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Pharmacokinetics of H002, a novel S1PR_1 modulator, and its metabolites in rat blood using liquid chromatography–tandem mass spectrometry

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Acta Pharmaceutica Sinica B 2016年第6期6卷 576-583页

作者： Jiaqi mi Manman Zhao Shu Yang Shuang Yang jing Jin Xiaojian Wang Qiong Xiao Jinping Hu Yan Li Department of Drug Metabolism Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD StudyKey Laboratory of Active Substances Discovery and Drug Ability Evaluation State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

A rapid and sensitive liquid chromatography–tandem mass spectrometry(LC–MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal *** samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL /min with an operating temperature of 20 1C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring *** detection responses were obtained from 0.2–100 ng/mL for H002 and H002-M, while 0.5–100 ng/mL for H002-P. The intra- and inter-day precision(RSD%) was within 11.76%, with the accuracy(RE%) ranging from –9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic *** method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.

关键词： S1P receptor S1PR1 modulator Sphingosine-1-phosphate S1P analogue Metabolite LC–MS/MS Pharmacokinetics Periphery blood lymphocyte

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Peripheral Leptin Signaling Mediates Formalin-Induced Nociception

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Neuroscience Bulletin 2018年第2期34卷 321-329页

作者： Zhi-jing Hu Wei Han Chang-Qing Cao Qi-Liang Mao-Ying Wen-Li mi Yan-Qing Wang Department of Integrative Medicine and Neurobiology School of Basic Medical Sciences Institutes of Brain Science Brain Science Collaborative Innovation Center State Key Laboratory of Medical Neurobiology Institute of Acupuncture and Moxibustion Fudan Institutes of Integrative Medicine Fudan University Shanghai 200032 China WuXi AppTec Shanghai 200131 China

Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a highfat diet, we found that:(1) the acute thermal pain sensory threshold did not change in obese mice;(2) the model obese mice had fewer nociceptive responses in formalininduced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation;(3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice,indicating the dysmodulation of topical leptin–leptin receptor signaling in these mice; and(4) leptin–leptin receptor signaling-deficient mice(ob/ob and db/db) or leptin–leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wildtype mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin–leptin receptor pathway could be a peripheral target against acute inflammatory pain.

关键词： Leptin Obesity Formalin test Nociception

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Thermal properties of high temperature vacuum receivers used for parabolic trough solar thermal power system

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Progress in Natural Science:Materials International 2017年第4期27卷 410-415页

作者： Qinghe Yu jing mi Yufan Lang miao Du Shijie Li Hailing Yang Lei Hao Xiaopeng Liu Lijun Jiang Department of Energy Material & Technology General Research Institute for Non-Ferrous Metals

The receiver's emittance and vacuum pressure are the two of great significance issues on the heat-loss which is the main factor reducing the efficiency of the parabolic though systems. In this paper, the thermal steady-state equilibrium method was used to test the receivers heat-loss. The receivers with increasing emittance were tested to study the variation of heat-loss. Meanwhile, the variable vacuum pressure in the annulus that affects the efficiency of the system was investigated. The influence of vacuumizing rate and getters on the vacuum pressure and heat-loss were discussed. The result shows that the emittance and vacuum pressure affect the receiver's heat-loss dramatically, and the emittance is the major influence factor on the thermal properties. The receiver with 0.08 emittance and 10-3Pa vacuum pressure has a satisfactory heat-loss of 215.6 W/m at 400 ℃.The analysis further reveals that the synergistic effect of both emittance and vacuum pressure on the heat-loss can be reflected by the packaging temperature of the glass tube, and a fitting formula has been established to estimate the receivers' heat-loss according to the packaging temperature of the glass tube.

关键词： Parabolic trough receiver Heat-loss Emittance Vacuum pressure

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New Extraction System for Lithium from Brine with High Magnesium Content

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Acta Geologica Sinica(English Edition) 2014年第S1期88卷 333-334页

作者： HE jing YANG Lixin WANG Yi FU mi Key Laboratory of Environmentally Friendly Chemistry and Application of ministry of Education College of ChemistryXiangtan University

Lithium is an important element with a wide variety of applications,especially in lithium ion batteries and in the exploration of nuclear *** lake brine is the most abundant lithium source available in world,comp-rising70%~80%of all known lithium *** can be abstracted from brines with low magnesium content and processed into kinds of lithium compound in Atacama and Hombre Muerto of South America(Nie et al.,2013).

关键词： tri-n-amyl phosphate perchlorate solvent extraction separation of lithium from magnesium

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FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation

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Science China Life Sciences 2025年

作者： Dake Xiao Haowen Ran Lishu Chen Yuanyuan Li Yan Cai Songyang Zhang Qinghui Qi Huiran Wu Cheng Zhang Shuailiang Cao Lanjuan mi Haohao Huang Ji Qi Qiuying Han Haiqing Tu Huiyan Li Tao Zhou Fangye Li Ailing Li Jianghong Man Nanhu Laboratory National Center of Biomedical Analysis School of Traditional Chinese Medicine Capital Medical University Department of Neurosurgery General Hospital of Central Theater Command of Chinese PLA School of Life and Health Sciences Huzhou College Department of Neurosurgery Beijing Fengtai Hospital Department of Neurosurgery First Medical Center of PLA General Hospital

The infiltration of glioblastoma multiforme(GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6(HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.

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Primary intratracheal neurilemmoma in a 10-year-old girl:A case report

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World Journal of Clinical Cases 2021年第29期9卷 8888-8893页

作者： Lei Wu mi-Cun Sha Xi-Ling Wu jing Bi Zhi-min Chen Ying-Shuo Wang Department of Pulmonology and Endoscopy Center The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310003Zhejiang ProvinceChina Department of Pediatrics Suqian People’s Hospital of Nanjing Drum-Tower Hospital GroupSuqian 223800Jiangsu ProvinceChina Department of Respiratory Medicine The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310002Zhejiang ProvinceChina Department of Otorhinolaryngology Head and Neck Surgery The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310000Zhejiang ProvinceChina Department of Pediatric Pulmonology The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Tracheal tumors are relatively rare in adults and uncommon in *** neurilemmoma is a rare condition in adults that usually affects middle-aged people,but it can also occur in *** the clinical presentation is nonspecific and insidious,diagnosis is often *** most common symptoms in these patients are stridor or wheezing(especially positional)and cough.A few patients are misdiagnosed and mistakenly treated for *** SUMMARY A 10-year-old girl was admitted to our unit with a 2-mo history of recurrent cough,dyspnea,and *** condition was more severe after *** symptoms progressed despite treatment with inhaled fluticasone/*** electronic laryngoscopy showed a red,smooth,and round mushroomshaped mass in the trachea,about 1 cm below the vocal *** surface of the mass was covered with several small and discontinuous blood *** 90%of the tracheal lumen was occupied by the mass.A multidisciplinary operation was *** surgically resected mass was diagnosed as benign neurilemmoma by immunohistochemical *** Intratracheal neurilemmoma is fairly rare in *** main symptoms include coughing,wheezing,and *** tumor’s size,location,and degree of intratracheal and extratracheal invasion can be measured by chest computed *** main treatment strategies used for tracheal neurilemmoma are surgical resection and endoscopic ***-term follow-up is warranted for the evaluation of outcomes and complications.

关键词： Airway obstruction Trachea Neurilemmoma Therapeutic bronchoscopy Child Case report

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综合理解韧性治理视角下的城市社区洪涝灾害韧性及分析框架

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灾害学 2025年第1期40卷 8-15页

作者：孔锋米胤瑜王一飞中国农业大学人文与发展学院北京100083 北京市科学技术协会防灾减灾专业智库基地北京100089 清华大学应急管理研究基地北京100084 中国气象局气象干部培训学院北京100081

气候变化背景下频发重发的洪涝灾害是人类社会可持续发展面临的重大挑战之一。该文首先从洪涝灾害治理的转变出发,深入探讨了从传统的洪涝风险管理向洪涝风险治理转变的深层含义,并概述了韧性城市发展的关键特征。接着,文章对韧性概念... 详细信息

气候变化背景下频发重发的洪涝灾害是人类社会可持续发展面临的重大挑战之一。该文首先从洪涝灾害治理的转变出发,深入探讨了从传统的洪涝风险管理向洪涝风险治理转变的深层含义,并概述了韧性城市发展的关键特征。接着,文章对韧性概念的发展历程进行了梳理,并对比分析了不同韧性理论及其侧重点。在城市韧性多学科视角下,提出了城市洪涝灾害韧性的主要特征与核心内涵,并回顾了相关研究进展,同时指出了社区韧性评价的主要聚焦点。再次,论述了城市社区在面对洪涝灾害时的稳健性、适应性和可转换性特征。最后,从韧性治理的角度,构建了“制度-网络-能力”的分析框架,并详细阐释了城市社区洪涝灾害韧性分析的五个维度:制度韧性、组织韧性、社会韧性、基础设施韧性和技术韧性,以及这些维度之间的内容特征和逻辑联系。

关键词：灾害韧性脆弱性社区洪涝灾害治理气候变化灾害治理的复杂性工程韧性生态韧性演进韧性

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Synthesis, Crystal Structure, Fluorescent and Thermal Properties of Sodium Tridecafluorodizirconate Na_5Zr_2F_(13) Compound

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Chinese Journal of Structural Chemistry 2006年第2期25卷 173-179页

作者： MAO Shao-Yu KANG You-Jun mi Jin-Xiao LI Man-Rong WEI Zan-Bin WU Xue-Yan ZHAO jing-Tai College of Chemistry and Chemical Engineering Xiamen University Xiamen 361005 China State Key Lab of High Performance Ceramic and Superfine microstructure Shanghai Institute of Ceramics The Chinese Academy of Sciences Shanghai 200050 China

Crystals of sodium tridecafluorodizirconate Na5Zr2F13 were synthesized under mild hydrothermal conditions, and the structure was refined by single-crystal X-ray diffraction. The compound crystallizes in monoclinic with crystallographic data： Mr = 544.39, C2/m （No. 12）, a = 11.5600（9）, b = 5.4759（4）, c = 8.3989（6） A°, β = 97.361（10）°, V= 527.28（7） A°^3, Z= 2, Dc = 3.429 g/cm^3, 2 = 0.71073A° ,μ = 23.48 cm^-1, F（000） = 504, T= 295 K, Ri = 0.0173 and wR2 = 0.0449 for 55 variables and 682 contributing uniqUe reflections. The crystal structure is constituted with sixand eight-fold sodium atoms, forming irregular trigonal prisms and irregular cubes, respectively. Here, the zirconium atoms are connected with seven fluorine atoms to form a mono-capped trigonal prism. [Zr2F13]^5- complex ions formed by comer-shared [ZrF7]^3- are comer- and edgeshared to [Na4F22] and [Na3F8] cages, leading to the network structure. Thermal analysis, X-ray excited luminescence and photoluminescence under UV light measurements were conducted on Na5Zr2F13 crystals.

关键词： sodium tridecafluorodizirconate hydrothermal synthesis crystal structure luminescent

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Neoadjuvant PD-1 blockade: a promising nonoperative strategy for mismatch repair–deficient, locally advanced rectal cancer

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Signal Transduction and Targeted Therapy 2022年第11期7卷 3989-3991页

作者： mi mi Chenyang Ye Ying Yuan Department of Medical Oncology Key Laboratory of Cancer Prevention and Interventionthe Second Affiliated Hospital of Zhejiang University School of Medicine310009HangzhouZhejiangChina Cancer Center Zhejiang University310058HangzhouZhejiangChina

In a prospective phase 2 study recently published in The New England Journal of Medicine,Cercek et *** the efficacy of the programmed death 1(PD-1)inhibitor dostarlimab in patients with mismatch repair–deficient(dMMR),locally advanced rectal cancer(LARC).The work aimed to present preliminary evidence for the revolutionary therapeutic transition from neoadjuvant chemotherapy/radiotherapy followed by surgery to immunotherapy followed by nonoperative management in this subgroup of patients.

关键词： operative al. rectal

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Experimental Investigation of the Electromagnetically Induced-Absorption-Like Effect for an N-Type Energy Level in a Rubidium BEC

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Chinese Physics Letters 2019年第4期36卷 15-18页

作者： Khan Sadiq Nawaz Cheng-Dong mi Liang-Chao Chen Peng-Jun Wang jing Zhang State Key Laboratory of Quantum Optics and Quantum Optics Devices Institute of Opto-ElectronicsShanxi University Collaborative Innovation Center of Extreme Optics Shanxi University

We study the electromagnetically induced-absorption-like(EIA-like) effect for an n-type system in an ^(87)Rb Bose–Einstein condensate(BEC) using the absorption imaging technique for coupling and driving lasers operating at the D_1 and D_2 lines of ^(87)Rb. The coherent effect is probed by measuring the number of atoms remaining after the BEC is exposed to strong driving fields and a weak probe field. The absorption imaging technique accurately reveals the EIA-like effect of the n-type system. This coherent effect in an n-type system is useful for optical storage, tunable optical switching, and so on.

关键词： 87Rb Bose–Einstein condensate lasers n-type system

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