Biology subjects

Lin, F.

Publications and source records attributed to Lin, F..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

PathoEye: a deep learning framework for the whole-slide image analysis of skin tissue

ObjectiveTo provide an interpretable computational framework for the examination of whole-slide images (WSI) in skin biopsies, PathoEye focuses on the dermis-epidermis junctional (DEJ) areas, also known as the basement membrane zone (BMZ), to enrich the pathological features of various skin diseases. MethodsWe presented PathoEye for WSI analysis in dermatology, which integrates epidermis-guided sampling, deep learning and radiomics. It enables unsupervised semantic segmentation of the BMZ and extracts distinct features associated with various skin conditions. ResultsPathoEye performs comparably with existing methods in binary classification tasks, while outperforming them in multi-classification tasks involving different skin conditions. It enables the investigation of histopathological aberrations in aged skin compared with young skin. Additionally, it highlighted the texture changes in the BMZ of young skin compared with aged skin. Further experimental analyses revealed that senescence cells were enriched in the BMZ, and the turnover of basement membrane (BM) components, including COL17A1, COL4A2, and ITGA6, was increased in aged skin. ConclusionPathoEye is a comprehensive tool for characterizing the unique features of different skin conditions associated with BMZ, thereby ensuring its potential applications in skin disease diagnosis and treatment planning.

bioinformatics↗

bioRxiv2025

Electroacupuncture promotes post-stroke motor recovery through miR-124-3p-mediated regulation of NRG1/ErbB4 signaling pathway

ObjectiveElectroacupuncture has demonstrated beneficial effects in post-stroke motor dysfunction, yet the molecular mechanisms underlying its therapeutic efficacy remain incompletely understood. This study aims to investigate whether electroacupuncture promotes post-stroke motor function recovery by modulating the interaction between miR-124-3p and the NRG1/ErbB4 signaling pathway, specifically exploring whether miR-124-3p directly targets NRG1 to regulate neural plasticity in a focal cerebral ischemia rat model. MethodsThe ischemic stroke model was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in adult rats. These rats were randomly divided into sham, model, electroacupuncture and model plus miR-124-3p inhibitor groups. The model group, electroacupuncture group and model plus miR-124-3p inhibitor group received EA intervention 24 h after modelling for 7 consecutive days. Behavioural function was assessed by Zea Longa score and mechanical pain rating. Hippocampal damage was detected by HE staining and neuronal apoptosis was observed by TUNEL staining. IL-1{beta} and IL-18 levels were measured by ELISA. PCR and Western blotting were used to detect the expression of miR-124-3p and inflammatory pathway proteins. The interaction between miR-124-3p and TLR4 was verified by dual-luciferase reporter assay. ResultsElectroacupuncture improved motor function in rat model of MCAO/R, as evidenced by improved Zea Longa scores and decreased mechanical withdrawal thresholds. Electroacupuncture significantly attenuated neuronal damage and also inhibited the inflammatory response by decreasing IL-18 and IL-1{beta} levels (P < 0.001). Notably, electroacupuncture upregulated miR-124-3p expression (P < 0.0001) and activated the NRG1/ErbB4 signaling pathway in the hippocampus. When miR-124-3p was inhibited, NRG1 protein expression decreased while GABA expression tended to increase. Dual-luciferase reporter assays confirmed that miR-124-3p directly targets the 3UTR of NRG1 mRNA and regulates its expression at the translational level. These findings suggest that electroacupuncture may alleviate neuronal and axonal damage by modulating miR-124-3p/NRG1/ErbB4 signalling and regulating GABA release. ConclusionElectroacupuncture can ameliorate motor dysfunction induced after brain I/R injury by targeting and modulating the NRG1-ErbB4 signaling pathway via miR-124-3p. These data are expected to provide new insights into the mechanisms of electroacupuncture for the prevention of potential targets for the recovery of motor dysfunction after stroke.

animal behavior and cognition↗

bioRxiv2025

Characterization of hyperoxia-induced senescent lung macrophages in neonatal mice

Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from mechanical ventilation and hyperoxia amongst other factors. We and others have shown that neonatal hyperoxia, known to lead to a BPD-like phenotype in rodent models, causes lung cellular senescence. In our 3-day hyperoxia model, the majority of senescent cells were lung macrophages, and these peaked at postnatal day (pnd) 7. The features of these senescent macrophages are not characterized. Here, we reanalyzed scRNA-seq datasets (GSE207866) of senescent lung cells from mice exposed to hyperoxia as neonates at pnd7 (SD7), and characterized their gene express profiling and compared them with air control (AirD7) and hyperoxia-exposed group without isolation of senescent cells at pnd7 (O2D7). We first classified the cells into epithelial, endothelial, immune, and mesenchymal cells to extract immune cells. By employing the workflow to the immune clusters, mixed populations of macrophages, monocytes, and dendritic cells and pure population of macrophages, we finally identified seven clusters of macrophages. In SD7 group, 65.9% senescent cells were macrophages, and comprised M1 (64%) and alveolar (62.8%) macrophages. Clusters 0 and 1 were M1 and alveolar macrophages, which were composed of 49.2% of senescent macrophages. These two clusters highly expressed genes involved in innate immunity, inflammation, DNA repair response and phagocytosis. Metabolic switch from mitochondrial respiration to glycolysis and pentose phosphate pathway was observed in these two clusters. Conclusively, senescent macrophages are heterogenous with distinct tissue compartments and metabolic dysregulation.

cell biology↗

bioRxiv2025

Fat taste responsiveness, but not dietary fat intake, is affected in Adipor1 null mice

Taste is a major driving force that influences food choices and dietary intake. Adiponectin has been shown to selectively enhance cellular responses to fatty acids by mediating the activation of AMPK and translocation of CD36 in taste cells via its receptor AdipoR1. Whether Adipor1 gene knockout affects fat taste responsiveness and dietary fat intake in animals remains unclear. In the present study, we evaluated cellular, neural, and behavioral responses to fat, as well as the dietary fat intake in global Adipor1 knockout mice and their WT controls. Sex-specific changes in cellular and behavioral responses to fatty acid were observed in Adipor1 knockout mice. Linoleic acid (LA)-induced calcium responsiveness appears to be reduced in taste cells from Adipor1-deficient males and increased in taste cells from Adipor1-deficient females. Brief-access taste testing revealed a loss of fat taste behavioral responsiveness in naive Adipor1-/- animals. Fat taste loss found in Adipor1-/- males was restored after fat exposure and showed no significant differences in taste behavioral responses to fatty acids with WT controls in two-bottle preference and conditioned taste aversion tests. Adipor1-/- females were found to have diminished preference for LA in two-bottle preference tests, lower intralipid/water lick ratio in a brief-access assay, and reduced avoidance for LA in conditioned taste aversion assay. Furthermore, the taste nerve responses to intralipid and the dietary fat intakes appeared to be the same between Adipor1-/- and WT mice. In the high-fat diet feeding study, Adipor1-/- females gained more weight, while no differences in body weight gain were found in males. Together, we show that adiponectin/AdipoR1 signaling plays crucial sex-specific roles in the modulation of fat taste and the maintenance of healthy body weight primarily by regulating energy expenditure rather than dietary fat intake in mice.

neuroscience↗

bioRxiv2025

Reduced inter-subject functional connectivity during movies in autism: Replicability across cross-national fMRI datasets

BackgroundAutism is a neurodevelopmental disorder characterized by repetitive behaviors and difficulties in social communication and interaction. Previous research has shown that these symptoms are linked to idiosyncratic behavioral and brain activity patterns while viewing natural social events in movies. This study aimed to investigate the replicability of brain activity idiosyncrasy in autistic individuals by comparing their inter-subject functional connectivity (ISFC) with that of neurotypical individuals. MethodsWe tested for ISFC differences between autistic and neurotypical groups using functional magnetic resonance imaging (fMRI) data from two independent datasets from Germany (Nneurotypical = 25, 7 Males, 18 Females; Nautism = 22, 12 Males, 10 Females) and Finland (Nneurotypical = 19, Nautism = 18; All males). Participants watched short movie stimuli, and pairwise ISFCs were computed across 273 brain regions. Group differences were evaluated using subject-wise permutation tests for each dataset. ResultsIn both datasets, the autistic group showed lower ISFCs compared to the neurotypical group, specifically between visual regions (e.g., occipital gyrus, cuneus) and parietal regions (e.g., superior and inferior parietal lobules), as well as between visual regions and frontal regions (e.g., inferior frontal gyrus, precentral gyrus). ISFC was higher in the Finnish autistic group in temporal regions associated with sound and speech processing. ConclusionsThe study confirmed the replicability of reduced ISFCs in autistic individuals during naturalistic movie-watching, especially between visual and parietal/frontal brain regions. These findings reinforce the utility of ISFC and naturalistic movie-watching paradigm in studying neural connectivity alterations in autism.

neuroscience↗

bioRxiv2025

From Local Interactions to Global Patterns: An Analysis of Silk Density in Spider Webs

This study explores the structural complexity of spider webs through information-theoretic and harmonicity-based frameworks to quantify spatial patterns in silk density across different web regions and reveal the underlying resource allocation strategies. Currently, there is no normalized approach for describing web structure and complexity, particularly for sheet-webs, and this methodology allows for non-destructive scanning and quantification of web characteristics. By analyzing the entropy of silk density distributions, a single scalar that captures the heterogeneity of material investment across the entire web, we observed that the entropy values follow a normal distribution with a mean of 1.24 {+/-} 0.22 bits when using 10 quantization levels. In the second part of the paper, by measuring the harmonicity of the silk density, we reveal that the silk density at a given point can be inferred from its neighbors, with an average harmonicity value of 0.0039 {+/-} 0.0017 (fraction of total points in point cloud data). The harmonic behavior is notable for its maximum principle, suggesting that the strongest parts of the web appear at the boundaries, aligning with existing knowledge of spider web construction. These findings provide a new technique for quantifying web-building strategies and offer new insights into spider behavior and evolution.

animal behavior and cognition↗

bioRxiv2024

Oncogene-induced senescence and senescence-associated secretory phenotype (SASP) determine the efficacy of palbociclib in PIK3CA mutated colorectal cancer

Palbociclib is an excellent CDK4/6 inhibitor, but its clinical application is mainly limited to the treatment of advanced ER+/HR+ and HER2- breast cancer. Its efficacy in colorectal cancer (CRC) is evaluated in multiple trials and so far remains undetermined. We found that the PIK3CA-mutant CRC cells were insensitive to palbociclib treatment compared with the PIK3CA wild-type counterparts, and they were in an OIS (oncogene-induced senescence) state which was predisposed to a strong senescence-associated secretory phenotype (SASP) upon treatment. These senescent cells excessively secreted various SASP factors LCN2, and ultimately caused palbociclib-resistance via upregulation of EGFR in the non-senescent CRC cells. Importantly, a drug combination screen identified that erlotinib could synergize with palbociclib to overcome the SASP-induced resistance. Overall, we found that PIK3CA mutation-induced senescence compromised the efficacy of palbociclib treatment in CRC but co-targeting EGFR could minimize the OIS-associated side effects while preserving the beneficial effects.

cancer biology↗

bioRxiv2024

Commensal gut virome regulates intestinal nutrient sensing via Th17 cells

The enteric microbiome and nutrient sensing in the small intestine play critical roles in maintaining host metabolic homeostasis. However, insight is limited to bacteria and fungi. The role of the enteric virome remains poorly understood. Here, we demonstrate that the enteric virome significantly influences carbohydrate digestion and absorption independently of bacteriome. Furthermore, the virome elicits distinct responses across different intestinal cell types. Specifically, it activates programs for carbohydrate digestion and absorption in intestinal epithelial cells, while simultaneously stimulating antigen presenting cells-Th17 cells to produce interleukin-22, a cytokine that curbs excessive carbohydrate uptake. The viromes effect on carbohydrate digestion and absorption--suppressive or stimulatory--depends on the presence or absence of immune surveillance. This intricate metabolic-immune interplay underscores the enteric virome as a pivotal regulator of host metabolism, and highlights its potential as a therapeutic target for metabolic disorders.

microbiology↗

bioRxiv2024

Dnajc3 (HSP40) Modulates Axon Regeneration in the Mouse Optic Nerve

A forward genetics approach was used to identify genomic elements enhancing axon regeneration in the BXD recombinant mouse strains. Axon regeneration was induced by knocking down Pten in retinal ganglion cells (RGCs) using adeno-associated virus (AAV) to deliver an shRNA followed by an intravitreal injection of Zymosan with CPT-cAMP that produced a mild inflammatory response. RGC axons were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by intravitreal injection of Cholera Toxin B (CTB) conjugated with Alexa Fluor 647. Two days later, labeled axons within the optic nerve were examined to determine the number of regenerating axons and the distance they traveled down the optic nerve. The analysis revealed a surprising difference in the amount of axonal regeneration across all 33 BXD strains. There was a 7.5-fold difference in the number of regenerating axons and a 4-fold difference in distance traveled by regenerating axons. These data were used to generate an integral map defining genomic loci modulating the enhanced axonal regeneration. A quantitative trait locus modulating axon regeneration was identified on Chromosome 14 (115 to 119 Mb). Within this locus were 16 annotated genes. Subsequent testing revealed that one candidate gene, Dnajc3, modulates axonal regeneration. Dnajc3 encodes Heat Shock Protein 40 (HSP40), which is a molecular chaperone. Knocking down Dnajc3 in the high regenerative strain (BXD90) led to a decreased regeneration response, while overexpression of Dnajc3 in a low regenerative strain (BXD34) resulted in an increased regeneration response. These findings suggest that Dnajc3 not only increases the number of regenerating axons, it also increases the distance those axons travel. This may prove to be critical for functional recovery in large mammals, where the distance axons travel to their target is considerably longer than that of the mouse. Thus, Dnajc3 may play a critical role for functional recovery in humans by increasing the number of regenerating axons and the distance the regenerating axons travel.

neuroscience↗

bioRxiv2024

An Atlas of Linkage Disequilibrium Across Species

Linkage disequilibrium (LD) is a key metric that characterizes populations in flux. To reach a genomic scale LD illustration, which has a substantial computational cost of[O] (nm2), we introduce a framework with two novel algorithms for LD estimation: X-LD, with a time complexity of[O] (n2m) suitable for small sample sizes (n < 104); X-LDR, a stochastic algorithm with a time complexity of[O] (nmB) for biobank-scale data (B iterations); n the sample size, and m the number of SNPs. These methods can refine the entire genome into high-resolution LD grids, such as more than 9 million grids for UK Biobank samples ([~]4.2 million SNPs). The efficient resolution for genome-wide LD leads to intriguing biological discoveries. I) High-resolution LD illustrations revealed how the pericentromeric regions and the HLA region lead to intense and extended LD patterns. II) Two universal LD patterns, identified as Norm I and Norm II patterns, provide insights on the evolutionary history of populations and can also highlight genomic regions of deviation, such as chromosomes 6 and 11 or ncRNA regions. III) The results of our innovative LD decay method aligned with the LD decay scores of 59.5 for Europeans, 60.2 for East Asians, and 33.2 for Africans; correspondingly, the length of the LD was approximately 2.85 Mb, 2.18 Mb, and 1.58 Mb for these three ethnicities. Rare or imputed variants universally increased LD. IV) An unprecedented LD atlas for 25 reference populations contoured interspecies diversity in terms of their Norm I and Norm II LD patterns, highlighting the impact of refined population structure, quality of reference genomes, and uncovered a profound status quo of these populations. The algorithms have been implemented in C++ and are freely available (https://github.com/gc5k/gear2).

genetics↗

bioRxiv2024

Adiponectin signaling modulates fat taste responsiveness in mice

We previously reported that the adiponectin receptor agonist AdipoRon selectively enhances cellular responses to fatty acids in a human taste cell line. The enhancement role of AdipoRon on fatty acid-induced cell responses is mediated by the activation of AMPK and translocation of CD36 on human taste cells. It has also been shown that adiponectin selectively increases taste behavioral responses to intralipid in mice. However, the molecular mechanism underlying the physiological effects of adiponectin on fat taste in mice remains unclear. Here we define AdipoR1 as the mediator responsible for the enhancement role of adiponectin/AdipoRon on fatty acid-induced responses in mouse taste bud cells. Calcium imaging data demonstrate that AdipoRon enhances linoleic acid-induced calcium responses in a dose-dependent fashion in mouse taste cells isolated from circumvallate and fungiform papillae. Similar to the human taste cells, the enhancement role of AdipoRon on fatty acid-induced responses was impaired by the co-administration of an AMPK inhibitor (Compound C) or a CD36 inhibitor (SSO). Utilizing Adipor1-deficient animals we determined the enhancement role of AdipoRon/adiponectin is dependent on AdipoR1 since AdipoRon/adiponectin failed to increase fatty acid-induced calcium responses in taste bud cells isolated from these mice. Brief-access taste tests were performed to determine whether AdipoRons enhancement role was correlated with any differences in taste behavioral responses to fat. Although AdipoRon enhances the cellular responses of taste bud cells to fatty acids, it does not appear to alter fat taste behavior in mice. However, fat naive Adipor1-/- animals were indifferent to increasing concentrations of intralipid, suggesting that adiponectin signaling may have profound effects on the ability of mice to detect fatty acids in the absence of previous exposure to fatty acids and fat-containing diets.

neuroscience↗

bioRxiv2024

Galvanotactic directionality of cell groups depends on group size

Motile cells migrate directionally in the electric field in a process known as galvanotaxis, important and under-investigated phenomenon in wound healing and development. We previously reported that individual fish keratocyte cells migrate to the cathode in electric fields, that inhibition of PI3 kinase reverses single cells to the anode, and that large cohesive groups of either unperturbed or PI3K-inhibited cells migrate to the cathode. Here we find that small uninhibited cell groups move to the cathode, while small groups of PI3K-inhibited cells move to the anode. Small groups move faster than large groups, and groups of unperturbed cells move faster than PI3K-inhibited cell groups of comparable sizes. Shapes and sizes of large groups change little when they start migrating, while size and shapes of small groups change significantly, lamellipodia disappear from the rear edges of these groups, and their shapes start to resemble giant single cells. Our results are consistent with the computational model, according to which cells inside and at the edge of the groups pool their propulsive forces to move but interpret directional signals differently. Namely, cells in the group interior are directed to the cathode independently of their chemical state. Meanwhile, the edge cells behave like individual cells: they are directed to the cathode/anode in uninhibited/PI3K-inhibited groups, respectively. As a result, all cells drive uninhibited groups to the cathode, while larger PI3K-inhibited groups are directed by cell majority in the group interior to the cathode, while majority of the edge cells in small groups win the tug-of-war driving these groups to the anode. Significance statementMotile cells migrate directionally in electric fields. This behavior - galvanotaxis - is important in many physiological phenomena. Individual fish keratocytes migrate to the cathode, while inhibition of PI3K reverses single cells to the anode. Uninhibited cell groups move to the cathode. Surprisingly, groups of PI3K-inhibited cells exhibit bidirectional behavior: larger/smaller groups move to the cathode/anode, respectively. A mechanical model suggests that inner and outer cells interpret directional signals differently, and that a tug-of-war between the outer and inner cells directs the cell groups. These results shed light on general principles of collective cell migration.

cell biology↗

bioRxiv2024

Salidroside Mitigates Malignant Arrhythmias by Restoring Sodium Channel Function During Ultra-Acute Myocardial Infarction

BackgroundThe ultra-acute phase (Phase 1a) of acute myocardial infarction (AMI) is marked by a high incidence of malignant arrhythmias, often occurring during the prehospital period. Currently, there are no effective treatment options available for managing these arrhythmias at this early stage. Methods and ResultsUsing dual-channel optical mapping, we simultaneously recorded membrane potentials and calcium transients during acute myocardial infarction. Calcium transient duration maps accurately localized the infarcted region, and action potential activation time maps revealed conduction heterogeneity in the infarcted zone. Patch-clamp recordings showed that Salidroside (Sal) (1 {micro}g/mL) significantly increased sodium current density from -59.27 {+/-} 2.15 pA/pF to -83.46 {+/-} 3.19 pA/pF (P<0.01) and shifted the Nav1.5 activation curve leftward (V1/2 from -37.27 {+/-} 0.5 mV to -44.55 {+/-} 0.7 mV, P<0.01). In rat and rabbit AMI models, Sal pre-treatment reduced conduction heterogeneity and arrhythmia incidence compared to controls. Optical mapping showed improved conduction velocity and uniformity in the Sal group. ConclusionsSal restores electrophysiological function in damaged myocardium by modulating sodium currents, reducing conduction heterogeneity, and decreasing malignant arrhythmia incidence during the ultra-acute phase of AMI. These findings suggest a novel therapeutic strategy for AMI, addressing a critical unmet need in antiarrhythmic therapy. What is New?O_LIThis study identifies Salidroside (Sal) as a novel agent that enhances sodium channel currents (Nav1.5), distinguishing it from traditional antiarrhythmic drugs which primarily target potassium channels or {beta}-adrenergic receptors. Sal improves conduction uniformity in the infarcted myocardium by restoring the electrophysiological function of damaged cardiac cells, eliminating slow conduction pathways, and reducing conduction heterogeneity. C_LIO_LIThis research introduces Sal as a promising candidate for preventing and treating arrhythmias during the critical early stages of MI, potentially improving patient outcomes. Sal administration during the ultra-acute phase (phase 1a) of myocardial infarction (MI) significantly reduces the incidence of malignant arrhythmias, a critical period characterized by high extracellular potassium and increased arrhythmia risk. C_LIO_LIUtilizing calcium transient imaging and optical mapping, this study provides precise localization of ischemic regions and detailed electrophysiological characterization, offering a robust methodology for assessing therapeutic efficacy. C_LI

pharmacology and toxicology↗

bioRxiv2024

CD6 Regulates CD4 T Follicular Helper Cell Differentiation and Humoral Immunity During Murine Coronavirus Infection

During activation the T cell transmembrane receptor CD6 becomes incorporated into the T cell immunological synapse where it can exert both co-stimulatory and co-inhibitory functions. Given the ability of CD6 to carry out opposing functions, this study sought to determine how CD6 regulates early T cell activation in response to viral infection. Infection of CD6 deficient mice with a neurotropic murine coronavirus resulted in greater activation and expansion of CD4 T cells in the draining lymph nodes. Further analysis demonstrated that there was also preferential differentiation of CD4 T cells into T follicular helper cells, resulting in accelerated germinal center responses and emergence of high affinity virus specific antibodies. Given that CD6 conversely supports CD4 T cell activation in many autoimmune models, we probed potential mechanisms of CD6 mediated suppression of CD4 T cell activation during viral infection. Analysis of CD6 binding proteins revealed that infection induced upregulation of Ubash3a, a negative regulator of T cell receptor signaling, was hindered in CD6 deficient lymph nodes. Consistent with greater T cell activation and reduced UBASH3a activity, the T cell receptor signal strength was intensified in CD6 deficient CD4 T cells. These results reveal a novel immunoregulatory role for CD6 in limiting CD4 T cell activation and deterring CD4 T follicular helper cell differentiation, thereby attenuating antiviral humoral immunity. ImportanceCD6 monoclonal blocking antibodies are being therapeutically administered to inhibit T cell activation in autoimmune disorders. However, the multifaceted nature of CD6 allows for multiple and even opposing functions under different circumstances of T cell activation. We therefore sought to characterize how CD6 regulates T cell activation in the context viral infections using an in vivo murine coronavirus model. In contrast to its role in autoimmunity, but consistent with its function in the presence of superantigens, we found that CD6 deficiency enhances CD4 T cell activation and CD4 T cell help to germinal center dependent antiviral humoral responses. Finally, we provide evidence that CD6 regulates transcription of its intracellular binding partner UBASH3a, which suppresses T cell receptor signaling and consequently T cell activation. These findings highlight the context dependent flexibility of CD6 in regulating in vivo adaptive immune responses, which may be targeted to enhance anti-viral immunity.

immunology↗

bioRxiv2024

Obscured Complexity: How External Cycles Simplify the Dynamics of the Endogenous Circadian Oscillator--take the time series of body temperature records as an example

BackgroundUnderstanding circadian rhythms is crucial in various fields of biological research, as they play a fundamental role in the regulation of diverse biological processes, ranging from gene expression to physiological functions. ObjectiveThis study aims to explore the complexity of circadian rhythm signals from a biological system. Without the permission of using experimental data, the mathematical model is utilized to simulate the intricate dynamics of the body temperatures circadian rhythms and investigate the impact of parameter variation on system behavior. MethodsThe Duffing equation is constructed as the mathematical model for simulating circadian rhythms. A thorough discussion justifies the selection of the Duffing equation and establishes the proper parameter range, ensuring chaotic behavior in the system. Four different values of the driving force parameter{gamma} (0.32, 0.33, 0.34, and 0.35) are chosen to represent specific cases. Fourier analysis is employed to analyze the simulation data, revealing the frequency components present in the circadian rhythm signals. Entropy analysis along the Poincare sections is utilized to measure the systems behavior and aggregation of points. ResultsThe simulations exhibit distinct characteristics in terms of plain visualization, Fourier analysis, and entropy analysis along the Poincare sections. Under normal work sleep conditions ({gamma} = 0.35), the system demonstrates specific resetting at particular times within a total period. In shift work ({gamma} = 0.34) conditions, some of the resetting behaviour diminishes and the initial phase of the time changes. In longterm constant temperature ({gamma} = 0:33) conditions, resembles that of normal work sleep conditions, with a noticeable reset at the beginning of the period. When all external driving forces are eliminated ({gamma} = 0:32), the system undergoes multiple resets within a given period. In such circumstances, the biological clock experiences more frequent resets to adapt to the independent operations of each subsystem. Without relying on external environmental cues for regulation, the biological clock relies on frequent resetting to maintain the stability and coordination of the entire system. ConclusionThe simulations reveals variations in resetting behavior and the importance of frequent resets in the absence of external cues. The complexity arising from chaos allows the biological system to adapt and adjust to the intricacies of the external environment. The endogenous clock within the system, despite its inherent complexity, can dynamically optimize its entrainment with external cycles. However, the full complexity of the endogenous clock may be concealed within the system and not readily observable. These findings contribute to a better understanding of the complex dynamics of circadian rhythms. Future research should aim to validate these results through comparisons with experimental data.

biophysics↗

bioRxiv2024

Propiconazole and Tianfengsu Regulated the Growth, Flavor, and Nutrition of Brassica rapa by Brassinosteroid Pathway

Propiconazole (PCZ) and Tianfengsu (TFS) are widely used plant growth regulators in vegetable production for improving crop growth, quality, and flavor. This study investigated the effects of PCZ and TFS, applied individually or in combination, on the growth, development, flavor quality, and nutritional components of choy sum (Brassica rapa) and Arabidopsis thaliana, as well as the underlying molecular mechanisms. The results showed that PCZ inhibited the growth of choy sum and Arabidopsis but enhanced the accumulation of flavor compounds such as soluble sugars, proteins, and vitamin C. In contrast, TFS promoted plant growth and increased the content of nutritional components, including chlorophyll and unsaturated fatty acids. Notably, the combined application of PCZ and TFS significantly improved overall plant quality, achieving the optimal balance of flavor and nutritional value while maintaining high yield. Transcriptomic analysis revealed the molecular mechanisms of PCZ and TFS in differentially regulating the expression of brassinosteroid (BR) signaling and downstream metabolism-related genes. Weighted gene co-expression network analysis (WGCNA) further identified key gene modules and hub genes controlling flavor metabolism in choy sum. This study elucidates the synergistic mechanisms of PCZ and TFS in regulating vegetable growth and quality formation, providing valuable insights for the safe production of high-quality choy sum and the development of novel plant growth regulators or elite varieties. HIGHLIGHTSO_LIPCZ and TFS treatments differentially modulate choy sum growth and development by regulating the BR pathway, with PCZ inhibiting while TFS promoting growth. C_LIO_LIPCZ enhances the accumulation of soluble sugars, soluble proteins, and vitamin C, while TFS increases photosynthetic pigments and unsaturated fatty acids, synergistically improving the flavor and nutritional quality of choy sum. C_LIO_LITranscriptomic analysis and WGCNA uncover key genes and modules controlling flavor metabolism in choy sum, providing potential targets for developing novel plant growth regulators or breeding elite varieties C_LI

plant biology↗

bioRxiv2024

Engineering PEG10 assembled endogenous virus-like particles with genetically encoded neoantigen peptides for cancer vaccination

Tumor neoantigen peptide vaccines hold potential for boosting cancer immunotherapy, yet efficiently co-delivering peptides and adjuvants to antigen-presenting cells in vivo remains challenging. Virus-like particle (VLP), which is a kind of multiprotein structure organized as virus, can deliver therapeutic substances into cells and stimulate immune response. However, the weak targeted delivery of VLP in vivo and its susceptibility to neutralization by antibodies hinder their clinical applications. Here, we firstly designed a novel protein carrier using the mammalian-derived capsid protein PEG10, which can self-assemble into endogenous VLP (eVLP) with high protein loading and transfection efficiency. Then, an engineered tumor vaccine, named ePAC, was developed by packaging genetically encoded neoantigen into eVLP with further modification of CpG-ODN on its surface to serve as an adjuvant and targeting unit to dendritic cells (DCs). Significantly, ePAC can efficiently target and transport neoantigens to DCs, and promote DCs maturation to induce neoantigen-specific T cells. Moreover, in mouse orthotopic liver cancer and humanized mouse tumor models, ePAC combined with anti-TIM-3 exhibited remarkable antitumor efficacy. Overall, these results support that ePAC could be safely utilized as cancer vaccines for antitumor therapy, showing significant potential for clinical translation.

cancer biology↗

bioRxiv2024

Transcriptomic and epigenetic responses shed light on soybean resistance to Phytophthora sansomeana

Phytophthora root rot caused by oomycete pathogens in the Phytophthora genus poses a significant threat to soybean productivity. While resistance mechanisms against Phytophthora sojae have been extensively studied in soybean, the molecular basis underlying immune responses to Phytophthora sansomeana remains unclear. We investigated transcriptomic and epigenetic responses of two resistant (Colfax and NE2701) and two susceptible (Williams 82 and Senaki) soybean lines at four time points (2, 4, 8, and 16 hours post inoculation, hpi) after P. sansomeana inoculation. Comparative transcriptomic analyses revealed a greater number of differentially expressed genes (DEGs) upon pathogen inoculation in resistant lines, particularly at 8 and 16 hpi, predominantly associated with ethylene and reactive oxygen species-mediated defense pathways. Moreover, DE transposons were predominantly up-regulated after inoculation and enriched near genes in Colfax. A long non-coding RNA (lncRNA) within the mapped region of the resistance gene exhibited exclusive up-regulation in the resistant lines after inoculation, potentially regulating two flanking LURP-one-related genes. Furthermore, DNA methylation analysis revealed increased CHH methylation levels in lncRNAs after inoculation, with delayed responses in Colfax compared to Williams 82. Overall, our results provide comprehensive insights into soybean responses to P. sansomeana, highlighting potential roles of lncRNAs and epigenetic regulation in plant defense.

plant biology↗