Biology subjects

Zhou, Q.

Publications and source records attributed to Zhou, Q..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Integrated Bioinformatics analysis and Metabolomic Responses in finding novel therapeutic approach to treat viral myocarditis

BackgroundMyocarditis is one of the most common health problems in young people. Despite imaging techniques and endomyocardial biopsies advancing, there is still inadequate for myocarditis characterization. Some studies have shown that myocarditis is closely associated with mitochondrial dysfunction. Therefore, this study was aimed to identify mitochondrial-related biomarkers and gene regulatory networks in myocarditis and potential therapeutic targets. MethodsWe downloaded GSE95368 dataset from GEO to get myocarditis gene expression profiles, then used EdgeR and AI algorithm for bioinformatics analysis of DEGs functions. Established CVB3-induced mouse myocarditis model via intraperitoneal injection, and assessed energy metabolism differences using targeted metabolomics. CVB3 stimulus induced myocarditis in H9C2 cells. We assessed mitochondrial dysfunction (ATP, MMP) with commercial kits, MAPK8 release via ELISA, and MAPK8, p-PI3K, p-AKT levels by western blot. Furthermore, a total of 8 patients primarily diagnosed with myocarditis were enrolled, and levels of MAPK8 and CK in serum were detected. SP600125, an inhibitor of MAPK8, was administrated to CVB3-infected mice to study its potential protective effect in viral myocarditis. ResultsWe obtained 77 DEGs enriched in myocarditis. Analysis yielded 11 modules, MEpurple module genes linked to myocarditis progression were identified via WGCNA. MAPK8, NAMPT and ALB are associated with mitochondrial function. CVB3-infected mice showed cardiac inflammation and high MAPK8 expression in serum or heart tissues.The target metabolism results indicated altered central carbon metabolism distinguished CVB3 group from control, with higher D-Glucose-1-phosphate and D-Glucose-6-phosphate and lower L-Cystine, dCMP, IMP and Xylulose-5-phosphate levels. CVB3 treatment caused mitochondrial dysfunction in H9C2 cells (decreased ATP, MMP), and increased MAPK expression. Western blot showed MAPK8 consolidated the levels of p-PI3K and p-AKT. CK activity was notably higher in myocarditis patients than healthy individuals. MAPK8 levels in myocarditis patients serum also exceeded those in healthy individuals. Pearson analysis indicated that MAPK8 and CK may contribute to myocarditis progression via distinct mechanisms. In CVB3-infected mouse model with SP600125 treatment, cardiac inflammation and MAPK8, p-PI3k, p-AKT expression were reduced, confirming MAPK8s crucial role in viral myocarditis. ConclusionOur study identified MAPK8 as a key biomarker of myocarditis, and it may be a potential therapeutic target for myocarditis.

pathology↗

bioRxiv2025

Discovery and optimization of antimicrobial peptides from extreme environments on global scale

The escalating crisis of global antimicrobial resistance (AMR) necessitates the discovery of novel antibiotics. Antimicrobial peptides (AMPs), particularly those from under-explored extreme environments, represent a promising therapeutic class. Here, we introduce SEGMA (Structure-aware Extremophile Genome Mining for Antimicrobial peptides), a computational framework that integrates structure information to systematically mine AMPs from extremophile genomes on a global scale. By analyzing 60,461 extremophile metagenome-assembled genomes (MAGs) from diverse habitats, SEGMA identified 3,298 novel AMPs (termed "extremocins"), which exhibit unique amino acid profiles and physicochemical properties. Leveraging a beam search-guided optimization strategy, we further enhanced selected extremocins to achieve broad-spectrum antimicrobial activity. Experimental validation confirmed potent in vitro efficacy against clinically relevant pathogens. This study underscores the value of structure-aware mining and extremophile microbiomes in expanding the antibiotic arsenal against AMR. HighlightsO_LISEGMA, a structure-aware deep learning framework, mines 3,298 novel antimicrobial peptides (extremocins) from 60,461 extremophile genomes on global scale. C_LIO_LIExtremocins exhibit unique sequence features, and expand known antibiotic space, few of which shows homology to existing AMP databases. C_LIO_LIA beam search-guided optimization strategy enhanced selected extremocins to achieve broad-spectrum activity against clinically relevant pathogens. C_LIO_LIExperimental validation confirmed that candidate extremocins exhibit potent in vitro and in vivo antimicrobial activity, highlighting their therapeutic potential. C_LI

bioinformatics↗

bioRxiv2025

Development and Genome-level Microevolution of Oral Microbiome during Surface Colonization

The oral microbiome is essential to human health, yet its de novo ecological succession and microevolutionary dynamics remain poorly understood due to the absence of tractable in vivo models. Dental implants provide a unique opportunity to investigate these processes by establishing a defined time-zero for initial bacterial attachment. In this cohort study, we performed shotgun metagenomics on 95 subgingival plaque samples from 19 participants, including peri-implant sites at weeks 1-4 after crown placement and adjacent teeth as controls. Peri-implant and adjacent periodontal microbiomes exhibited distinct taxonomic and functional profiles. Even the same taxa had different functional potential across the two sites. These findings indicated that oral microbiome development is a niche-specific process with selective colonization rather than passive microbial translocation from adjacent sites. Longitudinal analysis identified three microbial community modules driving the succession of oral microbiome, including pioneer colonizers, constitutive species, and late commensals. Each module followed distinct temporal abundance patterns and played unique ecological roles throughout the succession process. Strain-level resolution revealed divergent microevolutionary trajectories: pioneer colonizers and late commensals exhibited higher cumulative mutation rates and greater strain heterogeneity overtime, with enrichment of nonsynonymous single nucleotide variants in genes related to virulence and metabolism, whereas constitutive species remained evolutionarily stable by contrast. Our study reveals that the development, succession, and microevolution of the oral microbiome is structured, niche-dependent, and modulated by inter-species facilitation and selective genomic adaptation. These findings advance the understanding of oral microbiome ecology and provide a conceptual foundation for manipulating microbial succession in health and disease.

microbiology↗

bioRxiv2025

Molecular Mechanisms Underlying Human Vγ9Vδ2 T Cell Activation by Butyrophilin-3 (BTN3) Targeted Antibodies

{gamma}{delta} T cells express T cell receptors (TCRs) composed of paired {gamma} and {delta} chains. The V{gamma}9V{delta}2 T cells are the main subpopulation of {gamma}{delta} T cells in human peripheral blood, which responds to phosphoantigens (pAgs) through butyrophilins (BTN) molecules, such as BTN3A1/2/3 and BTN2A1. Antibodies targeting BTN3As, such as ICT01, can activate V{gamma}9V{delta}2 T cells independently of pAgs, although the underlying mechanism remains poorly characterized. In this study, we reveal the molecular basis of ICT01-mediated V{gamma}9V{delta}2 T cell activation using structural, biochemical, and cellular analyses. ICT01 binds to a unique region in the extracellular domain of BTN3As, destabilizing the BTN2A1-BTN3As interface and facilitating V{gamma}9V{delta}2 TCR engagement, ultimately resulting in activation of V{gamma}9V{delta}2 T cells. Our findings provide insights into the mechanism by which agonist antibodies induce {gamma}{delta} T cell activation and provide guide strategies for developing BTN-targeted immunotherapies.

immunology↗

bioRxiv2025

The role of medicinal Cu2+ salts in expanding the multi-pathway application of tigecycline against drug-resistant bacteria

Tetracyclines are highly susceptible to photolysis, causing pollution in water, land and other ecosystems, as well as posing threats to human health. In this study, we found that only tigecycline and minocycline reduce the antibacterial activity in light, and this inferiority has severely hindered their scope of clinical use. By strategically regulating the photolysis pathway, we identified chalcanthite, which primarily contains Cu2+. By conducting antibiotic susceptibility test and electron microscopy analysis, Cu2+ salts (including copper sulfate, copper chloride, and copper gluconate) were confirmed to restore the antibacterial activity of tigecycline under light exposure against all tested bacterial strains. Spectroscopic characterization combined with quantum chemical calculations elucidated the molecular mechanism by which Cu2+ selectively modulates the photolytic degradation pathway of tigecycline and structural determinants (dimethylamino groups on the D ring). Multi-omics technologies revealed the mechanism underlying the Cu2+-mediated (non-antibacterial) inhibition of bacterial ferric citrate transporter. Animal infection models were developed using diverse drug-resistant pathogens to validate the in vivo therapeutic efficacy of copper gluconate-tigecycline combination therapy under photic conditions. These findings revealed effective adjuvants that facilitate the development of topical tigecycline formulations, and the establishment of a scientific foundation for synthesizing photostable tetracycline-based antibiotics through structural optimization.

biochemistry↗

bioRxiv2025

Suppressing cortical glutamatergic neurons produces paradoxical interictal discharges and seizures

IntroductionSeizures are traditionally attributed to excessive excitation or deficient inhibition, yet recent clinical and slice data show they can also paradoxically arise when inhibition outweighs excitation. We chemogenetically suppressed neocortical glutamatergic neurons to test whether such suppression elicits epileptic activity in vivo. MethodsCaMKII-driven Gi-coupled hM4Di or Gq-coupled hM3Dq Designer Receptor Exclusively Activated by Designer Drug (DREADDs) were expressed in cortical glutamatergic neurons of Rasgrf2-jGCaMP8m and wildtype C57BL/6J mice. Widefield calcium imaging and 32-channel transparent electrocorticography were performed before and after systemic clozapine-N-oxide (CNO; 1.25-5 mg kg {superscript 1}). ResultsDREADD activation induced intermittent, large-amplitude, synchronized calcium transients confined to the CaMKII-hM4Di focus, accompanied by focal ECoG spikes that persisted for >3 h and sometimes evolved into seizures. By contrast, CNO activation of excitatory neurons via CaMKII-hM3Dq DREADDs desynchronized activity without epileptiform discharges. The same process duplicated in wild-type animals provoked similar epileptiform discharges. ConclusionSelective suppression of excitation can paradoxically drive cortical networks into hypersynchronous, epileptic states, challenging the simple excess-excitation model of ictogenesis. These findings highlight that seizures may result from relative inhibitory dominance, and that considering this excess inhibition mechanism could inspire new therapeutic approaches.

neuroscience↗

bioRxiv2025

Phosphoantigen-Driven Dissociation of Butyrophilin Oligomers Activates γδ T Cells

{gamma}{delta} T cells represent a promising avenue for cancer immunotherapy. The V{gamma}9V{delta}2 T cell receptor (TCR), expressed by the predominant subset of {gamma}{delta} T cells, responds to phosphoantigen (pAg)-engaged butyrophilins (BTNs) on various cancer cells. However, the molecular mechanism underlying pAg-mediated activation of V{gamma}9V{delta}2 TCRs remains a subject of debate. Here, we employed an integrative approach to elucidate the mechanism of pAg reactivity in V{gamma}9V{delta}2 T cells. Our results demonstrate that BTNs form higher-order oligomers in the absence of pAg. Upon pAg binding, these oligomers dissociate into tetramers, enabling V{gamma}9V{delta}2 TCR engagement. This pAg-induced dissociation of higher-order BTN complexes is critical for pAg-mediated activation of {gamma}{delta} T cells. Our findings reveal a mechanism of BTN dissociation-driven pAg sensing, providing valuable insight for future immunotherapeutic strategies.

immunology↗

bioRxiv2025

Gene copy number variation (gCNV) contributes to adaptation along environmental gradient

Gene copy number variations (gCNVs) are structural variations that represent a significant source of genetic polymorphism. While single nucleotide polymorphisms (SNPs) have been the primary focus of population and quantitative genomics, recent studies indicated that gCNVs could also play an important role in adaptation notably because of their multiallelic and quantitative nature. In this study, we investigate the role of gCNVs in local adaptation along environmental gradients using extensive genomic datasets in Norway spruce (Picea abies) and Siberian spruce (P. obovata). We used a robust pipeline for the detection and quantification of gCNVs from short-read exome capture data and used haploid samples for validation. We showed that gCNVs are pervasive, representing approximately 11% of the protein coding genes and are notably enriched in genes involved in response to environmental stress, such as temperature tolerance, immune response, and metal ion regulation. Population genetic structure at gCNV was similar to that observed at SNPs. However, some gCNVs also display distinctive adaptive signatures not captured by SNPs. Finally, we conducted gCNV-based genotype-environment association (GEA) and genome-wide association studies (GWAS) to further evidence that gCNVs contribute to local adaptation patterns and to the control of quantitative traits.

evolutionary biology↗

bioRxiv2025

Separately prestored proteasome components to prevent polyspermy

To ensure genome stability across generations, an egg must be fertilized by only a single sperm. However, how sperm actively contribute to preventing polyspermy has remained unknown. Here, we demonstrate that testis-specific 20S proteasome core particles (CPs) are pre-stored within the sperm heads of both mice and humans. Upon fertilization, these testis-specific 20S CPs assemble with oocyte-derived 19S regulatory particles (RPs), forming chimeric proteasomes that efficiently degrade Fetuin B, which is ubiquitinated by the E3 ligase MARCH3. The clearance of Fetuin B triggers ZP2 cleavage and subsequent zona pellucida hardening, thereby blocking additional sperm entry. The newly assembled chimeric proteasome in the zygote represents a novel strategy to prevent polyspermy during fertilization in mammals.

developmental biology↗

bioRxiv2025

Acoustic Transparency Enabling Functional Ultrasound Imaging Through Mouse and Human Skulls

Ultrasound is one of the most widely used non-invasive imaging modalities for internal organs, yet its application to the brain has been hindered for decades by the skulls acoustic barrier. This same barrier has kept functional ultrasound imaging (fUSI)--an emerging technology capable of capturing brain-wide neural activity in real time at sub-100 m resolution--from reaching its transformative potential in neuroscience and clinical medicine. Here, we present an acoustic transparency strategy by modulating skull acoustic properties, to render the brain visible to ultrasound. A brief topical application of an FDA-approved chelating agent matches the skulls acoustic impedance and sound speed to those of soft tissue, enabling nearly complete ultrasound transmission (94.0 {+/-} 4.4%) with minimal energy loss or distortion. Leveraging this discovery, we developed an acoustic-transparent fUSI platform that maps brain activation across the full brain depth at [~]20 m spatial resolution without skull removal. This method enables safe, longitudinal brain imaging, is fully reversible, and is demonstrated to be applicable to the ex vivo human skull. This conceptually distinct paradigm--controlling acoustic wave propagation via acoustic property modulation--offers a practical and generalizable solution to one of the most persistent obstacles in transcranial ultrasound imaging, opening the door to broader clinical and research application of ultrasound neuroimaging.

bioengineering↗

bioRxiv2025

Leveraging Large Language Models for Redundancy-Aware Pathway Analysis and Deep Biological Interpretation

Extracting coherent, biologically meaningful insights from vast, complex multi-omics data remains challenging. Currently, pathway enrichment analysis serves as a cornerstone for the functional interpretation of such data. However, conventional approaches often suffer from extensive functional redundancy caused by shared molecular components and overlapping pathway definitions across databases. This redundancy can obscure key biological signals and compromise the interpretability of pathway enrichment results. Here, we present MAPA (Functional Module Identification and Annotation for Pathway Analysis Results Using Large Language Models [LLM]), an open-source computational framework that resolves redundancy and enhances pathway analysis result interpretation. MAPA computes functional similarity between pathways using LLM-based text embeddings, enabling comparison across different databases. It constructs pathway similarity networks and identifies functional modules via community detection algorithms. Crucially, MAPA employs LLMs for automated functional annotation, integrating Retrieval-Augmented Generation (RAG) to generate comprehensive and real-time biological summaries and reduce hallucinations. Benchmarking demonstrated MAPAs superior performance: the biotext embedding similarity showed a large effect size (Cliffs {delta} = 0.96) compared with the Jaccard index ({delta} = 0.73), and module identification achieved high accuracy (Adjusted Rand Index [ARI] = 0.95) versus existing methods (ARI = 0.23-0.33). Human expert evaluation confirmed that MAPAs annotations match expert-quality interpretations. Finally, a multi-omics aging case study illustrates that MAPA uncovers coherent functional modules and generates insights extending beyond conventional pathway analyses. Collectively, MAPA represents a significant advance in redundancy-aware pathway analysis, transforming pathway enrichment results from fragmented lists into biologically coherent narratives. By leveraging the capabilities of LLMs, MAPA offers researchers a robust, scalable tool for deriving deep mechanistic insights from complex and vast multi-omics datasets, marking a new direction for AI-driven bioinformatics.

bioinformatics↗

bioRxiv2025

NuSAP1 promotes bipolar spindle assembly in Trypanosoma brucei by bundling spindle microtubules

The parasitic protozoan Trypanosoma brucei assembles a bipolar mitotic spindle and undergoes a closed mitosis to segregate its megabase chromosomes and mini-chromosomes through mechanisms that are distinct from its mammalian host. This parasite employs a subset of trypanosome-specific nucleus- and spindle-associated proteins (NuSAPs) to regulate mitosis, but the mechanistic roles of these proteins remain poorly understood. Here, we performed biochemical and molecular characterization of NuSAP1 and analyzed the functional interplay of NuSAP1 with its interacting and proximal proteins. NuSAP1 localizes to the mitotic spindle with spindle pole enrichment, and interacts with the spindle-associated and spindle pole-enriched proteins NuSAP4 and SPB1 through distinct structural motifs. NuSAP1 and NuSAP4 are interdependent for protein stability, and NuSAP1 is required for SPB1 localization. Further, NuSAP1 bundles microtubules in vitro, and depletion of NuSAP1 disrupts bipolar spindle assembly. Finally, knockdown of NuSAP1 disrupts the localization of its proximal proteins MAP103 and TbMlp2 to spindle poles. Together, these results uncover the mechanistic role of NuSAP1 in bipolar spindle assembly by bundling spindle microtubules and promoting spindle pole complex formation, underscoring unusual regulatory mechanisms for mitosis in this early divergent unicellular eukaryote.

cell biology↗

bioRxiv2025

Mediator Subunit MED16 Collaborates with UBP1-TFCP2 to Control Transcriptional Activation or Repression via Promoter Positional Specificity

The Mediator complex acts as a master transcriptional co-regulator, yet the mechanisms by which its individual subunits mediate gene-specific transcription remain incompletely defined. Here, we report that the Mediator subunit MED16 physically associates with the UBP1-TFCP2 heterodimer, which controls the context-dependent transcriptional activation or repression. Biochemical purification combined with mass spectrometry validated MED16 as a bona fide interactor of UBP1-TFCP2. Integrative transcriptomic analyses demonstrated that UBP1 recruits the Mediator complex through MED16 to activate a panel of silenced genes associated with lung homeostasis, angiogenesis and cell proliferation. By contrast, MED16-UBP1 co-occupancy at the HIV-1 transcription start site (TSS) represses viral transcription and sustains HIV latency by compromising pre-initiation complex assembly. Domain-mapping experiments revealed that MED16 must integrate into the intact Mediator complex to exert either activating or repressive function. Genomic analysis uncovered a positional regulatory logic: UBP1-TFCP2 binding motifs adjacent to the TSS promote transcription, while those overlapping the TSS elicit repression. Collectively, our work identifies an MED16-UBP1 regulatory module with dual transcriptional activity and highlights this signaling axis as a potential target for HIV-1 interventions.

biochemistry↗

bioRxiv2025

In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells

CRISPR/Cas9 has revolutionized genome editing with broad therapeutic applications, yet its repair patterns in vivo remain poorly understood. Here, we systematically profiled CRISPR/Cas9 editing outcomes at 95 loci using our established CRISPR/Cas9/AAV9-sgRNA system in skeletal muscle stem cells (MuSCs). Through comprehensive characterization of the repair outcomes, our findings demonstrate that the general rules governing CRISPR/Cas9-mediated editing in vivo largely align with those observed in vitro but with reduced editing precision. Additional to the anticipated small editing indels such as MMEJ mediated deletions and NHEJ mediated templated insertions, we uncovered a prevalent occurrence of large on-target modifications, including large deletions (LDs) characterized by microhomology (MH) and large insertions (LIs). Notably, the LIs comprise not only exogenous AAV vector integrations but also endogenous genomic DNA fragments (Endo-LIs). Endo-LIs preferentially originate from active genomic regions, with their integration shaped by three-dimensional chromatin architecture. By disrupting key components of the NHEJ and MMEJ repair pathways in vivo, we identified their distinct roles in regulating the large on-target modifications. Together, our work for the first time systematically profiles the CRISPR/Cas9 repair outcomes in vivo and offers valuable guidance for improving the safety of CRISPR/Cas9-based gene therapies.

genetics↗

bioRxiv2025

A Photo-regulatable Intein Based Trans-Splicing tool for Protein and Organelle Relocalization to Different Subcellular Compartments

The dynamics of protein subcellular localization are intricately regulated, requiring new tools for controlling protein translocation to uncover the biological significance of post-translational regulation of protein localization. Here, we developed a new method, Protein Rerouting via INtein-mediated Trans-Splicing (PRINTS), which enables precise control of protein translocation across diverse subcellular compartments. By reconstituting functional signaling peptides, PRINTS can efficiently relocalize fluorescent proteins to the 26S proteasome, nucleus, mitochondria, plasma membrane, endomembrane organelles, and liquid-liquid phase separation (LLPS) condensates. Furthermore, we incorporated the optically regulated dimerization domain CRY2clust into the PRINTS system, achieving light-mediated control of protein entry into the cell membrane and LLPS membraneless compartments. Strikingly, we observed that HNRNPA1 promiscuously recruit CRY2- or intein-containing proteins into LLPS condensate, whereas FXR1, another LLPS protein showed minimal non-specific activity. PRINTS also allow organelle relocalization, such as LLPS condensates or mitochondria to cell membrane in a light-controllable manner. Overall, PRINTS provides a versatile and robust platform for manipulating protein and organelle subcellular translocations, offering a powerful tool to investigate the regulatory coordination and crosstalk between membranous and membraneless compartments in response to physiological needs.

cell biology↗

bioRxiv2025

FvFT1-FvTFL1 epistasis drives flowering time adaptation in woodland strawberry

Floral transition and flower bud development during autumn and winter are common in plants inhabiting temperate and cold climates. However, our understanding of the natural variation and underlying molecular mechanisms of such life-history strategy remain largely limited to Brassicaceae model species. To address this gap, we investigated flowering time variation across a broad geographical and bioclimatic range in Fragaria vesca (woodland strawberry), a perennial herb from the Rosaceae family. We found that the timing of floral transition and subsequent flowering in F. vesca populations is primarily shaped by population structure, reflecting postglacial colonization patterns from distinct refugia, and is further modulated by adaptations to winter temperatures. The association of increasing expression of FvFT1, the strawberry ortholog of FLOWERING LOCUS T, with delayed flowering in accessions from diverse climatic and genetic backgrounds suggested FvFT1 as a major candidate gene regulating flowering time variation. We further demonstrated how distinct florigen and antiflorigen roles of FvFT1 are dependent on functional alleles of F. vesca TERMINAL FLOWER1 (FvTFL1) and how the epistatic relationship between FvFT1 and FvTFL1 controls adaptive flowering time variation by adjusting sensitivity to floral inductive photoperiod and vernalization. Our findings reveal a major molecular basis of how timing of floral transition has adapted to temperature in a Rosaceae model inhabiting multiple climatic zones and highlight lineage-specific adaptive mechanisms underlying convergent life-history strategy. Significance statementMolecular mechanisms underlying flowering time adaptation have been primarily investigated in annual plants that transit to flowering in spring. However, many perennial plant species in temperate climates form flower buds in autumn and winter to flower in the following spring. We uncover wide geographical and climatic patterns of flowering time adaptation in the perennial model species woodland strawberry. We report that natural variation in the expression of strawberry FLOWERING LOCUS T (FvFT1) gene originating ice ages ago and further driven by local temperature adaptations control flowering time variation in this species. Finally, we show how FvFT1 may function as both flowering promoter and repressor depending on the genetic background, thus revealing a novel mechanism of flowering time adaptation.

plant biology↗

bioRxiv2025

Two routes from the Fertile Crescent led to the introduction of common vetch into Europe.

Vicia sativa (common vetch, n=6) is an annual leguminous plant with high drought tolerance and high grain protein content. Historically and still today, vetches are important for nitrogen fixation to maintain cereal yields and feeding grazing livestock. In this study, we re-sequenced the genomes of 279 common vetch accessions from a wide geographic range covering western Eurasia and North Africa to construct a comprehensive nucleotide variation map. Population structure analyses indicate that the Middle Eastern region was the centre of origin of common vetch, which then entered Europe in two distinct waves. One wave propagated by humans through Turkey into the Carpathian Basin before spreading throughout Europe via "Danubian" and "Mediterranean" routes. Demographic inferences revealed a significant bottleneck for all common vetch groups initiated during the Last Glacial Maximum, followed by an expansion that coincides with the onset of the warm Holocene epoch and the Neolithic Revolution. Interestingly, we identified selective sweeps for the flowering time regulators VsSOC1 and VsFTb2 in northern latitude populations suggesting that both genes are important regulators of latitudinal adaptation. Overall, we provide valuable genomic resources for conservation and breeding programs to optimize food production in the face of population growth and reduced agricultural resources.

plant biology↗

bioRxiv2025

Diet-Seg: Dynamic Hardness-Aware Learning for Enhanced Brain Tumor Segmentation

Accurate brain tumor segmentation in magnetic resonance imaging (MRI) remains a critical challenge due to complex tumor heterogeneity, fuzzy boundaries, and significant inter-patient variability. In this study, we propose Diet-Seg (Difficulty-Informed Edge-enhanced Tiny Segmentation), a novel segmentation framework that integrates entropy-based pixel-wise hardness estimation into the training process via a dynamic learning rate modulation strategy. Specifically, we employ a pretrained 3D U-Net information model to quantify voxel-level prediction uncertainty, which is then used to guide the optimization of the main segmentation model. Diet-Seg is further enhanced by an RWKV-based U-Net backbone to capture global spatial dependencies and an EdgeNet module to preserve tumor boundaries through edge-aware fusion. Extensive experiments on the BraTS2018-2021 datasets demonstrate that Diet-Seg consistently outperforms state-of-the-art baselines across all tumor subregions. Notably, Diet-Seg achieves superior generalization when trained on one dataset and validated across multiple years. Moreover, the hardness maps offer interpretable insights into segmentation difficulty, potentially enabling human-AI collaboration in clinical practice. These results highlight the promise of entropy-aware training as a general strategy for robust and efficient medical image segmentation. The work is implemented in the open-source project available on GitHub (https://github.com/ManuelTurner/Diet-Seg)

bioinformatics↗