Biology subjects

Jie, Z.

Publications and source records attributed to Jie, Z..

16 recordsLinked to original sources

bioRxiv2026

Phagocytic activity of perivascular cell promotes CNS injury pathology

Injury, stroke, and neurological diseases cause persistent accumulation of cellular debris that deteriorates lesion microenvironment and impedes central nervous system (CNS) repair. Debris clearance in the injured CNS has long been attributed primarily to microglia and infiltrating macrophages. Here, we identify perivascular cells as previously unrecognized phagocytes that expand after injury and exhibit robust phagocytic activity. Perivascular cell phagocytosis is conserved across multiple mouse models of CNS injury and human stroke lesions. These cells exhibit key hallmarks of phagocytosis, including LC3-associated phagocytosis for efficient lysosomal degradation. Mechanistically, phosphatidylserine serves as the eat-me signal and Axl mediates myelin debris uptake. Myelin phagocytosis drives perivascular cell proliferation, fibrosis and lesion progression. Genetic deletion of Axl in perivascular cells or pharmacological inhibition with the FDA-approved Axl inhibitor Gilteritinib reduces pathology and improves functional recovery after spinal cord injury. Together, these findings establish Axl-dependent perivascular cell phagocytosis as a therapeutic target for CNS repair.

neuroscience↗

bioRxiv2022

Sex differences in the nasal microbiome of healthy young adults

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections (RTIs) between males and females. It is recently hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities, but without evidence. In this work, we study the nasal microbiome of healthy young adults in, as of today, the largest cohort based on deep shot-gun metagenomic sequencing. We mainly focus on the bacteriome, but also integrate the mycobiome to get a more holistic perspective. De novo assembly is performed to catalog the nasal bacterial colonizers/residents, which also identify and therefore account for uncharacterized components of the community. The bacteriome is then profiled based on the non-redundant metagenome-assembled genomes (MAGs) catalog constructed therefrom. Unsupervised clustering reveals clearly separable structural patterns in the nasal microbiome between the two sexes. Following this link, we systematically evaluate sex differences for the first time and reveal extensive sex-specific features in the nasal microbiome composition. More importantly, through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males. The analysis of the keystone bacteria of the communities reveal that the sex-dependent evolutionary characteristics might have contributed to this difference. HighlightsThe non-redundant nasal bacterial MAGs catalog constructed from ultra-deeply sequenced metagenomic data provides a valuable resource. Integrating nasal bacteriome and mycobiome data provides a more holistic perspective for the understudied human nasal microbiome. Unsupervised clustering helps uncover extensive sex differences in the nasal microbiome compositions. Network analyses capture markedly higher ecological stability and antagonistic potentials in the nasal microbiome of females than that of males. Sex-dependent genetic evolutionary forces play a role in the shaping of keystones in the nasal microbial community.

microbiology↗

bioRxiv2022

Integrated cyto-physiological and proteomic analyses reveal new insight into CMS mechanism in a novel upland cotton CMS line LD6A

Cytoplasmic male sterile (CMS) system has extensively been exploited for hybrid vigor in plant breeding programs. However, its application in many crops is limited due to poor understanding of molecular mechanism of fertility restoration. Using advanced analytical approaches, we elucidated molecular pathways regulating CMS induction and fertility restoration in cotton. Reproductive structures of a novel CMS (LD6A) and its maintainer (LD6B) line were analyzed for physiological and proteomic changes during the development process. Significant differential expression of proteins, such as Abrin, malate dehydrogenase, malic enzyme, isocitrate dehydrogenase, histone acetyltransferase was observed in CMS and its maintainer line. Transmission electron micrographs of anther tapetum showed that inner ridge of CMS mitochondria was relatively indistinct than that of LD6B with narrower membranous space at tetrad stage. Further, relatively higher reactive oxygen species were accumulated in the anther of CMS than its maintainer line at pollen mother cell and tetrad stage. We suggest that abnormal sequence of mitochondrial ribosome gene rps4 and rpl10 and high expression of ribosome-inactivating protein gene Abrin in CMS line damaged mitochondrial membrane and consequently induced pollen sterility. These data provide new insight into CMS mechanism in cotton crops and a tool to develop new CMS germplasm resources.

developmental biology↗

bioRxiv2021

Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome

The oral microbiota contains billions of microbial cells, which could contribute to diseases in a number of body sites. Challenged by eating, drinking and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1,915 individuals, for both the tongue dorsum and saliva. We identified five genetic loci associated with oral microbiota at study-wide significance (p < 3.16 x 10-11). Four of the five associations were well replicated in an independent cohort of 1,439 individuals: rs1196764 at APPL2 with Prevotella jejuni, Oribacterium uSGB 3339 and Solobacterium uSGB 315; rs3775944 at the serum uric acid transporter SLC2A9 with Oribacterium uSGB 1215, Oribacterium uSGB 489 and Lachnoanaerobaculum umeaense; rs4911713 near OR11H1 with species F0422 uSGB 392; and rs36186689 at LOC105371703 with Eggerthia. Further analyses confirmed 84% (386/455 for tongue dorsum) and 85% (391/466 for saliva) of genetic-microbiota associations including 6 genome-wide significant associations mutually validated between the two niches. Human genetics accounted for at least 10% of oral microbiome compositions between individuals. Machine learning models showed that polygenetic risk score dominated over oral microbiome in predicting predisposing risk of dental diseases such as dental calculus and gingival bleeding. These findings indicate that human genetic differences are one explanation for a stable or recurrent oral microbiome in each individual.

genetics↗

bioRxiv2020

Inter-determination of blood metabolite levels and gut microbiome supported by Mendelian randomization

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization (MR) analyses on 3,432 Chinese individuals with whole genome, whole metagenome, anthropometric, and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate, and selenium. Two-sample MR with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

genetics↗

bioRxiv2020

Personalized vagino-cervical microbiome dynamics after oral probiotics

The vaginal microbiota is presumably much simpler than the gut microbiome, and oral probiotics appear as a promising means to modulate its homeostasis in the general population. Here, 60 women were followed for over a year before, during and after a probiotic containing Lactobacillus rhamnosus GR-1 and L. reuteri RC-14. Shotgun metagenomic data of 1334 samples from multiple body sites did not support colonization of the probiotics to the vagino-cervical microbiome, yet the microbiome was stable in those dominated by Lactobacilli and some individuals have likely benefited from this medication-free intervention.

microbiology↗

bioRxiv2019

Over 50000 metagenomically assembled draft genomes for the human oral microbiome reveal new taxa

The oral cavity of each person is home for hundreds of bacterial species. While taxa for oral diseases have been well studied using culture-based as well as amplicon sequencing methods, metagenomic and genomic information remain scarce compared to the fecal microbiome. Here we provide metagenomic shotgun data for 3346 oral metagenomics samples, and together with 808 published samples, assemble 56,213 metagenome-assembled genomes (MAGs). 64% of the 3,589 species-level genome bins contained no publicly available genomes, others with only a handful. The resulting genome collection is representative of samples around the world and across physiological conditions, contained many genomes from Candidate phyla radiation (CPR) which lack monoculture, and enabled discovery of new taxa such as a family within the Acholeplasmataceae order. New biomarkers were identified for rheumatoid arthritis or colorectal cancer, which would be more convenient than fecal samples. The large number of metagenomic samples also allowed assembly of many strains from important oral taxa such as Porphyromonas and Neisseria. Predicted functions enrich in drug metabolism and small molecule synthesis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.

microbiology↗

bioRxiv2019

Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus

Emerging evidence has linked the gut microbiota to schizophrenia. However, the functional changes in the gut microbiota and the biological role of individual bacterial species in schizophrenia have not been explored systematically. Here, we characterized the gut microbiota in schizophrenia using shotgun metagenomic sequencing of feces from a discovery cohort of 90 drug-free patients and 81 controls, as well as a validation cohort of 45 patients taking antipsychotics and 45 controls. We screened 83 schizophrenia-associated bacterial species and constructed a classifier comprising 26 microbial biomarkers that distinguished patients from controls with a 0.896 area under the receiver operating characteristics curve (AUC) in the discovery cohort and 0.765 AUC in the validation cohort. Our analysis of fecal metagenomes revealed that schizophrenia-associated gut-brain modules included short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters including glutamate, {gamma}-aminobutyric acid, and nitric oxide. The schizophrenia-enriched gut bacterial species include several oral cavity-resident microbes, such as Streptococcus vestibularis. We transplanted Streptococcus vestibularis into the gut of the mice with antibiotic-induced microbiota depletion to explore its functional role. We observed that this microbe transiently inhabited the mouse gut and this was followed by hyperactivity and deficit in social behaviors, accompanied with altered neurotransmitter levels in peripheral tissues. In conclusion, our study identified 26 schizophrenia-associated bacterial species representing potential microbial targets for future treatment, as well as gut-brain modules, some of which may give rise to new microbial metabolites involved in the development of schizophrenia.

microbiology↗

bioRxiv2019

M-GWAS for the gut microbiome in Chinese adults illuminates on complex diseases

The gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no less than 20% genetic contribution to the gut microbiota. Using common variants-, rare variants- and copy number variations (CNVs)-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top 2 loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Genetically encoded responses to ectopic presence of oral bacteria in the gut appear to be a common theme in a number of diseases investigated by MWAS (Metagenome-wide association studies). Our two-stage M-GWAS (Microbiome genome-wide association studies) on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.\n\nHighlightsM-GWAS using high-depth whole genome identifies contributions from rare variants and CNVs.\n\nGut microbial modules such as butyrate, amino acids, mucin degradation show genetic associations.\n\nGender differential M-GWAS underscores differences in metabolic and psychological predispositions.\n\nSome of the MWAS markers for colorectal cancer and cardiometabolic diseases show genetic associations.

genetics↗

bioRxiv2019

Shotgun Metagenomics of 361 elderly women reveals gut microbiome change in bone mass loss

Bone mass loss contributes to the risk of bone fracture in the elderly. Many factors including age, obesity, estrogen and diet, are associated with bone mass loss. Mice studies suggest that the intestinal microbiome might influence the bone mass by regulating the immune system, however there has been little evidence from human studies. We have recruited 361 Chinese elderly women to collect data for a metagenomic-wide association study (MWAS) to investigate the influence of the gut microbiome on bone health. Gut microbiome data were produced using BGISEQ500 sequencing, BMD was calculated using Hologic dual energy X-ray machine, BMI (Body Mass Index) and age were also provided. This therefore data allows exploration of gut microbiome diversity and links to bone mass loss, as well as microbial species and modules as markers for bone mineral density. Making these data potentially useful in studying the role the gut microbiota might play in bone mass loss and offering exploration into the bone mass loss process.

microbiology↗

bioRxiv2019

The Urinary Microbiota in Relation to the Reproductive Tract Microbiota

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. The potential link between female urine and reproductive tract microbial communities is currently not clear. Here we collected the urine samples from 147 Chinese women of reproductive age, and explored the nature of colonization by 16S rRNA gene amplicon sequencing, real-time qPCR and live bacteria culture. To demonstrate utility intra-individual Spearmans correlation was used to explore the relationship between urine and multi-sites of the reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Types of diverse, Streptococcus-dominated, and Lactobacillus-dominated were the three most common types in the cohort. Detailed comparison of the urinary microbiota to the multi-sites of reproductive tract microbiota demonstrated the urinary microbiota was more similar to the microbiota in the cervix and uterine cavity instead of vagina in the same women. Our data demonstrates the potential connectivity of the microbiota in the female urogenital system and provided insight into the exploration of urethra and genital tract diseases.

microbiology↗

bioRxiv2019

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

More than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.

microbiology↗

bioRxiv2019

The vagino-cervical microbiome as a woman's life history

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.

microbiology↗

bioRxiv2019

Integrated multi-omics analysis to study the effects of simulated weightlessness on rhesus macaques (Macaca mulatta)

Safety and health of astronauts in space is one of the most important aspects of space exploration, however, the genomic research about how a weightless space can affect astronauts health was limited. In this study, we sequenced 25 transcriptomic, 42 metabolomic and 35 metagenomic data of 15 rhesus macaques (Macaca mulatta) spanning seven simulated weightlessness experiment stages. We identified 84 genes, 1911 features and 55 genera which are significantly changed in blood and muscle, hippocampal region, dorsomedial prefrontal cortex as well as fecal, respectively. Furthermore, performing the integrated analysis of three omics data, we found several pathways which were related to regulation of immune system process, glucose uptake, reaction to threatens, neurotoxic and bone or joints damage, such as tyrosine metabolism and tryptophan metabolism. Our results provided an initial attempt of "multi-omics" approaches which combined transcriptomics, metabolomics and metagenomics to illustrate some molecular clues for simulated weightlessness effect on the rhesus macaques and potential sight of microgravitys effect on astronauts health.

immunology↗

bioRxiv2018

Bacterial strain displacement in inflammatory bowel diseases after fecal microbiota transplantation

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has recently been used to treat inflammatory bowel disease (IBD). To elucidate the extent and principles of microbiota engraftment in IBD patients after FMT treatment, we conducted an interventional prospective cohort study. The cohort included two categories of patients: (1) patients with moderate to severe Crohns disease (CD) (Harvey-Bradshaw Index [≥] 7, n = 11, and (2) patients with ulcerative colitis (UC) (Montreal classification, S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples of the participants were collected along with their clinical metadata. For comparative analysis, 10 fecal samples from 10 healthy people were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent natural microbiota shifts during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as the most contributive factors for prediction accuracy.

clinical trials↗

bioRxiv2017

Characterization of a Novel Model of Overuse-Induced Calcific Achilles Tendinopathy in Mice: Contralateral Tendinopathy Following Unilateral Tenotomy

ObjectiveTo develop a simple but reproducible overuse induced animal model of Achilles tendinopathy in mice for better understanding the underlying mechanism and prevention of calcific Achilles tendinopathy.\n\nMethods80 C57/B6 mice (8-9 weeks old) were employed and randomly divided into control group and experimental group. Unilateral Achilles tenotomy was performed on the right hindlimb of experiment group. After 12 weeks, the onset of Achilles tedinopathy in the contralateral Achilles tendon was determined by radiological assessment, histological analysis, electron microscopy observation and biomechanical test.\n\nResultsThe onset of calcific Achilles tendinopathy in contralateral Achilles tendon was confirmed after 12 weeks unilateral tenotomy. The contralateral Achilles tendon of experimental group was characterized as hypercelluarity, neovascularization and fused collagen fiber disarrangement, compared to the control group. Importantly, intratendon endochondral ossification and calcaneus deformity was featured in contralateral Achilles tendon. Additionally, poor biomechanical properties in the contralateral Achilles tendon revealed the incidence of Achilles tedinopathy.\n\nConclusionWe hereby introduce a novel simple but reproducible spontaneous contralateral calcific Achilles tendinopathy model in mice, which represents the overuse conditions during the tendinopathy development in human-beings. It should be a useful tool to further study the underlying pathogenesis of calcific Achilles tendinopathy.

animal behavior and cognition↗