The characteristics of glucose metabolism and functional connectivity in posterior default network during nondemented aging: relationship with executive function performance.

BACKGROUND: Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults. OBJECTIVE: This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults. METHODS: We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance. RESULTS: The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits. CONCLUSIONS: Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.

Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice.

PURPOSE: Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. METHODS: Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. RESULTS: Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aß burden and proinflammatory IL-1ß and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. CONCLUSION: Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aß pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.

Biomolecular Markers of Brain Aging.

Characterized by the gradual loss of physiological integrity, impaired function, and increased susceptibility to death, aging is considered the primary risk factor for major human diseases, such as cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. The time-dependent accumulation of cellular damage is widely considered the general cause of aging. While the mechanism of normal aging is still unresolved, researchers have identified different markers of aging, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Theories of aging can be divided into two categories: (1) aging is a genetically programmed process, and (2) aging is a random process caused by gradual damage to the organism over time as a result of its vital activities. Aging affects the entire human body, and aging of the brain is undoubtedly different from all other organs, as neurons are highly differentiated postmitotic cells, and the lifespan of most neurons in the postnatal period is equal to the lifespan of the brain. In this chapter, we discuss the conserved mechanisms of aging that may underlie the changes observed in the aging brain, with a focus on mitochondrial function and oxidative stress, autophagy and protein turnover, insulin/IGF signaling, target of rapamycin (TOR) signaling, and sirtuin function.

Relationship between the disrupted topological efficiency of the structural brain connectome and glucose hypometabolism in normal aging.

Normal aging is accompanied by structural degeneration and glucose hypometabolism in the human brain. However, the relationship between structural network disconnections and hypometabolism in normal aging remains largely unknown. In the present study, by combining MRI and PET techniques, we investigated the metabolic mechanism of the structural brain connectome and its relationship with normal aging in a cross-sectional, community-based cohort of 42 cognitively normal elderly individuals aged 57-84 years. The structural connectome was constructed based on diffusion MRI tractography, and the network efficiency metrics were quantified using graph theory analyses. FDG-PET scanning was performed to evaluate the glucose metabolic level in the cortical regions of the individuals. The results of this study demonstrated that both network efficiency and cortical metabolism decrease with age (both p < 0.05). In the subregions of the bilateral thalamus, significant correlations between nodal efficiency and cortical metabolism could be observed across subjects. Individual-level analyses indicated that brain regions with higher nodal efficiency tend to exhibit higher metabolic levels, implying a tight coupling between nodal efficiency and glucose metabolism (r = 0.56, p = 1.15 × 10-21). Moreover, efficiency-metabolism coupling coefficient significantly increased with age (r = 0.44, p = 0.0046). Finally, the main findings were also reproducible in the ADNI dataset. Together, our results demonstrate a close coupling between structural brain connectivity and cortical metabolism in normal elderly individuals and provide new insight that improve the present understanding of the metabolic mechanisms of structural brain disconnections in normal aging.

Accelerating Structural Degeneration in Temporal Regions and Their Effects on Cognition in Aging of MCI Patients.

Age is the major risk factor for Alzheimer's disease (AD) and for mild cognitive impairment (MCI). However, there is limited evidence about MCI-specific aging-related simultaneous changes of the brain structure and their impact on cognition. We analyzed the brain imaging data from 269 subjects (97 MCI patients and 172 cognitively normal [CN] elderly) using voxel-based morphometry and tract-based spatial statistics procedures to explore the special structural pattern during aging. We found that the patients with MCI showed accelerated age-related reductions in gray matter volume in the left planum temporale, thalamus, and posterior cingulate gyrus. The similar age×group interaction effect was found in the fractional anisotropy of the bilateral parahippocampal cingulum white matter tract, which connects the temporal regions. Importantly, the age-related temporal gray matter and white matter alterations were more significantly related to performance in memory and attention tasks in MCI patients. The accelerated degeneration patterns in the brain structure provide evidence for different neural mechanisms underlying aging in MCI patients. Temporal structural degeneration may serve as a potential imaging marker for distinguishing the progression of the preclinical AD stage from normal aging.

Age-Related Decline in the Topological Efficiency of the Brain Structural Connectome and Cognitive Aging.

Brain disconnection model has been proposed as a possible neural mechanism for cognitive aging. However, the relationship between structural connectivity degeneration and cognitive decline with normal aging remains unclear. In the present study, using diffusion MRI and tractography techniques, we report graph theory-based analyses of the brain structural connectome in a cross-sectional, community-based cohort of 633 cognitively healthy elderly individuals. Comprehensive neuropsychological assessment of the elderly subjects was performed. The association between age, brain structural connectome, and cognition across elderly individuals was examined. We found that the topological efficiency, modularity, and hub integration of the brain structural connectome exhibited a significant decline with normal aging, especially in the frontal, parietal, and superior temporal regions. Importantly, network efficiency was positively correlated with attention and executive function in elderly subjects and had a significant mediation effect on the age-related decline in these cognitive functions. Moreover, nodal efficiency of the brain structural connectome showed good performance for the prediction of attention and executive function in elderly individuals. Together, our findings revealed topological alterations of the brain structural connectome with normal aging, which provides possible structural substrates underlying cognitive aging and sensitive imaging markers for the individual prediction of cognitive functions in elderly subjects.

Early prevention of cognitive impairment in the community population: The Beijing Aging Brain Rejuvenation Initiative.

Facing considerable challenges associated with aging and dementia, China urgently needs an evidence-based health-care system for prevention and management of dementia. The Beijing Aging Brain Rejuvenation Initiative (BABRI) is a community-based cohort study initiated in 2008 that focuses on asymptomatic stages of dementia, aims to develop community-based prevention strategies for cognitive impairment, and provides a platform for scientific research and clinical trials. Thus far, BABRI has recruited 10,255 participants (aged 50 and over, 60.3% female), 2021 of whom have been followed up at least once at a 2- or 3-year interval. This article presents aims and study design of BABRI; summarizes preliminary behavioral and neuroimaging findings on mild cognitive impairment (MCI) and results of clinical trials on MCI; and discusses issues concerning early prevention in community, MCI diagnosis methods, and applications of database of aging and dementia. BABRI is proposed to build a systematic framework on brain health in old age.

Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment.

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = -0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

Long-term efficacy of Chinese medicine Bushen Capsule on cognition and brain activity in patients with amnestic mild cognitive impairment.

Mild cognitive impairment (MCI), regarded as the prodromal stage before the clinical phase of Alzheimer's disease (AD), has been considered for early intervention. Unfortunately, many trials in this stage with drugs with single-target turned out to be little or no effect. Multi-targeting in nature based on the theory of Traditional Chinese Medicine (TCM) offers another prospect for intervention. Together with advanced functional magnetic resonance imaging (fMRI) technique for more sensitive and objective evaluation, we investigated the long-term therapeutic effects of a TCM compound on cognition and task-related neuronal activity. Sixty amnestic MCI (aMCI) participants from randomly divided into drug (30 with Bushen capsules (BSC)) and placebo (30 with placebo capsules) groups for this 2-years trial. Neuropsychological and N-back task-fMRI data were acquired at baseline and two follow-ups to assess, via linear mixed effect models, the changes of cognitive ability and brain activation over treatments. The drug group, compared with placebo group, exhibited improvement or stabilization in memory measures over time. Analyses of fMRI revealed that the placebo group exhibited higher activation magnitude and spatial extents at left superior parietal lobule; importantly, the greater activation identified in placebo group was related to more decline in the digit span. BSC showed long-term ameliorative effects on cognitive performances in aMCI patients, which might result from the regulation of abnormal brain activities. Our study provided evidence for the potential of TCM in early prevention of AD, as well as the feasibility of neuroimaging biomarkers in clinical trials.

The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Although it has been studied for years, the pathogenesis of AD is still controversial. Genetic factors may play an important role in pathogenesis, with the apolipoprotein E (APOE) gene among the greatest risk factors for AD. In this review, we focus on the influence of genetic factors, including the APOE gene, the interaction between APOE and other genes, and the polygenic risk factors for cognitive function and dementia. The presence of the APOE ε4 allele is associated with increased AD risk and reduced age of AD onset. Accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in ε4 carriers. The effect of the APOE promoter on cognition and the brain was confirmed by some studies, but further investigation is still needed. We also describe the effects of the associations between APOE and other genetic risk factors on cognition and the brain that exhibit a complex gene⁻gene interaction, and we consider the importance of using a polygenic risk score to investigate the association between genetic variance and phenotype.

SORL1 rs1699102 polymorphism modulates age-related cognitive decline and gray matter volume reduction in non-demented individuals.

BACKGROUND AND PURPOSE: SORL1 rs1699102 is associated with the risk of late-onset Alzheimer's disease. However, the effects of this single nucleotide polymorphism on cognition and brain structure during normal aging are unclear. This study aimed to examine the effects of the rs1699102 polymorphism on age-related cognitive decline and cortical gray matter reduction in the Chinese Han population. METHODS: A total of 780 non-demented adults completed a battery of neuropsychological tests. High-resolution T1-weighted structural magnetic resonance imaging data from 89 of these subjects were also collected using a Siemens Trio 3.0 Tesla scanner. RESULTS: The T allele carriers displayed an accelerated age-related change in episodic memory and processing speed tests relative to the CC genotype. A similar pattern was observed in the age-related gray matter volume (GMV) reduction of the right middle temporal pole. The GMV in this region was significantly positively correlated with the episodic memory scores. CONCLUSIONS: The SORL1 gene rs1699102 polymorphism has been found to be associated with age-related cognitive decline and GMV reduction of the right middle temporal pole in older adults. These findings elucidate how the SORL1 variants shape the neural system to modulate age-related cognitive decline and support the hypothesis that SORL1 may represent a candidate gene for late-onset Alzheimer's disease.

[Clinical application evaluation of Guidelines for Diagnosis and Treatment of Cancer in Traditional Chinese Medicine].

This study aims to evaluate the adaptability and applicability of Guidelines for the Diagnosis and Treatment of Cancer in Traditional Chinese Medicine. The assessment methods included adaptability assessment and applicability assessment. The adaptability assessment was based on the questionnaire survey to evaluate the familiarity, utilization, quality, and clinical application of the Guidelines; applicability assessment was based on the prospective observation of 853 clinical cases to investigate the applicability and effect of the Guidelines, including effectiveness, economy and safety. Statistical analysis for basic description, construction of different comparison groups for cross or hierarchical statistical test, multi-factor analysis, and confounding factors were used in the study. Adaptability assessment results showed that 63.03% of TCM doctors considered guidelines as good or very good applicability and 4.24% of TCM doctors considered guidelines with very poor applicability in clinical practice. For the applicability evaluation, TCM doctors considered that the "overall efficacy and technology level", "satisfactory degree" and "adaptability in clinical practice" of the guideline were 85.46%, 80.43% and 69.40% respectively. The results showed that guideline was well known among TCM doctors, especially junior TCM doctors. Adaptability and applicability of Guidelines were totally good but the quality and adaptability of the intervention schemes were still week, so the quality of Guidelines should be improved by revision.

Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients.

Some previous reports have suggested that hypertension is a risk factor for dementia and cognitive impairments. Using behavioral data from 1007 elderly human subjects (405 hypertensive patients) of Han ethnicity from Beijing, China, the present study aimed to assess the effects of hypertension on cognitive performance and explore related neuronal changes via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 84 of these subjects (44 hypertensive patients). Cognitively, we found that patients with hypertension showed decreased executive functions and attention compared with those with normotension in the large sample. In magnetic resonance imaging scan sample, using independent component analysis to examine the functional connectivity difference between the two groups, we found that the frontoparietal networks in the hypertensive group exhibited altered patterns compared with the control group, mainly in the inferior parietal lobe, left inferior frontal lobe, and precuneus. Using tract-based spatial statistics to investigate the between-group structural difference, we found that the hypertensive group showed significantly reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, using the mediation analysis, we found that the functional connectivity of the frontoparietal networks mediates the impact of white matter on executive function in the hypertensive group. The results demonstrate that hypertension targets a specific pattern of cognitive decline, possibly due to deficits in the white matter and functional connectivity in frontal and parietal lobes. Our findings highlight the importance of brain protection in hypertension. SIGNIFICANCE STATEMENT: Hypertension is a risk factor for cognitive decline and dementia. However, the neural mechanism underlying cognitive decline in hypertension is largely unknown. We studied the relationship among cognitive decline, brain functional, and structural changes in hypertensive patients via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data in a Chinese cohort. Hypertensive patients showed executive dysfunction, along with disrupted functional connectivity in frontoparietal (FP) networks and reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, the functional connectivity changes mediate the impact of white matter alterations on cognitive decline in the hypertensive group. Our findings provide a better understanding of the mechanism of cognitive decline in hypertension and highlight the importance of brain protection in hypertension.

Association of white matter integrity and cognitive functions in patients with subcortical silent lacunar infarcts.

BACKGROUND AND PURPOSE: Silent lacunar infarct (SLI) is a risk factor for dementia. This study investigated the white matter integrity abnormality and its relationship to the cognition impairments in SLI patients. METHODS: Between 27 patients with SLI in basal ganglia and 30 healthy controls, we assessed the difference in a batter of neuropsychological tests and in white matter integrity measurements, fractional anisotropy, and mean diffusivity, using tract-based spatial statistics. RESULTS: Compared with healthy controls, SLI patients performed worse in general mental status, memory, executive function, and language ability. They also had reduced fractional anisotropy and increase mean diffusivity in brain regions such as the body and genu of corpus callosum, the forceps minor, the bilateral superior and bilateral anterior corona radiate, and the left external capsule. Furthermore, we found that in SLI patients, fractional anisotropy measure in left external capsule was positively correlated to the performance in memory and language ability. CONCLUSIONS: SLI in basal ganglia leads to local and remote white matter integrity damages and to the cognition impairments.

Tree peony seed oil alleviates hyperlipidemia and hyperglycemia by modulating gut microbiota and metabolites in high-fat diet mice.

With the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high-fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short-chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD-induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.

Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.

BACKGROUND: Lipid metabolism changes occur in early Alzheimer's disease (AD) patients. Yet little is known about metabolic gene changes in early AD cortex. METHODS: The lipid metabolic genes selected from two datasets (GSE39420 and GSE118553) were analyzed with enrichment analysis. Protein-protein interaction network construction and correlation analyses were used to screen core genes. Literature analysis and molecular docking were applied to explore potential therapeutic drugs. RESULTS: 60 lipid metabolic genes differentially expressed in early AD patients' cortex were screened. Bioinformatics analyses revealed that up-regulated genes were mainly focused on mitochondrial fatty acid oxidation and mediating the activation of long-chain fatty acids, phosphoproteins, and cholesterol metabolism. Down-regulated genes were mainly focused on lipid transport, carboxylic acid metabolic process, and neuron apoptotic process. Literature reviews and molecular docking results indicated that ACSL1, ACSBG2, ACAA2, FABP3, ALDH5A1, and FFAR4 were core targets for lipid metabolism disorder and had a high binding affinity with compounds including adenosine phosphate, oxidized Photinus luciferin, BMS-488043, and candidate therapeutic drugs especially bisphenol A, benzo(a)pyrene, ethinyl estradiol. CONCLUSIONS: AD cortical lipid metabolism disorder was associated with the dysregulation of the PPAR signaling pathway, glycerophospholipid metabolism, adipocytokine signaling pathway, fatty acid biosynthesis, fatty acid degradation, ferroptosis, biosynthesis of unsaturated fatty acids, and fatty acid elongation. Candidate drugs including bisphenol A, benzo(a)pyrene, ethinyl estradiol, and active compounds including adenosine phosphate, oxidized Photinus luciferin, and BMS-488043 have potential therapeutic effects on cortical lipid metabolism disorder of early AD.

Altered synaptic currents, mitophagy, mitochondrial dynamics in Alzheimer's disease models and therapeutic potential of Dengzhan Shengmai capsules intervention.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aß42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aß42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear. Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment. Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA's roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP's main bioactives, underscoring their therapeutic potential. Conclusion: This research delineates UR-AP's pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP's potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

Plasma exosome proteomics reveals the pathogenesis mechanism of post-stroke cognitive impairment.

Exploration and utilization of exosome biomarkers and their related functions provide the possibility for the diagnosis and treatment of post-stroke cognitive impairment (PSCI). To identify the new diagnostic and prognostic biomarkers of plasma exosome were uzed label-free quantitative proteomics and biological information analysis in PSCI patients. Behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) between control group (n = 10) and PSCI group (n = 10). The blood samples were collected to analyse the biomarker and differentially expressed proteins of plasma exosome using label-free quantitative proteomics and biological information. The exosomes marker proteins were determined by Western blot. The exosome morphology was observed by transmission electron microscopy. The scores of MMSE and MoCA were significantly decreased in the PSCI group. The PT% and high-density lipoprotein decreased and the INR ratio increased in PSCI group. The mean size of exosome was approximately 71.6 nm and the concentration was approximately 6.8E+7 particles/mL. Exosome proteomics identified 259 differentially expressed proteins. The mechanisms of cognitive impairment are related to regulate the degradation of ubiquitinated proteins, calcium dependent protein binding, cell adhesive protein binding, formation of fibrin clot, lipid metabolism and ATP-dependent degradation of ubiquitinated proteins in plasma exosome of PSCI patients. Plasma levels of YWHAZ and BAIAP2 were significantly increased while that of IGHD, ABCB6 and HSPD1 were significantly decreased in PSCI patients. These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.

Characterization of Agronomic and Seed Oil Features for Different Cultivars of Tree Peony.

Tree peony is a unique oil plant resource in China, and tree peony seed oil is one of the healthy edible oils with a very promising future. However, the main oil tree peony cultivars promoted in China are Paeonia ostii 'Fengdan' and Paeonia rockii. In order to explore new oil tree peony cultivars, 68 tree peony cultivars were investigated and cultivars with oil potential were selected by cluster analysis and grey relational analysis (GRA) in this study. The results demonstrated that the 68 cultivars varied significantly in terms of agronomic characteristics (p < 0.05), with the coefficient of variation in seed yield per plant reaching a high of 75.36%. The oil content of 46 cultivars was higher than 'Fengdan' (20.87 ± 0.26%) and 'Zibanbai' (21.24 ± 1.01%), while the alpha-linolenic acids and total unsaturated fatty acid contents of 26 cultivars were higher than 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%) and 'Zibanbai' (40.51 ± 0.09% and 93.59 ± 0.09%). Finally, three cultivars with better integrated traits were selected by cluster analysis and grey relational analysis (GRA), comprising of 'Changshoule', 'Xianchizhenghui', and 'Yupantuojin'. The contents of alpha-linolenic acids and total unsaturated fatty acids in 'Changshoule' (47.98 ± 0.17% and 93.60 ± 0.08%), 'Xianchizhenghui' (49.44 ± 0.63% and 93.80 ± 0.06%), and 'Yupantuojin' (40.46 ± 0.26% and 93.58 ± 0.06%) were higher than that of 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%). In general, these cultivars can be used as hybrid parental materials for breeding new excellent oil tree peony cultivars.