhanced catalytic performance in aqueous solution.

关键词： coordination cage induced-fit polyoxometalates host-guest chemistry supramolecular catalysis

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Uncovering the oxidation mechanism of sphalerite(ZnS)in the absence and presence of water:A first-principles investigation

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International Journal of Mining Science and Technology 2025年第1期35卷 149-157页

作者： Yuanjia Luo Wei sun Haisheng Han Jian peng Feng Jiang School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083China

Herein,a first-principles investigation was innovatively conducted to research the surface oxidation of ZnS-like sphalerite in the absence and presence of H_(2)O .The findings showed that single O_(2) was preferred to be dissociated adsorption on sphalerite surface by generating SAO and Zn AO bonds,and the S atom on the surface was the most energy-supported site for O_(2) adsorption,on which a≡Zn-O-S-O-Zn≡structure will be ***,dissociated adsorption of single H_(2)O will not *** was preferred to be adsorbed on the top Zn atom on sphalerite surface in molecular form through Zn-O ***,sphalerite oxidation can occur as if O_(2) was present regardless of the presence of H_(2)O ,and when H_(2)O and O_(2) coexisted,the formation of sulfur oxide(SO_(2) )needed a lower energy barrier and it was easier to form on sphalerite surface than that only O_(2) *** the absence of H_(2)O ,when SO_(2) was generated,further oxidation of which would form neutral zinc *** the presence of H_(2)O ,the formation of SO_(2) on sphalerite surface was easier and the rate of further oxidation to form sulfate was also ***,the occurrence of sphalerite oxidation was accelerated.

关键词： First-principles Oxidation Sphalerite H_(2)O Lower energy barrier

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Boosting bidirectional sulfur conversion enabled by introducing boron-doped atoms and phosphorus vacancies in Ni_(2)P for lithium-sulfur batteries

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Journal of Energy Chemistry 2025年第1期100卷 760-769页

作者： Lin peng Yu Bai Hang Li Meixiu Qu Zhenhua Wang Kening sun Advanced Research Institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China Beijing Key Laboratory of Chemical Power Source and Green Catalysis School of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081China

Lithium-sulfur (Li-S) batteries have gained great attention due to the high theoretical energy density and low cost,yet their further commercialization has been obstructed by the notorious shuttle effect and sluggish redox ***,we supply a strategy to optimize the electron structure of Ni_(2)P by concurrently introducing B-doped atoms and P vacancies in Ni_(2)P (Vp-B-Ni_(2)P),thereby enhancing the bidirectional sulfur *** study indicates that the simultaneous introduction of B-doped atoms and P vacancies in Ni_(2)P causes the redistribution of electron around Ni atoms,bringing about the upward shift of d-band center of Ni atoms and effective d-p orbital hybridization between Ni atoms and sulfur species,thus strengthening the chemical anchoring for lithium polysulfides (LiPSs) as well as expediting the bidirectional conversion kinetics of sulfur ***,theoretical calculations reveal that the incorporation of B-doped atoms and P vacancies in Ni_(2)P selectively promotes Li2S dissolution and nucleation ***,the Li-S batteries with Vp-B-Ni_(2)P-separators present outstanding rate ability of 777 m A h g^(-1)at 5 C and high areal capacity of 8.03 mA h cm^(-2)under E/S of 5μL mg^(-1)and sulfur loading of 7.20 mg cm^(-2).This work elucidates that introducing heteroatom and vacancy in metal phosphide collaboratively regulates the electron structure to accelerate bidirectional sulfur conversion.

关键词： B-doped atoms P vacancies Nickel phosphide Bidirectional sulfur conversion Lithium-sulfur batteries

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CRL4B/PRC2 complex epigenetically regulates pancreatic δ cell paracrine interaction

CRL4B/PRC2 complex epigenetically regulates pancreatic δ ce...

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中国生理学会内分泌代谢、比较生理与应激生理学术会议

作者： Qing Li jin-peng sun Yaoqin Gong Xiao Yu Department of Physiology and Pathophysiology Shandong University School of Basic Medical Sciences Department of Biochemistry Shandong University School of Basic Medical Sciences Department of Genetics Shandong University School of Basic Medical Sciences

Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets:the maintenance of glucose metabolism through the control of the reciprocal secretion of insulin and *** of this circuit contributes to the development of ***,we address two questions:(1) how paracrine interactions are precisely controlled in islets of Langerhans in response to physiological stimuli,such as glucose,to maintain normal glucose homeostasis and(2) whether key epigenetic regulators,such as cullin family members,play important roles in pancreatic islet *** found that the protein levels of CUL4B are tightly controlled under different physiological conditions,and they modulate pancreatic δ cell secretion in an epigenetic ***,mechanistic studies showed that the CRL4B/PRC2 complex,under the control of Hhex,determines the levels of intracellular calcium and cAMP through histone post-translational-modifications,thereby altering expression of the Cav1.2 channel(cacnalc) and adenylyl cyclase 6(adcy6) and modulating somatostatin secretion.

关键词： somatostatin paracrine epigenetics calcium channe adenylyl cyclase

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A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy

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Tungsten 2025年第1期7卷 183-194页

作者： Xin-Ran sun Hao-Ming Yuan Guo-Da Zhang Chao Wang Shu-Juan sun peng-Fei Shi Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers School of Chemistry and Chemical Engineering Linyi University

The combination of photodynamic therapy（PDT） and chemodynamic therapy（CDT） in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione（GSH） overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework（Mn-TCPP） was constructed by the one-pot method and further used for immobilizing glucose oxidase（GOx） to obtain GOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide（H2O2） and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and GSH,thus greatly enhancing ***,benefiting from GOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by GOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

关键词： Chemodynamic therapy Immobilizing enzyme Metal–organic frameworks Photodynamic therapy Starvation therapy

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Ti_(3)C_(2)T_(x) Composite Aerogels Enable Pressure Sensors for Dialect Speech Recognition Assisted by Deep Learning

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Nano-Micro Letters 2025年第5期17卷 1-15页

作者： Yanan Xiao He Li Tianyi Gu Xiaoteng Jia Shixiang sun Yong Liu Bin Wang He Tian peng sun Fangmeng Liu Geyu Lu State Key Laboratory of Integrated Optoelectronics College of Electronic Science and EngineeringJilin UniversityChangchun 130012People’s Republic of China School of Integrated Circuits Tsinghua UniversityBeijing 100084People’s Republic of China International Center of Future Science Jilin UniversityChangchun 130012People’s Republic of China

Wearable pressure sensors capable of adhering comfortably to the skin hold great promise in sound ***,current intelligent speech assistants based on pressure sensors can only recognize standard languages,which hampers effective communication for non-standard language ***,we prepare an ultralight Ti_(3)C_(2)T_(x)MXene/chitosan/polyvinylidene difluoride composite aerogel with a detection range of 6.25 Pa-1200 k Pa,rapid response/recovery time,and low hysteresis(13.69%).The wearable aerogel pressure sensor can detect speech information through the throat muscle vibrations without any interference,allowing for accurate recognition of six dialects(96.2%accuracy)and seven different words(96.6%accuracy)with the assistance of convolutional neural *** work represents a significant step forward in silent speech recognition for human–machine interaction and physiological signal monitoring.

关键词： Pressure sensor Wearable sensor Ti_(3)C_(2)T_(x) composite aerogel Dialect speech recognition

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