Biology subjects

He, Y.

Publications and source records attributed to He, Y..

At least 235 records · Page 13Linked to original sources

bioRxiv2025

A piece of evidence for pathogenesis of cerebral small vessel disease caused by blood-brain barrier dysfunction

BackgroundBlood-brain barrier (BBB) dysfunction caused by endothelial cell injury is one of the widely accepted pathogenesis of small cerebral vessel disease (CSVD). However, the early microcirculation studies were notably deficient in providing compelling imaging evidence, which has hampered a comprehensive understanding of the pathophysiological processes underlying BBB dysfunction in CSVD. The onset of CSVD is insidious and the clinical manifestations are diverse, diagnosis of CSVD relies primarily on neuroimaging information currently. These MRI imaging features mainly represent the end-stage brain parenchyma injury, rather than the vascular lesion itself. Therefore, clarifying the pathophysiological processes related to cerebral microcirculation in CSVD is of great significance for early treatment intervention of CSVD. MethodsTwenty rats were used to prepare CSVD animal model by ultrasound combined with ultrasonic microbubble contrast agent. MRI, functional ultrasound (fUS) imaging and ultrasound localization microscopy (ULM) were used to evaluate microcirculation changes in acute and chronic models. ResultsCurrently, our research has successfully validated that the imaging characteristics of this model align with the four established criteria outlined in the STRIVE-2 classification. FUS shows increased microflow velocity in the molding area, which can be used for initial evaluation of CSVD models in the acute phase. ULM has revealed a progressive reduction in the density of both the short cortical arteries and the long medullary arteries, along with their respective branches, over time. Concurrently, there has been a noted deviation in blood flow velocity. ConclusionThis model offers compelling evidence at the microvascular level, suggesting that blood-brain barrier (BBB) dysfunction is a central pathophysiological mechanism in the etiology of CSVD. Then it provides a straightforward, efficient, and widely applicable tool and continuous monitoring method for the further investigation of CSVD from the macroscopic to the microscopic circulation level, with significant long-term implications for CSVD diagnosis and treatment.

neuroscience↗

bioRxiv2025

Unraveling the Neurocognitive Mechanisms of Delayed Punishment in Second- and Third-Party Contexts

Second-party punishment (SPP) and third-party punishment (TPP) are essential in regulating social behavior and maintaining social norms, yet the effectiveness may wane when punishment is delayed. Currently, the decision-making and neural mechanisms underlying SPP and TPP under temporal delays remain largely unexplored. This study investigated both SPP and TPP punishment decisions with time-delay (immediate vs. delayed) using a hypothetical criminal scenario assessment task with fMRI. Results showed increased activity in the bilateral precuneus and left temporoparietal junction (TPJ) and stronger left TPJ-dorsolateral prefrontal cortex (dlPFC) connectivity in SPP compared to TPP. Interestingly, third-parties imposed more severe punishment in delayed conditions than in immediate ones, accompanied by enhanced neural activity in dorsomedial prefrontal cortex (dmPFC), left TPJ, ventrolateral prefrontal cortex (vlPFC), ventromedial prefrontal cortex (vmPFC), and caudate nucleus. This delay effect was evident only in misdemeanor and felony cases, with no differences in capital offenses, suggesting a moderating effect of criminal severity. In contrast, SPP showed no significant changes in punishment or neural response across immediate and delayed conditions. Multivariate pattern analysis further indicated that dmPFC, TPJ, vlPFC, vmPFC and caudate function together to encode punishment severity in TPP contexts, a pattern not observed in SPP. These findings underscore distinct decision-making mechanisms between SPP and TPP under temporal delays, with implications for understanding justice-related processing in the human brain under time constraints. Significance statementWithin the justice system, punishing norm violators is often hindered when they flee, resulting in delayed punishments. However, little is known about how second-party (SPP) and third-party (TPP) implement punishment with time delays. The current study investigated this using real criminal scenarios with time delays under fMRI scanning. We found that third parties imposed more severe punishment on defendants in delayed conditions than in immediate ones, reflected by enhanced neural activity in the dorsomedial prefrontal cortex, left temporoparietal junction, ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and caudate nucleus. In contrast, no significant differences were observed in second-party punishment. We also found a moderating effect of criminal severity: the difference between immediate and delayed sanctions by third-parties was present in misdemeanor and felony cases but not in capital offenses. These results shed light on the decision-making mechanisms of SPP and TPP in contexts involving temporal delay, which may have deep impact in different disciplines, e.g., social science, cognitive neuroscience and legal system.

neuroscience↗

bioRxiv2025

MsyB-HU Interaction Modulates a Two-Tiered Bacterial Stress Response by Regulating DNA Supercoiling

Bacteria respond to stressful conditions through multiple pathways, including changes in gene expression patterns and mutations for adaptation. DNA supercoiling is a fundamental regulatory principle of bacterial gene expression, controlled antagonistically by DNA gyrase and topoisomerase I. Nucleoid-associated proteins, such as HU, also regulate supercoiling through interactions with DNA. Here, we identify Escherichia coli protein MsyB as a HU inhibitor and a {beta}-clamp binder. MsyB is fine-tuned under various stressful conditions, where it modulates the population of DNA-bound HU by forming a HU-MsyB complex. Consequently, the balance between DNA-bound HU and MsyB-bound HU adjusts the DNA supercoiling state, thereby influencing transcription for adaptation. Additionally, under prolonged starvation during the stationary phase, sustained high level of MsyB increases DNA exposure to damaging factors, acting as a damage inducer. The HU/MsyB/{beta}-clamp interaction suggests a model in which MsyB coordinates with HU and the {beta}-clamp to facilitate damage acquisition and error-prone DNA repair. Thus, MsyB-dependent supercoiling regulation represents a novel two-tiered bacterial stress response mechanism in gene expression and adaptive mutation. Our findings reveal a previously unrecognized regulatory mechanism of bacterial supercoiling, positioning HU as a promising antibiotic target.

microbiology↗

bioRxiv2025

High-throughput, unbiased single-molecule displacement mapping with deep learning reveals spatiotemporal heterogeneities in intracellular diffusivity

Single-molecule displacement/diffusivity mapping (SMdM) has revolutionized the study of molecular motion in live cells by providing high spatial resolution insights. However, its utility is restricted by measurement biases and low throughput, making it challenging to capture temporal dynamics of intracellular diffusivity. Here we report a high-throughput single-molecule diffusivity microscopy approach (Hi-SMdM) that rapidly and unbiasedly maps nanoscale heterogeneities in molecular motion inside mammalian cells, enabling time-resolved imaging of local diffusivity dynamics. Hi-SMdM employs a self-supervised deep-learning denoising framework with a general noise model to effectively restore the scarce signals of fast-moving single molecules, while eliminating artifact motions without relying on spatial redundancies or temporal correlations. It then provides unbiased estimations of nanoscale diffusion coefficient and improve both throughput and temporal resolution by up to an order of magnitude. We demonstrate the versatility of Hi-SMdM through time-resolved mapping of the spatially heterogeneous diffusivity of free proteins in the cytoplasm. Hi-SMdM also unveils the temporal dynamics of intracellular diffusion under hypotonic conditions in live cells. Additionally, Hi-SMdM tracks the spatiotemporal dynamics of intraorganellar diffusivity during rapid rearrangements of the ER network and functional activities of mitochondria. Overall, Hi-SMdM provides exceptional opportunities for high-throughput and unbiased single-molecule diffusivity mapping with excellent spatiotemporal resolution.

biophysics↗

bioRxiv2025

Spike sorting AI agent

Spike sorting is a fundamental process for decoding neural activity, involving preprocessing, spike detection, feature extraction, clustering, and validation. However, conventional spike sorting methods are highly fragmented, labor-intensive, and heavily reliant on expert manual curation, limiting their scalability and reproducibility. This challenge has become more pressing with advances in neural recording technology, such as high-density Neuropixels for large-scale neural recording or flexible electrodes for long-term stable recording over months to years. The volume and complexity of these datasets make manual curation infeasible, requiring an automated and scalable solution. Here, we introduce SpikeAgent, a multimodal large language model (LLM)-based AI agent that automates and standardizes the entire spike sorting pipeline. Unlike traditional approaches, SpikeAgent integrates multiple LLM backends, coding functions, and established algorithms, autonomously performing spike sorting with reasoning-based decision-making and real-time interaction with intermediate results. It generates interpretable reports, providing transparent justifications for each sorting decision, enhancing transparency and reliability. We benchmarked SpikeAgent against human experts across various neural recording technology, demonstrating its versatility and ability to achieve curation consistency that are equal to, or even higher than human experts. It also drastically reduces the expertise barrier and accelerates the curation and validation time by orders of magnitude. Moreover, it enables automated interpretability of the neural spiking data, which cannot be achieved by any conventional methods. SpikeAgent presents a paradigm shift in processing signals for neuroscience and brain-computer interfaces, while laying the ground for AI agent-augmented science across various domains.

neuroscience↗

bioRxiv2025

Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway

The decline in oocytes quality and developmental potential with female reproductive aging is well recognized, yet the underlying mechanisms remain insufficiently investigated. In this study, through an integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice, morphologically defective aged oocytes are identified with distinct transcriptomic features. Further analysis demonstrates that both apoptotic and ferroptotic pathways are activated in the defective aged oocytes, and simultaneously blocking both pathways reverses the defective morphology to the largest extent. The Plat gene, which encodes tissue-type plasminogen activator (tPA), is downregulated with oocyte aging, and Plat knockdown increases oocytes susceptibility to both apoptosis and ferroptosis. Mechanistically, tPA functions as an upstream signaling molecule for Erk1/2 activation by interacting with particular phosphorylation kinases such as Alk. Consequently, Plat loss downregulates Erk1/2 pathway activity in oocytes, leading to degeneration through programmed cell death. Supplementing exogenous tPA in in vitro oocyte maturation cultures reduces defect rate of aged oocytes, thereby improving oocyte quality and developmental potential. Collectively, Plat plays a pivotal role in protecting aged mouse oocytes from programmed cell death, and tPA supplementation may serve as a potential clinical strategy to enhance oocyte quality in females of advanced maternal age.

developmental biology↗

bioRxiv2025

A maize near-isogenic line population designed for gene discovery and characterization of allelic effects

In this study we characterized a panel of 1,264 maize near-isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). 884 of the nNILs were genotyped using genotyping-by-sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, were re-genotyped using a high-density SNP chip. A novel pipeline for calling introgressions, which does not rely on knowing the donor parent of each nNIL, was developed based on a hidden Markov model (HMM) algorithm. By comparing the introgressions detected using GBS data with those identified using chip data, we optimized the HMM parameters for analyzing the entire nNIL population. A total of 2,972 introgressions were identified across the 884 nNILs. Individual introgression blocks ranged from 21 bp to 204 Mbp, with an average size of 17 Mbp. By comparing SNP genotypes within introgressed segments to the known genotypes of the donor lines we determined that in about one third of the lines, the identity of the donors did not match expectation based on their pedigrees. We characterized the entire nNIL population for three foliar diseases. Using these data, we mapped a number of quantitative trait loci (QTL) for disease resistance in the nNIL population and observed extensive variation in effects among the alleles from different donor parents at most QTL identified. This population will be of significant utility for dissecting complex agronomic traits and allelic series in maize. Significance StatementThe study reports the characterization of a publicly available population of 1,264 maize near-isogenic lines largely derived from a single recurrent parent and 18 donor lines. This population is likely to be of significant utility for the characterization of allelic series at loci of interest.

plant biology↗

bioRxiv2025

Split-Small GTPase Reassembly as a Method to Control Cellular Signaling with User-Defined Inputs

Small GTPases are critical signaling enzymes that control diverse cellular functions such as cell migration and proliferation. However, dissecting the roles of these enzymes in cellular signaling is hindered by the lack of a plug-and-play methodology for the direct, temporal control of small GTPase activity using user-defined inputs. Herein, we present a method that pairs split-GTPases with user-defined chemical inducer of dimerization (CID) systems in a plug-and-play manner to directly control small GTPase signaling in living cells. The modularity of split-small GTPase systems allows for the selection of CIDs with minimal off-target effects on the pathway being studied. Our results highlight the ability to obtain consistent pathway activation with varying CID systems for direct control of MAPK signaling, filopodia formation, and cell retraction. Thus, split-small GTPase systems provide a customizable platform for development of temporally gated systems for directly controlling cellular signaling with user-defined inputs.

synthetic biology↗

bioRxiv2025

A novel mouse model of voluntary stretching and its application in breast cancer research

BackgroundStretching exercises such as yoga are recommended for cancer survivors to manage symptoms and promote wellbeing in clinical settings. Although other types of exercise (e.g. running) can reduce the growth of tumors in animal models, the role of stretching on tumor growth remains unclear, and the lack of a preclinical self-stretching model has impeded mechanistic studies on health benefits of stretching. We sought to develop a voluntary stretching animal model to address this research gap and apply it to breast cancer research. MethodsUsing food, water, and enrichment in the home cage as motivators for stretching, a two-week 24/7 behavior monitoring was conducted in a video-based customizable home-cage behavior tracking system, Noldus PhenoTyper, to promote self-stretching in FVB mice. Subsequently, this model was utilized in a comparative study of voluntary stretching and voluntary running on tumor growth and plasma protein profiles in the MET-1 orthotopic mammary tumor FVB mouse model. ResultsThe new voluntary stretching model effectively elicited mouse self-stretching in the custom cage setting in the long-term observation and significantly inhibited tumor growth as effectively as voluntary wheel running. Moreover, plasma proteomic analysis demonstrated that voluntary stretch versus voluntary running distinctly impacted systemic protein profiles, possibly linking to different cellular and molecular mechanisms underlying anti-cancer effects and, potentially, exercise-induced benefits in other health conditions. ConclusionOur work provides the first preclinical voluntary stretching model, which may be well suited to breast cancer research and a valuable research tool to facilitate investigations of stretching health benefits across various research fields.

physiology↗

bioRxiv2025

TransBrain: A computational framework for translating brain-wide phenotypes between humans and mice

Despite remarkable advances in whole-brain imaging technologies, the lack of quantitative approaches to bridge rodent preclinical and human studies remains a critical challenge. Here we present TransBrain, a computational framework enabling bidirectional translation of brain-wide phenotypes between humans and mice. TransBrain improves human-mouse homology mapping accuracy through: (1) a novel detached region-specific deep neural network trained on integrated multi-modal human transcriptomics to improve cortical correspondence (89.5% improvement over the original transcriptome), which revealed two evolutionarily conserved gradients explaining >50% of cortical organizational variance, and (2) random walk-based graph representation learning to construct a unified cross-species latent space incorporating anatomical hierarchies and structural connectivity. We demonstrated TransBrains utility through three cross-species applications: quantitative assessment of resting-state brain organizational features, inferring human cognitive functions from mouse optogenetic circuits, and translating molecular insights from mouse models to individual-level mechanisms in autism. TransBrain enables quantitative cross-species comparison and mechanistic investigation of both normal and pathological brain functions.

neuroscience↗

bioRxiv2025

AlphaCross-XL: a seamless tool for automated and proteome-scale map-ping of crosslinked peptides onto three-dimensional protein structures

Crosslinking mass spectrometry (XL-MS) is an exciting proteomics technology to capture native protein conformations in real time within biological systems. Historically, however, implementation of this technology has typically been limited to single purified recombinant proteins or in vitro assembled protein complexes. These limitations are associated with inherent challenges in XL-MS analysis, including extremely low abundance of crosslinked (XL) peptides and complex deconvolution of XL peptide-derived spectral data. However, impressive recent developments in computation and instrumentation have now made it feasible to address biological questions using proteome-wide XL-MS analysis. Although some XL mapping software tools exist, these require manual input of specific Protein Data Bank (PDB) structures at the single protein level, and do not function at the high throughput scale required to analyze datasets derived from thousands of proteins. To address this need, we therefore sought to develop a strategy enabling automated mapping of XL peptides onto the three-dimensional (3D) structures of proteins, at a proteome-wide scale. Herein we describe AlphaCross-XL, a first-in-class seamless computational tool for automated mapping of XL peptides onto the protein structures for intra-protein crosslinks and loop-links. The AlphaCross-XL software first retrieves protein structures from the AlphaFold Protein Structure Database and maps all the identified crosslinks onto the 3D structure. It also calculates the Euclidian distance between the crosslinked residues and reports the violated and satisfied crosslink distances based on a user-defined distance threshold, which is visually discriminated by color in PyMOL. Lastly, the tool also supports further validation of user-submitted protein structures, that can include any computer-predicted protein structure and experimentally derived protein structures (i.e., from PDB). AlphaCross-XL is available at https://github.com/sanjyotshenoy/alphacross-xl.

bioinformatics↗

bioRxiv2025

Super-omics and PCAS reveal rheumatoid arthritis as a tumor-like disease

Rheumatoid arthritis (RA) is a debilitating systemic autoimmune disorder that significantly impairs quality of life. To elucidate the molecular alterations in RA progression, we performed comprehensive super-omics analyses on synovial tissues from patients with joint trauma, arthritis, and RA. These analyses included transcriptomics, proteomics, metabolomics, microbiomics, and fourteen PTMs (phosphorylation, acetylation, lactylation, O-GlcNAc glycosylation, arginine monomethylation, lysine monomethylation, lysine dimethylation, lysine trimethylation, succinylation, malonylation, glutarylation, tyrosine nitration, N-glycosylation, and O-glycosylation). Additionally, we developed a protein-centered association study (PCAS) method to integrate these complex datasets. Using this approach, we identified key proteins, such as STK17B, and its interactors, which may be crucial in RA pathogenesis. Tumor-like features, including aberrant angiogenesis and epithelial-mesenchymal transition, were observed in RA, alongside the potential involvement of oncogenes and tumor suppressor genes. Finally, we constructed a molecular interaction blueprint of RA, providing a comprehensive framework for advancing RA pathogenesis, diagnosis, and therapy.

immunology↗

bioRxiv2025

Single-cell spatial transcriptome reveals pathological features of human hippocampus with sclerosis

More than half of epileptic patients ultimately turned to intractable epilepsy. Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), the most common type of intractable epilepsies, whose pathological mechanism remains elusive. Here, using 42 human hippocampal samples from surgical donors of MTLE (32 with and 10 without HS) through single-cell resolution Stereo-seq and histologcial experiments, we revealed spatially pathological changes of gene expression and cell type composition with HS systematically. After precise parcellation of hippocampal subregions and differentially expressed gene (DEG) analysis between each region with and without sclerosis, we found Cornu Ammonis (CA) subregions with higher number of DEGs were vulnerable to sclerosis, especially CA1 and CA3. Within CA1, we found that CA1-superficial and proximal areas were more vulnerable than CA1-deep and distal areas in sclerosis. Meanwhile, after analyzing 350,795 segmented cells from Stereo-seq, we found dramatically increasing density of astrocyte accompanied with significantly decreasing density of excitatory neurons in CA1, especially superficial and proximal CA1, and CA3 in sclerosis. In these two vulnerable subregions, proliferative astrocyte (P_astrocyte) and reactive astrocyte (R_astrocyte) were found to be enriched whereas apoptotic subtype of astrocyte (A_astrocyte), related with apoptotic pathway, was mainly located in alveus, which strengthened cell communication with reactive microglia (R_microglia) in HS, revealing the novel pathological feature in our work. The pseudotime analysis indicated that CA excitatory neurons underwent synaptic impairment, energy dysfunction, aging, and finally losing cell identity until death through autophagy or apoptosis. Besides, we also found a resilient subtype, EX_CA2-4.3, highly expressed extracellular matrix related genes including PDYN, and was increasing the interaction of BDNF-NTRK, NFASC-CNTN1 to withstand the damage from sclerosis. Together, our study provided a reference of human hippocampus with and without HS caused by MTLE, and highlighted the potential pathological mechanism on molecular and cellular level of MTLE-HS.

neuroscience↗

bioRxiv2025

Food pairing independently associated with cardiometabolic traits beyond dietary patterns across western and eastern populations

Cardiometabolic health is closely linked to diet. Both specific food choices and dietary indices are commonly used to guide cardiometabolic protection strategies. However, the balance between foods may also significantly impact cardiometabolic health. Here, we explore the balance and imbalance in long-term dietary food intake to quantify food pairing patterns (FPs), providing insights beyond conventional dietary indices and single-food intake frequencies. Using data from our GGMP (n = 6,994) and the NHANES (n = 7,350) cohorts, we observed that long-term food pairing patterns are independent of single food intake frequency and dietary indices. We identified 1,759 and 306 cardiometabolic-related long-term food pairing patterns from two cohorts (FDR < 0.05), respectively. Notably, around 80% of these pairing foods not individually associated with cardiometabolic traits, and food pairing pattern associations with cardiometabolic traits at hyper food group level were consistent across Eastern and Western populations. Besides, mediation analysis revealed that 72.7% of long-term food pairing patterns affected cardiometabolic traits through 31 microbial genera, with Clostridiumsensustricto1 playing a predominant role. Moreover, multi-step mediation analysis found that microbes mediated the impact of long-term food pairing patterns on cardiometabolic traits primarily through their metabolic pathways, such as pyruvate fermentation to propanoate and ergothioneine biosynthesis pathways. Our data suggest that balance between dietary foods is broadly associated with cardiometabolic traits by modulating gut microbial functionalities, in contrast to the lower occurrence when considering individual foods in isolation. These results offer a novel perspective for designing personalized dietary strategies beyond present dietary indices to enhance cardiometabolic health.

microbiology↗

bioRxiv2025

Alveolar metabolite availability facilitates secondary infection by Pseudomonas aeruginosa in acutely injured lungs

Secondary bacterial pneumonia is a frequent complication of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Prior efforts to explain increased pneumonia risk in ALI/ARDS have focused on impaired immunity and bacterial virulence, but have overlooked the potential contribution of ecological factors within acutely injured lungs. Here, we show that lung injury profoundly alters the alveolar metabolic microenvironment, a change that can be exploited by a common pneumonia pathogen. In mice and humans, we found that growth of Pseudomonas aeruginosa (the most prominent respiratory pathogen in a retrospective cohort of patients with ARDS) is enhanced by increased alveolar concentrations of multiple ALI/ARDS-associated metabolites, which are derived from the blood and cross the compromised alveolar-capillary barrier during alveolar leak. Collectively, this work reveals an ecological mechanism by which pathogens may survive in the injured lung microenvironment and identifies new potential targets for secondary pneumonia prevention and treatment.

microbiology↗

bioRxiv2025

Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain

Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. The interaction between the disordered N-terminal domain of PXN and the C-terminal targeting domain of FAK (FAT) is necessary and sufficient for localizing FAK to focal adhesions. Furthermore, PXN serves as a platform for recruiting other proteins that together control the dynamic changes needed for cell migration and survival. Here, we show that the PXN N-domain undergoes significant compaction upon FAT binding, forming a 48-kDa multi-modal complex with four major interconverting states. Although the complex is flexible, each state has unique sets of contacts involving disordered regions that are both highly represented in ensembles and conserved. PXN being a hub protein, the results provide a structural basis for understanding how shifts in the multi-state equilibrium (e.g. through ligand binding and phosphorylation) may rewire cellular networks leading to phenotypic changes. TeaserThe fuzzy complex between Paxillin and Focal adhesion targeting domain is resolved, with functional and translational implications.

biophysics↗

bioRxiv2024

Osthole Suppresses Prostate Cancer Progression by Modulating PRLR and the JAK2/STAT3 Signaling Axis

Prostate cancer is a common malignancy in men with limited effective treatment options, highlighting the urgent need for novel therapeutic approaches. Osthole, a natural coumarin compound with antitumor properties, has demonstrated potential in targeting various cancers. This study investigates the therapeutic effects of Osthole in prostate cancer by focusing on its ability to target the Prolactin Receptor (PRLR) and modulate the JAK2/STAT3 signaling pathway. Using a combination of network pharmacology, in vitro assays, and in vivo experiments, we first employed network pharmacology to predict Ostholes potential targets, identifying 68 targets shared with prostate cancer, including AKT1, TNF, IL6, STAT3, and CTNNB1. We then confirmed these targets and assessed the effects of Osthole on cell proliferation, migration, and apoptosis using the Cell Counting Kit-8 (CCK-8) and transwell invasion assays. To further elucidate the molecular interactions and protein expression levels, we employed molecular docking and western blot analysis. Our findings revealed that Osthole significantly inhibited prostate cancer cell proliferation and migration in a dose-dependent manner and reduced tumor volume in in vivo assays. Western blot analysis also indicated that Osthole downregulated PRLR expression and decreased the phosphorylation of JAK2 and STAT3, suggesting the inhibition of the JAK2/STAT3 pathway. These results collectively highlight the therapeutic potential of Osthole in targeting prostate cancer cells through PRLR and modulating the JAK2/STAT3 pathway, warranting further clinical exploration.

cancer biology↗

bioRxiv2024

Effects of Forefoot versus Rearfoot Landing on Biomechanical Risk Factors for Lower Limb Injuries and Performance During Stop-Jump Tasks

BackgroundLower limb injuries commonly occur during sudden deceleration movements. Instructing landing with forefoot or rearfoot is hard to answer, especially considering the injury prevention and keep the performance. Therefore, the purpose of this study is to evaluate the effect of the forefoot and rearfoot landing on the biomechanical risk of lower limb injury prevention and performance during the stop-jumping task. MethodTwenty-three male health subjects were recruited for this study. During a stop-jumping task, three-dimensional kinematic and kinetic, and performance data were collected under two conditions: forefoot landing at initial ground contact and rearfoot landing at initial ground contact. Statistical parametric mapping analysis was used to compare the differences between different landing strategies. ResultSignificant differences were found in ankle internal rotation angle and ankle joint moment at foot initial contact with ground between different landing strategies. Landing with forefoot has shorter stance time compared with landing with rearfoot. In the rearfoot strike, posterior ground reaction force (GRF) and GRF inclination angle were smaller than forefoot strike in 0-14% of the stance phase. ConclusionLanding with forefoot may decrease the risk of non-contact anterior cruciate ligament injuries and have an advancement in quick reaction time, as indicated by decreased stance time, but the risk of lateral ankle sprain may increase for the stop-jump task.

bioengineering↗