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Journal of Genetics and Genomics 2024年第1期51卷 61-74页

作者： Cheng Ji Yue Ou Wangjianfei Yu Jiaxin Lv Fanmiao Zhang Huashan Li Zeyun Gu Jiayuan Li zhaomin zhong Han Wang Center for Circadian Clocks Soochow UniversitySuzhouJiangsu 215123China School of Biology and Basic Medical Sciences Suzhou Medical CollegeSoochow UniversitySuzhouJiangsu 215123China

Thyroid-stimulating hormone(TSH)is important for the thyroid gland,development,growth,and *** in TSH production or the thyrotrope cells within the pituitary gland cause congenital hypothyroidism(CH),resulting in growth retardation and neurocognitive *** human TSH is known to display rhythmicity,the molecular mechanisms underlying the circadian regulation of TSH and the effects of TSH-thyroid hormone(TH)signaling on the circadian clock remain *** we show that TSH,thyroxine(T4),triiodothyronine(T3),and tshba display rhythmicity in both larval and adult zebrafish and tshba is regulated directly by the circadian clock via both E′-box and *** tshba^(−/−)mutants manifest congenital hypothyroidism,with the characteristics of low levels of T_(4)and T_(3)and growth *** or overexpression of tshba alters the rhythmicity of locomotor activities and expression of core circadian clock genes and hypothalamic-pituitary-thyroid(HPT)axis-related ***,TSH-TH signaling regulates clock2/npas2 via the thyroid response element(TRE)in its promoter,and transcriptome analysis reveals extensive functions of Tshba in ***,our results demonstrate that zebrafish tshba is a direct target of the circadian clock and in turn plays critical roles in circadian regulation along with other functions.

关键词： Thyroid-stimulating hormone subunitβa (tshba) Thyroid hormone Circadian rhythm TALEN Zebrafish

Ascorbic acid derived carbon dots promote circadian rhythm and contribute to attention deficit hyperactivity disorder

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Nano Research 2022年第9期15卷 8247-8254页

作者： Jian Huang Yun Wang zhaomin zhong Yurong Ma Keru Deng Changhong Liu Hui Huang Yang Liu Xin Ding Zhenhui Kang School of Biology&Basic Medical Science Soochow UniversitySuzhou 215123China Institute of Functional Nano and Soft Materials Laboratory(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123China Division of Neonatology Children’s Hospital of Soochow UniversitySuzhou 215003China Macao Institute of Materials Science and Engineering(MIMSE) MUST-SUDA Joint Research Center for Advanced Functional MaterialsMacao University of Science and TechnologyTaipa 999078MacaoChina

Attention deficit hyperactivity disorder(ADHD)is one of the most prevalent psychiatric disorders in children,and ADHD patients always display circadian ***,the ADHD drugs currently used in clinic have strong side effects,such as psychosis,allergic reactions,and heart ***,we demonstrated carbon dots derived from the ascorbic acid(VCDs)could strongly rescue the hyperactive and impulsive behaviour of a zebrafish ADHD disease model caused by per1b *** prolonged the circadian period of zebrafish for more than half an *** addition,the amplitude and circadian phase were also *** dopamine level was specifically increased,which may be caused by stimulation of the dopaminergic neuron development in the ***,it was found that the serotonin level was not altered by VCDs ***,the gene transcriptome effects of VCDs were discussed in present *** results provided the dynamic interactions of carbon dots with circadian system and dopamine signaling pathway,which illustrates a potential application of degradable and bio-safe VCDs for the treatment of the attention deficient and hyperactive disorder through circadian intervention.

关键词： carbon dots circadian rhythm dopamine attention deficit hyperactivity disorder(ADHD) zebrafish

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斑马鱼幼鱼在中药单体毒性检测的研究进展

黑龙江科学 2024年第10期15卷 123-126页

作者：顾瑾李蕊孟研玉郑彦文仲兆民苏州大学苏州医学院基础医学与生物科学学院江苏苏州215123 苏州大学附属第二医院江苏苏州215000

中药是多成分、多靶点的复杂体系,是我国几千年文明积累下来的宝贵资源,但由于中药的毒性研究缺乏,导致其使用安全范围不明确,限制了其广泛使用和推广,故对每种中药单体的毒性评价尤为重要。斑马鱼是一种重要的脊椎动物模型,用于低成本... 详细信息

中药是多成分、多靶点的复杂体系,是我国几千年文明积累下来的宝贵资源,但由于中药的毒性研究缺乏,导致其使用安全范围不明确,限制了其广泛使用和推广,故对每种中药单体的毒性评价尤为重要。斑马鱼是一种重要的脊椎动物模型,用于低成本的体内全生物中通量药物筛选和毒理研究。综述了利用斑马鱼检测多种中药单体的心脏毒性、肝毒性、神经毒性和发育毒性的研究进展,指出了其在中药单体毒性研究中存在的问题。斑马鱼是中药单体毒性及安全性评价的理想模式生物,未来,需建立标准规范和高通量测定方法对上千种中药单体进行安全性评价。

关键词：中药单体斑马鱼心脏毒性肝毒性神经毒性

Zinc finger transcription factor Sp7/Osterix acts on bone formation and regulates col10a1a expression in zebrafish

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Science Bulletin 2017年第3期62卷 174-184页

作者： Pengfei Niu zhaomin zhong Mingyong Wang Guodong Huang Shuhao Xu Yi HOU Yilin Yan Han Wang Center for Circadian Clocks Soochow University Suzhou 215123 China School of Biology ＆ Basic Medical Sciences Medical College Soochow University Suzhou 215123 China Institute of Neuroscience University of Oregon Eugene OR 97403-1254 USA

Sp7/Osterix as a zinc finger transcription factor is expressed specifically in *** lethality of Sp7 knockout mice,however,has prevented from examining the functions of Sp7 in osteoblast and bone formation in live *** we used TALEN,a versatile genome-editing tool,to generate one zebrafish sp7 mutant *** sp7-/- mutant zebrafish are able to survive to *** Red staining and Micro-CT analysis showed that sp7-/- larvae and adult fish fail to develop normal opercula,and display curved tail fins and severe craniofacial malformation,while Alcian Blue staining showed no obvious cartilage defects in sp7-/- *** RT-PCR showed that a number of osteoblast markers including spp1,phex,col1 ala,and col1a1 b are significantly down-regulated in sp7-/- ***,col10a1 a,whose ortholog is the cartilage marker in mice,was shown to be a novel downstream gene of Sp7 as an osteoblast marker in ***,these results suggest that Sp7 is required for zebrafish bone development and zebrafish sp7 mutants provide animal models for investigating novel aspects of bone development.

关键词：斑马鱼转录因子锌指骨形成定量RT-PCR 成骨细胞基因敲除细胞标记

Blue-light treatment in the morning combined with no blue-ray light treatment in the evening improves the circadian function and sleep quality of non-24-hour shiftworkers

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Blue-light treatment in the morning combined with no blue-ra...

中国睡眠研究会第十四届全国学术年会

作者： zhaomin zhong Xiaohui Tan Xingna An Jie Li Jing Cai Yunchun Jiang Bo Li Quan Shi Meng Zhao Qun Luo Han Wang Soochow University PLA Naval Medical Center

In modern 24-hour society, various round-the-clock services have entailed shiftwork, resulting in non-24-hour shift schedules. Previous studies have demonstrated the harmful impact of shiftwork or non-24-hour work regimes on circadian clock functions. However, the extent of behavioral and physiological alterations by non-24-hour schedules remains unclear, and particularly, effective interventions to restore the circadian functions of non-24-hour shift workers are rarely explored. Here we investigated the effects of a non-24-hour schedule simulating a submarine watchkeeping shift on daily rhythms of 16 participants. We found that the non-24-hour submarine shift significantly disrupted the daily rhythms of locomotor activity, wrist temperature, sleep, heart rate, blood pressure, oxygen saturation levels, fatigue and melatonin as well as damaged sleep quality. We further evaluated an intervention strategy with light spectral manipulation to improve or alleviate effects of non-24-hour schedule. The results show that administration of blue-light(shorter wavelength) in the morning(using blue eyeglasses) combined with no-blue-ray light(shield shorter wavelength) in the evening improves the amplitude of daily rhythms and sleep quality of the non-24-hour participants. Together, these findings demonstrate the harmful consequences of the non-24-hour submarine shift and provide a non-invasive strategy to improve the wellbeing and work efficiency of the non-24-hour shift population.

关键词：

Circadian clock protein Period3 contributes to sleep homeostasis through histamine and GABA signaling in zebrafish

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Circadian clock protein Period3 contributes to sleep homeost...

中国神经科学学会第十二届全国学术会议

作者： zhaomin zhong Xiaona XU Han WANG Center for Circadian Clocks Soochow University

The zebrafish（Danio rerio） has figured prominently as a vertebrate model for studying circadian clocks and sleep. It is known that both the homeostatic process（S） and the circadian process（C） contribute to regulation of sleep homeostasis. While we have a good understanding of circadian regulation, relatively little is known about molecular mechanisms underlying circadian regulation of sleep homeostasis and/or interaction between the circadian clock system and sleep. Here we reported characterization of zebrafish period3（per3） null mutants generated by TALEN. Locomotor assays showed that per3 mutant fish display 0.5-hour shortened period and approximately 3-hour phase advance compared with wild types under constant dark, and are completely arrhythmic under constant light;and also per1 a, per1 b and per2 are down-regulated in per3 mutant fish;indicating that per3 is essential for zebrafish circadian regulation. Intriguingly, per3 mutant fish display less sleep time, elevated arousal threshold and difficulty to restore sleep after sleep deprivation. As shown by ELISA, the GABA level is reduced while the histamine level is increased in per3 mutant fish at night-time, indicating that the disturbed sleep pattern of per3 mutant fish may be resulted from altered levels of endogenous GABA and histamine. Deep sequencing-based transcriptome analysis leads us to focus on two candidate genes, GABA A receptor gene rho2 a and histamine decarboxylase gene hdc, both up-regulated in the per3 mutant fish. Luciferase reporter assays showed that both rho2 a and hdc are circadian clock-controlled genes and Per3 negatively regulates their expression. Taken together, these results ascertain Per3’s essential roles in the zebrafish circadian system, demonstrate that Per3 acts through both histamine signaling and GABA signaling to contribute to sleep regulation, and provide an ideal sleep disorder vertebrate model for drug screen and pathogenesis analysis.

关键词： Circadian clocks Per3 Sleep GABA Histamine

Circadian clock protein Period3 contributes to sleep Homeostasis through GABA signaling in zebrafish

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Circadian clock protein Period3 contributes to sleep Homeost...

中国睡眠研究会第十一届全国学术年会

作者： zhaomin zhong Xiaona Xu Yingbin zhong Han Wang Soochow University

The zebrafish(Danio rerio) has figured prominently as a vertebrate model for studying circadian clocks and sleep. Zebrafish are a strong model for developmental biology research because of their fecundity, larval-stage transparency, short time to hatching and ease in handling;furthermore, they are well characterized in terms of development, neurobiology, and genetics. Moreover, there are many experimental tools not easily applied in mammalian models that can be readily applied to zebrafish. It is known that both the homeostatic process(S) and the circadian process(C) contribute to regulation of sleep homeostasis. While we have a good understanding of circadian regulation, relatively little is known about molecular mechanisms underlying circadian regulation of sleep homeostasis and/or interaction between the circadian clock system and sleep. A variable-number(4 or 5) tandem-repeat polymorphism in the coding region of the clock gene PERIOD3 was shown to confer vulnerability to sleep loss and circadian misalignment through its effects on sleep homeostasis in human beings. While Per3 knockout mice shows little impacts in circadian functions and sleeping behaviors. Here we reported characterization of zebrafish period3(per3) null mutants generated by TALEN method. Locomotor assays showed that per3 mutant fish display 1.1-hour shortened period and approximately 3-hour phase advance compared with wild types fish under constant dark condition, and are nearly 3 hours shortened period under constant light condition;and also bmal1b, per1a, per1b and per2 are down-regulated in per3 mutant fish;Deep sequencing-based transcriptome analysis also showed a lot of circadian genes were altered in per3 mutant fish, indicating that per3 is essential for zebrafish circadian regulation. Cell transfection experiments showed that zebrafish Per3 can regulate the expression of bmal1 b through RRE box. Intriguingly, per3 mutant fish display less sleep time in light dark condition, decreased ar

关键词：

Molecular genetic analysis of zebrafish circadian rhythms

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Molecular genetic analysis of zebrafish circadian rhythms

第二届全国发育生物学大会

作者： Han Wang Jian Huang zhaomin zhong Mingyong Wang Shuqing Zhang Yanqing Zhang Center for Circadian Clocks Soochow University

Zebrafish have figured as an important model for investigating vertebrate circadian ***,genetic dissection of zebrafish circadian rhythmicity has lagged behind largely due to the difficulties to obtain circadian *** set out to dissect molecular genetic mechanisms underlying zebrafish circadian *** retroviral insertional mutagenesis,TALEN or CRISPR/Cas9,we have generated zebrafish mutants for period(per)genes:per1a,per1b,per2 and *** assays showed that under light/dark(LD)condition,per1b mutant larvae were approximately three times more active than their wild-type counterparts,while per2mutant larvae had approximately 30%reduced activity amplitude in comparison with wild types;under constant darkness(DD)condition,locomotor activities of perlb mutant larvae were phase advanced by two hours,while locomotor activities of per2mutant larvae were phase delayed by two *** DD condition,the expression of perla,per2 and per3 was all significantly increased in perlb mutants,indicating that Perlb serves as a negative regulator of the three other per genes in the zebrafish circadian *** LD condition,bmalla and annat2 were significantly up-regulated but perla,perlb and bmallb were significantly down-regulated in the per2 mutant *** vitro cell transfection assays showed that Per2 not only represses E-Box-containing genes but also enhances RRE-box-containing *** also found that zebrafish perlb mutants display hyperactive,impulsive-,and attention deficit-like behaviors and low levels of dopamine,reminiscent of human Attention Deficit Hyperactivity Disorder(ADHD)*** circadian clock directly regulates the dopamine catabolism genes dbh and mao,and likely acts through genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum(PT).Our studies demonstrate that Per2 plays dual roles in zebrafish circadian regula

关键词： Abstract:Circadian Clocks Period ADHD Dopamine Zebrafish

基于化学反应的药物与辅料相容性对制剂有关物质影响分析

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华西药学杂志 2022年第6期37卷 704-710页

作者：李杰江娟丁锐邹洁仲兆民西南药业股份有限公司重庆市工业和信息化重点实验室重庆400038 成都与康科技有限公司新品开发实验室四川成都610000 苏州大学基础医学与生命科学学院江苏苏州215000

从化学反应机理的角度,分析药物与辅料的相容性及作用机制,以利于制剂工作者更好地进行处方设计。结合近年来国内外相关文献,分析辅料与药物的直接反应、辅料中杂质与药物的间接反应。药物与辅料的相互作用可改变药物的药剂学性质,影响... 详细信息

从化学反应机理的角度,分析药物与辅料的相容性及作用机制,以利于制剂工作者更好地进行处方设计。结合近年来国内外相关文献,分析辅料与药物的直接反应、辅料中杂质与药物的间接反应。药物与辅料的相互作用可改变药物的药剂学性质,影响药物的稳定性和有效性。药物与辅料间的化学反应类型繁多,且受多种因素的影响,开发者应合理选择辅料,规避潜在反应条件,以质量源于设计(QbD)的理念为指导进行研究。

关键词：化学反应活性药物成分辅料相容性制剂有关物质质量源于设计药动学

血清TLR4和PTEN与特发性膜性肾病患者临床病理特征及预后的相关性

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分子诊断与治疗杂志 2024年第2期16卷 295-299页

作者：钟娇影刘慧陈秀娟苏宝印朱昭明刘杰河北以岭医院肾病科河北石家庄050000

目的探究血清Toll样受体4(TLR4)、第10号染色体缺失性磷酸酶和张力蛋白同源物基因(PTEN)与特发性膜性肾病(IMN)患者临床病理特征及预后的相关性。方法选取2019年1月至2022年1月在河北以岭医院就诊治疗的IMN患者224例为IMN组,同时根据... 详细信息

目的探究血清Toll样受体4(TLR4)、第10号染色体缺失性磷酸酶和张力蛋白同源物基因(PTEN)与特发性膜性肾病(IMN)患者临床病理特征及预后的相关性。方法选取2019年1月至2022年1月在河北以岭医院就诊治疗的IMN患者224例为IMN组,同时根据其预后结果将其分为预后良好组174例、预后不良组50例;另选取同期在本院体检健康者100名作为对照组。采用酶联免疫吸附法(ELISA)检测研究对象血清TLR4、PTEN水平;采用pearson分析IMN患者血清TLR4水平和PTEN水平相关性;多因素Logistic回归分析IMN患者预后不良的影响因素;受试者工作特征曲线(ROC)分析血清TLR4和PTEN在评估IMN患者预后中的价值。结果 IMN组血清TLR4、PTEN水平较对照组均显著升高,差异有统计学意义(t=12.918,13.249,P<0.05);预后不良组血清TLR4、PTEN水平较预后良好组均显著升高,差异有统计学意义(t=11.608,12.965,P<0.05);IMN患者血清TLR4与PTEN水平呈正相关;TLR4、PTEN、IgG、合并高血压均为IMN患者预后不良的独立危险因素(P<0.05);血清TLR4、PTEN水平预测IMN患者预后是否不良的曲线下面积(AUC)分别为0.878、0.868,两者联合预测的AUC为0.941,高于两者单独预测(z=1.874、2.065,P<0.05),且特异度为0.89,灵敏度为0.88。结论血清TLR4、PTEN水平与IMN患者分期,肾小球硬化,二者对IMN预后具有一定的预测价值。

关键词： Toll样受体4 第10号染色体缺失性磷酸酶和张力蛋白同源物基因特发性膜性肾病