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Li, Q.

Publications and source records attributed to Li, Q..

At least 397 records · Page 22Linked to original sources

A Novel Hierarchical Network-Based Approach to Unveil the Complexity of Functional Microbial Genome

Biological networks are pivotal in elucidating intricate biological processes. While substantial research has delved into interspecies environmental interactions within biological networks, intraspecific functional gene interactions within individual microbes remain relatively untapped. The burgeoning availability of microbiome datasets underscores the imperative for a refined examination of microbial genome structures and functions. We innovatively introduce the concept of "Solid Motif Structures (SMS)" through a meticulous biological network analysis of genomes from the same genus, aiming to bridge the gap between the structural and functional intricacies of microbial genomes. Harnessing publicly available data from 162 high-quality Microcystis genomes, a globally prevalent freshwater cyanobacterium instrumental in microbial ecosystems, a comprehensive genome structure network for Microcystis was delineated. Employing a state-of-the-art deep learning scheme, we discerned 27 pivotal functional subnetworks and an array of functionally-associated SMS. Incorporating metagenomic data from seven geographically diverse lakes, we embarked on an exhaustive analysis of the functional stability of Microcystis across varied environmental matrices. This culminated in the identification of distinct functional interaction models for each lake. Our research amalgamates these insights into a comprehensive resource repository, furnishing unparalleled perspectives into the functional interplay within Microcystis. Leveraging advanced biological network analysis, our study pioneers the delineation of a novel network granularity, facilitating a more lucid comprehension of the dynamic interplay between genome structure and function interactions in microorganisms of the same genus. This study shed light on the plasticity and conservation of microbial functional genomes across diverse environments, offering insights into their evolutionary trajectories.

genomics↗

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT. The heightened bacterial burdens in Bhlhe40-/-mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-{gamma}, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in Bhlhe40-/- mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in Bhlhe40-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-{gamma} production by Th1 cells. Altogether, we identified Bhlhe40 as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against Chlamydia.

immunology↗

Dual long-axis reorganization of hippocampus in youth

The reorganization of human hippocampus, especially its interaction with cortex, remains largely undefined in youth. The organization of a single hippocampal long-axis has been predominantly characterized as monotonic1-6, despite recent indications of nonmonotonic features in neuron density7 and geometric eigenmodes8. While the human cortical hierarchy has been well recognized for significant developmental and evolutionary advantages9-12, hippocampus has been typically considered an evolutionarily conserved brain structure1,13,14, and overlooked regarding its integrative role of cortical hierarchical processing during development. Here, we corroborated the presence and significance of a dual long-axis representation of the hippocampal connectome and geometry including both linear and quadratic gradients along its long-axis in youth. This finding was robust across two independent large-scale developmental cohorts. Charting development of the dual long-axis gradients underscored their specific contributions to the cortical hierarchy maturation from the frontoparietal and salience/ventral attention networks. The observed developmental variability in spontaneous brain activities in youth parallels the gradients of myelin content. During childhood through adolescence to early adulthood, the hippocampus reorganized the dual long-axis by gradually relaxing its geometric constraints on the intrinsic network organization of cortical spontaneous activity for refined executive functions. Molecular processes underlying such reorganization of the dual long-axis in hippocampus are linked to neural growth, stress hormone regulation, and neuroactive signaling. Our findings enrich the understanding of hippocampal-cortical reorganizational principles across structural, functional, and molecular dimensions as well as its maturation, and define the plasticity distribution within the human hippocampus at systems level, holding potentials to enhance and translate neurodevelopment and neuropsychiatric healthcare.

neuroscience↗

A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer

BACKGROUND & AIMSPDAC is characterized by significant matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, it is not clear the connection between matrix stiffness and the Warburg effect and the mechanisms of action in tumor progression. METHODSThe relationship between matrix stiffness and the Warburg effect was investigated from clinical, cellular, and bioinformatical perspectives. The ChIP and luciferase reporter gene assays were used to clarify the regulation mechanism of matrix stiffness on the expression of CLIC1. The expression profile and clinical significance of CLIC1 were determined in GEO datasets and a TMA. Loss-of-function and gain-of-function technics were used to determine the in vitro and in vivo functions of CLIC1. GSEA and western blotting revealed the underlying molecular mechanisms. RESULTSPDAC matrix stiffness is closely associated with the Warburg effect, and CLIC1 is a key molecule connecting tumor matrix stiffness and the Warburg effect. Increased CLIC1 expression induced by matrix stiffness correlates with poor prognosis in PDAC. CLIC1 acts as a promoter of glycolytic metabolism and facilitates tumor growth in a glycolysis-dependent manner. Mechanistically, CLIC1 inhibits the hydroxylation of HIF1 via ROS, which then increases the stability of HIF1. Collectively, PDAC cells can sense extracellular matrix stiffness and upregulate the expression of CLIC1, which facilitates the Warburg effect through ROS/HIF1 signaling, thereby supporting tumor growth. CONCLUSIONSIn the context of tumor therapy, targeted approaches can be considered from the perspectives of both extracellular matrix stiffness and tumor metabolism, of which CLIC1 is one of the targets.

cancer biology↗

Co-existence of blaKPC-2 and blaVIM-2 in highly carbapenem-resistant Pseudomonas aeruginosa isolated in the ICU of a public hospital

In this study, highly carbapenem-resistant Pseudomonas aeruginosa (h-CRPA) 18102011 [the minimum inhibitory concentration (MIC) value of carbapenem antimicrobial imipenem (IP) for h-CRPA is 4,096 g/mL] was isolated from the bile of an intensive care unit (ICU) burn patient in China, and genomic sequencing revealed a complete genome. The genomes molecular characteristics were analyzed to assess the genetic environment of blaKPC-2 and blaVIM-2. Average nucleotide identity (ANI) comparisons were used for precise species-level identification, while serotyping, multi-locus sequence typing, and the identification of acquired resistance genes, and virulence genes were also carried out. The h-CRPA 18102011 strain carrying blaKPC-2 and blaVIM-2 was identified as strain ST2374 and the O4 serotype. Virulence genes (plcH, exoST) and resistance genes (aph(3)-IIb, aac(6)-Ib-cr, ant(2)-Ia, blaOXA-396, blaPAO, blaKPC-2, blaVIM-2, blaPER-1, sul1, catB7, qnrVC6, fosA) were both identified in the genome. In addition, the IncpRBL16 type mega-plasmid pP2011-1 carrying blaVIM-2 and the IncP6 type plasmid pP2011-2 carrying blaKPC-2 were identified in the strain. The genetic environment of blaVIM-2 and blaKPC-2 was specifically evaluated to assess their origins. blaVIM-2 was located in the region of In2075 (a novel type 1 integron) that was inserted into plasmid pP2011-1, this plasmid contained 3 novel recombination sites, as well as the typical recombination site 2 (umuC) observed for IncpRBL16 type plasmids. However, the core module Tn3-ISKpn27-blaKPC-{Delta}ISKpn6 was identified as the blaKPC-2 platform in plasmid pP2011-2. Conjugation experiments revealed that the plasmids pP2011-1 and pP2011-2 of the h-CRPA 18102011 strain could be transferred into Escherichia coli with a conjugation transfer efficiency of 10-6. The E. coli transconjugant carried blaKPC-2 and blaVIM-2 from the donor and the MIC value of IP to the E. coli transconjugant was 4,096 g/mL, which was the same as observed for the donor. Overall, this study revealed the molecular characteristics of a VIM-2 and KPC-2-co-producing strain that was typed as O4 and ST2374. The continuous monitoring of bacteria, such as the strain investigated here, that co-harbor different types of carbapenemase genes is critical for preventing the spread of these genes.

genomics↗

Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion

Inherited retinal diseases (IRDs) encompass a genetically diverse group of conditions in which mutations in genes critical to retinal function lead to progressive loss of photoreceptor cells and subsequent visual impairment. A handful of ribosome-associated genes have been implicated in retinal disorders alongside neurological phenotypes. This study focuses on the HBS1L gene, encoding HBS1 Like Translational GTPase which has been recognized as a critical ribosomal rescue factor. Previously, we have reported a female child carrying biallelic HBS1L mutations, manifesting growth restriction, developmental delay, and hypotonia. In this study, we describe her ophthalmologic findings, compare them with the Hbs1ltm1a/tm1a hypomorph mouse model, and evaluate the underlying microscopic and molecular perturbations. The patient was noted to have impaired visual function observed by electroretinogram (ERG), with dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound retinal thinning of the entire retina, specifically of the outer retinal photoreceptor layer, detected using in vivo imaging of optical coherence tomography (OCT) and retinal cross sections. TUNEL assay revealed retinal degeneration due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations in mass spectrometry analysis, with169 proteins increased and 480 proteins decreased including many critical IRD-related proteins. GO biological process and GSEA analyses reveal that these downregulated proteins are primarily involved in photoreceptor cell development, cilium assembly, phototransduction, and aerobic respiration. Furthermore, apart from the diminished level of PELO, a known partner protein, HBS1L depletion was accompanied by reduction in translation machinery associated 7 homolog (Tma7), and Endothelial differentiation-related factor 1(Edf1) proteins, the latter of which coordinates cellular responses to ribosome collisions. This novel connection between HBS1L and ribosome collision sensor (EDF1) further highlights the intricate mechanisms underpinning ribosomal rescue and quality control that are essential to maintain homeostasis of key proteins of retinal health, such as rhodopsin.

genetics↗

Potential intrahospital dissemination of Pseudomonas aeruginosa carrying the blaIMP-1 gene within a Tn7-like transposon

We aimed to determine the molecular characteristics of carbapenem-resistant Pseudomonas aeruginosa 18081308 and 18083286 isolated from the urine and sputum of two Chinese patients respectively, and analyzed the formation mechanism of the genetic environment in which it carries blaIMP-1. Bacterial genome sequencing was carried out on strains 18081308 and 18083286 to obtain their whole genome sequence. Average nucleotide identity (ANI) was used for their precise species identification. Serotyping and multilocus sequence typing were performed. Furthermore, the acquired resistance genes, and virulence factors of these strains were identified. The carbapenem-resistant P. aeruginosa strains isolated in the present study were of sequence type ST865 and serotype O6. They all carried the same virulence factors (PLC, ExoSTY) and resistance genes (aacC2, tmrB, and blaIMP-1). Tn6411, a Tn7-like transposon carrying blaIMP-1, was found in both strains. Detailed genetic dissection was applied to this transposon to display the genetic environment of blaIMP-1. The aacC2-tmrB region remnant-Tn6411 backbone was the original structure of this type of transposon. A Tn402-like type 1 integron (intl1-aac(6)-II-blaIMP-1) was inserted into it and formed a stable structure, which was localized in the chromosome by TnsD for transmission within P. aeruginosa; the original structure of Tn7-like transposon was localized on the plasmid by TnsE for horizontal transmission between bacterial species. The intrahospital dissemination of P. aeruginosa ST865 isolated in this study was episodic. The blaIMP-1-carrying Tn7-like transposon might enhance their ability to survive under drug selection pressure and aggravate the difficulty in treating infections.

genomics↗

Multimodal joint deconvolution and integrative signature selection in proteomics

Deconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods have not been extended to the proteomics research. Here we present a novel algorithm and tool to dissect bulk proteome by leveraging the information shared between transcriptome-proteome. Our tool first identifies potential cell marker proteins by integrating RNA and protein bulk expression profiles and then jointly quantifies the cell abundance in mixture proteomes without using a reference signature matrix, enabling the downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. This new method and the cspQTL analysis are implemented in the R package MIC-SQTL that also provides integrative visualization of bulk multimodal samples, available at https://bioconductor.org/packages/MICSQTL.

bioinformatics↗

Rolling 2D Bioelectronic film into 1D: a Suturable Long-term Implantable Soft Microfiber

Long-term implantable bioelectronics can efficiently evaluate the function of the nervous system. 1D fiber-shaped devices require small surgical incisions significantly benefiting long-term biocompatibility. We report a strategy of rolling to reduce the dimension of bioelectronic devices from 2D film to 1D microfiber. The soft and stretchable multifunctional microfiber accommodates more than 60-channel longitudinally-distributed electrodes for bio-electric and -mechanical monitoring. It can be sutured into muscle with tiny incision for 8-month bio-electrical monitoring in rats. Importantly, after 13-month implantation, the fibroblast encapsulation around the fiber is negligible. Moreover, it can wander inside a brain under magnetic field. This strategy not only opens up the study of multi-channel and -function soft and stretchable fiber-shaped sensors but offers a platform for minimally-invasive implantable bioelectronics. One-Sentence SummaryThe rolling enables stretchable electrode array along one single microfiber and multimodal long-term in-vivo monitoring.

neuroscience↗

Relative importance of bacterivorous mixotrophs in an estuary-coast environment

Mixotrophic eukaryotes are important bacterivores in oligotrophic open oceans, but their significance as grazers in more nutrient-rich waters is less clear. Here we investigated the bacterivory partition between mixotrophs and heterotrophs in a productive, estuary-influenced coastal region in East China Sea. We found ubiquitous, actively feeding phytoplankton populations and taxa with mixotrophic potential, by identifying ingestion of fluorescent prey surrogate and analyzing community 18S rRNA gene amplicons. Potential and active mixotrophs accounted for 10-63% of total eukaryotic community and 17-69% of bacterivores observed, respectively, contributing 6-48% of estimated in situ bacterivory. The much higher mixotroph fitness outside of the turbid plume were potentially driven by increased light and decreased nutrients availability. Our results suggest that, although heterotrophs dominated overall in situ bacterivory, mixotrophs were abundant and important bacterivores in this low-latitude mesotrophic coastal region. Scientific Significance StatementMixotrophy, the combing of photosynthetic and phagotrophic nutrition, can dramatically increase primary production and alter material movements in aquatic food webs. Understanding the distribution and fitness of phagotrophic mixotrophs in a range of habitats are therefore critical to properly understand the biogeochemical cycles of the ocean. We developed a robust method to estimate active mixotrophs in situ and demonstrate rapid shifts of bacterivory partition between mixotrophs and heterotrophs across an estuary-coast environment in East China Sea. Our results help fill the knowledge gap of mixotroph niches in mesotrophic coastal environments that are impacted by riverine discharge, shedding light on relationships among mixotrophy, light and nutrient conditions.

microbiology↗

imply: improving cell-type deconvolution accuracy using personalized reference profiles

Real-world clinical samples are often admixtures of signal mosaics from multiple pure cell types. Using computational tools, bulk transcriptomics can be deconvoluted to solve for the abundance of constituent cell types. However, existing deconvolution methods are conditioned on the assumption that the whole study population is served by a single reference panel, which ignores person-to-person heterogeneity. Here we present imply, a novel algorithm to deconvolute cell type proportions using personalized reference panels. imply can borrow information across repeatedly measured samples for each subject, and obtain precise cell type proportion estimations. Simulation studies demonstrate reduced bias in cell type abundance estimation compared with existing methods. Real data analyses on large longitudinal consortia show more realistic deconvolution results that align with biological facts. Our results suggest that disparities in cell type proportions are associated with several disease phenotypes in type 1 diabetes and Parkin-sons disease. Our proposed tool imply is available through the R/Bioconductor package ISLET at https://bioconductor.org/packages/ISLET/.

bioinformatics↗

Human disturbance increases spatiotemporal associations among mountain forest terrestrial mammal species

Spatial and temporal associations between sympatric species underpin biotic interactions, structure ecological assemblages, and sustain ecosystem functioning and stability. However, the resilience of interspecific spatiotemporal associations to human activity remains poorly understood, particularly in mountain forests where anthropogenic impacts are often pervasive. Here we applied context-dependent Joint Species Distribution Models to a systematic camera-trap survey dataset from a global biodiversity hotspot in eastern Himalaya to understand how prominent human activities in mountain forests influence species associations within terrestrial mammal communities. We obtained 10,388 independent detections of 17 focal species (12 carnivores and five ungulates) from 322 stations over 43,163 camera days of effort. We identified a higher incidence of positive associations in habitats with higher levels of human modification (87 %) and human presence (83 %) compared to those located in habitats with lower human modification (64 %) and human presence (65 %) levels. We also detected a significant reduction of pairwise encounter time at increasing levels of human disturbance, corresponding to more frequent encounters between pairs of species. Our findings indicate that human activities can push mammals together into more frequent encounters and associations, which likely influences the coexistence and persistence of wildlife, with potential far-ranging ecological consequences.

ecology↗

Visual Image Reconstruction from Human Brain Activity using Linear Image Decoders plus Nonlinear Noise Suppression

In recent years, substantial strides have been made in the field of visual image reconstruction, particularly in its capacity to generate high-quality visual representations from human brain activity while considering semantic information. This advancement not only enables the recreation of visual content but also provides valuable insights into the intricate processes occurring within high-order functional brain regions, contributing to a deeper understanding of brain function. However, considering fusion semantics in reconstructing visual images from brain activity involves semantic-to-image guide reconstruction and may ignore underlying neural computational mechanisms, which does not represent true reconstruction from brain activity. In response to this limitation, our study introduces a novel approach that combines linear mapping with nonlinear noise suppression to reconstruct visual images perceived by subjects based on their brain activity patterns. The primary challenge associated with linear mapping lies in its susceptibility to noise interference. To address this issue, we leverage a flexible denoised deep convolutional neural network, which can suppress noise from linear mapping. Our investigation encompasses linear mapping as well as the training of shallow and deep autoencoder denoised neural networks, including a pre-trained, state-of-the-art denoised neural network. The outcome of our study reveals that combining linear image decoding with nonlinear noise reduction significantly enhances the quality of reconstructed images from human brain activity. This suggests that our methodology holds promise for decoding intricate perceptual experiences directly from brain activity patterns without semantic information. Moreover, the model has strong neural explanatory power because it shares structural and functional similarities with the visual brain.

neuroscience↗

Tissue-specific transfer-learning enables retasking of a general comprehensive model to a specific domain

Machine learning (ML) has proven successful in biological data analysis. However, may require massive training data. To allow broader use of ML in the full spectrum of biology and medicine, including sample-sparse domains, re-directing established models to specific tasks by add-on training via a moderate sample may be promising. Transfer learning (TL), a technique migrating pre-trained models to new tasks, fits in this requirement. Here, by TL, we retasked Enformer, a comprehensive model trained by massive data, tailored to breast cancers using breast-specific data. Its performance has been validated through statistical accuracy of predictions, annotation of genetic variants, and mapping of variants associated with breast cancer. By allowing the flexibility of adding dedicated training data, our TL protocol unlocks future discovery within specific domains with moderate add-on samples by standing on the shoulders of giant models.

bioinformatics↗

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

X chromosome encoded histone demethylase UTX regulates mammalian axon regeneration via microRNA-124

Epigenetic regulation of neuronal transcriptomic landscape is emerging to be a key coordinator of mammalian neural regeneration. Here we investigated roles of two histone 3 lysine 27 (H3K27) demethylases Kdm6a/b in controlling neuroprotection and axon regeneration. Deleting either Kdm6a or Kdm6b led to enhanced sensory axon regeneration in the PNS, whereas in the CNS only deleting Kdm6a in retinal ganglion cells (RGCs) significantly enhanced optic nerve regeneration. Moreover, both Kdm6a and Kdm6b functioned to regulate RGC survival but with different mechanisms. Mechanistically, Kdm6a regulates RGC regeneration via distinct pathway from that of Pten and co-deleting Kdm6a and Pten resulted in long distance optic nerve regeneration passing the optic chiasm. In addition, RNA-seq profiling revealed that Kdm6a deletion switched the RGC transcriptomics into a developmental-like state and suppressed several known repressors of neural regeneration. Klf4 was identified as a direct downstream target of Kdm6a-H3K27me3 signaling in both sensory neurons and RGCs to regulate axon regeneration. These findings not only revealed different roles of Kdm6a and Kdm6b in regulation of neural regeneration and their underlying mechanisms, but also identified Kdm6a- mediated histone demethylation signaling as a novel epigenetic target for supporting CNS neural regeneration.

neuroscience↗

Thermal and Nutrient Stress Drove Permian-Triassic Marine Extinctions

The Permian-Triassic mass extinction coincides with extensive environmental changes (i.e., thermal stress, deoxygenation and potentially ocean acidification), but the primary drivers of extinction in them marine realm are currently unknown. To understand which factors caused extinctions, we quantitatively investigated the relationship between geochemical proxies and fossil record at the most intensively-studied locality for this event, the Meishan section, China. We found that {delta}18Oapatite (paleotemperature proxy) and {delta}114Cd (primary productivity proxy) best explain changes in species diversity and composition at Meishans paleoequatorial setting. These findings suggest that the physiological stresses induced by ocean warming and nutrient availability played a predominant role in driving equatorial marine extinctions during the Permian-Triassic event. This research enhances our understanding of the interplay between environmental changes and extinction dynamics during a past climate crisis. One-Sentence SummaryOcean warming and nutrient availability were key drivers of equatorial marine extinctions during the Permian-Triassic mass extinction.

evolutionary biology↗

A single-cell transcriptome analysis and prognostic model construction of stromal cells for renal cell carcinoma

Renal cell carcinoma (RCC) is among the top three cancers of the urinary system and its incidence keeps increasing worldwide in recent decades. However, methods for accurate prognosis evaluation and effective treatment are still lacking nowadays. Here, to explore the molecular expression features of RCC and establish a new RCC clinical prognosis evaluation model, a cell landscape of 187,263 renal cells obtained from eight patients with RCC was analyzed in this study. And by extracting and focusing on the main stromal cells from RCC tissues, innovative molecular characteristics and pathways of tumors were identified, like the well-known hypoxia pathway. By analyzing cell-cell communication, fibroblasts were found to promote tumor development by repressing natural killer cells. Based on Cox and least absolute shrinkage and selection operator regression analysis, four risk factors were screened and used to construct a reliable RCC clinical risk estimation model. In conclusion, our work provides new insights into the tumor microenvironment of RCC, as well as potential therapeutic targets and a clinical risk model for RCC invasiveness. Hopefully, these findings will be useful for cancer research and clinical treatment in future.

cancer biology↗