Biology subjects

Xu, T.

Publications and source records attributed to Xu, T..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

VRN2-PRC2 facilitates light-triggered repression of PIF signalling to coordinate growth in Arabidopsis

The polycomb protein VERNALIZATION2 (VRN2) is a plant-specific subunit of the polycomb repressive complex 2 (PRC2), a conserved eukaryotic holoenzyme that represses gene expression by depositing the histone H3K27me3 mark in chromatin. Previous work established VRN2 as an oxygen-regulated target of the N-degron pathway that may function as a sensor subunit connecting PRC2 activity to the perception of positional and environmental cues. Here we show that VRN2 is enriched in hypoxic meristematic regions and emerging leaves of Arabidopsis under non-stressed conditions, and that vrn2 mutants are larger than wild type, indicating that VRN2-PRC2 negatively regulates growth and development. This growth phenotype is caused by ectopic expression of genes that promote cell expansion, including many SAUR genes and other direct PIF transcription factor targets. Analysis of SAUR19 promoter activity and expression dynamics revealed that VRN2 is required to specifically repress these genes in the light. Moreover, we show that VRN2 is epistatic to PIF4, and directly binds and methylates histones of key loci in the PIF4 transcriptional network to provide robust light-responsive control of gene expression and growth. We propose that hypoxia-stabilised VRN2-PRC2 sets a conditionally repressed chromatin state at PIF-regulated hub genes early in leaf ontogeny coinciding with the cell division phase, and that this is required for enhancing their subsequent repression via a light-responsive signalling cascade as cells enter the expansion phase. Thus, we have identified VRN2-PRC2 as core component of a spatially regulated and developmentally encoded epigenetic mechanism that co-ordinates environment-responsive growth by facilitating light-triggered suppression of PIF signalling.

plant biology↗

bioRxiv2024

Single Cell Analysis of Treatment-Resistant Prostate Cancer: Implications of Cell State Changes for Cell Surface Antigen Targeted Therapies

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)--a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis (TMA) on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated, but also found that the expression of molecules targeted therapeutically, namely PSMA, STEAP1, STEAP2, TROP2, CEACAM5, and DLL3, varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer (SCLC) subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to novel antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types. SIGNIFICANCE STATEMENTTreatment of prostate cancer is rapidly evolving with several promising new drugs targeting different cell surface antigens. Selection of patients most likely to benefit from these therapies requires an understanding of how expression of these cell surface antigens varies across patients and how they change during disease progression, particularly in tumors that undergo lineage plasticity. Using immunohistochemistry and single cell mRNA sequencing, we reveal heterogeneity of cell states across a cohort of advanced disease prostate cancer patients; this heterogeneity is not captured by conventional histology-based designations of adenocarcinoma and neuroendocrine prostate cancer. We show these cell states can be identified by gene regulatory networks that could provide additional diagnostic precision based on their correlation with clinically relevant cell surface antigen expression.

cancer biology↗

bioRxiv2024

TopDIA: A Software Tool for Top-Down Data-Independent Acquisition Proteomics

Top-down mass spectrometry is widely used for proteoform identification, characterization, and quantification owing to its ability to analyze intact proteoforms. In the last decade, top-down proteomics has been dominated by top-down data-dependent acquisition mass spectrometry (TD-DDA-MS), and top-down data-independent acquisition mass spectrometry (TD-DIA-MS) has not been well studied. While TD-DIA-MS produces complex multiplexed tandem mass spectrometry (MS/MS) spectra, which are challenging to confidently identify, it selects more precursor ions for MS/MS analysis and has the potential to increase proteoform identifications compared with TD-DDA-MS. Here we present TopDIA, the first software tool for proteoform identification by TD-DIA-MS. It generates demultiplexed pseudo MS/MS spectra from TD-DIA-MS data and then searches the pseudo MS/MS spectra against a protein sequence database for proteoform identification. We compared the performance of TD-DDA-MS and TD-DIA-MS using Escherichia coli K-12 MG1655 cells and demonstrated that TD-DIA-MS with TopDIA increased proteoform and protein identifications compared with TD-DDA-MS.

bioinformatics↗

bioRxiv2024

Rapid High-Throughput Isolation and purification of Chicken Myoblasts Based on Deterministic Lateral Displacement Microfluidic Chips

Myoblasts are defined as stem cells containing skeletal muscle cell precursors. However, there are some challenges associated with the purification of myoblast samples, including long culture times and ease of bacterial contamination. In this study, we propose a microfluidic myoblast cell enrichment and purification platform based on the principle of deterministic lateral displacement (DLD). To achieve this, we designed a DLD chip with three outlets and tested it on 11-day-old Wenchang chicken pectoral muscle tissue. A cell suspension was prepared using the collagenase method, pretreated, and then passed into the designed DLD chip for myoblast enrichment and purification. In this study, the number of myoblasts and the diameter of myoblasts increased slowly before E9, and the diameter of myofibers decreased and the number of myofibers increased rapidly after E9. The period when the number of muscle fibers is highest is E12, and the period when the diameter of muscle fibers increases again after the lowest point is also E12. After E12, the diameter of the muscle fibers increased and the number of muscle fibers decreased. At E12, myoblasts clustered and fused, and the proliferation of myoblasts was greatly reduced. E12 is both intact myoblasts and the most vigorous proliferation period, so the best time to determine isolation is E12. We attained a myoblast cell recovery rate of 80%, a target outlet collection purity of 99%, and a chip throughput of 50 m/min. This study provides a novel and effective method for the isolation and purification of skeletal muscle myoblasts.

cell biology↗

bioRxiv2024

A shifting role of thalamocortical connectivity in the emergence of large-scale functional brain organization across early lifespan development

While cortical patterning has been a perennial research topic in neuroscience, the mechanism for its consequence, namely functional specialization at the macro scale, remains an open question in the human brain. Here, we focused on age-dependent changes of resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks across infancy, childhood and young adulthood. We found that the thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically-influenced axonal projection. This initial role of the thalamus, however, seems to change during childhood, by establishing connectivity with the salience network and decoupling externally- and internally-oriented functional processes. Developmental simulation and perturbation analyses corroborated these findings, demonstrating the highest contribution of thalamic connectivity, especially in the later age of youth, in the formation of key characteristics of the mature brain, such as functional gradient and cortical hierarchy. Our study highlights a developmentally shifting role of the thalamus in orchestrating complex brain organization and its potential implications for developmental conditions characterized by compromised internal and external processing.

neuroscience↗

bioRxiv2024

Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives using fecal metagenomics and metabolomics

Prior studies indicate no correlation between gut microbiota of healthy first-degree relatives (HFDRs) of Crohns disease (CD) patients and development of CD. Here, we utilized HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. Compared to non-relative controls, the use of HFDR controls identified fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter showed decreased abundances in CD-R, independent of inflammation, and correlated with fecal SCFAs. Validation with a large multi-center cohort confirmed decreased abundances in Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguished CD-R and CD-A from healthy individuals, in both the discovery and validation cohorts. Thus, the decreased presence of Faecalibacterium, Dorea, and Fusicatenibacter in CD-R likely contributed to disease relapse through reduced SCFA production, highlighting their potential as diagnostic markers and therapeutic targets for CD.

pathology↗

bioRxiv2024

Environmental and Historical Determinants of African Horse Sickness: Insights from Predictive Modeling

This study marks a pioneering effort in analyzing the global epidemiological patterns of African Horse Sickness (AHS) across different regions. By employing predictive modeling with a comprehensive set of environmental variables, we uncovered overarching global patterns in AHS dynamics, a first in this field. Our analysis revealed significant regional differences influenced by specific climatic conditions, highlighting the diseases complexity. The study also identifies new high-risk areas for AHS, underscoring the necessity for regionally tailored disease management strategies. Despite some limitations, such as the exclusion of wild equine data, this research offers critical insights for global AHS intervention and prevention, setting a path for future research incorporating broader datasets and socio-economic factors. Author SummaryAHS presents a significant challenge to the global equine industry, impacting both health and economic aspects. Our study highlights the profound effect of climate change, particularly the frequency of extreme climatic events including temperature and humidity variations, on the transmission dynamics of diseases like AHS. In our research, we focused on overcoming the challenges associated with identifying key environmental factors and determining the appropriate geographic scale for a comprehensive global understanding of AHS. Our aim was to bridge existing knowledge gaps and elucidate the fundamental principles governing AHS transmission. This study establishes a solid foundation for understanding the intricate dynamics of AHS and offers practical pathways for conservation efforts. It emphasizes the urgent need for environmentally conscious strategies to protect horse populations and the industries dependent on them. By highlighting the relationship between environmental factors, vector presence, and AHS transmission, our research underscores the importance of a holistic approach to disease mitigation. In conclusion, the findings of our study not only contribute to the scientific understanding of AHS but also serve as a guide for policymakers and practitioners in developing effective strategies for disease management and prevention, tailored to the specific environmental conditions and challenges faced in different regions around the world.

ecology↗

bioRxiv2024

ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 11 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brains mechanisms of language processing within the context of the Chinese natural language.

neuroscience↗

bioRxiv2024

A self-adaptive and versatile tool for eliminating multiple undesirable variations from transcriptome

Accurate identification of true biological signals from diverse undesirable variations in large-scale transcriptomes is essential for downstream discoveries. Herein, we develop a universal deep neural network, called DeepAdapter, to eliminate various undesirable variations from transcriptomic data. The innovation of our approach lies in automatic learning of the corresponding denoising strategies to adapt to different situations. The data-driven strategies are flexible and highly attuned to the transcriptomic data that requires denoising, yielding significant improvement in reducing undesirable variation originating from batches, sequencing platforms, and bio-samples with varied purity beyond manually designed schemes. Comprehensive evaluations across multiple batches, different RNA measurement technologies and heterogeneous bio-samples demonstrate that DeepAdapter can robustly correct diverse undesirable variations and accurately preserve biological signals. Our findings indicate that DeepAdapter can act as a versatile tool for the comprehensive denoising of the large and heterogeneous transcriptome across a wide variety of application scenarios.

bioinformatics↗

bioRxiv2024

Fast and accurate modeling and design of antibody-antigen complex using tFold

Accurate prediction of antibody-antigen complex structures holds significant potential for advancing biomedical research and the design of therapeutic antibodies. Currently, structure prediction for protein monomers has achieved considerable success, and promising progress has been made in extending this achievement to the prediction of protein complexes. However, despite these advancements, fast and accurate prediction of antibody-antigen complex structures remains a challenging and unresolved issue. Existing end-to-end prediction methods, which rely on homology and templates, exhibit sub-optimal accuracy due to the absence of co-evolutionary constraints. Meanwhile, conventional docking-based methods face difficulties in identifying the contact interface between the antigen and antibody and require known structures of individual components as inputs. In this study, we present a fully end-to-end approach for three-dimensional (3D) atomic-level structure predictions of antibodies and antibody-antigen complexes, referred to as tFold-Ab and tFold-Ag, respectively. tFold leverages a large protein language model to extract both intra-chain and inter-chain residue-residue contact information, as well as evolutionary relationships, avoiding the time-consuming multiple sequence alignment (MSA) search. Combined with specially designed modules such as the AI-driven flexible docking module, it achieves superior performance and significantly enhanced speed in predicting both antibody (1.6% RMSD reduction in the CDR-H3 region, thousand times faster) and antibody-antigen complex structures (37% increase in DockQ score, over 10 times faster), compared to AlphaFold-Multimer. Given the performance and speed advantages, we further extend the capability of tFold for structure-based virtual screening of binding antibodies, as well as de novo co-design of both structure and sequence for therapeutic antibodies. The experiment results demonstrate the potential of tFold as a high-throughput tool to enhance processes involved in these tasks. To facilitate public access, we release code and offer a web service for antibody and antigen-antibody complex structure prediction, which is available at https://drug.ai.tencent.com/en.

bioinformatics↗

bioRxiv2024

Mapping patterns of thought onto brain activity during movie-watching

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the here and now depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching. Our study established a novel method for mapping thought patterns onto the brain activity that occurs at different moments of a film, which does not disrupt the time course of brain activity or the movie-watching experience. We found moments when experience sampling highlighted engagement with multi-sensory features of the film or highlighted thoughts with episodic features, regions of sensory cortex were more active and subsequent memory for events in the movie was better--on the other hand, periods of intrusive distraction emerged when activity in regions of association cortex within the frontoparietal system was reduced. These results highlight the critical role sensory systems play in the multi- modal experience of movie-watching and provide evidence for the role of association cortex in reducing distraction when we watch films. Significance statementStates like movie-watching provide a window into the brain mechanisms behind cognition in daily life. However, we know relatively little about the mapping between brain activity during movies and associated thought patterns because of difficulties in measuring cognition without disrupting how brain activity naturally unfolds. We establish a novel method to link different experiential states to brain activity during movie-watching with minimal interruptions to viewers or disruptions to brain dynamics. We found states of sensory engagement occur in moments of films when activity in visual and auditory cortex are high. In contrast, states of distraction are reduced when activity in frontoparietal regions is high. Our study, therefore, establishes both sensory and association cortex as core features of the movie-watching experience.

neuroscience↗

bioRxiv2024

Characterization of RNA editing profiles in rice endosperm development

Rice (Oryza sativa L.) endosperm provides nutrients for seed germination and determines grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we conduct genome re-sequencing and RNA sequencing for rice endosperms across five successive developmental stages and perform systematic analyses to characterize RNA editing profiles during rice endosperm development. We find that the majority of their editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids, and affecting structures and functions of mitochondrial proteins. Comparative analysis of RNA editing profiles across the five developmental stages reveals that CDS-recoding sites present higher editing frequencies with lower variabilities, and recoded amino acids, particularly caused by these sites with higher editing frequencies, tend to exhibit stronger evolutionary conservation across many land plants. Based on these results, we further classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites. Besides, we identify a series of P- and PLS-class pentatricopeptide repeat (PPR) proteins with editing potential and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery. Author summaryRice endosperm development, a critical process determining quality and yield of our mankinds essential food, is regulated by RNA editing that provokes RNA base alterations by protein factors. However, our understanding of this regulation is incomplete. Hence, we systematically characterize RNA editing profiles during rice endosperm development. We find that editing sites resulting in amino acid changes, called "CDS-recoding", predominate in mitochondria, leading to increased hydrophobic amino acids and affecting structures and functions of proteins. Comparative analysis of RNA editing profiles during rice endosperm development reveals that CDS-recoding sites present higher editing frequencies with lower variabilities. Furthermore, evolutionary conservation of recoded amino acids caused by these CDS-recoding sites is positively correlated with editing frequency across many land plants. We classify mitochondrial genes into three groups that present distinct patterns in terms of editing frequency and variability of CDS-recoding sites, indicating different effects of these genes on rice endosperm development. In addition, we identify candidate protein factors associated closely with RNA editing regulation. To sum up, our findings provide valuable insights for fully understanding the role of RNA editing during rice endosperm development.

bioinformatics↗

bioRxiv2024

An arms race under RIG-I loss: 5'ppp-RNA and its alternative recognition receptor MDA5

The incessant arms race between viruses and hosts has led to numerous evolutionary innovations that shape lifes evolution. During this process, the interactions between viral receptors and viruses have garnered significant interest since viral receptors are cell surface proteins exploited by viruses to initiate infection. Our study sheds light on the arms race between the MDA5 receptor and 5ppp-RNA virus in a lower vertebrate fish, M. miiuy. Firstly, the frequent and independent loss events of RIG-I in vertebrates prompted us to search for alternative immune substitutes, with homology-dependent genetic compensation response (HDGCR) being the main pathway. Our further analysis suggested that MDA5 of M. miiuy and G. gallus, the homolog of RIG-I, can replace RIG-I in recognizing 5ppp-RNA virus, which may lead to redundancy of RIG-I and loss from the species genome during evolution. Secondly, as an adversarial strategy, 5ppp-RNA SCRV can utilize the m6A methylation mechanism to degrade MDA5 and weaken its antiviral immune ability, thus promoting its own replication and immune evasion. In summary, our study provides a snapshot into the interaction and coevolution between vertebrate and virus, offering valuable perspectives on the ecological and evolutionary factors that contribute to the diversity of the immune system.

immunology↗

bioRxiv2023

Systematic cross-species comparison of prefrontal cortex functional networks targeted via Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation method that safely modulates neural activity in vivo. Its precision in targeting specific brain networks makes TMS invaluable in diverse clinical applications. For example, TMS is used to treat depression by targeting prefrontal brain networks and their connection to other brain regions. However, despite its widespread use, the underlying neural mechanisms of TMS are not completely understood. Non-human primates (NHPs) offer an ideal model to study TMS mechanisms through invasive electrophysiological recordings. As such, bridging the gap between NHP experiments and human applications is imperative to ensure translational relevance. Here, we systematically compare the TMS-targeted functional networks in the prefrontal cortex in humans and NHPs. To conduct this comparison, we combine TMS electric field modeling in humans and macaques with resting-state functional magnetic resonance imaging (fMRI) data to compare the functional networks targeted via TMS across species. We identified distinct stimulation zones in macaque and human models, each exhibiting variations in the impacted networks (macaque: Frontoparietal Network, Somatomotor Network; human: Frontoparietal Network, Default Network). We identified differences in brain gyrification and functional organization across species as the underlying cause of found network differences. The TMS-network profiles we identified will allow researchers to establish consistency in network activation across species, aiding in the translational efforts to develop improved TMS functional network targeting approaches.

neuroscience↗

bioRxiv2023

Arterial mechanics, extracellular matrix, and smooth muscle differentiation in carotid arteries deficient for Rac1

Stiffening of the extracellular matrix (ECM) occurs after vascular injury and contributes to the injury-associated proliferation of vascular smooth muscle cells (SMCs). ECM stiffness also activates Rac-GTP, and SMC Rac1 deletion strongly reduces the proliferative response to injury in vivo. However, ECM stiffening and Rac can affect SMC differentiation, which, in itself, can influence ECM stiffness and proliferation. Here, we used pressure myography and immunofluorescence analysis of mouse carotid arteries to ask if the reported effect of Rac1 deletion on in vivo SMC proliferation might be secondary to a Rac effect on basal arterial stiffness or SMC differentiation. The results show that Rac1 deletion does not affect the abundance of arterial collagen-I, -III, or -V, the integrity of arterial elastin, or the arterial responses to pressure, including the axial and circumferential stretch-strain relationships that are assessments of arterial stiffness. Medial abundance of alpha-smooth muscle actin and smooth muscle-myosin heavy chain, markers of the SMC differentiated phenotype, were not statistically different in carotid arteries containing or deficient in Rac1. Nor did Rac1 deficiency have a statistically significant effect on carotid artery contraction to KCl. Overall, these data argue that the inhibitory effect of Rac1 deletion on in vivo SMC proliferation reflects a primary effect of Rac1 signaling to the cell cycle rather than a secondary effect associated with altered SMC differentiation or arterial stiffness.

cell biology↗

bioRxiv2023

Dissecting Multiparametric Cerebral Hemodynamics using Integrated Ultrafast Ultrasound and Multispectral Photoacoustic Imaging

Understanding brain-wide hemodynamic responses to different stimuli at high spatiotemporal resolutions can help study neuro-disorders and brain functions. However, the existing brain imaging technologies have limited resolution, sensitivity, imaging depth and provide information about only one or two hemodynamic parameters. To address this, we propose a multimodal functional ultrasound and photoacoustic (fUSPA) imaging platform, which integrates ultrafast ultrasound and multispectral photoacoustic imaging methods in a compact head-mountable device, to quantitatively map cerebral blood volume (CBV), cerebral blood flow (CBF), oxygen saturation (SO2) dynamics as well as contrast agent enhanced brain imaging with high spatiotemporal resolutions. After systematic characterization, the fUSPA system was applied to quantitatively study the changes in brain hemodynamics and vascular reactivity at single vessel resolution in response to hypercapnia stimulation. Our results show an overall increase in brain-wide CBV, CBF, and SO2, but regional differences in singular cortical veins and arteries and a reproducible anti-correlation pattern between venous and cortical hemodynamics, demonstrating the capabilities of the fUSPA system for providing multiparametric cerebrovascular information at high-resolution and sensitivity, that can bring insights into the complex mechanisms of neurodiseases.

bioengineering↗

bioRxiv2023

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↗

bioRxiv2023

Akkermansia muciniphila identified as key strain to function in pathogen invasion and intestinal stem cell proliferation through Wnt signaling pathway

As the largest mucosal surface, the gut has built a physical, chemical, microbial and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) model infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/{beta}-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We therefore identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila was reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in AIMD model. A. muciniphila was identified as key strain in FMT to promote proliferation and differentiation of intestinal stem cells by mediating the Wnt/{beta}-catenin signaling pathway.

microbiology↗