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基于AGE/RAGE信号通路探讨半夏泻心汤改善血管性痴呆大鼠认知功能障碍的作用机制
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作者 梁书志 赵中敏 +3 位作者 侯苏寓 罗丹丹 张艳 刘西建 《中国实验方剂学杂志》 北大核心 2026年第3期10-21,共12页
目的:该研究旨在探讨半夏泻心汤(BXT)通过调控糖基化终产物/晚期糖基化终产物受体(AGE/RAGE)信号通路降低神经炎症反应,改善血管性痴呆(VD)大鼠认知功能障碍的作用机制。方法:采用超高效液相色谱-四极杆-轨道阱串联质谱(UPLC-Q-Orbitrap... 目的:该研究旨在探讨半夏泻心汤(BXT)通过调控糖基化终产物/晚期糖基化终产物受体(AGE/RAGE)信号通路降低神经炎症反应,改善血管性痴呆(VD)大鼠认知功能障碍的作用机制。方法:采用超高效液相色谱-四极杆-轨道阱串联质谱(UPLC-Q-Orbitrap-MS/MS)技术对BXT进行成分检测,运用网络药理学、分子对接技术筛选出核心成分与关键作用通路。60只SPF级SD雄性大鼠随机数字表法分为假手术组(Sham)、造模组,采用改良双侧颈总动脉结扎法(2-VO)复制VD模型,将造模成功的大鼠按照随机数字表法分为模型组(Model),半夏泻心汤低、中、高剂量组(BXT-L、BXT-M、BXT-H)和尼莫地平组(NMP),BXT-L、BXT-M、BXT-H分别给予BXT 3.7485、7.497、14.994 g·kg^(-1),NMP给予NMP 0.0027 g·kg^(-1),Sham、Model予等量生理盐水,连续14 d灌胃给药。Morris水迷宫、Y迷宫、新物体识别实验评估大鼠认知功能障碍。苏木素-伊红(HE)染色评估大鼠海马组织病理学变化。实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠海马组织晚期AGE、RAGE、磷酸化核转录因子-κB p65(p-NF-κB p65)mRNA水平。蛋白免疫印迹法(Western blot)和免疫组化法(IHC)检测大鼠海马组织AGE/RAGE通信通路的相关蛋白表达。酶联免疫吸附测定法(ELISA)检测大鼠血清神经递质和炎症因子。结果:UPLC-Q-Orbitrap-MS/MS技术检测BXT化学成分。网络药理学、分子对接技术筛选出AGE/RAGE信号通路作为关键通路。与Sham比较,Model大鼠成功潜伏期延长,穿越平台次数、自主交替率、进入新臂次数、偏好指数、辨别指数显著降低(P<0.01);与Model比较,BXT-H、BXT-M大鼠成功潜伏期显著缩短(P<0.01)、穿越平台次数、自主交替率、进入新臂次数、偏好指数、辨别指数明显增加(P<0.05,P<0.01)。HE结果显示,与Sham比较,Model大鼠细胞排列松散杂乱,细胞核固缩。与Model比较,BXT海马组织病理损伤明显改善。Real-time PCR结果显示,与Sham比较,Model大鼠海马组织AGE、RAGE、p-NF-κB p65 mRNA显著升高(P<0.01),与Model比较,BXT-H、BXT-M大鼠AGE、RAGE、p-NF-κB p65 mRNA显著降低(P<0.01),Western blot结果显示,与Sham比较,Model大鼠AGE、RAGE、p-NF-κB p65、肿瘤坏死因子-α(TNF-α)表达明显增加(P<0.05),与Model比较,BXT-H大鼠AGE、RAGE、p-NF-κB p65、TNF-α表达明显降低(P<0.05),IHC结果显示,与Sham比较,Model大鼠RAGE表达显著增加(P<0.01),与Model比较,BXT-H、BXT-M大鼠RAGE表达显著降低(P<0.01),ELISA结果显示,与Sham比较,Model大鼠血清TNF-α、白细胞介素-1β(IL-1β)水平显著升高,乙酰胆碱(ACh)和多巴胺(DA)水平显著降低(P<0.01),与Model比较,BXT-L各剂量组大鼠血清TNF-α、IL-1β水平明显降低(P<0.05),ACh和DA水平明显升高(P<0.05)。结论:BXT可能通过下调AGE/RAGE信号通路,减轻神经炎症反应,调节神经递质含量,从而改善VD认知功能障碍。 展开更多
关键词 半夏泻心汤 血管性痴呆 神经炎症 认知功能障碍 糖基化终产物/晚期糖基化终产物受体(age/Rage)信号通路
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Zircon U-Pb ages of the volcanic rocks and their constraints on the ending of the Huoshiling Formation in the southeastern of Songliao Basin,NE China
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作者 Xue-jiao Qu Ming-kai Zhang +5 位作者 Pu-jun Wang Zhuo-long Yang You-feng Gao Kang-jun Wu Jia Wang Xian-feng Tan 《China Geology》 2026年第1期214-216,I0023,共4页
1.Objective The Songliao Basin(SB)is situated on the eastern margin of Eurasia continent(Northeast Asia).During the Late Jurassic to Early Cretaceous,hundreds of rifting basins developed in this area,and the SB is a u... 1.Objective The Songliao Basin(SB)is situated on the eastern margin of Eurasia continent(Northeast Asia).During the Late Jurassic to Early Cretaceous,hundreds of rifting basins developed in this area,and the SB is a unique case among them as it evolved into the largest rift basin.The rift basin filling of SB includes Huoshiling Formation,Shahezi Formation,and Yingcheng Formation in ascending order.The mega-rifting was controlled by the Mongol-Okhotsk Collisional Belt to the north and northwest and the Pacific Subduction Zone to the east(Wang PJ et al.,2016).As the first rifting succession,the Huoshiling Formation contains key information about the formation of the rifting basins and records the evolution of the Mongol-Okhotsk Collisional Belt and the Pacific Subduction Zone.However,the geological period of the Huoshiling Formation has not been well constrained for two main reasons.First,it is easily confused with the Yingcheng Formation,as both are dominated by volcanogenic-sedimentary successions.Second,there is lack of reliable dating samples from the uppermost part of the Huoshiling Formation due to its considerable burial depth. 展开更多
关键词 rift basin rift basinthe yingcheng formation ZIRCON U Pb ages rifting basins volcanic rocks huoshiling formationshahezi formationand
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Global Age Assurance Standards Summit 2026
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《China Standardization》 2026年第2期36-36,共1页
April 14-16,Manchester,United KingdomThe Global Age Assurance Standards Summit2026 brings together the international age assurance community for three days of practical insight,shared learning and real-world experienc... April 14-16,Manchester,United KingdomThe Global Age Assurance Standards Summit2026 brings together the international age assurance community for three days of practical insight,shared learning and real-world experience focused on implementing age assurance systems in live environments. 展开更多
关键词 live environments age assurance systems global age assurance standards summit practical insight real world experience age assurance shared learning implementing age assurance systems
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Cross-sectional analysis of hearing loss,age and tinnitus severity in a web-recruited cohort of 610 subjects
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作者 María Cuesta Pedro Cobo 《Journal of Otology》 2026年第1期38-49,共12页
Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for... Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for tinnitus while emotional disorders are risk factors for developing intrusive or bothersome tinnitus.Moreover,aging has also been identified as another risk factor.The aim of this paper was to analyse the correlation between hearing loss,age and tinnitus severity in a cohort of 610 tinnitus sufferers.Methods:Age,audiometric(hearing condition)and tinnitus(time duration and severity)data were assessed and analysed for all subjects just after recruiting(baseline).Furthermore,the average hearing loss(HL)curves of the participants for age groups were compared to these with the corresponding Age Related HL(ARHL).Results:For most of the age groups,the measured HL curves exceeded in 10-20 dB those of the ARHL.The average age of tinnitus onset(age minus tinnitus duration)was found to be 44-46 years in both men and women.Weak correlation between audiometric feature and tinnitus distress was observed.Conclusions:Hearing loss has been shown to be a clear risk factor for triggering tinnitus(86%of participants were hearing impaired).In this cohort,average measures of hearing loss showed,at most,weak associations with tinnitus-related distress,suggesting that non-audiological factors may play a predominant role. 展开更多
关键词 TINNITUS age Hearing loss Tinnitus-related distress
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Dietary glycyrrhizin enhances reproductive performance by improving intestinal microbiota,liver lipid metabolism and ovarian senescence in aged breeder hens
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作者 Zhenwu Huang Huchuan Liu +5 位作者 Guangju Wang Huan Ge Yanru Shi Jinghai Feng Chunmei Li Minhong Zhang 《Journal of Animal Science and Biotechnology》 2026年第1期299-317,共19页
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha... Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period. 展开更多
关键词 aged breeder hen GLYCYRRHIZIN Gut microbiota Lipid metabolism Reproductive performance
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Melatonin and mitochondrial stress: New insights into age-related neurodegeneration
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作者 Silvia Carloni Francesca Luchetti +3 位作者 Maria Gemma Nasoni Walter Balduini Walter Manucha Russel J.Reiter 《Neural Regeneration Research》 2026年第4期1564-1565,共2页
Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo... Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable. 展开更多
关键词 buildup changes neurodegenerative diseases aging neurodegenerative diseases MITOCHONDRIA mitochondrial stress MELATONIN age related neurodegeneration AGING
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Thermal decomposition and kinetics of diisopropyl methylphosphonate(DIMP),a chemical warfare agent simulant
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作者 Natalie Gese Hergen Eilers 《Defence Technology(防务技术)》 2026年第1期40-51,共12页
Chemical warfare agents(CWAs)remain a persistent hazard in many parts of the world,necessitating a deeper exploration of their chemical and physical characteristics and reactions under diverse conditions.Diisopropyl m... Chemical warfare agents(CWAs)remain a persistent hazard in many parts of the world,necessitating a deeper exploration of their chemical and physical characteristics and reactions under diverse conditions.Diisopropyl methylphosphonate(DIMP),a commonly used CWA surrogate,is widely studied to enhance our understanding of CWA behavior.The prevailing thermal decomposition model for DIMP,developed approximately 25 years ago,is based on data collected in nitrogen atmospheres at temperatures ranging from 700 K to 800 K.Despite its limitations,this model continues to serve as a foundation for research across various thermal and reactive environments,including combustion studies.Our recent experiments have extended the scope of decomposition analysis by examining DIMP in both nitrogen and zero air across a lower temperature range of 175℃ to 250℃.Infrared spectroscopy results under nitrogen align well with the established model;however,we observed that catalytic effects,stemming from decomposition byproducts and interactions with stainless steel surfaces,alter the reaction kinetics.In zero air environments,we observed a novel infrared absorption band.Spectral fitting suggests this band may represent a combination of propanal and acetone,while GCMS analysis points to vinyl formate and acetone as possible constituents.Although the precise identity of these new products remains unresolved,our findings clearly indicate that the existing decomposition model cannot be reliably extended to lower temperatures or non-nitrogen environments without further revisions. 展开更多
关键词 Chemical warfare agents Simulants Diisopropyl methylphosphonate Thermal decomposition Decomposition model PROPANAL Vinyl formate ACETONE
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当归补血汤通过AGEs/RAGE/NF-κB通路保护糖尿病肾病大鼠肾脏的机制研究
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作者 王月 郑琳琳 +3 位作者 吕哲 裴天琦 侯明君 郭登洲 《安徽中医药大学学报》 2026年第1期71-77,共7页
目的 基于晚期糖基化终末产物(advanced glycation end products,AGEs)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)/核因子-κB(nuclear transcription factor-kappa B,NF-κB)通路探讨当归补血汤对... 目的 基于晚期糖基化终末产物(advanced glycation end products,AGEs)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)/核因子-κB(nuclear transcription factor-kappa B,NF-κB)通路探讨当归补血汤对大鼠糖尿病肾病(diabetic kidney disease,DKD)的作用及其机制。方法 采用高糖高脂饲料联合腹腔注射链脲佐菌素方法复制DKD大鼠模型;将大鼠随机分为正常组,模型组,恩格列净组(0.01g/kg),当归补血汤高、中、低剂量组(2.88、1.44、0.72g/kg),每组8只;各给药组大鼠灌胃相应药物,正常组、模型组大鼠给予等体积生理盐水灌胃,每日灌胃1次,持续20周。检测各组大鼠24h尿蛋白、血清肌酐(serum creatinine,SCr)水平;ELISA法检测大鼠血清白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1beta,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平;光学显微镜下观察大鼠肾脏组织病理形态变化;Western blot法检测大鼠肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平;RT-qPCR法检测大鼠肾脏组织中RAGE、NF-κB p65mRNA表达水平。结果 与正常组比较,模型组大鼠24h尿蛋白、SCr水平均显著升高(P<0.05),血清IL-6、IL-1β、TNF-α水平均显著升高(P<0.05),肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平显著升高(P<0.05),肾脏组织中RAGE、NF-κB p65mRNA表达水平显著升高(P<0.05);肾小球体积增大,基底膜增厚,系膜增生。与模型组比较,各给药组大鼠24h尿蛋白、SCr水平均显著降低(P<0.05),血清中IL-6、IL-1β、TNF-α水平均显著降低(P<0.05),肾脏组织中AGEs、RAGE、NF-κB p65、p-NF-κB p65蛋白表达水平显著降低(P<0.05),肾脏组织中RAGE、NF-κB p65mRNA表达水平显著降低(P<0.05);肾脏组织病理学改变有不同程度减轻。结论 当归补血汤可能通过抑制AGEs/RAGE/NF-κB通路的表达,减轻炎症反应,降低肾脏病理损伤,减少蛋白尿,从而有效保护肾脏,缓解DKD进展。 展开更多
关键词 当归补血汤 糖尿病肾病 ages/Rage/NF-κB通路 炎症
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Hevin/sparcl-1 as a potential biomarker and therapy in age-associated cognitive decline
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作者 Felipe Cabral-Miranda Flávia C.A.Gomes 《Neural Regeneration Research》 2026年第6期2357-2358,共2页
Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structu... Astrocytes,a major class of glial cells,have emerged as crucial regulators of synaptic function,neuronal homeostasis,and cognitive processes(Cabral-Miranda et al.,2024).These star-shaped cells not only provide structural and metabolic support to neurons but also actively participate in modulating synaptic transmission,neurovascular coupling,and inflammatory responses in the brain. 展开更多
关键词 synaptic function modulating synaptic transmissionneurovascular ASTROCYTES neuronal homeostasis age associated cognitive decline glial cellshave hevin sparcl therapy
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Risk factors for paternal perinatal depression in Chinese advanced maternal age couples:A regression mixture model
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作者 Xing Yin Juan Du +1 位作者 Shao-Lian Cai Xing-Qiang Chen 《World Journal of Psychiatry》 2026年第1期267-277,共11页
BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recogn... BACKGROUND Paternal perinatal depression(PPD)is closely associated with maternal mental health challenges,marital strain,and adverse child developmental outcomes.Despite its significant impact,PPD remains under-recognized in family-centered clinical practice.Concurrently,against the backdrop of rising rates of delayed marriage and China’s Maternity Incentive Policy,the proportion of women giving birth at an advanced maternal age is increasing.Nevertheless,research specifically examining PPD among spouses of older mothers remains critically scarce,both in China and globally.AIM To investigate PPD and its influencing factors in Chinese advanced maternal age families.METHODS This cross-sectional study included 358 participants;it was conducted among fathers of pregnant women of advanced maternal age at five hospitals in the Pearl River Delta region of China from September 2023 to June 2024.Data were collected via a general information questionnaire,the Social Support Rating Scale,and the Edinburgh Postnatal Depression Scale.Latent profile analysis and regression mixture models(RMMs)were adopted to analyze the latent PPD types and factors that influenced PPD.RESULTS The incidence of PPD was 16.48%,and three profiles were identified:Low-symptomatic(175 cases,48.89%),monophasic(140 cases,39.10%),and high-symptomatic(43 cases,12.01%).The RMM analysis revealed that first pregnancy,low income(<¥3000/month),part-time work,and a history of abnormal pregnancy were positively associated with the high-symptomatic type(P<0.05).Conversely,high subjective support and support utilization were negatively associated with the high-symptomatic type compared with the low-symptomatic type(P<0.05).Good couple relationships,high objective and subjective support,and high support utilization were negatively associated with monophasic disorder(P<0.05).CONCLUSION PPD incidence is high among Chinese fathers with advanced maternal age partners,and the characteristics of depression are varied.Healthcare practitioners should prioritize individuals with low levels of social support. 展开更多
关键词 Advanced maternal age Paternal perinatal depression Fathers’mental health Regression mixture model Advanced-age pregnancy Latent profile analysis
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DYNAMICAL ANALYSIS OF AN AGE-STRUCTURED TUBERCULOSIS MODEL DRIVEN BY THE NOVEL M72/AS01_(E)VACCINE IN CONTAMINATED ENVIRONMENTS
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作者 Qian JIANG Zhijun LIU Lianwen WANG 《Acta Mathematica Scientia》 2026年第1期330-360,共31页
To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-en... To assess the effectiveness of vaccination in contaminated environments,this study introduces a modeling framework that encompasses two transmission routes,namely direct human-to-human contact and indirect human-to-environment contact,as well as the implementation of new M72/AS01_(E)vaccine.Motivated by this,a coupled age-structured tuberculosis(TB)model is proposed.Its well-posedness requirement is verified using the integrated semigroup theory.Furthermore,this study presents a comprehensive analysis of threshold dynamics associated with the proposed model.Specifically,the global stability of the disease-free and positive steady states is demonstrated by employing Lyapunov functionals.Lastly,the effects of the vaccination with M72/AS01_(E)and contaminated environments on TB control are numerically simulated.Experimental results indicate that high concentrations of Mycobacterium tuberculosis in contaminated environments may somewhat impede TB control efforts,but that large-scale deployment of new vaccine could significantly reduce the prevalence of TB. 展开更多
关键词 tuberculosis model age structure contaminated environments M72/AS01_(E)vaccine STABILITY
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Geochemical Characteristics and Origin of Natural Gas from the Ordovician Middle Gas-bearing Assemblage in the Ordos Basin:A Case Study of the Daniudi Gas Field
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作者 WU Xiaoqi WANG Ping +5 位作者 LIU Quanyou NI Chunhua ZHANG Yi ZHU Dongya JIA Huichong XIANG Liange 《Acta Geologica Sinica(English Edition)》 2026年第1期188-199,共12页
The Ordovician Majiagou Formation(O1m)in the Ordos Basin is a crucial exploration field for natural gas,and exploration of the Ordovician middle assemblage(O_(1)m_(5)^(5-7))has recently yielded great breakthrough.The ... The Ordovician Majiagou Formation(O1m)in the Ordos Basin is a crucial exploration field for natural gas,and exploration of the Ordovician middle assemblage(O_(1)m_(5)^(5-7))has recently yielded great breakthrough.The Daniudi gas field provides a good case study to determine the gas source for the strata.The O_(1)m_(5)^(5-7)gas displays C1/C1-5 ratios of 0.932-0.985 and CO_(2)contents of 1.56%-11.75%,and the detectable H2S content ranges from 0.0002%to 1.8617%.Theδ^(13)C1,δ^(13)C2,δ^(13)CCO_(2),andδD_(1)values are−39.7‰to−35.6‰,−30.4‰to−23.7‰,−12.4‰to−4.6‰,and−204‰to−185‰,respectively.Identification of the gas origin and source indicates that the gaseous alkanes are commonly coal-derived gas.The gas was generated from the coal measures in the Taiyuan Formation(C_(3t))and subsequently migrated.A small amount of oil-associated gas,mainly from O1m carbonate source rocks,has been incorporated into the gas reservoir.The natural gas has experienced insignificant alteration by thermochemical sulfate reduction,and the relatively high levels of CO_(2)are probably associated with corrosion alteration of carbonate reservoirs by injected fluid during acid fracturing. 展开更多
关键词 geochemical characteristics stable isotopic compositions genetic types thermochemical sulfate reduction gas-source correlation Ordovician Majiagou Formation Daniudi gas field
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Mechanism of action of synaptic mitochondrial damage in delayed cognitive recovery
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作者 Huihui Miao Qiang Liu +7 位作者 Yan-Ping Liu Bin-Bin Yan Xin-Hao Jiao Hai-Bi Wang Cheng-Hua Zhou Tianzuo Li Zhongcong Xie Yuqing Wu 《Neural Regeneration Research》 2026年第6期2457-2466,共10页
Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy s... Delayed neurocognitive recovery following anesthesia and surgery is a common complication in older adult patients.Synapses are fundamental to cognitive function.The activity of synapses heavily depends on the energy supplied by synaptic mitochondria,which are significantly influenced by oxidative stress.Sirtuin 3 is a histone deacetylase located in the mitochondrial matrix that plays a pivotal role in regulating mitochondrial function.However,it remains unclear whether and how sirtuin 3 is involved in the development of delayed cognitive recovery.Therefore,in this study,we investigated the potential role of sirtuin 3 in synapses during delayed neurocognitive recovery.Our results showed that anesthesia and surgery induced cognitive impairment in mice and reduced sirtuin 3 protein expression.Overexpression of sirtuin 3 inhibited opening of the mitochondrial permeability transition pore by reducing acetylation of K166 on cyclophilin D and also rescued cognitive impairment.Aged mice carrying the cyclophilin D-K166R mutation exhibited significantly reduced cognitive impairment.Similarly,administering the mitochondrial permeability transition pore blocker,cyclosporine A,effectively alleviated the decline in synaptic mitochondrial function and cognitive impairment caused by anesthesia and surgery in aged mice.These results indicate that the sirtuin 3/cyclophilin D-K166/mPTP signaling pathway in hippocampal synaptic mitochondria is involved in delayed neurocognitive recovery of aged mice,suggesting this pathway could serve as a potential target for treatment. 展开更多
关键词 acetylase aged mice cyclophilin D delayed neurocognitive recovery hippocampus long-term potentiation mitochondrial permeability transition pore sirtuin 3 synaptic mitochondria SYNAPTOSOME
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Combining Random Forest and Monte Carlo Method to Determine the Driving Factors and Uncertainty of Forest Age Prediction in Northwest China
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作者 ZENG Jia LIU Jincheng +1 位作者 LI Limin KHAN Tauheed Ullah 《Chinese Geographical Science》 2026年第1期144-156,I0004-I0007,共17页
Stand age plays a crucial role in forest biomass estimation and carbon cycle modeling.Assessing the uncertainty of stand age prediction models and identifying the key driving factors in the modeling process have becom... Stand age plays a crucial role in forest biomass estimation and carbon cycle modeling.Assessing the uncertainty of stand age prediction models and identifying the key driving factors in the modeling process have become major challenges in forestry research.In this study,we selected the Shaanxi-Gansu-Ningxia region of Northeast China as the research area and utilized multi-source datasets from the summer of 2019 to extract information on spectral,textural,climatic,water balance,and stand characteristics.By integrating the Random Forest(RF)model with Monte Carlo(MC)simulation,we constructed six regression models based on different combina-tions of features and evaluated the uncertainty of each model.Furthermore,we investigated the driving factors influencing stand age modeling by analyzing the effects of different types of features on age inversion.Model performance and accuracy were assessed using the root mean square error(RMSE),mean absolute error(MAE),and the coefficient of determination(R^(2)),while the relative root mean square error(rRMSE)was employed to quantify model uncertainty.The results indicate that the scenarios with more obvious improve-ment in accuracy and effective reduction in uncertainty were Scenario 3 with the inclusion of climate and water balance information(RMSE=25.54 yr,MAE=18.03 yr,R^(2)=0.51,rRMSE=19.17%)and Scenario 5 with the inclusion of stand characterization informa-tion(RMSE=18.47 yr,MAE=13.05 yr,R^(2)=0.74,rRMSE=16.99%).Scenario 6,incorporating all feature types,achieved the highest accuracy(RMSE=17.60 yr,MAE=12.06 yr,R^(2)=0.77,rRMSE=14.19%).In this study,elevation,minimum temperature,and diameter at breast height(DBH)emerged as the key drivers of stand-age modeling.The proposed method can be used to identify drivers and to quantify uncertainty in stand-age estimation,providing a useful reference for improving model accuracy and uncertainty assessment. 展开更多
关键词 stand age Randon Forest(RF)model Monte Carlo(MC)method Sentinel-2 National Forest Inventory(NFI) Shaanxi-Gansu-Ningxia(SGN) Northwest China
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基于网络药理学与实验验证研究地黄环烯醚萜苷调控AGEs/RAGE/MAPK通路保护2型糖尿病小鼠肝脏的作用机制 被引量:1
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作者 王慧森 张宏伟 +3 位作者 刘明 梁瑞峰 张雪侠 张明利 《中草药》 北大核心 2025年第14期5061-5073,共13页
目的基于网络药理学和动物实验验证探讨地黄环烯醚萜苷类(Rehmannia glutinosa iridoid glycosides,RIG)治疗2型糖尿病(type 2 diabetes,T2DM)的作用机制。方法利用Swisstargetprediction和PharmMapper数据库预测筛选RIG相关作用靶点,O... 目的基于网络药理学和动物实验验证探讨地黄环烯醚萜苷类(Rehmannia glutinosa iridoid glycosides,RIG)治疗2型糖尿病(type 2 diabetes,T2DM)的作用机制。方法利用Swisstargetprediction和PharmMapper数据库预测筛选RIG相关作用靶点,OMMI、Genecard、DisGeNET数据库获取T2DM的相关靶标基因,将获得的共同靶点导入STRING数据库构建蛋白相互作用(protein-protein interaction,PPI)网络,Cytoscape软件构建“药物-成分-靶点”和核心靶点网络,通过DAVID数据库和微生信平台进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。采用高糖高脂喂养联合ip链脲佐菌素建立T2DM小鼠模型,将造模成功的小鼠随机分为模型组、二甲双胍(250 mg/kg)组和RIG低、高剂量(200、400 mg/kg)组,每组9只,另取10只正常小鼠作为对照组。药物干预8周,每周测定体质量、空腹血糖(fasting blood glucose,FBG)。给药结束后,分离血清,检测低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、胰岛素(fasting insulin,FINS)水平,并计算胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR);采用苏木素-伊红(HE)、Masson和油红O染色观察小鼠肝脏病理变化;采用免疫组化法测定肝组织炎症因子白细胞介素-1(interleukin-1,IL-1)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达量;采用Western blotting法检测肝组织晚期糖基化终末产物(advanced glycation end products,AGEs)、晚期糖基化末端受体(receptor for advanced glycation end products,RAGE)蛋白表达及p-p38丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)/p38 MAPK水平;采用qRT-PCR法检测肝组织RAGE、p38 MAPK mRNA表达。结果共筛选得到RIG治疗T2DM潜在靶点175个,关键核心靶点有原癌基因酪氨酸蛋白激酶Src(proto-oncogene tyrosine-protein kinase Src,SRC)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)等。GO富集分析显示潜在作用靶点主要涉及炎症反应的调节等生物过程,KEGG通路分析筛选得到了277条信号通路,显示脂质和动脉粥样硬化、AGEs/RAGE信号通路和MAPK信号通路可能在治疗T2DM过程中发挥关键作用。动物实验结果显示,与模型组比较,RIG可以降低T2DM小鼠饮水量、FBG、FINS、HOMA-IR、LDL-C水平(P<0.01),升高HDL-C水平(P<0.01),改善肝细胞形态,减轻肝损伤,减少胶原沉积及脂质沉积,抑制肝组织IL-1、IL-6、TNF-α表达(P<0.01),下调肝组织AGEs、RAGE、p-p38 MAPK/p38 MAPK蛋白表达及RAGE、p38 MAPK mRNA表达(P<0.05、0.01)。结论RIG能够有效降低T2DM小鼠FBG,改善胰岛素抵抗,减轻炎症反应,保护肝组织,其机制可能与调控AGEs/RAGE/MAPK信号通路有关。 展开更多
关键词 地黄环烯醚萜苷 2型糖尿病 网络药理学 肝损伤 ages/Rage/MAPK信号通路
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早期强化胰岛素治疗通过AGEs/RAGE通路减轻糖尿病主动脉氧化应激及炎性反应
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作者 潘新艳 朱亚军 +2 位作者 张志梅 薛刚强 王超 《河北医药》 2025年第6期919-924,共6页
目的探讨早期强化胰岛素治疗对糖尿病大鼠主动脉糖基化反应、氧化应激及炎性反应的作用及其机制。方法构建2型糖尿病大鼠模型,40只大鼠分为对照组(NC组)、糖尿病对照组(DC组)、糖尿病早期胰岛素强化治疗组(DI组),糖尿病格列齐特治疗组(D... 目的探讨早期强化胰岛素治疗对糖尿病大鼠主动脉糖基化反应、氧化应激及炎性反应的作用及其机制。方法构建2型糖尿病大鼠模型,40只大鼠分为对照组(NC组)、糖尿病对照组(DC组)、糖尿病早期胰岛素强化治疗组(DI组),糖尿病格列齐特治疗组(DG组),每组10只。干预4周后测定空腹血清胰岛素(FINS)、空腹血糖(FBG)、C肽(C-P)、血脂,超氧化物歧化酶(SOD)、晚期糖基化终产物(AGEs)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)水平,计算胰岛素敏感指数(ISI);免疫组化检测主动脉AGEs、晚期糖基化终末产物受体(RAGE)、NF-κBp65表达;电镜观察主动脉结构;Western-blot检测主动脉RAGE、NF-κBp65蛋白表达。结果DC组的FBG最高,FINS、C-P最低,其余3组之间差异无统计学意义(P>0.05);DI组、DG组血脂较DC组减低,但2组间差异无统计学意义(P>0.05)。血清AGEs和MDA水平、主动脉RAGE和NF-κBp65蛋白表达在DC组、DI组、DG组较NC组升高,治疗后在DI组、DG组较DC组下降,DI组比DG组明显降低(P<0.05);SOD、GSH-PX水平在DI组、DG组比DC组升高,DI组比DG组升高显著(P<0.05);血清AGEs与FBG、MDA呈正相关(r值分别为0.740、0.873,P<0.05),与FIN、SOD、GSH-PX呈负相关(r值分别为-0.413、-0.910、-0.804,P<0.05);与DG组比较,DI组主动脉免疫组化显示RAGE、AGEs、NF-κBp65表达显著降低(P<0.05),电镜显示内皮病理病变显著减轻。结论早期强化胰岛素治疗能够通过减轻AGEs/RAGE轴的活化,减轻糖尿病大鼠主动脉炎性反应和氧化应激。 展开更多
关键词 早期强化胰岛素治疗 主动脉 ageS Rage 氧化应激 炎性反应
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越鞠丸挥发油调控AGE/PI3K/Akt通路抑制炎症发挥抗抑郁的作用机制研究 被引量:7
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作者 褚坦路 郭泽君 +6 位作者 章伟 王凌峰 吕姝睿 郭皖豫 钟晓明 仇凤梅 黄真 《中国中药杂志》 北大核心 2025年第11期3147-3158,共12页
研究越鞠丸挥发油的抗抑郁活性,探讨其相关分子机制。采用超临界CO_(2)提取越鞠丸挥发油;采用气相色谱-质谱法(GC-MS)联合网络药理学,鉴定越鞠丸挥发油中28个化学成分(萜类、内酯类),与抑郁症共存123个交集靶点,核心靶点有白细胞介素-1... 研究越鞠丸挥发油的抗抑郁活性,探讨其相关分子机制。采用超临界CO_(2)提取越鞠丸挥发油;采用气相色谱-质谱法(GC-MS)联合网络药理学,鉴定越鞠丸挥发油中28个化学成分(萜类、内酯类),与抑郁症共存123个交集靶点,核心靶点有白细胞介素-1β(IL-1β)、信号转导及转录激活蛋白3(STAT3)、半胱天冬酶3(CASP3)等,主要涉及催乳素、晚期糖基化终末产物/受体(AGEs/RAGE)和磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路。采用利血平诱导抑郁小鼠模型验证越鞠丸挥发油的治疗效果和作用机制。通过分析小鼠体质量、体温指数、悬尾不动时间、强迫游泳不动时间和蔗糖偏好变化评估越鞠丸挥发油对小鼠抑郁样行为的改善作用;苏木精-伊红(HE)染色法评估越鞠丸挥发油对小鼠大脑的神经保护特性。酶联免疫吸附测定(ELISA)法联合蛋白免疫印迹(Western blot)法检测小鼠大脑海马组织AGEs、IL-1β、PI3K、磷酸化PI3K(p-PI3K)、Akt、磷酸化Akt(p-Akt)、核因子κB(NF-κB)、脑源性神经营养因子(BDNF)的蛋白表达水平。行为学评估显示,越鞠丸挥发油能有效控制抑郁小鼠体质量和体温的下降,减少小鼠悬尾、游泳不动时间,并增强其对蔗糖的偏好。组织病理学检查显示,越鞠丸挥发油可减轻小鼠海马CA1区和齿状回(DG)区神经元的损伤。ELISA和Western blot结果显示,越鞠丸挥发油可显著提高小鼠海马中PI3K、Akt、BDNF的蛋白表达水平,显著降低AGEs、IL-1β、p-PI3K、p-Akt及NF-κB的蛋白表达水平;进而降低p-PI3K/PI3K、p-Akt/Akt比值,均以中、高剂量效果明显。研究结果提示,越鞠丸挥发油的芳香疗法能显著改善利血平诱导的小鼠抑郁样行为,其机制可能与降低神经元膜蛋白AGEs表达,降低PI3K和Akt磷酸化水平,抑制NF-κB入核,减少促炎因子释放和神经损伤有关。 展开更多
关键词 越鞠丸挥发油 抑郁症 GC-MS 网络药理学 age/PI3K/Akt通路
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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline 被引量:3
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作者 Lan Zhang Jingge Wei +5 位作者 Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei 《Neural Regeneration Research》 SCIE CAS 2025年第4期990-1008,共19页
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati... With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition. 展开更多
关键词 age aging Alzheimer’s disease ASTROCYTES cognitive decline dementia gut microbiota gut–brain axis microbial metabolites NEUROINFLAMMATION Parkinson’s disease
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Antibacterial and antioxidant activities of Cage silver(I)/sulfonated chitosan complexes 被引量:1
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作者 ZHOU Yiyu LIAN Zhifeng +4 位作者 LU Yan SUN Yiwei WU Huixiang YANG Hua HUANG Jianying 《微生物学报》 北大核心 2025年第11期4860-4876,共17页
The potent antibacterial activity of silver nanoparticles is primarily attributed to the release of silver ions,which disrupt cell membranes and inactivate essential enzymes through Ag−S bonding formation.[Objective]T... The potent antibacterial activity of silver nanoparticles is primarily attributed to the release of silver ions,which disrupt cell membranes and inactivate essential enzymes through Ag−S bonding formation.[Objective]To explore silver ion immobilization to minimize silver release.[Methods]A macrocyclic cryptand with nitrogen bridgeheads was prepared and subsequently chelated with silver ions to produce Cage silver(I),which was then coordinated with different ratios of sulfonated chitosan(SCS)to form SCS/Cage Ag(I)complexes(SCA1,SCA2,and SCA3).The antioxidant activities of the complexes were assessed by reducing power and 1,1-diphenyl-2-picrylhydrazyl(DPPH)free radical and hydrogen peroxide scavenging assays.The antibacterial activities of the complexes were evaluated based on the minimum inhibitory concentrations(MICs)and minimum bactericidal concentrations(MBCs)against Staphylococcus aureus ATCC 6538 and Escherichia coli O157:H7 and the inhibition rate on biofilm formation.[Results]Cage silver(I)exhibited strong antibacterial activity,with the MIC of 0.015 mg/mL and MBC of 0.031 mg/mL against S.aureus ATCC 6538,and the MIC of 0.031 mg/mL and MBC of 0.120 mg/mL against E.coli O157:H7.Significant antioxidant properties of Cage silver(I)were also observed,as demonstrated by the DPPH free radical scavenging rates of 42.2%and 53.1%at 326 nm and 517 nm,respectively.Cage silver(I)exhibited the highest antibacterial and antioxidant activities,followed by SCA1,SCA2,SCA3,and SCS,because the content of silver ions in Cage silver(I)was 10-fold higher than that in SCA1.The antibacterial and antioxidant activities of SCA1 were better than those of Cage silver(I),which further indicated that the sulfonic groups of SCS may intensely coordinate with silver ions to exert synergistic effects.[Conclusion]Combining the merits of silver ions and SCS improves the bioavailability of the agent at microbicidal concentrations,minimizes the accumulation in the environment,and reduces treatment costs.The method developed herein offers a sustainable approach to enhance microbial control while minimizing the impact on the environment. 展开更多
关键词 Cage silver ion(I) CHITOSAN antibiofilm formation antioxidant activity
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中药靶向AGEs防治糖尿病肾病的研究进展
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作者 张秉芳 王久香 +2 位作者 汪四海 桂依萍 王东明 《湖北民族大学学报(医学版)》 2025年第2期72-75,共4页
糖尿病肾病(DN)作为糖尿病主要的微血管并发症之一,已成为糖尿病患者的主要死因。近年来,中药在防治DN方面积累了丰富的临床经验,尤其在靶向晚期糖基化终末产物(AGEs)方面已取得显著成就。本文对近5年来在中药单体或提取物和中药复方、... 糖尿病肾病(DN)作为糖尿病主要的微血管并发症之一,已成为糖尿病患者的主要死因。近年来,中药在防治DN方面积累了丰富的临床经验,尤其在靶向晚期糖基化终末产物(AGEs)方面已取得显著成就。本文对近5年来在中药单体或提取物和中药复方、中成药作用于AGEs及其受体(RAGE)信号通路防治DN的主要作用机制做一分析,旨在为开发有效中药防治DN提供强有力的科学依据,更好地服务于临床。 展开更多
关键词 中药 ageS 糖尿病肾病 研究进展
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