Biology subjects

Zhao, T.

Publications and source records attributed to Zhao, T..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

resolveS: An ultra-fast, memory-efficient and reference-free tool for RNA-seq Strandedness Detection

Accurate specification of RNA-seq library strandedness is essential for read counting, transcript assembly and antisense transcription analysis, yet this information is frequently missing from public metadata. We present resolveS, a fast and lightweight method that infers strandedness from alignments to a compact universal rRNA database, avoiding the need for organism-specific reference genomes and annotations. Across benchmark datasets, resolveS provides robust strandedness calls while maintaining very low runtime and memory usage, making it suitable for both routine quality control and large-scale reanalysis of public RNA-seq data.

bioinformatics↗

bioRxiv2026

Microglia stabilize sleep homeostasis via adenosine A3 receptor signaling

Sleep homeostasis maintains the sleep-wake balance through sleep pressure, a process orchestrated by the accumulation of extracellular adenosine (eADO). Microglial Ca{superscript 2} activity has been implicated in sleep regulation, but the mechanism whereby microglia sense sleep pressure remains unclear. Here we show that microglia regulate sleep homeostasis through brain state-dependent Ca2+ activity driven by adenosine A3 receptor (A3R) signaling. Using miniaturized two-photon microscopy (mTPM) in freely behaving mice, we demonstrate that microglial Ca{superscript 2} activity is rapidly altered by brain-state transitions. Pharmacological experiments reveal that microglial Ca2+ dynamics are predominantly mediated by A3R in response to brain state-dependent eADO oscillations. Microglia-specific deletion of A3R attenuates these state-dependent Ca2+ dynamics, impairs microglial morphological plasticity across sleep-wake cycles, and leads to sleep fragmentation by increasing transitions between wakefulness and non-rapid eye movement (NREM) sleep. Together, these findings establish that microglia regulate sleep homeostasis by stabilizing both wakefulness and NREM sleep, a process critically dependent on eADO-A3R signaling.

neuroscience↗

bioRxiv2026

TMEM33 deletion potentiates anti-tumor CD8+ T cell immunity

Improving responses to cancer immunotherapies requires deeper insight into the cellular mechanisms governing T cell-mediated anti-tumor immunity. TMEM33 is an endoplasmic reticulum-resident transmembrane protein enriched across multiple tumor types, with reported functions in anti-viral immunity as well as calcium and lipid homeostasis, yet its role in tumor immunosurveillance remains unknown. Using murine genetic models, we demonstrate that host TMEM33 constrains anti-tumor CD8+ T cell responses. Constitutive Tmem33-/- mice exhibited delayed melanoma tumor growth and increased CD8+ T cell infiltration. Antigen-specific CD8+ compartments in tumors of Tmem33-/- mice showed TCF-1+PD-1+ progenitor-exhausted cell (Tpex) enrichment, elevated effector function and reduced exhaustion, alongside improved effector memory expansion and T-bet expression in draining lymph nodes. We highlight that TMEM33 functions intrinsically within the T cell compartment, as TMEM33 deletion (1) enhanced polyclonal activation of naive CD8+ T cells ex vivo, (2) promoted preferential Tpex accumulation among adoptively transferred naive OT-I cells in B16F10-OVA tumors and draining lymph nodes, and (3) improved the potency of ex vivo-expanded OT-I cells in controlling tumor growth during adoptive cell therapy. Finally, in a large, prospectively recruited metastatic melanoma cohort, lower TMEM33 expression in patient CD8+ T cells significantly correlated with improved survival and elevated TCF-7 (encoding TCF-1). Collectively, our findings define TMEM33 as a formerly unrecognized intrinsic determinant of tumor-directed CD8+ T cell fate that limits Tpex maintenance, and restrains cell therapy responses, suggesting that its modulation may strengthen immunotherapeutic efficacy. One sentence summaryTMEM33 intrinsically limits progenitor exhausted CD8+ T cells, scales anti-tumor responses and predicts melanoma patient survival.

immunology↗

bioRxiv2025

Developing High-Yield and Safe Therapeutic EVs by Ablating Tissue Factor-Mediated Toxicity

The clinical translation of extracellular vesicles (EVs) as next-generation drug delivery vehicles is currently stalled by two interrelated challenges: the difficulty of manufacturing EVs at an industrial scale ("the yield problem") and the risks of toxicity associated with systemic administration of high doses ("the safety ceiling"). In this comprehensive study, we present a two-pronged genetic engineering strategy to overcome these limitations. First, we discovered that overexpression of glycosylphosphatidylinositol (GPI)-anchored proteins, such as CD55 and CD59, significantly enhances EV production in HEK293T and Expi293F cells. By engineering a truncated CD55 variant (TR3) that retains the GPI-anchor but lacks functional domains, we developed the ExoBoost cell line, which boosts EVs yield by approximately 50-fold without altering vesicle morphology. Second, we observed acute toxicity in mice following intravenous administration of high-dose ExoBoost EVs, with symptoms resembling venous thromboembolism. Through comparative analysis of EVs derived from other cell types, including keratinocyte stem cells (KSCs) and mesenchymal stem cells (MSCs), we identified Tissue Factor (TF/F3) as the critical causative agent of this lethal response. Moreover, we completely abolished this toxicity by generating a F3-knockout cell line (ExoBoost2.0) using CRISPR/Cas9, thereby raising the safe dose to as high as 1.5E12 particles per mouse, as quantified by nano flow-cytometry (nFCM). Finally, using a novel CD46-nanoluciferase reporter system, we demonstrated that high-dose administration of these safe EVs saturates hepatic and splenic clearance pathways, leading to a dramatic increase of systemic EVs accumulation, particularly in hard-to-target tissues such as the brain ([~]10,000-fold) and muscle ([~]1,000-fold). Additionally, repeated high-dose administration of ExoBoost2.0 EVs did not upregulate inflammatory cytokines or production of IgG and IgM. In summary, these findings establish a scalable, safe, and highly biocompatible EVs platform, potentially revolutionizing the drug delivery system in clinical application.

bioengineering↗

bioRxiv2025

Engineering Apical Integrin-binding Cellular Patches to Directed Cell Reprogramming via Mechanical Remodeling

Engineering extracellular microenvironments to control stem cell fate remains a central challenge in regenerative medicine. Here, we develop ECM-mimetic cellular patches formed by the supramolecular assembly of laminin-derived, integrin-binding ligands. The resulting fibrillar networks exhibit well-defined molecular packing and nanoscale ligand distribution, enabling specific engagement of apical integrin {beta}1 on mesenchymal stem cells. This controlled interface converts molecular assembly into hierarchical mechanotransduction, coordinating cytoskeletal remodeling, nuclear deformation, and chromatin reorganization to drive neuronal reprogramming without genetic or chemical induction. Mechanistic studies reveal that the interplay between ligand assembly, spatial orientation, and network stability governs integrin activation and downstream transcriptional regulation These findings demonstrate how molecularly programmed assemblies can transform passive matrices into active, cell-instructive materials. This work establishes a framework for designing supramolecular systems that couple structural hierarchy with mechanotransductive control to direct stem cell fate and advance regenerative material strategies.

bioengineering↗

bioRxiv2025

Emergence of Individualized Functional Topography in the Neonatal Brain

The early postnatal period represents a critical phase for establishing the brains fundamental architecture. However, how individualized functional topography emerges and shapes long-term cognition remains unknown. Using multimodal neuroimaging data from 419 neonates, we map personalized functional topographies in the first weeks of life and reveal their association with 18-month neurocognitive outcomes. Unique and stable functional topographies are already present at birth, with interindividual variability organized along a conserved sensorimotor-to-association hierarchy. These individualized maps encode early brain maturity and robustly predict cognitive, language, and motor outcomes at 18-month of age, with predictive features concentrated at network boundaries. This functional refinement is structurally anchored by concurrent maturation in cortical myelination and sulcal depth. Preterm birth results in distinctive topographic alterations characterized by accelerated maturation of association networks. Our work establishes a foundation for precision models of early brain development and elucidates its significance for long-term neurocognitive outcomes.

neuroscience↗

bioRxiv2025

Convergent and divergent spatial topographies of individualized brain functional networks and their developmental origins

The human brain is intrinsically organized into canonical functional networks with distinct spatial topographies. While precision functional mapping delineates individualized topographies of single networks, the spatial coordination among networks and its developmental origin remains largely unknown. Here, we propose functional topography covariance analysis (FOCA), a novel framework that quantifies convergent and divergent spatial alignments across individualized functional networks and further delineates their internetwork relationships, neurobiological basis, ontogenetic layouts, and cognitive outcomes. Across two well-established task-free functional MRI (fMRI) datasets encompassing both conventional and densely sampled scans, FOCA consistently revealed self-clustered hierarchies in the coordination of functional topographies, closely aligned with existing functional gradients and characterized by convergent couplings within primary systems and divergent couplings in higher-order systems. Such pattern was well predicted by fundamental neurobiological attributes, especially aerobic glycolysis. In a large public neonatal cohort, FOCA matrix exhibited adult-inverted hierarchical couplings and marked changes in auditory and action-mode networks, primarily driven by prominent redistributions of negative couplings. Moreover, neonatal FOCA profiles in the primary visual system significantly predicted neurodevelopmental outcomes at 18 months. Finally, compared with conventional functional connectivity (FC), FOCA proved more robust to global signals and more sensitive to the maturation of negative couplings. These findings highlight the critical role of negative connectivity in brain functional reorganization and advance our understanding of the cooperative and competitive relationships among functional systems and their developmental origins.

neuroscience↗

bioRxiv2025

Epithelial FOXP3 Drives Pancreatic Fibrosis through O-glycosylated IL-6

BACKGROUND & AIMSThe transcription factor FOXP3, known for specifying regulatory T cell fate, is unexpectedly expressed in the epithelium of precancerous pancreatic lesions. Here we investigate its non-immune role in initiating pancreatic fibrosis, a process driving therapeutic resistance and organ failure in pancreatic ductal adenocarcinoma (PDAC) with unknown origins in early neoplasia. METHODSUsing human tissues and genetically engineered mouse models, we analysed FOXP3 expression in premalignant lesions. We employed epithelial-specific FOXP3 knockout and knock-in strategies to determine its functional impact on fibrogenesis and neoplasia progression. Mechanistic studies included chromatin immunoprecipitation, glycomic analyses, and signalling assays. RESULTSFOXP3 was consistently expressed in the epithelial compartment of human and murine precancerous pancreas. Epithelial-specific deletion of FOXP3 attenuated pancreatic fibrosis and delayed neoplasia, whereas its knock-in induced spontaneous stromal activation and accelerated PanIN progression. Mechanistically, epithelial FOXP3 directly transactivated the glycosyltransferase GALNT1. GALNT1, in turn, mediated O-glycosylation of interleukin (IL)-6, which was essential for its rapid secretion. CONCLUSIONSOur study establishes epithelial-derived FOXP3 as a master regulator of early pancreatic fibrocarcinogenesis. It drives a glycosylation-dependent amplification loop for IL-6 signalling, orchestrating sustained stromal activation. This pathway represents a promising target for intercepting pancreatic fibrosis and carcinogenesis at its origin.

cancer biology↗

bioRxiv2025

Morphological Identification of Ticks in district Swabi, Mardan, and Charsadda

Ticks are ectoparasitic arthropods that play a significant role in transmitting pathogens to humans and animals. This study aimed to address the research gap in understanding the morphological diversity and distribution of tick species in Swabi, Mardan, and Charsadda districts of Pakistan, where tick-borne diseases are prevalent but poorly documented. The primary objectives were to identify tick species, document their morphological characteristics, and map their distribution patterns across different habitats. Field surveys were conducted over nine months, collecting tick specimens from forests, grasslands, and residential areas. Specimens were preserved and analyzed using stereo-zoom microscopy and taxonomic keys for accurate classification. Key findings revealed a diverse tick fauna, including hard ticks (Ixodidae), with variations in body size, colour patterns, capitulum shape, and scutum features. Some species were widely distributed across all three districts, while others exhibited localized patterns. The study provides the first comprehensive morphological identification of tick species in these regions, highlighting their potential role in disease transmission. The implications of this research are significant for public health and disease control. The data can inform targeted interventions, enhance disease surveillance programs, and support the development of preventive measures to mitigate tick-borne diseases. By contributing to tick taxonomy and epidemiology, this study lays the groundwork for protecting public health in the study regions and beyond. This study addresses the lack of data on tick diversity in high-prevalence regions of Pakistan, providing critical insights for disease control and public health strategies. Limited information exists on the morphological diversity and distribution of tick species in Swabi, Mardan, and Charsadda districts. To identify tick species, document morphological characteristics, and map their distribution patterns in the study areas. Field surveys, specimen collection, stereo-zoom microscopy, and taxonomic classification were employed over nine months. Diverse tick fauna was identified, including hard ticks, with variations in morphology and distribution. Some species were widespread, while others were localized, highlighting potential disease transmission risks. The findings support targeted interventions, disease surveillance, and preventive measures, contributing to public health protection and tick-borne disease control in the region.

zoology↗

bioRxiv2025

Ambient mass spectrometry imaging enables spatial metabolomics of optimal cutting temperature compound (OCT)-embedded tumors

Mass spectrometry imaging (MSI) is emerging as a powerful tool for uncovering the distribution of metabolites in the tumor microenvironment and studying tumor metabolism in vivo. However, to date, MSI of primary patient biobanked tissues contextualized by patient data has been limited to peptides, proteins, and glycans - with few examples for metabolites. This is because most biobanked fresh-frozen tissue required for spatial metabolomics is embedded in optimal cutting temperature compound (OCT), which introduces high-abundance polymeric interferents. Herein, we use nanospray desorption electrospray ionization (nano-DESI) to demonstrate the MSI of metabolites in OCT-embedded tissue. Metabolite coverage and sensitivity for prepared tissue mimetic homogenates embedded in OCT and an MSI-compatible material, carboxymethylcellulose (CMC), showed excellent agreement. We apply our ambient MSI workflow to detect changes in intratumoral methionine using a preclinical cancer mouse model undergoing adoptive T-cell therapy. Eight days after tumor incubation, lymphoma-bearing mice were maintained on a complete or methionine-restricted diet for 2 days. Nano-DESI MSI revealed a heterogeneous tumor microenvironment, with multiple methionine-cycle intermediates (S-adenosylmethionine, S-adenosylhomocysteine) and related metabolites, including known T-cell modulators (1-methylnicotinamide, polyamines) localizing to tumor subregions. Methionine-restricted tumors exhibited reduced methionine levels and elevated S-adenosylmethionine, relative to the control group. Overall, this work demonstrates spatial metabolomics on fresh-frozen OCT-embedded tissue, unlocking the wealth of information stored in primary tissue biobanks and consequently accelerating our understanding of cancer metabolism and treatment.

cancer biology↗

bioRxiv2025

A novel 18F-labeled brain penetrant PET ligand for imaging poly(ADP-ribose) polymerase-1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a key mediator of DNA repair, and its inhibition has become a validated therapeutic strategy in homologous recombination-deficient cancers. However, tools for non-invasive assessment of PARP-1-specific expression remain limited. Here, we evaluated [18F]AZD9574, a next-generation PARP-1-selective PET radiotracer. [18F]AZD9574 was tested in a panel of breast, glioblastoma, prostate, and pancreatic cancer cell lines. Uptake correlated with PARP-1 expression and was dose-dependently blocked by a variety of clinically relevant PARP inhibitors, confirming its binding specificity. In 22Rv1 xenograft mouse models, the tracer demonstrated significant tumor accumulation that was specific to PARP-1, and ex vivo biodistribution confirmed organ uptake consistent with specific tumor binding and PARP-1 expression. Together, these findings establish [18F]AZD9574 as a promising PARP-1-targeted imaging agent with strong potential for advancing cancer research and therapeutic monitoring.

cancer biology↗

bioRxiv2025

Migration patterns and hybridization within the Asian stonechat complex in response to a major geographical barrier

Long-distance avian migration is thought to be under strong natural selection. Facing geographical barriers, migrants display various patterns considered to be adaptive. For example, they may detour along either side around the barrier or cross it, requiring specialized behavioral adaptations. Variations within closely related taxa are excellent sources for understanding the evolutionary background of migration and how barriers are shaping migration routes. In Asia, some species are assumed to have a migratory divide in response to the major geographical barrier, the Qinghai-Tibet Plateau (QTP), including the stonechat taxa (Siberian Stonechat Saxicola maurus maurus and Amur Stonechat S. stejnegeri). As they detour along either side of the QTP, these taxa are believed to disfavor a crossing over the highland. However, the more southernly distributed Tibetan Stonechat (S. m. przewalskii) breeds on the QTP, suggesting adaptation to high elevation. To investigate migration patterns and the potentially associated genetic differences, we studied migration routes and population genetics of four populations around the assumed migratory divide in Russia and Mongolia, and of one from the QTP in China. Our results confirmed the existence of a migratory divide between maurus and stejnegeri, albeit with extensive hybridization. We observed both the hypothesized western and eastern routes, but also found individuals employing intermediate routes crossing the QTP, of which two-thirds were clear hybrids. Meanwhile, przewalskii followed a highland-crossing route and was genetically differentiated from maurus and stejnegeri. The diverse migration routes among Asian stonechats show differential responses towards the geographical barrier. The intermediate route may be associated with hybridization, and its conditional viability may facilitate gene flow between maurus and stejnegeri. The Asian stonechat complex thus offers great opportunities for novel research of the genetics and evolution of migration. The specific evolutionary background associated with inhabiting and crossing the QTP can offer new perspectives in this field. Teaser textMigratory divides can arise in birds because alternative routes around migratory barriers would select for behaviors to restrict hybridization. Hybrids of parental types that employ alternative routes are hypothesized to embark on intermediate routes that would expose them to suboptimal conditions, resulting in post-zygotic reproductive isolation. However, this hypothesis is challenged when a sister taxon actually breeds on the geographical barrier. This is the case in the Asian stonechat complex that breeds near or on the Qinghai-Tibet Plateau (QTP), the roof of the world. We demonstrated a migratory divide in central Siberia to Mongolia for race maurus and stejnegeri, yet showed also evidence for extensive hybridization. Hybrids migrated along a newly discovered intermediate route, seemingly viable and overlaps with the migration trajectory of race przewalskii over the eastern part of the QTP. The Asian migratory divide relative to the QTP thus provided new insights to the evolution of landbird migration.

evolutionary biology↗

bioRxiv2025

Methionine regulates antitumor function of CD8⁺ T cells through polyamine synthesis

Methionine is an essential amino acid critical for T cell activation. While methionine restriction (MR) combined with immune checkpoint blockade has been shown to enhance T cell function, the impact of methionine on adoptive T cell therapies is largely unexplored. Here, we examined the functionality of T cells under MR and pharmaceutical inhibition of the methionine cycle (MAT2Ai), using primary T cells and a murine adoptive T cell therapy model. In vitro, transient MR or MAT2Ai treatment increased interferon gamma (IFN{gamma}) expression in CD8+ T cells, whereas sustained MR led to the upregulation of T cell exhaustion-associated markers. Mechanistically, transient MR suppressed the polyamine synthesis pathway, and supplementation with polyamines reversed MR-induced IFN{gamma} expression. Genetic ablation of s-adenosylmethionine decarboxylase, an enzyme in the polyamine synthesis pathway, recapitulated the effect of MR, indicating that transient MR enhances T cell function by inhibiting polyamine synthesis. Despite this, transient MR treatment of ovalbumin (OVA)-specific (OT-I) CD8+ T cells prior to adoptive transfer did not improve antitumor efficacy against EG7-OVA tumors in vivo. In contrast, sustained dietary MR accelerated EG7-OVA tumor growth in mice treated with OT-I T cells, demonstrating that methionine availability is essential for the activity of adoptively transferred T cells. These findings suggest that enhancing methionine availability in the tumor microenvironment may improve the efficacy of adoptive T cell therapies.

immunology↗

bioRxiv2025

Differentiation stage-specific use of cap-independent and cap-dependent translation initiation in hematopoiesis

Cell stress can increase the use of m7G-cap-independent, IRES-mediated translation initiation relative to cap-dependent translation (IRES/Cap). Reporters that quantify IRES/Cap have demonstrated differential activity across cultured cell types and stress conditions. By generating an IRES/Cap reporter mouse, we were able to systematically evaluate IRES/Cap across distinct tissues and cell types during physiological stresses and lineage commitment. Caloric stress invoked the expected boost in IRES/Cap translation regardless of differentiation state, but unexpectedly IRES/Cap progressively increased during hematopoietic and epithelial (hair follicle) differentiation under normal, homeostatic conditions. This was independent of total protein output or cell cycle. Even within cells of a given differentiation state, cells with lower relative-IRES utilization had markedly higher multipotent capability in vivo. The RNA processing protein PTBP1 is a mediator of this translation initiation preference. Therefore, low IRES/Cap is a signature of high stemness and suggests modulation of translation initiation participates in cell differentiation state.

developmental biology↗

bioRxiv2025

Synthesis and In Vitro Characterization of OGA-2506 as a High Affinity Radioligand for O-GlcNAcase

O-GlcNAcase (OGA) is a glycoside hydrolase that regulates protein O-GlcNAcylation, a dynamic post-translational modification implicated in numerous cellular processes. Dysregulation of OGA alters cellular O-GlcNAc homeostasis and has been linked to neurodegenerative and other chronic diseases. The development of radioligands targeting OGA, particularly those derived from well-characterized tool compounds, could substantially advance drug discovery in this area. Herein, we report the radiosynthesis of a novel tritium (3H)-labeled radioligand 7 (code name [3H]OGA-2506) derived from a chiral piperidine scaffold, and its preliminary in vitro binding evaluation. Starting from iodine precursor 8, palladium-catalyzed tritiation afforded [3H]7 with excellent molar activity (1822 GBq/mmol) and high radiochemical purity (>99%). Saturation binding studies revealed that [3H]7 binds OGA with high affinity to rat striatum homogenates (Kd = 3.56 nM; Bmax = 42.62 nM). Competition assays yielded an IC50 of 5.55 nM, and preliminary autoradiography demonstrated heterogeneous regional distribution in the brain with specific binding. These findings highlight [3H]7 as a valuable tool for OGA binding studies and provide a foundation for the future development of novel positron emission tomography (PET) ligands to probe O-GlcNAc signaling in the brain.

pharmacology and toxicology↗

bioRxiv2025

First Whole-Genome Chikungunya Virus Sequence Detected in Mosquitoes during the 2025 Foshan Outbreak: Evidence of Field Vector Infection and Transmission Potential in China

BackgroundSince July 2025, an outbreak of mosquito-borne chikungunya fever occurred in Foshan City, Guangdong Province, China. This was the second outbreak in China following the one that occurred in Dongguan City, Guangdong Province, in 2010. Moreover, the intensity of this outbreak was significantly greater than that of the previous one. Updates to 23 August, more than 10,000 human cases had been reported. Here, we present the first full genome sequence of the chikungunya virus (CHIKV) derived from field-trapped mosquitoes during the outbreak. MethodsAdult Aedes albopictus were BG-trap captured from residences and parklands in three hotspot towns with high density of confirmed human cases. Mosquitoes were morphologically identified and pooled by species, sex and environment types. RNA was extracted, screened by CHIKV RT-qPCR, then positive pools underwent sanger and whole-genome sequencing for complete sequences. Lineage and mutational profiles were inferred by maximum likelihood phylogenetic and comparison against human and mosquito genomes. The distribution of amino acid site mutations in different protein coding regions was also analyzed. ResultThrough 11 days of collection using 10 BG-traps, 2,803 mosquitoes were captured. 1569 (55.97%) female Ae. albopictus were divided into 77 pools and 9.09% (7/77) of the pools tested positive for CHIKV. The local Ae. albopictus minimum infection rate (MIR, per 1000 females) was 4.46, while the MIR for residences in Lecong Town was the highest at 9.17. The MIR for parklands was slight higher than for residences (4.60 vs. 4.30). All the 5 Ae. albopictus-derived complete CHIKV genome clustered within ECSA-Indian Ocean lineage genotype, closely related to human-derived genomes on 2025 Reunion Island. Amino-acid mutations E1-A226V/E2-L210Q were detected in the strains, which enhanced adaptability to Ae. albopictus and increased the transmission capacity. Novel mutation observed on E1 and E2 were totally consist to the patient-derived CHIKV in 2025 Reunion Island. ConclusionsIt was the first mosquito-derived CHIKV whole-genome during the 2025 Foshan outbreak, filling a critical gap between human case and entomological surveillance. Ae. albopictus was confirmed as the primary vector during the outbreak. The current outbreak CHIKV strain with particular amino-acid mutations had adapted to Ae. albopictus transmission. Compared to previous Chikungunya outbreaks over the past decade, the Foshan outbreak occurred earlier (early July), in a larger urban area (with a population of over 9.5 million), and with abundant breeding sites for the vector mosquito Ae. albopictus. However, the outbreak was quickly brought under control, with daily case numbers consistently decreasing, which is closely linked to the strong vector control measures implemented by the Chinese government in the early stages of the outbreak. Moreover, this event once again underscores the necessity of early monitoring of vector mosquitoes and the importance of implementing highly effective vector intervention measures as soon as possible after an outbreak occurs.

microbiology↗

bioRxiv2025

IRP1 deficiency alters mitochondrial metabolism and protects against metabolic syndrome pathologies

Iron regulatory protein 1 (IRP1) is a post-transcriptional regulator of cellular iron metabolism. In mice, loss of IRP1 causes polycythemia through translational de-repression of hypoxia-inducible factor 2 (HIF2) mRNA, which increases renal erythropoietin production. Here we show that Irp1-/- mice develop fasting hypoglycemia and are protected against high-fat diet-induced hyperglycemia and hepatic steatosis. Discovery-based proteomics of Irp1-/- livers revealed a mitochondrial dysfunction signature. Seahorse flux analysis in primary hepatocytes and differentiated skeletal muscle myotubes confirmed impaired respiratory capacity, with a shift from oxidative phosphorylation to glycolytic ATP production. This metabolic rewiring was associated with enhanced insulin sensitivity and increased glucose uptake in skeletal muscle. Under metabolic stress, IRP1 deficiency altered the redox balance of mitochondrial iron, resulting in inefficient energy production and accumulation of amino acids and metabolites in skeletal muscle, rendering them unavailable for hepatic gluconeogenesis. These findings identify IRP1 as a critical regulator of systemic energy homeostasis.

pathology↗

bioRxiv2025

SimSpace: a comprehensive in-silico spatial omics data simulation framework

Spatial omics technologies provide rich measurements of molecular states in their native tissue context, but the development and benchmarking of computational methods remain constrained by limited access to datasets with known ground truth. We present SimSpace, a flexible framework for simulating spatial omics data for method development, stress-testing, and controlled in silico experiments. SimSpace uses a hierarchical generative model that couples tissue-scale spatial organization, local cell-type interactions, and modular omics-profile generation. Its Markov random field-based spatial model enables controllable simulation of niche structure, cell-type co-localization, phenotype-dependent density, and spatially mediated molecular interactions. SimSpace supports both reference-free simulations under user-defined generative assumptions and reference-guided simulations that calibrate spatial parameters to real datasets while generating new spatial realizations. Across Xenium, MERFISH, and CODEX examples, SimSpace reproduced multiple evaluated spatial statistics, preserved key domain-level structure in reference-guided settings, and supported benchmarking of cell-type deconvolution and spatially variable gene detection methods. We further show that inferred interaction parameters can be perturbed to generate interpretable counterfactual spatial proteomics scenarios. SimSpace is implemented as an open-source Python package with reproducible workflows for rigorous benchmarking and methodological development in spatial omics.

bioinformatics↗