Biology subjects

Li, B.

Publications and source records attributed to Li, B..

At least 55 records · Page 3Linked to original sources

bioRxiv2026

SureQuant IS-PRM Enables Cross-Species Targeted Quantification of Retinoid Metabolism and Signaling Proteins in the Heart

Retinoic acid signaling is critical for cardiac development and homeostasis. Dysregulation of all-trans retinoic acid metabolism contributes to vascular atherogenesis, restenosis, calcification, and heart failure. Therefore, assessment of proteins involved in retinoid metabolism and signaling has gained interest for identifying potential biomarkers and therapeutic targets in cardiovascular disease. However, quantifying these proteins remains challenging due to limitations of antibody-based methods. We developed a targeted proteomics approach using SureQuant internal standard-triggered parallel reaction monitoring mass spectrometry to profile these proteins. We designed a panel of 80 stable isotope-labeled (heavy) peptides representing proteins involved in retinoid signaling and metabolism, with sequences applicable to human samples and conserved across multiple species. Survey experiments using directed data-dependent acquisition on the Orbitrap Fusion Lumos mass spectrometer determined precursor and product ion masses for each heavy peptide, which were programmed into the SureQuant method for continuous monitoring. Upon detection of these heavy internal standards, the instrument transitions to a targeted PRM acquisition mode in which repeated high-resolution MS/MS spectra of both endogenous (light) and heavy peptides are acquired. Using this method, retinoid pathway-associated proteins were quantified to as low as 10 attomoles for selected targets across multiple tissues and developmental stages. Distinct tissue-specific retinoid metabolic networks were identified across lung, liver, retinal cell lines and cardiac tissues. Developmental profiling of mouse and rat hearts revealed remodeling of retinoid pathway proteins from embryonic to postnatal and adult stages, suggesting a functional transition from retinoid-driven cardiac development toward maintenance of retinoid homeostasis in the mature heart.

biochemistry↗

bioRxiv2026

Task-Dependent and Cell-Type-Specific Modulation of the Mouse Dorsal Cortex of the Inferior Colliculus

Sensory responses in the auditory system are modulated by behavioral context, and this modulation extends as early as the inferior colliculus (IC). Where within the IC it occurs, which neurons it affects, what behavioral variables drive it, and whether it requires the auditory cortex remain unclear. We imaged the dorsal cortex of the IC (DCIC) with two-photon microscopy in head-fixed mice (n = 7) performing a two-alternative forced-choice tone-discrimination task, with blocks of passive listening to the same tones before and after, while recording orofacial movement, licking, and pupil diameter from synchronized video. Unsupervised clustering of sound-evoked responses in 1479 tracked neurons identified four functional response classes: onset-excited, sustained-inhibited, offset/motor-excited, and transient-inhibited. Task engagement modulated these classes in distinct and outcome-dependent ways, with the sustained-inhibited and transient-inhibited classes more suppressed and the offset/motor-excited class more excited during active trials, and with hit and miss trials driving most of the effect. Population activity discriminated active from passive trials above chance, and this discrimination outlasted the stimulus. A linear encoding model attributed a substantial share of the explained variance in three of the four classes to facial movement, whereas pupil diameter contributed little in any class. The correlation between orofacial motion and activity was itself context-dependent in the sustained-inhibited and transient-inhibited classes, but not in the offset/motor-excited class. Bilateral chemogenetic silencing of the auditory cortex (n = 3 mice, 171 matched neurons) altered task modulation only in the sustained-inhibited class. Task-related modulation in the DCIC is therefore heterogeneous across functionally defined neurons, is closely tied to movement, and depends on the auditory cortex in only one of these populations.

neuroscience↗

bioRxiv2026

Diagnostic Performance of Fluorescence-Based Rapid On-Site Specimen Evaluation for Helicobacter pylori Antimicrobial Susceptibility Testing Before and After Algorithm Optimization: A Two-Round Comparative Study

ObjectiveThis study was designed to evaluate the diagnostic performance of fluorescence-based rapid on-site specimen evaluation (F-ROSE) for antimicrobial susceptibility testing of Helicobacter pylori (H. pylori) and to compare test performance before and after iterative optimization of fluorescence image acquisition and of the artificial intelligence (AI) recognition algorithm, using two consecutive rounds of paired testing, so as to provide trial data supporting clinical implementation of rapid susceptibility testing. MethodsForty patients with a urea breath test (UBT) or rapid urease test (RUT) positive for H. pylori within the preceding 2 weeks, together with strongly positive endoscopic findings, were prospectively enrolled. In order of enrollment they were allocated to two rounds in which F-ROSE was compared with culture-based susceptibility testing. Twenty patients were tested in round 1 on an automated fluorescence immunoassay scanner running the original algorithm; a further 20 were tested in round 2 with the optimized algorithm. With in vitro culture and E-test as the reference standard, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of F-ROSE were calculated for each round for amoxicillin, levofloxacin hydrochloride and clarithromycin, and agreement between methods was assessed with Cohens kappa. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff of the fluorescence residual rate (FRR) and to determine how far threshold adjustment improved performance. ResultsCulture succeeded in 15 patients in round 1 and in 14 patients in round 2, leaving 29 evaluable samples. Overall diagnostic performance after algorithm optimization was clearly better than before. Pooled across the three antibiotics, sensitivity was 92.9%, specificity 71.0% and accuracy 77.8% before optimization; after optimization sensitivity rose to 100.0%, specificity increased slightly to 74.2% and accuracy to 81.0%. NPV reached 100.0% for all three agents after optimization, and no resistant isolate was missed. The gain was largest for clarithromycin, for which sensitivity rose from 85.7% to 100.0%, accuracy from 66.7% to 78.6% and kappa from 0.348 to 0.571, indicating a clear improvement in agreement between the two methods. ROC analysis showed that drug-specific optimal cutoffs derived from the Youden index improved specificity appreciably compared with the uniform 50% FRR threshold currently applied, the gain being most evident for levofloxacin hydrochloride. ConclusionsWith sharper fluorescence images and an improved AI recognition algorithm, F-ROSE performs better in H. pylori susceptibility testing, and the reduction in missed resistant strains is particularly noteworthy; the assay is therefore a plausible option for rapid susceptibility screening in clinical practice. Multicenter studies with larger samples are still required to confirm the stability of the technique.

microbiology↗

bioRxiv2026

Group Behaviors Foster Zebrafish Foraging Through Social Interaction

Group living enhances foraging efficiency, yet whether this benefit extends across developmental stages and how social coordination versus emotional buffering contribute remain unresolved. Using zebrafish (larvae 10 dpf, adults 80 dpf) in a Y-maze foraging task with high-resolution tracking and mirror experiments, we show that grouping reduces foraging latency in adults, but not larvae. Adults form coordinated groups (high polarization, small inter-individual distances), whereas larvae form loose aggregations. Adults, but not larvae, exhibit reduced freezing (social buffering) when grouped. Mirror-presented visual cues suffice to enhance foraging via emotional calming--reducing freezing and stabilizing speed--yet disrupt real-group coordination. Our results reveal a dual mechanism-- instrumental coordination and emotional buffering--by which group behavior promotes foraging. Both mechanisms are developmentally gated, emerging only after maturation, offering insights into the ontogeny of social competence and practical implications for aquaculture and conservation.

ecology↗

bioRxiv2026

Programmable and Dynamic DNA Localisation at Synthetic Cell Membranes

Spatial and temporal organisation of membrane-associated components is fundamental to cellular signalling, yet remains difficult to engineer in minimal synthetic systems. In synthetic cells, DNA and RNA nanotechnology offer programmable molecular organisation at membranes, while in vitro transcription (IVT) enables gene expression-driven regulation. However, integrating these systems within cell-like compartments, such as giant unilamellar vesicles (GUVs), remains challenging due to undesirable interactions between transcription machinery and nucleic acid assemblies. Here, we present a modular strategy that couples in situ RNA production to dynamic DNA localisation at GUV synthetic cell membranes. RNA strands, transcribed within GUVs, function as linkers that recruit DNA-conjugated cargo to lipid membranes, enabling programmable spatial organisation. Using this framework, we achieved reversible membrane localisation through toehold-mediated strand displacement and RNase H-mediated degradation. This work establishes a gene expression-driven platform for programmable and dynamic control of membrane-associated components in synthetic cells, providing a foundation for constructing dynamic signalling assemblies and higher-order cellular behaviours. O_FIG O_LINKSMALLFIG WIDTH=191 HEIGHT=200 SRC="FIGDIR/small/738173v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@1d6dbc4org.highwire.dtl.DTLVardef@f6419aorg.highwire.dtl.DTLVardef@14cff99org.highwire.dtl.DTLVardef@20b95a_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2026

Culture-Free Rapid Phenotypic Antimicrobial Susceptibility Testing for Helicobacter pylori Based on Fluorescence Rapid On-Site Evaluation Technology: A Preliminary Study

BackgroundPhenotypic antibiotic susceptibility testing (AST) for Helicobacter pylori (H. pylori) has relied on bacterial culture for three decades, requiring 5-7 days to yield results. Genotypic rapid tests can only detect known resistance mutations and fail to reliably identify amoxicillin resistance. To our knowledge, no culture-free rapid phenotypic AST method for H. pylori has been previously reported. MethodsWe developed a phenotypic AST method based on fluorescence rapid on-site evaluation (ROSE) technology that completely bypasses bacterial culture. Gastric mucosal biopsy specimens from 40 H. pylori-positive patients were homogenized and co-incubated with an acridine orange/ethidium bromide (AO/EB)-based viability staining reagent and three first-line antibiotics--amoxicillin, clarithromycin, and levofloxacin--at concentrations corresponding to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for H. pylori, at 37 {degrees}C for 1 hour. Fluorescence intensity was measured using a microplate reader. A reduction in fluorescence relative to an antibiotic-free control indicated susceptibility, whereas no significant reduction indicated resistance. Conventional culture-based AST (E-test) served as the reference method. The overall concordance rate, sensitivity, specificity, and Cohens kappa coefficient were calculated. ResultsFourteen of the 40 samples had unsuccessful culture and were excluded, leaving 26 samples for statistical analysis of each antibiotic. The overall concordance rates between the ROSE method and culture-based AST were 84.6% (22/26) for amoxicillin, 76.9% (20/26) for levofloxacin, and 69.2% (18/26) for clarithromycin. Cohens kappa coefficients indicated moderate agreement for all three antibiotics ({kappa} = 0.523, 0.539, and 0.412, respectively). Unlike genotypic methods, the ROSE method successfully assessed amoxicillin susceptibility in all 40 patients--a critical first-line antibiotic for which no reliable genetic resistance marker currently exists. The turnaround time was approximately 1 hour (55-65 minutes), compared with 5-7 days for culture-based methods; preliminary estimates indicated a cost reduction of approximately 3,000-5,000 Chinese yuan (CNY) per patient, mainly attributable to the elimination of culture media, prolonged incubation, and repeat clinic visits. ConclusionsThis study reports, for the first time, a culture-free 1-hour phenotypic AST for H. pylori. The method enables same-day, susceptibility-guided treatment decisions, addressing an unmet clinical need spanning three decades. Algorithm optimization and a prospective randomized controlled trial are currently underway to further improve diagnostic accuracy and validate clinical utility.

microbiology↗

bioRxiv2026

Accessible spatial host-microbe profiling in tumour tissues

The ability of current spatial transcriptomics platforms to sensitively and specifically detect tissue-resident microbes alongside the whole host transcriptome remains limited. Here we present HOst MicrobE Spatial-seq (HOMES-seq), a Visium-based workflow for joint spatial profiling of microbial species and the host transcriptome in formalin-fixed paraffin-embedded (FFPE) colorectal tumours. HOMES-seq incorporates an analytical framework to distinguish contaminant-derived signals from bona fide tissue-resident microbes while improving detection sensitivity and reducing sequencing costs relative to existing approaches.

microbiology↗

bioRxiv2026

Origin of Schooling and Collective Environmental Adaptation in Zebrafish

Zebrafish exhibit intricate schooling behaviors when swimming as a group. Such collective motion serves profound ecological functions and continuously inspires the design of highly coordinated artificial systems. Although the features and functions of schooling have been extensively studied, how this behavior originates over the course of individual development remains unknown, limiting a comprehensive understanding of its biological consequences. To address this gap, we developed a cross-scale, multi-modal experimental platform to capture zebrafish schooling and integrated AI-based algorithms to track fine-scale body posture and eye movements. We find that schooling emerges within a discrete developmental window, coinciding with coordinated changes in locomotor architecture and visual perceptual capacity. Specifically, structural remodeling of the caudal fin, enhanced muscle bundling, and an expanded visual perceptual range together provide the physical and sensory basis for the stabilization of polarized group movement. Network analyses under different representational frameworks reveal that the biological function of schooling is a collective group strategy for adapting to the external geometric environment. Our work provides a fundamental explanation of zebrafish schooling from a developmental perspective and elucidates a collective strategy that could inform the design of underwater robot arrays.

ecology↗

bioRxiv2026

Peri-Locus Coeruleus Controls Endothelial Cell Heterogeneity in Enriched Environments via Region-Specific Norepinephrine Signaling

The brain acts as a central integrator that enables organisms to interpret environmental stimuli and coordinate adaptive responses across the body. While enriched environments are known to enhance neural plasticity and cognitive function, their impact on peripheral organ systems remains less understood. Here, we show that enriched environmental conditions activate a peri-locus coeruleus (peri-LC) neuronal ensemble that preserves CD31hiEMCNhi type H endothelium, a specialized bone-associated endothelial subtype, against age-associated decline, thereby enhancing femoral bone density. Chemogenetic activation and ablation experiments further revealed that this peri-LC ensemble is functionally distinct from other sympathetic regulatory brain regions in its control of bone endothelial heterogeneity and skeletal mass. Three-dimensional bone clearing and spatial analyses showed that CD31hiEMCNhi endothelium is closely associated with sympathetic nerve terminals. The peri-LC mediates this process through sympathetic signaling and {beta}2-adrenergic receptors on bone vascular endothelial cells. In vivo imaging further demonstrated that norepinephrine release is spatially restricted, with sprouting endothelial cells near the growth plate exhibiting the highest sensitivity. Together, these findings reveal a refined brain-periphery regulatory logic in which distinct sympathetic brain circuits engage spatially restricted norepinephrine signaling to coordinate organ-specific vascular and skeletal adaptations.

neuroscience↗

bioRxiv2026

Therapy-induced senescent-like cancer cells drive macrophage-mediated immunosuppression in cholangiocarcinoma

Cholangiocarcinoma (CCA) is a lethal biliary cancer in which chemoresistance is nearly universal, and its tumor immune microenvironment is dominated by immunosuppressive tumor-associated macrophages (TAMs) that exclude cytotoxic CD8+ T cells. How tumor cells sustain this immunosuppressive state during chemotherapy is undefined. Here we demonstrate that therapy-induced senescent-like (Sen-L) cancer cells accumulate after gemcitabine/cisplatin in human and murine CCA, are predominantly cancer cells, and predict shorter survival. Genetic elimination of Sen-L cancer cells reduces tumor burden, lowers TAM abundance, and restores intratumoral CD8+ T cells, establishing them as causal drivers. Growth differentiation factor 15 (GDF-15) is the dominant Sen-L-secreted factor and reprograms macrophages to suppress CD8+ T cells through the non-canonical receptor TGFBR2 and STAT6, and p16-restricted Gdf15 silencing phenocopies Sen-L elimination. Combined with chemotherapy, Sen-L elimination improves survival beyond chemotherapy alone. These findings establish Sen-L cancer cells and their GDF-15 output as causal, targetable drivers of macrophage-mediated immune evasion in CCA. SIGNIFICANCE STATEMENTTherapy-induced senescent-like cancer cells, not stromal cells, are the dominant senescent-like and immunosuppressive population in cholangiocarcinoma, and their elimination restores antitumor immunity. GDF-15 is their dominant secreted effector and engages a non-canonical macrophage receptor, TGFBR2, identifying a cancer-cell-to-macrophage axis and a Sen-L-elimination strategy to restore chemosensitivity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/734341v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@7d3fd8org.highwire.dtl.DTLVardef@ea9efborg.highwire.dtl.DTLVardef@16ba16borg.highwire.dtl.DTLVardef@132b821_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. Senescent-like CCA cells promote tumor immunosuppression through TAMs polarization by GDF-15 C_FIG

Cancer Biology↗

bioRxiv2026

Development and Analytical Validation of a Smartphone-Based Quantitative Lateral Flow Immunoassay for Serum Cystatin-C

Cystatin-C is an important renal function biomarker, and conventional quantification requires centralized laboratory analyzers, which limits timely testing in primary care and resource-limited settings. To address this need, we developed and validated a simple, rapid, and quantitative smartphone-based (SP) lateral flow immunoassay (LFIA) for measuring serum Cystatin-C. The SP-LFIA platform consists of a colorimetric LFIA strip and a custom SP reader with uniform LED illumination and macro lens for image capture. Quantitative image analysis of the colorimetric signal is performed by a dedicated application using a pre-defined third order polynomial calibration model. Following systematic optimization, the assay demonstrated a wide quantitative range of 0.32-8.00 mg/L, with a limit of detection of 0.15 mg/L. Analytical validation conducted according to CLSI guidelines showed excellent precision, with intra- and inter-assay coefficients of variation below 10%, and no significant interference from bilirubin, triglycerides, hemoglobin, or rheumatoid factor. Accelerated stability testing confirmed robust strip performance after storage at 50 {degrees}C for 28 days. Method comparison using 100 clinical serum samples showed high agreement with a commercial PETIA reference method (R{superscript 2} = 0.993) and minimal bias. These results indicate that the developed smartphone-based LFIA provides a reliable, cost-effective, and practical tool for point-of-care Cystatin-C monitoring.

biochemistry↗

bioRxiv2026

Muscle Loss as a Foundational Step in the Development and Evolution of the Turtle Shell

Modern biodiversity is built on a series of disparate body plans whose origins are obscured by deep time. Our most direct source of clarifying data is the fossilized skeleton, where morphology reflects an evolving functionality realized through the development of associated tissues. We apply this dualistic perspective to the shelled body plan of turtles whose Paleozoic initiation is marked by a derived relationship between ribs and dermis (Lyson & Bever, 2020). Current developmental models remain in conflict with an increasingly informative fossil record, suggesting critical steps remain unrecognized. Here we explore the hypothesis that the breakdown of rib-spanning muscles--an evolutionary transformation mirrored in embryogenesis--is one such step. Multi-modal imaging of turtle embryos, including a novel application of histology-based deep learning (Kiemen et al., 2022; Matos-Romero et al., 2025; Forjaz et al., 2026), establishes intercostal muscle degradation as preceding turtle-specific rib development and highlights the heuristic power of 3D, whole-embryo analysis (Forjaz et al., 2026). Quantified divergence from mouse pinpoints the timing and tempo of this organized, apoptotic breakdown. Initial evidence suggests an associated non-pathological inflammatory response, which has been shown capable of driving evolutionarily stable hyperossification (Rashid et al., 2023). These patterns support trunk muscles as a critical signalling centre whose ontogenetic loss set the phylogenetic stage for a morphogenetic transformation remarkable in a non-metamorphic species.

evolutionary biology↗

bioRxiv2026

VrySure: A Multi-Task AI Scientific Fraud Detection Platform for Identifying Manipulated and AI-Generated Biomedical Research Images

Integrity of scientific data is critical in biomedical research, where images often serve as primary evidence for experimental observations and conclusions. Advances in image-editing technologies and generative artificial intelligence (AI) have increased the accessibility and realism of visual manipulation, making detection through manual review increasingly challenging. To empower our laboratory researchers to continuously monitor and uphold scientific rigor and data integrity, and serve the global scientific community, we developed VrySure, an easy-to-deploy, AI-driven multi-task platform for automated image-integrity screening in biomedical research. VrySure integrates four detection modules: cross-image transformation detection, within-image copy-move detection, splicing detection in blot and gel images, and AI-generated image detection. The system identifies potentially manipulated images and, when possible, localizes suspicious regions using bounding-box outputs to support downstream verification. To support development and evaluation, we constructed task-specific datasets by combining public biomedical image resources, curated manipulated examples, and synthetic images generated by multiple generative AI systems. We evaluated VrySure using region-level F1 score, recall, precision, false negative rate (FNR), and false discovery rate (FDR) across multiple manipulation categories and compared its performance with two commonly used commercial image-integrity screening platforms under a predefined benchmark protocol. Under the tested conditions, VrySure achieved a higher F1 score and recall, lower FNR, and maintained a low FDR for within-image copy-move detection, splicing detection, and AI-generated image detection, while showing comparable performance in transformation detection. Beyond automated screening, VrySure is designed to support source-data comparison and evidence-based assessment in scientific integrity investigations. By integrating multiple detection capabilities into a unified and scalable workflow, VrySure provides a practical framework to improve the efficiency and consistency of image-integrity screening in biomedical research.

bioinformatics↗

bioRxiv2026

Hypoxia Promotes Wound Healing via Dynamical-Mechanical Balance and Adhesion Remodeling

Wound healing is a tightly orchestrated physiological process governed by dynamic cell-cell and cell-matrix interactions, yet how hypoxic microenvironments regulate migratory behavior in cells with latent lineage plasticity remains fully elucidated. Here, utilizing human embryonic kidney (HEK293T) and Madin-Darby Canine Kidney (MDCK) cells as a genetically tractable model, we investigate the cellular and molecular mechanisms driving hypoxia-accelerated collective wound repair. Time-lapse live-cell imaging and morphometric analyses reveal that hypoxic exposure significantly accelerates migration, shifts cell cycle dynamics toward the S/G2/M proliferative phases, and induces pronounced morphological spreading. Mechanistically, hypoxia induces a persistent, time-dependent downregulation of the desmosomal cadherin desmoglein-2 (DSG2), thereby weakening intercellular cohesion. Concurrently, the cell-matrix adhesion molecule integrin {beta}3 (ITGB3) exhibits a distinctive biphasic kinetic response--an initial sharp upregulation followed by a sustained decline-which serves to optimize focal adhesion traction and subsequent trailing-edge detachment. Transcriptomic profiling further corroborates these phenotypic transitions, demonstrating a global enrichment of gene networks associated with plasma-membrane adhesion organization, receptor activity, and ion homeostasis that independently mirrors the altered junctional dynamics and accelerated cellular responses. Collectively, our findings uncover a novel cooperative mechanism by which hypoxic stress coordinates cell-cell and cell-matrix adhesion remodeling to facilitate efficient tissue repair, highlighting the valuable utility of plastic cellular models in decoding microenvironmental stress responses.

Cell Biology↗

bioRxiv2026

Neural Innervation Invigorates Yolk Sac Biological Functions beyond Nutrient Reservoir during Zebrafish Embryo Development

The zebrafish yolk sac (YS) is traditionally viewed as a nutrient reservoir. By reconstructing the complete progression of embryonic neural development via live-cell imaging, we previously observed that axonal projections extending from brain cranial neurons come to cover the yolk sac surface, hinting at its uncharacterized functional roles beyond nutrient storage. Using transgenic lines and long-term live imaging, we characterized a dynamic neuro-vascular-metabolic interface on the YS surface. We observed that peripheral neural networks expand radially and mature through hierarchical integration, sharing the same structural and dynamical features as those in the brain and spinal cord. Unexpectedly, YS surface cells harbor transient calcium flashes, reflecting primitive intercellular communication in response to neural innervation. Furthermore, we characterized activity-dependent neuronal pruning and stress-induced lipid droplet crystallization as indicators of developmental refinement and homeostatic collapse, respectively. Finally, we identified directional blood flow occurring before the formation of endothelial tubes, indicating a pre-vascular transport mechanism. These findings demonstrate that neural innervation enables the YS to serve as a coordinated developmental hub, facilitating complex crosstalk between neural, vascular, and metabolic systems during early vertebrate embryogenesis. Significance StatementTraditional paradigms view the embryonic yolk sac simply as a nutrient reservoir. Using advanced live-cell imaging in zebrafish, we uncover that the yolk sac can be innervated by brain-expanded axonal networks during development, invigorating its biological functions, including neural signal, vascular flow, and metabolic activity. Rather than maintaining local neuronal bodies, these long-distance nerve extensions map out an early topological scaffold that may guide future internal organ innervation during yolk resorption. Furthermore, we capture pre-vascular blood transport and stress-induced metabolic shifts on the yolk sac surface. These findings redefine the yolk sac as a neural-controlled functional hub before organs form.

neuroscience↗

bioRxiv2026

MZF1-mediated GAPDH overexpression drives glycolytic reprogramming and neuroendocrine progression in advanced prostate cancer

Drug resistance to the androgen receptor (AR) antagonist is a critical obstacle in the clinic for advanced prostate cancers. Especially, AR antagonist treatment-induced neuroendocrine progression represents a lethal and therapy-resistant subtype. Although transcriptional and epigenetic lineage plasticity have been extensively implicated in treatment-induced neuroendocrine progression, the contribution of metabolic adaptation remains incompletely understood. Here, we identified a previously unrecognized metabolic reprogramming mechanism induced by AR antagonists in castration-resistant prostate cancer (CRPC) models. AR antagonist treatment markedly enhanced glycolytic activity and induced glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. Genetic depletion of GAPDH suppressed AR antagonist-induced glycolytic activation, altered transcriptomic and metabolic programs, reduced neuroendocrine-associated marker expression, and inhibited xenograft tumor growth. Mechanistically, GAPDH promoter pulldown coupled with mass spectrometry, siRNA screening, and chromatin immunoprecipitation assays identified myeloid zinc finger-1 (MZF1) as a key transcription factor for Enzalutamide-induced GAPDH gene expression. Pharmacological inhibition of GAPDH using koningic acid (KA) or penta-O-galloyl-{beta}-D-glucopyranose (PGG) significantly suppressed tumor growth and attenuated neuroendocrine-associated molecular programs in CRPC cell-derived xenograft and patient-derived t-NEPC xenograft models. Collectively, our findings identify an AR antagonist-induced MZF1-GAPDH signaling axis that promotes glycolytic activation and neuroendocrine-associated metabolic adaptation during treatment resistance. These results support targeting GAPDH-dependent metabolic reprogramming as a potential therapeutic strategy for treatment-resistant prostate cancer. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/729867v1_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@10480b2org.highwire.dtl.DTLVardef@9d2ed8org.highwire.dtl.DTLVardef@16e8705org.highwire.dtl.DTLVardef@1627ad2_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2026

Plant growth forms shaping biodiversity patterns can guide conservation planning on the Qinghai-Tibet Plateau

Plant growth forms effectively reflect profound evolutionary adaptations that underpin ecosystem functioning; however, how their biogeographic disparities influence conservation prioritization remains poorly understood. We here integrate a comprehensive phylogeny with high-resolution distribution data for 14,468 vascular plant species across the Qinghai-Tibet Plateau, showing that growth-form identity decouples the spatial patterns of taxonomic and phylogenetic diversity, with distinct forms exhibiting marked differences in geographic range sizes and elevational optima (2,200-3,300 m). Although herbs dominate plant assemblages across spatial scales, their proportional abundance decreases along a northwest-to-southeast aridity gradient, yielding to structurally complex, non-herbaceous forms in humid, species-rich regions. Consequently, priority conservation areas derived for individual growth forms exhibit low spatial similarity. Despite this divergence, we identify trees and climbers as highly effective umbrella growth forms: prioritizing these functional groups captures [≥]75% of the multidimensional diversity of all other growth forms within a minimal spatial footprint. Our findings demonstrate that accounting for growth-form-based functional identity is essential for maximizing conservation efficacy, providing a scalable framework for biodiversity hotspots worldwide.

ecology↗

bioRxiv2026

Molecular evolution of baculovirus IE1 protein, an essential multi-functional regulator of transcription and replication

Immediate-early protein IE1 is an essential protein of baculoviruses that is involved in transcription and replication. In the present study, we provide several lines of evidence for how ancient IE1 evolved into its current version. Using progressive truncations and site-directed mutations coupled with fluorescence microscopy, surprisingly, we showed that the previously identified nuclear localization sequence (NLS), basic domain II, was essential for sequence non-specific DNA binding, but not required for IE1 nuclear import, and demonstrated that, BmNPV IE1 (BmIE1) possesses not only a unique bipartite NLS that contains a monopartite NLS but also a cryptic non-canonical NLS that is correlated with sequence non-specific DNA binding. The non-canonical NLS alone was sufficient to launch infection. We also found that N-terminally truncated IE1 can enter the nucleus through its sequence non-specific binding ability. Remarkably, the monopartite NLS, when fused to the N-terminus of EGFP, can form a novel NLS that is also functional in a mammalian cell line. Moreover, residues 58 to 151 of BmIE1 were shown to be dispensable, and residue 152 was found to be critical for launching a productive infection. To gain insight into how ancient IE1 acquired its multi-functionality, we reorganized the N-terminal 23 aa and 132 aa of BmIE1 with EGFP in a variety of manners and found that both fragments are separable and transferable. Notably, we observed that the nuclear levels of BmIE1 should reach certain thresholds to initiate infection. Additionally, we found that BmNPV could launch infection more efficiently in a BmN cell line over another BmN cell line by increasing transcription levels of immediate early genes. Collectively, these findings suggest a hypothesis where ancient IE1 might have evolved the two additional NLSs and acquired the N-terminal 132 aa through gene fusion so as to reach infection-initiating thresholds at a faster pace. Author SummaryBasic domain II was previously shown to be the NLS of AcMNPV IE1 protein. In the present study, we demonstrated that it is essential for sequence non-specific DNA binding, but not required for IE1 nuclear import, and found that BmNPV IE1 (BmIE1) possesses not only a unique bipartite NLS that contains a monopartite NLS but also a cryptic non-canonical NLS that is correlated with sequence non-specific DNA binding. We also found that N-terminally truncated BmIE1 can enter the nucleus through its sequence non-specific binding ability. Remarkably, the monopartite NLS, when fused to the N-terminus of EGFP, can form a novel NLS that is also functional in a mammalian cell line. Moreover, the domains of BmIE1 was shown to be separable and transferable. We also demonstrated that higher expression of functionally impaired BmIE1 achieved by higher MOIs or higher transfection efficiency can partially complement its compromised functions. Consistently, we found that BmNPV could launch infection more efficiently in a BmN cell line over another BmN cell line by increasing transcription levels of immediate early genes.

microbiology↗