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PubMed2026

Association of IL-10 promoter and IL-12 gene polymorphisms with the risk of symptomatic Helicobacter pylori infection.

BACKGROUND: The host's immune response to Helicobacter pylori (H. pylori) infection is largely determined by its cytokine profile. Genetic variations within crucial immunomodulatory genes, including those for interleukin-10 (IL-10) and interleukin-12 (IL-12), are thought to influence an individual's vulnerability to the infection and its clinical consequences by modifying cytokine production. Nonetheless, research data derived from diverse human populations continue to show inconsistent results. AIM: This case-control analysis sought to examine a potential link between symptomatic H. pylori infection susceptibility in an Iranian population and specific genetic variants in the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) genes. METHODS: In this investigation, 68 individuals with confirmed symptomatic H. pylori infection diagnosed by a positive rapid urease test and elevated anti-H. pylori IgG levels exceeding 90 ng/ml via ELISA were enrolled alongside 68 healthy controls. The control group was carefully matched to the patient group based on age, sex, and ethnic background. Genotyping for the IL-10 (-1082G > A, -819 C > T) and IL-12 (+ 1188 A > C) polymorphisms was conducted using the Amplification Refractory Mutation System-PCR (ARMS-PCR) method. To evaluate associations, the distribution of genotypes and alleles between the groups was contrasted using logistic regression, applying additive, dominant, and recessive inheritance models. The strength of any association was expressed as odds ratios (ORs) accompanied by 95% confidence intervals (CIs). RESULTS: The analysis revealed no statistically significant correlations linking the investigated IL-10 and IL-12 gene variants to an increased predisposition for H. pylori infection. A notable methodological observation was the deviation from Hardy-Weinberg equilibrium (HWE) across all studied polymorphisms in the control group. Regarding the IL-10 -1082G > A locus, the AA genotype was associated with a marginally elevated risk estimate; however, this finding was not statistically significant (OR = 3.45, 95% CI: 0.29-41.36; p = 0.327). Likewise, for the IL-12 + 1188 A > C polymorphism, the CC genotype, while more prevalent in the patient cohort, also demonstrated no significant association with infection risk (OR = 1.43, 95% CI: 0.42-4.87; p = 0.567). CONCLUSION: This investigation did not establish a significant link between the specific IL-10 and IL-12 gene variants analyzed and susceptibility to symptomatic H. pylori infection in the studied population. Although minor genetic associations were noted, they lacked statistical significance. Future research with larger sample sizes is required to validate these results and to investigate additional genetic determinants that may affect infection risk.

Humans↗

PubMed2025

Innovations in Transgene Integration Analysis: A Comprehensive Review of Enrichment and Sequencing Strategies in Biotechnology.

Understanding the integration of transgene DNA (T-DNA) in transgenic crops, animals, and clinical applications is paramount for ensuring the stability and expression of inserted genes, which directly influence desired traits and therapeutic outcomes. Analyzing T-DNA integration patterns is essential for identifying potential unintended effects and evaluating the safety and environmental implications of genetically modified organisms (GMOs). This knowledge is crucial for regulatory compliance and fostering public trust in biotechnology by demonstrating transparency in genetic modifications. This review highlights recent advancements in T-DNA integration analysis, specifically focusing on targeted DNA enrichment and sequencing strategies. We examine key technologies, such as polymerase chain reaction (PCR)-based methods, hybridization capture, RNA/DNA-guided endonuclease-mediated enrichment, and high-throughput resequencing, emphasizing their contributions to enhancing precision and efficiency in transgene integration analysis. We discuss the principles, applications, and recent developments in these techniques, underscoring their critical role in advancing biotechnological products. Additionally, we address the existing challenges and future directions in the field, offering a comprehensive overview of how innovative DNA-targeted enrichment and sequencing strategies are reshaping biotechnology and genomics.

Transgenes↗

PubMed2026

Boosting β-carotene in rice and wheat grains through seed-specific expression of a modified wheat or gene.

Vitamin A deficiency is a major public health problem affecting up to 50% of the world's population, as staple food crops like wheat and rice, which are often poor in many essential micronutrients such as vitamin A, are major staple food crops. Biofortification of cereal crops with β-carotene (provitamin A) through genetic engineering is a potential solution to overcome vitamin A deficiency. The Orange (Or) protein is involved in the regulation of carotenoid accumulation and previous studies demonstrated high carotenoid accumulation due to a single-nucleotide polymorphism (SNP) in the CDS leading to substitution of Arg to His in the OR protein results in carotenoid accumulation. In the present study, we showed that this substitution of a single amino acid at position 110 (Arg to His) of wild-type wheat TaOr (referred to as TaOrHis110) increased β-carotene accumulation in transgenic wheat and rice plants overexpressing TaOrHis110 under the control of the seed-specific promoter Glu1D1. HPLC analysis revealed increase in β-carotene content in rice grain up to eightfold in case of TP309 (japonica) cultivar, 13-fold in case of IET10364 (indica) cultivar and sevenfold in wheat cv. CPAN1676. Additionally, most of the carotenoid biosynthetic pathway genes were found to be upregulated in TaOrHis110 overexpressing seeds of TP309 and IET10364, which positively correlates with maximum increase in β-carotene content.

Oryza↗

PubMed2026

High-efficiency genome-editing, transgene evaluation, and antimicrobial efficacy testing using Citrus medica L. hairy roots.

Huanglongbing (HLB) disease, associated with the fastidious bacterium Candidatus Liberibacter asiaticus (CLas), has a significant impact on citrus production worldwide. Conventional biochemical and genetic evaluation studies to identify potential disease resistance strategies have been mainly hindered due to the inability to culture CLas in a defined medium and the general recalcitrance of Citrus cultivars (grapefruits and oranges) to Agrobacterium-mediated plant transformation. We previously demonstrated the utility of plant hairy roots to co-cultivate CLas. In this study, we developed a hairy root transformation system using citron (Citrus medica L.), which is highly amenable to Rhizobium-mediated hairy root transformation. The explant survival and hairy root transformation efficiencies were up to 100% and 73%, respectively, and transgenic roots can be attained in as little as 30-60 days. We demonstrate the utility of this citron-based hairy root transformation for rapid CRISPR/Cas9-mediated gene editing, transgene evaluation, and antimicrobial efficacy testing. The citron-based hairy root transformation system will significantly help the research community to speed-track the assessment of potential HLB disease resistance strategies.

Citrus↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2025

Disruption of HaVipR1 confers Vip3Aa resistance in the moth crop pest Helicoverpa armigera.

The global reliance on Bacillus thuringiensis (Bt) proteins for controlling lepidopteran pests in cotton, corn, and soybean crops underscores the critical need to understand resistance mechanisms. Vip3Aa, one of the most widely deployed and currently effective Bt proteins in genetically modified crops, plays a pivotal role in pest management. This study investigates the molecular basis of Vip3Aa resistance in Australian Helicoverpa armigera through genetic crosses, and integrated genomic and transcriptomic analyses. We identified a previously uncharacterized gene, LOC110373801 (designated HaVipR1), as potentially important in Vip3Aa resistance in two field-derived resistant lines. Functional validation using CRISPR/Cas9 knockout in susceptible lines confirmed the gene's role in conferring high-level resistance to Vip3Aa. Despite extensive laboratory selection of Vip3Aa-resistant colonies in Lepidoptera, the biochemical mechanisms underlying resistance have remained elusive. Our research identifies HaVipR1 as a potential contributor to resistance, adding to our understanding of how insects may develop resistance to this important Bt protein. The identification of HaVipR1 contributes to our understanding of potential resistance mechanisms and may inform future resistance management strategies. Future work should explore the biochemical pathways influenced by HaVipR1 and assess its interactions with other resistance mechanisms. The approach utilized here underscores the value of field-derived resistant lines for understanding resistance in agricultural pests and highlights the need for targeted approaches to manage resistance sustainably.

Animals↗

PubMed2026

Enhanced Cas12i3 system enables precise OsAUX3 editing for rice grain improvement.

An optimized Cas12i3 genome-editing system enables highly efficient and predictable editing of regulatory sequences in rice. Precise promoter engineering fine-tunes gene expression, improves grain size, and enhances production potential, demonstrating a powerful new approach for crop improvement through targeted regulation rather than gene disruption.

Oryza↗

PubMed1979

Efficient cap-dependent translation of polycistronic prokaryotic mRNAs is restricted to the first gene in the operon.

Certain polycistronic prokaryotic mRNAs, when modified at their 5'-termini with a cap structure, are translated as efficiently as, or more efficiently than eukaryotic mRNAs in a eukaryotic cell-free protein synthesising system. However, in this case efficient cap-dependent translation is apparently restricted to the 5'-proximal coding sequence. Moreover, certain translational regulatory signals potentially used by these prokaryotic mRNAs to regulate their levels of expression seem to be recognised by the eukaryotic translational components. The evolutionary significance and practical implications of these results are discussed.

Base Sequence↗

PubMed2024

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.

Cohesin complexes carrying STAG1 or STAG2 organize the genome into chromatin loops. STAG2 loss-of-function mutations promote metastasis in Ewing sarcoma, a pediatric cancer driven by the fusion transcription factor EWS::FLI1. We integrated transcriptomic data from patients and cellular models to identify a STAG2-dependent gene signature associated with worse prognosis. Subsequent genomic profiling and high-resolution chromatin interaction data from Capture Hi-C indicated that cohesin-STAG2 facilitates communication between EWS::FLI1-bound long GGAA repeats, presumably acting as neoenhancers, and their target promoters. Changes in CTCF-dependent chromatin contacts involving signature genes, unrelated to EWS::FLI1 binding, were also identified. STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, likely affecting DNA looping dynamics. These results illuminate how STAG2 loss modifies the chromatin interactome of Ewing sarcoma cells and provide a list of potential biomarkers and therapeutic targets.

Sarcoma, Ewing↗

PubMed2026

Expression dynamics of mCry3A and eCry3.1Ab transgenes in Bt corn hybrids across growth and environments.

In 2017 and 2018, studies were conducted in Iowa, US across three environments with a history of greater than expected corn rootworm injury i.e., greater than one node of injury to (US EPA 2009) and one environment without rootworm injury, and at different growth stages, to determine the expression levels of mCry3A and eCry3.1Ab transgenes in the roots of different Bt corn hybrids namely the molecular stack (MZIR098), breeding stack (MIR604 × 5307), 5307 and MIR604. ELISA results showed that expressions of both mCry3A and eCry3.1Ab transgenes, were higher in the MZIR098 molecular stack and breeding stack (MIR604 × 5307), than the MIR604 and 5307 at V3 and VT growth stages over both years. To protect the roots from feeding damage by the corn rootworm larvae, expression of the transgenes must be high at the V3 growth stage. The expression of the transgene was significantly impacted by the stage of plant growth while the environments with greater than expected corn rootworm injury did not impact expression of the transgenes. It was found that the expression of mCry3A and eCry3.1Ab transgenes were high at the V3 plant growth stage compared to the VT growth stage. Stacking two or more genes together in the same plant such as the molecular and breeding stacks have the potential to protect roots in environments with higher-than-expected damage and slow down the evolution of resistance in field populations of rootworms.

Zea mays↗

PubMed2026

Widespread marine and freshwater distributions of active sulfoquinovose-degrading bacteria.

Sulfoquinovose (SQ), a sulfonated sugar produced on a gigaton scale each year, contributes to global sulfur cycling, yet the microbes and pathways mediating its turnover in the environment have been inferred largely from genomic potential rather than direct activity. Here, we coupled incubations of environmental samples with 13C-labeled SQ to DNA-stable isotope probing to identify active SQ carbon assimilators across estuary, mangrove, and lake ecosystems. In estuarine communities, Vibrio and Cognatishimia incorporated SQ-derived 13C; Novosphingobium dominated in the mangrove, and Agrobacterium in the lake. Pure-culture experiments, coupled with comparative proteomics and gene knockout validation, demonstrated that Vibrio strains degrade SQ via modified sulfoglycolytic Embden-Meyerhof-Parnas and Entner-Doudoroff pathways to produce the environmentally significant organosulfur 2,3-dihydroxypropanesulfonate. Comparative genomic analyses suggested that closely related genome representatives of Novosphingobium, Cognatishimia, and Agrobacterium encode the sulfolytic SQ monooxygenase pathway. A global survey of aquatic microbial genomes indicated that over 9% harbor SQ degradation clusters, supporting a widespread distribution of bacterial SQ catabolic potential in aquatic environments.

Fresh Water↗

PubMed1975

The effects of 5-fluorouracil and 5-fluorodeoxyuridine used alone and in combination with normal nucleic acid precursors on development of mice in lines selected for low and high expression of Strong's luxoid gene.

Pregnant female mice selected for plus- and minus-modifying genes of the limb-skeleton effects of Strong's luxoid gene (1st) were injected ip on day 10 of gestation with 10 or 20 mg/kg 5-fluorouracil (5-FU) or 5-fluorodeoxyuridine (5-FUdR). The incidence and degree of expression of the effects (polydactyly, ectrodactyly, radial hemimelia, tibial hemimelia, pelvic girdle shifts, deformed caudal vertebrae) varied according to the teratogen and dose level. The addition of an equimolecular amount of thymidine, thymine, or uracil greatly potentiated the effects of 20 mg/kg 5-FU, usually resulting in death of the embryos. The addition of an equimolecular amount of thymidine but not of the embryos. The addition of an equimolecular amount of thymidine but not of thymine or uracil partly protected against the effects of 5-FUdR. Both teratogens increased the expression of ist on the limb skeleton. The interactions of the teratogens with the major gene were inhibited by minus- and promoted by plus-modifying genes of 1st. The effects of the teratogenic treatments may be mediated by cell death.

Abnormalities, Drug-Induced↗

PubMed2026

Magnetic nanoparticle-mediated genetic transformation and gene editing system in loquat (Eriobotrya japonica).

Loquat (Eriobotrya japonica Lindl.) is a valuable subtropical fruit tree whose genetic improvement has been significantly constrained by the absence of an efficient genetic transformation system. Although Agrobacterium-mediated transformation is the most widely used method, it proves ineffective in loquat due to the species' recalcitrance to in vitro regeneration. Pollen-based transformation offers a promising alternative by bypassing the need for tissue culture. However, the pollen wall poses a major physical barrier to the uptake of exogenous DNA. In this study, we investigated magnetic nanoparticle (MNP)-mediated transformation as a novel strategy for loquat. We confirmed that loquat pollen contains tricolporate apertures with diameters ranging from 3.0 to 5.0 μm, which are structurally suitable for the entry of MNPs-DNA. Based on this finding, we developed and optimized a transformation protocol using polyethyleneimine-coated Fe3O4 nanoparticles to deliver genetic material into loquat pollen grains. Using this approach, we successfully generated stable transgenic loquat lines, including both overexpression and gene-edited mutants. To our knowledge, this is the first report of successful MNP-mediated pollen transformation in a woody plant species. This work establishes a robust and efficient genetic transformation platform for loquat, providing a valuable tool for functional genomics and molecular breeding, as well as a potentially applicable strategy for other recalcitrant woody plants.

Eriobotrya↗

PubMed2025

Antisense oligonucleotide-mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington's disease iPSC-derived striatal neurons.

Expanded CAG alleles in the huntingtin (HTT) gene that cause the neurodegenerative disorder Huntington's disease (HD) are genetically unstable and continue to expand somatically throughout life, driving HD onset and progression. MSH3, a DNA mismatch repair protein, modifies HD onset and progression by driving this somatic CAG repeat expansion process. MSH3 is relatively tolerant of loss-of-function variation in humans, making it a potential therapeutic target. Here, we show that an MSH3-targeting antisense oligonucleotide (ASO) effectively engaged with its RNA target in induced pluripotent stem cell (iPSC)-derived striatal neurons obtained from a patient with HD carrying 125 HTT CAG repeats (the 125 CAG iPSC line). ASO treatment led to a dose-dependent reduction of MSH3 and subsequent stalling of CAG repeat expansion in these striatal neurons. Bulk RNA sequencing revealed a safe profile for MSH3 reduction, even when reduced by >95%. Maximal knockdown of MSH3 also effectively slowed CAG repeat expansion in striatal neurons with an otherwise accelerated expansion rate, derived from the 125 CAG iPSC line where FAN1 was knocked out by CRISPR-Cas9 editing. Last, we created a knock-in mouse model expressing the human MSH3 gene and demonstrated effective in vivo reduction in human MSH3 after ASO treatment. Our study shows that ASO-mediated MSH3 reduction can prevent HTT CAG repeat expansion in HD 125 CAG iPSC-derived striatal neurons, highlighting the therapeutic potential of this approach.

Huntington Disease↗

PubMed2026

Maternal secretor status and human milk oligosaccharides influence the infant gut resistome.

The infant gut resistome is established early in life and is shaped by perinatal exposures, yet the mechanisms underlying its modulation remain unclear. We combined shotgun metagenomics of fecal samples from 57 one-month-old infants and paired milk samples from 50 mothers in the MAMI cohort to investigate the influence of maternal secretor status on early-life resistome development. Longitudinal follow-up at 6 and 12 months, and also further validation in the independent Lifelines NEXT (LLNEXT) cohort, support our findings. Cesarean section (C-section) was associated with increased antibiotic resistance gene (ARG) diversity, whereas exclusive breastfeeding reduced ARG abundance and diversity. Maternal secretor status further modified resistome composition among exclusively breastfed infants. Human milk oligosaccharide profiling identified specific glycans underlying these associations, with 2'-fucosyllactose and 6'-sialyllactose showing negative correlations with distinct ARG classes. These findings identify human milk composition as a key determinant of early-life resistome assembly and a potential target for modulating antimicrobial resistance.

Humans↗

PubMed2026

The durable resistance gene Tm-22 remains partially resistant to tomato brown rugose fruit virus.

The tomato Tm-22 gene is a highly effective, and durable resistance gene in agriculture that has protected tomato production against viruses of the Tobamovirus genus, such as tomato mosaic virus (ToMV) and tobacco mosaic virus (TMV) for over 60 years. This dominant R gene, originally sourced from wild tomato species (Solanum peruvianum), acts by recognizing the viral movement protein (MP) and triggering an immune response, often resulting in extreme resistance (ER). However, this durable protection is challenged by a recently emerged new tobamovirus named tomato brown rugose fruit virus (ToBRFV, Tobamovirus fructirugosum). ToBRFV-encoded MP is responsible for ER breakdown. Here, we present evidence that while ToBRFV can evade Tm-22-mediated ER, Nicotiana benthamiana and tomato plants carrying Tm-22 still remain partially resistant to ToBRFV. We show that ToBRFV MP is recognized by and interacts with Tm-22 to trigger an attenuated hypersensitive response. Moreover, we discover that overexpression of Tm-22 can enhance resistance to ToBRFV. These findings demonstrate the practical value of Tm-22 in ongoing resistance breeding programs and open a potential avenue to restore Tm-22 immunity through upregulation of Tm-22 expression.

Solanum lycopersicum↗

PubMed2026

Advances in CRISPR multiplex gene editing to map and modify stress-responsive transcription factor networks for crop improvement.

The development of CRISPR multiplex genome-editing (MGE) tools is rapidly transforming plant functional genomics and accelerating crop improvements. By simultaneously targeting two or more DNA loci, it allows scientists to precisely edit multiple genes at the single-nucleotide level, within the target genome. Simultaneous manipulation of multiple targets has revolutionized the functional elucidation studies, particularly the dissection of complex genetic pathways. Due to its superior precision and feasibility, CRISPR-MGE is widely accepted and has largely replaced alternative editing tools such as TALENs and ZFNs. Several CRISPR-MGE strategies, including the use of individual expression cassettes, tRNA-processing enzymes, Csy4 or ribozymes, have been successfully deployed in plants. Recent advancements, such as Cpf1, transgene-free methods, or ultra-multiplexing approaches, have further refined the technology into a powerful, efficient, and robust toolkit. MGE enables complex genome editing, including multiple-gene knockouts, base alterations, transcriptional regulation, metabolic engineering, or their combinations. Consequently, it is ideal for elucidating the function of transcription factors that are key molecular players in regulating diverse plant responses, especially in stress pathways. Several stress-responsive TFs have been functionally characterized via CRISPR-MGE, and more advanced tools are being employed. This review evaluates multiplexing tools, their diverse applications, and the current progress toward developing advanced MGE tools. Ultimately, we provide evidence to encourage the use of advanced MGE tools for functional characterization studies of stress-responsive TFs, thereby highlighting their potential to accelerate crop improvement.

Gene Editing↗

PubMed2026

Genomic Characterization of ETV6::RUNX1-Positive Childhood B-ALL in a Chinese Cohort: Novel Fusion Partners, Co-Occurring Mutations, and Risk-Stratifying Biomarkers.

BACKGROUND: ETV6::RUNX1 is the most common genetic abnormality in pediatric B-cell acute lymphoblastic leukemia (ALL; ∼25%), yet the comprehensive genetic architecture and molecular predictors of intermediate-risk (IR) stratification remain incompletely characterized. METHODS: We performed whole-transcriptome sequencing (Illumina NovaSeq 6000, rRNA depletion, 41.70 Gb/sample) on bone marrow samples from 93 pediatric ETV6::RUNX1-positive B-ALL patients. Bioinformatics analysis included STAR alignment, MuTect2 variant calling, FusionCatcher fusion detection, and VEP annotation. The Jaccard index with permutation testing assessed mutation co-occurrence; logistic regression identified independent predictors of IR classification. RESULTS: Beyond ETV6::RUNX1, we identified 51 distinct fusion genes across the cohort, including the reciprocal RUNX1-ETV6 (73.1%), chr8::KLF1210 (38.7%), and KLF12-chr8 (34.4%). Somatic mutations in 249 genes were detected; the most frequent were KIAA1715 (17.2%), KRAS (11.8%), and NSD2 (10.8%). Network analysis revealed significant chromatin modifier co-occurrence (KIAA1715-KMT2C: J = 0.136, p = 0.015) and KRAS-NRAS mutual exclusivity (J = 0.000, p = 0.042). PTCH1 (OR = 3.50, 95% CI 0.21-58.49, p = 0.41) and GNB1 (OR = 6.5, 95% CI 1.2-34.8, p = 0.029) mutations independently predicted IR classification. chr8::KLF1210 fusion correlated with higher Day-19 MRD levels (p = 0.038). CONCLUSIONS: GNB1 mutation represents a novel independent predictor of IR stratification in ETV6::RUNX1-positive B-ALL. The chromatin modifier co-occurrence module and extensive fusion architecture reveal biological heterogeneity within this favorable-risk subtype, with potential implications for risk-adapted therapeutic strategies.

B‐ALL↗