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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.

ScopeAntioxidants, including vitamin E (VE) and grape seed extract, as anti-aging supplementation have been widely used to improve human health. However, the role of gut microbiota in dietary antioxidant supplementation is debatable. This study aimed to assess the longitudinal impact of dietary supplementation with antioxidant compounds on body health and the gut microbiota.Methods and resultsOne hundred and twenty healthy individuals were randomly divided into a placebo group (amylodextrin) and three experimental groups ingesting different supplement (VE, grape seed extract, or mixed berry juice). Blood and fecal samples were collected during three intervention phases. We found that VE and mixed berry juice ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances ofLachnospirasp. andFaecalibacteriumspp. increased in the VE and berry juice groups. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species.ConclusionJuice and VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.

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.

Genes related to human longevity have not been studied so far, and need to be investigated thoroughly. This study aims to explore the relationship among ABO gene variants, lipid levels, and longevity phenotype in individuals (≥90yrs old) without adverse outcomes. A genotype-phenotype study was performed based on 5803 longevity subjects and 7026 younger controls from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Four ABO gene variants associated with healthy longevity (rs8176719 C, rs687621 G, rs643434 A, and rs505922 C) were identified and replicated in the CLHLS GWAS data analysis and found significantly higher in longevity individuals than controls. The Bonferroni adjusted p-value and OR range were 0.013-0.020 and 1.126-1.151, respectively. According to the results of linkage disequilibrium (LD) analysis, the above four variants formed a block on the ABO gene (D'=1, r2range = 0.585-0.995). The carriers with genotypes rs687621 GG, rs643434 AX, or rs505922 CX (prange = 2.728 x 10-107-5.940 x 10-14; ORrange = 1.004-4.354) and haplotype CGAC/XGXX (p = 2.557 x 10-27; OR = 2.255) had a substantial connection with longevity, according to the results of genetic model analysis. Following the genotype and metabolic phenotype analysis, it has been shown that the longevity individuals with rs687621 GG, rs643434 AX, and rs505922 CX had a positive association with HDL-c, LDL-c, TC, TG (prange = 2.200 x 10-5-0.036, ORrange = 1.546-1.709), and BMI normal level (prange = 2.690 x 10-4-0.026, ORrange = 1.530-1.997). Finally, two pathways involving vWF/ADAMTS13 and the inflammatory markers (sE-selectin/ICAM1) that co-regulated lipid levels by glycosylation and effects on each other were speculated. In conclusion, the association between the identified longevity-associated ABO variants and better health lipid profile was elucidated, thus the findings can help in maintaining normal lipid metabolic phenotypes in the longevity population.

Hepatocellular carcinoma (HCC) is the fourth main reason of cancer-related death. Codonopsis pilosula is a commonly used traditional Chinese medicine (TCM) for patients with HCC. However, its potential mechanism for treatment of HCC remains unclear. Here, we used transcriptomics and network pharmacology to explore the potential molecular mechanisms of Codonopsis pilosula. In our study, twelve differentially expressed genes (DEGs) (5 upregulated and 7 downregulated) of Codonopsis pilosula treating HepG2 cells (a kind of HCC cell) were identified. Among the 12 DEGs, HMOX1 may play an essential role. Codonopsis pilosula mainly affects the mineral absorption pathway in HCC. We acquired 2957, 1877, and 255 targets from TCMID, SymMap, and TCMSP, respectively. Codonopsis pilosula could upregulate HMOX1 via luteolin, capsaicin, and sulforaphane. Our study provided new understanding of the potential pharmacological mechanisms of Codonopsis pilosula in treating HCC and pointed out a direction for further experimental research.

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.

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.

Hepatocellular carcinoma (HCC) is the fourth main reason of cancer-related death.

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.

Background The human skin microbiota is considered to be essential for skin homeostasis and barrier function. Comprehensive analyses of its function would substantially benefit from a catalog of reference genes derived from metagenomic sequencing. The existing catalog for the human skin microbiome is based on samples from limited individuals from a single cohort on reference genomes, which limits the coverage of global skin microbiome diversity. Results In the present study, we have used shotgun metagenomics to newly sequence 822 skin samples from Han Chinese, which were subsequently combined with 538 previously sequenced North American samples to construct an integrated Human Skin Microbial Gene Catalog (iHSMGC). The iHSMGC comprised 10,930,638 genes with the detection of 4,879,024 new genes. Characterization of the human skin resistome based on iHSMGC confirmed that skin commensals, such as Staphylococcus spp, are an important reservoir of antibiotic resistance genes (ARGs). Further analyses of skin microbial ARGs detected microbe-specific and skin site-specific ARG signatures. Of note, the abundance of ARGs was significantly higher in Chinese than Americans, while multidrug-resistant bacteria (“superbugs”) existed on the skin of both Americans and Chinese. A detailed analysis of microbial signatures identified Moraxella osloensis as a species specific for Chinese skin. Importantly, Moraxella osloensis proved to be a signature species for one of two robust patterns of microbial networks present on Chinese skin, with Cutibacterium acnes indicating the second one. Each of such “cutotypes” was associated with distinct patterns of data-driven marker genes, functional modules, and host skin properties. The two cutotypes markedly differed in functional modules related to their metabolic characteristics, indicating that host-dependent trophic chains might underlie their development. Conclusions The development of the iHSMGC will facilitate further studies on the human skin microbiome. In the present study, it was used to further characterize the human skin resistome. It also allowed to discover the existence of two cutotypes on the human skin. The latter finding will contribute to a better understanding of the interpersonal complexity of the skin microbiome.

Additional file 4: Figure S3. Evaluation of iHSMGC integrity. Genome coverage of (a) Malassezia sp., (b) top 10 genera of fungi, (c) top 25 genera of viruses, (d) top 60 genera of prokaryotes, each dot in (b-d) represents a species in the genera. Genome coverage of (e) Cutibacterium sp. and Staphylococcus sp., (f) Moraxella sp. and (g) Streptococcus sp.

Additional file 6: Figure S5. Factors correlated with drug resistance potential in Chinese. a, Bar chart comparing the explained variance (R2) of factors impacting the relative abundance of ARGs using the Adonis test. The L-value represents skin color from dark to white, the b-value is skin color from blue to yellow. b, Bar chart depicting the types of antibiotics corrected with age by the Spearman correlation. c, Bar chart showing the correlation with skincare habit (p < 0.05).

Additional file 2: Figure S1. Construction of the iHSMGC (integrated Human Skin Microbial Gene Catalog). The metagenomic sequencing data from the Chinese and North American cohorts were processed with an in-house pipeline to generate their respective gene catalogs. The two catalogs were merged to form a Two Cohorts nonredundant Gene Catalog (2CGC). Sequenced microbial genomes or draft genomes coverage by 2CGC were regarded as potentially containing sequences of human skin origin. Therefore, microbial genomes were filtered by 2CGC, and the retained microbial genomes were then used to generate the SGC. Finally, the 2CGC was merged with the skin gene catalog (SGC) to generate the iHSMGC.

Additional file 7: Figure S6. Differences in skin microbiota between Singapore Chinese and North Americans. a, Principal component analysis presenting the separation of skin microbiota of Singaporean Chinese (NCBI No. PRJNA277905) versus North Americans (HMP SRA bio-project 46333). The microbes, which were the main contributors to the separation, are indicated by arrows. b, The boxplot showing the prominent species that differ significantly in abundance between Singaporean Chinese and North Americans.

Additional file 12: Figure S11. Octylphenol polyethoxylates transformation and beta-carotene biosynthesis between the two skin cutotypes. a, Reaction step for the conversion of octylphenol polyethoxylates to alkylphenol ethoxylates. The histogram compares the abundance of the genes encode for the two enzymes within the two cutotypes (* p< 0.05, ** p < 0.01; Wilcoxon test). b, Reaction steps for the biosynthesis of beta-carotene in microorganisms. The green box represents the enrichment of the KOs in the M-cutotype, the white box represents no significant difference.

Additional file 3: Figure S2. Host information, coverage and completeness of the iHSMGC. a, Box plot comparing the reads mapping rate of the HMP dataset between HMP skin catalog and the iHSMGC. b, The Bee swarm plot showing the percentage of sequenced reads mapping to human hg19 of each sample. Different anatomical sites are indicated by different colors. c, Rarefaction curve based on gene profiles of 1,361 samples using the Chao2 estimator. d, Box plots demonstrating the read mapping rate from the dataset of Singapore Chinese (NCBI No. PRJNA277905), Italians (NCBI No. PRJNA281366) and another Singapore Chinese (NCBI No. PRJEB26427) by using the iHSMGC. AD-atopic dermatitis. Ea-External auditory canal, Ra-Retroarticular crease, Oc-Occiput, Ba-Back, Mb-Manubrium, Na-Nare, Ac-Antecubital fossa, Id-Interdigital web, Pc-Popliteal fossa, Ic-Inguinal crease, Vf-Volar forearm, Hp-Hypothenar palm, Tw-Toe webspace, Tn-Toenail, Ph-Plantar heel.

Additional file 5: Figure S4. Drug-resistant spectrum based on ARGs in different skin sites. a, Sankey diagram depicting the distribution of the top 15 types of antibiotics ranked by the corresponding ARG abundance. The height of the rectangles indicates the ARGs relative abundance against the corresponding drug resistance potential within the site. Each site and drug resistance potential is indicated in distinct colors. Fh-Forehead, Ck-Cheek, Ns-Nose, Ea-External auditory canal, Ra-Retroarticular crease, Oc-Occiput, Ba-Back, Mb-Manubrium, Na-Nare, Ac-Antecubital fossa, Id-Interdigital web, Pc-Popliteal fossa, Ic-Inguinal crease, Vf-Volar forearm, Hp-Hypothenar palm, Tw-Toe webspace, Tn-Toenail, Ph-Plantar heel. b-c, The pie chart showing the proportion of drug resistance (b) and resistance mechanisms (c). d, Principal component analysis indicating separation of drug-resistant spectrum within the different anatomical sites.

Additional file 8: Figure S7. Intraindividual differences are smaller than interindividual differences. Boxplots of Bray-Curtis distance depicts the similarity between anatomical sites in the face of the same individuals (intraindividual comparisons) or between the same/different sites of different individuals (interindividual comparisons). The left side of the dotted line shows the intraindividual differences, the right side the interindividual differences. The significance levels in the Wilcoxon rank-sum test are: +, p < 0.05; *, p < 0.01; **, p < 0.001.

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.

Background: Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD. Methods and Results: Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs. Conclusion: Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.

Research based on a strategy of single-cell low-coverage whole genome sequencing (SLWGS) has enabled better reproducibility and accuracy for detection of copy number variations (CNVs). The whole genome amplification (WGA) method and sequencing platform are critical factors for successful SLWGS (

Accurate genotyping is important for genetic testing. Sanger sequencing-based typing is the gold standard for genotyping, but it has been underused, due to its high cost and low throughput. In contrast, short-read sequencing provides inexpensive and high-throughput sequencing, holding great promise for reaching the goal of cost-effective and high-throughput genotyping. However, the short-read length and the paucity of appropriate genotyping methods, pose a major challenge. Here, we present RCHSBTreliable, cost-effective and high-throughput sequence based typing pipelinewhich takes short sequence reads as input, but uses a unique variant calling, haploid sequence assembling algorithm, can accurately genotype with greater effective length per amplicon than even Sanger sequencing reads. The RCHSBT method was tested for the human MHC loci HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1, upon 96 samples using Illumina PE 150 reads. Amplicons as long as 950bp were readily genotyped, achieving 100% typing concordance between RCHSBT-called genotypes and genotypes previously called by Sanger sequence. Genotyping throughput was increased over 10 times, and cost was reduced over five times, for RCHSBT as compared with Sanger sequence genotyping. We thus demonstrate RCHSBT to be a genotyping method comparable to Sanger sequencing-based typing in quality, while being more cost-effective, and higher throughput. (C) 2013 Wiley Periodicals, Inc.

We have developed a new method for non-invasive prenatal testing (NIPT) of paternally inherited fetal mutants for β-thalassemia (β-thal). Specially designed primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) were used to detect four major mutations [IVS-II-654, HBB: c.316-197C > T; codon 17 (A > T), HBB: c.52A > T; -28 (A > G), HBB: c.-78A > G and codons 41/42 (-TTCT), HBB: c.126_129delCTTT] causing β-thal in China. The PIRA-PCR assay was first tested in a series of mixed DNA with different concentrations and mixed proportions. Subsequently, this assay was further tested in 10 plasma DNA samples collected from pregnant women. In the DNA mixture simulation test, the PIRA-PCR assay was able to detect 3.0% target genomic DNA (gDNA) mixed in 97.0% wild-type gDNA isolated from whole blood. For plasma DNA testing, the results detected by PIRA-PCR assay achieved 100.0% consistency with those obtained from the amniocentesis analysis. This new method could potentially be used for NIPT of paternally inherited fetal mutants for β-thal.