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Zhao, Z.

Publications and source records attributed to Zhao, Z..

At least 55 records · Page 3Linked to original sources
bioRxiv2026

The Cu-induced ScsD reductase is a membrane-bound redox partner of ScsB in the Salmonella envelope

The intracellular environment Salmonella confronts during infection is characterized by multiple redox stressors including reactive oxygen species (ROS) and copper (Cu) ions. Under these conditions, alternative systems of thiol oxidoreductases such as the Cu induced Scs system are required to protect and repair periplasmic proteins. The scsABCD operon encodes three Dsb-like enzymes, ScsB, ScsC, and ScsD, and an accessory protein, ScsA. These proteins are required both for Cu resistance and H2O2 tolerance. ScsB and ScsC function analogously to the canonical DsbD/DsbC redox pair of thiol oxidoreductases. The absence of ScsC was shown to affect the folding/activity of periplasmic proteins involved in amino acid transport and redox homeostasis. Here, we focus in ScsD, the least characterized member of this system. Upon Cu-induced expression, ScsD localizes to the inner membrane, enabling its predicted C-terminal Dsb-like domain to be exposed to the periplasm. Functional analysis indicates that ScsD exists in a reduced state in the Salmonella envelope and serves as a redox partner of ScsB. ScsD exhibits in vivo disulfide reductase activity and restores a deficient disulfide reduction pathway in Salmonella. Similar to ScsC and ScsB, ScsD binds Cu(I) via the Cys residues of its Dsb-like domain; however, this metal interaction appears to lack relevance in Cu detoxification as no impact on intracellular Cu levels was observed. Our results define ScsD as a specialized membrane-bound thiol-disulfide reductase in the Salmonella envelope and highlight the versatility of the Scs system in maintaining periplasmic proteostasis when canonical pathways are compromised by host-imposed Cu stress. ImportanceCopper is a key component of the innate immune system, serving as a primary defense against pathogens like Salmonella. Copper overload targets the bacterial envelope, specifically attacking protein sulfhydryl groups. This causes protein misfolding and inactivation, disrupting essential processes like metabolism, transport and virulence. To survive this stress and restore thiol homeostasis, Salmonella utilizes the scsABCD operon. While the ScsB-ScsC redox pair is well-documented and some protein substrates identified, the role of ScsD remains undefined. This work characterizes ScsD as an inner-membrane-anchored thiol reductase and a new redox partner for ScsB. The ScsD/ScsB pair expands the bacteriums protein quality control capacity, allowing Salmonella to maintain envelope homeostasis within the hostile, copper-rich environment of the host.

microbiology↗
bioRxiv2026

Genomic Decoding of Specialized Aromatic Hydrocarbon Degradation in Mangrove-Derived Gordonia sp. B7 2

Petroleum pollution has increased worldwide, driving the search for microorganisms with efficient hydrocarbon-degrading capabilities. Here, we report a novel bacterium, Gordonia sp. B7-2, isolated from mangrove sediments in Hainan, China. Phylogenetic analysis based on the 16S rRNA gene and whole-genome sequences, together with digital DNA-DNA hybridization and average nucleotide identity values, supported its classification as a new species within the genus Gordonia. The complete genome of strain B7-2 consists of a single circular chromosome of 5.39 Mb with a G+C content of 65.99%, and encodes 4,887 protein-coding genes. Genomic annotation revealed a complete pathway for aromatic hydrocarbon degradation, including genes encoding protocatechuate 3,4-dioxygenase and biphenyl-2,3-diol 1,2-dioxygenase, whereas genes involved in the initial oxidation of alkanes were absent. Consistent with these genomic predictions, strain B7-2 degraded 64.33% of crude oil (300 mg/L) within 28 days, with rapid degradation during the initial 14 days, followed by a slower phase thereafter, reflecting the dynamics of complex hydrocarbon mixtures. Together, these results demonstrate that strain B7-2 is specialized for the degradation of aromatic hydrocarbons and highlight its potential for targeted petroleum bioremediation. IMPORTANCEMangrove ecosystems are highly vulnerable to petroleum contamination, yet the microorganisms responsible for hydrocarbon turnover in these environments remain poorly characterized. This study describes a new bacterial species, Gordonia sp. B7-2, that exhibits a strong metabolic specialization for aromatic hydrocarbon degradation. Unlike many known oil-degrading bacteria that preferentially utilize alkanes, strain B7-2 targets aromatic components of crude oil, which are among the most persistent and toxic fractions.Its ability to efficiently degrade crude oil highlights its potential in the bioremediation of contaminated coastal environments and expands our understanding of microbial contributions to hydrocarbon cycling in mangrove sediments

microbiology↗
bioRxiv2026

Multi-layer transcriptomic characterization of age-related immune dynamics

Despite the pivotal role of mRNA isoform diversity in governing immune cell function, current investigations into peripheral immune aging predominantly focused on gene-level expression, obscuring deeper regulatory layers of transcriptome complexity. Here, we leveraged a 5' scRNA-seq atlas comprising approximately 2.5 million PBMCs from 378 healthy donors. We demonstrate that immune aging is characterized by profound, non-linear transcriptional reprogramming that extends beyond gene-level shifts to include fine-tuned regulation of alternative transcription initiation and splice site selection. By quantifying the transcriptional activity of cis-regulatory elements, we resolved their contributions to age-related expression dynamics. Notably, we identified a subset of endogenous retroviruses that are reactivated in older individuals, some of which served as alternative promoters driving the production of chimeric transcripts. Furthermore, our analysis revealed EDA as a top-ranked gene consistently upregulated with age across multiple independent cohorts. Increasing EDA expression in in vitro-stimulated naive CD4+ T cells from young individuals recapitulated aged phenotypes. This comprehensive resource elucidates the multi-layered transcriptomic landscape of the aging immune system and facilitates the identification of novel drivers of immune aging.

bioinformatics↗
bioRxiv2026

Revisiting the diversity of secondary endosymbionts in the major pest oat aphid, Rhopalosiphum padi

There is disagreement on whether secondary endosymbionts are found in the major cereal pest aphid, Rhopalosiphum padi. Some papers report a diversity of secondary bacterial endosymbionts while others have failed to find evidence of these bacteria in this species. Here we revisit this issue by summarizing the relevant literature and through additional sampling of the species in Australia, China and Denmark using a combination of molecular approaches. We find a general absence of secondary endosymbionts beyond the obligate endosymbiont Hamiltonella defensa in R. padi. While the inconsistency in survey results may reflect rapid changes in endosymbiont turnover in populations and/or the impact of ecological factors such as host plant type on endosymbiont diversity, we are concerned that technical issues may be at least partly responsible for inconsistencies in the literature. This leads us to emphasize the importance of multiple sources of evidence required to establish and characterize endosymbiont infections, including PCR and qPCR assays, DNA Sanger sequencing and 16SrRNA gene metabarcoding. We note that several major aphid pests show a low incidence of secondary endosymbionts which raises issues about the importance of these endosymbionts in aphids that constitute pests, even though endosymbionts can in some cases increase host fitness and therefore pest impact.

microbiology↗
bioRxiv2026

Volumetric Cyclic Immunofluorescence for 3D Spatial Profiling of Immune Structures in Human FFPE Tissue

Mapping how parenchymal, immune, and stromal cells interact with extended structures such as blood vessels and nerves is challenging using conventional thin-section tissue imaging. Volumetric methods such as light-sheet fluorescence microscopy (LSFM) are ideal in these cases and LSFM is widely used in animal models such as fish and mice. This is enabled by well-established clearing methods, genetically encoded reporters, and vascular dyes. However, LSFM is rarely utilized for human tissue, which is primarily available as formaldehyde-fixed paraffin embedded (FFPE) specimens. Here, we present an approach to volumetric cyclic immunofluorescence (v-CyCIF) that enables 40-plex or greater imaging of immune and other cell types in human specimens up to 1 mm thick. We demonstrate the use of v-CyCIF to study neuroimmune interactions and lymphoid structures in normal and cancer tissues. Following LSFM imaging, specimens can be re-embedded and sectioned to ~50 {micro}m thick for high-resolution confocal imaging of punctate structures and cell-cell junctions. v-CyCIF therefore provides a flexible framework for multi-scale 3D profiling of clinical specimens across imaging formats and resolutions.

cancer biology↗
bioRxiv2026

Dual curvature sensing governs cell orientation and curvotaxis

Cells lying in a curved environment can respond to the surface curvature by reorienting their shape. However, whether cells respond to the mean curvature and/or the Gaussian curvature remains largely unexplored. Here, inspired by experimental observations of how ovarian theca cells (TCs) orient themselves on substrates with different curvatures, we propose a theoretical framework for active nematic layers on curved surfaces. In this model, we assume that the nematic directors of the cells respond to both the mean curvature and the Gaussian curvature of the underlying substrate surface. Our theory predicts specific cell orientation patterns on hemicylindrical, hourglass- and dome-like substrates, consistent with experimental observations. In addition, by incorporating a curvotaxis traction, our model successfully recapitulates the experimental observation of TC accumulation at convex regions of hemicylindrical substrates as well as saddle-shaped regions of more complex geometries. Overall, our work reveals the unexpected role of cell curvature sensing in driving collective migration and pattern formation on various substrate curvatures. SIGNIFICANCESubstrate surface curvature is a critical environmental cue that can influence multicellular organization and functions. Yet how cells collectively align and migrate on complex curved surfaces remains unclear. Here, we proposed a hydrodynamic theory of active nematic layers over curved surfaces for contractile theca cells (TCs), where we assume that the nematic directors of cells can respond to both the mean curvature and the Gaussian curvature of the underlying substrates. Our theory predicts distinct cell orientation patterns on hemicylindrical, hourglass- and dome-like substrates, consistent with experimental observations. Furthermore, by introducing curvotaxis traction, our model recapitulates experimentally observed accumulation of TCs at the convex regions of hemicylindrical substrates as well as saddle-shaped regions of more complex geometries. Together, our study provides a simple theoretical framework to unify our understanding of curvature sensing across complex topology, providing insights into geometric control of tissue pattern formation.

biophysics↗
bioRxiv2026

Towards autonomous biology: Compiler-Verified Protocols as a Foundation for Real World AI Execution

Artificial intelligence has advanced from analyzing experimental data to autonomously generating hypotheses, designing experiments, and coordinating closed loop discovery. Yet the translation from computational reasoning to physical execution remains bottlenecked by the experimental protocol, which in biology still relies on ambiguous natural-language descriptions: a medium other engineering disciplines abandoned decades ago in favor of compiler verified specification languages. This deficit fragments reproducibility along three axes: protocol accuracy, pre execution verification, and cross platform portability. Existing formalisms address only subsets of these challenges, trading expressiveness for rigor, portability for standardization, or usability for provenance. Here we introduce the Biology Protocol Language (BPL), a domain specific language with a biology-native type system in which every quantity carries physical units, every reagent declares its physical form, and every container maintains compiler-tracked state, so that implicit assumptions must be stated explicitly and physically impossible operations are rejected at compile time. We further develop BPL-COGEN, a pipeline that couples a fine tuned 30 billion parameter language model with the deterministic compiler in a closed generate validate repair loop, iteratively correcting the translation from natural language SOPs to BPL through compiler diagnostics until all physical, dimensional, and state constraints are satisfied. On a benchmark of 300 published Nature Protocols papers, BPL COGEN achieved an overall fidelity score of 95.1 against the source protocols as ground truth. Wet-lab experiment and cross-platform validation in GFP expression library construction and HPLC to UHPLC method translation confirmed that a single BPL source yielded reproducible execution across manual and liquid handler assisted contexts. The results established a novel pipeline that generates compiler-verified protocols, which is an essential prerequisite for physically embodied AI in biology.

synthetic biology↗
bioRxiv2026

Coordinated phase separation and phase transition underlie synaptic ribbon condensate formation and plasticity

Mesoscale molecular apparatuses with diverse functions are widespread in cells. How mesoscale cellular apparatuses are formed and regulated is poorly understood. The synaptic ribbon in sensory neurons, which can dynamically adjust its size and shape in response to light or sound, is a mesoscale molecular assembly. In this study, we demonstrate that RIBEYE, the backbone protein of synaptic ribbons, via combined ordered and disordered interactions, forms micron-sized dynamic molecular assemblies. Integrated cryo-electron microscopy and tomography studies revealed that the N-terminal SAM domain and the C-terminal B domain of RIBEYE form distinct nanoscale filaments and further assemble into ribbon-like architectures via phase transition. Unexpectedly, the N-terminal intrinsically disordered region of RIBEYE softens the solid mesoscale ribbon structures via phase separation. The mesoscale size and shape of the RIBEYE condensate are bidirectionally tuned by physiological modulators such as Piccolino and CtBP1, linking synaptic ribbon structural plasticity to functional adaptability. Thus, our study demonstrates that combined phase transition and phase separation of nanoscale protein oligomers can build mesoscale functional cellular apparatuses.

biochemistry↗
bioRxiv2026

Evolution of songbird vocal imitation involved multiple cellular innovations

A central goal of evolutionary neuroscience is to link behavioral adaptations to changes across the central nervous system. The dorsal telencephalon (i.e., pallium) varies widely in macrostructure across vertebrate clades and is thought to underlie the diversity of complex vertebrate behaviors. Yet, pallial cell types appear comparatively constrained in their evolutionary specializations relative to other parts of the nervous system, even across species with notable behavioral adaptations. Instead, differences among pallial neurons largely reflect their topographic organization. Here, we show that although transcriptomic identities of cell types in the songbird pallium largely follow this pattern, multiple cellular innovations exist within the vocal imitation brain regions distributed across the pallium. These include behavior-linked specializations to glutamatergic cell types in each region and the presence of PV- and SST-like GABAergic neurons unique to vocal imitation circuits. Additionally, we identify a concerted increase in glial composition that is accounted for by elevated proportions of astrocytes across vocal imitation circuits. These findings demonstrate that complex learned behaviors, such as vocal imitation, can be associated with the emergence of novel, behavior-associated cell types in the pallium; suggesting that selective pressures can, in some uncommon cases, favor functional specialization over conserved developmental constraints.

neuroscience↗
bioRxiv2026

Turep: Detecting cross-cancer tumor-reactive T cells in single-cell and spatial transcriptomics data

Tumor-infiltrating lymphocytes are essential for anti-tumor immunity, yet distinguishing tumor-reactive T cells from non-reactive bystander cells remains a significant challenge. Existing signatures, often derived from single cohorts, lack robustness in cross-cancer prediction. We present Turep, a deep learning method designed for robust, cross-cancer prediction of tumor-reactive T cells using single-cell or spatial transcriptomics data. By integrating paired single-cell RNA and T cell receptor sequencing data from seven human malignancies, we identified a pan-cancer tumor-reactive gene signature and leveraged generative data augmentation to address data imbalance. Turep consistently outperformed existing biomarkers, achieving a mean area under the receiver operating characteristic curve of 0.870 across cancer types. In validation across diverse cohorts, we found that Turep-predicted tumor-reactive T cell proportions could predict clinical response to immunotherapy. Furthermore, extending Turep to spatial transcriptomics revealed that tumor-reactive T cells preferentially resided in spatial niches where target cells exhibited elevated antigen presentation. Overall, Turep provides a powerful, generalizable tool for identifying tumor-reactive T cells and their spatial architectures, facilitating personalized cancer immunotherapy strategies.

bioinformatics↗
bioRxiv2026

Amyloid plaques drive long-range circuit reorganization in a mouse model of Alzheimer's disease

Amyloid plaques are a pathological hallmark of Alzheimers disease, but how they drive widespread neuronal dysfunction remains unclear. While studies in anesthetized animals show that plaques drive local hyperactivity1,2, it is unknown how this pathology shapes functional hippocampal maps in freely behaving animals. We combined chronic 1-photon calcium imaging, local field potential recordings, and post hoc 2-photon plaque imaging in freely behaving APP/PS1 mice across behavior and sleep to correlate real-time hippocampal activity and place coding with precise plaque topography. Here we show that plaques exert nonlocal, long-range effects on hippocampal activity that depend on plaque size, laminar position, and the animals behavioral state. Place cells, which encode spatial position and are normally uniformly distributed, are preferentially enriched near plaques, revealing an aberrant reorganization of plaque-adjacent neurons into the hippocampal map of space. In longitudinal experiments, pre-existing place cell locations do not predict future plaque sites, whereas hyperactivity during slow-wave sleep weakly predicts future amyloid deposition. These findings identify a mechanism by which amyloid pathology reorganizes brain circuits, degrading the functional architecture of the hippocampus and contributing to widespread dysfunction and cognitive impairment in Alzheimers disease.

neuroscience↗
bioRxiv2026

Heterogeneous transmission estimation and strategy optimization for Chikungunya: a vector-borne modeling study differentiating age and sex

Against the backdrop of global climate change and accelerating population mobility in 2025, chikungunya fever (CHIKF) exhibited a trend of worldwide spread, significantly increasing the difficulty of controlling tropical mosquito-borne diseases. To enhance the precision of intervention strategies, this study developed an age- and sex-structured human-mosquito interaction dynamic model based on data from the largest CHIKF outbreak ever recorded in China, and conducted a targeted analysis of prevention and control strategies. By decomposing the basic reproduction number and examining population heterogeneity, asymptomatic males aged 15-59 years were identified as the core transmission group. Optimal control analysis revealed that the synergistic implementation of three measures-- reducing the effective human-to-mosquito transmission rate, reducing the effective mosquito-to-human transmission rate, and suppressing mosquito population density--could reduce the overall infection rate by 95.7586%. Among these, mosquito population suppression should be prioritized as a universal core strategy; however, its protective effect on females aged 60 years and above was relatively weak, warranting particular attention. The study further demonstrated that asymmetric intensity combinations targeting these three intervention pathways--such as intensity profiles of "10%, 90%, 90%" or "60%, 80%, 90%"--could achieve effective outbreak control. This research elucidates population-specific transmission patterns and key pathways for intervention intensity, providing a theoretical and strategic foundation for the precise control of mosquito-borne diseases. It also provides actionable operational insights to support rapid response and strategy optimization for future emerging outbreaks. Author summaryCHIKF is a mosquito-borne viral disease that is gradually spreading from tropical regions to other areas. To achieve more precise control of this disease, we developed an age- and sex-structured analytical model based on the largest CHIKF outbreak in China, aiming to provide a scientific basis for responding to potential future outbreaks with inherent uncertainties. The study found that asymptomatic males aged 15-59 years were the primary drivers of transmission and should be prioritized as a key population for reducing viral spread in prevention efforts. When evaluating the effectiveness of different intervention strategies, females aged 60 years and above were the least affected by the implemented measures, indicating that this group should strengthen personal protection to lower their infection risk. Among all control measures, mosquito suppression was the most effective, suggesting that vector control strategies should be prioritized in future outbreak responses.

pathology↗
bioRxiv2026

Chemogenetic Pericyte Activation Reveals Broad Contractile Ability and Limbic Vulnerability to Capillary Flow Deficits

Capillary pericytes contact most of the brains microvasculature. Yet, their influence on blood flow remains incompletely understood both locally in capillary networks and across brain regions. Here, we sparsely expressed the chemogenetic actuator Gq-DREADD in mouse brain pericytes to stochastically probe their contractility and influence on tissue perfusion and oxygenation. Chemogenetic stimulation induced robust contraction of pericytes over minutes, including those with thin processes on capillary segments proximal to venules, indicating control of vascular tone across the entire capillary bed. Pericyte contraction combined circumferential compression with longitudinal tension applied through thin processes, resulting in vasoconstriction and hypoperfusion. Histology revealed hypoxic microdomains induced by sparse pericyte contraction across the brain, and enriched hypoxia in limbic structures including the amygdala and hippocampus. These microscale perfusion deficits were undetectable by arterial spin labeling MRI. Our findings reveal the in vivo mechanics of pericyte contraction and identify limbic system vulnerability to capillary flow impairment.

neuroscience↗
bioRxiv2026

Physical theory of epigenetic memory and its biological implications

Epigenetic memory encoded via histone modifications must remain robust across cell divisions. However, the physical rules governing how chromatin architecture regulates the maintenance and reorganization of epigenetic patterns remain unclear. Here, we develop a spreading-writing-erasing theory of epigenetic memory incorporating chromatin compartmentalization, enzyme limitation, and mark spreading. Our model demonstrates that self-sustaining epigenetic patterns emerge naturally without sequence insulators, while the establishment and erasure of heterochromatic compartments is governed by finite thresholds. Crucially, we uncover that the power-law exponent of chromatin contact probability dictates memory stability by buffering against spontaneous compartment collapse or expansion. Our theory also predicts progressive compartment fusion over cell generations, setting an upper limit of about 60 generations before senescence for human cells and explaining Hi-C map dynamics in senescent cells. Our theory also predicts a positive correlation between the contact-decay exponent and organismal complexity across species, supported by analysis of Hi-C maps across 873 species.

cell biology↗
bioRxiv2026

Serial Thermal Ablation Induces Abscopal Antitumor Immunity and Reveals Targetable CSF1R-Dependent Resistance in Pancreatic Cancer

Thermal ablation is increasingly used for local control of pancreatic ductal adenocarcinoma (PDAC), but its capacity to induce systemic antitumor immunity and the mechanisms limiting this response remain incompletely defined. Using a bilateral LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) flank tumor model, we show serial radiofrequency ablation (RFA) enhances local tumor control and induces a robust abscopal response. This effect was associated with increased activation of CD8 T cells and natural killer cells, and was abrogated by CD8 T cell depletion. Single-cell RNA sequencing revealed expansion of cytotoxic immune programs alongside induction of a CSF1R-driven myeloid response consistent with adaptive immune resistance. Although combinatorial blockade of PD-L1 and CD73 augmented systemic antitumor responses, and the addition of CSF1R inhibition in this context further enhanced both local and distant tumor control. These findings identify a CSF1R-dependent myeloid resistance program which constrains ablation-induced systemic immunity and demonstrate that rational combination immunotherapy can potentiate the systemic efficacy of tumor ablation in PDAC. STATEMENT OF TRANSLATIONAL RELEVANCERadiofrequency ablation is a local thermal therapy that induces tumor destruction and modulation of the tumor microenvironment used for treatment of many solid tumors, including pancreatic cancer. Serial thermal ablations induce a CD8+ T cells and NK cell antitumor immunological response; however, Nt5e (CD73) is increased in tumor cells, PD-1 is increased in CD8+ T cells, and serial ablations increase a CSF1R+ macrophage cluster in ablated tumors. Combinational targeting of CD73, PD-L1, and CSF1R alleviates CSF1R-dependent therapeutic resistance and enhances local and systemic tumor control. This study identifies targetable countervailing mechanisms to local ablation therapy and provides a rationale for combinatorial strategies integrating serial tumor ablation with systemic immunomodulatory agents. Future prospective studies should evaluate the influence of timing, dosage, and sequence of ablation on immune priming to improve clinical interventions in pancreatic cancer.

cancer biology↗
bioRxiv2026

Geometry-enhanced protein language modeling enables discovery of novel antibiotic resistance genes

The global antibiotic resistome remains largely unexplored, not because antibiotic resistance genes (ARGs) are rare in the environment, but because many are evolutionarily distant from known ARGs. Current computational approaches primarily rely on sequence homology, and thus miss distant homologues. We develop GeoARG, a geometry-enhanced framework that integrates structural features with protein language models through knowledge distillation, enabling efficient large-scale screening using sequence input alone. Across multiple benchmarks, GeoARG substantially improves the detection of remotely homologous ARGs, particularly under low sequence identity and fragmented conditions. Large-scale metagenomic analysis uncovers 1,485 high-confidence ARG candidates that are highly divergent from known ARGs, expanding the phylogenetic and functional landscape of the resistome. Structural analyses further show that these candidates preserve active-site geometry and maintain stable ligand-binding configurations consistent with known resistance mechanisms. These results demonstrate that geometric constraints enable systematic expansion of the resistome and facilitate the discovery of evolutionarily distant yet functionally conserved genes. A public web server is available at https://ycclab.cuhk.edu.cn/GeoARG/.

bioinformatics↗
bioRxiv2026

End-to-end bimodal anti-counterfeiting by informational DNA nanoparticles

The superior stealth properties and high information density make DNA a sought-after candidate in the field of molecular steganography. Here, we developed the InfinMark end-to-end DNA steganography framework for anti-counterfeiting applications by combining the characteristics of both the Internet of Things (IoT) and DNA-of-Things (DoT). InfinMark includes five modules: Information Transcoding, Fingerprint Writing, Nano-encapsulation, Invisible Marking, and Multi-level Rapid Authentication. It ensures precise anti-counterfeiting information reading and writing through a dynamic DNA-compatible transcoding algorithm, achieves seamless embedding by developing scalable nanoparticle manufacture methods, and supports cross-scenario on-site verification, ultimately granting it comprehensive anti-counterfeiting capabilities spanning from source labeling to terminal tracing. By addressing the bottlenecks in IoT and DoT integration, lifecycle tracking, as well on-site product authentication, this research constructs a full-chain bimodal anti-counterfeiting system, thereby showcasing the practical application of informational DNA nanoparticles in various aspects of production and daily life.

synthetic biology↗
bioRxiv2026

Sustained interferon exposure creates a hyper-metastatic subset of melanoma cells

We generated interferon signaling reporters in human and mouse melanoma cells and observed heterogeneity in interferon responses among cells in the same tumors. This was marked by inflamed regions within primary tumors that contained increased numbers of interferon-expressing macrophages/monocytes and elevated type I interferon signaling in melanoma cells. Melanoma cells that expressed GFP-Interferon stimulated gene 15 (ISG15) or GFP-Interferon-induced protein with tetraticopeptide repeats 3 (IFIT3) fusion reporters exhibited a profoundly increased ability to form metastatic tumors as compared to GFP-ISG15- melanoma cells from the same tumors, particularly when transplanted into immunocompetent mice. The increased metastatic potential of GFP-ISG15+ cells was driven partly by increased CD47 expression, which protected metastasizing cells from phagocytosis by macrophages. Macrophages are thus a double-edged sword, inhibiting the development of metastatic disease by phagocytosing disseminated melanoma cells, but promoting the emergence of a hyper-metastatic subpopulation of cells in inflamed regions of primary tumors as a consequence of sustained interferon production. One sentence summarySustained interferon exposure within inflamed regions of primary tumors dramatically increases the metastatic potential of a subpopulation of melanoma cells, partly by promoting CD47 expression, which protects against phagocytosis by macrophages.

cancer biology↗