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Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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Acta Pharmaceutica sinica B 2024年第3期14卷 1283-1301页

作者： Qian Zhao Jiale Dong Han Liu Hui Chen Huan Yu shuyin Ye shuangjin Yu Yu Li Longhui Qiu nazi song Hongjiao Xu Qi Liu Zhiteng Luo Yuyi Li Rui Wang Guodong Chen Xianxing Jiang school of Pharmaceutical sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006China Zhongshan school of Medicine Sun Yat-sen UniversityGuangzhou 510006China shenzhen Turier Biotech.Co. Ltd.Shenzhen 518118China school of Life sciences Key Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China

The role of co-agonists of glucagon-like peptide-1 receptor(GLP-1R)and glucagon receptor(GCGR)in chronic kidney disease(CKD)remains *** we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease ***,GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction(UUO).Based on the importance of GLP-1R and GCGR in CKD,we reported a novel monomeric peptide,1907-B,with dual-agonism on both GLP-1R and *** data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys(~2-3 fold)and exhibited better therapeutic contribution to CKD than best-in-class monoagonists,semaglutide,or glucagon,in db/db mice and UUO *** lock-of-function models,including selective pharmacological activation and genetic knockdown,confirmed that 1907-B’s effects on ameliorating diabetic nephropathy in db/db mice,as well as inhibiting kidney fibrosis in UUO mice,were mediated through GLP-1 and glucagon *** findings highlight that 1907-B,a novel GLP-1R and GCGR co-agonist,exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

关键词： GLP-1 receptor Glucagon receptor Chronic kidney disease Diabetic nephropathy Kidney fibrosis Dual-agonism

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Accelerating Role of Clay in Photo-Oxidation of Polypropylene/Clay Multifilament Yarns

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Chinese Journal of Polymer science 2014年第5期32卷 609-619页

作者： s.Aslanzadeh R.semnani Rahbar M.nazi Department of Textile and Leather Faculty of Chemistry and Petrochemical Engineering Standard Research Institute (SRI)

Photo-oxidative degradation of polypropylene/clay multifilament yarns containing different amounts of clay was investigated. These samples and pure polypropylene （PP） multifilametns were exposed to long wavelength radiations （λ〉 300 nm） under atmospheric condition of constant temperature and relative humidity. The photo-oxidative stability was studied using FTIR spectroscopy, tensile testing and microscopy. The results indicate that the addition of clay particles decreases the stability of PP/clay composites to photo-oxidative degradation according to comparison with pure PP. From FTIR study and tensile properties, it was also found that the multifilaments with higher clay loading reveals a faster loss of mechanical properties, higher photo-oxidative product formation and more reduction in the induction time of photo-oxidation. Moreover, the crack formation on surface of irradiated filaments corresponds well to the conclusions in tensile properties and FTIR characterization.

关键词： Photo-oxidation Polypropylene Multifilarnent yams Nanoclay UV radiation.

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Phenylalanin Ammonia-lyase Activity,Total Phenolics and Flavonoids Contents in Flowers,Leaves,Hulls and Kernels of Three Pistachio(Pistacia vera L.) Cultivars

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植物研究 2012年第5期32卷 519-525页

作者： Nadernejad nazi Ahmadimoghadam Ali Hosseinifard Javad Pourseyedi shahram Biology Department Faculty of ScienceShahid Bahonar University of Kerman Nutrition and Irrigation Department Iran's Pistachio Research Institute Plant Breeding Department Faculty of AgricultureShahid Bahonar University of Kerman

Phenylalanin ammonia-lyase(PAL) plays a pivotal role in the production of phenolic compounds,which are responsible for the success of the defense strategies in harsh environments in response to different *** of the PAL activity,total phenolics,total flavonoids and anthocyanin contents were performed in flowers,leaves and fruits of three pistachio cultivars "Ahmadaghaii","Ohadi" and "Kallehghuchi".The results showed that PAL activity was different in cultivars and in plant organs of pistachio trees(flowers,leaves and fruits).The highest activity rate of their compounds was observed in Ahmadaghaii cultivar.A positive correlation was observed between PAL activity,total phenolics and total flavonoids in leaves,and a negative correlation between PAL activity and anthocyanin contents in leaves and flowers of Ahmadaghaii *** activity and total phenolics in fruits of pistachio suffered a decrease when the maturation processes *** is suggested that the hulls of the pistachio fruits,containing high level of phenolic compounds(especially in Ahmadaghaii cultivar),may function as a protective layer of defense chemicals against ultraviolet radiation and *** final concentration of phenolic compounds,flavonoids and antocyanins in the kernel depend on PAL activity in the kernel's *** results led to the conclusion that increase in PAL activity,phenolic compounds and flavonoids in Ahmadaghaii can help the plant to cope with the stresses better than the other *** phenolic compounds are antioxidant and scavenge free oxygen,it is postulated that Ahmadaghaii is the most resistant cultivar to the environmental stresses.

关键词：药用植物植物研究 PAL

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The Functional Gradient Description Method of space Coordinate Transformation

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Journal of Geodesy and Geoinformation science 2019年第1期2卷 66-71页

作者： Pengshuo DUAN Genyou LIU Youliang GONG Xiaoguang HAO nazi WANG state Key Laboratory of Geodesy and Earth’s Dynamics Institute of Geodesy and GeophysicsChinese Academy of SciencesWuhan 430077China University of Chinese Academy of sciences Beijing 100049China The Information Engineering University Institute of Geographic Spatial InformationZhengzhou 450052China

The 3-dimension coordinate datum transformation is very important in ***,there are small angle coordinate transformation model (i.e.,Bursa model,et al) and large angle coordinate transformation model (i.e.,Rodrigo matrix model,et al).However,these papers only focus on the fixed and static situation regardless of the small or large *** paper proposes the conception of coordinate transformation gradient field,which can realize the space coordinate transformation from small angle to arbitrary angle,and from static to *** on the equivalent characteristics of the unit quaternion rotation matrix and the Rodrigo matrix,through studying the mathematical relationship between the spatial coordinate transformation and the functional gradient,we derive a functional gradient expression of the arbitrary transformation formula in *** study shows that the essence of spatial coordinate transformation is a kind of potential field *** potential field conception can unify all the space coordinate *** is the theoretical foundation for the further study of time continuous space coordinate transformation,and this study gives a new solution for the attitude determination of motion carriers.

关键词： spatial coordinate transformation functional gradient field complete equivalence

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Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis

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Acta Pharmaceutica sinica B 2022年第5期12卷 2443-2461页

作者： nazi song Hongjiao Xu Jiahua Liu Qian Zhao Hui Chen Zhibin Yan Runling Yang Zhiteng Luo Qi Liu Jianmei Ouyang shuohan Wu suijia Luo shuyin Ye Runfeng Lin Xi sun Junqiu Xie Tian Lan Zhongdao Wu Rui Wang Xianxing Jiang school of Pharmaceutical sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China Department of Parasitology of Zhongshan school of Medicine Sun Yat-sen UniversityGuangzhou 510006China Key Laboratory of Tropical Disease Control Ministry of EducationSun Yat-sen UniversityGuangzhou 510006China Provincial Engineering Technology Research Center for Biological Vector Control Sun Yat-sen UniversityGuangzhou 510006China Research Unit of Peptide science Chinese Academy of Medical SciencesLanzhou 730000China Key Laboratory of Preclinical study for New Drugs of Gansu Province School of Basic Medical SciencesLanzhou UniversityLanzhou 730000China shenzhen Turier Biotech.Co. Ltd.Shenzhen 518118China Guangdong Pharmaceutical University Guangzhou 510006China

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor(GLP-1 R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl_(4), a-naphthyl-isothiocyanate(ANIT), bile duct ligation(BDL) and schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix(ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream smad signaling pathways particularly in CCl_(4)-and s. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of proinflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha(NFκB/IKBa) pathways as well as cJun N-terminal kinase(JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1 R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl_(4)-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

关键词： GLP-1R GCGR Liver fibrosis Inflammation Apoptosis Candidate peptides

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匡建军教授从伏邪化火论治痛风性关节炎经验

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中国中医骨伤科杂志 2024年第8期32卷 89-91,96页

作者：刘科张乐张子鸣华盛汤祖宇赵浩茗熊逸啸陈柯如彭娜姿匡建军湖南中医药大学长沙410208 湖南省中医药研究院湖南省中医药研究院附属医院

本文从病因病机、分期论治等方面综合总结了匡建军教授从伏邪化火论治痛风性关节炎的临床经验。匡建军教授指出本病与伏邪相似,伏匿期以正虚为本,邪伏为标;发作期时伏邪受外因感召,内外互相作用,转而化火,从而由里出外,出现红肿热痛症状... 详细信息

本文从病因病机、分期论治等方面综合总结了匡建军教授从伏邪化火论治痛风性关节炎的临床经验。匡建军教授指出本病与伏邪相似,伏匿期以正虚为本,邪伏为标;发作期时伏邪受外因感召,内外互相作用,转而化火,从而由里出外,出现红肿热痛症状;治疗上伏匿期分邪伏三阴证、寒邪内伏证、痰湿伏脾证、瘀毒痼结证,根据不同证型特点,予以扶正、温寒、健脾、活血等法;伏邪化火期予以急清火毒,同时配合外治疗法,临床疗效甚佳。

关键词：痛风性关节炎痹证伏邪化火分期论治名医经验

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Life Balance of Mothers of Children with Cerebral Palsy

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International Journal of Clinical Medicine 2017年第11期8卷 583-594页

作者： s.pideh nazi Narges shafaroodi Laleh Lajevardi Afsoon Hassani Mehraban Farzaneh Yazdani samaneh Hosseinzadeh Department of Occupational Therapy School of Rehabilitation Sciences Iran University of Medical Sciences Tehran Iran Faculty of Health and Life sciences Oxford Brookes University Oxford UK Department of statistics and Computer sciences University of Social Welfare and Rehabilitation Sciences Tehran Iran

Purpose: Having the child with Cerebral palsy is a very stressful experience for the family that could affect daily patterns and routines, habits, needs and occupational performances of all family members specially mothers. This study aimed to investigate life balance of mothers of children with Cerebral palsy (MCCPs) based on the Life Balance Model. Method: Fifty MCCPs aged 3 to 9 years with sample convenient method participated in this descriptive and cross-sectional study. The severity of cerebral palsy was determined by Gross Motor Function Classification system (GMFCs) and Manual Ability Classification system (MACs) and the life balance of mothers was evaluated by Persian version of the LBI (P_LBI). The collected data were evaluated and analyzed using sPss software. Results: The total mean score of LBI and its subscales showed that there is no balanced or very balanced life in mothers and they could be categorized to unbalanced (n = 21) and very unbalanced (n = 29). The total mean score of LBI was 1.46. χ2 test revealed statistically significant difference between two categories (unbalanced and very unbalanced) of mothers regarding GMFCs level (p = 0.009). Also, the total mean score of LBI and its subscales showed no significant difference between two categories (unbalanced and very unbalanced) regarding mother job and age and child age (p > 0.05) but it has significant difference regarding mother education (p = 0.009). Evaluation of the results of LBI and its different subscales indicated that the life balance at balanced or very balanced levels was not observed in any of the studied mothers, and they could be categorized in 2 groups of unbalanced (21 mothers ) and very unbalanced (29 mothers) (Table 2). Discussion: Based on the result of this study, mothers of Cerebral Palsy do not experience balanced life and this feeling of unbalance is related to the level of their child’s disability. Thus, it is necessary to consider this fact in family-centered evaluatio

关键词： Life Balance Cerebral Palsy Main Caregiver

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Research on sea surface Height Measurement Based on GNss-IR Dual Frequency Data Fusion

Research on Sea Surface Height Measurement Based on GNSS-IR ...

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第十一届中国卫星导航年会

作者： Jie Wang Tianhe Xu nazi Wang Yunqiao He Fan Gao Chang’an University Institute of space science Shandong University state Key Laboratory of Geo-information Engineering

It is an important application of GNss in marine remote sensing to measure sea level by using Global Navigation satellite system Interferometry Reflectometry(GNss-IR),which provides a new direction fo

关键词： GNss-IR sea surface height sNR LsP analysis the peak weighting method

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Coastal GNss-R code delay altimetry using GPs L5 signals

Coastal GNSS-R code delay altimetry using GPS L5 signals

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第十一届中国卫星导航年会

作者： Xinyue Meng Fan Gao Tianhe Xu Yunqiao He Ti Chu nazi Wang school of space science and Physics Shandong University Institute of space science Shandong University shandong Provincial Key Laboratory of Optical Astronomy and solar-Terrestrial Environment and Institute of Space SciencesShandong University College of Marine and space Information China University of Petroleum

In recent years, with the gradual completion of different GNss constellations, the available L-band navigation signals have become more abundant. Not only can they be used for PNT(Positioning, Navigat

关键词： GNss-R Code phase delay altimetry L5

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Climate Change Trend Observations in Morocco: Case study of Beni Mellal-Khenifra and Darâa-Tafilalt Regions

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Journal of Geoscience and Environment Protection 2018年第7期6卷 34-50页

作者： Ait Ouhamchich Kamal Karaoui Ismail Arioua Abdelkrim Kasmi Atika Elhamdouni Driss Elfiraoui Fatima Ezzahra Arioua Zakaria nazi Fatima Nabih Nadia Earth sciences Department Faculty of Sciences and Technologies Béni Mella Morocco Regional Meteorology Office Béni Mellal Morocco

Despite the extreme events impact on various climate events frequency and intensity in many developing countries, there has been dearth information on daily climate trends and climatic extremes. This study comes to characterize the climate type and its evolution in Morocco, specially the two regions Beni Mellal-Khenifra and Daraa-Tafilalt. RClimdex software has been used to calculate pluvio-thermal and ombro-thermic indices in the studied stations to reveal climate type in the two regions, their evolutions, and the daily extreme temperatures and precipitations. A cartographic representation has been done for the calculated indices and climatic trends in the stations from 1970 to 2016. As results, the temperature trend for hot day’s number shows a significant increase, while the cold night’s numbers, warm sequences, and precipitation are gradually decreases especially at Khouribga and Midelt. These observed modifications influence negatively the annual rainfall total in the year, the consecutive wet days, the maximums rainy days, and the increase of consecutively dry days. As a conclusion, the Martonne aridity and ombro-thermic indices, show that the temperatures and precipitations evolutions do not induce a change in the climate type for the studied regions.

关键词： Climate Trends Precipitation Temperature RClimdex Beni Mellal-Khenifra Daraa-Tafilalt

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