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Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes

Acta Pharmaceutica Sinica B 2024年第4期14卷 1693-1710页

作者： Xiong Chen Jinfu Qian shiqi liang Jianchang Qian Wu Luo Yujuan Shi Hong Zhu Xiang Hu Gaojun Wu Xiaokun Li Guang liang Department of Endocrinology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China Department of Wound Repair the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Department of Cardiology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China School of Pharmaceutical Sciences Hangzhou Medical CollegeHangzhou 311399China

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

关键词： Diabetic cardiomyopathy Protein tyrosine kinases FGFR1 Cardiomyocytes Inflammatory responses Toll-like receptor4 c-Src NFkB

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Molecular basis of CONSTANS oligomerization in FLOWERING LOCUS T activation

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Journal of Integrative Plant Biology 2022年第3期64卷 731-740页

作者： Xiaolin Zeng Xinchen Lv Rui Liu Hang He shiqi liang Lixian Chen Fan Zhang Liu Chen Yuehui He Jiamu Du Peking-Tsinghua Center for Life Sciences School of Advanced Agricultural SciencesPeking UniversityBeijing100871 China National Key Laboratory of Plant Molecular Genetics&Shanghai Center for Plant Stress Biology Chinese Academy of Sciences Center for Excellence in Molecular Plant SciencesShanghai201602 China Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes Institute of Plant and Food ScienceDepartment of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen518055 China Peking University Institute of Advanced Agricultural Sciences Weifang261000 China

The transcription factor CONSTANS(CO)integrates day-length information to induce the expression of florigen FLOWERING LOCUS T(FT)in Arabidopsis.We recently reported that the C-terminal CCT domain of CO forms a complex with NUCLEAR FACTOR-YB/YC to recognize multiple cis-elements in the FT promoter,and the N-terminal tandem B-box domains form a homomultimeric assembly.However,the mechanism and biological function of CO multimerization remained unclear.Here,we report that CO takes on a head-to-tail oligomeric configuration via its B-boxes to mediate FT activation in long days.The crystal structure of B-boxesCOreveals a closely connected tandem B-box fold forming a continuous head-to-tail assembly through unique CDHH zinc fingers.Mutating the key residues involved in CO oligomerization resulted in a non-functional CO,as evidenced by the inability to rescue co mutants.By contrast,a transgene encoding a human p53-derived tetrameric peptide in place of the B-boxesCOrescued co mutant,emphasizing the essential role of BboxesCO-mediated oligomerization.Furthermore,we found that the four TGTG-bearing cis-elements in FT proximal promoter are required for FT activation in long days.Our results suggest that CO forms a multimer to bind to the four TGTG motifs in the FT promoter to mediate FT activation.

关键词： B-box domain CONSTANS crystal structure FLOWERING LOCUS T photoperiod

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Constant charge method or constant potential method:Which is better for molecular modeling of electrical double layers?

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Journal of Energy Chemistry 2024年第7期94卷 54-60页

作者： liang Zeng Xi Tan Xiangyu Ji shiqi Li Jinkai Zhang Jiaxing Peng Sheng Bi Guang Feng State Key Laboratory of Coal Combustion Schoolof Energy and PowerEngineeringHuazhong Universityof Science and Technology(HUST)Wuhan 430074HubeiChina Sorbonne Universite CNRSPhysico-chimie des Electrolytes et Nanosystemes InterfaciauxPHENIXF-75005 ParisFrance

In molecular modeling of electrical double layers(EDLs),the constant charge method(CCM)is prized for its computational efficiency but cannot maintain electrode equipotentiality like the more resourceintensive constant potential method(CPM),potentially leading to inaccuracies.In certain scenarios,CCM can yield results identical to CPM.However,there are no clear guidelines to determine when CCM is sufficient and when CPM is required.Here,we conduct a series of molecular simulations across various electrodes and electrolytes to present a comprehensive comparison between CCM and CPM under different charging modes.Results reveal that CCM approximates CPM effectively in capturing equilibrium EDL and current-driven dynamics in open electrode systems featuring ionic liquids or regular concentration aqueous electrolytes,while CPM is indispensable in scenarios involving organic and highly concentrated aqueous electrolytes,nanoconfinement effects,and voltage-driven dynamics.This work helps to select appropriate methods for modeling EDL systems,prioritizing accuracy while considering computationalefficiency.

关键词： Electrochemical interface Molecular dynamics Electrode polarization modeling Nanoconfinement effect

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Regulation of different light conditions for efficient biomass production and protein accumulation of Spirulina platensis

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Journal of Oceanology and Limnology 2024年第1期42卷 174-186页

作者： Yufei ZHANG Xianjun LI Yuhui LI shiqi LIU Yanrui CHEN Miao JIA Xin WANG Lu ZHANG Qiping GAO liang ZHANG Daoyong YU Baosheng GE State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology China University of Petroleum(East China)Qingdao 266580China Tongwei Co. Ltd.Healthy Aquaculture Key Laboratory of Sichuan ProvinceChengdu 610093China

Light plays an important role in the photosynthesis and metabolic process of microalgae.However,how different light conditions regulate the biomass production and protein accumulation of microalgae is mostly unknown.In this study,the influence of different light conditions,including light colors,densities,and light:dark cycles on the cell growth and biochemical composition of Spirulina platensis was symmetrically characterized.Under different colored lights,S.platensis all shows an increase trend within the increased light intensity ranges;however,each showing different optimal light intensities.At the same light intensity,different colored lights show different growth rate of S.platensis following the sequence of red>white>green>yellow>blue.The maximum growth rate and protein accumulation were determined as 21.88 and 5.10 mg/(L·d)when illuminated under red LED.The energy efficiency of different light sources was calculated and ranked as red>white>blue≈green>yellow.Transcriptomic analysis suggests that red light can promote cell growth and protein accumulation by upregulating genes related to photosynthesis,carbon fixation,and C-N metabolism pathways.This study provides a conducive and efficient way to promote biomass production and protein accumulation of S.platensis by regulating light conditions.

关键词： microalgae light emitting diode protein accumulation biomass production transcriptomic analysis

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Ultrafast modulable 2DEG Huygens metasurface

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Photonics Research 2024年第5期12卷 1004-1015页

作者： HONGXIN ZENG XUAN CONG shiqi WANG SEN GONG LIN HUANG LAN WANG HUAJIE liang FENG LAN HAOYI CAO ZHENG WANG WEIPENG WANG SHIXIONG liang ZHIHONG FENG ZIQIANG YANG YAXIN ZHANG TIE JUN CUI Terahertz Communication Laboratory School of Electronic Science and EngineeringUniversity of Electronic Science and Technology of ChinaChengdu 611730China Zhangjiang Laboratory Shanghai 201210China Yangtze Delta Region Institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou 313098China National Key Laboratory of Solid-State Microwave Devices and Circuits Hebei Semiconductor Research InstituteShijiazhuang 050051China Institute of Electromagnetic Space and State Key Laboratory of Millimeter Waves Southeast UniversityNanjing 210096China

Huygens metasurfaces have demonstrated remarkable potential in perfect transmission and precise wavefront modulation through the synergistic integration of electric resonance and magnetic resonance.However,prevailing active or reconfigurable Huygens metasurfaces,based on all-optical systems,encounter formidable challenges associated with the intricate control of bulk dielectric using laser equipment and the presence of residual thermal effects,leading to limitations in continuous modulation speeds.Here,we present an ultrafast electrically driven terahertz Huygens metasurface that comprises an artificial microstructure layer featuring a two-dimensional electron gas(2DEG)provided by an AlGaN/GaN heterojunction,as well as a passive microstructure layer.Through precise manipulation of the carrier concentration within the 2DEG layer,we effectively govern the current distribution on the metasurfaces,inducing variations in electromagnetic resonance modes to modulate terahertz waves.This modulation mechanism achieves high efficiency and contrast for terahertz wave manipulation.Experimental investigations demonstrate continuous modulation capabilities of up to 6 GHz,a modulation efficiency of 90%,a transmission of 91%,and a remarkable relative operating bandwidth of 55.5%.These significant advancements substantially enhance the performance of terahertz metasurface modulators.Importantly,our work not only enables efficient amplitude modulation but also introduces an approach for the development of high-speed and efficient intelligent transmissive metasurfaces.

关键词： heterojunction precise surface

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腹部手术患者围术期六种低体温特征与异体红细胞输注的关联性分析

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四川大学学报（医学版） 2023年第6期54卷 1256-1262页

作者：刘雨薇梁诗琪范美龄龚仁蓉李卡四川大学华西医院普通外科/四川大学华西护理学院成都610041 护理学四川省重点实验室成都610041

目的探索腹部手术患者围术期多种体温特征与异体红细胞输注的关联性。方法回顾性分析2019年10月–2021年7月于四川大学华西医院行腹部手术的患者资料,患者核心体温由穿戴式无线体温传感器围术期全程连续监测,计算进入手术室至麻醉结束... 详细信息

目的探索腹部手术患者围术期多种体温特征与异体红细胞输注的关联性。方法回顾性分析2019年10月–2021年7月于四川大学华西医院行腹部手术的患者资料,患者核心体温由穿戴式无线体温传感器围术期全程连续监测,计算进入手术室至麻醉结束后24 h内的体温最低值、体温最大跌幅、低体温持续时长占比、时间加权平均温度、36℃曲线下面积和37℃曲线下面积。采用限制性立方样条结合多因素logistic回归模型评估上述6种体温特征与围术期异体红细胞输注的关联。结果共有3 119例患者纳入研究,其中异体红细胞输注率为2.8%。限制性立方样条模型显示,异体红细胞输注与围术期体温最低值(P_(overall)=0.048)和36℃曲线下面积有关(P_(overall)=0.026),非线性检验无统计学意义;其他体温特征关联无统计学意义。根据模型结果取截点对体温特征分组,多因素logistic回归显示体温最低值<35.5℃(OR=2.47,95%CI:1.21~5.03)、36℃曲线下面积≥100℃·min(OR=2.24,95%CI:1.09~4.58)与围术期异体红细胞输注需求增加有关。结论低体温与围术期异体红细胞输注需求增加有关,并且存在时间维度上的累积效应。针对出血风险高的患者应注意避免围术期体温过低、减少低体温的累积暴露量,以降低输血需求。

关键词：腹部手术围术期低体温输血可穿戴设备生命体征

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Nonlinear wave propagation in acoustic metamaterials with bilinear nonlinearity

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Chinese Physics B 2023年第4期32卷 405-411页

作者：梁诗琪刘杰惠赖耘刘晓宙 Key Laboratory of Modern Acoustics Institute of Acoustics and School of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China State Key Laboratory of Acoustics Institute of AcousticsChinese Academy of SciencesBeijing 100190China

Nonlinear phononic crystals have attracted great interest because of their unique properties absent in linear phononic crystals.However,few researches have considered the bilinear nonlinearity as well as its consequences in acoustic metamaterials.Hence,we introduce bilinear nonlinearity into acoustic metamaterials,and investigate the propagation behaviors of the fundamental and the second harmonic waves in the nonlinear acoustic metamaterials by discretization method,revealing the influence of the system parameters.Furthermore,we investigate the influence of partially periodic nonlinear acoustic metamaterials on the second harmonic wave propagation,and the results suggest that pass-band and band-gap can be transformed into each other under certain conditions.Our findings could be beneficial to the band gap control in nonlinear acoustic metamaterials.

关键词： bilinear nonlinearity phononic crystal band-gap manipulation nonlinear acoustic metamaterial

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上消化道手术患者术前肺功能检查指标对术后肺炎的预测价值研究

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中国胸心血管外科临床杂志 2022年第7期29卷 923-929页

作者：梁诗琪刘雨薇林琳李卡四川大学华西护理学院/四川大学华西医院成都610041 四川大学华西护理学院/四川大学华西医院胃肠外科成都610041 四川大学华西护理学院/四川大学华西医院胸外科成都610041

目的分析上消化道手术患者术前肺功能指标与术后肺炎的关系。方法前瞻性收集与分析2020年9月—2021年1月在四川大学华西医院接受肺功能检查并行上消化道手术303例患者的临床资料,其中男217例、女86例,平均年龄(61.61±10.42)岁。肺功能... 详细信息

目的分析上消化道手术患者术前肺功能指标与术后肺炎的关系。方法前瞻性收集与分析2020年9月—2021年1月在四川大学华西医院接受肺功能检查并行上消化道手术303例患者的临床资料,其中男217例、女86例,平均年龄(61.61±10.42)岁。肺功能从通气功能、肺容量、弥散功能和气道阻力4个方面进行评价,本研究收集的肺功能指标均用实测值占预计值的百分比表示。结局指标为术后30 d内是否发生肺炎。应用logistic回归分析术前肺功能指标与术后肺炎的关系。结果全组共196例胃癌患者和107例食管癌患者,上消化道手术患者术后肺炎的发生率为26.7%(81/303)。术前低最大呼气流量患者发生术后肺炎的风险是正常患者的3.094倍[OR=3.094,95%CI(1.362,7.032),P=0.007]。未发现其它术前肺功能指标与术后肺炎的相关性。结论术前最大呼气流量可能为预测上消化道手术患者术后肺炎发生的重要指标。

关键词：上消化道手术肺功能检查术后肺炎预测

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半潜式波浪能养殖平台与系泊系统的耦合动力分析

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太阳能学报 2022年第8期43卷 463-471页

作者：黄硕梁诗琪盛松伟马山陈纪康李建东中山大学海洋工程与技术学院珠海519000 南方海洋科学与工程广东省实验室(珠海) 珠海519000 中国科学院广州能源研究所广州510640 哈尔滨工程大学船舶工程学院哈尔滨150001

以“澎湖号”半潜式波浪能养殖平台为研究对象,开展养殖平台及其系泊系统在浪、流联合作用下水动力性能的研究。基于三维势流理论,应用一阶泰勒展开边界元方法对其频域水动力进行计算,研究不同浪向下平台的运动响应和二阶波浪漂移力。... 详细信息

以“澎湖号”半潜式波浪能养殖平台为研究对象,开展养殖平台及其系泊系统在浪、流联合作用下水动力性能的研究。基于三维势流理论,应用一阶泰勒展开边界元方法对其频域水动力进行计算,研究不同浪向下平台的运动响应和二阶波浪漂移力。采用间接时域分析方法和异步耦合方法实现平台和系泊系统的时域耦合动力求解,对不同浪流组合工况下平台的时域运动与锚链张力进行分析。研究表明,在南海常规海况中平台稳定性较好,立柱间水动力干扰尤为明显,顺浪时平台所受的二阶波浪漂移力最小。在与系泊系统的耦合作用下,平台的横摇与纵摇运动受入射波浪向的影响较大,入射波波高对顺浪下的平台横摇运动和横浪与斜浪下平台纵摇运动影响明显。

关键词：波浪能频域分析时域分析养殖平台系泊系统

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术前肝功能指标对原位肝移植大量输血的预测研究

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四川大学学报（医学版） 2023年第4期54卷 771-776页

作者：胡艳杰袁星竹梁诗琪杨小玲罗艳丽李卡四川大学华西护理学院/四川大学华西医院成都610041 四川大学华西医院肝脏外科/四川大学华西护理学院成都610041 四川大学华西医院手术室/四川大学华西护理学院成都610041

目的探讨术前肝功能指标对原位肝移植术中大量输血的预测作用,并建立预测模型。方法回顾性分析2015年1月1日–2021年6月30日四川大学华西医院肝脏外科行原位肝移植手术的607例患者相关资料,根据术中输注红细胞悬液量分为大量输注组(mass... 详细信息

目的探讨术前肝功能指标对原位肝移植术中大量输血的预测作用,并建立预测模型。方法回顾性分析2015年1月1日–2021年6月30日四川大学华西医院肝脏外科行原位肝移植手术的607例患者相关资料,根据术中输注红细胞悬液量分为大量输注组(massive blood transfusion,MBT)及非大量输注组(non-massive blood transfusion,NMBT),采用单因素、多因素logistic回归对原位肝移植术中大量输血的危险因素进行分析,通过Hosmer-Lemeshow检验评价模型的校准度,受试者工作特征(receiver operating characteristic,ROC)曲线下面积(area under the curve,AUC)衡量模型的区分度。结果logistic回归提示,丙氨酸转氨酶(alanine transaminase,ALT)、天冬氨酸转氨酶(aspartate transaminase,AST)、血清总胆红素(total bilirubin,TBIL)、血清直接胆红素(direct bilirubin,DBIL)、白蛋白(albumin,ALB)、child-Pugh评分与原位肝移植术中大量输血风险无相关性;血小板计数(platelet count,PLT)[比值比(odds ratio,OR)=0.90,95%置信区间(confidence interval,CI)(0.09~0.19),P=0.02]、国际标准化比值(international normalized ratio,INR)[OR=19.43,95%CI(7.64~19.44),P<0.01]、凝血酶原时间(prothrombin time,PT)[OR=1.43,95%CI(1.25~1.63),P<0.01]、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)[OR=0.92,95%CI(0.90~0.95),P<0.01]是原位肝移植手术患者术中大量输血的危险因素,Hosmer-Lemeshow检验提示模型校准能力较好(χ^(2)=9.06,P=0.48);AUC为0.80,95%CI为0.77~0.83(P<0.01)。结论基于原位肝移植患者术前PLT、INR、PT、APTT建立预测模型可用于预测术中大量输血的风险。

关键词：原位肝移植肝功能指标大量输血回顾性

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