Biology subjects

Sun, F.

Publications and source records attributed to Sun, F..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Basophils activate splenic B cells and Dendritic cells via IL-13 signaling in acute Traumatic Brain Injury

Peripheral consequences following traumatic brain injury (TBI) are characterized by both systemic inflammatory responses and autonomic dysregulation, with almost all peripheral organs affected. One of the main immune regulatory organs, the spleen, shows high interaction with the brain which is controlled by both circulating mediators as well as autonomic fibers targeting splenic immune cells. The brain-spleen axis does not function as a one-way street, it also shows reciprocal effects where the spleen affects neuroinflammatory and cognitive functions post injury. To date, systemic and splenic inflammatory responses are measured by cells or mediators located in circulation. Nevertheless, most of the signaling and inflammation post injury takes place in the organs. Therefore, we set out to investigate the early signaling landscape in the spleen following TBI, using phospho-proteomic signaling approaches and immunofluorescence stainings to investigate novel molecular and cellular players. Based on the signaling signature, we found a rapid influx of basophil granulocytes towards the spleen, which are recruited via CXCL1 expressed by B-cells and dendritic cells. The basophils activate B cells and dendritic cells (DCs) via the IL-13/IL-13Ra1 signaling pathway to enhance protein translation through the long non-coding RNA NORAD. The early recruitment of basophils and subsequent activation of B cells and DCs, is short lived and sets at 3dpi. Interestingly, the rapid recruitment of basophils is inhibited by ethanol intoxication in TBI. In conclusion, basophils recruitment to the spleen may serve as an early mediator of systemic inflammatory responses to TBI with potential implications for research on biomarkers and therapeutic targets.

neuroscience↗

bioRxiv2025

EGFR activation correlates with intracranial pressure and outcome in a mixed intracranial bleeding porcine model

Intracranial hypertension is a major driver of secondary injury after acute subdural hematoma (ASDH), yet how mechanical stress is translated into neuroinflammatory signaling remains poorly understood. Here, we identify a mechanosensitive astrocyte signaling pathway that links elevated intracranial pressure (ICP) to inflammatory amplification in the injured brain. Using a clinically relevant porcine ASDH model combined with mechanistic studies in human iPSC-derived astrocytes, we demonstrate that sustained ICP elevation induces bilateral neuroinflammation together with coordinated upregulation of mechanosensitive ion channels and receptor tyrosine kinase (RTK) pathways. Integrative analysis of molecular and physiological datasets identified astrocytes as the principal cellular responders to ICP and revealed epidermal growth factor receptor (EGFR) as the astrocyte-associated RTK most strongly correlated with ICP dynamics, inflammatory chemokine expression, and survival. Pharmacological activation of the mechanosensitive channel Piezo1 in human astrocytes was sufficient to trigger EGFR internalization, site-specific phosphorylation, and ERK signaling, promoting structural remodeling and robust induction of pro-inflammatory mediators including CCL2, IL-6, and IL-8. Conversely, EGFR inhibition attenuated inflammatory signaling while enhancing astrocytic programs associated with water handling and edema containment. In vivo, increased expression of EGFR ligands together with elevated EGFR phosphorylation supported sustained pathway engagement following ASDH, and correlation analyses linked Piezo1 expression and EGFR activation with ICP severity and adverse outcome. Together, these findings define a mechanotransduction axis in which astrocytic Piezo1 signaling integrates mechanical stress with EGFR-dependent neuroimmune responses, positioning EGFR as a translationally accessible target to modulate inflammation-driven secondary brain injury.

neuroscience↗

bioRxiv2025

Phase separation of Polycomb-like (PCL) proteins drive PRC2 complex condensates to regulate gene expression

Polycomb group (PcG) proteins function as two major multicomponent protein complexes: Polycomb repressive complex 1 (PRC1) and 2 (PRC2) to repress key developmental genes and maintain epigenetic memory of cell identity during development. Phase-separation has long been implicated in PRC1 mediated gene silencing, but it is still unclear whether PRC2 also utilize a similar mechanism to regulate gene expression. Here we report that Polycomb-like (PCL) proteins, PRC2 accessory factors, can phase-separate in vitro and generate dynamic puncta in vivo. Biochemical and cellular analyses reveal that PCL proteins (hereafter referred to as PCLs) have intramolecular interaction between N- and C-terminal domains, which make PCLs into more compact conformations. The intramolecular interaction not only controls the size of the PCLs phase separation droplets, but also affects the chromatin association of PRC2. Finally, we show that CpG islands, key DNA regulatory elements in mammalian promoters, disrupt the N-C intramolecular interaction of PCLs to expose their middle intrinsically disordered regions (IDRs), which in turn trigger PCLs driven PRC2 condensates formation. Together, this study provides a new perspective on the regulation of PRC2 by PCLs, implicating PCLs read CpG islands to fine-tune their oligomerization to overcome the threshold for PRC2 recruitment to corresponding genomic loci via multivalent interaction with CpG islands chromatin.

biochemistry↗

bioRxiv2025

Essential role of CFAP77-CCDC105-TEX43 subcomplex in connecting axonemal A and B tubules for mammalian sperm motility

The assembly and physiological function of cilia and flagella depend on the stable association of A and B tubules, which form axonemal microtubule doublets (DMTs). CFAP77 encodes a core outer junction (OJ) protein within DMTs that is conserved across species and cell types. However, whether and how CFAP77 mediates the connection of B tubules to A tubules of DMTs in mammalian cilia/flagella are unknown. In this study, Cfap77-KO mice were generated to reveal that CFAP77 is essential for sperm progressive motility and male fertility. Loss of CFAP77 led to opened B tubules specifically at the OJ regions of axonemal DMTs as revealed by conventional transmission electron microscopy. Cryo-electron tomography further resolved the in situ structure of sperm axonemal DMTs from Cfap77-KO mice, which exhibited a loss of large filamentous density corresponding to the CFAP77-CCDC105-TEX43 ternary subcomplex at the OJ regions. Additionally, sperm proteomic analysis confirmed that CFAP77 knockout led to the complete loss of this ternary complex. Our work not only explores the physiological role of OJ protein CFAP77 on axonemal A-B tubule connection in mammals but also combines in situ structural biology and knockout mice to reveal the underlying structural/molecular mechanism.

cell biology↗

bioRxiv2025

Diammonium glycyrrhizinate injection promotes zebrafish angiogenesis through the mTOR/HIF-1 signaling pathway

(1) BackgroundGlycyrrhizic acid (GA) is the main component of the traditional Chinese medicine Glycyrrhiza glabra. Many GA preparations in the pharmaceutical market have good efficacy in hepatoprotection and the treatment of liver diseases. However, the pro-angiogenic effects for GA-based agents have not been researched specifically. The aim of this study was to investigate the pro-angiogenic activity of GA preparations commonly used in clinical practice and screen the representative angiogenesis promotor to further elucidate the mechanism of action (2) MethodsA zebrafish vascular injury model induced by PTK787 was used to assess the pro-angiogenic effect of GA preparations. The pro-angiogenic activity of diammonium glycyrrhizinate injection (DGI) was further systematically evaluated by detecting the growth of the intersegmental vessels (ISVs) and subintestinal vein vessels (SIVs) in zebrafish. The underlying mechanism of action for DGI was explored by transcriptomics analysis and RT-qPCR validation; (3) ResultsThe results showed that magnesium isoglycyrrhizinate injection (MII), DGI, compound glycyrrhizinate tablets (CGT), and diammonium glycyrrhizinate enteric-coated capsules (DGEC) could demonstrate significantly pro-angiogenic effects. Among them, DGI exhibited the strongest activity. Transcriptomic analysis showed that the pro-angiogenic activity of DGI was closely associated with the mTOR signaling pathway. RT-qPCR results indicated that the expression levels of key genes of the mTOR/HIF- pathway were significantly upregulated in DGI-treated zebrafish relative to the PTK787 group; (4) ConclusionsGA preparations have an obvious pro-angiogenic effect, in which DGI can exert particularly strong activity by activating the mTOR/HIF-1 signaling pathway. This study broadens the clinical application of GA agents and provides new insights into the pharmacodynamics and potential mechanisms of DGI as a candidate agent for treating ischemic diseases

pharmacology and toxicology↗

bioRxiv2024

GlioME: A Novel Organoid Model Retaining the Glioma Mi-croenvironment for Personalized Drug Screening and Thera-peutic Evaluation

Glioma is an aggressive brain tumor with a poor prognosis. Establishing an in vitro culture model that closely replicates the cellular composition and microenvironment of the original tumor has been challenging, limiting its clinical applications. Here, we present a novel approach to generate glioma organoids with a microenvironment (GlioME) from patient-derived glioma tissue. These organoids maintain the genetic and epigenetic characteristics of the primary tumor and preserve cell-to-cell interactions within the tumor microenvironment, including resident immune cells. Bulk RNA sequencing, whole exome sequencing, and DNA methylation analysis were used to confirm the molecular similarities between the organoids and primary glioma tissues. Immunofluorescence and flow cytometry were used to assess immune cell viability, comparing GlioME with floating glioma organoids. GlioME exhibited high responsiveness to chemotherapy and targeted therapy, demonstrating its potential for therapeutic screening applications. Notably, GlioME accurately predicted patient response to the recently approved MET inhibitor, vebreltinib. Thus, this organoid model provides a reliable in vitro platform for glioma microenvironment-related research and clinical drug screening.

cancer biology↗

bioRxiv2024

Radiation damage behavior of soft matter in ultrafast cryo-electron microscopy (cryo-UEM)

Whether time-modulated pulsed-electron imaging in ultrafast electron microscopy (UEM) can mitigate the electron radiation damage that occurs to samples, is still controversial. The effectiveness of such mitigation effect and relevant potential application in cryo-EM remain to be explored. Herein, we built an ultrafast cryo-EM (cryo-UEM) device based on an ultrafast laser system. Using such equipment and the saturated aliphatic hydrocarbon compounds (C44H90), the fading curves of diffraction intensity and corresponding critical electron doses (Ne) of the samples were carefully measured under different imaging modes, temperatures, imaging dose rates and pulsed repetition rates. Our experimental results show that, the fading curves and Ne values of the C44H90 crystals are uncorrelated with the imaging electron dose rates and do not show dependence on the dose-rate effect. As the temperature decreased, the Ne values of the sample increased, indicating the cryoprotective effect on radiation damage to the samples. Surprisingly, at a constant temperature, the fading curves and Ne values of the sample in multi-electrons-packet and near-single-electron-packet pulsed modes are all approximately the same as those in conventional continuous electron-beam mode, even when the results are obtained at different pulsed repetition rates. These results show that the time-modulated pulsed electron beam does not seem to mitigate the electron radiation damage that occurs on samples. Our findings offer new insights and experimental basis for the radiation damage behavior of samples under electron beams, and provide guidance and inspiration for elucidating the fundamental principles of radiation damage.

biophysics↗

bioRxiv2024

ANKRD5: a key component of the axoneme required for spermmotility and male fertility

Sperm motility is essential for male fertility and depends on the structural integrity of the sperm axoneme, which features a canonical "9+2" microtubule arrangement. This structure comprises nine outer doublet microtubules (DMTs) that are associated with various macromolecular complexes. Among them, the nexin-dynein regulatory complex (N-DRC) forms crossbridges between adjacent DMTs, contributing to their stabilization and enabling flagellar bending. In this study, we investigated Ankyrin repeat domain 5 (ANKRD5, also known as ANK5 or ANKEF1), a protein highly expressed in the sperm axoneme. We found that ANKRD5 interacts with DRC5/TCTE1 and DRC4/GAS8, two key components of the N-DRC, and these interactions occur independently of calcium regulation. Male Ankrd5-/- mice exhibited impaired sperm motility and infertility. Cryo-electron tomography revealed a typical "9+2" axoneme structure with intact DMTs in Ankrd5 null sperm; however, the DMTs showed pronounced morphological variability and increased structural heterogeneity. Notably, ANKRD5 deficiency did not alter ATP levels, reactive oxygen species (ROS) levels, or mitochondrial membrane potential. These findings suggest that ANKRD5 may attenuate the N-DRCs mechanical buffering-akin to a "car bumper"-between adjacent DMTs, thereby compromising axonemal stability under high mechanical stress during vigorous flagellar beating. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/626701v3_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1ca36eforg.highwire.dtl.DTLVardef@dcafe3org.highwire.dtl.DTLVardef@9f6086org.highwire.dtl.DTLVardef@17a0a0b_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance StatementMale infertility affects approximately 8%-12% of men globally, with defects in sperm motility accounting for over 80% of these cases. The axoneme, which functions as the motor apparatus of the sperm, adopts a canonical "9+2" microtubule arrangement, where the nexin-dynein regulatory complex (N-DRC) plays a critical role in providing structural support between adjacent outer microtubule doublets. Elucidating the interplay between the structural organization and protein composition of the N-DRC is essential for advancing the understanding of male reproductive biology. In this study, we identify ANKRD5 as a new component of N-DRC that is essential for maintaining normal sperm motility. These findings contribute to the molecular understanding of sperm motility and highlight ANKRD5 as a potential target for the development of novel male contraceptives.

developmental biology↗

bioRxiv2024

Chaperonin TRiC bridges radial spokes for folding proteins locally translated in mammalian sperm flagella

As animals evolved from external to internal fertilization, sperm flagella, which once transiently propelled sperm in water to reach nearby eggs, developed to beat for days or even longer within the female reproductive tract. How flagella were remodeled accordingly remains unclear. Unlike externally fertilizing zebrafish and sea urchin, mammalian sperm flagella feature a unique barrel-shaped bridge between axonemal radial spokes RS1 and RS2, though its components and function remain unknown. Here, using cryo-EM and cryo-ET combined with mass spectrometry and immunofluorescence staining, we reveal that this RS1-RS2 barrel (RRB) in mammalian sperm flagella is a group II chaperonin TRiC/CCT. We purified and resolved the unforeseen cryo-EM structure of TRiC from bovine sperm flagella, discovering that flagella TRiC contains the testis-specific CCT6B subunit. Additionally, we resolved the cryo-ET map of mouse sperm flagella RSs, containing the RRB, achieving unprecedented local resolution of 10-14 [A]. The in-situ RRB map displays two extra densities within its chambers in a polarized manner, suggesting the presence of folding substrates and a co-chaperone (likely phosducin-like 2). Notably, mammalian flagella also contain components of translation machineries and actively synthesize proteins. Our results suggest that the RRB TRiC folds locally translated proteins to sustain mammalian flagella, providing new insights into flagellar remodeling in internally fertilizing species. Our findings also shed lights on male fertility and potential treatments for infertility.

biophysics↗

bioRxiv2024

De novo identification of protein domains in cryo-electron tomography maps from AlphaFold2 models

In situ cryo-electron tomography (cryo-ET) enables visualization of protein complexes within their native cellular environments. However, sub-tomogram averaging (STA) often fails to achieve resolutions sufficient for atomic model building based on side-chain information, hindering accurate protein identification and assignment. To address this challenge, we developed DomainSeeker, a computational workflow that integrates AlphaFold2-predicted structures with experimental data to identify protein domains in cryo-ET density maps. DomainSeeker partitions AlphaFold2-predicted structures into domains using clique analysis based on predicted aligned errors and then fits these domains into target densities segmented from input cryo-ET maps. Each domain-density fit is evaluated globally and locally to derive prior probabilities, which are subsequently integrated with complementary data, such as cross-linking mass spectrometry (XL-MS), through Bayesian inference to compute posterior probabilities. Applying DomainSeekers prior probability analysis to densities from mouse sperm microtubule doublets revealed substantially higher recognition accuracy and resolution robustness compared with existing approaches. Incorporating XL-MS data for yeast nuclear pore complex densities further enhanced both recognition performance and confidence. Finally, we implemented an interactive ChimeraX plugin to facilitate user access. Together, DomainSeeker overcomes a key bottleneck in in situ structural biology, providing a robust and accessible tool for visual proteomics to uncover the structural and functional organization of native cellular assemblies.

biophysics↗

bioRxiv2024

Pangenome Reveals Gene Content Variations and Structural Variants Contributing to Pig Characteristics

Pigs are among the most essential sources of high-quality protein in human diets. Structural variants (SVs) are a major source of genetic variants associated with diverse traits and evolutionary events. However, the current linear reference genome of pigs limits the presentation of position information for SVs. In this study, we generated a pangenome of pigs and a genome variation map of 599 deep-sequenced genomes across Eurasia. Moreover, a section-wide gene repertoire was constructed, which indicated that core genes were more evolutionarily conserved than variable genes. Subsequently, we identified 546,137 SVs, their enrichment regions, and relationships with genomic features and found significant divergence across Eurasian pigs. More importantly, the pangenome-detected SVs could complement heritability estimates and genome-wide association studies based only on single nucleotide polymorphisms. Among the SVs shaped by selection, we identified an insertion in the promoter region of the TBX19 gene, which may be related to the development, growth, and timidity traits of Asian pigs and may affect the gene expression. Our constructed pig pangenome and the identified SVs provide rich resources for future functional genomic research on pigs.

genomics↗

bioRxiv2024

In-cell structural insight into the asymmetric assembly of central apparatus in mammalian sperm axoneme

In motile cilia or flagella, the axoneme typically exhibits a "9+2" configuration, with the central apparatus (CA) consisting of extensively modified microtubules C1 and C2 to regulate ciliary motility. How C1 and C2 are interconnected asymmetrically remains unknown due to the lack of complete structural model of CA. Here, we utilized the in situ cryo-electron tomography approach to solve the in-cell structure of intact mouse sperm CA at sub-nanometer resolution and built its near-complete atomic model with the aid of AlphaFold2. We identified 39 different CA-associated proteins with 8 never reported from isolated specimen. We assigned the long chain-like ASH-containing proteins CFAP47 and HYDIN responsible for connecting C1 and C2. Sperm from Cfap47-knockout mice displayed a hollowing bridge in the CA structure, correlating with its reduced progressive motility. Our findings elucidate the molecular mechanisms of CA components in ciliary motility, and the implications of their mutations in human ciliopathies.

molecular biology↗

bioRxiv2024

FAST-STEM: A human pluripotent stem cell engineering toolkit for rapid design-build-test-learn development of human cell-based therapeutic devices

Very recent clinical advances in stem cell derived tissue replacement and gene therapy, in addition to the rise of artificial intelligence-aided scientific discovery, have placed the possibility of sophisticated human cell-based therapies firmly within reach. However, development of such cells and testing of their engineered gene circuit components, has proven highly challenging, due to the need for generating stable cell lines for each design-build-test-learn engineering cycle. Current approaches to generating stable human induced pluripotent stem cell (hiPSC) lines are highly time-consuming and suffer from lack of control, poor integration efficiency, and limited functionality. Validation in clinically relevant stem cell derived tissues is also broadly lacking. Such drawbacks are prohibitive to repeatably conducting cutting-edge stem cell engineering with broad application within a realistic timeframe and will not scale with the future of regenerative medicine. We have developed FAST-STEM (Facile Accelerated Stem-cell Transgene integration with SynBio Tunable Engineering Modes), a hPSC engineering platform that drastically reduces the time to generate differentiation ready stem cell lines from several weeks to 5 days, exhibiting a ~612-fold improvement in transgene integration rate over previous methodologies. Additional FAST-STEM innovations include: (i) rapid and highly efficient transgene integration; (ii) copy number control; (iii) simultaneous or consecutive integration of multiple gene cassettes; (iv) library screen capability. In addition to this unique functional versatility, platform transportability and broad use case for stem cell-engineering was confirmed by differentiation into eight different cell types across nine different laboratories. This platform dramatically lowers the bar for integration of synthetic biology with regenerative medicine, enabling experiments which were previously deemed logistically impossible, thus paving the way for sophisticated human cell device development.

bioengineering↗

bioRxiv2024

DeepGene: An Efficient Foundation Model for Genomics based on Pan-genome Graph Transformer

Decoding the language of DNA sequences is a fundamental problem in genome research. Mainstream pre-trained models like DNABERT-2 and Nucleotide Transformer have demonstrated remarkable achievements across a spectrum of DNA analysis tasks. Yet, these models still face the pivotal challenge of (1) genetic language diversity, or the capability to capture genetic variations across individuals or populations in the foundation models; (2) model efficiency, specifically how to enhance performance at scalable costs for large-scale genetic foundational models; (3) length extrapolation, or the ability to accurately interpret sequences ranging from short to long within a unified model framework. In response, we introduce DeepGene, a model leveraging Pan-genome and Minigraph representations to encompass the broad diversity of genetic language. DeepGene employs the rotary position embedding to improve the length extrapolation in various genetic analysis tasks. On the 28 tasks in Genome Understanding Evaluation, DeepGene reaches the top position in 9 tasks, second in 5, and achieves the overall best score. DeepGene outperforms other cutting-edge models for its compact model size and superior efficiency in processing sequences of varying lengths. The datasets and source code of DeepGene are available at GitHub (https://github.com/wds-seu/DeepGene).

bioinformatics↗

bioRxiv2024

A single cell atlas of the mouse seminal vesicle

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

genomics↗

bioRxiv2024

Multiomics Analysis Reveals Extensive Remodeling of the Extracellular Matrix and Cellular Metabolism Due to Plakophilin-2 Knockdown in Guinea Pigs

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death (SCD) in young individuals, yet the mechanisms underlying its pathogenesis, particularly the role of plakophilin-2 (PKP2), remain incompletely understood. This study aimed to elucidate the profile of molecular and metabolic consequences of PKP2 knockdown in a guinea pig model of ARVC. We employed adeno-associated virus serotype 9 (AAV9) to deliver PKP2 shRNA, establishing a model that recapitulates key features of human ARVC, including right ventricular (RV) enlargement, sudden death, and cardiac lipid accumulation. Proteomic analysis revealed significant dysregulation of extracellular matrix (ECM) proteins, PI3K-Akt signaling, and energy metabolism in PKP2-deficient RVs. Metabolomic profiling further highlighted alterations in lipid metabolism and inter-metabolites of TCA cycle, with a notable shift towards fatty acid oxidation. These findings suggest that PKP2 deficiency triggers a cascade of molecular events leading to ECM remodeling, metabolic reconfiguration, and potential mitochondrial dysfunction, which may contribute to the development of ARVC. Our study provides novel insights into the early molecular mechanisms of ARVC and identifies potential therapeutic targets for this underexplored disease.

genetics↗

bioRxiv2024

Exo70 promotes herpesvirus secretory vesicle tethering and virion release in an exocyst complex-dependent manner

The exocyst complex, a multisubunit protein complex, mediates secretory vesicles fusion with the plasma membrane (PM) to deliver materials to the cell surface or to release cargoes to the extracellular space, but whether it is related to viral secretory vesicles tethering and virion release is unknown. Here, we identified that the exocyst complex subunit Exo70 promotes the trafficking of herpesvirus secretory vesicles and the release of mature virions in an exocyst complex-dependent manner. Mechanistically, mutation of Exo70 Lys632 and Lys635 diminishes viral secretory vesicles anchoring to PM. Moreover, the small GTPase Rab11a is necessary for the transport of viral secretory vesicles, and the Snapin-Exo70-SNAP23 axis is involved in fusion of viral secretory vesicles to the PM and release of virions. Most significantly, we discovered that Endosidin2 (ES2), an inhibitor of exocytosis via the exocyst complex, provides protection against herpesvirus infection in cells and mice. Overall, these findings unveil a previously uncharacterized role and mechanism of the exocyst complex in viral replication, highlighting its potential as an effective strategy against herpesvirus infection. Author summaryHerpesviruses, such as herpes simplex virus 1 (HSV-1) and bovine herpes virus type 1 (BoHV-1), are highly prevalent pathogens that establish lifelong infections and cause various diseases in humans and animals. While the mechanisms underlying the transport of herpesvirus secretory vesicles from the Golgi to the PM and the subsequent viral release are still poorly understood. In our study, we have discovered that Exo70 promotes the trafficking of HSV-1 and BoHV-1 secretory vesicles and facilitates the release of mature virions in an exocyst complex-dependent manner. Mechanistically, both knockdown of Exo70 and a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-binding-deficient mutant of Exo70 caused virions to be trapped in the cytoplasm and unable to tether to PM, indicating that the binding of Exo70 to PI(4,5)P2 is critical for the docking virus secretory vesicles with PM. Additionally, the Snapin-Exo70-SNAP23 axis plays a pivotal role in the fusion between viral secretory vesicles and the PM, ultimately facilitating the release of virions. We found that Rab11a is necessary for viral secretory vesicle trafficking mediated by Exo70. Most importantly, we discovered that ES2, a transport inhibitor that combines with Exo70 to terminate the final stage of exocytosis via the exocyst complex, can protect cells and mice from -herpesvirus infection.

microbiology↗

bioRxiv2024

FECDO-Flexible and Efficient Coding for DNA Odyssey

DNA has been pursued as a compelling medium for digital data storage during the past decade. While large-scale data storage and random access have been achieved in artificial DNA, the synthesis cost keeps hindering DNA data storage from popularizing into daily life. In this study, we proposed a more efficient paradigm for digital data compressing to DNA, while excluding arbitrary sequence constraints. Both standalone neural networks and pre-trained language models were used to extract the intrinsic patterns of data, and generated probabilistic portrayal, which was then transformed into constraint-free nucleotide sequences with a hierarchical finite state machine. Utilizing these methods, a 12%-26% improvement of compression ratio was realized for various data, which directly translated to up to 26% reduction in DNA synthesis cost. Combined with the progress in DNA synthesis, our methods are expected to facilitate the realization of practical DNA data storage.

bioinformatics↗