Search Results (3,973)

Plum pox virus (PPV) is one of the most destructive pathogens affecting stone fruit trees. It causes sharka disease and severe yield losses. The genetically modified plum cultivar ‘HoneySweet’ was developed to provide long-lasting resistance to PPV via RNA interference. Long-term field trials of ‘HoneySweet’ have been conducted in the Czech Republic since 2001, involving the artificial inoculation of the cultivar with PPV alone, and with apple chlorotic leaf spot virus (ACLSV) and prune dwarf virus (PDV) in combination. This study evaluates the impact of viral infection on tree growth after 24 years in the field. Growth parameters—trunk cross-sectional area (TCSA) and canopy volume—were measured and analysed using ANOVA and Tukey’s test. The results show that infected trees exhibit significantly reduced growth compared to non-infected controls, with the strongest inhibition observed in trees inoculated with PPV + PDV + ACLSV. The presence of ACLSV had the most pronounced negative effect on growth, while PDV did not significantly influence tree vigour. These findings emphasise the importance of using virus-free rootstocks and certified planting material to prevent growth suppression in HoneySweet orchards. Full article

End-stage kidney disease (ESKD) is a global health challenge, with kidney transplant demand outstripping supply. Allotransplantation remains the gold standard for treatment but organ scarcity leads to prolonged waiting times and high mortality. Xenotransplantation, using genetically modified porcine kidneys, offers a novel and potentially sustainable solution. Genetic engineering and immunosuppression advances have enabled xenotransplantation to transition from a theoretical possibility to feasible solution. This review explores the evolution of xenotransplantation, the scientific advancements in overcoming immunological barriers, and emerging clinical data. Furthermore, we discuss emerging approaches such as central immune tolerance induction, the ongoing risks of cross-species infection, and the ethical and environmental considerations inherent to scaling up porcine organ donation. With the commencement of the first formal clinical trials, progress in the field could transform kidney transplantation, though questions remain regarding long-term outcomes and societal impact. Full article

This study presents an integrated workflow for the multiobjective optimization of directional well trajectories in underground gas storage (UGS) reservoirs. A modular well-path construction model is developed, enabling flexible assembly of linear and curved segments in a local reference frame and their transformation into the reservoir. The optimization problem is formulated to simultaneously maximize working-gas capacity and minimize total drilling length for ten new directional wells. A calibrated UGS reservoir with more than 30 years of production history is used as the simulation environment, and solution quality is explored using the NSGA-II (non-dominated sorting genetic algorithm) evolutionary algorithm. The results reveal a diverse Pareto front of feasible designs. The best configurations achieve either an 8.6% reduction in total drilling length while still delivering a 2.12% capacity increase, or a 3.18% capacity enhancement at a modest drilling-length increase of 4%. These outcomes demonstrate that strategic redesign of well trajectories alone can deliver measurable improvements in UGS performance without modifying well controls or facility constraints. The proposed methodology provides a generalizable and computationally efficient framework for large-scale multiwell planning in UGS systems. Its modularity supports future extensions, including collision avoidance, perforation optimization, and adaptive well-control strategies. Full article

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle that contains a unique apolipoprotein(a) [apo(a)] component covalently bound to apolipoprotein B-100. Elevated levels of Lp(a) have been identified as a well-established and genetically determined risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, and calcific aortic valve stenosis. In contrast to other lipids, Lp(a) concentrations are minimally influenced by lifestyle or traditional lipid-lowering therapies, emphasizing the necessity for novel treatment approaches. This narrative review summarizes current and emerging therapeutic strategies for reducing Lp(a) levels. Such strategies include traditional agents such as niacin and PCSK9 inhibitors, as well as innovative therapies such as antisense oligonucleotides, RNA interference-based molecules, and small-molecule inhibitors. The mechanisms of action of these agents, in addition to clinical trial data and their capacity to modify cardiovascular outcomes, are explored in further detail. Furthermore, the current status of clinical guidelines and the evolving role of Lp(a)-targeted therapies in cardiovascular risk stratification are reviewed. A particular emphasis is placed on therapies that are in the advanced stages of clinical development. These include late-phase outcome trials and orally administered agents, which have the potential to significantly impact future clinical practice. The integration of mechanistic data with ongoing and completed clinical studies has been undertaken in order to provide a comprehensive framework for understanding the therapeutic potential of Lp(a) in the context of cardiovascular prevention. Full article

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by loss-of-function mutations in the dystrophin gene, leading to progressive muscle degeneration, motor decline, respiratory compromise, and cardiomyopathy. Diagnosis typically occurs in early childhood following recognition of motor delays, markedly elevated creatine kinase, and confirmatory genetic testing. Over the past decade, the therapeutic landscape for DMD has expanded substantially, evolving from exclusively supportive care to patient-centric multifaceted treatment paradigms, including corticosteroids, mutation-specific therapies, small molecule disease-modifying approaches, and gene replacement strategies. Despite these advances, no currently available therapy restores full-length dystrophin or completely halts disease progression. This review provides a clinically oriented comprehensive overview of currently Food and Drug Administration (FDA)-approved medications for DMD, with particular emphasis on corticosteroids, exon-skipping therapies, nonsense mutation readthrough agents, recently approved gene therapy, and select ongoing gene therapy trials. We summarize mechanisms of action, clinical efficacy, safety considerations, regulatory status, and highlight the challenges of integrating these therapies into longitudinal care. Through illustrative clinical vignettes, we highlight the real-world complexity of treatment selection, shared decision-making, and longitudinal care planning in contemporary DMD management. Full article

The overreliance on chemical pesticides in sub-Saharan African (SSA) for agriculture poses major challenges to sustainable agriculture, ecosystem and human health, biodiversity, and environmental sustainability. While genetically modified (GM) crops have demonstrated potential to lower pesticide use and increase crop yield, their widespread adoption remains limited across SSA, with gaps in knowledge on their yield, benefits and policies impacting their uptake. In this study, a literature-based approach was used to synthesize evidence from peer-reviewed articles and government reports published between 2010 and 2025 on pesticide use, farm productivity, and wellbeing of farmers across three focus countries: Nigeria, South Africa, and Burkina Faso. The summary of approved GM crops, events and utilisation across the three focus countries was also retrieved from the International Service for the Acquisition of Agri-biotech Applications (ISAAA) database. Cross-country comparisons were conducted to highlight lessons learned from successful and stalled GM crop programs and to identify regulatory, socio-cultural, and economic factors shaping adoption. It is shown that while GM crops can significantly reduce pesticide usage and production costs, challenges such as public hesitancy, regulatory hurdles, limited farmer awareness, and concerns about ecological consequences continue to hinder wider uptake across the continent. Similarly, weak seed systems and the lack of regionally harmonized biosafety regulations also constrain adoption. In areas where GM crops have been successfully adopted, it was demonstrated that supportive policy frameworks, transparent biosafety regulations, effective seed certification and distribution systems, and sustained community engagement increased farmer confidence and accelerated adoption. Hence, for GM crops to be more widely adopted for sustainable crop protection in sub-Saharan Africa, governments and stakeholders must strengthen biosafety systems, invest in farmer education, promote regional regulatory coordination, and facilitate public–private partnerships. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) arises predominantly from activating KRAS mutations, yet individual genetic variants differ markedly in signaling output and clinical impact. G12D, the most prevalent variant, strongly drives oncogenic programs, whereas G12R signals less efficiently through the AKT and ERK pathways and is associated with longer patient survival than G12D-driven PDAC. Methods: To elucidate how these differences influence early cellular transformation, we expressed a panel of KRAS mutants in non-cancerous pancreatic ductal epithelial cells as a model of early PDAC initiation and profiled transcriptional and phospho-proteomic responses. We next examined whether epigenetic differences translate into mutation-specific changes in nuclear organization using quantitative imaging of G12D- and G12R-expressing nuclei at 24 and 48 h. Results: Each variant established a unique regulatory program enriched for chromatin remodelers, histone modifiers, and nuclear structural factors, indicating that variant-specific KRAS signaling rapidly develops divergent epigenetic states. Integrated transcriptomic and phospho-proteomic analyses identified G12D and G12R as the most divergent variants. G12D induced pronounced nuclear remodeling, including increased nuclear size, irregular morphology, and reorganization of the nucleolus and spliceosome, consistent with extensive chromatin and transcriptional reprogramming. In contrast, G12R elicited a weaker response, with minimal or delayed structural changes. Conclusions: Together, these findings demonstrate that KRAS mutational context in pancreatic ductal epithelial cells shapes early transcriptional reprogramming that actively remodels nuclear architecture and nuclear sub-compartments. This work establishes nuclear structural remodeling as a structural state of KRAS-driven epigenetic dysregulation during PDAC initiation. Full article

Diet is a major, modifiable determinant of cardiometabolic, cancer, and inflammatory disease risk, yet individuals frequently exhibit substantial heterogeneity in metabolic and clinical responses to similar dietary exposures. Genetic susceptibility and its interplay with diet plausibly contribute to this variability, motivating gene–diet (G×D) interaction research and the broader ambition of precision nutrition. Translation has lagged, however, because interaction effects are typically modest, context-dependent, and difficult to reproduce, particularly in the presence of pervasive dietary measurement error, heterogeneous exposure definitions, and stringent multiplicity correction. A methodologically oriented synthesis is presented across eight domains of contemporary G×D epidemiology: classical regression interaction models; efficient study designs; dietary assessment and measurement error; dietary patterns, mixtures, and non-linear modeling; genome-wide and polygenic approaches; causal inference frameworks; multi-omics integration; and machine learning. Central concepts include the recognition that “interaction” is a scale-dependent estimand and that transparent reporting of coding choices and effect-modification metrics—including additive interaction when relevant for public health interpretation—is essential. Credible inference further depends on high-quality, harmonized dietary phenotyping with explicit energy adjustment and, where feasible, biomarker calibration, alongside robust control of population structure and gene–diet correlation using ancestry adjustment, mixed models, and family-based designs. Genome-wide and polygenic risk-based approaches expand discovery potential but require disciplined multiplicity strategies, discovery-replication workflows, and explicit evaluation of portability and equity across ancestries. Causal inference methods can strengthen etiologic interpretation when assumptions are defensible and sensitivity analyses are routinely implemented. Multi-omics and machine learning may enhance mechanistic and predictive insight, but only under rigorous quality control, validation, and reproducible pipelines. Overall, harmonized measurement, clear estimands, multi-ancestry replication, and integrated evidence pipelines are pivotal for producing robust and actionable G×D evidence. Full article

Modern agriculture is undergoing a paradigm shift toward eco-friendly methodologies that enhance seed material quality while minimizing chemical inputs. This study evaluates the impact of Effective Microorganism (EM) exposure (variants E1 and E2) on the morpho-physiological parameters and phytosanitary health of potato tubers. The primary objective was to determine the efficacy of microbial priming in suppressing the infection rates of Streptomyces scabies (common scab) and Rhizoctonia solani (black scurf) across 14 genetically diverse cultivars. A three-year field experiment (2019–2021) was conducted using a split-plot design with three replications. The study analyzed the interaction between EM exposure times and the genetic resistance potential of the selected cultivars. Statistical analysis confirmed that pre-planting microbial treatments significantly inhibited pathogen development. EM applications (E1 and E2) reduced the infection rates of both S. scabies and R. solani through an “escape mechanism,” whereby treated tubers exhibited accelerated biomass accumulation and reached physiological maturity before peak pathogen pressure. Furthermore, treatments optimized the physiological state and vigor of the tubers, establishing a robust physiological barrier against soil-borne infections. The application of EMs proves to be a highly effective, non-invasive biostimulation method. A significant difference was observed in the responding varieties between EM treatments and the cultivars innate genetic resistance, particularly in cultivars with higher baseline resistance. The use of EM biostimulants significantly modifies the health of tubers, and the direction of these changes is strictly determined by the variety factors. The results suggest that microbial priming not only enhances plant growth kinetics but also induces systemic resistance, offering a viable ecological alternative to traditional chemical seed dressings in sustainable potato production. Full article

Background: Acquired epidermodysplasia verruciformis (AEV) is a rare cutaneous disorder arising in immunocompromised individuals. AEV is characterized by flat-topped, wart-like, or hypopigmented lesions predominantly on sun-exposed areas. Unlike classic genetic EV, AEV develops in the absence of germline mutations or family history. AEV most commonly arises in patients receiving iatrogenic immunosuppressive therapy for organ transplantation, autoimmune disease, or hematologic disorders. Methods: A comprehensive literature review was conducted via the PubMed database. Case reports and case series studies describing AEV in transplant and non-transplant iatrogenic immunosuppression were identified through a literature search. There were no restrictions on language or publication year. The last search was conducted in July 2025. Reports were analyzed for patient demographics, immunosuppressive agents, HPV subtypes, clinical and histopathologic features, and treatment outcomes. Results: AEV occurs across a broad spectrum of immunosuppressive therapies, including calcineurin inhibitors, antimetabolites, biologics, tyrosine kinase inhibitors, and cytotoxic chemotherapy. β-HPV subtypes, most commonly HPV 5 and 8, drive lesion formation in the context of impaired cell-mediated immunity. Histopathology demonstrates keratinocyte vacuolization, acanthosis, and perinuclear halos. Lesions may persist despite immunosuppressive adjustment, due to viral latency and incomplete immune reconstitution. Treatment strategies are varied and include topical retinoids, immune response modifiers, systemic retinoids, and HPV vaccination, and have variable efficacy. AEV carries an elevated risk of cutaneous squamous cell carcinoma, particularly in transplant recipients, and highlights the need for proactive dermatologic management. Conclusions: AEV represents a clinically significant consequence of immunosuppression mediated by β-HPV. Early recognition, monitoring for malignant transformation, and individualized multimodal therapy are critical. Future studies should evaluate targeted interventions to enhance antiviral immunity and establish standardized treatment guidelines. Full article

According to the Global Burden of Disease 2019 analysis, there were 606,300 new cases of chronic kidney disease due to glomerulonephritis worldwide, with 17.3 million prevalent cases and 183,700 deaths More interestingly, between 1990 and 2019, the global burden of glomerulonephritis increased by 77% in incidence and 81% in prevalence, mainly due to demographic aging and population growth. Among primary glomerulopathies, IgA Nephropathy (IgAN), also known as Berger’s disease, is the most common primary glomerulopathy worldwide, with significant geographic and ethnic variation in incidence, with the highest prevalence in Europe and Asia and the lowest in Africa. Its pathogenesis reflects a complex interaction between polygenic susceptibility and environmental modifiers, mucosal immune activation, infections of the upper respiratory and gastrointestinal tracts, dietary factors, and alterations in the gut microbiome. In addition, IgAN increasingly coexists with other chronic diseases, such as hypertension and diabetes, which complicates both diagnosis and treatment in aging societies. All these observations suggest that in the coming years, the epidemiology of IgAN will gradually transform from a description of “case counts” to a predictive tool that integrates genetic, environmental, and molecular biomarker data. In this sense, epidemiology is increasingly becoming the foundation of precision nephrology—allowing not only for disease risk prediction but also for the design of effective therapeutic strategies. The conceptual shift in IgAN—from a disease defined by biopsy prevalence to one understood through integrative epidemiology—illustrates the broader transition of GN research toward biomarker-based risk stratification and precision medicine. This review focuses on IgA nephropathy as the most prevalent primary glomerulonephritis and uses it as a reference disease to illustrate broader epidemiological patterns, outcome trajectories, and methodological limitations relevant to primary glomerulonephritides. Full article

Proiphys amboinensis has considerable potential as a commercial ornamental plant due to its attractive foliage, distinctive flowers, and long flowering period. This study established an in vitro micropropagation protocol and evaluated the genetic fidelity of regenerated bulblets using Inter Simple Sequence Repeat (ISSR) markers and flow cytometry. Twin-scale explants were cultured on Murashige and Skoog (MS) medium supplemented with 0, 0.5, 1.0, and 2.0 mg/L N⁶-benzyladenine (BA) for 12 weeks. Bulblet formation efficiency ranged from 60.00 ± 16.33% to 70.00 ± 11.55%, with no significant differences among treatments. A significant increase in bulblet number was observed at 1.0 mg/L BA compared with the control and 0.5 mg/L BA; however, bulblet fresh weight did not differ significantly among these treatments. Sucrose concentrations (30–90 g/L) had no significant effects on bulblet weight and diameter. Root induction was evaluated using indole-3-butyric acid (IBA) and α-naphthaleneacetic acid (NAA) at concentrations of 0–1.0 mg/L, with 0.5 mg/L IBA identified as the optimal treatment. Following acclimatization, regenerated bulblets exhibited high survival rates (90–100%). ISSR and flow cytometric analyses revealed no detectable genetic variation, with a consistent genome size between regenerated bulblets and the mother plants, indicating high genetic uniformity. The protocol provides a micropropagation system for P. amboinensis with high genetic fidelity, supporting its commercial and research potential. Full article

Optimizing cryo-resuscitation from frozen sperm would improve access to cryopreserved rat models. In this study, the possibility of replacing intracytoplasmic sperm injection (ICSI) with in vitro fertilization (IVF) for model cryo-resuscitation from frozen–thawed sperm was investigated. Rat IVF protocol was modified to allow the procedures to be performed during a 9 h workday. The possibility of genetic background-specific modification of the superovulation protocol for the improvement in IVF outcomes was explored. Wild-type and genetically modified Sprague Dawley (SD), Long Evans (LE) and Fischer 344 (F344) rats were used. Sperm freezing and IVF were conducted as previously described. Cleavage, blastocyst formation and hatching of the resulting embryos were used to assess their developmental potential in vitro. The results showed that, with limited repetitions, current sperm freezing and IVF protocols resulted in cleavage rates ranging from 58 ± 11% to 87 ± 7% and blastocyst rates ranging from 21 ± 25% to 54 ± 23%, which are acceptable for the cryo-resuscitation of rat models. With slight modifications, the procedure can be fit into a 9 h workday (SD: 48 ± 35%; F344: 36 ± 13%). Strain/stock-specific differences in oocyte maturation timing were observed: LE females had a two-hour delay compared to SD and F344 rats in response to the same superovulation protocol. However, modifying the protocol for LE rats did not significantly improve IVF outcomes (34 ± 6 vs. 32 ± 12%). Overall, while IVF with frozen–thawed sperm is a promising alternative to ICSI, significant variability remains across strains/stocks and protocols. Continued research is necessary to advance our understanding of factors affecting the efficiency and repeatability of rat sperm freezing and IVF. Full article

This study investigated the mechanism by which different fractions of chickpea protein influenced the formation of oleogels. Total chickpea protein (CPP, 0.5 wt%), chickpea albumin (ALB, 0.5 wt%), globulin (GLO, 0.5 wt%), and glutelin (GLU, 0.5 wt%) were separately used as oleogelators by combining with xanthan gum (XG, 0.5 wt%) at pH 7 to construct soybean oil-based oleogels via the emulsion-templated method. Particle size measurement revealed that the GLU-XG (526 nm) exhibited the smallest particle size compared to CPP-XG (605 nm), ALB-XG (642 nm), and GLO-XG (819 nm). The four complexes exhibited increasing surface hydrophobicity and conformational flexibility (as revealed by fluorescence spectroscopy) in the order of GLO-XG < ALB-XG < CPP-XG < GLU-XG. Compared with other complexes, the higher surface hydrophobicity, smaller particle size, and more flexible structure of GLU-XG conferred a superior surface activity. Consequently, the fabricated emulsion demonstrated a smaller droplet size (13.91 μm) and enhanced centrifugal stability (94.64%). The confocal laser scanning microscope images confirmed that the oleogel based on GLU-XG exhibited the most uniform and densest network, leading to the highest oil-binding capacity (98.7%) and storage/loss modulus, followed by those based on CPP-XG (97.2%), ALB-XG (95.6%), and GLO-XG (93.9%). This research provides a theoretical basis for using chickpea protein in oleogel formulations and enhances understanding of the structural and interfacial properties of these protein fractions. Full article

Background/Objectives: The discovery of antimalarial compounds with novel mechanisms of action and distinct rates of kill (RoK) is essential to address emerging drug resistance in Plasmodium falciparum. Natural product libraries represent a valuable and chemically diverse source of potential new antiplasmodial scaffolds. This study aimed (i) to evaluate a modified bioluminescence relative rate-of-kill (mBRRoK) assay as a rapid triage platform for screening large compound libraries with previously unknown antiplasmodial activity, enabling simultaneous assessment of potency and RoK, and (ii) to identify novel compounds with potent and selective in vitro erythrocytic activity. Methods: A fixed two-concentration mBRRoK screen was applied to 1165 compounds from the PhytoQuest natural product library. Antiplasmodial activity and RoK profiles were assessed over 48 h using two genetically distinct luciferase-expressing P. falciparum strains (Dd2^luc and NF54^luc) with distinct drug resistance backgrounds. Reproducibility was evaluated across biological replicates. Selected hits underwent secondary profiling, including EC₅₀ determination and HepG2 cytotoxicity assessment to establish potency and selectivity. Results: The primary screen identified 36 lead compounds demonstrating potent activity within 48 h, encompassing both fast- and slow-acting phenotypes. Activity was reproducible and largely strain-independent across both parasite lines. Secondary profiling prioritised four compounds (100657, 101158, 101160, and 101173) with nanomolar-to-micromolar antiplasmodial potency and favourable selectivity indices relative to mammalian cell cytotoxicity. Conclusions: The mBRRoK assay provides a robust and scalable framework for integrating potency and pharmacodynamic assessment in early antimalarial discovery. This strategy enabled efficient prioritisation of selective natural product-derived leads with distinct killing profiles, supporting their progression toward further optimisation and preclinical development. Full article