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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li jingli yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Sex-specific and dose-response relationships of urinary cobalt and molybdenum levels with glucose levels and insulin resistance in U.S. adults

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Journal of Environmental Sciences 2023年第2期124卷 42-49页

作者： jingli yang Yongbin Lu Yana Bai Zhiyuan Cheng College of Earth and Environmental Sciences Lanzhou UniversityLanzhou 730000China Department of Epidemiology and Statistics School of Public HealthLanzhou UniversityLanzhou 730000China School of Public Health and Emergency Management Southern University of Science and TechnologyShenzhen 518055China

Growing studies have linked metal exposure to diabetes ***,these studies had inconsistent *** used a multiple linear regression model to investigate the sexspecific and dose-response associations between urinary metals(cobalt(Co)and molybdenum(Mo))and diabetes-related indicators(fasting plasma glucose(FPG),hemoglobin A1c(HbA1c),homeostasis model assessment for insulin resistance(HOMA-IR),and insulin)in a cross-sectional study based on the United States National Health and Nutrition Examination *** urinary metal concentrations of 1423 eligible individuals were stratified on the basis of the quartile *** results showed that the urinary Co level in males at the fourth quartile(Q4)was strongly correlated with increased FPG(β=0.61,95%CI:0.17–1.04),HbA1c(β=0.31,95%CI:0.09–0.54),insulin(β=8.18,95%CI:2.84–13.52),and HOMA–IR(β=3.42,95%CI:1.40–5.44)when compared with first quartile(Q1).High urinary Mo levels(Q4 vs.Q1)were associated with elevated FPG(β=0.46,95%CI:0.17–0.75)and HbA1c(β=0.27,95%CI:0.11–0.42)in the overall *** linear dose-response associations were observed between urinary Co and insulin(Pnonlinear=0.513)and HOMA–IR(Pnonlinear=0.736)in males,as well as a positive linear dose-response relationship between urinary Mo and FPG(Pnonlinear=0.826)and HbA1c(Pnonlinear=0.376)in the overall *** sex-specific and dose-response relationships were observed between urinary metals(Co and Mo)and diabetes-related indicators,and the potential mechanisms should be further investigated.

关键词： Bayesian kernel machine regression Cobalt Diabetes Insulin resistance Molybdenum

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Epidemic Features of COVID-19 and Potential Impact of Hospital Strain During the Omicron Wave—Australia,2022

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China CDC weekly 2023年第7期5卷 165-169,I0001-I0006页

作者： jingli yang Hannah McClymont Liping Wang Sotiris Vardoulakis Wenbiao Hu School of Public Health and Social Work Queensland University of TechnologyBrisbaneAustralia College of Earth and Environmental Sciences Lanzhou UniversityLanzhou CityGansu ProvinceChina Division of Infectious Diseases Chinese Center for Diseases Control and PreventionBeijing MunicipalityChina National Centre for Epidemiology and Population Health College of Health and MedicineThe Australian National UniversityCanberraAustralia Healthy Environments And Lives(HEAL)National Research Network Australia

Summary What is already known about this topic?Hospitals have experienced a surge in admissions due to the increasing number of Omicron *** the epidemiological features of coronavirus disease 2019(COVID-19)and the strain it places on hospitals will provide scientific evidence to help policymakers better prepare for and respond to future *** is added by this report?The case fatality rate of COVID-19 was 1.4 per 1,000 persons during the Omicron wave.

关键词： Impact COV policy

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Comparative Analysis of Vaccine Inequity and COVID-19 Transmission Amid the Omicron Variant Among Countries--Six Countries,Asia-Pacific Region,2022

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China CDC weekly 2023年第33期5卷 731-736,I0001-I0006页

作者： jingli yang Hannah McClymont David JWarne Liping Wang Wenbiao Hu School of Public Health and Social Work Queensland University of TechnologyBrisbaneAustralia College of Earth and Environmental Sciences Lanzhou UniversityLanzhou CityGansu ProvinceChina School of Mathematical Sciences Queensland University of TechnologyBrisbaneAustralia Centre for Data Science Queensland University of TechnologyBrisbaneAustralia Division of Infectious Diseases Chinese Center for Diseases Control and PreventionBeijingChina.

What is already known about this topic?The coronavirus disease 2019(COVID-19)persists as a significant global public health *** predominant strain,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),notably the Omicron variant,continues to undergo *** vaccination is heralded as the paramount solution to cease the pandemic,challenges persist in providing equitable access to COVID-19 *** is added by this report?The distribution of vaccine coverage exhibited disparities between high-income and middle-income countries,with middle-income countries evidencing lower levels of *** data further suggested that countries with lesser vaccination levels tended to display a higher case fatality *** indicated that an increase in population-wide vaccination was effective in mitigating COVID-19 related *** are the implications for public health practice?The findings of this research underscore the pressing necessity for equitable access to vaccines to effectively mitigate the COVID-19 pandemic within the Asia-Pacific region.

关键词： COV income vaccination

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Somatic embryogenesis and plant regeneration in Betula platyphalla

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Journal of Forestry Research 2021年第3期32卷 937-944页

作者： jingli yang Da yang Wanqiu Lü Xin Zhang Miaomiao Ma Guifeng Liu Jing Jiang Chenghao Li State Key Laboratory of Tree Genetics and Breeding Northeast Forestry UniversityHarbin 150040People’s Republic of China

Betula platyphylla is a native tree species in northern China that has high economic and medicinal *** developed an efficient protocol for the induction of somatic embryogenesis in *** from immature zygotic embryos and assessed the effects of explant type,genotype,and plant growth regulators(PGRs)on embryogenic callus *** the various explants evaluated,embryogenic callus was only produced from mature and immature zygotic embryos on medium with added 2,4-dichlorophenoxyacetic acid(2,4-D).Supplementation of 2,4-D-containing medium with cytokinins increased the frequency of embryogenic callus *** the 20 days after pollination,immature zygotic embryos that had been collected in mid-May yielded embryogenic tissue at the highest frequency(16.8%)when cultured on half-strength MS medium supplemented with 2.0 mg L^(-1)2,4-D and 0.2 mg L^(-1)6-benzylaminopurine(6-BA).The process of proliferation of embryogenic callus,somatic embryo formation,and subsequent plantlet conversion occurred under optimal culture *** regenerated plants weretransplanted to soil,95%of them developed normally and grew *** somatic embryogenesis system required 3–4 months for the regeneration of *** plantlets from immature zygotic embryos.

关键词： Betula platyphalla Somatic embryo Embryogenic callus Immature embryo

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Over expression of TaFer gene from Tamarix androssowii improves iron and drought tolerance in transgenic Populus tomentosa

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Journal of Forestry Research 2019年第1期30卷 171-181页

作者： Bo Zhao jingli yang Wenjing Yao Boru Zhou Wei Zheng Tingbo Jiang State Key Laboratory of Tree Genetics and Breeding Northeast Forestry University Department of Pharmacy Heilongjiang University of Chinese Medicine Research Center on Life Sciences and Environmental Sciences Harbin University of Commerce

Ferritin, a universal intracellular protein, can store large amounts of iron and improve plant resistance to abiotic and biotic stress. In this study, a ferritin gene(TaFer) from Tamarix androssowii Litv. was transferred into Populus tomentosa Carr. cv 'BJR01' via Agrobacterium. Six independent transgenic lines were obtained with a tolerance to kanamycin and three were randomly selected for further analysis. The PCR and RT-PCR results indicate that the TaFer gene had been integrated into the poplar genome. The effect of the gene on abiotic stress tolerance was tested, and the results show that transgenic plants improve growth, had higher chlorophyll and lower MDA contents, and higher relative electrical conductivity,fewer changes of SOD and POD activities, higher iron content, higher root ferric reductase activity and lower levels of ROS accumulation and cell death in response to drought, Fe-insufficient or Fe-excess tolerance. These results indicate that the TaFer gene can improve abiotic stress tolerance in transgenic Populus tomentosa.

关键词： Tarmarix andnssowii Ferritin Iron Genetic transformation Stress resistance

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In vitro anther culture and Agrobacterium-mediated transformation of the AP1 gene from Salix integra Linn. in haploid poplar(Populus simonii × P. nigra)

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Journal of Forestry Research 2018年第2期29卷 320-329页

作者： jingli yang Kun Li Chunyan Li Junxiu Li Bo Zhao Wei Zheng Yuchi Gao Chenghao Li State Key Laboratory of Tree Genetics and Breeding Northeast Forestry University Department of Pharmacy Heilongjiang University of Chinese Medicine Research Center on Life Sciences and Environmental Sciences Harbin University of Commerce Annoroad Gene Technology Co. Ltd

A reliable,efficient anther culture system,the dominant technique for generating haploid plants in breeding programs,that can be used for generating transgenic poplar plants has been *** the present study,therefore,an anther culture system was developed using isolated mid-and late-uninucleate anthers of poplar(Populus simonii x ***).From a combination of SSR and ploidy analyses,six double haploid and two haploid lines were characterized from 86 plants grown from 16 regenerated anther cultured *** 48 months of development,two plant lines from the regenerated plants maintained their haploid level in vitro for over 2 years.A number of haploid plants from the different lines weretransferred to *** leaves of these transplants were then used as explants for transformation with the APETALA1(AP1) gene using Agrobacterium *** of AP1 in haploid poplar induced early flowering with obvious petals when ectopically *** our knowledge,this is the first report on changes in flowering time in AP1-trangenic poplar,which is important for elucidating the regulatory mechanism of tree flower development.

关键词： Pollen grain Populus Flower development Haploid APETALA1

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PuHox52 promotes coordinated uptake of nitrate,phosphate, and iron under nitrogen deficiency in Populus ussuriensis

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Journal of Integrative Plant Biology 2023年第3期65卷 791-809页

作者： Ming Wei Mengqiu Zhang Jiali Sun Ying Zhao Solme Pak Miaomiao Ma Yingxi Chen Han Lu jingli yang Hairong Wei Yuhua Li Chenghao Li State Key Laboratory of Tree Genetics and Breeding School of ForestryNortheast Forestry UniversityHarbin 150040China College of Life Sciences Northeast Forestry UniversityHarbin 150040China College of Forest Resources and Environmental Science Michigan Technological UniversityHoughtonMichigan 49931USA Key Laboratory of Saline-alkali Vegetation Ecology Restoration(Northeast Forestry University) Ministry of EducationHarbin 150040China

It is of great importance to better understand how trees regulate nitrogen(N) uptake under N deficiency conditions which severely challenge afforestation practices, yet the underlying molecular mechanisms have not been well elucidated. Here,we functionally characterized PuHox52, a Populus ussuriensis HD-ZIP transcription factor, whose overexpression greatly enhanced nutrient uptake and plant growth under N deficiency. We first conducted an RNA sequencing experiment to obtain root transcriptome using PuHox52-overexpression lines of P. ussuriensis under low N treatment. We then performed multiple genetic and phenotypic analyses to identify key target genes of PuHox52 and validated how they acted against N deficiency under PuHox52 ***52 was specifically induced in roots by N deficiency, and overexpression of PuHox52promoted N uptake, plant growth, and root development. We demonstrated that several nitrate-responsive genes(PuNRT1.1, PuNRT2.4,PuCLC-b, PuNIA2, PuNIR1, and PuNLP1),phosphate-responsive genes(PuPHL1A and PuPHL1B), and an iron transporter gene(PuIRT1) were substantiated to be direct targets of PuHox52. Among them, PuNRT1.1, PuPHL1A/B, and PuIRT1 were upregulated to relatively higher levels during PuHox52-mediated responses against N deficiency in PuHox52-overexpression lines compared to WT. Our study revealed a novel regulatory mechanism underlying root adaption to N deficiency where PuHox52 modulated a coordinated uptake of nitrate, phosphate, and iron through 'PuHox52-PuNRT1.1', 'PuHox52-PuPHL1A/PuPHL1B', and'PuHox52-PuIRT1' regulatory relationships in poplar roots.

关键词： HD-Zip transcription factor iron transport nitrate transport nitrogen deprivation phosphate absorption Populus ussuriensis root architecture target gene

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维生素E生物合成的相关进展

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科学通报 2020年第35期65卷 4037-4046页

作者：杨景丽孙鸿宋浩天津大学化工学院天津300072 天津大学合成生物学前沿科学中心/系统生物工程教育部重点实验室天津300072

维生素E是具有抗氧化活性的脂溶性化合物,是维持机体代谢的必需维生素,被广泛应用于食品、医药及化妆品等多个领域,市场需求量极大.市场上的维生素E主要来自化学合成和从植物油馏出物中提取.传统的化学合成方式因不能合成特定的立体构... 详细信息

维生素E是具有抗氧化活性的脂溶性化合物,是维持机体代谢的必需维生素,被广泛应用于食品、医药及化妆品等多个领域,市场需求量极大.市场上的维生素E主要来自化学合成和从植物油馏出物中提取.传统的化学合成方式因不能合成特定的立体构型而受到限制.植物提取的方法也受制于有限的植物资源和高的时间成本.利用微生物合成特定构型的复杂天然化合物是一种经济、清洁的方法.本综述首先总结了维生素E生物合成的代谢途径及其研究进展,其次对维生素E生物合成的关键中间体尿黑酸和牻牛儿基牻牛儿基焦磷酸的代谢途径在模式微生物中的代谢工程改造进行了总结,最后对于利用微生物来生物合成维生素E的现状进行了概述,并对其前景进行了展望.

关键词：维生素E 尿黑酸牻牛儿牻牛儿焦磷酸合成生物学

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一种用于场地-建筑群体系地震响应分析的二维耦合法

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振动与冲击 2023年第18期42卷 100-111页

作者：韩冰梁建文杨晶丽天津城建大学土木工程学院天津300384 天津大学建筑工程学院天津300354

该文章发展了一种用于计算场地-建筑群体系地震响应的二维耦合法,其中采用间接边界元法模拟远场土体,采用有限元法模拟近场土体,用解析算法的刚性基础-等效均质块体模型模拟建筑群。该耦合法的优势是建筑群无需离散单元,计算量小,结构... 详细信息

该文章发展了一种用于计算场地-建筑群体系地震响应的二维耦合法,其中采用间接边界元法模拟远场土体,采用有限元法模拟近场土体,用解析算法的刚性基础-等效均质块体模型模拟建筑群。该耦合法的优势是建筑群无需离散单元,计算量小,结构参数简单直观,且无需人工边界即可满足场地无穷远处辐射条件。通过与已有文献结果对比,验证了该文章耦合法计算准确,精度较高。通过数值计算分析了场地-建筑群效应对结构动力响应的影响,研究表明:场地-建筑群效应可能明显放大结构地震响应幅值,这与整个场地-建筑群的特性及地震波特性有关;当建筑群中结构参数相同且结构刚度较大时,场地-建筑群效应可能对结构地震响应幅值的影响较大,尤其是处于建筑群中心位置的结构,该文章算例中放大率达36.17%;当建筑群将相同参数结构分区布置(如多层区、高层区)时,场地-建筑群效应可能对各区中心位置结构的地震响应幅值的影响较大。

关键词：场地-建筑群效应耦合法地震响应放大作用土-结构动力相互作用

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