Biology subjects

Su, L.

Publications and source records attributed to Su, L..

At least 19 recordsLinked to original sources

bioRxiv2026

Circular DNA interacts with Cathelicidin LL37 to efficiently activate plasmacytoid dendritic cells

Circulating cell-free DNA in inflamed tissues contains different forms of DNA, including extrachromosomal circular DNA (eccDNA). The role of DNA topology in innate immune sensing remains poorly understood. Here we show that circular DNA is a potent ligand for human plasmacytoid dendritic cells (pDCs) and that the cathelicidin host defense peptide LL37 selectively enhances circular DNA-induced activation. Across eccDNA, minicircle and synthetic circular DNA species, LL37 strikingly amplified type I interferon (IFN-I) and pro-inflammatory cytokine production, whereas linearized counterparts of identical sequence remained inactive. LL37-circular DNA complexes signaled through endosomal TLR9, as activation was abrogated by chloroquine and by the TLR9 antagonist IRS869. Mechanistically, LL37 promoted preferential retention of circular DNA in EEA1-positive early endosomes, and surface plasmon resonance revealed enhanced TLR9 binding to circular versus linear DNA, without differential LL37 binding. DNA topology rather than sequence, therefore, determines the immunostimulatory potential of cell-free DNA in pDCs. These findings define a mechanism by which LL37 and circular DNA jointly drive TLR9-dependent IFN-I responses, with implications for autoimmunity, cancer and nucleic acid therapeutics.

immunology↗

bioRxiv2026

Human brain white matter charts in international populations

Brain charts provide normative references for identifying neurodevelopmental milestones and clinically meaningful deviations. Existing white matter (WM) charts are derived predominantly from European and North American populations, limiting generalizability. Here, we established the first set of population-specific WM charts of 198 morphological and microstructural phenotypes for both Chinese (N=19,215) and Western (N=15,584) populations across the human lifespan. Developmental trajectories and spatial organization of WM maturation and degeneration were broadly conserved across the populations, whereas maturational timing varied across pathways and metrics. The Chinese population showed earlier maturation in several projection and sensorimotor pathways, but more protracted maturation in higher-order association and limbic pathways. Chinese population-matched charts more accurately predicted WM phenotypes and detected more extreme disease-related deviations in brain health in the Chinese population than Western-derived models. Individual deviation patterns further discriminated patients from healthy controls and predicted cognitive performance and plasma biomarkers. Our findings reveal population-specific WM maturation and show that reference-population mismatch can reduce the accuracy and clinical sensitivity of normative brain charts.

neuroscience↗

bioRxiv2026

Promyelocytic leukemia (PML) suppresses hepatitis B virus cccDNA transcription through SUMOylation- and SMC5/6-dependent mechanisms

Chronic hepatitis B virus (HBV) infection persists under current antiviral therapy because covalently closed circular DNA (cccDNA) remains in the infected hepatocytes as a durable transcriptional template. Although type I interferon (IFN-I) can reduce HBV cccDNA gene expression, the host effectors and mechanisms that restrict cccDNA remain incompletely defined. Using a minicircle-based HBV cccDNA expressing a Gaussia luciferase reporter gene (mcHBV-GLuc), we investigated how promyelocytic leukemia protein (PML) suppresses HBV cccDNA activity. Multiple PML isoforms reduced cccDNA-driven reporter activity and HBsAg production, and HBx-deficient ({Delta}X) mcHBV cccDNA was more susceptible than wild-type cccDNA to PML-mediated inhibition. Interestingly, efficient antiviral activity required the major PML SUMOylation sites. Disruption of SMC5/6 function attenuated PML-mediated repression of HBx-deficient cccDNA, associated with reduced PML SUMOylation and PML nuclear-body organization. These findings identify PML as a SUMO-dependent inhibitor of HBV cccDNA activity and reveal a context-dependent functional relationship between PML and SMC5/6 that is modulated by HBx.

immunology↗

bioRxiv2026

Imaging-Based Age- and Sex-specific Cardiovascular and Skeletal Phenotypes in Fbn1C1041G/+ Mice

Marfan syndrome is a multisystem connective tissue disorder with age-dependent and sex-dependent phenotypic variability. This study characterized early cardiovascular, valvular, transmitral flow, and skeletal changes in Fbn1C1041G/+ mice. Male and female wild-type and Fbn1C1041G/+ mice were examined from 4 to 20 weeks of age. Transthoracic echocardiography was used to measure aortic root and ascending aortic diameters, anterior mitral leaflet length, and mitral inflow Doppler parameters. Lateral X-ray imaging was used to quantify kyphosis angle. Fbn1C1041G/+ mice of both sexes developed progressive aortic dilation, with earlier and broader aortic root involvement in males and delayed annular dilation in females. Anterior mitral leaflet elongation was detected from 8 weeks in males and at 20 weeks in females. In contrast, reduced E-wave velocity and E/A ratio were present from 4 weeks in both sexes, without changes in A-wave velocity. Kyphosis was detectable earlier in females than in males. These findings show that early Fbn1-related phenotypes follow organ-specific and sex-dependent temporal patterns, supporting age-resolved and sex-stratified assessment in preclinical Marfan syndrome studies.

pathology↗

bioRxiv2026

Genic Position and Methylation Context Shape DNA Methylation-Expression Relationships in Rice Internode Development

Elongating rice internodes present a developmental gradient from dividing meristem to mature cells, providing an elegant pseudo-time course for study of plant vegetative development. We tested the hypothesis that DNA methylation regulates gene expression during rice internode development by integrating RNA-seq and bisulfite DNA sequencing across eight internode segments. Previously described topologically associated chromatin domain borders aligned with transcription start sites of constitutive expressed genes. CpG and CHG differential methylation was enriched in young segments, consistent with maintenance methylation; whereas CHH methylation showed similar differential abundance in young and old segments. CHH and CHG methylation in upstream regions, CpG methylation within gene bodies, and any methylation in 5' and 3' untranslated regions were permissive of moderate to high gene expression. Very low expression was associated with CpG methylation upstream, CHG and CHH methylation within gene bodies, and CpG and CHG methylation downstream. A nonrandom subset of genes, including cell wall-related glycoside hydrolases, lignin and tricin biosynthesis enzymes, and WD40 proteins, showed methylation-expression correlations, with expression changes enriched in triple-marked elements. These results suggest that internode phenotypes of DNA methylation machinery mutants relate to alteration of specific target genes, opening approaches for grass culm improvement for lodging resistance and biomass production. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/737558v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@b726eaorg.highwire.dtl.DTLVardef@5bd017org.highwire.dtl.DTLVardef@1bac873org.highwire.dtl.DTLVardef@1be3474_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance statementStems of cereals and other grasses have an important function in supporting grain production and serving as a source of carbon for the bioeconomy. This study supports methylation of the cytosine bases of DNA as a regulator of chromatin structure and gene expression in the stems of rice. Different methylation contexts are implicated in specific roles in both positive and negative gene expression regulation that might be leveraged to improve stem properties.

plant biology↗

bioRxiv2026

Unearthing a fungal giant: Dianjunaceae fam. nov., a novel Paleocene lineage of Xylariales harbouring Dianjunus rex gen. et sp. nov.

During mycological surveys in Yunnan Province, China, specimens of a fungus producing massive, upright stromata up to 50 cm high and individually 2.2 Kg in weight were sampled. Through an integrative taxonomic approach combining detailed morphology, multilocus phylogeny (ITS, LSU, RPB2, TUB2), and phylogenomic analyses, this fungus is proposed as the new species Dianjunus rex gen. et sp. nov., the type of the new family Dianjunaceae (Xylariales). Phylogenetic analyses robustly place Dianjunaceae as a distinct sister clade to Graphostromataceae. Divergence time estimation dates the origin of this family to the early Paleocene ([~]65 Mya), coinciding with the post-K-Pg extinction period, when an estimated 75% of all plant and animal species went extinct, and a significant ecological reorganization of life on earth happened. The stromata of D. rex represent the largest fructifications documented within the Ascomycota, significantly expanding the known morphological range of the Xylariales. The study provides a comprehensive description, including a nodulisporium-like anamorph with periconiella-like branching patterns, and discusses the taxons phylogenetic placement, and distinctive morphology. This discovery highlights the unexplored fungal diversity in East Asian forests.

microbiology↗

bioRxiv2026

Dynein-microtubule forces drive nucleokinesis and transmigration in T cells

Beyond the mechanical capacity of canonical actomyosin-driven amoeboid motility in permissive extracellular environments, the nucleus becomes the principal barrier to T cell migration in confining tissues. We establish the dynein-microtubule (MT) force-transmission axis as an essential mechanism for nuclear translocation during confined T cell migration and transmigration. We argue that dynein acts both as a motor and as an F-actin-anchored force-transmission element (fulcrum), sliding MTs and the MT-coupled nucleus along the cell cortex to drive nucleokinesis and productive cell displacement. Dynein is the primary driver of nucleokinesis: its inhibition arrests nucleus movement independently of myosin II activity, while F-actin dynamics remain spatiotemporally decoupled from nuclear oscillations. During transmigration, dynein and actomyosin act cooperatively and non-redundantly, and only combined inhibition abolishes nuclear passage. Computational modeling demonstrates that dynein-mediated pulling, together with volume exclusion imposed by the nucleus, is sufficient to generate self-organized nuclear oscillations. Dynein inhibition in zebrafish Langerhans cells impairs protrusion dynamics in situ, identifying the dynein-MT axis as an evolutionarily conserved mechanobiological program. Collectively, these findings identify the dynein-MT mechanical unit as a potential target for engineering T cells with enhanced solid-tumor infiltration.

cell biology↗

bioRxiv2026

Acyl amides derived from a bacterial symbiont control development of its nematode host

Symbiotic bacteria frequently regulate host development through small-molecule signals. In the entomopathogenic Steinernema nematode - Xenorhabdus bacterium symbiosis, which is widely used in biological pest control, the signals that trigger nematode development have remained unknown. Using a phenotypic screen of Xenorhabdus mutants, we identified bacterial acyl amides, which we named stripteamides, as signals required for efficient recovery of Steinernema infective juveniles. Stripteamides are synthesized from phenylethylamine and activated fatty acid substrates by StaS, a previously uncharacterized amide synthase. Mechanistic and structural analyses indicate that StaS evolved from the initiation module of a nonribosomal peptide synthetase (NRPS) and was repurposed to generate signaling metabolites for host development. Stripteamide signaling is conserved across Xenorhabdus species and operates in different Steinernema hosts. These findings reveal a new function for widespread bacterial acyl amides that previously have been shown as cytotoxic and affecting bacterial quorum sensing, highlighting the context dependence of microbial natural product language.

microbiology↗

bioRxiv2026

HEPLISAV-B Breaks Immune Tolerance and Induces HBV Control via CD4 T Cell-Dependent Mechanisms in a Chronic Hepatitis B Mouse Model

BackgroundChronic hepatitis B virus (HBV) infection (CHB) affects nearly 300 million individuals globally and remains incurable with current antiviral therapies, which suppress viral replication but rarely achieve functional cure defined by sustained loss of hepatitis B surface antigen (HBsAg). CHB is characterized by profound virus-induced immune tolerance that limits the efficacy of conventional therapeutic vaccination strategies. ObjectiveTo evaluate the therapeutic efficacy and immunological mechanisms of HEPLISAV-B, a CpG-1018-adjuvanted HBsAg vaccine, in breaking immune tolerance and inducing functional cure-like responses in a murine model of CHB. DesignUsing the adeno-associated virus-HBV (AAV-HBV) mouse model, mice with high levels of persistent HBV viremia were vaccinated with two doses of HEPLISAV-B. Virological outcomes in the blood and liver, immune responses and mechanisms were assessed. ResultsHEPLISAV-B induced rapid and durable HBsAg clearance, markedly reduced circulating and intrahepatic HBV DNA and RNA, and suppressed viral replication without hepatocellular injury. Vaccination elicited robust, sustained anti-HBs IgG1 and IgA responses, enhanced HBsAg-specific T and B cell immunity, reduced CD4 regulatory T cells, and decreased PD-1 expression on CD4 T cells. Therapeutic efficacy was strictly dependent on CD4 T cells and the CD40/CD40L signaling pathway, but independent of CD8 T cells, indicating a CD4-driven, non-cytolytic antiviral mechanism critical for HEPLISAV-B induced HBV control. ConclusionHEPLISAV-B effectively breaks HBV-induced immune tolerance and restores coordinated antiviral immunity through a CD4 T cell-/CD40L-dependent pathway. The findings support its potential as a therapeutic vaccine in CHB patients. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSChronic HBV infection is marked by profound virus-induced immune tolerance, current antiviral therapies and vaccines fail to reliably induce HBsAg loss or restore effective antiviral immunity, highlighting the need for immune-based therapeutic strategies. What this study addsThis study demonstrates that the clinically approved vaccine HEPLISAV-B can break HBV immune tolerance in a chronic HBV mouse model, inducing durable HBsAg clearance and anti-HBs immunity, non-cytolytic depletion of intrahepatic HBV DNA, through a mechanism strictly dependent on CD4 T cells and CD40/CD40L signaling. How this study might affect research, practice or policyThese findings defined a CD4 T cell-CD40L/CD40 axis that is critical in CHB functional cure, and support testing HEPLISAV-B as a therapeutic vaccine in CHB patients. O_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC="FIGDIR/small/711721v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f78e63org.highwire.dtl.DTLVardef@1a54631org.highwire.dtl.DTLVardef@1a33ee2org.highwire.dtl.DTLVardef@75a2bd_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

immunology↗

bioRxiv2025

Receptor-tethered orthogonal IL-2 enhances regulatory T cell therapy

Regulatory T cell (Treg) therapy is an emerging platform for controlling immune overactivation. Efficacy of Treg therapy is limited by the poor persistence of infused Tregs due to insufficient IL-2, which is essential for Treg survival and function. IL-2 activates many immune cells besides Tregs, imposing a challenge for the selective provision of IL-2 to infused Tregs. In this study, we found infusions of orthogonal (ortho) IL-2 failed to enhance Tregs engineered with a corresponding orthoIL-2 receptor (IL-2R) in a mouse model of autoimmune diabetes. We then developed a receptor-tethered orthoIL-2 by optimizing the combination of IL-2, IL-2R, and the linker connecting them to achieve autocrine signaling selectively in engineered Tregs. Tregs expressing the tethered orthoIL-2 showed autocrine IL-2 signaling in vitro, enhanced CD25, CTLA-4, and Foxp3 expression, persisted without exogenous IL-2 in vivo, and prevented autoimmune diabetes using as few as 2,000 Tregs. Knocking the tethered orthoIL-2 construct into the Foxp3 locus enabled Treg-specific expression, with the additional benefit of positively reinforcing tethered orthoIL-2 expression through the activation of the Foxp3 gene by enhanced IL-2 signaling. Together, these results illustrate a safe and effective cell-engineering solution for overcoming Tregs dependency on exogenous IL-2, thereby achieving superior therapeutic efficacy.

immunology↗

bioRxiv2025

Global analysis of membrane protein S-acylation in the model plant Arabidopsis thaliana

Protein S-acylation is the addition of fatty acids to the cysteine residues in a protein, catalyzed by protein S-acyltransferases (PATs). Despite extensive research on protein S-acylation in animals, our understanding of this process in plants remains limited. In this study, we sought to characterize the S-acylproteome of membrane proteins in Arabidopsis and identify potential substrates for two important plant immunity-related PATs (PAT5 and PAT9). To achieve this, S-acylated membrane proteins were first enriched via our optimized acyl-biotinyl exchange strategies at both the protein-level and peptide-level. The enriched samples were then analyzed by label-free quantitative liquid chromatography-mass spectrometry. The results from the two enrichment methods demonstrated that they were complementary in identifying S-acylated proteins and S-acylation sites. Using these methods, over 2500 S-acylation sites in more than 2000 putative S-acylated proteins were identified. Proteins involved in vesicle trafficking, plant phosphorylation, immune responses, and signal transduction pathways were significantly enriched. Additionally, certain amino acid patterns surrounding the S-acylation sites were identified. Comparisons of the S-acylproteomes between the wild type and the PAT5 and PAT9 mutants revealed over 100 potential substrates for both S-acyltransferases. The high quality of our data was supported by the significant overlap with the previously reported data and successful experimental verification of selected candidate proteins. Overall, our study revealed a well-represented S-acylproteome for Arabidopsis (especially its membrane proteins) and identified potential substrates for PAT5 and PAT9. These findings will facilitate the functional characterization of S-acylated proteins in plants.

plant biology↗

bioRxiv2025

Targeting ZNRF3 and RNF43 to Restore Regeneration and Reverse Metabolic Dysfunction-Associated Steatotic Liver Disease

Liver regeneration and hepatocyte metabolic identity are disrupted in metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), yet the mechanisms of restore liver regeneration and reprogram metabolism for disease reversal remains poorly understood. Here, we show that {beta}-Catenin activity progressively declines in hepatocytes during MASH in both humans and mice, coinciding with impaired regeneration and defective lipid clearance. Targeted deletion of the endogenous WNT pathway inhibitors ZNRF3 and RNF43 in hepatocytes after MASH onset reactivates {beta}-Catenin signaling, leading to robust regression of steatosis, inflammation, and fibrosis, and restoring regenerative capacity across multiple fatty liver disease models. Mechanistically, this therapeutic effect is driven by {beta}-Catenin-dependent induction of the alternative bile acid synthesis pathway without disrupting systemic lipid homeostasis. Importantly, both short-and long-term deletion of ZNRF3/RNF43 restores liver function without triggering tumorigenesis or hepatotoxicity, indicating a safe therapeutic window. These findings reveal that physiological activation of WNT/{beta}-catenin signaling via ZNRF3 and RNF43 offers a viable regenerative and metabolic strategy for reversing fatty liver disease.

cell biology↗

bioRxiv2025

Brain Network Analysis in Alzheimer's Disease and Mild Cognitive Impairment using High-Density Diffuse Optical Tomography

Dementia is associated with altered resting state connectivity, measures of which could aid in its early detection and monitoring. High-density diffuse optical tomography (HD-DOT) is well-suited to detect these alterations at scale due to its numerous practical advantages, but it has not yet been applied to dementia. In this study, we investigated resting state functional connectivity across the prefrontal cortex in individuals with Mild Cognitive Impairment (MCI, n = 22), Alzheimers Disease (AD, n = 21), and in healthy controls (n = 22). A graph theoretical approach was taken to characterise both global and local patterns of connectivity over a five-minute resting period. We found that individuals with AD and MCI exhibited denser and stronger networks, with shorter path lengths, as well as a loss of consistent key network hubs with worsening cognitive impairment. These results indicate that networks in dementia are more globally connected, albeit in a disorganised manner, perhaps reflecting the recruitment of additional connections for short-term stability which may be ultimately damaging in the long-term. Following the demonstration of HD-DOTs capacity to detect differences between healthy ageing and dementia, this work opens up new possibilities for the use of optical imaging in the study of this clinical population and HD-DOTs potential for scalable clinical use.

neuroscience↗

bioRxiv2025

Harnessing the Power of Single-Cell Large Language Models with Parameter Efficient Fine-Tuning using scPEFT

Single-cell large language models (scLLMs) capture essential biological insights from vast single-cell atlases but struggle in out-of-context applications, where zero-shot predictions can be unreliable. To address this, we introduce a single-cell parameter-efficient fine-tuning (scPEFT) framework that integrates learnable, low-dimensional adapters into scLLMs. By freezing the backbone model and updating only the adapter parameters, scPEFT efficiently adapts to specific tasks using limited custom data. This approach mitigates catastrophic forgetting, reduces parameter tuning by over 96%, and decreases GPU memory usage by more than half, significantly enhancing scLLMss accessibility for resource-constrained researchers. Validated across diverse datasets, scPEFT outperformed zero-shot models and traditional fine-tuning in disease-specific, cross-species, and under-characterized cell population tasks. Its attention-mechanism analysis identified COVID-related genes associated with specific cell states and uncovered unique blood cell subpopulations, demonstrating scPEFTs capacity for condition-specific interpretations. These findings position scPEFT as an efficient solution for improving scLLMs utilities in general single-cell analyses.

cell biology↗

bioRxiv2025

Phloem-Specific Translational Regulation of Soybean Nodulation: Insights from a Phloem-Targeted TRAP-Seq Approach

Soybean (Glycine max) root nodulation is a symbiotic process that requires complex molecular and cellular coordination. The phloem plays a crucial role not only in nutrient transport but also in long-distance signaling that regulates nodulation. However, the molecular mechanisms underlying phloem-specific regulation during nodulation remain poorly characterized. Here, we developed a phloem-specific Translating Ribosome Affinity Purification sequencing (TRAP-seq) system to investigate the translational dynamics of phloem-associated genes during nodulation. Using a phloem-specific promoter (Glyma.01G040700) combined with the GAL4-UAS amplification system, we successfully captured the translatome of soybean root phloem at early (72 hours post-inoculation, hpi) and late (21 days post-inoculation, dpi) nodulation stages. Differential expression analysis revealed dynamic translational reprogramming, with 2,636 differentially expressed genes (DEGs) at 72 hpi and 8,422 DEGs at 21 dpi. Gene ontology and pathway enrichment analyses showed stage-specific regulatory shifts, including early activation of ethylene and defense pathways and late-stage enhancement of nutrient transport and vascular development. Transcription factor analysis identified GmbHLH121 as a key phloem-specific regulator of nodulation. Functional validation using RNAi knockdown and overexpression experiments demonstrated that GmbHLH121 negatively regulates nodule formation, likely acting downstream of or independently from early nodulation signaling pathways. Additionally, we uncovered dynamic regulation of cell wall-modifying enzymes (PME and PMEI) in the phloem, implicating their role in modulating plasmodesmata permeability and facilitating symplastic connectivity during nodulation. Our findings highlight the critical role of phloem-mediated translational regulation in coordinating root nodulation, emphasizing the phloem as an active regulatory hub for long-distance signaling and symbiotic efficiency.

plant biology↗

bioRxiv2025

Synergistic biodegradation of polyethylene by experimentally evolved bacterial biofilms

Polyethylene, one of the most widely used synthetic polymers, presents significant environmental challenges due to its resistance to biodegradation. Its surface offers a unique ecological niche for microbial colonization and serves as a primary habitat for degrading microorganisms. Despite the pivotal role microbial communities play in plastic degradation, there has been limited research on constructing stable, interacting microbial consortia. In this study, we explored the potential of evolving bacterial biofilm communities to enhance polyethylene degradation. Through long-term experimental evolution, six microbial populations underwent 40 selection cycles using polyethylene as their sole carbon source. The resulting evolved communities formed robust, multi-species biofilms with enhanced degradation capabilities, outperforming their ancestral populations in biofilm production. Pseudomonas stutzeri emerged as the dominant species, orchestrating a synergistic interaction with two other isolates through metabolic division of labor. (Meta)-transcriptomics analysis revealed that Pseudomonas primarily contributed to the expression of enzymes involved in microbe-mediated degradation of polyethylene, whereas the other community members were responsible for secreting extracellular polysaccharides, improving biofilm formation. This study highlights the potential of experimentally evolved microbial consortia to synergistically accelerate plastic biodegradation, offering promising strategies for environmental bioremediation.

microbiology↗

bioRxiv2025

Mapping functional hemodynamic and metabolic responses to dementia: a broadband spectroscopy pilot study

SignificanceBroadband near-infrared spectroscopy (bNIRS) can simultaneously monitor several chromophores including the oxidative state of cytochrome c-oxidase (oxCCO), an oxygen metabolism biomarker whose activity is altered in Alzheimers disease. Being a portable and non-invasive neuromonitoring technique, bNIRS could thus provide accessibility to brain-specific biomarkers and aid in the dementia diagnostic pathway. AimWe use bNIRS recorded functional haemodynamic and oxCCO changes to assess their relevance in Alzheimers disease dementia as potential biomarkers. ApproachUsing a visual-stimulus paradigm, we recorded functional changes in oxy-, deoxy-haemoglobin and oxCCO in three similarly aged cohorts: healthy controls (n=5), individuals with mild cognitive impairment (n=7) and individuals with Alzheimers dementia (n=7). We then selected features from these functional responses to find the best correlation with clinical cognitive markers (cognitive and behavioural test scores and clinical diagnosis) using canonical correlation analysis. ResultsWe found individual variations in peak amplitude and time-to-peak for all the stimulus-evoked bNIRS signals across the three cohorts. Canonical correlation analysis showed a strong correlation between bNIRS features and the clinical cognitive markers (r=0.902). However, repeating the same analysis by excluding the bNIRS oxCCO features leads to a significantly lower correlation (r=0.687) with the clinical markers. ConclusionsoxCCO could be a crucial biomarker, partly explaining cognitive differences with dementia. bNIRS uniquely provides a portable and non-invasive technique to monitor several chromophores simultaneously including oxCCO with potential future applications in tracking dementia progression.

bioengineering↗

bioRxiv2025

scBSP: A fast and accurate tool for identifying spatially variable features from high-resolution spatial omics data

Emerging spatial omics technologies empower comprehensive exploration of biological systems from multi-omics perspectives in their native tissue location in two and three- dimensional space. However, sparse sequencing capacity and growing spatial resolution in spatial omics present significant computational challenges in identifying biologically meaningful molecules that exhibit variable spatial distributions across different omics. We introduce scBSP, an open-source, versatile, and user-friendly package for identifying spatially variable features in high-resolution spatial omics data. scBSP leverages sparse matrix operation to significantly increase computational efficiency in both computational time and memory usage. In diverse spatial sequencing data and simulations, scBSP consistently and rapidly identifies spatially variable genes and spatially variable peaks across various sequencing techniques and spatial resolutions, handling two- and three-dimensional data with up to millions of cells. It can process high-definition spatial transcriptomics data for 19,950 genes across 181,367 spots within 10 seconds on a typical desktop computer, making it the fastest tool available for handling such high-resolution, sparse spatial omics data while maintaining high accuracy. In a case study of kidney disease using 10x Xenium data, scBSP identified spatially variable genes representative of critical pathological mechanisms associated with histology.

bioinformatics↗