Biology subjects

Gu, X.

Publications and source records attributed to Gu, X..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Prefrontal encoding of an internal model for emotional inference

A key function of brain systems mediating emotion is to learn to anticipate unpleasant experiences based on predictive sensory cues in the environment. While organisms readily associate sensory stimuli with aversive outcomes, higher-order forms of emotional learning and memory require inference to extrapolate the circumstances surrounding directly experienced aversive events to other indirectly related contexts and sensory patterns which werent a part of the original experience. To achieve this type of learning requires internal models of emotion which flexibly track directly experienced and inferred aversive associations. While the brain mechanisms of simple forms of aversive learning have been well studied in areas such as the amygdala, whether and how the brain represents internal models of emotionally relevant associations is not known. Here we report that neurons in the rodent dorsomedial prefrontal cortex (dmPFC) encode an internal model of emotion by linking sensory stimuli in the environment with aversive events, whether they were directly or indirectly associated with that experience. These representations are flexible, and updating the behavioral significance of individual features of the association selectively modifies corresponding dmPFC representations. While dmPFC population activity encodes all salient associations, dmPFC neurons projecting to the amygdala specifically represent and are required to express inferred associations. Together, these findings reveal how internal models of emotion are encoded in dmPFC to regulate subcortical systems for recall of inferred emotional memories.

neuroscience↗

bioRxiv2024

RGS10 deficiency facilitates distant metastasis by inducing epithelial-mesenchymal transition in breast cancer

AbstractDistant metastasis is the major cause of death in patients with breast cancer. Epithelial-mesenchymal transition (EMT) contributes to breast cancer metastasis. Regulator of G protein-signaling (RGS) proteins modulate metastasis in various cancers. This study identified a novel role for RGS10 in EMT and metastasis in breast cancer. RGS10 protein levels were significantly lower in breast cancer tissues compared to normal breast tissues, and deficiency in RGS10 protein predicted a worse prognosis in patients with breast cancer. RGS10 protein levels were lower in the highly aggressive cell line MDA-MB-231 than in the poorly aggressive, less invasive cell lines MCF7 and SKBR3. Silencing RGS10 in SKBR3 cells enhanced EMT and caused SKBR3 cell migration and invasion. The ability of RGS10 to suppress EMT and metastasis in breast cancer was dependent on lipocalin-2 and miR-539-5p. These findings identify RGS10 as a tumor suppressor, prognostic biomarker, and potential therapeutic target for breast cancer.

cancer biology↗

bioRxiv2024

Integrated multi-omics analyses reveal the pro-inflammatory and pro-fibrotic pulmonary macrophage subcluster in silicosis

BackgroundSilicosis is a lethal occupational disease caused by long-term exposure to respirable silica dust. Pulmonary macrophages play a crucial role in mediating the initiation of silicosis. However, the phenotypic and functional heterogeneities of pulmonary macrophages in silicosis have not been well-studied. MethodsThe silicosis mouse model was established by intratracheal administration of silica suspension. Bronchoalveolar lavage fluids (BALFs) of mice were collected for the multiplex cytokine analysis. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics were performed to reveal the heterogeneity and spatial localization of macrophages in the lung tissues. The formation of the fibrotic nodules was characterized by histology, hydroxyproline assay, and immunohistochemical staining, respectively. The expression of the pro-inflammatory or pro-fibrotic genes was investigated by quantitative polymerase chain reaction (qPCR). ResultsWe found that the level of pro-inflammatory cytokines and chemokines is significantly increased in the BALFs of silicosis mice. Apparent collagen deposition can also be observed in the silicotic lung tissues. By scRNA-seq, we have identified a subpopulation of Mmp12hi macrophages significantly expanding in the lung tissues of mice with silicosis. Spatial transcriptomics analysis further confirmed that the Mmp12hi macrophages are mainly enriched in silicosis nodules. Pseudotime trajectory showed that these Mmp12hi macrophages, highly expressing both pro-inflammatory and pro-fibrotic genes are derived from Ly6c+ monocytes. Additionally, 4-octyl itaconate (4-OI) treatment, which can alleviate pulmonary fibrosis in silicosis mice, also reduces the enrichment of the Mmp12hi macrophages. Moreover, we found a subset of macrophages in BALFs derived from patients with silicosis exhibited similar characteristics of Mmp12hi macrophages in silicosis mice models. ConclusionsOur study suggested that a group of Mmp12hi macrophages highly express both pro-inflammatory and pro-fibrotic factors in silicosis mice, and thus may contribute to the progression of fibrosis. The findings have proposed new insights for understanding the heterogeneity of lung macrophages in silicosis, suggesting that the subset of Mmp12hi macrophages may be a potential therapy target to further halt the progression of silicosis.

bioinformatics↗

bioRxiv2024

Blockade of TREM2 ameliorates pulmonary inflammation and fibrosis by modulating sphingolipid metabolism

Pulmonary fibrosis is a chronic interstitial lung disease involving systemic inflammation and abnormal collagen deposition. Dysregulations in lipid metabolism, such as macrophage-dependent lipid catabolism, have been recognized as critical factors for the development of pulmonary fibrosis. However, little is known about the signaling pathways involved and the key regulators. Here we found that triggering receptor expressed on myeloid cells 2 (TREM2) plays a pivotal role in regulating the lipid handling capacities of pulmonary macrophages and triggering fibrosis. By integrating analysis of single-cell and bulk RNA sequencing data from patients and mice with pulmonary fibrosis, we revealed that pulmonary macrophages consist of heterogeneous populations with distinct pro-fibrotic properties, and found that both sphingolipid metabolism and the expression of chemotaxis-related genes are elevated in fibrotic lungs. TREM2, a sensor recognizing multiple lipid species, is specifically upregulated in a subset of monocyte- derived macrophages. Blockade of TREM2 by gene knock-out or soluble TREM2 administration can both attenuate bleomycin-induced pulmonary fibrosis. By utilizing scRNA Seq and lipidomics, we found that Trem2 deficiency downregulates the synthesis of various sphingomyelins, and inhibits the expression of chemokines such as Ccl2. Together, our findings not only reveal the alterations in lipidomic profiles and the atlas of pulmonary macrophages during pulmonary fibrosis, but also suggest that targeting TREM2, the crucial regulator affecting both pulmonary sphingolipid metabolism and the chemokines secretion, can benefit pulmonary fibrosis patients in the future.

pharmacology and toxicology↗

bioRxiv2024

Hormetic effect induced by Beauveria bassiana in Myzus persicae

Myzus persicae, a serious sap-sucking pest of a large variety of host plants in agriculture, is traditionally controlled using chemical insecticides but there is interest in using biopesticides as restrictions are increasingly placed on the use of broad-spectrum pesticides. Here we show that in petri dish experiments high concentrations of the fungal entomopathogen Beauveria bassiana (strain PRRI 5336) lead to rapid mortality of M. persicae but at a low concentration (1 x 104 conidia mL-1) there is a hormetic effect where longevity and fecundity are enhanced. Hormetic effects persisted across a generation with reduced development times and increased fecundity in the offspring of M. persicae exposed to B. bassiana. Whole plant experiments point to a hormetic effect being detected in two out of three tested lines. The impact of these effects might also depend on whether M. persicae was transinfected with the endosymbiont Rickettsiella viridis, which decreases fecundity and survival compared to aphids lacking this endosymbiont. This fecundity cost was ameliorated in the generation following exposure to the entomopathogen. While B. bassiana is effective in controlling M. persicae especially at higher spore concentrations, utilization of this entomopathogen requires careful consideration of hormetic effects at lower spore concentrations, and further research to optimize its application for sustainable agriculture is recommended. AUTHOR SUMMARYBiopesticides such as Beauveria bassiana can be effective alternatives to chemical insecticides to control insect pests. We tested the efficacy of this biopesticide against the important agricultural pest aphid Myzus persicae in laboratory experiments. We also tested whether the potential biological control agent and endosymbiont Rickettsiella viridis could provide protection against mortality caused by B. bassiana. While high doses of B. bassiana caused rapid mortality in aphids, low doses enhanced aphid fecundity and survival. This enhancement persisted into the next generation, with shortened development times and increased fecundity regardless, even when high doses were used in the previous generation. The endosymbiont R. viridis did not provide clear protection against B. bassiana, in contrast to previous studies in other aphid species, but beneficial effects at low doses also occurred in this aphid line. We also observed hormesis on experiments on whole plants, but only for some aphid genotypes. To a lesser extent, we also observed beneficial effects of low doses of B. bassiana in experiments on whole plants, but only in some aphid genotypes. Fitness enhancement by biopesticides at low doses raises concerns for field applications but further research is required to understand its underlying mechanisms.

ecology↗

bioRxiv2023

Castration Model Illuminates Sex Differences in Healthy Aging: Insights from Metabolome and Transcriptome Analyses

BackgroundSex, as a critical biological variable, has historically been underappreciated, despite the pervasive influence of sexual dimorphism across physiological and pathological processes. A significant obstacle to advancing sex-biased biological research is the absence of an effective animal model. In recent years, castration has emerged as a potential model for elucidating sex-based differences in the context of healthy aging, where it has been shown to equalize lifespan and growth trajectories in genetically diverse mice. However, the molecular shifts induced by castration in common laboratory models, such as C57BL/6 mice, and the broader applicability of this model to other sex-related biological contexts remain largely unexplored. MethodsWe employed multi-omics and observational analyses to investigate the molecular changes associated with sex and sex hormones following castration. We analyzed serum, kidney, and liver samples from 12-week-old and 18-month-old castrated male C57BL/6 mice, alongside intact male and female counterparts. The castration model was further applied to assess differences in cisplatin-induced toxicity and age-related cognitive decline in comparison to unaltered controls. ResultsLC-MS/MS metabolomics revealed that castrated males exhibited substantial alterations in steroid hormone levels and increased concentrations of antioxidant compounds, such as taurine, despite identical diets. Integrated metabolome-transcriptome analysis confirmed distinct patterns of lipid peroxidation and oxidative stress across sham-operated female, male, and castrated male mice. Histopathological evaluations following cisplatin treatment and aging-related behavioral tests demonstrated the models utility in investigating sex-dependent drug toxicity and cognitive decline. These findings underscored the critical role of sex hormones in modulating both toxicity defense mechanisms and cognitive performance. ConclusionThis study provides a systematic multi-omics spectrum on the castration model and demonstrates its capacity to feminize metabolic and transcriptomic profiles, establishing it as a valuable tool for exploring sex hormone-driven biological differences. Our findings lay the groundwork for further mechanistic studies and broaden the potential applications of the castration model in diverse biomedical research domains.

systems biology↗

bioRxiv2023

Engineered dsRNA-protein nanoparticles for effective long-distance transport, delivery and gene silencing in plants

Long-distance transport of exogenous biologically active RNA molecules in higher plants has not been reported. Here, we report that cationized bovine serum albumin (cBSA) avidly binds double-stranded beta-glucuronidase RNA (dsGUS RNA) to form nucleic acid-protein nanocomplexes. Using tobacco and poplar plants, we have shown effective uptake and long-distance transport of cBSA/dsGUS RNA nanocomplexes from basal ends of leaf petioles to leaf blades as well as from basal ends of shoots to their apexes and apical leaves. We have further demonstrated that the cBSA/dsGUS RNA nanocomplexes are highly effective in silencing both conditionally inducible DR5-GUS gene and constitutively active 35S-GUS gene in leaf, shoot and shoot meristem tissues. This cBSA/dsRNA delivery technology may provide a convenient, fast, and inexpensive tool for characterizing gene functions in plants, and potentially for in planta gene-editing.

molecular biology↗

bioRxiv2023

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues

Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer. However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. PKM2 is known to be upregulated in various cancers, including prostate adenocarcinoma (AdPCa). In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatic analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues, including developing, benign and cancerous prostate. We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in some NEPCa samples. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of PCa specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. These findings lay the groundwork for understanding PKMs role in PCa carcinogenesis and NEPCa progression. The distinct expression pattern of PKM isoforms in different PCa subtypes may offer insights into potential therapeutic strategies for treating PCa.

cancer biology↗

bioRxiv2023

CodonBERT: Large Language Models for mRNA Design and Optimization

AO_SCPLOWBSTRACTC_SCPLOWmRNA based vaccines and therapeutics are gaining popularity and usage across a wide range of conditions. One of the critical issues when designing such mRNAs is sequence optimization. Even small proteins or peptides can be encoded by an enormously large number of mRNAs. The actual mRNA sequence can have a large impact on several properties including expression, stability, immunogenicity, and more. To enable the selection of an optimal sequence, we developed CodonBERT, a large language model (LLM) for mRNAs. Unlike prior models, CodonBERT uses codons as inputs which enables it to learn better representations. CodonBERT was trained using more than 10 million mRNA sequences from a diverse set of organisms. The resulting model captures important biological concepts. CodonBERT can also be extended to perform prediction tasks for various mRNA properties. CodonBERT outperforms previous mRNA prediction methods including on a new flu vaccine dataset.

bioinformatics↗

bioRxiv2023

YiNet: An Integrated Traditional Chinese and Western Medicine Platform for Viral Infectious Diseases

Viral infectious diseases (VIDs) impose a heavy burden on global public health. Traditional Chinese medicine (TCM) has previously and is currently contributing to the prevention and treatment of infectious diseases. Omics and information technology enable the precise identification of virus characteristics, virus-host interactions and TCM mechanisms. In this study, we constructed the YiNet platform to better integrate the novel techniques and historical experience of TCM in infectious diseases. YiNet comprises three modules: knowledge base, database and toolkit. The YiNet knowledge base involves 43 VIDs, thereby systematically integrating the knowledge regarding viruses, host symptoms and TCM and Western medicine (commonly used chemical drugs, 6,899 herbs and 2,481 formulas). The YiNet database module includes multiple databases, comprising 57,340 genome sequences of 45,791 viral strains and 5,726 multi-omics datasets such as RNA-seq, ChIP-seq and ATAC-seq from different tissues and cell models. It also integrates 1,105 real-world TCM clinical cases. We adopted visual analysis tool to investigate pathogen-host-herb relationships. To explore pharmacological mechanisms for the core herbs, we added formula data mining and network pharmacology analysis pipelines and visualisation tools. YiNet can facilitate the mechanistic study of TCM and drug development for VIDs. The YiNet platform is publicly available at http://yinet.gene.ac/.

bioinformatics↗

bioRxiv2023

BAC Transgenic Expression of Human TREM2-R47H Remodels Amyloid Plaques but Unable to Reprogram Plaque-associated Microglial Reactivity in 5xFAD Mice

BackgroundGenetic study of late-onset Alzheimers disease (AD) reveals that a rare Arginine-to-Histamine mutation at amino acid residue 47 (R47H) in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) results in increased disease risk. TREM2 plays critical roles in regulating microglial response to amyloid plaques in AD, leading to their clustering and activation surrounding the plaques. We previously showed that increasing human TREM2 gene dosage exerts neuroprotective effects against AD-related deficits in amyloid depositing mouse models of AD. However, the in vivo effects of the R47H mutation on human TREM2-mediated microglial reprogramming and neuroprotection remains poorly understood. MethodHere we created a BAC transgenic mouse model expressing human TREM2 with the R47H mutation in its cognate genomic context (BAC-TREM2-R47H). Importantly, the BAC used in this study was engineered to delete critical exons of other TREM-like genes on the BAC to prevent confounding effects of overexpressing multiple TREM-like genes. We crossed BAC-TREM2- R47H mice with 5xFAD [1], an amyloid depositing mouse model of AD, to evaluate amyloid pathologies and microglial phenotypes, transcriptomics and in situ expression of key TREM2-dosage dependent genes. We also compared the key findings in 5xFAD/BAC-TREM2-R47H to those observed in 5xFAD/BAC-TREM2 mice. ResultBoth BAC-TREM2 and BAC-TREM2-R47H showed proper expression of three splicing isoforms of TREM2 that are normally found in human. In 5xFAD background, elevated TREM2-R47H gene dosages significantly reduced the plaque burden, especially the filamentous type. The results were consistent with enhanced phagocytosis and altered NLRP3 inflammasome activation in BAC- TREM2-R47H microglia in vitro. However, unlike TREM2 overexpression, elevated TREM2- R47H in 5xFAD failed to ameliorate cognitive and transcriptomic deficits. In situ analysis of key TREM2-dosage dependent genes and microglial morphology uncovered that TREM2-R47H showed a loss-of-function phenotype in reprogramming of plaque-associated microglial reactivity and gene expression in 5xFAD. ConclusionOur study demonstrated that the AD-risk variant has a previously unknown, mixture of partial and full loss of TREM2 functions in modulating microglial response in AD mouse brains. Together, our new BAC-TREM2-R47H model and prior BAC-TREM2 mice are invaluable resource to facilitate the therapeutic discovery that target human TREM2 and its R47H variant to ameliorate AD and other neurodegenerative disorders.

neuroscience↗

bioRxiv2023

Testis morphogenesis and fetal Leydig cell development are mediated through ERK signaling activated by platelet derived growth factor receptor alpha

Platelet derived growth factor receptor alpha (Pdgfra) plays a crucial role in the morphogenesis and differentiation of the fetal testis, but the molecular signaling involved in these processes remains unclear. Here, we use XY Pdgfra-null knock-in (KI) gonads to investigate the molecular mechanisms underlying Pdgfra-mediated testis cord formation and development of fetal Leydig cells (FLCs). The extracellular signal-regulated kinase (ERK) pathway, a well-known mitogen-activated protein kinase signaling pathway, was significantly inhibited in XY Pdgfra KI gonads, suggesting that ERK signaling is activated downstream of PDGFRA. Using ex vivo whole-organ culture, small interfering RNA (siRNA) cell culture methods, transwell assays and a genetic mouse model to disrupt ERK signaling in gonadal cells, we found that the ERK pathway promoted testis cord formation via early growth response 1 (Egr1)-mediated cell migration and regulated the expression of steroidogenic enzymes in FLCs via activating the transcription factor cAMP responsive element binding protein 1 (CREB; official name CREB1). These findings highlight the significance of PDGFRA and its downstream signaling in fetal testis morphogenesis and cellular differentiation, thus providing insights into the etiology of and potential therapeutic targets for disorders related to gonadal development.

developmental biology↗

bioRxiv2023

The Prolonged Terminal Phase of Human Life Induces Survival Response in the Skin Transcriptome

Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life. As such organismal death process unfolds, do cells of the human body adapt for postmortem cellular survival? Organs with low energy cost-of-living, such as the skin, are better suited for postmortem cellular survival. In this work, the effect of different durations of terminal phase of human life on postmortem changes in cellular gene expression was investigated using RNA sequencing data of 701 human skin samples from the Genotype-Tissue Expression (GTEx) database. Longer terminal phase (slow-death) was associated with a more robust induction of survival pathways (PI3K-Akt signaling) in postmortem skin. Such cellular survival response was associated with the upregulation of embryonic developmental transcription factors such as FOXO1, FOXO3, ATF4 and CEBPD. Upregulation of PI3K-Akt signaling was independent of sex or duration of death-related tissue ischemia. Analysis of single nucleus RNA-seq of post-mortem skin tissue specifically identified the dermal fibroblast compartment to be most resilient as marked by adaptive induction of PI3K-Akt signaling. In addition, slow death also induced angiogenic pathways in the dermal endothelial cell compartment of postmortem human skin. In contrast, specific pathways supporting functional properties of the skin as an organ were downregulated following slow death. Such pathways included melanogenesis and those representing the skin extracellular matrix (collagen expression and metabolism). Efforts to understand the significance of death as a biological variable (DABV) in influencing the transcriptomic composition of surviving component tissues has far-reaching implications including rigorous interpretation of experimental data collected from the dead and mechanisms involved in transplant-tissue obtained from dead donors.

genomics↗

bioRxiv2023

A generalizable computational mechanism underlying the interaction between momentary craving and decision-making

Substance craving and maladaptive choices are intertwined across addictive disorders. However, the computational mechanisms connecting craving and decision-making remain elusive. Here, we tested a hypothesis that momentary craving and value-based decision-making influence each other during substance-related reinforcement learning. We measured momentary craving as two groups of human participants (alcohol drinkers and cannabis users; total n=132) performed a reinforcement learning task in which they received group-specific addictive cue or monetary rewards. Using computational modeling, we found that, across both groups, momentary craving biased learning rate related to substance-associated prediction errors (RPEs), but not monetary RPEs. Additionally, expected values and RPEs jointly influenced elicited craving across reward types and participant groups. Alcohol and cannabis users also differed in the extent to which their craving and decision-making influenced each other, suggesting important computational divergence between the two groups. Finally, regressions incorporating model-derived parameters best predicted substance use severity in the alcohol, but not cannabis group, supporting the utility of using these model-based parameters in making clinical predictions for selective substance groups. Together, these findings provide a computational mechanism for the interaction between substance craving and maladaptive choices that is generalizable across addictive domains.

neuroscience↗

bioRxiv2023

Stromal netrin-1 coordinates renal arteriogenesis and mural cell differentiation

The kidney vasculature has a uniquely complex architecture that is essential to proper renal function. Little is known about the molecular mechanisms that direct where and when blood vessels form during kidney development. We identified a regionally-restricted, stroma-derived signaling molecule, netrin-1 (Ntn1), as a putative regulator of vascular patterning. We generated a stromal progenitor-specific knockout of netrin-1 (Ntn1SPKO) that resulted in smaller postnatal kidneys with altered epithelial development and profound defects in arterial and capillary architecture. We also found significant loss of arterial vascular smooth muscle cell (vSMC) coverage and ectopic smooth muscle cell deposition at the kidney cortex. Transcriptomic analysis of Ntn1SPKO kidneys revealed downregulation of Klf4, which we find expressed in stromal progenitors. Deletion of Klf4 in the stroma largely phenocopies loss of Ntn1, and expression of Klf4 in Ntn1SPKO kidneys rescues ectopic vSMC deposition. Vascular defects observed in Ntn1SPKO are transient, as both arterial and smooth muscle coverage defects resolve late in development, however ectopic peripheral smooth muscle perdures perinatally. These data suggest a stromal-intrinsic Ntn1-Klf4 axis acting as an essential mediator of stromal crosstalk and vascular progenitor differentiation.

developmental biology↗

bioRxiv2023

Uncovering the Hidden Gems of Psoriasis Literature: An Neural Language Model-Assisted Interactive Web Tool

BACKGROUNDThe comprehensive data on psoriasis research are numerous and complex, making it difficult to retrieve and classify manually. The ability to quickly mine literature based on various fine topics using deep learning natural language processing technology to assess research topics and trends in the field of psoriasis disease will have a significant impact on doctors research and patients health education METHODA neural topic model is used to identify fine topics of psoriasis literature published in the PubMed database from 2000 to 2021. Dermatologists evaluate the algorithm-modeled topics, summarize the categories into the most effective topics, and perform linear trend model analysis. The accurate classified topics are presented on an interactive web page to identify research hotspots and trends. RESULTSAt the categorical level, after review by clinicians, 158 out of 160 generated topics were found effective and categorized into 8 groups: Therapeutic methods (34.34%), pathological mechanisms (23.46%), comorbidity (20.04%), Clinical manifestations and differential diagnosis (12.77%), experimental modalities and methods (3.22%), diagnostic tools (2.99%), epidemiology (1.75%), and meetings/guidelines (1.43%). A linear regression model had good accuracy (MSE=0.252602, SSE=42.1845) and strong correlation (R-Squared=0.898009). ANOVA results showed that categories significantly impacted the model (p<=0.05), with experimental modalities and methods having the strongest relationship with year, and clinical manifestations and differential diagnosis having the weakest. An interactive web tool (https://psknlr.github.io) facilitates quick retrieval of titles, journals, and abstracts in different categories, as well as browsing literature information under specific topics and accessing corresponding article pages for professional knowledge on psoriasis. CONCLUSIONSThe neural topic model and interactive web tool can effectively identify the research hotspots and trends in psoriasis literature, assisting clinicians and patients in retrieving and comparing pertinent topics and research accomplishments of various years.

bioinformatics↗

bioRxiv2023

Integrated Cell Landscape and Dynamics in the Progression of Bone Repair

Bone homeostasis and repair is a systematic progress with spatiotemporal interaction of multiple cell types involved in skeletal and immune system. Precise spatiotemporal regulation of cell type-specific functions in bone repair contributes to further development of tissue engineering and regenerative medicine. Here, we utilized single-cell RNA sequencing to illustrate a map of cell landscape and dynamics in the progression of rodent bone self-healing and a perturbation by lymphoid cell-deficiency. We identified different functions of myeloid cell and lymphoid cell to osteogenesis and angiogenesis during bone repair and their mutual complementation under lymphoid cell-deficient condition. Additionally, we used CD34+ humanized reconstituted mice to reveal further insights into the mechanism of human bone homeostasis and repair. Our integrated cellular analysis of bone repair explores the functional diversity and complementation between myeloid cells and lymphoid cells during bone healing process and provides further therapeutic implications for the treatment of bone disease and degeneration following ageing.

cell biology↗

bioRxiv2023

Spanve: an Effective Statistical Method to Detect Spatially Variable Genes in Large-scale Spatial Transcriptomics Data

Depicting gene expression in a spatial context through spatial transcriptomics would be beneficial for inferring cell function mechanisms. The identification of spatially variable genes is a crucial step in leveraging the spatial transcriptome to understand intricate spatial dynamics. In this study, we developed Spanve, a nonparametric statistical method for detecting spatially variable genes in large-scale ST data by quantifying expression differences between spots and their spatial neighbours. This method offers a nonparametric approach to identifying spatial dependencies in gene expression without assuming specific distributions. Compared to traditional methods, Spanve decreases the number of false-positive outcomes, leading to more accurate identification of spatially variable genes. Furthermore, Spanve could facilitate downstream spatial transcriptomics analyses, including spatial domain detection and cell type deconvolution. These results show the broad applications of Spanve in advancing our understanding of spatial gene expression patterns within complex tissue microenvironments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/527623v3_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@1574cfcorg.highwire.dtl.DTLVardef@7f3f56org.highwire.dtl.DTLVardef@1732a3org.highwire.dtl.DTLVardef@fdaafa_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗