SEARCH · PubMed Health

Results for “dual platform”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2026

Navigating Social Media: Balancing Connectivity With Media Literacy to Combat Misinformation and Protect Mental Well-Being.

BACKGROUND: The pervasive use of social media has created a complex digital ecosystem where high connectivity coexists with significant challenges, including the rapid spread of misinformation, particularly regarding mental health, and documented negative impacts on psychological well-being. Platform architectures designed for engagement maximization have been identified as central factors in both issues. OBJECTIVE: This paper critically analyzes the interconnected relationships between social media use, misinformation dissemination, and mental health impacts, with particular attention to psychiatric misinformation across diagnostic categories (e.g., depression, anxiety, ADHD). A primary objective is to evaluate the potential of advanced critical digital literacy frameworks to serve as protective mechanisms against these dual threats. METHODS: A systematic search was conducted following PRISMA 2020 guidelines across APA PsycInfo, PubMed, JSTOR, and Google Scholar for literature published between January 2018 and March 2026 (updated from the original 2023 search). The search yielded 2672 records. After removing 624 duplicates, 2048 records underwent title and abstract screening, with 1802 excluded. The remaining 246 full-text articles were assessed for eligibility, resulting in 86 studies included in the final qualitative synthesis. Inter-rater reliability was established (Cohen's κ = 0.82). Quality assessment was conducted using the Joanna Briggs Institute Checklist, AXIS, and CASP tools, with findings weighted by methodological quality. A thematic analysis was undertaken to synthesize findings. RESULTS: The analysis reveals that core architectural features of social media platforms, algorithmic curation and engagement-based metrics, simultaneously foster environments ripe for misinformation spread and contribute to psychological distress, including anxiety, depression, and harmful social comparison. Psychiatric misinformation specifically (e.g., inaccurate claims about treatment effectiveness, diagnostic criteria, and medication side effects) represents a growing concern, particularly on image- and video-based platforms. The findings indicate that conventional media literacy approaches focused solely on fact-checking are insufficient. Instead, a critical digital literacy framework encompassing algorithmic awareness, data literacy, and emotional awareness is essential for building user resilience, with evidence from high-quality systematic reviews supporting this approach. CONCLUSIONS: Navigating the complexities of modern social media requires an integrated approach combining "pedagogies of play" for experiential skill development with advocacy for structural change (e.g., algorithmic transparency, well being by design principles). This dual strategy empowers individual users to critically engage with digital content while advocating for ethical platform design, thereby safeguarding both mental well-being and democratic discourse. Implications for educators, mental health professionals (including competencies for addressing patient encounters with psychiatric misinformation), policymakers, and platform designers are discussed.

Humans↗

PubMed2025

A Reporter Platform to Study Therapy-Induced Senescence in Live Cancer Cells.

Senescence is a durable state of cell cycle arrest that can be induced by various stressors, including DNA damage caused by chemotherapeutic agents or ionizing radiation. In the context of cancer, therapy-induced senescence (TIS) plays a dual role: while it effectively halts tumor cell proliferation, TIS also carries the risk of promoting tumor relapse through the senescence-associated secretory phenotype (SASP). Beyond its direct impact on tumor cells, cancer therapies leading to TIS often induce short- and long-term side effects that significantly affect the quality of life for patients. However, the lack of universal biomarkers for TIS hinders a comprehensive understanding of its characteristics and its role in cancer therapies. A lamin-based senescence reporter platform is developed to reliably detect and sort live senescent cancer cells. This versatile tool supports live-cell imaging, enabling real-time tracking of senescence induction and escape to investigate heterogeneity in treatment response. Additionally, it allows high-content screening and marker integration, for example incorporating IL6 as SASP marker. It is therefore a valuable tool for fundamental research addressing new questions in the field of TIS as well as for drug discovery, including the development of novel senolytics.

Humans↗

PubMed2026

An integrated culturomic and genomic database and analysis platform for methanogenic archaea.

Methanogenic archaea research is challenged by limited strain resources, fragmented genomic data, inconsistent genome quality, substantial uncultured lineages, and difficulties in laboratory culturing, hindering advances in biogas production, climate mitigation, and microbial ecology. These archaea play crucial roles in global carbon cycling and anaerobic environments, yet scattered data and unculturable strains limit systematic studies and applications. To address this, we created MethArDB (Methanogenic Archaeal Genome Database), a specialized database for methanogenic archaea, compiling 3919 genomes, 87 host-associated plasmids, and 42 phages, with standardized quality classifications (complete, scaffold, draft), protein sequences, and metadata on geography, habitats, metabolism, and inheritable elements. Integrated MethArCT (Methanogenic Archaeal Culturomics Toolkit) employs a dual-threshold orthologous/paralogous protein analysis to evaluate metabolic pathway completeness, predicting cultivation parameters and suggesting candidate cultivation strategies, including potential medium formulations and conditions, to support strain isolation. Overall, MethArDB and MethArCT form an integrated platform combining genomics and culturomics to facilitate methanogenic archaea research. Database URL:  http://methardb.cn.

Genome, Archaeal↗

PubMed2026

T-rex: standardized analysis of germline variants in whole-exome sequencing trios.

Whole-exome sequencing (WES) enables the identification of rare germline variants contributing to pediatric diseases. Trio-based sequencing, comparing affected children with their parents, is particularly effective for rare disease genetics. However, WES data analysis requires bioinformatics expertise, varies across institutions, and is often incompatible with clinical workflows. We developed T-Rex (Trio Rare variant analysis of EXomes), a cross-platform desktop application that enables the standardized and local analysis of WES germline Trio data without the need for programming knowledge. T-Rex integrates state-of-the-art tools for alignment, dual-variant calling (GATK HaplotypeCaller + VarScan2), annotation (SNPEff/SNPSift), rare-variant filtering based on population frequencies (gnomAD), and family-based statistical testing, including the Transmission Disequilibrium Test with multiple-testing correction. Benchmarking of the dual-caller strategy on the Genome in a Bottle Ashkenazim Trio demonstrates high precision (99.2%) while maintaining robust sensitivity (91.1%). User testing (n = 13) confirmed quick learning across clinicians and researchers. Application to a cohort of n = 121 pediatric cancer Trio datasets, filtering for rare protein-coding variants (MAF ≤ 0.1% in gnomAD v4.1), validated all assessable previously reported pathogenic variants. Overall, T-Rex enables clinicians to robustly analyze WES Trio data in compliance with data protection regulations without requiring additional software licenses. As one of the first platforms for comprehensive WES Trio analysis that requires no programming expertise while providing reproducible, end-to-end workflows for clinical genomics, T-Rex facilitates collaborative research between clinics and reduces reliance on external providers.

Humans↗

PubMed2025

Novel approaches to clinical trial design in cancer neuroscience.

The emerging field of cancer neuroscience has revealed profound bidirectional interactions between the nervous system and cancer cells, identifying novel therapeutic vulnerabilities across diverse malignancies. This review examines the unique challenges and strategies for translating these insights into effective therapies. We propose innovative approaches to overcome these barriers through drug repurposing, enhanced biomarker development, and optimized trial designs. Repurposing neuroactive drugs with established safety profiles offers an accelerated path to clinical impact, particularly for targeting glutamatergic, adrenergic, and neurotrophic signaling pathways. Emphasizing mitigation of neurotoxicity and improved patient quality of life will be paramount moving forward. Repurposed agents that show preliminary potential for "dual use" (i.e., simultaneous toxicity mitigation and synergistic anti-tumor effects) are highlighted for special consideration. Master protocols and window-of-opportunity trials provide platforms to rapidly validate mechanisms while addressing patient-centered outcomes. By systematically addressing these foundational elements across disciplines, cancer neuroscience can translate its profound mechanistic insights into meaningful therapeutic advances for patients with treatment-resistant malignancies.

Humans↗

PubMed2025

Lentiviral CRISPRa/i in the adult prairie vole brain: modulating neuronal gene expression without DNA cleavage.

Prairie voles (Microtus ochrogaster) are a powerful model for studying the neurobiology of social bonding, yet tools for region- and cell type-specific gene regulation remain underdeveloped in this species. Here, we present a lentivirus-mediated CRISPR activation and interference (CRISPRa/i) platform for somatic gene modulation in the prairie vole brain. This system enables non-mutagenic, titratable regulation of gene expression in the adult brain without germline modification. Our dual-vector system includes one construct expressing dCas9-VPR (VP64-p65-Rta) referred to as CRISPRa or dCas9-KRAB-MeCP2 (Kruppel-associated box-methyl CpG binding protein 2), referred to as CRISPRi under a neuron-specific promoter, and a second construct delivering a U6-driven sgRNA (single guide RNA) alongside an elongation factor 1 alpha (EF1α)-driven mCherry reporter. We detail the design, production, and stereotaxic delivery of these tools and demonstrate their application by targeting four genes implicated in social behavior (Oxtr, Avpr1a, Drd1, and Drd2) across two mesolimbic brain regions: the nucleus accumbens and ventral pallidum. Gene expression analyses confirmed robust, bidirectional transcriptional modulation for selected targets, establishing a proof of concept for CRISPRa/i in this non-traditional model. The dual-vector design is readily adaptable to other gene targets, cell types, and brain regions, and can be multiplexed to provide a flexible and scalable framework for investigating gene function in behaviorally relevant circuits. These advances represent the first successful implementation of somatic CRISPRa/i in prairie voles and expand the genetic toolkit available for this species.

Avpr1a↗

PubMed2026

CRISPGen: A deep generative framework for multi-objective CRISPR/Cas9 guide RNA design via Conditional Latent Diffusion and Dual-Critic Reinforcement Learning.

MOTIVATION: The CRISPR-Cas9 system offers transformative potential for precision genome editing, yet its clinical translation remains constrained by the risk of unintended off-target double-strand breaks. While current discriminative models excel at evaluating pre-specified candidate guides, resolving the fundamental antagonism between on-target cleavage efficiency and off-target specificity within a fixed sequence search space remains a major challenge. RESULTS: We present CRISPGen, a unified deep generative framework that reframes sgRNA design as a multi-objective constrained sequence synthesis problem. It integrates (i) DNABERT-2 genomic-language embeddings, (ii) a conditional latent diffusion generator conditioned on a user-specified on-target efficiency target, and (iii) a dual-critic reinforcement-learning (RL) stage that couples a frozen on-target efficiency critic with a cross-attention off-target discriminator (validation Pearson R=0.8157) trained on a unified corpus of experimental off-target events from six detection platforms. Across 1000 generated sgRNAs, CRISPGen reduces the mean off-target discriminator score by 99.7% relative to the pre-RL baseline and, under an exhaustive whole-genome screen of all 302,631,056 NGG PAM sites in GRCh38, yields zero perfect-match and only 55 one-mismatch genomic hits. We further show, transparently, that the internal on-target critic saturates under RL optimization - an instance of Goodhart's Law - and therefore assess on-target viability using an independent external CRISPRon screen (mean 47.10/100). Repeating the RL fine-tuning stage under three random seeds (with the diffusion generator, DNABERT-2 embeddings, and off-target discriminator held fixed) yields a stable operating point across seeds. Full diversity, per-mismatch, and reproducibility statistics are reported in the Results. AVAILABILITY: Source code is available at https://github.com/malekpouri/CRISPGen; the pre-trained checkpoints and the 3,000,000-sequence library are hosted on Hugging Face (https://huggingface.co/malekpouri/CRISPGen-Checkpoints) and archived on Zenodo under DOI 10.5281/zenodo.21428641.

CRISPR-Cas9↗

PubMed2024

Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites.

Brain metastasis of advanced breast cancer often results in deleterious consequences. Metastases to the brain lead to significant challenges in treatment options, as the blood-brain barrier (BBB) prevents conventional therapy. Thus, we hypothesized that creation of a nanoparticle (NP) that distributes to both primary tumor site and across the BBB for secondary brain tumor can be extremely beneficial. Here, we report a simple targeting strategy to attack both the primary breast and secondary brain tumors utilizing a single NP platform. The nature of these mitochondrion-targeted, BBB-penetrating NPs allow for simultaneous targeting and drug delivery to the hyperpolarized mitochondrial membrane of the extracranial primary tumor site in addition to tumors at the brain. By utilizing a combination of such dual anatomical distributing NPs loaded with therapeutics, we demonstrate a proof-of-concept idea to combat the increased metabolic plasticity of brain metastases by lowering two major energy sources, oxidative phosphorylation (OXPHOS) and glycolysis. By utilizing complementary studies and genomic analyses, we demonstrate the utility of a chemotherapeutic prodrug to decrease OXPHOS and glycolysis by pairing with a NP loaded with pyruvate dehydrogenase kinase 1 inhibitor. Decreasing glycolysis aims to combat the metabolic flexibility of both primary and secondary tumors for therapeutic outcome. We also address the in vivo safety parameters by addressing peripheral neuropathy and neurobehavior outcomes. Our results also demonstrate that this combination therapeutic approach utilizes mitochondrial genome targeting strategy to overcome DNA repair-based chemoresistance mechanisms.

Brain Neoplasms↗

PubMed2026

An All-in-One Photothermal Nanocomposite Hydrogel for Controlling Inducible Transgene Expression.

We have developed a remotely near-infrared (NIR)-activated, implantable fibrin hydrogel for the controlled induction of transgene expression, designed to decouple the therapeutic efficacy of rapamycin from its systemic toxicity. Rapamycin, a drug widely used in clinical practice as an immunosuppressant and antiproliferative agent, is a potent transcriptional inducer that enables tightly regulated temporal transgene expression through chemically induced dimerization. However, its utility as a dimerizer is hindered by the unintended systemic immunosuppression and off-target effects inherent to its conventional administration. To address this, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate rapamycin, aiming to facilitate localized delivery and enhance drug stability. Engineered cells harboring a dual heat- and dimerizer-responsive gene switch exhibited robust reporter transgene expression following nanoparticle treatment and thermal activation. Nanoencapsulation preserved rapamycin activity against thermal and hydrolytic degradation, enabling superior, long-term dimerizer function compared to the free drug. To create a remotely actuated platform, we developed photothermal hydrogels by incorporating hollow gold nanoparticles and rapamycin-loaded PLGA nanoparticles within a fibrin matrix hosting the reporter cells. In mice, NIR irradiation of subcutaneously implanted constructs achieved transgene induction levels comparable to systemic administration of rapamycin. Notably, nanoparticle-mediated delivery resulted in negligible circulating rapamycin concentrations. Furthermore, localized rapamycin release initially promoted a pro-healing M2 macrophage phenotype, followed by a late-stage transition toward an M1-dominant profile that likely facilitated the clearance of scaffold degradation products. In hydrogels incorporating cells harboring a gene switch to control human VEGF165 production, NIR irradiation triggered a robust angiogenic cascade characterized by transient erythema followed by an increase in CD31+ microvascular density. Collectively, these data demonstrate the potential of this light-triggered and rapamycin-dependent platform as a customizable and safe tool for achieving the control required to advance the next-generation of site-specific, transgenic protein therapies.

Animals↗

PubMed2026

Genomic characterisation of ST233 Pseudomonas aeruginosa co-producing KPC-2 and VIM-2 in Northeastern Brazil during the COVID-19 pandemic: Evidence of independent horizontal acquisition events.

BACKGROUND: Dual-carbapenemase-producing Pseudomonas aeruginosa poses a major therapeutic and epidemiological challenge worldwide, yet systematic data on KPC and VIM co-production in Brazil remain limited. The COVID-19 pandemic intensified antimicrobial use, a period temporally associated with increased carbapenemase detection globally. OBJECTIVES: To characterise the molecular epidemiology and resistance profiles of KPC and VIM co-producing P. aeruginosa isolates from Brazil (2019-2023). METHODS: Between 2019 and 2023, 1489 multidrug-resistant P. aeruginosa isolates were screened by multiplex PCR for carbapenemase-encoding genes. Co-producing isolates underwent pulsed-field gel electrophoresis (PFGE) for clonal profiling, followed by whole-genome sequencing (WGS) for high-resolution phylogenomic analysis. Antimicrobial susceptibility testing and plasmid characterisation using next-generation sequencing platforms were also performed. RESULTS: Forty-two isolates (2.8%) harboured both blaKPC-2 and blaVIM-2, with detection occurring exclusively between 2020 and 2023, temporally coinciding with the COVID-19 pandemic. PFGE identified eight distinct clonal groups, providing evidence for independent horizontal gene transfer (HGT) events, whilst WGS confirmed all isolates as the high-risk ST233 lineage. Chromosomally integrated blaVIM-2 within class 1 integrons predominated; 2 isolates carried dual chromosomal copies. Plasmid-borne blaKPC-2 was identified across heterogeneous replicons (43.3-430.1 kb), suggesting multiple independent acquisition events. All co-producing isolates displayed extensive drug resistance, retaining in vitro susceptibility only to cefiderocol and colistin. CONCLUSIONS: ST233 co-producing KPC and VIM, represents a high-risk resistance phenotype of epidemiological significance. Divergent genomic architectures suggest active horizontal dissemination across diverse genetic backgrounds rather than clonal expansion, highlighting the need for enhanced surveillance and infection control strategies.

Bacterial genomic characterisation↗

PubMed2025

MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer.

BACKGROUND: This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS: We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS: The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS: This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.

Humans↗

PubMed2026

Volumetric DNA microscopy for mapping spatial transcriptomes in three dimensions.

The architecture and function of biological systems are inherently three-dimensional, yet most existing spatial transcriptomic technologies remain restricted to thin tissue sections, limiting their capacity to resolve cellular organization and microenvironments within intact tissue volumes. To address this limitation, we developed volumetric DNA microscopy, a scalable, optics-free approach for spatial transcriptome profiling directly within intact biological specimens. The method encodes spatial information into DNA molecules that form a dense intermolecular network in situ, enabling the reconstruction of three-dimensional spatial relationships through short-read sequencing and computational analysis. Here we detail the complete workflow including in situ cDNA synthesis, spatial encoding through DNA nanoball formation, dual-scale proximity bridging between neighboring nanoballs and spatial reconstruction via geodesic spectral embedding. Sequencing libraries can be generated within 7-8 d by a competent graduate-level molecular biologist, followed by standardized downstream computational analysis. Because the workflow requires only routine molecular biology reagents and a benchtop sequencer, volumetric DNA microscopy provides a versatile platform for exploring genetic and morphological features in intact tissues.

Spatial Transcriptomics↗

PubMed2026

Development of a PCR-based technique for genotyping UGT1A1 gene and distribution of rs3064744 alleles in the Russian population.

BACKGROUND: Accurate determination of tandem thymine-adenine (TA) repeat numbers in the UGT1A1 promoter region (rs3064744) is essential for diagnosing Gilbert's syndrome and personalizing therapy with toxic agents like irinotecan and atazanavir. However, traditional polymerase chain reaction (PCR) assays face severe limitations due to the AT-rich sequence and overlapping melting temperatures (Tm) of the highly homologous 7TA and 8TA alleles. In this context, melting curve analysis (MCA) employing fluorophore-quencher systems has emerged as a promising alternative. The purpose of this study was to develop a novel genotyping approach combining optimized aPCR-MCA analysis with an automated classifier to overcome the limitations posed by the differentiation of highly homologous alleles and to demonstrate its practical application, providing the distribution of rs3064744 genotypes across four regional cohorts of the Russian population. METHODS: A specialized Dual Head 1D-convolutional neural network (1D-CNN) ensemble with Test-Time Augmentation (TTA) was developed. The model was trained and internally validated on 1,620 engineered plasmid samples, and independently evaluated on an external clinical test set of 440 unique patient genomic DNA specimens. Real-time PCR was performed on CFX96 and DTprime platforms. Additionally, population-wide screening was conducted on 997 archival clinical samples from Moscow, Sakha (Yakutia), Dagestan, and Rostov regions. RESULTS: While 5TA and 6TA alleles were easily separated, absolute Tm distributions of 7TA and 8TA alleles overlapped significantly, and non-uniform Tm shifts of 0.8 °C-1.4 °C occurred across platforms. Conventional absolute Tm thresholding was therefore inadequate. By assessing relative morphological curve divergence against co-amplified 7TA/7TA and 7TA/8TA reference anchors, the 1D-CNN ensemble neutralized instrument noise. It achieved 100% accuracy on internal validation and 100% concordance (440/440) with clinical reference pyrosequencing. Population screening revealed that Dagestan, Yakutia, and Rostov cohorts closely align with the European population. Rare 5TA and 8TA alleles were detected at low frequencies in Yakutia and Moscow. CONCLUSION: Combining LNA-modified aPCR-MCA with a comparative 1D-CNN model successfully circumvents thermodynamic limitations and eliminates human operator bias. This integrated system offers an accessible, high-throughput, and clinically valid solution for routine UGT1A1 pharmacogenetic testing.

1D-CNN↗

PubMed2026

ALPINE: a scalable pipeline for comprehensive classification of gene-editing outcomes from long-read amplicon sequencing.

SUMMARY: CRISPR genome editing has enabled precise genetic modification for gene and cell therapies, but edits often produce heterogeneous on-target outcomes, including homology-directed repair (HDR) knock-ins, DNA repair template integrations, and structural variants. Existing tools are frequently limited to short reads or lack viral vector-specific integration categories needed for therapeutic development. Here, we present ALPINE (Amplicon Long-read Pipeline for INtegration Evaluation), a scalable and reproducible pipeline for classifying and quantifying gene-editing outcomes from long-read amplicon sequencing supporting both PacBio HiFi and Oxford Nanopore platforms. ALPINE classifies reads into 10+ categories, including DNA repair vector integration subtypes, and performs variant calling near the gene-edited site with batch, multi-sample reporting. Uniquely, ALPINE can distinguish between cells treated with multiple DNA repair vectors and identify distinct molecular features, such as inverted terminal repeats (ITRs), enabling comprehensive characterization of complex gene editing outcomes. Dual-target benchmarking on simulated datasets demonstrated high accuracy for transgene integration events. Independent validation on public crosslinked-HDR dataset confirmed ALPINE's integration detection capabilities, and application to edited T cell samples demonstrated comprehensive gene-editing outcome profiling. AVAILABILITY: ALPINE is available under MIT license at https://github.com/Maggi-Chen/ALPINE and https://doi.org/10.5281/zenodo.20272510. All analysis scripts and visualization code used in this manuscript are available at https://github.com/Maggi-Chen/ALPINE-manuscript-analysis. Simulated datasets are deposited at Zenodo (https://doi.org/10.5281/zenodo.20260865). Public dataset PRJNA913199 is available through NCBI SRA.

Gene Editing↗

PubMed2026

Bacterial Outer Membrane Vesicles in Colorectal Cancer: Interdomain Communication Hubs in Pathogenesis and Immunotherapy.

The complex interaction between the intestinal microbiota and host mucosal immunity plays a defining role in colorectal cancer (CRC) development and therapeutic outcomes. Recently, bacterial outer membrane vesicles (OMVs)-nano-sized, lipid-bilayered extracellular particulates released by both commensal and pathogenic microorganisms-have emerged as critical long-range signaling vehicles within the gut. This review provides a comprehensive synthesis of the dual functionalities of OMVs in CRC pathogenesis and oncology. Mechanistically, pathogenic OMVs cross compromised mucosal barriers to drive horizontal gene transfer (HGT) of chimeric episomes, such as SPHINX DNAs and Bovine Meat and Milk Factors (BMMFs), thereby promoting genomic instability and neoplastic transformation. Conversely, there is a paradigm shift toward exploiting next-generation probiotic and engineered OMVs as highly tunable therapeutic platforms. By combining cutting-edge bioengineering strategies-such as biomimetic mineralization to neutralize local tissue acidity and chemotherapeutic packaging-these nanovectors effectively reprogram the immunosuppressive tumor microenvironment (TME). Specifically, optimized OMVs modulate macrophage polarization from an M2 to an M1 phenotype and stimulate CXCL10-mediated CD8+ T-cell infiltration, effectively turning immunologically "cold" tumors "hot." Finally, the great translational challenges regarding systemic endotoxicity, scalability, and target delivery, providing a strategic approach for the integration of OMV-based platforms into synergistic immune checkpoint inhibition regimens.

Colon cancer↗

PubMed2026

A Biomimetic Dual-Targeting Nano-APA-Editor Reprograms the 3'UTR Landscape for Tongue Squamous Cell Carcinoma Therapy.

Targeting post-transcriptional dysregulation of tumor suppressors represents a new frontier in cancer therapy. Here, we identify the alternative polyadenylation (APA) regulator NUDT21 as a pivotal therapeutic target in oral squamous cell carcinoma (OSCC). NUDT21 is highly upregulated, correlating strongly with poor survival and advanced clinical stage. We outline a pathogenic mechanism whereby NUDT21 drives this phenotype by forcing a network of tumor suppressor transcripts, notably PTEN, into translationally-repressed, long-3'UTR isoforms. To therapeutically "re-engineer" this APA switch, we design a "Nano-APA-editor." This platform features an HMSN core with an sgRNA-NUDT21 payload and a hierarchical targeting strategy: a cancer-educated dendritic cell (DC) membrane for biomimetic camouflage and homotypic affinity, "gated" by a TA-aptamer for final precision. This system enables potent and selective NUDT21 silencing, driving a shift toward short-3'UTR isoforms. Consequently, the Nano-APA-editor effectively reinstates PTEN and associated suppressors and inhibits multiple malignant phenotypes in vitro. In an orthotopic OSCC model, it demonstrates profound tumor regression, outperforming conventional chemotherapy (PTX) with excellent biocompatibility. In vivo analysis confirmed target engagement (NUDT21-down) and functional restoration (PTEN-, WEE1-, TGF-β-up). This work validates a "post-transcriptional re-engineering" strategy, executed by a logically designed nanoplatform, as a powerful and safe modality for precision gene therapy.

Humans↗

PubMed2026

Engineered Transformer Base Editor with Enhanced Editing Efficiency.

Canonical cytosine base editors (CBEs) achieve precise C-to-T conversions without inducing DNA double-strand breaks (DSBs), yet their clinical potential remains hampered by substantial off-target (OT) mutations. The recently developed transformer base editor (tBE) significantly reduces both genomic and transcriptomic OT mutations by using a cleavable deoxycytidine deaminase inhibitor (dCDI) domain. However, the modest base editing efficiency limits its broader applications. Here, through rational deaminase engineering and fusion of a uracil DNA glycosylase inhibitor (UGI) domain, we developed the engineered tBE (etBE). The etBE exhibited substantially enhanced editing efficiencies compared with the parental tBE (up to 35.11-fold improvement), while maintaining high editing fidelity and background levels of OT mutations. As a therapeutic proof-of-concept, dual adeno-associated virus (AAV)-mediated delivery of etBE targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-established therapeutic target for cardiovascular diseases, was evaluated in a humanized mouse model. The treatment achieved efficient in vivo base editing (up to 35.13%), resulting in substantial reductions in plasma PCSK9 protein (24%) and low-density lipoprotein cholesterol (LDL-C) levels (33%), while inducing only minimal OT mutations. Collectively, etBE represents a highly efficient and specific base editing platform with enormous potential for both basic research and clinical applications.

CRISPR‐Cas9↗

PubMed2025

Multiplexed Dual-Color Fluorescence-Based Distinction Between Nuclear Trapping and Translocation of FOXO3.

FOXO3 is a transcription factor that mainly exerts its functions in the cell nucleus. The amino acid sequence of FOXO3 contains a nuclear localization sequence (NLS) and a nuclear export sequence (NES) allowing for nuclear/cytoplasmic shuttling that plays an important role in regulating FOXO3 activity. Nuclear accumulation of FOXO3 proteins can be the result of translocation to the nucleus triggered by upstream regulatory input or trapping of FOXO3 within the nucleus through the inhibition of its nuclear export via the receptor CRM1. In order to distinguish these two modes of FOXO3 activation, we have generated a multiplexed assay. The development of this platform includes a reporter cell line that monitors CRM1 activity by using RFP-labeled HIV-1 Rev. protein with a strong heterologous NES. Simultaneously, the intracellular localization of FOXO3 can be monitored by a second cell line stably expressing GFP-FOXO3. Here we describe a detailed protocol on how to co-culture these reporter cell lines and use them to interrogate compound-induced FOXO3 activation in order to understand the mode of action.

Forkhead Box Protein O3↗