Biology subjects

Wang, L.

Publications and source records attributed to Wang, L..

At least 307 records · Page 17Linked to original sources

bioRxiv2025

Impact of Science Beliefs, Teaching Efficacy, and Incentives on Preschool Science Teaching: A Moderated-Mediation Model

Preschool teachers ability and willingness to adopt scientific practice teaching are affected by internal and external factors. A question therefore arises: Do organizational incentives, as an external environmental factor (extrinsic motivation), strengthen or weaken the effect of science beliefs (internal factor) on preschool teachers scientific practice teaching? We conducted a study with 1,331 teachers from kindergartens in China using voluntary, online, and anonymous questionnaires, implemented through the questionnaire Star application. Evidence shows that science beliefs have a significant positive effect on scientific practice teaching, with teaching efficacy mediating this relationship. Organizational incentives have a significant negative moderating effect on the relationship between science beliefs and scientific practice teaching and teaching efficacy. In this way, organizational incentives and scientific beliefs have a substitutional effect on scientific practice teaching and teaching efficacy. Therefore, preschools with lower incentive levels should aim to implement effective organizational incentives and target teachers beliefs. Those with higher incentive levels should ensure their incentives are effective and enhance teachers science beliefs to further strengthen teachers scientific practice teaching.

scientific communication and education↗

bioRxiv2025

Process optimization for enhanced enzymatic nylon deconstruction

Plastics such as polyamides (PAs) possess unique physicochemical properties that make them indispensable in modern society. However, their energy-intensive production and challenging end-of-life management highlight the urgent need for efficient recycling or remanufacturing solutions. Enzymatic depolymerization offers a promising route toward circular recycling, yet remains constrained by limited enzyme characterization, lack of validation under industrially relevant conditions, and overall performance. Here we optimized the reaction conditions for three recently discovered nylon-degrading enzymes. One of them, Nyl12, achieved product titers with PA6 and PA66 that exceed previously reported values, without enzyme engineering or substrate pretreatment. We further demonstrated the scalability of the process and its application to complex PA-based materials used in microelectronic components. Analysis of substrate features, including surface area and particle size, revealed key parameters governing enzymatic activity and provided a framework for future pretreatment and process optimization efforts. In combination, these efforts provide a new benchmark for enzymatic nylon recycling.

biochemistry↗

bioRxiv2025

Learning the mechanism of collective microbial function via random community-media pairing

In microbial systems, many biochemical functions arise from pathways encoded and executed at the community level. The collective nature of these functions complicates bottom-up efforts to determine each species contribution. Previous work has shown that regression over randomly sampled datasets of collective functions succeeds at predicting those functions. Building on this top-down idea, this paper asks whether regression can also reveal mechanistic insight into a cross-feeding relationship. For this, we propose extending the random sampling method to vary the growth environment, cultivating each community in the spent medium of another randomly constructed community. With a model-based analysis, we show that the new protocol extracts more mechanistic information, enabling assignment of species to the correct cross-feeding pathway steps and identification of species essential to the collective function, both achieved with simple LASSO regressions. More generally, our work illustrates that the utility of machine learning-based approaches can be greatly enhanced by a synergistic experimental design.

ecology↗

bioRxiv2025

Genomic signature of repeated transitions to diurnality in spiders

Repeated transitions to diurnality represent a major behavioral shift in spiders, yet their genomic underpinnings remain largely unknown. Here, we assembled high-quality genomes for nine diurnal spiders using long-read sequencing and compiled diel activity phenotypic data through a combination of meta-analysis and field assessments. By integrating all publicly available spider genomes, we examined the genomic evolutionary dynamics of 67 species including at least 5 independent origins of diurnality. Across diurnal spider lineages, hundreds of genes exhibited convergent shifts in selection, including intensified selection on neural, locomotion, and visual system genes, and relaxed selection on several core phototransduction components. Notably, diurnal spiders showed convergent deceleration in evolutionary rates in circadian regulators, such as CLOCK and CRTC1, and they harbored distinct repertoires of positively selected genes relative to non-diurnal species. In addition, convergent amino acid substitutions were enriched in diurnal hunting spiders. Comparative multi-tissue transcriptomics showed that genes under convergent selection, particularly those involved in vision, sensory processing, nervous system development, and locomotion, tended to exhibit stronger eye- and brain-biased tissue specificity in diurnal species. Altogether, our results reveal convergent genomic changes associated with repeated evolution of diurnality and illustrate how ecological light environments repeatedly shape the molecular evolution of complex animal behavior.

evolutionary biology↗

bioRxiv2025

Robustness of Ancestral Recombination Graph Inference Tools to Phasing Errors

Ancestral Recombination Graphs (ARGs) are fundamental population genetic structures that encode the genealogical history of a sample of haplotypes along the genome. They have recently received substantial attention as they can be used to provide accurate estimates of population history, form the foundation for selection scans, provide time-labeled estimates of changes in mutation rates, and more. ARGs can be inferred using multiple different methods, but these methods all rely on computational haplotype phasing. Previous studies have shown that the accuracy of haplotype phasing can be low when done in small or medium-sized samples, which are typical for most non-model organisms. Conventional wisdom would, therefore, suggest that ARG inferences are of limited utility in most non-model organisms. To test this assumption, we benchmark the robustness of four ARG inference methods -- Relate, SINGER, Threads, and tsinfer+tsdate -- to phasing errors. Their performance with imperfect phasing was tested under simple and realistic demographic models, and evaluated in terms of estimated pairwise coalescence times, counts of inferred recombination breakpoints, and estimated branch-length-based diversity. We observe only a slight degradation in performance when using computational phasing across all four methods and all tested demographic scenarios, demonstrating a surprising robustness of ARG inference methods to phasing inaccuracies. These findings support broader application of ARG inference in settings where large reference panels are not available.

genetics↗

bioRxiv2025

Deconvolution of Sparse-count RNA Sequencing Data for Tumor Cells Using Embedded Negative Binomial Distributions

Estimating tumor-specific transcript proportions from mixed bulk samples has potential to inform novel biology. However, estimation accuracy using existing methods in sparse-count data such as microRNA-seq and spatial transcriptomics has yet to be established. We generated a mixed small RNA benchmark dataset to demonstrate analytical challenges. To resolve them, we developed DeMixNB, a semi-reference-based deconvolution model assuming a sum of negative binomial distributions. Applications to miRNA-seq from 856 patients with breast cancer and 3,755 spatial spots from lung cancer generated either clinical or mechanistic insights into tumor cell plasticity. This supports the important utility of DeMixNB to investigate cancer RNomes.

bioinformatics↗

bioRxiv2025

Torque-based immune cell chemotaxis in complex environments

Directed migration in chemical gradients is crucial to the immune response, yet how immune cells navigate complex tissues remains incompletely understood. Using in vitro migration assays and theoretical modeling, we uncover distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). DCs actively steer toward chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias movement by modulating angular noise and speed. A quantitative Fokker-Planck framework decomposes these behaviors into deterministic and stochastic components. Cytoskeletal perturbations show that microtubules enable torque-based navigation in DCs in collagen gels, whereas actomyosin contractility is required for noise modulation employed by neutrophils and DCs in 2D confined migration assays. Despite both achieving directed migration, the two strategies result in opposing macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. These results reveal distinct navigation aligned with immune function and demonstrate that immune cell chemotaxis is tuned by cytoskeletal architecture and environmental context.

biophysics↗

bioRxiv2025

Harmonized Protocol for Segmentation of the Hippocampal Tail on High-Resolution in vivo MRI from the Hippocampal Subfields Group (HSG)

The hippocampus is a heterogeneous structure with cytoarchitectonically distinct subfields that exhibit heterogeneous lifespan trajectories and are differentially susceptible to diseases. Advances in high-resolution imaging have accelerated research on these structures, yet variability in segmentation protocols limits cross-study comparability. The Hippocampal Subfields Group (HSG) is an international consortium addressing this challenge by developing a reliable, accessible, and freely available segmentation protocol for high-resolution T2-weighted 3 tesla MRI scans (http://www.hippocampalsubfields.com). Here, we present the harmonized protocol for the posterior portion of the hippocampus (the "tail"), complementing the previously established "body" protocol, and with an anterior "head" protocol under development. The tail protocol provides standardized definitions of the external boundaries for the posterior-most extent of the hippocampus, facilitating consistent segmentation from surrounding tissues. The research community was extensively involved through an online survey that incorporated comprehensive protocol details, feasibility assessments, tutorial videos, and illustrative segmentations. Through this collaborative process, consensus emerged to exclude subfield labeling in the hippocampal tail due to limited visibility of internal landmarks and substantial anatomical variability in this region. All proposed boundary guidelines were deemed clear and agreed upon via a Delphi procedure. The harmonized tail protocol has high intra-(Averaged ICC(2,1) > 0.98; Averaged Dice Similarity Coefficient = 0.92) and inter-rater reliability (Averaged ICC(2,k) > 0.98; Averaged Dice Similarity Coefficient = 0.86) and offers a practical framework for replicable segmentation. By establishing standardized guidelines, this protocol enhances comparability of findings across developmental, aging, and clinical research and is compatible with ongoing technological advances.

neuroscience↗

bioRxiv2025

Proline transporters balance the salicylic acid-mediated trade-off between regeneration and immunity in plants

A robust immune response and regenerative capacity are both essential for survival after injury. In plants, salicylic acid (SA) is essential for activating immunity but simultaneously suppresses regenerative capacity. The mechanisms coordinating the trade-off between immunity and regeneration remain poorly understood. Here, we identify proline transporters as key regulators of this balance. Mutations in two wound-induced proline transporters, ProT2 and ProT3, rescued exogenous proline-induced suppression of de novo root regeneration (DNRR) and enhanced DNRR. ProTs are required for SA-mediated suppression of regeneration, without affecting SA-dependent defense responses. Mechanistically, a ProT3-CPK1 complex modulates the dynamics of wound-induced reactive oxygen species (ROS), sustaining a ROS level that restricts DNRR after wounding. Notably, pharmacological inhibition of proline transport rescued SA-mediated suppression of regeneration and enhanced regeneration across multiple plant species. These findings establish proline transporter as a regulatory hub integrating stress-induced proline metabolism, SA signaling, and ROS homeostasis to balance immunity and regeneration, and highlight chemical inhibition of proline transport as a strategy to improve crop regeneration under biotic stresses without compromising disease resistance.

plant biology↗

bioRxiv2025

A Syngeneic Immunocompetent Mouse Model of Gallbladder Cancer Reveals Tumorigenesis and Therapeutic Response

PurposeGallbladder cancer (GBC) is a rare but highly lethal malignancy with one of the poorest prognoses among cancers of the digestive system cancers. However, current experimental models of GBC face critical limitations, particularly their dependence on immunodeficient hosts, which precludes the investigation of the tumor microenvironment. We aimed to establish a novel syngeneic immunocompetent mouse model that recapitulates human GBC and enables the investigation of tumor-immune interactions. Experimental DesignWe engineered a murine cell line (mGBC1-ZH) from normal mouse gallbladder organoids expressing Kras and Trp53 (encoding mouse p53) mutations. Tumorigenic potential of mGBC1-ZH was evaluated by subcutaneous and orthotopic implantation. RNA-Seq and WES was used to demonstrate its characterization and similarity with human GBC. Immunohistochemistry, CCK8, and transwell assays wereused to investigate the role of CXCL5 in GBC. Therapeutic responses to standard first-line chemotherapeutic agents was evaluated in the syngeneic GBC model. ResultsThis model supports both subcutaneous and orthotopic tumor growth in immunocompetent C57BL/6J hosts while preserving hallmark features of human GBC, including biliary epithelial differentiation (CK7+/CK19+), aggressive histopathology, and an immunosuppressive "cold" tumor microenvironment. Genomic characterization revealed recurrent chromosomal instability and copy number alterations mirroring human GBC. Comprehensive transcriptomic profiling revealed profound gene expression changes during the model development, and resembled transcriptional features between mGBC1-ZH and human GBC cell lines and samples. CXCL5 was found to be upregulated in human GBC, and promote proliferation, metastasis, and neutrophils infiltration of GBC in the syngeneic mouse model. Functional validation of the syngeneic GBC model demonstrated therapeutic responsiveness to frontline chemotherapeutics gemcitabine and cisplatin with significant in vivo tumor regression. ConclusionsIn summary, we establised a novel syngeneic GBC mouse model, overcoming the limitations of traditional models by enabling studies in immunocompetent hosts. This model provides valuable insights into the molecular evolution from normal gallbladder cells to transformed cancer cells and establishes a robust platform for both mechanistic studies and therapeutic development.

cancer biology↗

bioRxiv2025

Multidimensional Single-Cell Transcriptomic Profiling of Uterine Leiomyosarcomas Identifies Molecular Subtypes with Distinct Therapeutic Vulnerabilities

Uterine leiomyosarcoma (ULMS) is an orphan disease that frequently recurs and metastasizes, with patients undergoing multiple lines of chemotherapy due to lack of effective therapeutic targets. To address this gap, we used single-cell RNA sequencing and spatial transcriptomic analysis to comprehensively profile ULMS. We uncovered multiple states of tumor cells, including tumor cells with mesenchyme-like features, ischemic tumor cells defined by a MYC program, inflammatory tumor cells with active interferon signaling, and stem cell-like hormone receptor-positive cells. The inferred spatial correlates of these tumor cell states demonstrated unique localization patterns. By correlating these signatures to bulk RNA sequencing data, we demonstrate the relevance of these findings to clinical outcomes. Finally, using the single-cell integration and drug response prediction algorithm (scIDUC), we propose drug predictions that may target specific tumor states. Our findings suggest new avenues for further exploration of individualized and multifaceted therapeutic strategies to treat ULMS.

cancer biology↗

bioRxiv2025

Combinatorial Cell-Adhesion and Activity Codes Instruct Cortical Modality Identity

The emergence of functional sensory modalities requires precise cortical arealization and appropriate thalamocortical targeting. Although early morphogen gradients set broad cortical territories, the mechanisms that specify sensory identity and guide modality-specific thalamocortical targeting remain unknown. Here, we identify an embryonic set of activity-independent cortical "protogenes", prominently enriched for cell-adhesion molecules, that are differentially expressed between primary somatosensory (S1) and visual (V1) cortices prior to thalamic innervation. These adhesion programs are selectively localized to layer 4, the main thalamo-recipient layer, and strikingly mirror the adhesion profiles of their corresponding thalamic nuclei, suggesting partner recognition. Disrupting thalamic activity alters modality-specific spontaneous cortical dynamics and the postnatal expression of another set of modality-specific genes, indicating a modulatory role for thalamic activity in cortical identity. These findings support a two-step model in which cortical identity is primed by adhesion codes driving modality-specific thalamocortical targeting, and later refined by patterned thalamic activity to establish functional cortical modalities.

neuroscience↗

bioRxiv2025

Inherited retinal degenerations: PARP regulates calpain activation via TRPM2 channels in rd1 mouse photoreceptors

Inherited retinal degeneration (IRD) refers to untreatable blinding diseases characterized by progressive photoreceptor loss. Photoreceptor degeneration is often associated with an excessive activation of poly (ADP-ribose) polymerase (PARP) and Ca2+-dependent calpain-type proteases. To explore the interplay between PARP and calpain activity, we employed organotypic retinal explant cultures derived from wild-type mice and from the rd1 mouse model for IRD. Retinae were treated with the PARP inhibitors INO1001 or Olaparib, the poly (ADP-ribose) glycohydrolase (PARG) inhibitor JA2131, or the transient receptor potential channel M2 (TRPM2) blocker 8-Br-ADPR. Readouts included the TUNEL assay to detect cell death, in situ activity assays for histone-deacetylases (HDAC), PARP, and calpain, as well as immunostaining for activated calpain-2, and poly (ADP-ribose) (PAR). PARP, PARG, and TRPM2 inhibition reduced calpain activity and calpain-2 activation. PARP activity was decreased by PARP and TRPM2 inhibitors but not by PARG inhibition. Remarkably, the PARP inhibitor INO1001 increased HDAC activity unlike any of the other compounds. When combined with the PARG inhibitor JA2131, INO1001 reduced photoreceptor cell death in a synergistic fashion, although such synergy was not observed for calpain or PARP activity. Moreover, synergistic photoreceptor preservation was not observed when JA2131 was combined with the PARP inhibitor Olaparib. Overall, these results indicate that in rd1 photoreceptors, PARP controls calpain activity via PARG and TRPM2-induced Ca2+ influx. We also characterize INO1001 as potentially more beneficial for IRD treatment than Olaparib. Our study details the complexity of PARP-signalling in photoreceptors and identifies PARG and TRPM2 as new targets for IRD therapy development.

neuroscience↗

bioRxiv2025

Myosin VI orchestrates estrogen-driven gene expression in breast cancer cells.

Approximately 75% of breast cancer cases are estrogen receptor (ER)-positive, with endocrine therapies forming the foundation of treatment. However, therapeutic resistance remains a major clinical challenge, necessitating the identification of new molecular targets. Myosin VI (MVI), a motor protein increasingly linked to cancer, directly interacts with the ER and plays a key role in the spatial regulation of RNA Polymerase II. Notably, expression levels of MVI and ER are positively correlated across breast cancer tissues. Here, we present a multidisciplinary investigation combining advanced imaging, genomic profiling, and phenotypic characterisation to elucidate the interplay between MVI and the ER. We demonstrate that MVI nuclear localisation is dynamically regulated by estrogen signalling and ER activity. Conversely, ER nuclear localisation requires active MVI, suggesting a reciprocal regulatory mechanism. Furthermore, MVI influences subnuclear architecture, modulating ER transcriptional activity and downstream gene expression programmes that govern cell proliferation and migration. Importantly, pharmacological inhibition of MVI enhances the effect of hormone therapy, resulting in greater disruption of ER function than monotherapy alone. Moreover, MVI inhibition also suppresses the activity of hormone-resistant ER mutants, highlighting its potential to overcome therapy resistance. Our findings establish MVI as a critical regulator of ER nuclear dynamics and gene expression, supporting its candidacy as a novel therapeutic target in ER-positive breast cancer.

cancer biology↗

bioRxiv2025

Structural and Functional Insights into HBx-Smc6 Targeting for HBV Inhibition

The hepatitis B virus (HBV) X protein (HBx) is a multifunctional regulator essential for HBV replication and HBV-associated hepatocarcinogenesis. Despite its central role, the molecular basis of HBx function has remained elusive. Here, we present the first cryo-electron microscopy structure of the human HBx-CRL4-Smc5/6 complex at 3.1 [A] resolution. In this reconstituted ten-subunit assembly, HBx adopts a Zn2 {square}-stabilized Y-shaped architecture that simultaneously engages the DDB1 and the Smc6 subunit. A composite helix-turn-helix (HTH) pocket in HBx accommodates a conserved "Leucine Key" motif (LRCKL) on Smc6, forming a critical interface essential for complex stability and function. Molecular docking and biochemical validation reveal that the compound Tranilast binds this HTH pocket, disrupts the HBx-Smc6 interaction, and suppresses HBV replication. These findings define the structural mechanism by which HBx counteracts host restriction and establish the HBx-Smc6 interface as a previously unrecognized and druggable target for antiviral intervention.

cell biology↗

bioRxiv2025

A BCG toxic effector induces mitochondrial DNA compaction to refrain protective immunity

Innate immune memory typically emphasizes nuclear chromatin remodeling that determines transcriptional memory in monocytes and macrophages. Here, we show that compaction of mitochondrial DNA (mtDNA), governed by mitochondrial transcription factor A (TFAM) abundance and mtATP-dependent remodeling, defines the transcriptional and functional state of trained macrophages. While typical pathogen-associated molecular pattern (PAMPs) triggered mtDNA accessibility, Bacillus Calmette-Guerin (BCG) effector PE18 directly interacted with and activated SLC25A5 to reduce mtATP levels, thereby inhibiting TFAM degradation by AFG3L2. Accumulated TFAM restricts mtDNA accessibility, suppressing the transcription of the mtNd1 and thereby reducing mtNd1-mediated mtROS production, which diminishes the trained capacity of macrophages against secondary infections. Notably, BCG{Delta}pe18 maintains macrophages cytokine transcriptional capacity independent of classical nuclear histone modifications. Moreover, BCG{Delta}pe18 provides robust and lifelong protective immunity against Mycobacterium tuberculosis (Mtb) infection. These findings reveal mitochondrial genome as a regulatory entity in trained immunity, and suggest a potential strategy for improving vaccine performance.

immunology↗

bioRxiv2025

Design, synthesis, and pharmacological evaluation of novel PROTAC degraders targeting 11β-HSD1 for metabolic disease intervention

Hydroxysteroid 11-beta dehydrogenase 1 (11{beta}-HSD1) plays a critical role in metabolic homeostasis by catalyzing the intracellular conversion of cortisone to cortisol. Dysregulated 11{beta}-HSD1 activity is closely associated with metabolic disorders such as type 2 diabetes mellitus, obesity, and glucocorticoid-related inflammation. While small-molecule inhibitors of 11{beta}-HSD1 have shown promise, they primarily suppress enzymatic activity without modulating protein abundance. Here, we report the development of the 11{beta}-HSD1-targeting PROTAC degraders. A series of bifunctional molecules were synthesized based on CRBN- and VHL-recruiting ligands, with AZD8329-derived warheads linked via polyethylene glycol chains. Cellular assays demonstrated efficient, ubiquitin-proteasome-dependent degradation of 11{beta}-HSD1, with H-3-V identified as the most potent degrader. In vivo, H-3-V treatment improved glucose tolerance and enhanced glucose-stimulated insulin secretion in a high-fat diet-induced T2DM mouse model. Molecular dynamics simulations revealed that the H-3-V ternary complex exhibited superior binding energetics compared to less active analogs. Collectively, this study introduces a novel chemical modality for 11{beta}-HSD1 modulation and lays the groundwork for future therapeutic development targeting metabolic disease via selective protein degradation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/687522v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@60aa3borg.highwire.dtl.DTLVardef@484120org.highwire.dtl.DTLVardef@1abca2eorg.highwire.dtl.DTLVardef@166b1a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

A 5'-end based Molecular Marker Enables Identification and Deployment of a Functional Rpi-vnt1.1 Allele for Durable Late Blight Resistance in Potato

Potato (Solanum tuberosum) is a globally important food crop, yet its production is severely threatened by late blight, caused by Phytophthora infestans. Deploying resistance (R) genes in breeding programs offers a sustainable approach for disease management. Rpi-vnt1.1 is a broad-spectrum R gene cloned from wild Solanum species Solanum venturii. Here, we developed a PCR marker targeting the 5'-end extension of Rpi-vnt1.1, which enables efficient and specific detection of the resistant alleles. Screening of advanced breeding lines from the International Potato Center (CIP) identified line C1848, which carries a functional Rpi-vnt1.1 allele. Inoculation assays confirmed C1848 confers strong resistance to P. infestans. Subsequent functional assays, including RNAi-mediated silencing in C1848 and heterologous expression in Nicotiana benthamiana, demonstrated that this resistance is specifically mediated by the Rpi-vnt1.1 allele. This specific marker provides a rapid, low-cost tool for marker-assisted breeding, facilitating the deployment of potato cultivars carrying Rpi-vnt1.1.

plant biology↗