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Overcoming adaptive resistance in AML by synergistically targeting FOXO3A-GNG7-mTOR axis with FOXO3A inhibitor Gardenoside and rapamycin

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Genes & Diseases 2024年第1期11卷 397-412页

作者： Zhe Chen qian guo Shichen Huang Lei Li Feng Wu Zhilong Liu Zhigang Li Tao Chen Guanbin Song Shuangnian Xu Jieping Chen Yu Hou Department of Hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Institute of Life Sciences Chongqing Medical UniversityChongqing 400016China Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Chongqing Foreign Language School Chongqing 400039China

Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive response signaling weakens the cytotoxic effect of FOxO3A depletion on AML cells.Here,we show that FOxO3A deficiency induces a compensa-tory response involved in the reactive activation of mTOR that leads to signaling rebound and adaptive resistance.Mitochondrial metabolism acts downstream of mTOR to provoke activa-tion of JNK/c-JUN via reactive oxygen species(ROS).At the molecular level,FOXO3A directly binds to the promoter of G protein gamma subunit 7(GNG7)and preserves its expression,while GNG7 interacts with mTOR and restricts phosphorylated activation of mTOR.Consequently,combinatorial inhibition of FOXO3A and mTOR show a synergistic cytotoxic effect on AML cells and prolongs survival in a mouse model of AML.Through a structure-based virtual screening,we report one potent small-molecule FOxO3A inhibitor(Gardenoside)that exhibits a strong effect of anti-FOXO3A DNA binding.Gardenoside synergizes with rapamycin to substantially reduce tumor burden and extend survival in AML patient-derived xenograft model.These results demonstrate that mTOR can mediate adaptive resistance to FOxO3A inhibition and validate a combinatorial approach for treating AML.

关键词： AML Combinatorial inhibition FOXO3A GNG7 mTOR

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Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli

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Biomedical and Environmental Sciences 2024年第2期37卷 228-232页

作者： YE Qiao HUO Jia Nan LUO Yuan MEI Zhu Song FANG Long Mei guo Bing qian WANG Guang Yun Laboratory of clinical medicine Air Force Medical CenterAir Force Medical UniversityBeijing 100142China

As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibitio... 详细信息

关键词： hypoxic Sodium observing

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Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

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Zoological Research 2024年第3期45卷 617-632页

作者： Jing-Hang Jiang Yi-Fu Wang Jie Zheng Yi-Ming Lei Zhong-Yuan Chen Yi guo Ya-Jie guo Bing-qian guo Yu-Fang Lv Hong-Hong Wang Juan-Juan Xie Yi-Xuan Liu Ting-Wei Jin Bi-Qi Li Xiao-Shu Zhu Yong-Hua Jiang Zeng-Nan Mo Center for Genomic and Personalized Medicine Guangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Medical UniversityNanningGuangxi 530021China Department of Urology First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530021China Reproductive Medicine Center Jingmen People’s HospitalJingChu University of Technology Affiliated Central HospitalJingmenHubei 448000China School of Computer Science and Engineering Yulin Normal UniversityYulinGuangxi 537000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Department of Pathology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China Department of Obstetrics and Gynecology Second Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530007China

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://***:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

关键词： Tree shrew Adrenal gland Dehydroepiandrosterone Genome-wide association studies Disease model

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Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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Nano Research 2024年第5期17卷 4329-4337页

作者： Yang Liu Xuwei He Zewei Lian qian guo Jimei Chi Xiaoxue Lin Liyue Zhang Zheng Liu Yingyuan Liu Meng Su Keyu Wang qiangguo Ao Qingli Cheng Department of Nephrology The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China Chinese PLA Medical School Beijing 100853China Key Laboratory of Green Printing CAS Research/Education Center for Excellence in Molecular SciencesBeijing Engineering Research Center of Nanomaterials for Green Printing TechnologyBeijing National Laboratory for Molecular Sciences(BNLMS)Institute of ChemistryChinese Academy of Sciences(ICCAS)Beijing 100190China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of Clinical Laboratory The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China

Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of patients.In this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the point-of-care.We confirmed its efficacy in the early diagnosis of AKI using clinical urine specimens.Direct quantitative detection of uKIM-1 was achieved within 10 min.The lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal microarray.Consequently,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community settings.Rapid,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare costs.It highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.

关键词： photonic crystal point-of-care testing urine kidney injury molecule-1(KIM-1) acute kidney injury

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Free radicals trigger the closure of open pores in lignin-derived hard carbons toward improved sodium-storage capacity

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Journal of Energy Chemistry 2024年第7期94卷 551-559页

作者： Wen-Jun Ji Zong-Lin Yi Ming-Xin Song Xiao-qian guo Yi-Lin Wang Yi-Xuan Mao Fang-Yuan Su Jing-Peng Chen Xian-Xian Wei Li-Jing Xie Cheng-Meng Chen CAS Key Laboratory of Carbon Materials Institute of Coal ChemistryChinese Academy of SciencesTaiyuan 030001ShanxiChina University of Chinese Academy of Sciences Beijing 100049China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China School of Environment and Safety Taiyuan University of Science and TechnologyTaiyuan 030001ShanxiChina

The chemical activation of various precursors is effective for creating additional closed pores in hard carbons for sodium storage.However,the formation mechanism of closed pores under the influence of pore-forming agents is not well understood.Herein,an effective chemical activation followed by a high-temperature self-healing strategy is employed to generate interconnected closed pores in lignin-derived hard carbon(HCs).By systematic experimental design combined with electron paramagnetic res-onance spectroscopy,it can be found that the content of free radicals in the carbon matrix influences the closure of open pores at high temperatures.Excessively high activation temperature(>700 C)leads to a low free radical concentration,making it difficult to achieve self-healing of open pores at high tempera-tures.By activation at 700°C,a balance between pore making and self-healing is achieved in the final hard carbon.A large number of free radicals triggers rapid growth and aggregation of carbon microcrys-tals,blocking pre-formed open micropores and creating additional interconnected closed pores in as-obtained hard carbons.As a result,the optimized carbon anode(LK-700-1300)delivers a high reversible capacity of 330.8 mA h g^(-1) at 0.03 A g^(-1),which is an increase of 86 mA h g^(-1) compared to the pristine lignin-derived carbon anode(L-700-1300),and exhibits a good rate performance(202.1 mA h g^(-1) at 1 A g^(-1)).This work provides a universal and effective guidance for tuning closed pores of hard carbons from otherprecursors.

关键词： Hard carbon Chemical activation Free radical Self-healing Closed pores Sodium ion batteries

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“公转铁”政策对京津冀绿色物流效率的影响

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中国流通经济 2024年第3期38卷 45-55页

作者：郭茜韩嵩李倩北京物资学院统计与数据科学学院北京市101149

为落实绿色发展理念,促进京津冀物流业高质量发展,有效发挥“公转铁”政策对绿色物流效率的提升效应,在系统梳理“公转铁”政策促进绿色物流效率理论机制的基础上,用2010—2020年京津冀地区面板数据,通过双重差分模型、广义双重差分模... 详细信息

为落实绿色发展理念,促进京津冀物流业高质量发展,有效发挥“公转铁”政策对绿色物流效率的提升效应,在系统梳理“公转铁”政策促进绿色物流效率理论机制的基础上,用2010—2020年京津冀地区面板数据,通过双重差分模型、广义双重差分模型和中介效应模型,研究“公转铁”政策对绿色物流效率的促进效应以及作用机制。研究发现,“公转铁”政策在京津冀地区的实施对提升绿色物流效率具有显著的促进效应,并且该效应在经过稳健性检验后依旧成立;政策实施力度对绿色物流效率存在显著的影响,绿色物流效率随着政策实施力度增强而不断提升;“公转铁”政策通过改变物流企业的运输方式偏好,增强铁路运输对公路运输的替代作用,提升绿色物流效率;绿色物流效率提升还受到铁路设施水平、区域建设水平、经济水平、创新能力等多种因素的影响。因此,京津冀绿色物流效率提升,应该考虑多种因素的综合影响,以多层次和系统性支撑政策推动“公转铁”政策的实施;以改变承担社会物流活动企业运输偏好为导向;充分考虑当地内外部环境,结合产业结构、创新能力等因素调整“公转铁”政策实施力度。

关键词： “公转铁”政策京津冀绿色物流效率双重差分模型

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陕西省动物疫病防控和信息化建设

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动物医学进展 2024年第5期45卷 114-117页

作者：逄国梁郭倩陕西省畜牧技术推广总站陕西西安710016 陕西省动物卫生与屠宰管理站陕西西安710016

针对目前动物疫病防控现状和非洲猪瘟等重大疫病、布鲁氏菌病等人畜共患病防控中暴露出的主要问题,结合陕西省动物防疫和检疫工作的实际,提出了动物疫病防控信息化建设的对策,以《动物防疫法》中的动物疫病防控制度要求为主线,依托“陕... 详细信息

针对目前动物疫病防控现状和非洲猪瘟等重大疫病、布鲁氏菌病等人畜共患病防控中暴露出的主要问题,结合陕西省动物防疫和检疫工作的实际,提出了动物疫病防控信息化建设的对策,以《动物防疫法》中的动物疫病防控制度要求为主线,依托“陕西动物卫生监督管理平台”“陕西智慧动监微信公众号”和“陕西动物检疫证明出证系统”,以“检疫出证”为抓手,建设管理相对人和畜禽运输车辆备案、动物追溯、动物检疫流程、指定通道和落地监管等5个管理系统,建立动物防疫与检疫相关联的工作机制,在一定程度上解决目前动物疫病防控中管理相对人责任落实不到位、动物疫病工作人员力量不足的问题,以期实现对动物养殖、运输和屠宰全链条信息化监管,并逐步转向数据化、智慧化监管,为动物疫病防控提供参考。

关键词：动物疫病防控信息化监管

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基于等效电路模型参数计算的光伏组件隐裂故障诊断方法

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太阳能学报 2024年第5期45卷 481-489页

作者：高剑郭倩卫东顾鑫磊中国计量大学机电工程学院杭州310018 中国计量大学现代科技学院杭州310018

基于等效电路模型参数计算,提出一种光伏组件隐裂故障诊断方法。通过分析隐裂、热斑、电势诱导衰减(PID)和老化故障的产生和演化机理,研究不同故障对光伏组件输出特性的影响作用、模型参数的变化规律及其差异性。建立包含正/反向特性的... 详细信息

基于等效电路模型参数计算,提出一种光伏组件隐裂故障诊断方法。通过分析隐裂、热斑、电势诱导衰减(PID)和老化故障的产生和演化机理,研究不同故障对光伏组件输出特性的影响作用、模型参数的变化规律及其差异性。建立包含正/反向特性的光伏组件等效电路模型,根据模型参数计算结果,确定故障诊断特征量,提出隐裂故障的诊断方法。实验结果表明:所得光伏组件等效电路模型参数计算结果能够较高精度地拟合实验获得的I-V特性曲线;所确定的故障诊断特征量能够有效表征隐裂的发生和演化过程;所提故障诊断方法能够实现可靠的隐裂故障原因判定和程度估算。

关键词：光伏组件故障诊断参数提取等效电路模型隐裂

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基于三边匹配理论的应急救援分配决策

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中国安全科学学报 2024年第3期34卷 222-229页

作者：郭茜周伊可吴刚西南交通大学交通运输与物流学院四川成都611756 西南交通大学唐山研究院河北唐山063000

为解决大型地质灾害背景下应急救援初期救援人员、应急救援装备与受灾地点的分配问题,提高应急救援的效率和质量,首先,将应急救援三方主体之间的选择过程描述为三边匹配问题;然后,标准化处理匹配三方主体的多属性偏好评价信息,构造多属... 详细信息

为解决大型地质灾害背景下应急救援初期救援人员、应急救援装备与受灾地点的分配问题,提高应急救援的效率和质量,首先,将应急救援三方主体之间的选择过程描述为三边匹配问题;然后,标准化处理匹配三方主体的多属性偏好评价信息,构造多属性综合偏好得分矩阵,并以系统稳定性和总偏好效用最大化为目标,建立应急救援初期背景下的三边匹配满意稳定模型;最后,通过算例验证模型的可行性和有效性。结果表明:该模型考虑各主体偏好对于资源分配的影响,能实现应急救援背景下救援人员、应急救援装备与受灾地点三方主体的合理匹配,有助于缩短应急救援部署时间,提高应急救援的效率和质量。

关键词：应急救援三边匹配分配决策偏好值满意稳定匹配模型

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Pathologic features and clinical outcome of central neurocytoma:analysis of 15 cases

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Chinese Journal of Cancer Research 2012年第4期24卷 284-290页

作者： Yu Li Xiu-Feng Ye guo qian Yu Yin qian-Guan Pan Institute of Neuroscience Department of PathologyChongqing Medical University

Objective： To get better recognition of central neurocytoma and diminish misdiagnosis. Methods： A retrospective review identified 15 cases of central neurocytoma. All cases of central neurocytoma were analyzed for their clinical symptoms, pathologic changes, immunohistochemical staining, prognosis and differential diagnosis. Clinical follow up was performed. Results： There were 8 males and 7 females aged 10-64 years （median 32.93 years）. The most common presenting symptoms were those related to increased intracranial pressure （ICP）, including headache （100%）, papilledema （93 %） and vomiting （80%）. All tumors were located in the ventricular system. The tumors were composed of uniform cells with round nuclei and a fine chromatin pattern, and in some areas, small cells with perinuclear halo could be seen. In particular, the anuclear areas may have a fine fibrillary matrix （neuropil）. Nuclear atypia and vascular proliferation appeared in two cases, respectively. Focal necrosis could be seen in one case. Immunohistochemical findings included expression of synaptophysin （15/15）, neuron specific enolase （12/15） and glial fibrillary acidic protein （GFAP）（3/15）. MIB-1 proliferation index ranged from 0.8- 12.5%, and was more than 2% in 3 of 15 cases assessed. Follow-up information of 11 patients was available. Conclusions： Central neurocytoma has a favorable prognosis in general, but in some cases, the clinical course could be aggressive. Increase of GFAP positivity, proliferation index and vascular proliferation might suggest a more malignant process.

关键词： Central neurocytoma histopathology immunohistochemistry proliferation MIB-1 labeling index

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