Biology subjects

Lyu, S.

Publications and source records attributed to Lyu, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Linking plant-soil feedback with resource competition to understand plant coexistence

1. Plant-soil feedback (PSF) is increasingly recognized as an important mechanism influencing plant coexistence, but most studies have examined PSF in isolation under controlled conditions. Under natural conditions, PSF operates together with other processes such as resource competition, yet how these processes jointly shape plant coexistence across environmental gradients remains poorly understood. 2. We combined field and greenhouse experiments to assess the contribution of PSF to plant coexistence at low- and high-elevation sites in the Swiss Alps. In the field, we quantified total niche and fitness differences and predicted interaction outcomes for nine plant species pairs, integrating PSF, resource competition, and other processes. In a complementary greenhouse experiment, we used soil microbial communities conditioned during the field experiment to isolate PSF-driven niche and fitness differences for the same species pairs. 3. PSF alone generated strong fitness differences but weak niche differences in the greenhouse experiment, predominantly predicting competitive exclusion. Interaction outcomes predicted from PSF alone corresponded poorly with those in the field, suggesting that PSF in isolation poorly explain plant coexistence under natural conditions. Nevertheless, PSF-driven niche and fitness differences were related to those quantified in the field, which were likely driven largely by resource competition, suggesting that PSF may contribute to coexistence by reinforcing or counteracting other ecological processes. These relationships varied between elevations, highlighting the context dependence of PSF contributions to coexistence. 4. Synthesis. Our study shows that the impacts of plant-soil feedback on plant coexistence cannot be understood from their effects in isolation. Instead, their contribution depends on how they interact with other ecological processes and on the environmental context in which these processes operate. Together, our findings emphasize the need to move beyond studying PSF in isolation towards quantifying how it combines with other mechanisms that drives coexistence under natural conditions.

ecology↗

bioRxiv2026

Low-cost monophasic transcranial magnetic stimulator

Transcranial magnetic stimulation (TMS) excites neurons noninvasively by electromagnetic induction and is used in neurophysiology research and in approved therapy for depression. Commercial stimulators cost tens of thousands of dollars. Existing open-source designs are either low-energy and unvalidated or rely on expensive switches and laboratory infrastructure. We present a monophasic, fixed-pulse-shape TMS device built at a parts cost of ~USD 700 which, under specific modeling assumptions, can exceed average human motor thresholds. Our design assumes access to basic, off-the-shelf equipment such as a 24 V power supply unit, an oscilloscope, and a few basic tools. The device charges a 230 F film-capacitor bank and discharges it through a self-wound figure-of-eight coil using a thyristor, producing a fixed pulse with a positive lobe lasting approximately 90 s. A Zero-Voltage Switching (ZVS) driver-based charging circuit charges the capacitor bank up to 1460 V from a 24 V bench supply. Three galvanically isolated voltage domains, redundant interlocks, and passive and active discharge paths help mitigate the safety risks involved with handling lethal energy levels. We also present a low-cost way to characterize the device by reconstructing coil di/dt from pickup-coil dB/dt maps to estimate the induced cortical E-fields. At the maximum capacitor voltage, the recovered maximal di/dt is 110.86 A/s, giving estimated 99.9th percentile cortical E-fields of 159 V/m at Oz and 196 V/m at C3 on an example anatomy. Although not yet approved for clinical trials and routine stimulation, the device demonstrated the possibility of a cost-effective TMS unit.

bioengineering↗

bioRxiv2025

Identification and characterization of emNagⅡ, a novel β-1,2-N-acetylglucosaminidase from Elizabethkingia meningoseptica

N-Acetylglucosamine exists in various forms and linkage patterns within organisms, playing a crucial role in numerous vital biological processes. However, research focusing on {beta}-1,2-linked N-acetylglucosamine within complex biantennary N-glycans on the cell surface remain largely unexplored. Currently, there is a lack of efficient tools and methods capable of directly modifying terminal N-acetylglucosamine on living cells. In this study, we identified a novel {beta}-N-acetylhexosaminidase from Elizabethkingia meningoseptica, which demonstrated favorable enzymatic stability within a pH range of 5-8 and at temperatures from 4 {degrees}C to 37 {degrees}C. This enzyme specifically cleaves non-reducing terminal {beta}-1,2-N-acetylglucosamine, enabling direct removal of this modification from oligosaccharides and native glycoproteins. More importantly, we demonstrate for the first time that this enzyme successfully removes {beta}-1,2-linked N-acetylglucosamine on living cell surfaces. Given its microbial origin and potential utility in living cell glycan editing, we have named it emNagII or cell-surface glycan-editing N-acetylglucosaminidase (csgeNagII). Through sequence analysis and alanine scanning mutagenesis, we identified a predicted active pocket containing the catalytic residue pair Asp317-Glu318, with Asp317 being essential for enzymatic activity. In summary, our findings provide an effective and reliable method for the targeted removal of {beta}-1,2-N-acetylglucosamine on living cell surfaces, establishing a foundation for further functional studies and practical applications.

biophysics↗

bioRxiv2025

Modification of RNAs in natural rG4 (MoRNiNG), A Database of RNA Modification Sites Associated with the Dynamics of RNA Secondary Structures

RNA structures are essential building blocks of functional RNA molecules. Profiling secondary structures in vivo and in real-time remains challenging because RNAs exhibit dynamic structures and complex conformations. Besides the stem-loop canonical secondary structure, the non-canonical structure RNA G-quadruplex (rG4) is of great interest for its potential as a drug target. Early studies have demonstrated that RNAs can form distinct secondary structures. However, it is not well understood how distinct RNA structures, formed from the same RNA sequences, function within the transcriptome. The factors driving and regulating structure transitions remain poorly investigated. Inspired by a segment in the HOXB9 mRNA capable of forming multiple structures, we found that many RNA segments across the transcriptome exhibit multi-faceted structure-forming potential. For the HOXB9 case, we demonstrated that RNA modification influences RNA structure and binding with RNA binding proteins. Therefore, we collected RNA modification sites naturally occurring in the putative G-quadruplex-forming sequences (PQSs) of transcripts and developed MoRNiNG, a freely accessible database at https://www.cityu.edu.hk/bms/morning. The database is designed and organized by reliability tiers determined by the resolution of RNA modification sites and capable of including various large datasets. We experimentally validated the influence of m6A, m5C, and A-to-I editing on rG4-forming sequences and provided evidence to support the modification switch concept. The diversity and transition of secondary structures from the same RNA segment offers valuable insights into the regulation of RNA structure dynamics.

systems biology↗

bioRxiv2025

Identification and characterization of a novel exo-glycosidase activity of NGLY1 on ENGase-digested N-GlcNAc proteins in vitro

N-Glycanase 1 (NGLY1) is known for its activity to completely remove conjugated N-glycans from glycoproteins. Early studies illustrated that NGLY1 defects were associated with a rare disease named NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG). Although extensive research has been conducted over the past decade on the biological impact of NGLY1s endo-(N-)glycanase activity in cells and on disease, whether NGLY1 also exhibits an exo-(N-)glycanase activity remains open. In this study, an exo-(N-)glycanase activity of NGLY1 on the N-GlcNAc proteins was firstly reported and characterized in vitro. To distinguish for the conventional endo-(N-)glycanase activity and the newly reported exo-(N-)glycanase activity of NGLY1, the active sites of exo-NGLY1 were predicted and compared with those of endo-NGLY1. In addition, the correlation between NGLY1s exo-(N-)glycanase activity in vitro and NGLY1-CDDGs clinical characterization was investigated and discussed. The observation of NGLY1s novel exo-(N-)glycanase activity expanded the functional repertoire of NGLY1 beyond canonical endo-(N-)glycanase-mediated deglycosylation, and may provide a new framework to explain the clinical heterogeneity of NGLY1-CDDG.

biochemistry↗

bioRxiv2025

The Dayhoff Atlas: scaling sequence diversity for improved protein generation

Organized information powers modern biology, a framework pioneered by Margaret Dayhoffs Atlas of Protein Sequence and Structure and advanced by todays databases and computational methods. Here, we extend this paradigm for the AI era, presenting the Dayhoff Atlas of protein sequence data and generative models to accelerate protein biology and design. The Atlas introduces GigaRef, the largest open dataset of natural proteins, spanning 3.34B genomic and metagenomic sequences across 1.70B clusters, and BackboneRef, which distills structural information from 240,811 synthetic backbones into 46M synthetic sequences. Leveraging these datasets, we trained the Dayhoff protein language models, which can predict mutation effects, scaffold structural motifs, and generate novel proteins within families. Training on metagenomic and structure-based synthetic sequences increased the expression rates of generated proteins, demonstrating the value of data diversity and scale. We release the Dayhoff Atlas code, datasets, and models under a permissive license to empower computation in protein design.

bioengineering↗

bioRxiv2025

Endothelial Cells retain inflammatory memory through chromatin remodeling

Sepsis survivors face a heightened risk of secondary infections and chronic vascular dysfunction despite clinical recovery, yet the underlying mechanisms remain poorly defined. Our study identifies a novel mechanism of endothelial inflammatory memory, wherein transient inflammatory exposure induces durable chromatin remodeling, priming endothelial cells for exaggerated responses to subsequent inflammatory insults. Utilizing a clinically relevant two-hit mouse model, cecal ligation and puncture (CLP) followed by secondary Streptococcus pneumoniae (SP) infection, we reveal persistent transcriptional activation in endothelial cells (ECs), characterized by amplified expression of inflammatory cytokines, adhesion molecules (e.g., ICAM-1), complement factors, and interferon-stimulated genes. Genome-wide ATAC-seq analyses demonstrated stable chromatin accessibility at key inflammatory loci, indicative of epigenetic priming. Mechanistically, we uncovered a critical role for the AP-1 transcription factor JunB in mediating this epigenetic remodeling. JunB knockdown attenuated chromatin accessibility and subsequent transcriptional amplification upon secondary challenge, pinpointing JunB-driven chromatin modifications as central to endothelial reprogramming. Our findings offer mechanistic insights into how transient inflammation creates lasting epigenetic states within the endothelium, highlighting JunB as a potential therapeutic target to mitigate chronic endothelial dysfunction and increased susceptibility to secondary infections post-sepsis.

cell biology↗

bioRxiv2025

Clustered VEGF Nanoparticles in Microporous Annealed Particle (MAP) Hydrogel Accelerates Functional Recovery and Brain Tissue Repair after Stroke

Ischemic stroke, a blockage in the vasculature of the brain that results in insufficient blood flow, is one of the worlds leading causes of disability. The cascade of inflammation and cell death that occurs immediately following stroke drives vascular and functional loss that does not fully recover over time, and no FDA-approved therapies exist that stimulate regeneration post-stroke. We have previously developed a hydrogel scaffold that delivered heparin nanoparticles with and without VEGF bound to their surface to promote angiogenesis and reduce inflammation, respectively. However, the inclusion of the naked heparin nanoparticles warranted concern over the development of bleeding complications. Here, we explore how microporous annealed particle (MAP) scaffolds functionalized with VEGF coated heparin nanoparticles can both reduce inflammation and promote angiogenesis - without the inclusion of free heparin nanoparticles. We show that our updated design not only successfully promotes de novo tissue formation, including the development of mature vessels and neurite sprouting, but it also leads to functional improvement in a photothrombotic stroke model. In addition, we find increased astrocyte infiltration into the infarct site correlated with mature vessel formation. This work demonstrates how our biomaterial design can enhance endogenous regeneration post-stroke while eliminating the need for excess heparin.

bioengineering↗

bioRxiv2024

A genome-wide-level insight into HSF gene family of Rhodomyrtus tomentosa and the functional characterization of RtHSFA2s genes in thermal adaption

Heat shock transcription factor (HSF) is one of the most important regulatory elements in plant development and stress response. Rhohomyrtus tomentosa has many advantages in adapting to high temperature and humidity climates, whereas the inherence has barely been elucidated. In this study, we aimed to characterize the HSF family and investigate the thermal adaption mechanisms of R. tomentosa. We identified 25 HSF genes in the R. tomentosa genome. They could be classified into three classes: HSFA, HSFB, and HSFC. Gene duplication event is a major motivation for the expansion of the RtHSF gene family. Most of the genes in the same subclass share similar conserved motifs and gene structures. The cis-acting elements of the promoter regions of RtHSF genes are related to development, phytohormone signaling, and stress responses, and they vary among the genes even in the same subclass, resulting in different expression patterns. Especially, there exists subfunctionalization in the RtHSFA2 subfamily in responding to various abiotic stresses, viz. RtHSFA2a is sensitive to drought, salt, and cold stresses, whilst RtHSFA2b is mainly induced by heat stress. We further prove that RtHSFA2b might be of more importance in R. tomentosa thermotolerance, for Arabidopsis with overexpressed RtHSFA2b outperformed those with RtHSFA2a under heat stress, and RtHSFA2b has much higher transcription activity than RtHSFA2a in regulating certain heat shock response (HSR) genes. RtHSFA2a plays a role in transactivating RtHSFA2b. All these results provide a general prospect of the RtHSF gene family and enclose a basal thermal adaption mechanism of R. tomentosa.

plant biology↗

bioRxiv2024

Functional traits predict outcomes of current and novel competition under warmer climate

Functional traits offer a potential avenue to generalize and forecast the impacts of changing competition on plant communities, including changing outcomes of competition among species that currently interact (current competition) or that will interact in the future following range shifts (novel competition). However, it remains unclear how well traits explain variation in the outcomes of current and novel competition, as well as the underlying processes determining coexistence or competitive exclusion, under changing climate. Here, we conducted a field experiment in which pairs of high and low-elevation species interacted in three sites across an elevation gradient in the Swiss Alps. For each species pair, we quantified the population-level outcomes of competition (invasion growth rates), relative fitness differences and niche overlap and related these to 15 functional traits that were measured in each site. Most traits were significantly associated with invasion growth rates at the low elevation, where species had greater relative fitness differences, but these associations were much weaker towards higher elevations. This appears to be because traits, particularly those associated with light competition, captured species relative fitness differences at lower elevations, but not at the high elevation site. Greater relative fitness differences towards lower elevations suggest that climate warming may increase the likelihood of competitive exclusion of species that are poor competitors for light. In addition, novel competitors tended to show greater niche overlap than current competitors, leading to stronger overall competitive effects. But in general, trait differences predicted competitive outcomes of novel and current competitors similarly well, suggesting that traits can be used to predict interactions between species that do not yet interact. Our study reinforces the importance of considering changing interactions for predicting species responses to climate change and provides experimental evidence supporting the usefulness of functional trait differences in forecasting the impacts of future plant interactions under changing climate.

ecology↗

bioRxiv2024

The conversion of forests to agricultural land reduced the content of soil black carbon fractions in a karst rocky desertification area of Southwest China

Understanding the effects of land use on soil black carbon (BC) is critical for correctly interpreting the role of BC in the carbon cycle of karst areas. This study investigated the distribution characteristics of organic carbon (OC), BC, char, and soot and soil physicochemical properties of the soil profiles (0-40 cm) of secondary forest, shrub, farmland, and wasteland in a rocky desertification area of Guangxi Province, a typical karst rocky desertification area in Southwest China. We used a combination of soot/char and {delta}13CBC isotope analysis to identify the source of BC of these soils. The average value of soil BC was the highest in secondary forest, followed by shrub, farmland, and wasteland in the 0-40 cm soil layer. BC had a positive correlation with OC, char, soot,soil nitrogen, phosphorus and potassium, showed a negative correlation with bulk density. In the black carbon component, char occupies a greater proportion than soot, with the heavy fraction OC exhibiting a higher concentration of BC than the light fraction OC. Conclusively, the BC content was mainly due to C3 plant burning, vehicle exhaust emissions, and fossil fuel utilization.Vegetation restoration improved the soil BC content associated with OC sequestration in the typical karst rocky desertification mountainous area of Southwest Guangxi.

ecology↗

bioRxiv2024

Down regulation of Engase in Caenorhabditis elegans may improve its stresses adaptivity

Endo-beta-N-acetylglucosaminidase (ENGASE) is one of the key enzymes involved in the regulation of structure and function of glycoproteins. It is conserved from prokaryotic to eukaryotic cells. Although their activities in vitro and applications have been well studied, the biological function of ENGASE remains to be illustrated. In this study, we analyzed the molecular and physiological function of Engase from Caenorhabditis elegans homolog eng-1(CeEngase). We found that CeEngase knockout or knockdown increased the environmental stresses adaptability, such as heat stress and osmotic stress. Preliminary glycomics analysis showed that the basement membrane proteins of extracellular matrix may be the main targets of CeENGASE. In addition, CeENGASE may selectively prefer to N2H7 glycans on glycoproteins. In conclusion, our data illustrated that the defection and/or down regulation of CeEngase may provide a beneficially adaptation for stresses.

biochemistry↗

bioRxiv2024

A nanobody-enzyme fusion protein targeting PD-L1 and sialic acid exerts anti-tumor effects by affecting tumor associated macrophages

Cancer cells employ various mechanisms to evade immune surveillance. Their surface features, including a protective "sugar coat" and immune checkpoints like PD-L1 (programmed death ligand 1), can impede immune cell recognition. Sialic acids, which carry negative charges, may hinder cell contact through electrostatic repulsion, while PD-L1 transmits immunosuppressive signals to T cells. Furthermore, cancer cells manipulate macrophages within the tumor microenvironment to facilitate immune escape. Prior research has demonstrated the effectiveness of separately blocking the PD-L1 and sialic acid pathways in eliciting anti-tumor effects. In this study, we investigated the relationship between PD-L1 expression and genes associated with sialic acid in clinical databases. Subsequently, we developed a novel nanobody enzyme fusion protein termed Nb16-Sia to simultaneously target both PD-L1 and sialic acid pathways. In vivo experiments confirmed the anti-tumor activity of Nb16-Sia and highlighted its dependence on macrophages. Further investigations revealed that Nb16-Sia could polarize macrophages towards the M1 phenotype through the C-type lectin pathway in vitro and eliminate tumor-associated macrophages in vivo. In conclusion, our findings demonstrate that the fusion of PD-L1 nanobody with sialidase effectively targets tumor-associated macrophages, resulting in significant anti-tumor effects. This approach holds promise for drug development aimed at enhancing immune responses against cancer.

pharmacology and toxicology↗

bioRxiv2023

Identification and characterization of a beta-1,4 Galactosidase from Elizabethkingia meningoseptica and its application on living cell surface

The biological function of terminal galactose on glycoprotein is an open field of research. Although progress had being made on enzymes that can remove the terminal galactose on glycoproteins, there is a lack of report on galactosidases that can work directly on living cells. In this study, a unique beta 1,4 galactosidase was isolated from Elizabethkingia meningoseptica (Em). It exhibited favorable stability at various temperatures (4-37) and pH (5-8) levels and can remove {beta}-1, 4 linked galactoses directly from glycoproteins. Using Alanine scanning, we found that two acidic residues (Glu-468, and Glu-531) in the predicted active pocket are critical for galactosidase activity. In addition, we also demonstrated that it could cleave galactose residues present on living cell surface. As the enzyme has a potential application for living cell glycan editing, we named it glycan editing galactosidase I or geGalaseI. In summary, our findings lay the groundwork for prospective investigations by presenting a prompt and gentle approach for the removal of galactose moieties from cell surface.

biochemistry↗

bioRxiv2023

A consistent map in the medial entorhinal cortex supports spatial memory

The medial entorhinal cortex (MEC) is hypothesized to function as a cognitive map for memory-guided navigation. How this map develops during learning and influences memory remains unclear. By imaging MEC calcium dynamics while mice successfully learned a novel virtual environment over ten days, we discovered that the dynamics gradually became more spatially consistent and then stabilized. Additionally, grid cells in the MEC not only exhibited improved spatial tuning consistency, but also maintained stable phase relationships, suggesting a network mechanism involving synaptic plasticity and rigid recurrent connectivity to shape grid cell activity during learning. Increased c-Fos expression in the MEC in novel environments further supports the induction of synaptic plasticity. Unsuccessful learning lacked these activity features, indicating that a consistent map is specific for effective spatial memory. Finally, optogenetically disrupting spatial consistency of the map impaired memory-guided navigation in a well-learned environment. Thus, we demonstrate that the establishment of a spatially consistent MEC map across learning both correlates with, and is necessary for, successful spatial memory.

neuroscience↗

bioRxiv2023

ProteinVAE: Variational AutoEncoder forTranslational Protein Design

There have recently been rapid advances in deep learning models for protein design. To demonstrate proof-of-concept, these advancements have focused on small proteins with lots of data for training. This means that they are often not suitable for generating proteins with the most potential for high clinical impact -due to the additional challenges of sparse data and large size many therapeutically relevant proteins have. One major application that fits this category is gene therapy delivery. Viral vectors such as Adenoviruses and AAVs are a common delivery vehicle for gene therapy. However, environmental exposure means that most people exhibit potent pre-existing immune responses to many serotypes. This response, primarily driven by neutralizing antibodies, also precludes repeated administration with the same serotype. Rare serotypes, serotypes targeting other species, and capsid engineering, have all been deployed in the service of reducing neutralization by pre-existing antibodies. However, progress has been very limited using conventional methods and a new approach is urgently needed. To address this, we developed a variational autoencoder that can generate synthetic viral vector serotypes without epitopes for pre-existing neutralizing antibodies. A compact generative computational model was constructed, with only 12.4 million parameters that could be efficiently trained on the limited natural sequences (e.g., 711 natural Adenovirus hexon sequences with average length of 938 amino acids). In contrast to the current state-of-the-art, the model was able to generate high-quality Adenovirus hexon sequences that were folded with high confidence by Alphafold2 to produce structures essentially identical to natural hexon structures. Molecular dynamics simulations confirmed that the structures are stable and protein-protein interfaces are intact. Local secondary structure and local mobility is also comparable with natural serotype behavior. Our model could be used to generate a broad range of synthetic adenovirus serotype sequences without epitopes for pre-existing neutralizing antibodies in the human population. It could be used more broadly to generate different types of viral vector, and any large, therapeutically valuable proteins, where available data is sparse.

synthetic biology↗

bioRxiv2022

A gene expression analysis and immune infiltration between lesioned and preserved subchondral bone in osteoarthritis

BackgroundOsteoarthritis (OA) is a degenerative disease which need more research. The purpose of this study was to performed gene expression analysis and immune infiltration between lesioned and preserved subchondral bone, and validation with datasets and experiment of multiple tissues. MethodsThe different expressed genes(DEGs) of GSE51588 datasets between lesioned and preserved tibial plateaus of OA patients were conducted. Moreover, functional annotation and protein-protein interaction (PPI) network were applied for exploring the potential therapeutic targets in OA subchondral bones between lesioned and preserved sides. In addition, multiple tissues were used to screen out co-expressed genes and the expression levels of identified candidate DEGs was detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OA. Finally, immune infiltration analysis was conducted. ResultsA total of 1010 DEGs were identified, including upregulated 423 genes, 587 downregulated genes. Upregulated genes showed that BP terms were enriched in "skeletal system development", "sister chromatid cohesion","ossification" etc. Pathways were enriched in "Wnt signaling pathway," "Proteoglycans in cancer," Downregulated genes showed that BP terms were enriched in "inflammatory response," "xenobiotic metabolic process", "positive regulation of inflammatory response". Pathways were enriched in "Neuroactive ligand-receptor interaction", "AMPK signaling pathway" etc. JUN, TNF, IL1B,were the hub genes in the PPI network. Col1A1 and LRRC15 were screened out by multiple datasets and validated by experiments. Immune infiltration showed adipocytes and endothelial cells infiltrated less in lesioned samples. ConclusionOur research might provide valuable information for exploring the pathogenesis mechanism of OA and identifying the potential therapy targets for OA diagnosis.

molecular biology↗

bioRxiv2022

Competition contributes to both warm and cool range edges

Competition plays an important role in shaping species spatial distributions. However, it remains unclear where and how competition regulates species range limits. In a field experiment with plants originating from low and high elevations and conducted across an elevation gradient in the Swiss Alps, we find that both lowland and highland species can better persist in the presence of competition within than beyond their elevation ranges, suggesting that competition helps set both lower and upper elevation range limits of these species. Furthermore, the reduced ability of pairs of lowland or highland species to coexist beyond their range edges is mainly driven by diminishing niche differences; changes in both niche differences and relative fitness differences drive weakening competitive dominance of lowland over highland species with increasing elevation. These results highlight the need to account for competitive interactions and investigate underlying coexistence mechanisms to understand current and future species distributions.

ecology↗