Road traffic fatalities constitute a critical and preventable public health burden in Ghana, yet granular subnational analyses of monthly mortality patterns across the country's sixteen administrative regions remain sparse. This study uses a Bayesian spatio-temporal negative binomial (NB) model to analyse monthly road traffic death counts across sixteen Ghanaian regions from January 2019 to December 2022, disaggregated by vehicle type (commercial, private, and cycle). The model decomposes the expected death count into a global intercept, fixed effects for vehicle type, accident counts entered as a log-transformed covariate rather than an offset, and temporal trend, together with region-specific spatial random effects (ui) and year-level temporal random effects (vt). Overdispersion (variance-to-mean ratio = 18.6) is explicitly accommodated by the NB distribution. Posterior inference was conducted using the no-U-turn sampler (NUTS) implemented in brms (version 2.21) under R 4.5, with four chains of 2000 iterations each (1000 warm-up), target acceptance rate δ = 0.90, and random seed 2024. Spatial random effects were specified as independent hierarchical Normal priors, not CAR/BYM priors, with a HalfNormal(0, 1.5) hyperprior on the regional standard deviation. The Bayesian NB model achieved superior fit (LOO-CV ELPD = - 2381.4; AIC = 4646; BIC = 4739 reported for comparison) relative to the competing count-data specifications. The posterior mean for the global intercept was β0 = 2.070 (SD = 0.339; 94% HDI: 1.458, 2.677), corresponding to a baseline expected monthly death count of approximately 7.9. Substantial spatial heterogeneity was confirmed (σ_region = 1.139; 94% HDI: 0.786, 1.574), with Greater Accra and Ashanti exhibiting the largest positive spatial random effects (both ui = 1.699). A statistically significant negative monthly trend (βm = - 0.084; 94% HDI: - 0.160, - 0.013) was identified, while the annual temporal trend remained uncertain (βt = 0.043; 94% HDI: - 0.325, 0.361; HDI includes zero). Year-level random effects were small, and their credible intervals broadly included zero, indicating modest inter-annual variation beyond the linear trend. No divergent transitions were detected; all [Formula: see text] values were ≤ 1.01, and bulk ESS was > 350. Marked regional heterogeneity and vehicle-type-specific mortality patterns underscore the need for spatially differentiated road safety interventions.
Sepsis-induced acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung condition with high mortality and no specific pharmacological treatments. The complex spatial heterogeneity of the lung during sepsis hinders the discovery of effective therapies. This study aimed to use spatial transcriptomics to map the septic lung's molecular landscape to identify and validate a novel therapeutic agent. We performed spatial transcriptomics on lung tissues from mice subjected to cecal ligation and puncture (CLP) to model sepsis. A computational drug screen identified Mavacamten. In vitro, lipopolysaccharide-stimulated murine alveolar epithelial cells were used to assess Mavacamten's effects on inflammation and cell injury. In vivo, CLP mice received Mavacamten, and we assessed survival, lung function, pulmonary edema, histology, and inflammatory markers. The underlying mechanism was investigated by analyzing the PI3K/AKT/mTOR pathway and autophagy markers. Statistical analyses included ANOVA, t-tests, and Kaplan-Meier analysis. Spatial transcriptomics revealed distinct cellular clusters that were dramatically rearranged during sepsis. In vitro, Mavacamten significantly attenuated lipopolysaccharide-induced inflammation, cellular injury, and oxidative stress. In the CLP mouse model, Mavacamten treatment markedly improved 7-day survival, restored arterial oxygenation, reduced pulmonary edema, and lessened histological lung injury. Mavacamten also significantly lowered local and systemic pro-inflammatory cytokine levels. Mechanistically, Mavacamten reversed the sepsis-induced inhibition of autophagy and suppressed the activation of the PI3K/AKT/mTOR signaling pathway in lung tissues. Mavacamten confers robust protection against sepsis-induced ARDS in a preclinical model by mitigating inflammation and lung injury, leading to improved survival. Its therapeutic action is mediated by inhibiting the PI3K/AKT pathway and restoring protective autophagy. Mavacamten is a promising candidate for repurposing in the treatment of sepsis-induced ARDS.
The foreign body reaction to implanted electrodes in the brain has long been recognized as a major challenge impacting the performance and reliability of indwelling neurotechnologies. Spatially resolved transcriptomic approaches have enabled high-resolution mapping of cellular and molecular dynamics at the device-tissue interface, yielding novel insight into both acute and chronic tissue responses. Recent whole-transcriptome profiling methods generate exceptionally dense gene expression datasets from individual samples, offering unprecedented resolution and analytical power. Yet, limited studies have explored aggregated results from larger datasets and sample-to-sample variation within an implanted cohort using such techniques due to high costs and complicated downstream analyses. In this work, we provide a comprehensive report of spatial transcriptomics data collected from an expanded cohort of rats (n = 14 rats) implanted with silicon microelectrode arrays in the motor cortices for 1 week (acute) and 6 weeks (chronic). This larger dataset enabled us to explore the variation in results across samples, assess outliers, and examine potential batch effects. We employed differential expression analysis to identify top differentially expressed genes (DEGs) in spatially defined regions at the device-tissue interface to reveal novel biomarkers in the aggregated dataset. We assessed sample-to-sample variabilities, and applied a factorization strategy to identify prominent cell-type contributors of the top DEGs. Using network-based co-expression analysis, we identified gene modules, hub genes, and central regulatory processes governing the device-tissue interface. Our results show: (a) greater variation of top DEGs across samples at the 1-week time point with notable microglial and astroglial cell-type contributors, (b) lower variation of top DEGs across samples and a shift to prominent astroglial cell-type contributors at the 6-week time point, and (c) novel biomarkers that suggest major macrophage- and microglial mediated processes and homeostasis events at the 1-week time point, and greater tissue remodeling, apoptotic and synaptic changes at the 6-week time point. These findings support previous ideas on the evolving tissue response to implanted devices, and present novel details on biomarkers, biological processes and sample variation. Additionally, this study provides a framework for assessing larger datasets employing high-dimensional spatial transcriptomics and highlight key considerations related to across-sample variability and batch effects.
Equity in maternal health is critical to achieving Sustainable Development Goals and Universal Health Coverage. Unequal distribution of maternal health resources threatens access and outcomes, particularly in Low- and Middle-Income Countries (LMICs) like Iran. This study assesses spatial and socioeconomic inequalities in the availability of human and physical maternal health resources across Iranian provinces in 2023. This cross-sectional study analyzed data from 20 maternal health resource indicators collected in 2023 across all 31 provinces of Iran. Among these, 7 variables represented human resources and 13 represented physical resources. Data aggregation was performed at multiple levels, including provincial boundaries, geographic regions, deprivation categories, and classification of provinces as border or central, to comprehensively assess spatial and socioeconomic disparities. Composite indices for human and physical resources were constructed using min-max normalization followed by averaging relevant variables. Inequality was quantified using the Gini coefficient across provinces and data processing and statistical computations were performed using R software. Findings reveal generally moderate inequalities in maternal health resource distribution (Gini mostly below 0.5) with advantaged and border provinces showing higher resource availability. Specialized facilities and supervisory staff remain concentrated in select regions, while frontline workers show more equitable distribution. The concentration of border‑specific facilities in a limited number of provinces explains part of the observed regional disparities. While important progress has been made in expanding maternal health services, spatial and socioeconomic inequities in the distribution of resources persist across provinces in Iran. Policy efforts should prioritize equity-oriented resource allocation, strengthen services in deprived provinces, and implement continuous inequality monitoring to support more equitable maternal health outcomes.
The socioeconomic consequences of schistosomiasis have forced the integration of control strategies. Currently, all control efforts have tended to involve the control of snail intermediate hosts. However, the integration of snail control into the general schistosomiasis control strategy has not yet been effective in Burkina Faso. While snail occurrence data have been collected intermittently since the last systematic assessment in 1980, there has been no recent synthesis of the distribution of intermediate host snails in Burkina Faso. The aim of this study was to integrate historical and recent datasets to assess temporal shifts in species distribution, identify key climatic drivers, and produce spatially explicit risk maps to support targeted control strategies in Burkina Faso. Snail occurrence data were compiled for three time periods: 1980, 2018, and 2021. Data from 1980 and 2018 were obtained through a comprehensive literature review, while field sampling was conducted in 2021 in two basins: the Mouhoun basin and the Nakanbé basin. The Maximum Entropy (Maxent) modeling approach was used to predict changes in species distributions over time by integrating occurrence records from each period with relevant environmental variables. Model performance was evaluated using the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve and the Boyce index. The contribution of each environmental variable was assessed using a jackknife test. Five schistosomiasis intermediate hosts were collected: Bulinus truncatus, Bulinus forskalii, Bulinus senegalensis, Bulinus globosus, and Biomphalaria pfeifferi. The number of snail intermediate host species for schistosomes did not significantly change between 1980 and 2021. Except for B. umbilicatus, the results show that the two basins host almost the same species of snail intermediate host of schistosomes. The rivers, reservoirs, and irrigated plains provide favorable conditions for the occurrence of all species of snail intermediate hosts. The area under the curve (AUC) of the selected variables ranged from 0.877 to 0.985. Except for B. globosus, the Boyce index ranged from 0.6 to 0.924. Spatial distribution modeling indicated that the western part of the Volta Basin is more suitable for the occurrence of schistosome intermediate host snails. Schistosomiasis intermediate host snails are common in the Nakanbé and Mouhoun basins, where suitable habitats are widespread. The Maxent model successfully identified areas with high environmental suitability for these intermediate host snails. This study integrated historical and recent occurrence data to assess temporal changes in intermediate host snail distribution, identify key climatic drivers of distribution shifts over the past 40 years, and highlight priority areas for targeted snail control in Burkina Faso.
Typhoid fever (Salmonella Typhi) has declined dramatically in Korea over three decades, but residual seasonality, demographic patterns and provincial spatial concentration have not been systematically reanalysed. Using all 3535 typhoid cases reported to the Korea Disease Control and Prevention Agency between 2001 and 2024 (3051 domestic and 484 imported [13.7%]), we quantified the long-term annual trend with the Hamed-Rao modified Mann-Kendall test (τ = -0.667, p = 0.0011) and a negative-binomial generalized linear model (GLM) yielding a Sen slope of -7.3%/year (95% CI -9.9 to -4.4); a parametric-bootstrap analysis of the runner-up 1-breakpoint GLM identified 2018 as the most likely structural change point (95% CI [2009, 2022]). A continuous Morlet wavelet transform of the weekly series revealed annual periodicity that exceeded a 1000-simulation AR(1) red-noise null by a factor of 2.60. Direct age standardization and age-band-specific Mann-Kendall tests showed statistically significant declines in every age stratum. Provincial spatial analysis (16 sido) gave a global Moran's I of 0.403 (p = 0.0083, 9999 permutations) under a Queen + k-nearest-neighbor-2 baseline scheme, with the southeastern coastal cluster (Gyeongnam-Busan-Ulsan-Gyeongbuk axis) preserved across 12 alternative weighting schemes after empirical Bayes shrinkage of sigungu-level rates and across two equal-length time strata; one province (Ulsan) survived Benjamini-Hochberg FDR adjustment of the 16 LISA p-values. Korean typhoid has continued its long-term decline; residual incidence concentrates in the southeastern coastal corridor, and imported cases-including ciprofloxacin-resistant H58 strains from South Asia-now form a substantial fraction of notifications, motivating pre-travel counseling and post-travel vigilance.
Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent age-related changes, including accumulation of senescent T cells near the epithelial layer, increased expression of ribosomal protein S6 kinase (mTOR target), upregulation of glycolytic enzyme (GAPDH) linked with metabolic reprogramming and elevated apoptosis activity (caspase 3). Together, these molecular signatures point to a progressive dysregulation of mucosal immune homeostasis highlighting reduced tissue resilience as we age. Furthermore, our assessment revealing increased gut-homing of aged naïve human T cells towards the mucosa suggests that exposure to antigenic stimulation at the mucosa is driving this senescence state. Although further investigations are needed to elucidate the causal mechanisms. Our findings highlight the therapeutic potential of pharmacological drugs (e.g., metformin, senolytics) and lifestyle-based approaches (such as caloric restriction) targeting key pathways reported to modulate the immune-epithelial interactions and support intestinal homeostasis during ageing.
Oral potentially malignant disorder (OPMD) remains a critical clinical challenge for cancer interception. However, the progression of OPMD toward oral squamous cell carcinoma (OSCC) is driven by profound cellular heterogeneity and dynamic microenvironmental remodeling. The mechanisms underlying these processes are not yet fully understood. Recent advancements in single-cell and spatial omics have facilitated high-resolution decoding of the precancerous landscape, unveiling multistep epithelial cell plasticity, fibroblast heterogeneity with extracellular matrix remodeling, immune suppression, and inflammatory reprogramming, as well as coupled metabolic and redox alterations that govern malignant transformation. These insights into the cellular mechanisms have led to a paradigm shift in the understanding of OPMD, reclassifying it as an ecosystem-level disease rather than a purely epithelial pathology. Nanomedicine is a potent platform for translating mechanistic knowledge into precision diagnostics and interventions at the precancerous stage. Nanomaterial-based strategies have been demonstrated to facilitate several critical processes, including enabling early lesion visualization and risk stratification, immune microenvironment reactivation, anti-fibrotic and anti-inflammatory remodeling, and targeted regulation of metabolic and oxidative stress pathways. A mounting body of evidence from preclinical and clinical studies lends support to the notion that nanotechnology-assisted early detection, microenvironmental reprogramming, and the interception of malignant transformation across oral and other precancerous conditions are indeed feasible. This review integrates single-cell-resolved mechanisms of OPMD progression with state-of-the-art nanomedicine-based diagnostic and therapeutic strategies, highlighting convergent biological axes and translational opportunities. By integrating single-cell biology with nanotechnology-driven precision medicine, this work is expected to improve the development of a nanomedicine framework for early cancer detection and treatment and outline future directions and challenges toward clinical implementation.
Human activities disrupt the parasitoid-mediated control of invasive alien species by fragmenting habitats and intensifying temperature-driven pest proliferation. However, the synergistic effects of changes in human-modified landscapes and climatic gradients on parasitoid-herbivore interactions remain underexplored, limiting integrated pest management. Here, we mapped the habitat suitability and dispersal-risk corridors of two invasive agromyzid leafminers (Liriomyza sativae and Liriomyza trifolii) and evaluated the effects of human activities and climate on the spatial association patterns of parasitoids-agromyzid leafminers on Hainan Island. The core risk patches and high-risk dispersal corridors of the two species were concentrated in towns and cultivated crop-growing areas in the northern plains and coastal regions, underscoring the key role of human activities in driving pest establishment and dispersal. As the temperature increased, human activities reduced the spatial association between agromyzid leafminers and parasitoids. In contrast, land use intensity strengthened their spatial association, likely indicating a trade-off between habitat fragmentation and cropland resource diversity in the spatial association patterns of these two populations. Our study reveals that human activities and climatic factors synergistically reduce spatial association patterns between parasitoids and invasive agromyzid leafminers. This pattern highlights a novel mechanism underlying pest-natural enemy mismatches and provides a conceptual basis for landscape-level strategies to enhance biological control. © 2026 Society of Chemical Industry.
Induced mutagenesis is a cornerstone of crop functional genomics, yet the extent to which distinct radiation sources reshape the spatial distribution of mutations remains difficult to evaluate in reduced-representation datasets. Here, we analyze a published genotyping-by-sequencing (GBS) panel (192,040 loci) to compare proton-beam and gamma-ray mutagenesis in Sorghum bicolor. Because GBS sampling is nonuniform, all analyses were conducted within an explicitly defined GBS-callable sequence space. Within this callable space, 96-channel trinucleotide spectra were broadly similar between radiation types, whereas spatial summaries differed. Macroscale analysis using the Gini coefficient indicated that proton-treated lines exhibit a highly unequal, spike-like distribution of mutations, whereas gamma-treated lines show a more diffuse window-level distribution. Microscale spatial statistics were consistent with clustering patterns that were more prominent in proton-treated lines, including an aggregation scale of ∼500 kb, with a substantial fraction of the mutational burden falling into high-density tracks. Within the callable locus set, coding- and promoter-proximal categories were not depleted of induced mutation events (single-nucleotide variants) across treatments. Furthermore, we did not detect a negative association between total mutational load and the coding-region mutation fraction in this dataset. These findings suggest that, within this dataset, proton mutagenesis is characterized not by unique chemical signatures but by a distinct spatial geometry that concentrates detectable mutation events. Because proton irradiation was represented by a single dose, whether proton treatment produces stronger clustering than gamma irradiation at equal mutational burden remains to be directly tested. Proton beams and gamma rays are used to create mutations for crop breeding, but they may damage DNA in different physical ways. We reanalyzed a published sorghum genotyping‐by‐sequencing (GBS) dataset to compare where induced mutations fall along the genome after proton‐beam versus gamma‐ray irradiation. Because GBS samples the genome unevenly, we defined the measurable “callable space” for each line and restricted all comparisons to that space. Within callable space, the two radiation types showed similar base‐change patterns, but proton‐treated lines had a far more uneven, spike‐like mutation landscape. Spatial analyses showed stronger clustering in proton lines, with many mutations concentrated into high‐density tracks on the scale of hundreds of kilobases. These results suggest that, in this dataset, proton mutagenesis is distinguished mainly by where detectable mutation events occur, highlighting why callable‐space correction is essential for reduced‐representation mutagenesis studies.
Hepatic echinococcosis (HE) is a major zoonotic disease in endemic regions, caused predominantly by Echinococcus granulosus sensu lato (cystic echinococcosis, CE) and Echinococcus multilocularis (alveolar echinococcosis, AE). Lesion progression reflects a prolonged host-parasite stalemate in which immunoregulation converges with angiogenesis and fibrovascular remodeling to enable chronic persistence, yet the cellular drivers and niche-specific interactions that sustain these lesions remain incompletely defined. While bulk omics has established a valuable foundation by delineating global perturbations in immune pathways, vascular programs, and extracellular matrix remodeling, these approaches average signals across heterogeneous lesions and adjacent liver, limiting the resolution of discrete cell states and intercellular communication that underpin persistence. Recent advances in single-cell RNA sequencing (scRNA-seq) and emerging spatial transcriptomics (ST) are beginning to overcome these limitations by enabling cell-resolved, niche-aware profiling of HE tissues. Early applications in HE have implicated late-stage expansion of SPP1+ macrophages, exhausted T-cell programs, and pro-angiogenic myeloid-endothelial crosstalk, providing a more mechanistic and spatially grounded view of fibrovascular remodeling and chronic inflammation. In this review, we synthesize key insights from scRNA-seq and ST studies of HE lesions and adjacent liver, discuss analytical considerations that are particularly relevant to fibrotic and necrotic tissues, and emphasize stage-aware and lesion-zone-aware interpretation. Taken together, we propose an integrative framework that links cell-state diversity to spatial context to prioritize actionable pathways and guide next-generation multi-omic investigations of HE.
The spatial organization of microorganisms plays a pivotal role in regulating microbial physiology, community behavior, and ecological interactions. However, reconstructing such three-dimensional (3D) microbial architecturesin vitroremains a major challenge because conventional culture systems rely on solid or gel-based matrices that restrict microbial motility and molecular diffusion. Here, we introduce 'floatony', a liquid-based strategy for the fabrication of spatially defined microbial colonies using liquid drawing technology. This approach enables the formation and retention of 3D microbial assemblies entirely within a liquid environment, without solidification or crosslinking. UsingE. colias a model organism, we examined how the rheological properties of the supporting liquid matrix influenced the stability of drawn structures of microbial assemblies. Although the optimal conditions depend on the molecular architecture of thickening agents, we identified an empirical design criterion-tanδ< 1.8-under which 3D structures of microbial assemblies were stably retained while maintaining low viscosity (∼10-1Pa·s) conducive to efficient molecular diffusion. Enzymatic activity assays confirmed thatE. colimaintained functional enzyme activity within the supporting liquid matrix, and that the diffusion of low-molecular-weight reaction products was preserved. Furthermore, complex two-dimensional and 3D structures of microbial assemblies were successfully fabricated and visualized in a liquid, including floating 3D structures, as confirmed by fluorescence imaging. This liquid drawing-based approach provides a new experimental framework for reconstructing and studying spatially organized microbial systems, offering opportunities for investigating microbial interactions and developing engineered living materials beyond conventional solid-supported platforms.
During morphogenesis, cell divisions are precisely regulated in space and time. The biological objectives achieved by such regulation are not fully understood. Here, by applying a newly developed lineage-reconstruction pipeline to Drosophila pupal wing, we reveal that the wing is composed of distinct cell groups that differ in division number, timing, and spatial positioning relative to wing veins. We show that the frequencies of these lineages, together with their initial cell sizes and growth profiles, converge to achieve a highly conserved average cell size. Our data further suggest that distance from veins provides spatial information that biases where distinct lineages arise, and that loss of veins caused by perturbation of EGFR signaling suppresses a specific lineage and disrupts cell-size control. Finally, our results point to a multiscale organization of division patterns, in which vein-associated spatial information is integrated with local neighbor effects in a manner that would mitigate mechanical instability within the tissue. Together, these findings delineate a cell-size control mechanism based on coordinated divisions of distinct cell groups that supports robust morphogenesis and functional tissue design.
Human-modified landscapes alter species interactions, yet the spatial scale at which landscape features influence predator-prey interactions remains poorly understood. Caudal autotomy, a widespread antipredator defense in many reptile species, has been proposed as a proxy of predation pressure. We investigated landscape-scale variation in tail autotomy frequency in two synanthropic lizards, Podarcis muralis and P. siculus, across four metropolitan areas in Italy. We combined extensive field sampling (386 individuals) across 33 localities along a gradient of urbanization with multi-scale analyses of landscape composition and configuration, as well as proxies of predator occurrence (citizen-science records, species distribution models, and the distribution of colonies of free-ranging cats). Using generalized linear mixed models, we assessed which landscape features and spatial scales best explained variation in autotomy frequency. Overall, 66% of individuals exhibited autotomy. The frequency of autotomy was higher in P. muralis than in P. siculus and increased significantly with body size. Landscape composition strongly influenced the frequency of autotomy. Forest cover within 50 m of capture sites was the strongest predictor of autotomy, with individuals from areas characterized by lower forest cover showing a higher probability of tail loss. The explanatory power of landscape composition decreased at broader spatial scales. Instead, neither landscape configuration metrics, estimated predator richness, nor proximity to cat colonies significantly improved model performance. The frequency of caudal autotomy in Podarcis lizards varies along the urbanization gradient and is primarily associated with fine-scale habitat structure. These findings underscore the strong role of landscape composition in shaping multiple animal traits and support the use of morphological indicators to assess the ecological effects of human-driven landscape change.
Spinocerebellar ataxia type 3 (SCA3) shows marked phenotypic heterogeneity and clinico-radiological dissociation, wherein macrostructural atrophy often fails to fully account for clinical severity. Although structural and functional connectivity abnormalities are well recognized, their potential interaction and neurobiological mechanisms remain poorly understood. This study aimed to identify potential biomarkers for SCA3 by linking structural connectivity-functional connectivity (SC-FC) coupling to mitochondrial function, neurotransmitter distribution, and gene expression. This dual-center study included discovery (117 SCA3, 165 healthy controls [HC]) and independent validation (24 SCA3, 48 HC) cohorts. Participants underwent multimodal 3 T magnetic resonance imaging (MRI) and clinical assessments (Scale for the Assessment and Rating of Ataxia [SARA]; International Cooperative Ataxia Rating Scale [ICARS]; Montreal Cognitive Assessment [MoCA]; Hamilton Depression Rating Scale [HAMD]). Regional and network-level SC-FC coupling was quantified using multiple regression and compared across disease-duration strata. Coupling alterations were spatially mapped to biological atlases (Allen Human Brain Atlas, MitoBrainMap, and positron emission tomography [PET]-based neurotransmitter receptor atlases) using bootstrapped Spearman's correlations (false discovery rate [FDR]-corrected). Gene enrichment analysis was implemented to characterize enriched biological pathways. SCA3 patients exhibited significant, atrophy-independent SC-FC decoupling in the bilateral dorsolateral putamen (dlPu), which correlated with ICARS scores. This decoupling pattern spatially aligned with mitochondrial complex II, 5-HT2A/5-HT4 receptors densities, and genes enriching for synaptic regulation and cellular homeostasis. By integrating SC-FC coupling with biological atlases, this study reveals the pathological underpinnings of clinico-radiological dissociation in SCA3 and identifies dlPu decoupling as a promising early-stage candidate imaging marker, providing an early and objective target for future neuroprotective trials. Chinese Clinical Trial Registry (ChiCTR): 1800019901, 2000039434. © 2026 International Parkinson and Movement Disorder Society.
Brain tumors, including primary intracranial tumors and brain metastases (BrMs), represent a major threat to human health and are associated with extremely poor prognoses. The brain tumor microenvironment (BTME) is a complex ecosystem composed of various elements, including tumor cells, immune cells, neurons, the vascular system, the extracellular matrix, and cytokines. These elements not only coexist spatially but are also functionally connected, interacting through intricate networks that collectively influence tumor initiation, progression, and therapeutic efficacy. In recent years, the application of novel technologies such as single-cell and spatial transcriptomics has uncovered complex cellular heterogeneity and spatial organization within the BTME. This review comprehensively summarizes the key components and functions of the BTME in tumor development and therapy, the mechanisms underlying intercellular interactions, with an emphasis on their clinical potential and challenges.
Photoacoustic tomography is a contrast agent-free imaging technique capable of visualizing blood vessels and tumor-associated vascularization in breast tissue. While sophisticated breast imaging systems have been recently developed, there is yet much to be gained in imaging depth, image quality and tissue characterization capability before clinical translation is possible. In response, we have developed a hybrid photoacoustic and ultrasound tomographic system (PAM3). The photoacoustic component has for the first time, in a full-view hemispherical breast system, three-dimensional multi-wavelength imaging capability and implements substantial technical advancements in critical hardware and software sub-systems. The ultrasound component enables three-dimensional ultrasound (computed) tomography from both reflected and transmitted signals from which we currently extract an image of the sound speed. For the first time, in vivo sound speed images were reconstructed using a fully 3D full-waveform inversion (FWI) algorithm, which demonstrated excellent quantitative as well as spatial accuracy. The sound speed image of the breast was then incorporated in photoacoustic reconstruction to correct for acoustic inhomogeneities, enabling accurate target recovery. The results demonstrate identification of blood vessels to depths of up to 48 mm, with a more uniform field of view than hitherto, and an isotropic spatial resolution comparable to the in-plane resolution of clinical breast Magnetic Resonance Imaging. The in vivo performance achieved, and the complementary diagnostic value of interrogating angiogenesis-driven optical contrast as well as tumor mass sound speed contrast, gives confidence in the system's clinical potential.
Metal ions are key regulators of the neuro-immune-tumor axis. Recent studies provide concrete evidence that neuronal Ca2+ pulses drive tumor-neuron integration and shape immune signaling. Synaptic Zn2+ and ZIP transporters modulate synaptic transmission and tumor growth. Tumor iron accumulation fuels proliferation while creating a clear ferroptosis vulnerability. Copper promotes angiogenesis, lysyl oxidase (LOX)-mediated extracellular matrix (ECM) remodeling and metastasis, and implicates cuproptosis as a therapeutic target. Mn potentiates cyclic GMP-AMP synthase (cGAS)-STING signaling and serves as both an immune adjuvant and manganese-enhanced magnetic resonance imaging (MEMRI) contrast. Besides, Mg and K+ regulate kinase/T-cell receptor (TCR) function and tumor-neuron excitability, respectively. Despite these advances, major gaps persist, notably limited spatial and temporal mapping of labile metal pools, a paucity of cell-type-specific causal perturbations, and underdeveloped tumor-targeted metal-modulating therapies with proven safety. We therefore propose a focused research agenda: integrate spatial metallomics with single-cell multiomics, deploy metal-sensitive longitudinal imaging, apply conditional genetic and chemogenetic perturbations and organotypic models to dissect neuro-immune cross-talk, and implement preclinical pipelines emphasizing tumor-selective delivery and comprehensive safety testing.
Tumor-educated platelets (TEPs) have recently emerged as an important component of liquid biopsy, yet the clinical relevance in colorectal cancer (CRC) remains unclear. Here, we employed 10 machine learning algorithms to develop a stable, accurate TEP-related gene signature (TEPGS) to explore its links to tumor-associated macrophages (TAMs) and spatial platelet abundance. TEPGS correlated strongly with poor prognosis and outperformed 71 published gene signatures in predicting CRC overall survival. Multi-omics analysis displayed that high TEPGs were marked by increased TP53 mutations, copy number alterations, diminished immune features, enrichment of pro-tumor SPP1+/FCN1+ TAMs, and elevated spatial platelet abundance. Patients with high TEPGS exhibited resistance to immunotherapy but responded to a BRAF V600E inhibitor, while TEPGS showed tentative value for predicting cetuximab response and preliminary utility for bevacizumab. Functional assays confirmed ARPC1B as an oncogene. Our findings establish TEPGS as a valuable biomarker for prognostic stratification and tailored therapy selection in CRC.
Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.