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PubMed2026

Simultaneous detection of glyphosate and glufosinate target-site resistance in Eleusine indica via multiplex TaqMan qPCR.

BACKGROUND: Continuous use of glyphosate followed by glufosinate-ammonium has selected for multiple resistance to both herbicides in Eleusine indica worldwide. Managing such resistant weeds requires fast, accurate molecular detection assay. To address this critical need, we developed a robust multiplex TaqMan quantitative (q)PCR assay that simultaneously detects five well-characterized target-site resistance markers in E. indica: EPSPS copy number variation; T102I in EPSPS; P106A and P106S in EPSPS; and S59G in GS1-1. RESULTS: The multiplex qPCR assay showed analytical specificity when tested on genomic DNA from nine reference accessions: three susceptible, three glyphosate-resistant (with EPSPS CNV) and three multiple-resistant. Subsequent analysis of 56 field-collected samples demonstrated 98.2% concordance (55 of 56) with Sanger sequencing across all five resistance-associated markers: EPSPS CNV, T102I, P106A, P106S and GS1-1 S59G, confirming the reliability and practical value of the multiplex qPCR assay. Only samples 7-8 showed discordance at EPSPS position 102, where Sanger chromatograms showed overlapping peaks at this position, which is likely to be a result of heterozygous mutation distribution among amplified EPSPS gene copies. This case further underscores the advantages of the multiplex qPCR assay over Sanger sequencing in detection sensitivity and accuracy. Moreover, a strong correlation (R2 = 0.8935) in gene copy number estimation between the two methods across all samples further supports the reliability of the qPCR assay. CONCLUSIONS: In summary, this study delivers a simple, robust and high-throughput diagnostic tool for the rapid, simultaneous identification of dual herbicide target-site resistance in goosegrass, offering superior sensitivity, quantitative resolution and throughput compared with Sanger sequencing. © 2026 Society of Chemical Industry.

Herbicides↗
PubMed2026

Target-Site Selection by Transcription Factors: Roles of DNA, Chromatin, and Cofactor-Mediated Regulation.

Transcription factors (TFs) are sequence-specific DNA-binding proteins that regulate gene-expression programs and cell fate. The ability of a defined combination of four TFs to reprogram differentiated cells into induced pluripotent stem cells illustrates the powerful role of TFs in determining cellular identity. However, TFs usually recognize short and degenerate DNA motifs of approximately 6-12 base pairs, generating thousands to millions of potential motif matches in mammalian genomes. In living cells, TFs occupy only a restricted subset of these sites, indicating that motif presence alone is insufficient for functional target selection. Several layers of regulation contribute to this selective occupancy, including DNA methylation, nucleosome organization, histone modifications, chromatin remodeling, TF oligomerization, TF availability and localization, and cofactors that regulate DNA-binding domains. This review outlines how DNA/chromatin features and TF-centered mechanisms contribute to target-site selection. The principal aim is to highlight DNA-binding domain-directed cofactor regulation as an underappreciated mechanism that modulates TF-DNA binding and may help explain selective genomic occupancy.

Target-site selection↗
PubMed2026

Historical metabolic adaptation potentiates the rapid evolution of flonicamid resistance in Myzus persicae.

Rapid adaptation to novel environments is often shaped not only by newly acquired mutations but also by historical genetic backgrounds established through prior evolutionary events. However, the extent to which such historical contingency contributes to the rapid evolution of insecticide resistance remains poorly understood. Here, we investigated the emergence of resistance to flonicamid, a recently deployed insecticide, in the green peach aphid, Myzus persicae. We show that constitutive overexpression of the P450 enzymes CYP6CY3 and CYP6CY4, already widespread in populations of M. persicae before flonicamid deployment, confers a previously cryptic tolerance phenotype to flonicamid. However, biochemical and transgenic analyses demonstrated that these metabolic adaptations provide only weak protection against flonicamid. Following flonicamid deployment, however, a novel target-site mutation, NaamV251I, in the recently identified molecular target of 4-trifluoromethylnicotinamide (TFNA-AM), emerged in M. persicae on a genetic background of CYP6CY3 or CYP6CY4 overexpression. Structural modeling, enzymatic assays, and CRISPR-Cas9 genome editing demonstrated that this mutation reduces target sensitivity and independently confers moderate resistance. Strikingly, combining the nicotinamidase (Naam) mutation with pre-existing CYP6CY3 or CYP6CY4 overexpression produced substantially elevated resistance phenotypes that far exceeded the effects of either mechanism alone. Our results demonstrate that the pre-existing metabolic background did not itself evolve further following flonicamid deployment but fundamentally altered the phenotypic consequences of a subsequently acquired target-site mutation. These findings provide direct evidence that historical adaptive variation can potentiate rapid resistance evolution to newly introduced insecticides and reveal how interactions between past and contemporary adaptations shape evolutionary responses to novel environmental challenges.

Animals↗
PubMed2026

Herbicide Resistance Genes in Crops: Mechanisms, Progress, and Future Perspectives.

While previous reviews have largely focused on individual crops or single target-site mechanisms, the full-chain comparative landscape across major cereal crops remains unexplored. Here, we fill this critical gap by providing the first systematic, cross-crop comparative review that spans herbicide targets, resistance mechanisms, and breeding applications across four major cereals-rice, maize, wheat, and sorghum. Weed infestation is a serious constraint on crop production. Chemical weed control faces challenges such as herbicide resistance evolution and ecological risks. Developing herbicide-resistant varieties is a fundamental approach to achieve green and sustainable weed management. This review systematically summarizes research progress on herbicide resistance genes from three aspects: herbicide classification, resistance mechanisms, and crop breeding applications. It highlights key differences among four major cereal crops (rice, maize, wheat, and sorghum) in resistance-gene discovery and translational progress. Rice has the richest target-site resistance-gene resources. Maize leads in commercialization of transgenic herbicide resistance. Wheat focuses on endogenous precise editing due to genome complexity and regulatory constraints. Sorghum relies on specific mutations to serve cereal-legume intercropping systems. Based on this comparison, this review identifies the core trends in resistance breeding: from single-gene to multi-gene stacking, and from exogenous gene introduction to endogenous gene editing. It also points out common bottlenecks, including insufficient systematic mining of resistance-gene resources, lagging elucidation of non-target-site resistance regulatory networks, and strong genotype dependence in genetic transformation. Future efforts should focus on exploring broad-spectrum resistance genes, optimizing precise editing technologies, and developing sustainable resistance management strategies. This review provides a theoretical framework and practical references for molecular breeding of herbicide-resistant crops.

crop breeding↗
PubMed2026

Primer design for the voltage-gated sodium channel, the pyrethroids' target site, in the triatomine vector Triatoma infestans (Hemiptera: Reduviidae).

Resistance to pyrethroid insecticides has become more frequent in triatomines, associated with point mutations in their target site, the voltage-gated sodium channel (VGSC). These mutations have been reported in Argentina, Bolivia and Mexico, by means of nested PCR. In Chile, the repeated intradomiciliary presence of the vector Triatoma infestans after spraying may be related to resistance; however, target-site mutations have yet to be evaluated. Using a partial sequence of the VGSC as a search query for the T. infestans genome, the complete VGSC gene sequence was obtained. Ten primer pairs were generated with Primer-BLAST and tested in silico by BLAST against the T. infestans genome and against the NCBI nucleotide database (nr) to discard those with low specificity. Conventional PCRs were performed with T. infestans' DNA and the remaining primers, selecting one pair based on sensitivity and the absence of nonspecific bands. The 993 bp sequenced product allows for the evaluation of the three point mutations reported in the VGSC of triatomines. Primer validation was performed with L925I mutation-positive samples from Argentina. Chilean samples from five localities were also amplified and Sanger sequenced in search of mutations. The L925I mutation was detected only in the Argentinean controls. None of the variants evaluated were found in the Chilean samples. These primers will allow rapid evaluation of point mutations in the VGSC, which may be associated with reduced affinity of pyrethroids for their target site; thereby facilitating insecticide resistance surveillance.

Animals↗
PubMed2026

Retrotransposon-based mechanisms for transgene addition to the human genome.

When human disease arises from a loss of function caused by diverse mutant alleles of the same gene, the patient population could be best served by a clinical therapy that achieves genome safe-harbor supplementation with a functional transgene. Until recently, transgene delivery strategies have shared the disadvantages of induced immune responses and/or genome mutagenesis from untargeted DNA insertion. As a different strategy, several groups recently described the use of retrotransposon proteins to accomplish transgene insertion by RNA-templated cDNA synthesis directly into the genome. In some strategies, gene insertion relies on the retrotransposon protein to bring a transgene-encoding template RNA to the target site. Retrotransposon protein positioning of template RNA for cDNA synthesis minimizes the requirement for RNA base-pairing to target-site DNA. This review presents an overview of RNA-templated DNA synthesis in cells as backdrop for describing recent uses of retrotransposon reverse transcriptases to supplement the human genome.

Journal Article↗
PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗
PubMed2026

The genomic alchemist's arsenal: A comprehensive review of gene recruitment, regulatory rewiring, and the evolutionary arms race in snake envenomation.

Snake venom represents a striking example of evolutionary innovation, in which ancestral physiological gene networks have been co-opted into potent biochemical weapons. Advances in multi-omics, single-cell genomics, and structural bioinformatics have catalyzed a conceptual shift from descriptive toxin cataloging to a systems-level understanding of venom evolution, regulation, and function. This Review integrates genomic, cellular, and structural perspectives to delineate the molecular architecture underpinning venom diversification and target-site co-evolution. Emphasis is placed on regulatory mechanisms driving rapid expression plasticity, including super-enhancer activity, transposable element insertion, spatial heterogeneity within the venom gland, and non-coding RNA-mediated modulation. At the protein level, the review examines how hypervariable toxins engage in structural arms races with prey targets, and how multi-toxin complex formation, functional synergy, and molecular dynamics simulations inform models of lethality and resistance. A comparative framework is provided by contrasting high-potency predatory snake venoms with low-potency defensive venoms of hymenopterans such as bees and wasps, revealing how ecological selective pressures shape toxin potency, composition, and target specificity across taxa. Finally, current translational strategies are evaluated, with a focus on the relative merits of recombinant human monoclonal antibodies versus catalytic-site small-molecule inhibitors as deployable interventions for snakebite. By synthesizing evolutionary genomics, structural biology, comparative toxinology, and synthetic antivenomics, this Review outlines a predictive framework for anticipating venom evolutionary trajectories and for designing broad-spectrum, next-generation therapeutics.

Animals↗