Biology subjects

Wei, J.

Publications and source records attributed to Wei, J..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

METTL1/WDR4-mediated m7G Hypermethylation of SCLT1 mRNA Promotes Gefitinib Resistance in Non-small Cell Lung Cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have produced durable complete responses, but the eventual development of acquired resistance presents a huge challenge in the treatment of non-small cell lung cancer (NSCLC). N7-methylguanosine (m7G), a prevalent post-transcriptional modification within RNA, play regulatory roles in RNA stability, expression dynamics, and functional diversity. Despite these insights, the contribution of m7G methylation to EGFR-TKIs resistance remains poorly characterized. Here, we identified substantial upregulation of mRNA internal m7G modifications and their associated methyltransferase complex composed of methyltransferase-like 1 (METTL1) /WD repeat domain 4 (WDR4) were significantly elevated in NSCLC specimens, correlating with therapeutic resistance. Functional assays confirmed that METTL1/WDR4 enhances gefitinib resistance in both cellular and animal models via the internal RNA m7G methyltransferase activity in NSCLC. Mechanistically, m7G MeRIP-seq coupled with RNA-seq identified sodium channel and clathrin linker 1 (SCLT1) as the m7G target of METTL1/WDR4. METTL1/WDR4 knockdown may result in a decrease in both the demethylation level and mRNA stability of the SCLT1 transcript, while overexpression of wild-type METTL1, but not its catalytically inactive mutant, rescues mRNA stability. METTL1/WDR4-mediated m7G modification of SCLT1 regulates gefitinib resistance by activating the NF-{kappa}B signaling. These results establish aberrant mRNA internal m7G modification as a novel resistance mechanism and propose therapeutic targeting of the METTL1/WDR4-SCLT1-NF-{kappa}B axis cascade to overcome EGFR-TKIs resistance.

molecular biology↗

bioRxiv2025

Silicon regulation of pectin methyl-esterification and cellulose microfibril organization modulates FERONIA-mediated cell wall integrity signaling for rice adaption to salt stress

The beneficial element silicon (Si) plays a crucial role in mitigating salt stress in plants and can activate intracellular signal transduction pathways that reprogram the transcriptome of salt-stressed plants. However, the mechanisms by which plants perceive Si nutrition, induce the expression of Si-responsive genes, and regulate the activity of Si-responsive proteins remain inadequately understood. In this study, we found that Si enhances cell wall integrity by increasing the degree of pectin methyl-esterification and changing the cellulose microfibril arrangement and functions as a regulatory switch for the activities of cell wall integrity sensors (FER homologs OsFLR1 and OsFLR2) during rice plant adaptation to high salinity. Furthermore, the inhibition of OsFLR1 and OsFLR2 through FER-specific inhibitors could negate the beneficial effects of Si and affect the uptake and accumulation of Si in rice seedlings. In conclusion, these findings suggest that Si signaling initiation involves FER-mediated cell wall integrity signaling pathways during salt stress adaptation in rice.

plant biology↗

bioRxiv2025

Aedes aegypti aminopeptidase N3 is a functional binding receptor of Bacillus thuringiensis subsp. israelensis Cry4Ba toxin

Bacillus thuringiensis is widely employed for biological control. It can effectively suppress populations of various mosquito species, including Aedes aegypti. However, the precise mechanism underlying the action of cry toxin secreted by Bacillus thuringiensis on Ae. aegypti remains elusive. In this study, we investigated one of the binding receptors of cry toxin, aminopeptidase N. Through comprehensive bioinformatics analysis involving whole-genome screening, genetic mapping, structural characterization, phylogenetic analysis, and spatiotemporal expression profiling, we identified twenty-nine homologs of Ae. aegypti aminopeptidase N. Further, we successfully expressed GST-APN3 protein in E. coli and demonstrated through ligand blot and ELISA assays that APN3 exhibits high affinity binding to Cry4Ba toxin (Kd = 20.53 nM). To elucidate the functional role of APN3 as a receptor mediating Cry4Ba activity in Ae. aegypti midgut cells (some of which express this gene at high levels), CRISPR/Cas9 technology was employed to knock out APN3. Our bioassay results revealed that APN3 knockout mosquito larvae had 2.9 to 4.1-fold higher resistance against Cry4Ba, indicating its crucial involvement as an active receptor mediating Cry4Ba activity. Overall, this study provides a foundation for elucidating the specific larvicidal mechanisms of Bt against mosquito populations.

molecular biology↗

bioRxiv2025

Small-molecule screen in C. elegans identifies benzenesulfonamides as inhibitors of microsporidia spores

Microsporidia, a large group of fungal-related intracellular parasites, infect several economically significant animals, leading to substantial economic losses. As currently available anti-microsporidia therapies are either ineffective or come with numerous adverse effects, there is a need for alternative microsporidia inhibitors. Here we screen a subset of the ChemBridge DIVERset library, comprising 2500 diverse compounds, using Caenorhabditis elegans infected with its natural microsporidian parasite, Nematocida parisii. By testing these compounds at 60 M in 96-well assay plates, we identified 26 hits that restored the ability of C. elegans to produce progeny in the presence of N. parisii. We confirmed that out of 20 tested compounds, 18 ChemBridge compounds effectively inhibit N. parisii infection in C. elegans. Of these 18, 10 were benzenesulfonamide derivatives which inhibit microsporidia infection by inactivating spores. We screened an additional 475-compound benzenesulfonamide library, successfully identifying three compounds that are effective at a lower concentration than the initial hits. We further show that one benzenesulfonamide compound displays inhibitory activity against several species of microsporidia, inhibiting infection of species belonging to the Nematocida, Enterocytozoon, and Encephalitozoon genera. Together our results suggest that benzenesulfonamides are a potential scaffold for the development of microsporidia antiseptics.

microbiology↗

bioRxiv2025

HKU5 bat merbecoviruses use divergent mechanisms to engage bat and mink ACE2 as entry receptors

Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy (cryo-EM) analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

microbiology↗

bioRxiv2024

Cell fate specification modes shape transcriptome evolution in the highly conserved spiral cleavage

Early animal development can be remarkably variable, influenced by lineage-specific reproductive strategies and adaptations. Yet, early embryogenesis is also strikingly conserved in some groups, like Spiralia (e.g., snails, clams, and many marine worms). In this large clade, a shared cleavage program -- the so-called spiral cleavage -- and similar cell lineages are ancestral to at least seven animal phyla. Why early development is so conserved in specific groups and plastic in others is not fully understood. Here, we investigated two annelid species -- Owenia fusiformis and Capitella teleta -- with spiral cleavage but different modes of specifying their primary progenitor cells. By generating high-resolution transcriptomic time courses from the oocyte and fertilisation until gastrulation, we show transcriptional dynamics are markedly different between these species during spiral cleavage and instead reflect their distinct timings of embryonic organiser specification. However, the end of cleavage and gastrulation exhibit high transcriptomic similarity. At these stages, orthologous transcription factors share gene expression domains, suggesting this period is a previously overlooked mid-developmental transition in annelid embryogenesis. Together, our data reveal hidden developmental plasticity in the genetics underpinning spiral cleavage, indicating an evolutionary decoupling of morphological and transcriptomic conservation during early animal embryogenesis.

developmental biology↗

bioRxiv2024

Electron-density informed effective and reliable de novo molecular design and lead optimization with ED2Mol

Generative drug design opens new avenues for discovering novel compounds within the vast chemical space rather than conventional screening against limited compound libraries. However, the practical utility of the generated molecules is frequently constrained, as many designs prioritize a narrow range of pharmacological properties while neglecting physical reliability, which hinders the success rate of subsequent wet-lab evaluations. To address this, we propose ED2Mol, a deep learning-based approach that leverages fundamental electron density information to improve de novo molecular generation and lead optimization. The extensive evaluations across multiple benchmarks demonstrate that ED2Mol surpasses existing methods in terms of generation success rate and >97% physical reliability. It also facilitates automated lead optimization that is not fully implemented by other methods using fragment-based strategies. Furthermore, ED2Mol exhibits generalizability to more challenging, unseen allosteric pocket benchmarks, attaining consistent performance in both de novo molecule generation and lead optimization. More importantly, ED2Mol has been applied to various real-world essential targets, successfully identifying wet-lab validated bioactive compounds, ranging from FGFR3 orthosteric inhibitors to CDC42 allosteric inhibitors and GCK allosteric activators. The directly generated binding modes of these compounds with target proteins are close to predictions through molecular docking and further validated via the X-ray co-crystal structure. All these results highlight ED2Mols potential as a useful tool in realistic drug design with enhanced effectiveness, physical reliability, and practical applicability.

bioinformatics↗

bioRxiv2024

Modulating Prestimulus Alpha and Beta Power with tRNS Establishes Their Causal Role in Visual Perception

Variability in visual perception in response to consistent stimuli is a fundamental phenomenon linked to fluctuations in prestimulus low-frequency neural oscillations--particularly in the alpha (8-13 Hz) and beta (13-30 Hz) bands--typically measured by their power in electroencephalography (EEG) signals. However, the causal role of these prestimulus alpha and beta power fluctuations in visual perception remains unestablished. In this study, we investigated whether prestimulus alpha and beta power causally affect visual perception using transcranial random noise stimulation (tRNS). In a sham-controlled, single-blind, within-subject design, 29 participants performed a visual detection task while receiving occipital tRNS. Online functional near-infrared spectroscopy (fNIRS) was used to measure cortical excitability during stimulation, and offline EEG signals were collected after stimulation. Mental fatigue was incorporated as a state-dependent factor influencing tRNS effects. Our findings demonstrate that, primarily under low fatigue states, tRNS increased cortical excitability during stimulation (indicated by increased fNIRS oxyhemoglobin amplitude), decreased subsequent prestimulus EEG alpha and beta power, and consequently reduced the visual contrast threshold (VCT), indicating enhanced visual perception. Sensitivity analysis revealed that alpha oscillations contributed more significantly to visual perception than beta oscillations under low fatigue. Additionally, the state-dependent effects of tRNS may result from different sensitivities of VCT to neural oscillations across fatigue states. These results provide causal evidence linking prestimulus alpha and beta power to visual perception and underscore the importance of considering brain states in neuromodulation research. Our study advances the understanding of the neural mechanisms underlying visual perception and suggests potential therapeutic applications targeting neural oscillations. Significance statementUnderstanding why we perceive identical visual stimuli differently is a fundamental question in neuroscience. This study provides causal evidence that prestimulus alpha and beta neural oscillations directly influence visual perception, particularly under low mental fatigue state. By using tRNS alongside fNIRS and EEG recordings, we demonstrate that modulating neural excitability can alter perceptual outcomes. Our findings highlight the importance of considering brain state--such as fatigue levels--in neuromodulation research. This work advances our understanding of the neural mechanisms underlying visual perception and opens avenues for developing targeted interventions to enhance sensory processing and cognitive functions, potentially benefiting individuals with perceptual or attentional disorders.

neuroscience↗

bioRxiv2024

Better Prior Distribution for Antibody Complementarity-Determining Regions Design

Designing antibodies with desired binding specificity and affinity is essential for pharmaceutical research. While diffusion-based models have advanced the co-design of the Complementarity-Determining Regions (CDRs) sequences and structures, challenges remain, including non-informative prior distribution, incompatibility with discrete amino acid types, and impractical computational cost in large-scale sampling. To address these, we proposed FlowDesign, a sequence-structure co-design approach based on Flow Matching, offering: (1) Flexible selection of prior distributions; (2) Direct matching of discrete distributions; (3) Enhanced computational efficiency for large-scale sampling. By leveraging various priors, data-driven structural models proved the most informative. FlowDesign outperformed baselines in Amino Acid Recovery (AAR), RMSD, and Rosetta energy. We also applied FlowDesign to design antibodies targeting the HIV-1 receptor CD4. FlowDesign yielded antibodies with improved binding affinity and neutralizing potency compared to the antibody Ibalizumab across multiple HIV mutants, validated by Biolayer Interferometry (BLI) and pseudovirus neutralization. This highlights FlowDesigns potential in antibody and protein design. A record of this papers Transparent Peer Review process is included in the Supplemental Information.

bioinformatics↗

bioRxiv2024

Blocking SHP2 benefits FGFR2 inhibitor and overcomes its resistance in FGFR2-amplified gastric cancer

Fibroblast growth factor receptor 2 (FGFR2) is an important member of receptor tyrosine kinase (RTK) family. FGFR2 amplification occurs at a high frequency in gastric cancer (GC) and has been proven to be closely associated with poor prognosis and insensitivity to chemotherapy or immunotherapy. Current FGFR2-targeted therapies have limited efficacy. Hence, how to enhance efficacy and reverse resistance are urgent problems clinically. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) serves as the shared downstream mediator of all RTKs and a prominence immunosuppressive molecule. In this study, we identified FGFR2 amplification in 6.2% (10/161) of GC samples in our center. Then we showed that dual blocking SHP2 and FGFR2 enhanced the effects of FGFR2 inhibitor (FGFR2i) in FGFR2-amplified GC both in vitro and in vivo via suppressing RAS/ERK and PI3K/AKT pathways. We further showed that it overcame FGFR2i resistance by reversing the feedback activation mediated by other RTKs and continuously suppressing FGFR2-initiated downstream pathways. Notably, SHP2 blockade could suppress PD-1 expression and promoted IFN-{gamma} secretion of CD8+ T cells, enhancing the cytotoxic functions of T cells in tumor immune microenvironment. Overall, our findings suggest that dual blocking SHP2 and FGFR2 is a compelling rationale with both targeted treatment and immune regulation for FGFR2-amplified GC. Impact statementDual blocking SHP2 and FGFR2 can not only promote the targeted tumor-killing effects and overcome FGFR2 inhibitor resistance caused by feedback activation, but also activate T cell-mediated anti-tumor immunity by inhibiting PD-1 pathway in FGFR2-amplified GC. Funding informationThis work was funded by Grants from National Natural Science Foundation of China (82403862, 82403835), Jiangsu Provincial Natural Science Foundation Youth Project (BK20230151, BK20240247), Jiangsu Provincial Major Science and Technology Program (BG2024026), the Wu Jieping Medical Foundation Special Fund for Targeted Cancer Therapy (Youth Research Project) (320.6750.2023-11-30), Jiangsu Provincial Youth Science and Technology Talent Support Project (JSTJ-2025-715) and General Project of Nanjing Health Science and Technology Development Program (YKK24084).

cancer biology↗

bioRxiv2024

Site-specific DNA insertion into the human genome with engineered recombinases

Technologies for precisely inserting large DNA sequences into the genome are critical for diverse research and therapeutic applications. Large serine recombinases (LSRs) can mediate direct, site-specific genomic integration of multi-kilobase DNA sequences without a pre-installed landing pad, but current approaches suffer from low insertion rates and high off-target activity. Here, we present a comprehensive engineering roadmap for the joint optimization of DNA recombination efficiency and specificity. We combined directed evolution, structural analysis, and computational models to rapidly identify additive mutational combinations. We further enhanced performance through donor DNA optimization and dCas9 fusions, enabling simultaneous target and donor recruitment. Top engineered LSR variants achieved up to 53% integration efficiency and 97% genome-wide specificity at an endogenous human locus, and effectively integrated large DNA cargoes (up to 12 kb tested) for stable expression in challenging cell types, including non-dividing cells, human embryonic stem cells, and primary human T cells. This blueprint for rational engineering of DNA recombinases enables precise genome engineering without the generation of double-stranded breaks.

bioengineering↗

bioRxiv2024

Integration of the DD-genome reshapes gene transcription, chromatin architecture and metabolome of allohexaploid wheat leading to enhanced adaptability

The integration, through hybridization, of the DD genome into domesticated tetraploid wheat gave rise to allohexaploid wheat, the most cultivated wheat globally growing across diverse environmental conditions. However, the regulatory basis of this integration on increased environmental adaptability in allohexaploid remains largely unexplored. Here, we investigated the change of transcriptome, epigenome as well as the chromatin interactome, and metabolome in three independent polyploidization events representing DD genome integration. Our findings reveal that polyploidization events induce the activation of defense-related genes through comprehensive reorganization of epigenome and chromatin architecture. DD integration not only brings an additional gene copy but also activates the homoeologs existing in the A and B subgenomes through chromatin interactions. Furthermore, secondary metabolites represented by alkaloids and flavonoids that are crucial for environmental adaptation, are significantly enriched following polyploidization. Thus, hexaploid wheat exhibits enhanced tolerance to alkalinity, UV-B light stress and high salt conditions was observed. These results highlight the indispensable role of DD genome integration in the adaptability of allohexaploid wheat during its evolution.

plant biology↗

bioRxiv2024

Assessment of drive efficiency and resistance allele formation of a homing gene drive in the mosquito Aedes aegypti

Aedes aegypti, known for transmitting viruses such as dengue, zika, and yellow fever, poses a significant public health threat. Conventional insecticides give rise to a range of issues, including ecological contamination and insect resistance. Hence, there is a pressing demand for environmentally friendly, safer, and more efficacious strategies for mosquito control. With the rapid advancement of the CRISPR/Cas9 system in gene function exploration and pest population control, substantial progress has been achieved in utilizing CRISPR/Cas9-based gene drive systems across various mosquito species. Only a few studies on gene drive technology have been conducted in A. aegypti. In this study, we constructed two complete drives for A. aegypti with different Cas9 promoters, each targeting kmo. Our drive based on Pub-Cas9 had limited activity, but one with exu-Cas9 exhibited super-Mendelian inheritance rates of approximately 60%. We observed low but detectable somatic activity of the drive and no evidence of maternally deposited Cas9. Germline resistance allele formation rates were similar to drive conversion rates, but most wild-type alleles in the germline remained uncut. Injections into the exu-Cas9 drive line had 100% knockout efficiency among surviving offspring at three separate target genes. These results support the development and application of novel genetic pest control technologies aimed at combating A. aegypti.

genetics↗

bioRxiv2024

IGF2BP3 Promotes Autophagy-Mediated TNBC Metastasis via M6A-Dependent, Cap-Independent c-Met Translation

Tumor metastasis involves a series of complex processes and is a major challenge in clinical treatment. The cooperation of epigenetic modifications and metabolic adaptations endows tumor cells with dynamic adaptations for survival in variable environments, which is crucial for tumor metastasis and worth exploring in depth. In this study, we found IGF2BP3 could link epigenetic modification and metabolic adaptation in promoting autophagy-mediated triple-negative breast cancer (TNBC) metastasis. As a TNBC specifically high expressed N6-methyladenosine (m6A) binding protein, IGF2BP3 could bind to the m6A motif of c-Met mRNA, regulating autophagy-mediated epithelial-to-mesenchymal transition (EMT) progress by c-Met/PI3K/AKT/mTOR pathway. Moreover, through the recruitment of eIF4G2 as a collaborator, IGF2BP3 induced the changes in c-Met protein expression not by affecting mRNA stability, but by facilitating its mRNA translation initiation in an m6A-dependent and cap-independent manner. In conclusion, our study extended the role of IGF2BP3 in autophagy mediated TNBC metastasis, found IGF2BP3 could bind to the m6A motif on the 5', 3'-UTR of c-Met mRNA to facilitate its translation in a cap-independent manner.

cancer biology↗

bioRxiv2024

Overabundant endocannabinoids in neurons are detrimental to cognitive function

2-Arachidonoylglycerol (2-AG) is the most prevalent endocannabinoid involved in maintaining brain homeostasis. Previous studies have demonstrated that inactivating monoacylglycerol lipase (MAGL), the primary enzyme responsible for degrading 2-AG in the brain, alleviates neuropathology and prevents synaptic and cognitive decline in animal models of neurodegenerative diseases. However, we show that selectively inhibiting 2-AG metabolism in neurons impairs cognitive function in mice. This cognitive impairment appears to result from decreased expression of synaptic proteins and synapse numbers, impaired long-term synaptic plasticity and cortical circuit functional connectivity, and diminished neurogenesis. Interestingly, the synaptic and cognitive deficits induced by neuronal MAGL inactivation can be counterbalanced by inhibiting astrocytic 2-AG metabolism. Transcriptomic analyses reveal that inhibiting neuronal 2-AG degradation leads to widespread changes in expression of genes associated with synaptic function. These findings suggest that crosstalk in 2-AG signaling between astrocytes and neurons is crucial for maintaining synaptic and cognitive functions and that excessive 2-AG in neurons alone is detrimental to cognitive function.

neuroscience↗

bioRxiv2024

Transdiagnostic Symptom Domains are Associated with Head Motion During Multimodal Imaging in Children

BackgroundHead motion is a challenge for neuroimaging research in developmental populations. However, it is unclear how transdiagnostic symptom domains including attention, disruptive behavior (e.g., externalizing behavior), and internalizing problems are linked to scanner motion in children, particularly across structural and functional MRI. The current study examined whether transdiagnostic domains of attention, disruptive behavior, and internalizing symptoms are associated with scanner motion in children during multimodal imaging. MethodsIn a sample of 9,045 children aged 9-10 years in the Adolescent Brain Cognitive Development (ABCD) Study, logistic regression and linear mixed-effects models were used to examine associations between motion and behavior. Motion was indexed using ABCD Study quality control metrics and mean framewise displacement for the following: T1-weighted structural, resting-state fMRI, diffusion MRI, Stop-Signal Task, Monetary Incentive Delay task, and Emotional n-Back task. The Child Behavior Checklist was used as a continuous measure of symptom severity. ResultsGreater attention and disruptive behavior problem severity was associated with a lower likelihood of passing motion quality control across several imaging modalities. In contrast, increased internalizing severity was associated with a higher likelihood of passing motion quality control. Increased attention and disruptive behavior problem severity was also associated with increased mean motion, whereas increased internalizing problem severity was associated with decreased mean motion. ConclusionTransdiagnostic domains emerged as predictors of motion in youths. These findings have implications for advancing development of generalizable and robust brain-based biomarkers, computational approaches for mitigating motion effects, and enhancing accessibility of imaging protocols for children with varying symptom severities.

neuroscience↗

bioRxiv2024

Erythropoietin-dependent Acquisition of CD71hiCD105hi Phenotype within CD235a- Early Erythroid Progenitors

The development of committed erythroid progenitors and their continued maturation into mature erythrocytes requires the cytokine erythropoietin (Epo). Here, we describe the immunophenotypic identification of a unique Epo-dependent colony-forming unit-erythroid (CFU-E) cell subtype that forms during early erythropoiesis (EE). This previously undescribed CFU-E subtype, termed late-CFU-E (lateC), lacks surface expression of the characteristic erythroid marker CD235a (glycophorin A) but has high levels of CD71 and CD105. LateCs could be prospectively detected in human bone marrow (BM) cells and, upon isolation and reculture, exhibited the potential to form CFU-E colonies in medium containing only Epo (no other cytokines) and continued differentiation along the erythroid trajectory. Analysis of ex vivo cultures of BM CD34+ cells showed that acquisition of the CD7hiCD105hi phenotype in lateCs is gradual and occurs through the formation of four EE cell subtypes. Of these, two are CD34+ burst-forming unit-erythroid (BFU-E) cells, distinguishable as CD7loCD105lo early BFU-E and CD7hiCD105lo late BFU-E, and two are CD34- CFU-Es, also distinguishable as CD71loCD105lo early CFU-E and CD7hiCD105lo mid-CFU-E. The transition of these EE populations is accompanied by a rise in CD36 expression, such that all lateCs are CD36+. Single cell RNA-sequencing analysis confirmed Epo-dependent formation of a CFU-E cluster that exhibits high coexpression of CD71, CD105, and CD36 transcripts. Gene set enrichment analysis revealed the involvement of genes specific to fatty acid and cholesterol metabolism in lateC formation. Overall, in addition to identifying a key Epo-dependent EE cell stage, this study provides a framework for investigation into mechanisms underlying other erythropoiesis-stimulating agents.

developmental biology↗

bioRxiv2024

Transient dynamics response analysis of the limb under impact loading

The limb vibrations are initiated at paw-strike in animals normal movement. The short ground contact duration suggests that there exists the transient dynamic response of the impact between the leg and ground, which is a high nonlinear problem and not well understood. The purpose of this study is to investigate the transient dynamic response of the lower limb of the felid during the moving. A kinematic model of the musculoskeletal system of a small felid is constructed from the anatomical measurement data. The elastic moduli are measured and calculated for different parts of the lower limb by a Nano-indentation technique. On the basis of the measured material parameters, the substructure technique is employed to numerically solve the contact-impact behavior of the lower limb. The high speed imaging system and a designed electronic detection system are employed in the experiment to testify the numerical results, which demonstrate that the initial impact has an important influence on the performance of the lower limb during the movement especially the high speed movement, and the paw-pad has good damping effects during the impact. The multiple impacts exist between limbs and the soil, which may provide the feedback energy for the felids high-speed running, though it may also increase the risk of the stress fracture of the limbs.

bioengineering↗