Biology subjects

Shang, H.

Publications and source records attributed to Shang, H..

14 recordsLinked to original sources

bioRxiv2026

Orthologous synteny provides robust structural evidence for the ancestral angiosperm ε-WGD

The ancestral angiosperm whole-genome duplication ({varepsilon}-WGD) is a pivotal yet contentious event that has long been debated. A recent study refuted its occurrence based on deviations from expected retention patterns of dosage-sensitive genes. Here, we provide both structural (orthologous synteny) and phylogenetic (subgenome-aware) evidence to revisit this debate. With improved annotation of the Ginkgo genome, we uncover a clear 1:2 orthologous synteny ratio between Ginkgo and early-diverging angiosperms (Amborella and Aristolochia), which lack lineage-specific WGDs. Subgenome-aware phylogenomic analyses further demonstrate that the Amborella/Aristolochia subgenomes diverged after the gymnosperm-angiosperm split but before the radiation of extant angiosperms. Together, these findings provide direct structural evidence for an ancestral angiosperm tetraploidization in the early Jurassic, following divergence from gymnosperms. We argue that the recent refutation of the {varepsilon}-WGD relies on restrictive assumptions regarding ploidy level and duplicate retention that may not hold for deep-time polyploidy events. Our results provide a robust resolution to this long-standing debate and reaffirm the {varepsilon}-WGD as a shared synapomorphy of extant angiosperms.

evolutionary biology↗

bioRxiv2025

Intratumoral microbiota-derived S1P sensitizes the combination therapy of Capecitabine and Nivolumab

Clinical responses of colorectal cancer (CRC) treatments vary considerably due to the heterogeneity of tumor micro-environment (TME), where intratumoral microbiota may reshape the unique inflammation imprints. However, its complex mechanistic underpinnings remain incompletely elucidated. Herein we sought to delineate the critical role of intratumoral microbiota in potentiating combination therapeutics against CRC. By comparing germ-free (GF) and specific pathogen-free (SPF) mouse models of 33 potential CRC treatments, we screened out the combination regimen of Capecitabine-Nivolumab significantly augmented by intratumoral microbiota in tumor regression and survival prolongation. The enrichment of Bacteroides fragilis induced by Capecitabine-Nivolumab was concomitant with elevated microbial sphingosine-1-phosphate (S1P), which further upregulated tumoral PD-L1 expression by enhancing histone deacetylation at the CD274 locus. Activation of microbial sphingosine kinase 2 (SphK2) ultimately led to an expansion of effector memory CD8+ T cells and reduction of exhausted T cell subsets within TME. To conclude, these findings advance our understanding of the intricate interplay among intratumoral microbiota, sphingolipid metabolites and immunochemotherapeutics. It highlights microbial sphingolipids as potential predictive biomarkers for strategies of targeting intratumoral microbiota in CRC management.

microbiology↗

bioRxiv2024

Phytop: A tool for visualizing and recognizing signals of incomplete lineage sorting and hybridization using species trees output from ASTRAL

Incomplete lineage sorting (ILS) and introgression/hybridization (IH) is prevalent in nature and thus frequently result in discrepancies within phylogenetic tree topologies, leading to misinterpretation of phylogenomic data. Despite the availability of numerous tools for detecting ILS and IH among species, many of these tools are lacking effective visualization, or are time-consuming, or require prior predetermination. Here, we addressed these shortcomings by developing a fast-running, user-friendly tool called Phytop. By defining ILS and IH indices to quantify ILS and IH, this tool can detect the extent of ILS and IH among lineages with high reliability, and can visualize them based on the gene tree topology patterns constructed using ASTRAL. We tested Phytop extensively using both simulated and real data, and found that it enables users to quickly and conveniently estimate the extent of ILS and IH, thus clarifying the phylogenetic uncertainty. Phytop is available at https://github.com/zhangrengang/phytop and is expected to conveniently contribute to the intuitive inference of genetic relationships among lineages in future research.

bioinformatics↗

bioRxiv2024

Natural killer cell migration in HIV-infected individuals is inhibited by impairment of HIF-1alpha-mediated glycolysis

Natural killer (NK) cells serve as the first line of defense of the immune system and play a crucial role in fighting against HIV infection. The effective function of NK cells is closely related to their migration ability, but the status of NK cell migration in HIV-infected individuals and the regulation mechanism for NK cell migration remains unknown. Here, we found that NK cell migration was significantly impaired in HIV-infected individuals, lower in immune non-responders (INRs) compared with immune responders (IRs), and positively correlated with CD4+ T cell counts. Further investigations showed that the decreased NK cell migration in HIV infection was caused by the impairment of glycolysis. Mechanistically, we found that NK cell migration was regulated by HIF-1 pathway, and inhibitory receptor TIGIT restrained HIF-1 expression by inhibiting PI3K/AKT/mTORC1 or ERK signaling pathway, consequently weakening the glycolysis of NK cells in HIV-infected individuals, and ultimately leading to down-regulation of migration. Collectively, we uncovered a mechanism of reduced NK cell migration in HIV infection and provided a new insight for immunotherapy in HIV infection. In BriefThe effective function of NK cells is closely related to its migration ability. The authors show that impaired NK cell migration in HIV-infected individuals is caused by TIGIT inhibiting HIF-1-mediated glycolysis via PI3K/AKT/mTORC1 or ERK pathway.

immunology↗

bioRxiv2024

From Understudied to Understood: Multi-Omics Analysis with MiniENCODE Exemplified by Zebrafish

Building multi-omics resources for understudied organisms requires assay selection, public-data curation, gene identifier handling, portal deployment, and visualization, yet these tasks are rarely packaged into a reusable framework. To fill this gap, we developed the mini Omics Data Portal (miniODP), which combines species pages, gene-centric modules, genome browsing, and sequence search with configuration files, species onboarding workflows, and demonstration data for self-deployment. Alongside the software, we propose miniENCODE core assays: a reduced RNA-seq, ATAC-seq, and H3K27ac profiling set for regulatory analysis. Current miniODP includes seven species, covering 3,568 bulk runs, 3.61 million cells, and 1,865 genome-browser tracks. Matched core-assay datasets support regulatory outputs. As a zebrafish benchmark, using datasets from three core assays and 17 samples, we identified 52,350 enhancer-like signatures (ELSs) and constructed ELS-to-gene linkages and gene regulatory networks (GRNs). Genes near H3K27ac-supported ELSs were expressed at higher levels than those near ATAC-only distal peaks. Literature curation of top TFs from zebrafish and cattle GRNs found 19 direct, 15 indirect, and six unsupported cases among 40 candidates. Datasets lacking matched core assays still provide browsing, visualization, and search functions. miniODP serves as a reusable framework for constructing and extending multi-omics resources for understudied organisms. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/573815v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1542265org.highwire.dtl.DTLVardef@9e5424org.highwire.dtl.DTLVardef@a630d5org.highwire.dtl.DTLVardef@d0163c_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2023

Lhcb9-dependent photosystem I structure in moss reveals evolutionary adaptation to changing light conditions during aquatic-terrestrial transition

In plants and green algae, light-harvesting complexes I and II (LHCI and LHCII) constitute the antennae of photosystem I (PSI), thus effectively increasing the cross-section of the PSI core. The moss Physcomitrium patens (P. patens) represents a well-studied evolutionary intermediate between green algae and flowering plants. P. patens possesses at least three types of PSI with different antenna sizes. The largest PSI form (PpPSI-L) exhibits a unique organization found neither in flowering plants nor in algae. Its formation is mediated by the P. patens-specific LHC protein, Lhcb9. While previous studies revealed the overall architecture of the PpPSI-L, its assembly details and the relationship between different PpPSI types remain unclear. Here, we report a high-resolution structure of the PpPSI-L. We identified 14 PSI core subunits, one Lhcb9, one phosphorylated LHCII trimer, and eight LHCI monomers arranged as two belts. Our structural analysis established the essential role of Lhcb9 and the phosphorylated LHCII in stabilizing the complex. In addition, our results suggest that PpPSI switches between three different types, which share identical modules. This feature may contribute to the quick and dynamic adjustment of the light-harvesting capability of PSI under different light conditions.

plant biology↗

bioRxiv2022

Underlying beneficial effects of Rhubarb on constipation-induced inflammation, disorder of gut microbiome and metabolism

BackgroundAlthough constipation is a common syndrome and a worldwide health problem. Constipation patients are becoming younger with a 29.6% overall prevalence in the children, which has captured great attention because of its epigenetic rejuvenation and recurrent episodes. Despite the usage of rhubarb to relieve constipation, novel targets and genes involved in target-relevant pathways with remarkable functionalities should still be sought after. Materials and methodsWe established a reliable constipation model in C57B/6N male mice using intragastric administration diphenoxylate and the eligible subjects received 600mg/25g rhubarb extraction to ameliorate constipation. Resultant constipation was morphological and genetically compared with the specimen from different groups. ResultsThe constipation mice exhibited thicker muscle layers, improved content of cytokines, including IL-17 and IL-23, and lower content of IL-22. The bacterial abundance and diversity varied tremendously. Notably, the alterations were reversed after rhubarb treatment. Additionally, SCFA and MLCFA were significantly influenced by constipation accompanied by enhanced expressions of SCFA receptors, GPR41 and GPR43. ConclusionThis thesis has provided an insight that rhubarb promoted the flexibility of collagen fiber, reduced pro-inflammatory cytokines and enhanced anti-inflammatory cytokines, and maintained intestinal microflora balance with potential effects on affecting the metabolism of fatty acids and polyamines.

pharmacology and toxicology↗

bioRxiv2022

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals Cytoskeleton is An Inhibitor for C. neoformans Invasion into Brain

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART-naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans, yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced "Trojan Horse" in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage "Trojan Horse", myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

microbiology↗

bioRxiv2021

Conserved genomic landscapes of differentiation across Populus speciation continuum

Speciation, the continuous process by which new species form, is often investigated by looking at the variation of nucleotide diversity and differentiation across the genome (hereafter genomic landscapes). A key challenge lies in how to determine the main evolutionary forces at play shaping these patterns. One promising strategy, albeit little used to date, is to comparatively investigate these genomic landscapes as a progression through time by using a series of species pairs along a divergence gradient. Here, we resequenced 201 whole-genomes from eight closely related Populus species, with pairs of species at different stages along the divergence gradient to learn more about speciation processes. Using population structure and ancestry analyses, we document extensive introgression between some species pairs, especially those with parapatric distributions. We further investigate genomic landscapes, focusing on within-species (nucleotide diversity and recombination rate) and among-species (relative and absolute divergence) summary statistics of diversity and divergence. We observe highly conserved patterns of genomic divergence across species pairs. Independent of the stage across the divergence gradient, we find support for signatures of linked selection (i.e., the interaction between natural selection and genetic linkage) in shaping these genomic landscapes, along with gene flow and standing genetic variation. We highlight the importance of investigating genomic patterns on multiple species across a divergence gradient and discuss prospects to better understand the evolutionary forces shaping the genomic landscapes of diversity and differentiation.

evolutionary biology↗

bioRxiv2019

Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKTpathway

BackgroundAnlotinib is a multi-tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the functional mechanisms whereby anlotinib mediates against deadly drug-resistant colorectal cancer (CRC) has not been fully described-specifically, the potential mechanisms that inhibit proliferation and induce apoptosis remain largely unknown. MethodsMTT assays were used to detect cell viability and calculate the resistance index. Colony formation was used to evaluate the proliferation of resistant cells. DAPI staining was used to detect cell apoptosis morphologically. Annexin V-FITC with PI staining was used to detect early and late-stage apoptosis of cells. Cell cycle distribution was determined by Flow cytometry. Transwell assays were performed to examine the ability of migration and invasion. Cyclin D1 Survivin, CDK4, Bcl-2, Bax and changes of PI3K/AKT pathway were detected by Western blotting. Compared as a single agent or combined with anlotinib or LY294002, PI3K inhibitor (LY294002) was used to verify whether it inhibited drug-resistant CRC cells by lowering PI3K/AKT. ResultsHCT-8/5-FU cells showed multiple drug resistance. Drug resistance index of 5-FU, ADM and DDP were 390.27, 2.55 and 4.57, respectively. Anlotinib was shown to inhibit cell viability on HCT-8/5-FU and HCT-8 cells for 24 h and 48 h in a dosage- and time-dependent pattern. Compared with 48 h, intervened with anlotinib (0 M, 10 M, 20 M and 40 M) for 24 h, the HCT-8/5-FU cells were sensitive to anlotinib, and their sensitivity was greater than that of the parent cell line (HCT-8) at 24 h. Further, anlotinib inhibited the number of cloned cells significantly and had a significant inhibitory effect on cell cycle, mainly by blocking G1 transferring to S phase. Moreover, anlotinib could down-regulate the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, vimentin, MMP-9, and N-cadherin, while up-regulating cleaved-caspase-3, Bax and E-cadherin. Anlotinib inhibited the activity of the PI3K/AKT pathway and induced apoptosis in HCT-8/5-FU cells. Using LY294002, a specific PI3K inhibitor, our experiment found anlotinib can inhibit drug-resistant CRC cells by reducing PI3K and p-AKT activity-induce apoptosis. ConclusionsAnlotinib inhibited the proliferation, metastasis and induced apoptosis of HCT-8 / 5-FU cells; and the mechanism could be that anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway.

pharmacology and toxicology↗

bioRxiv2018

A draft reference genome sequence for Scutellaria baicalensis Georgi

Scutellaria baicalensis Georgi is an important medicinal plant used worldwide. Information about the genome of this species is important for scientists studying the metabolic pathways that synthesise the bioactive compounds in this plant. Here, we report a draft reference genome sequence for S. baicalensis obtained by a combination of Illumina and PacBio sequencing, which was assembled using 10 X Genomics and Hi-C technologies. We assembled 386.63 Mb of the 408.14 Mb genome, amounting to about 94.73% of the total genome size, and the sequences were anchored onto 9 pseudochromosomes with a super-N50 of 33.2 Mb. The reference genome sequence of S. baicalensis offers an important foundation for understanding the biosynthetic pathways for bioactive compounds in this medicinal plant and for its improvement through molecular breeding.

plant biology↗

bioRxiv2017

Single Molecule Sequencing of Cell-free DNA from Maternal Plasma for Noninvasive Trisomy Detection

The demand of non-invasive prenatal testing for autosomal aneuploidy using cell-free fetal DNA (cffDNA) in maternal plasma is a highly sought-after diagnostic, with a rapidly growing market. Current approaches developed by next generation sequencing (NGS) need PCR amplifcation during sample preparation, which results in amplification bias in GC-rich areas of the human genome. With these approaches, the minimum fetal fraction in maternal plasma is 4% for the small differences in circulating cfDNA between trisomic and disomic pregnancies to be detectable. In this paper, we performed single molecule sequencing of cell-free DNA from maternal plasma for noninvasive trisomy 13, 18 and 21 detections using the GenoCare platform. We found that single molecule sequencing is sensitive enough to detect these chromosome abnormalities when the fetal DNA fraction is as low as 2%. Compared to the Hiseq2500 platform, no significant GC bias was observed. The improved sensitivity and unbiased GC readout make GenoCare a promising platform for autosomal aneuploidy detections, even in the very early stage of pregnancy.

genomics↗

bioRxiv2017

Resequencing the Escherichia coli genome by GenoCare single molecule sequencing platform

Next generation sequencing (NGS) has revolutionized life sciences research. Recently, a new class of third-generation sequencing platforms has arrived to meet increasing demands in the clinic, capable of directly measuring DNA and RNA sequences at the single-molecule level without amplification. Here, we use the new GenoCare single molecule sequencing platform from Direct Genomics to resequence the E. coli genome and show comparable performance to the Illumina MiSeq system. Our platform detects single-molecule fluorescence by total internal reflection microscopy, with sequencing-by-synthesis chemistry. With a consensus sequence of 99.71% nucleotide identity to that of the Illumina MiSeq systems, GenoCare was determined to be a reliable platform for single-molecule sequencing, with strong potential for clinical applications.

genomics↗

bioRxiv2017

Single Molecule Sequencing Of M13 Virus Genome Without Amplification

Third generation sequencing is a direct measurement of DNA/RNA sequences at the single molecule level without amplification. In this study, we report sequencing of the genome of the M13 virus by a new single molecule sequencing platform. Our platform detects single molecule fluorescence by the total internal reflection microscope technique, with sequencing-by-synthesis chemistry. We sequenced the genome of M13 to a depth of 316x and 100% coverage. The consensus sequence accuracy is 100%. We demonstrated that single molecule sequencing has no significant GC bias.

genomics↗