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Numerous studies have investigated the risk factors of Alzheimer’s disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aβ generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseases/traits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle-aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long-lived individuals. We further stratified PRSs into cell-type groups and significance-level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p-values (p ≤ 1x10

Numerous studies have investigated the risk factors of Alzheimer’s disease (AD), however, AD- risk factors related miRNAs were rarely reported. In this study, AD- risk factor related miRNAs of 119 Chinese individuals (47 AD patients and 62 cognitively normal controls) were investigated. The results showed that education, tea consumption, leisure activity, and social connection were low Body Mass Index (BMI), depression, and smoking were potentially risk factors for AD patients. Moreover, we screened exosome microRNAs (miRNAs) for the aforementioned lifestyle-related factors. Canonical correlation analyses revealed that our clinical observations were correlated with the miRNA expression profile for education, depression, leisure activity, and social connection. Furthermore, we predicted the targets of differentially expressed miRNAs and found that many of them were reported to be involved in the generation and clearance of Amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMs to assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment.

Biological age (BA) has been proposed to evaluate the aging status instead of chronological age (CA). Our study shows evidence that there might be multiple "clocks" within the whole-body system: systemic aging drivers/clocks overlaid with organ/tissue-specific counterparts. We utilize multi-omics data, including clinical tests, immune repertoire, targeted metabolomic molecules, gut microbiomes, physical fitness examinations, and facial skin examinations, to estimate the BA of different organs (e.g., liver, kidney) and systems (immune and metabolic system). The aging rates of organs/systems are diverse. People's aging patterns are different. We also demonstrate several applications of organs/systems BA in two independent datasets. Mortality predictions are compared among organs' BA in the dataset of the United States National Health and Nutrition Examination Survey. Polygenic risk score of BAs constructed in the Chinese Longitudinal Healthy Longevity Survey cohort can predict the possibility of becoming centenarian.

Exosomal microRNA (miRNA) is an emerging source for biomarkers of Alzheimer’s disease (AD). Here, we profiled miRNA expression in AD, mild cognitive impairment (MCI), and controls. The assessment and validation of differentially expressed miRNA represented their potential to be novel biomarkers for AD and MCI. We conducted 13 co-expression networks and a miRNA network module linked to neural function emerged as the most significantly associated with AD diagnosis. The conservation analysis revealed the M1 was highly preserved in controls but dysfunction in AD and MCI. The module pattern between MCI and NC was similar, but significantly differed from AD, suggesting that the neural network regulated by miRNA changed during the mild cognitive stage, and the total miRNA expression altered in AD stage. Additionally, 24 out of 26 M1 hub-miRNAs were derived from brain tissue, and 15 had been reported as AD biomarkers. We consequently proposed the other 11 miRNAs could play important roles in AD. Our study highlights that co-expression network analysis can provide a new path for finding novel biomarkers.

Background Aging is closely associated with the occurrence and development of many complex diseases such as cardiovascular conditions, type 2 diabetes, gastrointestinal (GI) and renal diseases. Detecting changes as early as possible in the human body due to aging is thus crucial significant to potentially mitigate its impacts on physical health. Methods Here, we present a comprehensive metagenome association study and serum metabolomics profiling in a registry Guangxi-Longevity cohort aged from 20–111 years (n=151) and Kunming cohort ages ranging from 20–80 years (n=80). Results We identified uremic toxins as key factors in serum metabolomics highly associated with aging, and this finding has been validated in an independent Kunming-Aging cohort aged from 20–80 years (n=80). We also observed that aging-associated systemic inflammation levels were positively associated with uremic toxins. Moreover, the increased Escherichia coli, Odoribacter splanchnicus, Bilophila wadsworthia and Parabacteroides spp. abundances were related to serum levels of uremic toxins, and the accumulating rate of uremic toxins and specific microbial species was robustly much slower in centenarians than in nonagenarians. We further investigated the frailty and health status in long-living individuals aged above 90 years, and found that the frailty status might be a putative extreme aging phenomenon characterized by novel uremic toxin accumulation patterns. Conclusions Our findings reveal novel potential links between gut microbiota alterations, uremic toxins and aging, and highlight the preponderance of gut microbiota and serum metabolism in aging.

A strong body of evidence supports a role for immune dysregulation across many psychiatric disorders including depression, the leading cause of global disability. Recent progress in the search for genetic variants associated with depression provides the opportunity to strengthen our current understanding of etiological factors contributing to depression and generate novel hypotheses. Here, we provide an overview of the literature demonstrating a role for immune dysregulation in depression, followed by a detailed discussion of the immune-related genes identified by the most recent genome-wide meta-analysis of depression. These genes represent strong evidence-based targets for future basic and translational research which aims to understand the role of the immune system in depression pathology and identify novel points for therapeutic intervention., Highlights • Dysregulated immune function has been strongly linked to depression. • Recent genome-wide association studies support this relationship. • These genes represent strong candidates for etiological and translational research.

Depression is the world's leading cause of disability. Greater understanding of the neurobiological basis of depression is necessary for developing novel treatments with improved efficacy and acceptance. Recently, major advances have been made in the search for genetic variants associated with depression which may help to elucidate etiological mechanisms. The present review has two major objectives. First, we offer a brief review of two major biological systems with strong evidence for involvement in depression pathology: neurotransmitter systems and the stress response. Secondly, we provide a synthesis of the functions of the 269 genes implicated by the most recent genome-wide meta-analysis, supporting the importance of these systems in depression and providing insights into other possible mechanisms involving neurodevelopment, neurogenesis, and neurodegeneration. Our goal is to undertake a broad, preliminary stock-taking of the most recent hypothesis-free findings and examine the weight of the evidence supporting these existing theories and highlighting novel directions. This qualitative review and accompanying gene function table provides a valuable resource and guide for basic and translational researchers, with suggestions for future mechanistic research, leveraging genetics to prioritize studies on the neurobiological processes involved in depression etiology and treatment.

Dense and crack-free barium titanate (BaTiO₃, BTO) thin films with a thickness of less than 4 μm were prepared by using sub-micrometric scale, layer-by-layer electrohydrodynamic jet (E-jet) deposition of the suspension ink which is composed of BTO nanopowder and BTO sol. Impacts of the jet height and line-to-line pitch of the deposition on the micro-structure of BTO thin films were investigated. Results show that crack-free BTO thin films can be prepared with 4 mm jet height and 300 μm line-to-line pitch in this work. Dielectric constant of the prepared BTO thin film was recorded as high as 2940 at 1 kHz at room temperature. Meanwhile, low dissipation factor of the BTO thin film of about 8.6% at 1 kHz was also obtained. The layer-by-layer E-jet deposition technique developed in this work has been proved to be a cost-effective, flexible and easy to control approach for the preparation of high-quality solid thin film.

The study with pot experiment showed that with increasing Cu concentration, soil urease, invertase, catalase and polyphenol oxidase activities decreased gradually. There was a significant correlation between Cu concentration and soil enzyme activities, with the correlated degree followed the order of invertasepolyphenol oxidaseureasecatalase. Under a fixed Cu concentration, soil enzyme activities changed with time, and the changes were different between high and low Cu concentrations, being increased slightly under low Cu concentration (500 mg x kg(-1)), but decreased gradually as Cu concentration increased (500-3000 mg x kg(-1)). Statistical analysis indicated that within the range of test Cu concentrations, the activities of test soil enzymes were significantly different among different Cu concentration (P0.01), which was accorded with the seedlings growth status. Soil pH was decreased, while electric conductivity was increased with increasing Cu concentration (500-3000 mg x kg(-1)), but they were increased with time under a fixed Cu concentration, with significant difference among different Cu concentration (P0.01) . Soil pH and electric conductivity were highly related to soil enzyme activities, with the order of polyphenol oxidaseinvertasecatalaseurease. The test soil enzyme activities could be used as the indices of soil environment quality.

Through pot experiment and physiological-biochemical analysis, the study showed that the electric conductivities of Conyza canadensis collected from heavy Cu pollution (I), light Cu pollution (II) and control (III) sites were enhanced, while the chlorophyll (a + b) contents were reduced with increasing Cu concentration. The protein and proline contents in I were increased at first and then reduced, but those in II and III were reduced with increasing Cu concentration. The activities of SOD, POD and CAT were intensified under Cu stresses. When the Cu concentration was 1 200 mg x kg(-1), their activities in I, II and III were increased 194.1%, 206.2% and 118.6%, 170.1%, 182.9% and 111.3%, and 115.1%, 155.4% and 107.3%, respectively, in comparing with the control, which illustrated that the tolerance of Conyza canadensis was in order of heavy Cu pollution sitelight Cu pollution sitecontrol site, and the three ecotypes showed distinct differences in tolerance.

A pot experiment was installed to study the effects of Alternaria azukiae inoculation on the cell membrane permeability, pigment and MDA contents, and activities of SOD, POD and CAT of Trifolium repens. The results showed that A. azukiae infection made T. repens leaf tissue increase its cell membrane permeability, electric conductivity, over-oxidation and MDA content, but decrease its pigment content. The electric conductivity and MDA content were positively related with infection time, whereas the pigment content was negatively related with it. Due to the stimulation by A. azukiae, the over-oxidation of cell membrane was intensified, which resulted in a large amount of active oxygen accumulated and beyond the defense ability, the active oxygen metabolism system was destroyed, and the balance of protective enzyme system was broken. After 12 days of A. azukiae inoculation, the activities of SOD and CAT decreased by 55.2% and 37.8%, respectively, while the POD activity increased by 1.6 times.