Biology subjects

Li, H.

Publications and source records attributed to Li, H..

At least 379 records · Page 21Linked to original sources

bioRxiv2025

Super-pangenome analysis of 3562 human and animal papillomavirus isolates illuminates their genome and pathogenicity evolution

Papillomaviruses (PVs) are groups of ubiquitous DNA viruses infecting a wide range of vertebrate hosts, including human. The infection of some human PVs (i.e., HPVs) are strongly associated with cancers, but it remains elusive how such pathogenicity evolved at the genomic level. Here we performed a super-pangenome analysis on a compendium of well-curated 3562 human and animal PV genomes. We found their global genomic diversity being strongly associated with their body sites and tissue origins, but not with their host, geographical, or disease specificity. By reconciling time-resolved phylogenies of PVs and their hosts, we revealed a high-resolution view on how virus-host cospeciation, horizontal host switches, and duplication/loss turnovers collectively shaped the evolution of PVs. We identified key selection-driven mutations that defined the genus-specific divergence of PVs, with those underlying the rise of Alpha-PVs highly enriched in the N-terminal domain of E1 gene. Especially, we identified a group of risk-defining variant sites showing contrasting genotypes between low-risk and high-risk HPVs. With four independent PV genome cohorts, we further validated their high sensitivity and specificity on HPV risk classification even at single site level, underscoring their application values in large-scale HPV screening tests. Finally, with cervical and oropharyngeal cancer patient cohorts assembled by this study, we also evaluated the prognostic value of specific HPV16 variants in predicting patient survival. Taken together, such illumination on the genome and pathogenicity evolution of PVs paves the road for better prevention, control, and treatment of PV-related cancers. Significance statementPapillomaviruses (PVs) are ancient and widespread DNA viruses co-evolved with many vertebrate hosts, including human. Some human PVs (e.g., HPV16 and HPV18) bear strong association with cancers, raising a pressing public health challenge. A better understanding of how such pathogenicity evolved holds the key in addressing this challenge. Here we systematically investigated the genomic and evolutionary diversity of PVs via a pangenome study on over 3500 human and animal PV isolates, which revealed key selection-driven mutations shaping their genome and pathogenicity evolution. With independently acquired HPV-associated cancer cohorts, we further demonstrated how some of these important HPV variants can serve as clinically informative predictive and prognostic biomarkers. Such comprehensive characterization on PVs genome diversity, pathogenicity evolution, and clinical implication paves the road for better prevention, control, and treatment of PV-related cancers.

genomics↗

bioRxiv2025

A conserved small RNA-generating gene cluster undergoes sequence diversification and contributes to plant immunity

Small RNA-mediated gene silencing contributes to plant immunity. The secondary small interfering RNA (siRNA) pathway promotes defense by silencing target genes in invading fungal and oomycete pathogens. Many secondary siRNAs derive from transcripts potentially encoding pentatricopeptide repeat (PPR) proteins. Here, we report that siRNA production is an ancient function of an evolutionarily conserved clade of PPR genes that undergo extensive within-species diversification. In Arabidopsis thaliana, siRNA-source PPRs are physically clustered in one locus on Chromosome 1. These sequences are diversified through gene duplication followed by sequence diversification as well as accumulation of high-impact variations including pseudogenization. This diversity leads to the accumulation of a diverse PPR-siRNA pool, consistent with an engagement in a co-evolutionary arms race with the pathogens. This study defines siRNA-producing PPRs as a family of defense genes and highlights the potential of PPR-siRNA-based engineering for enhancing broad-spectrum disease resistance.

plant biology↗

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

Detecting Foldback Artifacts in Long Reads

Long-read sequencing data is useful for detecting large and complex structural variations; however, technical artifacts can lead to false structural variant calls. In our analyses, we became aware of a foldback artifact in long-read data. Therefore, we developed the open-source Breakinator tool to flag putative foldback artifact reads, as well as previously known chimeric artifacts. Through an alignment-based approach, Breakinator can detect artifacts missed by existing quality control tools. We profiled the occurrences of foldbacks and chimeric reads in both Oxford Nanopore and PacBio sequences across a range of specimens, library types, sequencing chemistries, sequencing machines, and base-calling software.

bioinformatics↗

bioRxiv2025

QOBRA: A Quantum Operator-Based Autoencoder for De Novo Molecular Design

We introduce a variational quantum autoencoder tailored for de novo molecular design named QOBRA (Quantum Operator-Based Real-Amplitude autoencoder). QOBRA le circuits for real-amplitude encoding and the SWAP test to estimate reconstruction and latent-space regularization errors during back-propagation. Adjoint encoderand decoder unitary transformations and a generative process that ensures accurate reconstruction as well as novelty, uniqueness, and validity of the generated samples. We showcase QOBRA as applied to de novo design of Ca2+-, Mg2+-, and Zn2+-binding metalloproteins after training the generative model with a modest dataset. Significance StatementRecent advancements in classical generative machine learning have shown significant strides in molecular design for targeted applications. Nonetheless, these advancements are fundamentally limited by classical computation based on binary units. We introduce a quantum computation-based ML framework employing qubits, which exhibits the ability to synthesize de novo molecular instances with specified properties from limited datasets. Quantum networks require exponentially fewer parameters than classical ones, enhancing their trainability and efficiency. While our demonstration focuses on metalloprotein primary sequences, the paradigm is adaptable to diverse molecular designs. This integration of AI and quantum computing holds potential to expand the scientific and technological frontiers of both domains within a practical framework.

biochemistry↗

bioRxiv2025

Loss of FMRP in microglia promotes degeneration of parvalbumin neurons and audiogenic seizures via progranulin insufficiency

Fragile X syndrome (FXS) results from loss of FMR1-encoded FMRP and is associated with reduced density of parvalbumin (PV) neurons; however, the mechanism underlying this abnormality remains unknown. Here we report that microglial FMRP regulates PV neuron density through lysosomal function. Mice with Fmr1 deletion in microglia exhibited audiogenic seizures (AGS) and decreased PV neuron density in the cortex and AGS-associated inferior colliculus (IC). FMRP increased the expression of lysosomal genes in microglia, including the progranulin-encoding Grn gene. Its loss in microglia led to impaired lysosomal function and increased apoptosis in microglia and PV neurons. Furthermore, PV neuron density in the IC was reduced similarly in male Grn+/-, Fmr1-/y, and Grn+/-;Fmr1-/y mice, and AAV8-mediated overexpression of progranulin rescued AGS and PV neuron loss in Fmr1-/y mice. This indicates that progranulin insufficiency is a determinant for PV neuron loss in FXS and elevating progranulin is a therapeutic strategy for FXS.

neuroscience↗

bioRxiv2025

Measure Sodium Transport in Cells with NMR

Sodium ions (Na+) are fundamental to numerous physiological functions, such as maintaining electrolyte balance, enabling nerve impulse transmission, and facilitating muscle contraction. Dysregulation of Na+ transport across cell membranes is implicated in a range of health issues, including metabolic syndromes, neurological conditions, and cardiovascular diseases. However, current methods for assessing cellular Na+ activity often face limitations; they can be invasive or fail to capture dynamic changes. In this study, we introduce a non-invasive 23Na nuclear magnetic resonance (NMR) methodology designed to directly quantify the transport rate of sodium ions in living cells. Our technique integrates relaxation exchange spectroscopy (REXSY) with a multi-site exchange model, enabling the investigation of Na+ transport dynamics on a timescale of sub-seconds. A key advantage is its ability to differentiate between intracellular and extracellular Na+ pools based on the endogenous NMR relaxation difference, thereby avoiding the need for potentially disruptive exogenous reagents. Experiments conducted on human cell lines successfully demonstrated the techniques capacity to distinguish between various physiological states, such as when ion channels are pharmacologically blocked or activated. The resulting measurements of Na+ transport rates and intracellular Na+ fractions show a clear correlation with cellular metabolic activity, offering valuable quantitative markers for monitoring transmembrane ion dynamics in vitro.

cell biology↗

bioRxiv2025

Celastrol sensitizes bicalutamide to enhance immunogenic Cell death in the treatment of castration-resistant prostate

BackgroundProstate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. MethodsIn this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro. ResultsOur findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. ConclusionOur study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding informationThe author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003).

cancer biology↗

bioRxiv2025

Stage- and tissue-specific gene editing using 4-OHT inducible Cas9 in whole organism

Vertebrate genes usually function in specific tissues at specific stages, and thus their functional studies require conditional knockout or editing. In the zebrafish, spatiotemporally inducible genome editing, especially during early embryonic development, is still challenging. Here, we report inducible Cas9-based gene editing in specific cell types at desired stages in zebrafish. We show that the nCas9ERT2 fusion protein consisting of Cas9 and estrogen receptor flanked by two nuclear localization signals is normally located in the cytoplasm and efficiently translocated into the nucleus upon 4-hydroxytamoxifen (4-OHT) treatment in cultured cells or embryos. As a proof-of-concept, we demonstrate that target genes in primordial germ cells or germ cells of transgenic zebrafish embryos or adults with stable expression of nCas9ERT2 and gene-specific guide RNAs (gRNAs) can be induced to mutate by application of 4-OHT. This inducible nCas9ERT2 system also works in mouse early embryos. Thus, this inducible gene editing approach will be another choice for studying the temporospatial function of genes at the organismal level. Hence, the inducible nCas9ERT2 system expands the tissue- and stage-specific gene editing toolkit.

developmental biology↗

bioRxiv2025

Buyang Huanwu Decoction Ameliorates Peripheral Nerve Injury by Promoting Cell Cycle through Activation of PI3K/AKT/mTOR/HIF-1α Pathway

BackgroundPeripheral nerve injury (PNI) can lead to partial or even total motor and sensory dysfunction, severely affecting the work and life of patients, but recovery of nerve function is often poor due to the complexity of the nerve repair and regeneration process. Cumulative evidence suggests the contribution of cell cycle regulation in repairing PNI injury, and p27KIP1 is a key molecule in regulating the cell cycle. ObjectiveThe aim of this study is to elucidate the repair mechanism of peripheral nerve injury (PNI) from the point of view of regulating cell cycle and to explore the therapeutic effect of Buyang Huanwu Decoction (BHD). To provide new strategies for the treatment of PNI and to explore valuable drugs initially. MethodsThe clamp injury model was chose as a PNI model and different doses of BHD extract were administered by gavage for 14 days. Limb motor function, sciatic nerve index and sciatic nerve pathology were assessed and p27Kip expression level was determined. The in vivo chemical composition of BHD extract was determined and drug targets were retrieved by TCMSP, STITCH and Swiss Target Prediction to predict the mechanism of BHD treatment for PNI using network pharmacology. Pathway-related proteins including P-PI3K, P-AKT, P-mTOR and HIF-1a were validated by western blotting assay. ResultsCompared with control rats, PNI rats had abnormal motor function, sciatic nerve damage and reduced p27Kip expression. Administration of BHD for 14 days significantly improved PNI in rats, which not only repaired sciatic nerve function, attenuated sciatic nerve pathology and inhibited p27Kip expression to regulate the cell cycle in PNI rats, but also activated the PI3K/AKT/mTOR/HIF-1a pathway. ConclusionThe above results suggest that PI3K/AKT/mTOR/HIF-1a mediated cell cycle regulation may be an important repair mechanism for PNI, and that BHD can improve PNI by accelerating the cell cycle to promote neural repair and regeneration.

cell biology↗

bioRxiv2025

Gut Microbiota Succession and Metabolic Pathway Remodeling in the Progression of Type 2 Diabetes Mellitus in Adult Rats

BackgroundEmerging evidence highlights the complex interplay between gut microbiota and type 2 diabetes mellitus (T2D); however, the temporal trajectory of microbial community succession and the concomitant shifts in associated metabolic pathways across the disease lifecycle remain poorly characterized. In this study, we conducted a multi-dimensional analysis of gut microbiota composition and functional pathways in rats, spanning the continuum from health, through the T2D pathological state, to post-intervention recovery phases. ResultsHealthy aged rats exhibited significantly greater gut microbial diversity compared to both younger healthy cohorts and T2D rats. In the absence of intervention, progressive T2D development led to a sustained decline in microbial diversity that persisted until death. Notably, {beta}-tocotrienol ({beta}-T3), metformin hydrochloride (MET) and healthy dietary interventions not only improved fasting blood glucose (FPG) levels in T2D mice but also restored their gut microbial diversity and metabolic functions. At the phylum level, the ratio of p Bacteroidota to p Firmicutes exhibited an age-dependent increase in healthy rats but displayed a progressive decline in T2D rats. Notably, species-specific expansions were observed across both healthy and pathological states. For example, s Bacteroides_acidifaciens (B. acidifaciens) showed a significant expansion in early T2D stage disease, while s Anaerostipes_hadrus became the dominant species in advanced-stage T2D. Among intervention groups, s Phascolarctobacterium_faecium was enriched in the {beta}-tocotrienol ({beta}-T3) group; the abundance of s Escherichia_coli (E. coli) increased dramatically in the deceased rats. Gut metabolites also exhibited distinct characteristics across different physiological stages. In young rats, the metabolite profile was characterized by lower abundances of most metabolites, which stabilized with age accompanied by upregulation of select molecules in older rats. Notably, during T2D progression, the metabolite profile displayed a largely opposite pattern compared to healthy controls. Importantly, dietary interventions including healthy food, {beta}-T3, MET partially restored metabolic homeostasis in T2D rats. Further analysis revealed that key differential metabolites across groups were enriched in bile acids (BAs), amino acids, benzene and its substituted derivatives, and organic acids with their derivatives. Specifically, amino acid metabolism was more active in healthy rats, whereas BA and benzene derivative metabolism were upregulated in T2D. Key microbial species driving these shifts included s Lactobacillus_johnsonii, s Lactobacillus_reuteri, and B. acidifaciens, which exhibited positive correlations with BAs and select amino acids. The B. acidifaciens could be a biomarker of T2D and glycoursodeoxycholic acid, sohyodeoxycholic acid, beta-muricholic acid and allocholic acid were the key BAs to regulate glycometabolism of the host. ConclusionsDuring the T2D stage, both gut microbiota composition and metabolic profiles exhibited distinct characteristics compared to those of healthy age-matched older rats. Notably, {beta}-T3 and MET interventions not only facilitated the recovery of gut microbial diversity and metabolite levels in T2D mice but also promoted the proliferation of specific dominant species, each intervention favoring distinct taxa. In this context, B. acidifaciens emerged as a dominant bacterial species in T2D, exerting regulatory effects on glycometabolism through BA and amino acid metabolic pathways. Collectively, these findings advance our understanding of T2D pathophysiology and highlight the potential of probiotic-based therapies for its management. ImportanceThe T2D is a kind of chronic disease and the gut microbiota shows a continuously slow succession from some microbial populations to other ones in the disease progress. Uncovering the rule of change in gut bacteria from healthy rats to T2D ones and the recovering capacity of gut microbiota through interventions of healthy food, {beta}-T3 and antidiabetic drug are beneficial to understand the real regulation mechanism of gut bacteria in T2D progress. Then the results lay the foundation of developing probiotics and researching new metabolic therapeutic target of gut microorganisms. In addition, to research the metabolic regulation mechanism of gut bacteria, using multi-omics including microbiomics and metabonomics is an effective way.

microbiology↗

bioRxiv2025

Bromodomain protein IBD1 bridges histone acetylation and H2A.Z deposition to fine-tune transcription and prevent hyperactivation in Tetrahymena thermophila

Eukaryotic gene expression is dynamically regulated through the interplay between histone modifications and chromatin remodeling, yet how these processes are coordinated remains incompletely understood. Here, we identify IBD1 as a critical adaptor that bridges histone acetylation and SWR-mediated H2A.Z deposition. We demonstrate that the bromodomain of IBD1 recognizes histone acetylation, specifically H3K9/14 di-acetylation to recruit the SWR complex subunit ARP6, ensuring precise H2A.Z incorporation into chromatin. Genetic disruption of IBD1, either by deletion or bromodomain mutation, attenuates H2A.Z occupancy at target loci, confirming its essential role in H2A.Z deposition. Strikingly, perturbation of the histone acetylation-IBD1-H2A.Z axis triggers transcriptional hyperactivation, revealing a dual function of H2A.Z in sustaining basal transcription while preventing aberrant gene induction. This defines a novel regulatory paradigm in which IBD1 couples acetyl-mark decoding to SWR-dependent H2A.Z deposition, establishing transcriptional homeostasis. Our findings resolve a central ambiguity by demonstrating that H2A.Z acts as a repressive buffer in highly acetylated regions, counterbalancing the inherent activation potential of acetylation. This study provides a framework for investigating H2A.Z functions and reveals new perspectives on how chromatin modifications and histone variants interplay in transcriptional regulation.

genetics↗

bioRxiv2025

Interactome Analysis of the CC2D1A Scaffold Reveals Novel Neuronal Interactions and a Postsynaptic Role

Loss of the protein scaffold Coiled-coil and C2 domain containing 1A (CC2D1A) leads to intellectual disability (ID), autism spectrum disorder (ASD), and other neurodevelopmental presentations in humans. CC2D1A interactions have been studied in different cell lines proposing diverse roles in endolysosomal maturation and intracellular signaling, but the composition and functional mechanisms of the CC2D1A interactome remain poorly understood, especially in the brain. We performed comprehensive proteomic analyses to characterize CC2D1A binding partners, first comparing immunoprecipitations with three different anti-CC2D1A antibodies in HEK293 cells and then probing the mouse hippocampus. In HEK cells, Gene Ontology (GO) analysis revealed broad interaction networks in the nucleus, mitochondrion, and cytoplasmic vesicles sharing functions in organelle organization, vesicle mediated transport, and protein metabolism. These are unified by the best characterized CC2D1A interactor, the ESCRT III component CHMP4B, and define a pleiotropic role for CC2D1A in membrane trafficking and protein homeostasis. In the hippocampus, using stringent criteria and additional controls, including a Cc2d1a hypomorph mouse line, we identified 10 high-confidence interactors in addition to CHMP4B (TNIK, G3BP2, CEP135, MAPKAP1, SHFL, PPT1, PNKD, VAMP5, and PPP6R2) revealing roles for RNA regulation and synaptic function. The HEK studies had also pointed to CC2D1B, the only paralog of CC2D1A, as an interactor. We confirmed that not only the two proteins can bind in the brain, but also localize in different synaptic compartments, showing that CC2D1A is uniquely enriched in the post-synapse. This supports a unique function of CC2D1A in regulation of synaptic transmission that could explain the more severe cognitive deficits in humans and mice upon its loss. To our knowledge these findings provide the most comprehensive characterization of the CC2D1A interactome to date, elucidating novel, multifaceted, and dynamic cellular functions, providing potential implications for its role in neurodevelop-mental disorders.

molecular biology↗

bioRxiv2025

Label-Free Mapping of Subcellular Dynamics using Wide-field Interferometric Scattering Microscopy and Spectral Exponent Analysis

Interferometric scattering (iSCAT) microscopy combines label-free detection with nanometer-scale motion sensitivity. It captures temporal signal fluctuations from sub-diffraction movements of scatterers in live cells, including macromolecules and cell membranes. Here, we investigate label-free mapping of subcellular dynamics by calculating the power spectral density (PSD) of the iSCAT time series. Using a wide-field iSCAT, we observe an inverse-power-law relationship S(f) = {beta}f- over 30 - 1250 Hz in multiple cell types. We compute pixel-wise PSDs and obtain a color-coded spectral exponent map based on the fitted spectral exponent () and amplitude ({beta}), which indicates the characteristics and strength of subcellular movements. We also incorporate the goodness-of-fit as color saturation to enhance the contrast of the spectral exponent map. Following this approach, we demonstrate label-free imaging of live cells while effectively distinguishing between benign and malignant thyroid cancer subtypes, mitotic and interphase cells, as well as live and apoptotic cells. Dynamic imaging using wide-field iSCAT provides an intrinsic, label-free marker of cellular states and mechanical properties, which may benefit studies in mechanobiology, cancer diagnostics, and stem cell therapies.

bioengineering↗

bioRxiv2025

Genome Mining and Characterization of a Heme-Dependent Enzyme Catalyzing Intermolecular Nitrogen-Nitrogen Bond Formation in Hydrazinosuccinic Acid Biosynthesis

Nitrogen-nitrogen (N-N) bond-forming enzymes are rare but play vital roles in both primary and secondary metabolism. Guided by a nitric oxide synthase (NOS)-based genome mining strategy, we report the discovery and characterization of a new heme-dependent enzyme system that catalyzes intermolecular N-N bond formation. Using both in vivo and in vitro reconstitution approaches, we demonstrated that a protein complex, comprising a heme enzyme and a 2[4Fe-4S] ferredoxin partner, mediates the coupling of the -amine group of L-aspartate with inorganic nitrogen oxide species, such as nitrite or nitric oxide, to generate hydrazinosuccinic acid, a key biosynthetic precursor in several natural product pathways. Structural modeling and site-directed mutagenesis suggest a plausible catalytic mechanism involving the formation of a reactive nitrogen intermediate, potentially a heme-bound nitrene species. These findings reveal a new family of N-N bond-forming biocatalysts that leverage inorganic nitrogen sources, offering valuable tools for genome mining and the synthetic biology.

biochemistry↗

bioRxiv2025

Genetic mapping of lifespan and mitochondrial stress response in C. elegans

The mitochondrial unfolded protein response (UPRmt) is one of the mito-nuclear regulatory circuits that restores mitochondrial function upon stress conditions, promoting metabolic health and longevity. However, the complex gene interactions that govern this pathway and its role in aging and healthspan remain to be fully elucidated. Here, we activated the UPRmt using doxycycline (Dox) in a genetically diverse C. elegans population comprising 85 strains and observed large variation in Dox-induced lifespan extension across these strains. Through multi-omic data integration, we identified an aging-related molecular signature that was partially reversed by Dox. To identify the mechanisms underlying Dox-induced lifespan extension, we applied quantitative trait locus (QTL) mapping analyses and found one UPRmt modulator, fipp-1/FIP1L1, which was functionally validated in C. elegans and humans. In the human UK Biobank, FIP1L1 was associated with metabolic homeostasis, underscoring its translational relevance. Overall, our findings demonstrate a novel UPRmt modulator across species and provide insights into potential translational research.

genetics↗

bioRxiv2025

Transient chromatin decompaction by histone deacetylation inhibition preferentially radiosensitizes cancerous breast epithelial cells at lower radiation doses

Radiation therapy plays a prominent role in breast cancer treatment, but the high doses of radiation damage both healthy and cancerous cells. Therefore, additional research is needed into combination therapies that could preferentially radiosensitize cancer cells compared to surrounding healthy tissue without causing deleterious side effects. Histone deacetylase inhibitor drugs (HDACis) have been tested as radiosensitizers in both basic research and clinical trials, but the long exposure time typically used in these treatments and the lack of matched healthy cell controls often leave aspects of their mechanism of action unclear. Here, we show that transient (2 hour) trichostatin A (TSA) treatment of cancerous and non-tumorigenic breast epithelial cell lines increases immediate DNA damage and decreases long term cell viability in both cell types at high radiation doses. Transient TSA treatment also causes an increase in DNA damage signals after 5 Gy in other cancer and healthy cell types: A375 melanoma cells and BJ5-ta fibroblasts. This suggests that chromatin decompaction acts to increase cellular vulnerability to initial DNA damage from high doses of radiation DNA damage in a cell type independent manner that does not rely on changes to DNA repair pathways caused by longer TSA treatment. However, responses to lower doses of radiation and long term survival are more cell type specific: only MCF7 cells experience an effect of TSA on DNA damage after 1 Gy radiation while MCF10a cells experience somewhat more evident cell viability effects of combined TSA and radiation treatment long term. Scope statementThis manuscript covers several topics that are core to the mission of Frontiers in Cell and Developmental Biology, including cancer cell biology as compared to non-cancerous cell function, cell death vs. survival, and epigenetics and chromosome structure. While some of the implications of this work touch on cancer therapeutics, the study itself focuses on the basics of the interplay between genome architecture and DNA damage and cellular survival / response. We noted several recent articles on related topics in this journal, including the effects of combination treatments on cancer cells (doi 10.3389/fcell.2025.1636288), radiotherapy effects on cells (doi 10.3389/fcell.2025.1568634), and DNA damage (doi 10.3389/fcell.2025.1575483). Our work is well suited for a Brief Research Report as it provides key but focused data on comparisons of radiosensitivity in response to transient chromatin decompaction in cancer vs. healthy cells.

cancer biology↗

bioRxiv2025

Whole genome sequence-based characterization of foodborne Staphylococcus aureus isolated from pork in 2018 and 2023.

This study characterizes the genomic epidemiology of 111 Staphylococcus aureus isolates collected from retail meat in Beijing and Copenhagen during 2018 and 2023 using whole-genome sequencing. Our analysis identified concerning antimicrobial resistance patterns, with methicillin-resistant S. aureus (MRSA) prevalence rising from 19.51% to 24.13% over the study period. The livestock-associated CC398 lineage (27.03% of isolates) demonstrated strong correlations with tetracycline resistance (tetM) and persisted as the dominant clone in Beijing, increasing from 33.33% to 40.91% prevalence. In contrast, we observed the rapid emergence of community-associated CC8 strains in Denmark, reaching 71.43% prevalence by 202327. Virulence profiling revealed MSSA strains frequently carried enterotoxin genes (seg/sei in 55.8% of isolates), while mobile genetic elements like SCCmec IV in ST59-t437 contributed significantly to pathogenicity. Phylogenetic analysis delineated five major clades and highlighted the expansion of multidrug-resistant CC398 strains in Beijing. These findings demonstrate the dynamic evolution of S. aureus at the human-animal interface and emphasize the urgent need for integrated One Health surveillance systems to track resistance gene dissemination. Future research should prioritize investigating zoonotic transmission pathways and the role of horizontal gene transfer in driving the convergence of virulence and resistance traits in foodborne pathogens.

genomics↗