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At least 19 recordsLinked to original sources

PubMed2025

Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.

Recombinant adeno-associated viruses (AAVs) are leading vectors for in vivo human gene therapy. An integral vector element is promoters, which control transgene expression in either a ubiquitous or cell-type-selective manner. Identifying optimal capsid-promoter combinations is challenging, especially when considering on- versus off-target expression. Here, we report a pipeline for in vivo promoter biopanning in AAV building on our AAV capsid barcoding technology and illustrate its potential by screening 53 promoters in 16 murine tissues using an AAV9 vector. Surprisingly, the 2.2-kb human glial fibrillary acidic protein (GFAP) promoter was the top hit in the liver, where it outperformed robust benchmarks such as the human α-1-antitrypsin promoter or the clinically used liver-specific promoter 1 (LP1). Analysis of hepatic cell populations revealed preferred GFAP promoter activity in hepatocytes. Notably, the GFAP promoter also surpassed the LP1 and cytomegalovirus promoters in human hepatocytes engrafted in an immune-deficient mouse. These findings establish the GFAP promoter as an exciting alternative for research and clinical applications requiring efficient and specific transgene expression in hepatocytes. Our pipeline expands the arsenal of technologies for high-throughput in vivo screening of viral vector components and is compatible with capsid barcoding, facilitating the combinatorial interrogation of complex AAV libraries.

Dependovirus↗

PubMed2026

A stable and potent buffalo EF1α1 promoter for robust gene expression in mammalian systems.

This study reports the first isolation and characterization of the buffalo EF1α1 promoter, demonstrating its strong gene expression activity both in vitro across diverse cultured cell types and in vivo across multiple mouse organs. Although viral promoters, such as cytomegalovirus (CMV) and simian virus (SV40), are widely used for their strong expression in various cell lines in mammalian expression systems and in animal tissues, they are prone to methylation-induced transcriptional silencing and subsequent loss of exogenous gene expression. The most effective alternative to viral promoters is the synthetic hybrid CAG promoter (cytomegalovirus major immediate-early enhancer combined with the chicken beta-actin promoter) or mammalian cellular promoter such as human elongation factor 1 alpha (hEF1α), which drives strong gene expression but lacks consistency and is limited in their in vivo expression potential due to their vulnerability to epigenetic silencing. To overcome these challenges, the bbEF1α1 promoter was cloned and evaluated both in vitro and in vivo. It consistently drives higher levels of exogenous gene expression than CMV in diverse cell lines. Importantly, transgene expression was achieved in various organs of transgenic mice and in muscle tissue following in vivo electroporation. These findings establish the bbEF1α1 promoter as a powerful ubiquitous driver of gene expression, offering high stability with broad applications in gene therapy, biopharmaceutical production, and functional genomics.

Animals↗

PubMed2025

Novel photoreceptor-specific promoters for gene therapy in mid- to late-stage retinal degeneration.

Inherited retinal degenerations (IRDs) cause progressive photoreceptor loss, leading to vision impairment. Gene therapy using adeno-associated viral (AAV) vectors holds immense promise for treating these conditions. However, achieving optimal gene expression at mid to late stages of retinal degeneration remains challenging due to scarcity of efficient photoreceptor-specific promoters expressed at these disease stages. This study aimed to identify and validate novel promoters capable of robust and specific transgene expression when ≥50% of photoreceptors are lost. Analysis of transcriptomic data from two naturally occurring canine IRD models, laser capture microdissection of retinal cryosections followed by qPCR, and RNA in situ hybridization identified six promising genes with sustained or upregulated expression in photoreceptors in late-stage disease. Upstream cis-regulatory elements of both canine and human orthologs were identified and characterized using in silico analyses and dual-luciferase assays. Short promoters (≤840 base pairs) derived from GNGT2, IMPG2, and PDE6H genes exhibited robust reporter gene expression in photoreceptors when delivered via AAV to the subretinal space of two non-allelic canine IRD models at mid and late disease stages. These findings provide a strategy to enhance AAV-mediated gene therapy by enabling sustained transgene expression in degenerating retinas, improving treatment outcomes for patients with progressive vision loss.

Retinal Degeneration↗

PubMed2026

Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection.

Candida parapsilosis is a major human fungal pathogen, with recent global outbreaks driven by fluconazole-resistant (FLCR-Cp) isolates that are difficult to eradicate and associated with poor clinical outcomes. However, the microbial traits enabling persistence of these outbreak lineages remain poorly defined. Here, we show that FLCR-Cp isolates responsible for prolonged, multi-country outbreaks consistently exhibit a striking low-biofilm-producing (LBP) phenotype. Contrary to the prevailing view that robust biofilm formation promotes persistence, LBP strains displayed enhanced stress tolerance, increased cell wall masking, and reduced immune recognition. These traits conferred resistance to neutrophil and macrophage killing and enhanced survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Whole-genome sequencing (WGS) of a global isolate collection further demonstrated that the LBP phenotype has emerged independently multiple times, supporting convergent evolution under host selection. Functional genomic analyses suggest that biofilm attenuation arises through multigenic changes, and disruption of key biofilm-associated transcriptional regulators enhanced fitness during immune interactions. Together, our findings overturn the assumption that robust biofilm formation drives outbreak persistence and instead identify biofilm attenuation as an adaptive tradeoff that promotes immune evasion and long-term survival. These results redefine our understanding of C. parapsilosis adaptation during healthcare-associated outbreaks and shift attention toward host-driven evolutionary processes than environmental persistence alone.

Biofilms↗

PubMed2025

The snakehead retrovirus promoter functions independently of the 3'ORF protein and its products are maternally inherited in transgenic zebrafish.

The exogenous snakehead retrovirus (SnRV) is an unclassified member of the Orthoretrovirinae subfamily, discovered in cell lines derived from several fish species. SnRV resembles complex lentiviruses and potentially encodes accessory proteins, including the product of the 3' open reading frame (3'ORF). The 3'ORF protein was suggested to function as a transactivator of transcription (Tat). Here, we constructed an infectious molecular clone for SnRV and tested the effects of 3'ORF mutations on SnRV transcription. Although replacing 3'ORF with foreign sequences strongly reduced virus expression and production, an out-of-frame point mutation in 3'ORF had only a minimal effect on SnRV replication. This latter result suggests that the 3'ORF protein does not function as Tat and that SnRV transcription is largely independent of the product of this ORF. We also show that in vitro, the SnRV promoter is versatile and robustly functioning in both fish and mammalian cultured cells. Finally, the SnRV promoter was transiently active in injected zebrafish embryos as early as the blastula stage. In transgenic zebrafish, this promoter drives enhanced expression in sensory organs and gonads, and its generated products are maternally inherited. Considering these characteristics, the SnRV promoter emerges as a promising candidate for developing versatile expression vectors applicable to research and biotechnological applications.

Animals↗

PubMed2025

"It just feels morally not right to Sell the data": Ethical and social perspectives on human genomic data sharing in Uganda-A phenomenological qualitative study.

While genomic data sharing enhances transparency and research efficiency, it also raises significant ethical and social challenges. This study explored stakeholders' perspectives on these issues, particularly around privacy, confidentiality, and equity in collaborative research. A phenomenological qualitative study was conducted between August and December 2023 at Makerere University College of Health Sciences, other research-intensive institutions, and national regulatory bodies. The study engaged 86 participants: 47 key informants (16 researchers, 14 ethics committee members, nine community advisory board members, and eight research regulators) and four deliberative focus group discussions with 39 participants. Interviews were transcribed verbatim, and thematic analysis was conducted using NVivo 14. Three major themes emerged: (1) stakeholders' experiences in genomic research, including their roles as participants, implementers, or overseers; (2) ethical concerns, such as informed consent, third-party data access, inequities between high-income and low- and middle-income country (LMIC) researchers and participants, and the lack of benefit-sharing frameworks; and (3) social implications, including stigma, discrimination, labeling, community perceptions of fairness, and the need for meaningful engagement. Participants emphasized the importance of protecting participant rights, promoting equity, and ensuring robust data governance and security. The theoretical frameworks of principlism and distributive justice provided a valuable lens for examining these concerns, particularly by highlighting the need to safeguard privacy and fairly distribute responsibilities and benefits in global collaborations. Participants also noted that perceptions of fairness are shaped by trust, local context, and past experiences with research factors that are critical for building equitable and respectful partnerships. This study underscores the urgent need to strengthen protections for research participants and promote fairness in genomic data sharing. Policies should, if adopted, emphasize culturally contextualized consent, active community engagement, restricted third-party data access, and strong data protection mechanisms to address existing inequities and prevent misuse.

LMICs↗

PubMed2025

Pituitary Neuroendocrine Tumor or Pituitary Adenoma? Let's Ask the Epigenome!

The introduction of the term pituitary neuroendocrine tumor (PitNET) to replace pituitary adenoma has sparked a versatile debate among experts. The controversy surrounding this nomenclature change includes the question of whether these tumors' biological identity truly corresponds to neuroendocrine tumors. In this meta-analysis, DNA methylation data were interrogated to clarify whether the old or new nomenclature more accurately reflects the epigenome of these tumors. Publicly available DNA methylation data of 100 NETs, 100 PitNETs/adenomas, and 100 adenomas of various origins and lineages were compiled from 18 different publications. Epigenomic signatures characteristic of NETs and adenomas were defined and compared to those of PitNETs/adenomas. Promoter CpG methylation levels were investigated for hallmarks of cellular differentiation. Comparative DNA methylation analyses demonstrated that all 100 PitNETs/adenomas aligned more closely with NETs than with adenomas. Focusing on promoter-associated CpGs moreover confirmed robust epigenomic features associated with neuroendocrine differentiation in PitNETs/adenomas. These findings indicate that PitNETs/adenomas resemble NETs rather than adenomas on the epigenomic level and support PitNET as the biologically more accurate term. Of note, appropriately addressing the broad spectrum of clinical behaviors in these tumors remains a critical issue in the current pituitary tumor classification framework and nomenclature.

Humans↗

PubMed2026

CaMYB121-CaABF2 negative feedback loop modulates CaNHX2 expression to confer salt tolerance in pepper.

Salt stress is a major abiotic factor that severely restricts pepper (Capsicum annuum) production. Although abscisic acid (ABA) is vital for salt tolerance, the transcriptional regulatory networks governing ABA-mediated salt defense remain largely unknown. Here, we uncovered a negative feedback loop between CaMYB121 and CaABF2.1/2 that modulates the expression of CaNHX2.1/2/3, thereby enhancing salt tolerance in pepper plants. RNA-seq analysis revealed that CaMYB121 displayed an expression pattern consistent with that of CaNHX2 after salt treatment. Silencing CaMYB121 markedly reduced salt tolerance and inhibited root growth. Mechanistically, CaMYB121 directly binds to the CaNHX2 promoter to activate transcription, thereby promoting salt resilience. Salt stress also robustly triggered ABA signaling genes, with CaABF2.1/2 displaying expression patterns closely mirroring those of CaMYB121. Transient silencing of CaABF2.1/2 results in phenotypes similar to those observed with CaMYB121 suppression. Notably, CaMYB121 activates CaABF2.1/2 transcription by binding to its promoters, whereas CaABF2.1/2 represses CaMYB121 expression by directly targeting its promoter, forming a self-regulating feedback loop that prevents excessive defense activation. Collectively, our findings reveal a CaMYB121-CaABF2 feedback circuit that dynamically balances growth and defense to optimize salt tolerance in pepper plants.

Salt Tolerance↗

PubMed2025

SETD1B-mediated broad H3K4me3 controls proper temporal patterns of gene expression critical for spermatid development.

Epigenetic programming governs cell fate determination during development through intricately controlling sequential gene activation and repression. Although H3K4me3 is widely recognized as a hallmark of gene activation, its role in modulating transcription output and timing within a continuously developing system remains poorly understood. In this study, we provide a detailed characterization of the epigenomic landscapes in developing male germ cells. We identified thousands of spermatid-specific broad H3K4me3 domains regulated by the SETD1B-RFX2 axis, representing a previously underappreciated form of H3K4me3. These domains, overlapping with H3K27ac-marked enhancers and promoters, play critical roles in orchestrating robust transcription and accurate temporal control of gene expression. Mechanistically, these broad H3K4me3 compete effectively with regular H3K4me3 for transcriptional machinery, thereby ensuring robust levels and precise timing of master gene expression in mouse spermiogenesis. Disruption of this mechanism compromises the accuracy of transcription dosage and timing, ultimately impairing spermiogenesis. Additionally, we unveil remarkable changes in the distribution of heterochromatin marks, including H3K27me3 and H3K9me2, during the mitosis-to-meiosis transition and completion of meiotic recombination, which closely correlates with gene silencing. This work underscores the highly orchestrated epigenetic regulation in spermatogenesis, highlighting the previously unrecognized role of Setd1b in the formation of broad H3K4me3 domains and transcriptional control, and provides an invaluable resource for future studies toward the elucidation of spermatogenesis.

Male↗

PubMed2026

AISP position statement: Standardising biological sample collection and handling for advanced diagnostics and multi-omic analyses in pancreatic cancer.

The quality of biological samples is a major determinant of analytical reliability and translational relevance in patients with pancreatic ductal adenocarcinoma (PDAC). However, variability in specimen procurement, handling, transport, processing, and storage can substantially affect tissue integrity and the robustness of downstream analyses. This paper, promoted by the Pathology and Basic Science Task Force of the Italian Association for the Study of the Pancreas (AISP), brings together experts in pathology, molecular biology, translational research, medical oncology, and gastroenterology to provide practical recommendations for the collection, handling, and pre-analytical management of biological samples. Draft recommendations were discussed during dedicated working group meetings and approved by consensus among all authors, supported by key literature. The document identifies the biological specimen as the critical link between patient care, pathology, and research, and provides guidance for clinicians and professionals involved in sample procurement and processing. By addressing the requirements of different analytical platforms, including genomics, organoid generation, immunophenotyping, pharmacogenomics, and multiplex/spatial analyses, this paper aims to reduce pre-analytical variability, improve diagnostic accuracy, and enhance the clinical and translational value of molecular investigations in pancreatic cancer. Standardised procedures across centres may facilitate comparable data collection, support multicentre studies, and strengthen collaboration between clinicians, pathologists, and research laboratories.

Biobanking↗

PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗

PubMed2025

Deep learning guided programmable design of Escherichia coli core promoters from sequence architecture to strength control.

Core promoters are essential regulatory elements that control transcription initiation, but accurately predicting and designing their strength remains challenging due to complex sequence-function relationships and the limited generalizability of existing AI-based approaches. To address this, we developed a modular platform integrating rational library design, predictive modelling, and generative optimization into a closed-loop workflow for end-to-end core promoter engineering. Conserved and spacer region of core promoters exert distinct effects on transcriptional strength, with the former driving large-scale variation and the latter enabling finer gradation. Based on this insight, Mutation-Barcoding-Reverse Sequencing approach was used and constructed a synthetic promoter library comprising 112 955 variants with minimal redundancy and a 16 226-fold expression range. A Transformer-based model trained on this dataset achieved a Pearson correlation of 0.87 with experimentally measured promoter strengths. When combined with a conditional diffusion model, the system enabled de novo generation of promoter sequences with defined strengths, achieving a design-to-measurement correlation of 0.95 and maintaining high accuracy (R = 0.93) across varied sequence contexts. The designed promoters consistently preserved their intended strength gradients, demonstrating robust plug-and-play functionality. This work establishes a scalable and extensible platform (www.yudenglab.com) for deep learning-guided programmable design of Escherichia coli core promoters, enabling precise transcriptional control.

Promoter Regions, Genetic↗

PubMed2026

Context-Dependent cGAS-STING Activation Shapes Metastatic Progression and Dormancy.

Cancer cells survive, proliferate, and metastasize in part because the immune system fails to detect and eliminate them. Moreover, the tumor microenvironment (TME) that surrounds the tumor supports cancer cell survival and resistance to chemo- and immunotherapies by inhibiting antitumor immune responses and thereby reducing the efficacy of immunotherapeutic interventions. cGAS-STING signaling senses cytoplasmic DNA and coordinates innate immune responses that shape tumor-intrinsic outcomes and the TME. Emerging evidence reveals a context-dependent, dualistic role for cGAS-STING in metastatic progression and cancer dormancy. Acute, robust activation in antigen-presenting cells promotes type I interferon responses, leading to suppression of tumor growth. By contrast, chronic, low-level cancer-intrinsic STING signaling can engage inflammatory programs that foster immune suppression and therapy resistance. Dormant disseminated tumor cells exploit niche cues to downregulate STING signaling and evade immune detection, whereas reactivation of dormant cells often involves restoration of STING activity that can promote immune elimination. In this article, we review mechanisms linking genome instability and cytoplasmic DNA to STING activation, summarize evidence for tumor-suppressive versus tumor-promoting functions across metastatic niches, and discuss how STING agonists and combination strategies may be optimized to maximize antitumor immunity while avoiding protumorigenic effects.

Humans↗

PubMed2014

Genome-wide computational analysis reveals cardiomyocyte-specific transcriptional Cis-regulatory motifs that enable efficient cardiac gene therapy.

Gene therapy is a promising emerging therapeutic modality for the treatment of cardiovascular diseases and hereditary diseases that afflict the heart. Hence, there is a need to develop robust cardiac-specific expression modules that allow for stable expression of the gene of interest in cardiomyocytes. We therefore explored a new approach based on a genome-wide bioinformatics strategy that revealed novel cardiac-specific cis-acting regulatory modules (CS-CRMs). These transcriptional modules contained evolutionary-conserved clusters of putative transcription factor binding sites that correspond to a "molecular signature" associated with robust gene expression in the heart. We then validated these CS-CRMs in vivo using an adeno-associated viral vector serotype 9 that drives a reporter gene from a quintessential cardiac-specific α-myosin heavy chain promoter. Most de novo designed CS-CRMs resulted in a >10-fold increase in cardiac gene expression. The most robust CRMs enhanced cardiac-specific transcription 70- to 100-fold. Expression was sustained and restricted to cardiomyocytes. We then combined the most potent CS-CRM4 with a synthetic heart and muscle-specific promoter (SPc5-12) and obtained a significant 20-fold increase in cardiac gene expression compared to the cytomegalovirus promoter. This study underscores the potential of rational vector design to improve the robustness of cardiac gene therapy.

Animals↗

PubMed2026

Protein persulfidation emerges as a conserved component of the redox response to DNA damage.

Genotoxic stress is frequently accompanied by alterations in cellular redox homeostasis; however, the mechanisms linking redox regulation to the DNA damage response (DDR) remain incompletely understood. Here, we investigated the early redox response to DNA damage induced by methyl methanesulfonate (MMS) in Saccharomyces cerevisiae, focusing on cysteine oxidative post-translational modifications (PTM). We show that activation of the DNA damage response is accompanied by rapid redox changes that occur in the absence of a generalized oxidative stress response. MMS exposure promotes selective remodeling of cysteine oxidative modifications, characterized by decreased free thiols, robust induction of protein persulfidation, and comparatively modest changes in sulfenylation. These alterations are accompanied by increased intracellular hydrogen sulfide levels, supporting the involvement of reactive sulfur species in the cellular response to DNA damage. Proteome-wide analyses revealed that cysteine oxidative modifications preferentially target proteins involved in central metabolism, nucleotide biosynthesis, and genome maintenance. Consistent with these observations, MMS-induced genotoxic stress promotes metabolic adaptation characterized by increased mitochondrial respiration, elevated ATP production, and mitochondrial morphological remodeling, linking bioenergetic adaptation to redox regulation. Importantly, perturbation of intracellular redox balance using N-acetylcysteine compromises survival under DNA-damaging conditions, supporting a functional role for redox signaling during the DDR. Finally, MMS treatment also induces protein persulfidation in mammalian cells. Moreover, exposure to etoposide, a mechanistically distinct genotoxic agent that induces DNA double-strand breaks through topoisomerase II inhibition, showed a similar trend, suggesting that protein persulfidation may not be restricted to alkylation-induced DNA damage. Together our findings identify protein persulfidation as a prominent component of the redox response to DNA damage and provide new insight into the functional interplay between mitochondrial metabolism, cysteine-based redox regulation, and genome maintenance.

Oxidation-Reduction↗

PubMed2026

Replication stress links Geminin depletion to centrosome amplification.

The timing of DNA replication and centrosome duplication is tightly regulated with cell cycle progression to ensure the faithful duplication of the genome during cell division. Both DNA and centrosomes are licensed for replication in late telophase/early G1, replicated in S phase and segregated during mitosis; yet how defects in DNA replication licensing are coupled to centrosome homeostasis remains poorly understood. Here, we show that depletion of the replication licensing inhibitor Geminin in proliferating mouse embryonic fibroblasts induces robust centrosome amplification together with impaired primary cilium assembly. Rather than promoting whole-genome reduplication, knockdown of Geminin triggers a replication stress response, characterized by DNA damage accumulation throughout the cycle, and activation of an ATR-dependent DNA damage response. Mechanistically, Geminin depletion-induced replication stress activates the ATR-Chk1-Wee1 checkpoint axis prolonging G2 and leading to premature centriole disengagement and centrosome amplification. These findings identify replication stress as the signaling module that couples defective DNA replication licensing to centrosome amplification.

DNA damage↗

PubMed2026

Comparative phylogenomics and transcriptional regulatory networks of AQPs, HSPs, and LEA proteins in salt-stressed Portulaca oleracea.

Soil salinization severely threatens global food security, necessitating systematic investigations of halophytes like Portulaca oleracea to decode the molecular mechanisms of environmental resilience. Utilizing an integrated framework of deep learning-based genome annotation (58,817 predicted genes; 96.5% BUSCO completeness), multi-tissue RNA-Seq, phylogenomics, and gene regulatory network (GRN) inference, the synergistic orchestration of 78 aquaporins (AQPs), 525 heat shock proteins (HSPs), and 119 late embryogenesis abundant (LEA) proteins was elucidated. The active transcriptome, encompassing 39,065 expressed loci, revealed a systemic growth-defense trade-off. Tissues displayed distinct adaptive mechanisms: leaves modulated intracellular water balance via specialized AQPs, whereas adult roots maintained proteostasis through robust HSP20/HSP70 induction. Phylogenomic clustering across 154 species demonstrated that salinity tolerance constitutes an evolutionary mosaic, identifying 81 halophyte-exclusive orthogroups and 1129 species-specific clusters. Comparative topology across six independent GRNs (4.2M-5.3 M edges) unmasked a highly modular transcriptional reprogramming strategy governed by a core apparatus of 22 stress-exclusive regulators, with functional enrichment heavily prioritizing protein dimerization and chromatin remodeling. Theoretically, the distinct convergence of Trihelix transcription factors with guard cell differentiation pathways offers a candidate transcriptomic framework to explain the plant's characteristic C4-CAM photosynthetic plasticity under severe osmotic pressure. Practically, these evolutionary blueprints and specific master switches transcend single-gene transgenic limitations. Utilizing these root-sustained and stress-inducible targets under localized promoters provides a naturally optimized, network-level precision engineering roadmap to transfer robust, compartmentalized halotolerance to sensitive glycophytic crops.

Gene Regulatory Networks↗

PubMed2026

Clinical performance of the urine-based TERT promoter AbsoluteQ Digital PCR for non-invasive detection of bladder cancer.

Bladder cancer (BC) is the ninth most common cancer worldwide, with urothelial carcinoma accounting for approximately 90% of all cases and presenting predominantly as non-muscle-invasive disease. Due to its high recurrence rate and the need for long-term surveillance, BC is associated with the highest lifetime treatment costs per patient among all cancers, making its effective management a significant clinical and economic challenge. The most frequently identified variants in the TERT gene promoter are c.-124C>T (C228T) and c.-146C>T (C250T), located within a region characterized by high guanine-cytosine (GC) content, which makes amplification challenging. We aimed to validate the AbsoluteQ Digital PCR assay for the detection of urine-based TERT promoter variants for the diagnosis of urothelial bladder cancer and to assess its diagnostic performance in comparison with standard methods. Urine samples were collected from patients with histopathologically confirmed bladder cancer (n = 58) and compared with a control group (n = 55). The C228T and C250T variants were tested using the AbsoluteQ Digital PCR assay. Sensitivity, specificity, and predictive values were calculated to evaluate the performance of the assessed method. The AbsoluteQ Digital PCR demonstrated superior diagnostic performance compared to conventional Sanger sequencing for detecting TERT promoter variants, achieving a sensitivity of 89.65% (95% CI: 78.16-95.72) and a specificity of 100% (95% CI: 91.87-100), with no false positives observed. Given its robustness and clinical relevance, AbsoluteQ Digital PCR is emerging as a promising tool for non-invasive molecular diagnostics targeting TERT promoter variants.

Humans↗