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Hao, Z.

Publications and source records attributed to Hao, Z..

At least 37 records · Page 2Linked to original sources

Latitudinal scaling of aggregation with abundance and its consequences for coexistence in species rich forests

The search for simple principles underlying the complex spatial structure and dynamics of plant communities is a long-standing challenge in ecology1-6. In particular, the relationship between the spatial distribution of plants and species coexistence is challenging to resolve in species-rich communities7-9. Analysing the spatial patterns of tree species in 21 large forest plots, we find that rare species tend to be more spatially aggregated than common species, and a latitudinal gradient in the strength of this negative correlations that increases from tropical to temperate forests. Our analysis suggests that latitudinal gradients in animal seed dispersal10 and mycorrhizal associations11,12,13 may jointly generate this intriguing pattern. To assess the consequences of negative aggregation-abundance correlations for species coexistence, we present here a framework to incorporate the observed spatial patterns into population models8 along with an analytical solution for the local extinction risk14 of species invading from low abundances in dependence of spatial structure, demographic parameters, and immigration. For example, the stabilizing effect of the observed spatial patterns reduced the local extinction risk of species when rare almost by a factor of two. Our approach opens up new avenues for integrating observed spatial patterns into mathematical theory, and our findings demonstrate that spatial patterns, such as species aggregation and segregation, can contribute substantially to coexistence in species-rich communities. This underscores the need to understand the interactions between multiple ecological processes and spatial patterns in greater detail.

ecology↗

Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China

Sharing among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 E. coli and S. enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance in Escherichia coli and susceptibility in Salmonella enterica. Many of these genes were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

genomics↗

Accurate and Rapid Detection of Peritoneal Metastasis from Gastric Cancer by AI-assisted Stimulated Raman Cytology

Peritoneal metastasis (PM) is the most common form of distant metastasis and one of the leading causes of death in gastric cancer (GC). For locally advanced GC, clinical guidelines recommend peritoneal lavage cytology for intraoperative PM detection. Unfortunately, current peritoneal lavage cytology is limited by low sensitivity (<60%). Here we established the stimulated Raman cytology (SRC), a chemical microscopy-based intelligent cytology. By taking advantages of stimulated Raman scattering in label-free, high-speed, and high-resolution chemical imaging, we firstly imaged 53951 exfoliated cells in ascites obtained from 80 GC patients (27 PM positive, 53 PM negative), at the Raman bands corresponding to DNA, protein, and lipid, respectively. Then, we revealed 12 single cell features of morphology and composition that were significantly different between PM positive and negative specimens, including cellular area, lipid protein ratio, etc. Importantly, we developed a single cell phenotyping algorithm to further transform the above raw features to feature matrix. Such matrix was crucial to identify the significant marker cell cluster, the divergence of which was finally used to differentiate the PM positive and negative. Compared with histopathology, the gold standard of PM detection, our SRC method assisted by machine learning classifiers could reach 81.5% sensitivity, 84.9% specificity, and the area under receiver operating characteristic curve of 0.85, within 20 minutes for each patient. Such remarkable improvement in detection accuracy is largely owing to incorporation of the single-cell composition features in SRC. Together, our SRC method shows great potential for accurate and rapid detection of PM from GC.

biophysics↗

mrHARDIflow : A pipeline tailored for the preprocessing and analysis of Multi-Resolution High Angular diffusion MRI and its application to a variability study of the PRIME-DE database

The validation of advanced methods in diffusion MRI requires finer acquisition resolutions, which is hard to acquire with decent Signal-to-Noise Ratio (SNR) in humans. The use of Non-Human Primates (NHP) and anaesthesia is key to unlock valid microstructural maps, but tools must be adapted and configured finely for them to work well. Here, we propose a novel processing pipeline implemented in Nextflow, designed for robustness and scalability, in a modular fashion to allow for maintainability and a high level of customization and parametrization, tailored for the analysis of diffusion data acquired on multiple spatial resolutions. Modules of processes and workflows were implemented upon cutting edge and state-of-the-art MRI processing technologies and diffusion modelling algorithms, namely Diffusion Tensor Imaging (DTI), Constrained Spherical Deconvolution (CSD) and DIstribution of Anisotropic MicrOstructural eNvironments in Diffusion-compartment imaging (DIAMOND), a multi-tensor distribution estimator. Using our pipeline, we provide an in-depth study of the variability of diffusion models and measurements computed on 32 subjects from 3 sites of the PRIME-DE, a database containing anatomical (T1, T2), functional (fMRI) and diffusion (DWI) imaging of Non-Human Primate (NHP). Together, they offer images acquired over a range of different spatial resolutions, using single-shell and multi-shell b-value gradient samplings, on multiple scanner vendors, that present artifacts at different level of importance. We also perform a reproducibility study of DTI, CSD and DIAMOND measurements outputed by the pipeline, using the Aix-Marseilles site, to ensure our implementation has minimal impact on their variability. We observe very high reproducibility from a majority of diffusion measurements, only gamma distribution parameters computed on the DIAMOND model display a less reproducible behaviour. This should be taken into consideration when future applications are performed. We also show that even if promising, the PRIME-DE diffusion data exhibits a great level of variability and its usage should be done with care to prevent instilling uncertainty in statistical analyses.

neuroscience↗

Integrated Multi-Omics Data Reveals the Molecular Subtypes of Prostate Cancer

Prostate cancer (PCa), the second most common male malignancy, is the fifth leading cause of cancer-related death and places notable burdens on medical resources. Most of the previous subtypes only focused on one or fewer types of data or ignored the genomic heterogeneity among PCa patients with diverse genetic backgrounds. Therefore, it is essential to precisely identify the specific molecular features and judge potential clinical outcomes based on multi-omics data. In the current study, we first identified the PCa multi-omics classification (PMOC) system based on the multi-omics, including mRNA, miRNA, lncRNA, DNA methylation, and gene mutation, using a total of ten state-of-the-art clustering algorithms. The PMOC1 subtype, also called the inflammatory subtype, contains the highest expression levels of immune checkpoint proteins, moderate activated immune-associated pathways. The PMOC2 tumor-activated subtype demonstrated the worst prognosis, which might be impacted by the activated cell cycle and DNA repair pathways, and also characterized by the most genetic alterations of mutant TP53, mutant APC and copy number alteration of 8q24.21 region. The PMOC3 subtype is likely to be a balance subtype, with the activated oncogenic signaling pathways, including hypoxia, angiogenesis, epithelial mesenchymal transition, and PI3K/AKT pathways. As well as with the activated proinflammatory pathways, including IL6/JAK/STAT3, IL2/STAT5, Notch and TNF- signaling. Additionally, PMOC3 subtype also linked with the activation of the androgen response and the high response rate of ARSI treatment. Taken together, we defined the PMOC system for PCa patients via multi-omics data and consensus results of ten algorithms, this multi-omics consensus PCa molecular classification can further assist in the precise clinical treatment and development of targeted therapy.

cancer biology↗

Effect of water temperature on the behavior of Neptunea cumingii and the histology, immune enzyme activity, and transcriptome of its gills and kidneys

The behavior of the marine snail Neptunea cumingii cultured at different temperatures (0, 4, 8, 12, 16 (control), 20, 24, and 28{degrees}C) and the histology, immune enzyme activity, and transcriptome of its gills and kidneys were studied using ecological and molecular methods. At 0{degrees}C, most of the snails shrank in size and did not eat during the first 6 h. At 28{degrees}C, snails also did not eat, death began to occur at 24 h. when the temperature was 8 {degrees}C and 12 {degrees}C, there was no significant difference in the mean feed intake of N. cumingii (P>0.05). And it was higher than the average conch intake under other temperature conditions. However, the histology of the gills and kidneys differed among test temperatures. At 0{degrees}C, the morphology of the gill pieces was difficult to judge. At 24{degrees}C, edema was present in the small gills, and at 28{degrees}C the small gills were severely deformed, the distance between the gill capillaries and the surrounding area was enlarged, and the gill tissue was severely damaged. Temperature increase or decrease from 16{degrees}C caused the columnar cells of the kidney to become shorter and more numerous. The total antioxidant capacity (T-AOC), catalase (CAT) and superoxide dismutase activities (SOD) of the gill and kidney differed significantly among the temperature conditions (p < 0.05). Transcriptome results showed that temperature change resulted in up-regulation of 2339 genes and down-regulation of 2058 genes in the gills, and in up-regulation of 2300 genes and down-regulation of 2060 genes in the kidneys of N. cumingii. Furthermore, the DEGs were subject to GO and KEGG enrichment analysis, and which showed that most of the DEGs in gill were involved in protein folding, defolding, translation, ribosome, and most of the DEGs in kidney were involved in DNA recombination, nuclear euchromatin, RNA-directed DNA polymerase activity. Finally, the results from this study show that N. cumingii prefers the temperature range was 8 to 16, temperature increase or decrease from that range, many aspects of N. cumingii biology could be significantly affected.

physiology↗

Genomic inference of a human super bottleneck in the Early Stone Age

The demographic history is a foundation of human evolutionary studies. However, the ancient demographic history during the Mid-Pleistocene is poorly investigated while it is essential for understanding the early origin of humankind. Here we present the fast infinitesimal time coalescent (FitCoal) process, which allows the analytical calculation of the composite likelihood of a site frequency spectrum and provides the precise inference of demographic history. We apply it to analyze 3,154 present-day human genomic sequences. We find that African populations have passed through a population super bottleneck, a small effective size of approximately 1,280 breeding individuals between 930 and 813 thousand years ago. Further analyses confirm the existence of the super bottleneck on non-African populations although it cannot be directly inferred. This observation, together with simulation results, indicates that confounding factors, such as population structure and selection, are unlikely to affect the inference of the super bottleneck. The time interval of the super bottleneck coincides with a gap in the human fossil record in Africa and possibly marks the origin of Homo heidelbergensis. Our results provide new insights into human evolution during the Mid-Pleistocene.

evolutionary biology↗

GRAMMAR-Lambda: An Extreme Simplification for Genome-wide Mixed Model Association Analysis

A highly efficient genome-wide association method, GRAMMAR-Lambda is proposed to make simple genomic control for the test statistics deflated by GRAMMAR, producing statistical power as high as exact mixed model association method. Using the simulated and real phenotypes, we show that at a moderate or above genomic heritability, polygenic effects can be estimated using a small number of randomly selected markers, which extremely simplify genome-wide association analysis with an approximate computational complexity to naive method in large-scale complex population. Upon a test at once, joint association analysis offers significant increase in statistical power over existing methods.

bioinformatics↗

Generalized Hierarchical Mixed Model Association Analysis

In genome-wide association analysis (GWAS) for binary traits, we stratified the genomic generalized linear mixed model (GLMM) into two hierarchies--the GLMM regarding genomic breeding values (GBVs) and a generalized linear regression of the normally distributed GBVs to the tested marker effects. In the first hierarchy, the GBVs were predicted by solving for the genomic best linear unbiased prediction for GLMM with the estimated variance components or genomic heritability in advance, and in the second hierarchy, association tests were performed using the generalized least square (GLS) method for the GBVs. Like the Hi-LMM for regular quantitative traits, the so-called Hi-GLMM method exhibited higher statistical power to detect quantitative trait nucleotides (QTNs) with better genomic control for complex population structure than existing methods, especially when the GBVs were estimated precisely and using joint association analysis for QTN candidates obtained from a test at once. Application of the Hi-GLMM to re-analyze maize kernel colors and six human diseases illustrated its advantage over existing GLMM-based association methods in terms of computing efficiency and statistical power.

bioinformatics↗

Efficient Genomic Control for Mixed Model Associationsin Large-scale Population

Among linear mixed model-based association methods, GRAMMAR has the lowest computing complexity for association tests, but it produces a high false-negative rate due to the deflation of test statistics for complex population structure. Here, we present an optimized GRAMMAR method by efficient genomic control, Optim-GRAMMAR, that estimates the phenotype residuals by regulating downward genomic heritability in the genomic best linear unbiased prediction. Even though using the fewer sampling markers to evaluate genomic relationship matrices and genomic controls, Optim-GRAMMAR retains a similar statistical power to the exact mixed model association analysis, which infers an extremely efficient approach to handle large-scale data. Moreover, joint association analysis significantly improved statistical power over existing methods.

bioinformatics↗

Conserved, divergent and heterochronic gene expression during Brachypodium and Arabidopsis embryo development

Embryogenesis, transforming the zygote into the mature embryo, represents a fundamental process for all flowering plants. Current knowledge of cell specification and differentiation during plant embryogenesis is largely based on studies of the dicot model plant Arabidopsis thaliana. However, the major crops are monocots and the transcriptional programs associated with the differentiation processes during embryogenesis in this clade were largely unknown. Here, we combined analysis of cell division patterns with development of a temporal transcriptomic resource during embryogenesis of the monocot model plant Brachypodium distachyon. We found that early divisions of the Brachypodium embryo were highly regular, while later stages were marked by less stereotypic patterns. Comparative transcriptomic analysis between Brachypodium and Arabidopsis revealed that the early and late embryogenesis shared a common transcriptional program, whereas mid-embryogenesis was divergent between species. Analysis of orthology groups revealed widespread heterochronic expression of potential developmental regulators between the species. Interestingly, Brachypodium genes tend to be expressed at earlier stages than Arabidopsis counterparts, which suggests that embryo patterning may occur early during Brachypodium embryogenesis. Detailed investigation of auxin-related genes shows that the capacity to synthesize, transport, and respond to auxin is established early in the embryo. However, while early PIN1 polarity could be confirmed, it is unclear if an active response is mounted. This study presents a resource for studying Brachypodium and grass embryogenesis, and shows that divergent angiosperms share a conserved genetic program that is marked by heterochronic gene expression. Key messageDevelopmental and transcriptomic analysis of Brachypodium embryogenesis, and comparison with Arabidopsis, identifies conserved and divergent phases of embryogenesis, and reveals widespread heterochrony of developmental gene expression.

plant biology↗

Effects of Ca2+ on encystment and growth in Scrippsiella trochoidea

Cysts serve as a seed source for the initiation and recurrence of a harmful algal bloom (HAB) caused by dinoflagellates. And the influence of calcium on cyst formation has been relatively understudied. In the present study, we investigated the effects of calcium (Ca2+) on the growth and encystment of Scrippsiella trochoidea. We incubated S. trochoidea in modified f/2 media in flasks which were divided into five groups and treated with different Ca2+ concentrations (0, 0.2, 0.4, 0.6, and 0.8 g{middle dot}L-1). We revealed that cell density increased with increasing Ca2+ concentrations; however, cell density was reduced when Ca2+ concentrations exceeded 0.2 g{middle dot}mL-1. Additionally, the number of cysts and the cyst formation rate similarly increased as Ca2+ concentrations increased, but these were reduced when Ca2+ concentrations exceeded 0.4 g{middle dot}mL-1. Lastly, S. trochoidea absorbed Ca2+ from the water when cysts were formed and under high Ca2+ concentrations, more calcareous thorn cysts formed.

ecology↗

A novel high-accuracy genome assembly method utilizing a high-throughput workflow

Across domains of biological research using genome sequence data, high-quality reference genome sequences are essential for characterizing genetic variation and understanding the genetic basis of phenotypes. However, the construction of genome assemblies for various species is often hampered by complexities of genome organization, especially repetitive and complex sequences, leading to mis-assembly and missing regions. Here, we describe a high-throughput gold standard genome assembly workflow using a large-scale bacterial artificial chromosome (BAC) library with a refined two-step pooling strategy and the Lamp assembler algorithm. This strategy minimizes the laborious processes of physical map construction and clone-by-clone sequencing, enabling inexpensive sequencing of several thousand BAC clones. By applying this strategy with a minimum tiling path BAC clone library for the short arm of chromosome 2D (2DS) of bread wheat, 98% of BAC sequences, covering 92.7% of the 2DS chromosome, were assembled correctly for this species with a highly complex and repetitive genome. We also identified 48 large mis-assemblies in the reference wheat genome assembly (IWGSC RefSeq v1.0) and corrected these large mis-assemblies in addition to filling 92.2% of the gaps in RefSeq v1.0. Our 2DS assembly represents a new benchmark for the assembly of complex genomes with both high accuracy and efficiency.

genomics↗

Effects of long-term closed environment on human saliva microbiota and salivary cytokines

Compared with the normal environment, the microbiota in controlled closed cabins such as space capsules, Lunar/Mars bases have changed. To ensure the health of crewmembers, its necessary to understand the effects of these changes on human symbiotic microorganisms and immunity. In this study, the experimental platform "Lunar Palace 1" with a similar closed and controlled environment was used to research the effects of changed microbial exposure on human saliva microbiota and salivary cytokines. This paper studied on four crewmembers who participated in the third phase of the "Lunar Palace 365" experiment, analyzing the dynamic changes of saliva microbiota and salivary cytokines, and further studying the correlation between salivary cytokines and highly abundant genera. According to our data, the crewmembers saliva microbiota and salivary cytokines fluctuated smoothly throughout the whole experiment. Although a part of microbes increased or decreased some times, they recovered quickly after leaving the controlled environment. The level of IL-6, IL-10 and TNF- in crewmembers saliva decreased from normal environment to the controlled environment, showing reduced levels of oral inflammatory response in crewmembers. In addition, although there were significant individual differences in crewmembers saliva microbiota, sharing living space reduced the difference. Furthermore, the level of TNF- showed a consistent positive correlation with the abundance of Actinomyces and Rothia in the controlled environment, indicating healthy individuals oral mucosal barrier may be sensitive to changes in saliva microbiota. According to the result, semi-sterile environments in controlled closed cabins didnt cause persistent changes in human saliva microbiota and oral immunity. Besides, it provides a new idea for future research on the impact of the controlled environment on crewmembers health, and provides guidance for studying the effect of semi-sterile environments on human immunity based on saliva microbiota. Key pointsO_LISaliva microbes kept stable for individual but got convergent when sharing space; C_LIO_LIThe level of salivary cytokines reduced after entering the controlled environment; C_LIO_LIThere were complex correlations between salivary cytokines and saliva microbes; C_LIO_LIThe crewmembers adapt well to the controlled environment. C_LI

microbiology↗

A negative feedback model to explain regulation of SARS-CoV-2 replication and transcription

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription mechanisms of SARS-CoV-2 has recently emerged, their regulation remains unclear. ResultsBased on reanalysis of public data, we propose a negative feedback model to explain the regulation of replication and transcription in--but not limited to--SARS-CoV-2. The key step leading to new discoveries was the identification of the cleavage sites of nsp15--an RNA uridylate-specific endoribonuclease, encoded by CoVs. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) and genomic RNAs (gRNAs) by cleaving transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nps15 to reach equilibrium between the replication and transcription of CoVs. ConclusionsThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g. uridine derivatives) against CoVs.

bioinformatics↗

Tumor Immunity Microenvironment-based classifications of bladder cancer for enhancing cancer immunotherapy

BackgroundBladder cancer is composed by a mass of heterogenetic characteristics, immunotherapy is a potential way to save the life of bladder cancer patients, but only benefit to about 20% patients. Methods and materialsA total of 4003 bladder cancer patients from 19 cohorts was enrolled in this study, collecting the clinical information and mRNA expression profile. The unsupervised non-negative matrix factorization (NMF) and nearest template prediction (NTP) algorithm was used to divide the patients to immune activated, immune exhausted and non-immune class. Verified gene sets of signatures were used to illustrate the characteristic of immunophenotypes. Clinical and genetic features were compared in different immunophenotypes. ResultsWe identified the immune class and non-immune classes in from TCGA-BLCA cohort. The 150 top different expression genes between these two classes was extracted as the input profile for the reappearing of the classification in the other 19 cohorts. As to the activated and exhausted subgroups, a stromal activation signature was conducted by NTP algorithm. Patients in the immune classes shown the highly enriched signatures of immunocytes, while the exhausted subgroup also shown an increased signature of TITR, WNT/TGF-{beta}, TGF-{beta}1 activated, and C-ECM signatures. Patients in the immune activated shown a lower CNA burden, better overall survival, and favorable response to anti-PD-1 therapy. ConclusionWe defined and validated a novel classifier among the 4003 bladder cancer patients. Anti-PD-1 immunotherapy could benefit more for the patients belong to immune activated subgroup, while ICB therapy plus TGF-{beta} inhibitor or EP300 inhibitor might be more effectiveness for patients in immune exhausted subgroup.

immunology↗

Species packing and the latitudinal gradient in local beta-diversity

The decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide here a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogs. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographic heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.

ecology↗

Immune Response Drives Outcomes in Prostate Cancer: Implications for Immunotherapy

BackgroundThe heterogeneity of the immune microenvironment leads to the different response results of immune checkpoint blockade therapy. We aimed to propose a robust molecular classification of prostate cancer microenvironment to identify ideal patients for delivering effective immunotherapy. MethodsA total of 1,557 prostate cancer patients were enrolled in the current study, including 69 real-world samples from the AHMU-PC cohort. Non-negative matrix factorization algorithm was employed to virtually microdissect the patients to immune and non-immune subclasses. The patients in the immune class were dichotomized to immune activated and suppressed subtypes by the nearest template prediction of activated stroma signature. The curative effects of different immune subclasses in response to immunotherapy were also predicted. ResultsWe termed the newly identified molecular class of tumors as "immune class", which was characterized by a high enrichment of T cell, B cell, NK cell, macrophage associated signatures, etc., compared with the non-immune class (all, P < 0.05). Subsequently, the immune class was subclassified into immune activated and suppressed subtypes determined by the activation status of WNT/TGF-{beta}, TGF-{beta}1, and C-ECM signatures. As a result, around 14.9% to 24.3% of overall patients belonged to the immune activated subgroup, and they were proved with the favorable recurrence-free survival outcomes than others and showed potential curative effects in response to the anti-PD-1/PD-L1 immunotherapy. ConclusionOur study identifies a novel immune class in prostate cancer, which is further described by active or exhausted immune responses. These findings provide novel insights into tailoring immunotherapeutic strategies for different prostate cancer subgroups. Highlights{blacksquare} Immunotherapy could trigger a durable response in advanced prostate cancer, but it only benefits a minority of patients; {blacksquare}Immune response drives recurrence-free survival outcomes in prostate cancer; {blacksquare}The robust molecular classification system helps identify more ideal patients for delivering anti-PD-1/PD-L1 immunotherapy.

immunology↗