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Decoding aging: examining the non-evolutionary event from an evolutionary perspective

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Science China Life Sciences 2024年

作者： yannan guo Kang Xu Jianping Cai Zhao Wang Beijing Institute of Geriatrics Beijing Hospital Protein Science Key Laboratory of the Ministry of Education School of Pharmaceutical Sciences Tsinghua University

In an era marked by increased longevity,a deeper understanding of the older population is vital. By introducing an overlooked evolutionary perspective on aging, this article challenges traditional biogerontology, which primarily focuses on biological and clinical aspects. It articulately differentiates between chronological and physiological aging, suggesting that aging is an evolutionary byproduct rather than a direct evolutionary event.

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Ellagic acid ameliorates cisplatin-induced acute kidney injury by regulating inflammation and SIRT6/TNF-α signaling

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Food Science and Human Wellness 2023年第6期12卷 2232-2241页

作者： Yuqi Gao Kezheng Peng Yida Wang yannan guo Chenye Zeng Rui Hua Qingfei Liu Xue Li Ying Qiu Zhao Wang The Ministry of Education Key Laboratory of Protein Science School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China School of Medicine Tsinghua UniversityBeijing 100084China

De spite cisplatin has been widely used in the treatment of various cancers,the noteworthy nephrotoxicity greatly constrained its clinical value.For this reason,finding novel targeted therapies to attenuate the nephrotoxicity of cisplatin should be pretty significant.Our previous study found that histone deacetylase sirtuin 6(SIRT6)could be an ideal target for the treatment of cisplatin-induced acute kidney injury.In this study,we explored the protective effects of ellagic acid,a natural polyphenol compound that activates SIRT6,on cisplatin-induced nephrotoxicity.Pre-treatment of ellagic acid attenuated cytotoxicity of cisplatin in primary renal cells and TCMK-1 cells.Moreover,ellagic acid ameliorated renal dysfunction,apoptosis and fibrosis induced by cisplatin in mice.Furthermore,ellagic acid reduced nephrotoxicity-associated inflammatory factor interleukin(IL)-1βand IL-6 expression both in vitro and in vivo.Mechanistically,ellagic acid reversed cisplatin-reduced SIRT6 expression and diminished cisplatin-induced tumor necrosis factor(TNF)-αexpression.And SIRT6 knockdown abrogated the protective effects of ellagic acid on cisplatin-induced cell apoptosis,indicating the renal-protective effects of ellagic acid are mainly dependent on ellagic acid-mediated SIRT6 activation.Our results provide preclinical rationale for using ellagic acid as a feasible and promising agent to ameliorate cisplatin-induced acute kidney injury,and support ellagic acid as a potential adjunctive therapy for future cancer treatment.

关键词： Ellagic acid Nephrotoxicity Cisplatin SIRT6 TNF-α

GPP(composition of Ganoderma lucidum polysaccharides and Polyporus umbellatus polysaccharides) protects against DSS-induced murine colitis by enhancing immune function and regulating intestinal flora

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Food Science and Human Wellness 2022年第4期11卷 795-805页

作者： Liyuan Li yannan guo Qing Huang Xiaojin Shi Qingqing Liu Fang Wang Qingfei Liu Kang Yu Zhao Wang MOE Key Laboratory of Protein Science School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Tsinghua UniversityBeijing 100084China Tianjin Research Institute for Advanced Equipment Tianjin 300300China Department of Clinical Nutrition and Department of Health Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China

Previous study have demonstrated that a compound composed of water-soluable Ganoderma lucidum polysaccharides(GLP)and Polyporus umbellatus polysaccharides(PUP)in a ratio of 3:1 named GPP enhances innate immune function in mice through enhancing the function of macrophage cells and activity of natural killer(NK)cells.Here in our research,we further investigated the effect of GPP on the diversity and composition of intestinal flora,and explored its effect on colitis model mice.The immunoregulatory verification experiments of GPP were conducted in both normal and DSS-induced mice model.Our research showed that GPP increased the diversity of intestinal microorganisms in mice with the extension of administration time.Daily GPP intake attenuated DSS-induced colon injury,protected the splenic lymphocyte proliferation ability,enhanced the serum hemolysin synthesis,and increased peripheral phagocytes and NK cell activity in model mice.Comparisons of the predominant gene pathways of the bacterial microbiota showed that DNA repair and recombination,base mismatch repair pathways was stronger in GPP-treatment group than in control group,indicating the possible molecular mechanisms of immune function regulation.Our study showed that GPP regulated immune function in both health and colitis model,and had a positive effect on maintaining intestinal flora homeostasis.

关键词： Ganoderma lucidum polysaccharides Polyporus umbellatus polysaccharides Immune function Intestinal flora Colitis

High-starchy carbohydrate diet aggravates NAFLD by increasing fatty acids influx mediated by NOX2

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Food Science and Human Wellness 2023年第4期12卷 1081-1101页

作者： Yuqi Gao Rui Hua Kezheng Peng Yuemiao Yin Chenye Zeng yannan guo Yida Wang Liyuan Li Xue Li Ying Qiu Zhao Wang MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China School of Medicine Tsinghua UniversityBeijing 100084China

Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.

关键词： Starchy carbohydrates Nonalcoholic fatty liver disease NADPH oxidase 2 Fatty acid influx

深度学习重建算法改善腹盆部血管低剂量扫描图像质量的研究

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中华放射学杂志 2024年第6期58卷 647-652页

作者：屈婷婷曹乐程燕南陈丽虹李雅楠郭银霞李剑颖杨建郭建新西安交通大学第一附属医院医学影像科西安710061 通用医疗中国CT科研中心北京100176

目的探讨TrueFidelity深度学习重建算法在腹盆部CT血管成像(CTA)低剂量扫描时的应用价值。方法前瞻性纳入2020年6月至2021年3月就诊于西安交通大学第一附属医院,临床申请行腹盆部CTA的患者。所有患者均行低剂量腹盆部CTA扫描,管电压为80... 详细信息

目的探讨TrueFidelity深度学习重建算法在腹盆部CT血管成像(CTA)低剂量扫描时的应用价值。方法前瞻性纳入2020年6月至2021年3月就诊于西安交通大学第一附属医院,临床申请行腹盆部CTA的患者。所有患者均行低剂量腹盆部CTA扫描,管电压为80 kV,管电流为智能管电流(100~720 mA),扫描完成后均使用传统滤波反投影(FBP)、自适应统计迭代重建算法(ASIR-V 50%)、TrueFidelity算法[降噪强度:中等强度(TF-M)和高强度(TF-H)]4种重建算法对图像进行重建。测量腹主动脉、同层腰大肌及皮下脂肪的CT值和CT值的标准差(SD),计算信噪比(SNR)和对比噪声比(CNR),另外测量腰大肌密度均匀区域的CT值偏度,同时使用5分法评价所有图像的颗粒度、模糊度及股骨头层面的硬化伪影。客观评价指标采用重复测量单因素方差分析进行检验。结果共纳入46例患者。CT检查的辐射剂量为(1.09±0.31)mGy。4组重建图像血管和肌肉的CT值比较差异无统计学意义(P>0.05),SD值比较差异有统计学意义(P<0.001),FBP组的SD值最大,TF-H组的SD值最小。SNR和CNR比较差异有统计学意义(P<0.001),整体趋势与SD值趋势相反。偏度值比较4组差异无统计学意义。颗粒度评分FBP组评分最高,TF-H组评分最低,4组间差异有统计学意义。模糊度评分TF-H组评分稍高于其余3组,但差异无统计学意义。硬化伪影评分FBP和ASIR-V 50%组评分最差,TF-H最好(P<0.001)。结论综合考虑图像噪声、模糊度、均匀度和硬化伪影的表现,在腹盆部CTA低剂量扫描时,相比于FBP和ASIR-V,TrueFidelity重建算法可以提供更优的图像质量,其中TF-H的图像质量最佳。

关键词：体层摄影术,X线计算机重建算法深度学习

补肾健脾活血方调控Apaf-1/CHOP-Caspase-9/Bcl-2通路抑制成骨细胞氧化应激

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中国骨质疏松杂志 2024年第5期30卷 649-654页

作者：李颖林燕平黄佳纯杜书军李燕南郭海威暨南大学祈福医院广东广州511495 广州中医药大学第三附属医院广东广州510378 广东省中医骨伤研究院广东广州510378 广州中医药大学岭南医学研究中心广东广州510405

目的探讨补肾健脾活血方对减轻大鼠成骨细胞氧化应激损伤和调控线粒体介导的细胞凋亡的机制。方法提取大鼠原代成骨细胞,通过CCK8实验检测补肾健脾活血方干预下对成骨细胞增殖活性的影响、碱性磷酸酶(alkaline phosphatase,ALP)染色检... 详细信息

目的探讨补肾健脾活血方对减轻大鼠成骨细胞氧化应激损伤和调控线粒体介导的细胞凋亡的机制。方法提取大鼠原代成骨细胞,通过CCK8实验检测补肾健脾活血方干预下对成骨细胞增殖活性的影响、碱性磷酸酶(alkaline phosphatase,ALP)染色检测成骨细胞ALP活性、茜素红染色检测成骨细胞的矿化情况、实时定量PCR检测Apaf-1和CHOP基因的mRNA表达、蛋白质印迹检测Caspase-9和Bcl-2蛋白表达量。结果CKK8实验和碱性磷酸酶染色表明氧化应激损伤的大鼠成骨细胞增殖活性显著降低,成骨分化受抑制,同时Apaf-1和CHOP的mRNA表达以及Caspase-9的蛋白表达明显增加(P≤0.01),Bcl-2蛋白表达则显著减少(P≤0.01);经补肾健脾活血方干预后,成骨细胞增殖活性得到明显的增强、成骨分化增加,Apaf-1和CHOP的mRNA及Caspase-9的蛋白表达均显著减少(P<0.05),而Bcl-2的蛋白表达则显著升高(P≤0.0001)。结论补肾健脾活血方可以促进成骨细胞增殖和成骨分化,显著降低Apaf-1和CHOP的mRNA及Caspase-9的蛋白表达,升高Bcl-2的蛋白表达量。补肾健脾活血方在减轻成骨细胞的氧化应激损伤和调控线粒体介导的细胞凋亡中起着重要作用。

关键词：补肾健脾活血方骨质疏松症氧化应激线粒体成骨细胞

腹主动脉联合常规一站式胸痛三联CTA检查在急性胸痛患者诊疗中的价值

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西安交通大学学报（医学版） 2024年第4期45卷 542-546页

作者：屈婷婷曹乐李雅楠陈丽虹樊钢练程燕南郭银霞郭建新西安交通大学第一附属医院医学影像科陕西西安710061

目的探讨腹主动脉联合常规胸痛三联CT血管成像(triple rule-out computed tomography angiography, TRO-CTA)检查在急性胸痛患者检查中的价值。方法回顾性纳入1 482例急性非创伤性胸痛患者,414例患者接受传统的TRO-CTA扫描,1 068例患... 详细信息

目的探讨腹主动脉联合常规胸痛三联CT血管成像(triple rule-out computed tomography angiography, TRO-CTA)检查在急性胸痛患者检查中的价值。方法回顾性纳入1 482例急性非创伤性胸痛患者,414例患者接受传统的TRO-CTA扫描,1 068例患者在临床医师的要求下接受包括腹主动脉的TRO-CTA扫描(TRO-CTAwAA)。两组患者主动脉期的扫描范围不同:常规TRO-CTA只扫描胸主动脉,TRO-CTAwAA扫描整个主动脉,其余所有的扫描参数均相同。采用卡方检验对两组主动脉主要血管异常(主动脉夹层、动脉瘤、穿透性溃疡、壁内血肿、血管闭塞和血栓形成)的检出率进行比较。采用方差分析(ANOVA)对两组辐射剂量(CTDIvol和DLP)和扫描时间进行比较。结果 TRO-CTAwAA组的主动脉异常检出率明显高于TRO-CTA组(35.1%vs. 4.8%,P<0.001)。在TRO-CTAwAA组中,有26.5%的血管异常在胸主动脉和腹主动脉上均可检出,另外8.6%只发生在腹主动脉上。两组间辐射剂量相比,TRO-CTAwAA组的总DLP明显高于常规TRO-CTA(P<0.001)。两组扫描时间对比差别无统计学意义(P=0.410)。结论腹主动脉联合常规TRO-CTA检查,可显著提高急性胸痛患者主动脉血管异常的检出率,不增加检查流程。

关键词：胸痛一站式胸痛三联CTA 腹主动脉CTA 检查流程

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Supercritical CO_(2)-Tailored 2D Oxygen-doped Amorphous Carbon Nitride for Enhanced Photocatalytic Activity

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Energy & Environmental Materials 2022年第3期5卷 912-917页

作者： Lina Du Qingyong Tian Xiaoli Zheng Wenjing guo Wei Liu yannan Zhou Feng Shi Qun Xu College of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001China Henan Institutes of Advanced Technology Zhengzhou UniversityZhengzhou 450052China

Simultaneously adjusting the surface,crystallographic and electronic structures of nanomaterials provide a new avenue for rational design of advanced photocatalyst yet it is challenging.In this work,a surface and structural engineering strategy is developed to simultaneously realize the 2D amorphous structure and oxygen(O)-doping in graphitic carbon nitride(g–C_(3)N_(4))via the assistance of supercritical carbon dioxide(SCCO_(2)).The 2D O-doped amorphous g-C_(3)N_(4)nanosheets display greatly enhanced photocatalytic CO_(2)reduction and methylene blue degradation performances.The synthesis method as well as the mechanism of the enhanced photocatalytic activity was investigated,wherein the introduction of 2D amorphous structure and O dopant in the g-C_(3)N_(4)contributes to the increased surface area,abundant active sites,wider visible-light absorption range and efficient charge separation property,and thus the outstanding photocatalytic activities can be obtained.Its photocatalytic CH_(4)evolution rate and MB degradation rete are 5.1 and 7.0 times enhancement over bulk crystalline g-C_(3)N_(4),respectively.This work presents a great promising way for designing and developing advanced photocatalysts.

关键词： amorphous graphitic carbon nitride oxygen-doping photocatalytic activity supercritical carbon dioxide

影响能谱CTU虚拟平扫尿路结石检出的因素分析

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西安交通大学学报（医学版） 2024年第4期45卷 535-541页

作者：程燕南李雅楠孙精涛田倩杨建同维杨健郭建新西安交通大学第一附属医院医学影像科陕西西安710061 西安交通大学第一附属医院临床研究中心陕西西安710061

目的基于Logistic回归分析评估影响能谱CT尿路造影(CTU)虚拟平扫图像检出尿路结石的因素。方法回顾性纳入150例尿路结石并行能谱CTU的患者(记录所用碘对比剂)。将平扫图像重建为120 kVp-like图像,静脉期和排泄期的增强图像采用碘去除... 详细信息

目的基于Logistic回归分析评估影响能谱CT尿路造影(CTU)虚拟平扫图像检出尿路结石的因素。方法回顾性纳入150例尿路结石并行能谱CTU的患者(记录所用碘对比剂)。将平扫图像重建为120 kVp-like图像,静脉期和排泄期的增强图像采用碘去除技术分别重建为静脉期和排泄期的虚拟平扫图像。2位医师独立评估以上3组图像,并记录3组图像的尿路结石数量、所在解剖位置及虚拟平扫图像是否有碘残留;结石大小和CT值仅在真实平扫图像上测量。结石大小、CT值、结石所在位置和所用碘对比剂纳入Logistic回归分析,用于评估影响虚拟平扫尿路结石检出的因素。受试者工作特征(ROC)曲线用于绘制各指标的曲线下面积(AUC)值、诊断灵敏度和特异度及最佳临界值。结果真实平扫上检出304枚结石,而静脉期和排泄期虚拟平扫结石检出率分别为92.4%和71.4%。结石大小和CT值是影响静脉期和排泄期虚拟平扫结石检出的独立风险因素(P<0.01),结石大小和CT值在静脉期虚拟平扫结石检出的AUC值达0.96以上,诊断临界值分别是3.52 mm和469 HU,而在排泄期虚拟平扫结石检出的结石大小、CT值及解剖位置等指标的综合AUC值降为0.88。排泄期虚拟平扫结石检出率在碘对比剂组间无统计学差异(P=0.57)。另外,排泄期肾盂肾盏处虚拟平扫结石检出率明显降低(P<0.001)。结论在增强CT的2个扫描期相中,静脉期虚拟平扫结石检出效果更佳。结石大小和CT值是影响虚拟平扫结石检出的重要因素。肾盂肾盏处排泄期虚拟平扫结石检出率低与碘去除效果欠佳相关。

关键词：能谱CT尿路造影(CTU) 尿路结石虚拟平扫检出 Logistic回归

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