Search Results (5,139)

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies because of aggressive tumor biology, pervasive therapeutic resistance, rapid adaptive reprogramming, and a profoundly immunosuppressive tumor microenvironment. This review summarizes recent advances in KRAS-targeted therapies, DNA damage response (DDR)-directed strategies, immune-redirection platforms, and tumor microenvironment modulation. Methods: We conducted a narrative review of peer-reviewed publications, clinical trial reports, trial registries, and selected conference data addressing emerging therapeutic strategies for PDAC. Results: KRAS-targeted therapies, including KRAS G12D-selective and multi-selective RAS(ON) inhibitors, have demonstrated substantial preclinical and emerging clinical activity while revealing diverse mechanisms of adaptive resistance. DDR-directed approaches are expanding beyond BRCA-mutated disease toward functional homologous recombination deficiency, replication stress, and synthetic lethality. In parallel, bispecific antibodies, T-cell engagers, and CAR-T-cell therapies have generated preliminary evidence of antitumor activity, although stromal exclusion, antigen heterogeneity, and immune suppression remain major barriers. These advances indicate that therapeutic resistance in PDAC is a dynamic process involving interconnected oncogenic, genomic, stromal, metabolic, and immune mechanisms. Conclusions: Future progress will require biologically informed treatment frameworks integrating complementary therapeutic modalities according to baseline tumor biology and treatment-induced adaptive states, supported by longitudinal biomarkers and rational clinical trial design. Full article

Barley (Hordeum vulgare) is one of the earliest domesticated cereal crops and remains important for global feed, food, and malting industries. Although high-quality genomic resources are now available, its large repeat-rich genome has complicated genome-wide characterization of genomic features associated with barley evolution and domestication. Here, we integrated comparative genomics, methylomics, population genomics, and Hi-C analyses to investigate genome evolution and domestication in barley. Comparative analyses across representative grass species revealed that barley exhibits lineage-specific genome expansion associated with the extensive proliferation of long terminal repeat retrotransposons. Genome-wide DNA methylation analyses revealed distinct cytosine methylation landscapes in barley. Population genomic analyses of 291 wild and domesticated barley accessions revealed relatively slow linkage disequilibrium decay and identified 243 candidate domestication-associated genes. These candidate genes were enriched in starch and sucrose metabolism pathways. Comparative Hi-C analyses of three barley accessions further uncovered differences in A/B chromatin compartments and topologically associating domain (TAD) organization despite their largely conserved gene content. In addition, the enrichment of DNA transposons and Copia retrotransposons at TAD boundaries suggests potential associations between specific TE classes and higher-order chromatin organization. Together, these complementary analyses connect genome expansion, epigenetic regulation, domestication-associated selection, and chromatin organization into a unified framework for understanding barley genome evolution and domestication. Full article

This study investigated the effects of supplementing Tris semen extender with protocatechuic acid (PCA) at doses of 25, 50, and 100 µg/mL on the quality of ram spermatozoa after cryopreservation. We evaluated motility, kinematic parameters, DNA integrity, redox status, plasma membrane–acrosome integrity (PMAI), viability, and high mitochondrial membrane potential (HMMP). PCA supplementation produced concentration-dependent and parameter-specific responses. The 25 µg/mL PCA group exhibited the most favorable functional profile, demonstrating improved progressive and total motility alongside reduced DNA damage. This protective effect was evidenced by lower tail length, tail DNA percentage, and tail moment in the comet assay. Conversely, treatment with 100 µg/mL PCA appeared to exert a notable effect on the redox balance, indicated by lower malondialdehyde, total oxidant status, and oxidative stress index levels, alongside an elevated total antioxidant status (p < 0.05). However, this higher concentration (100 µg/mL) did not provide parallel DNA protection and was associated with increased comet assay indices. PMAI, viability, and HMMP were not significantly affected by PCA supplementation (p > 0.05). These findings indicate that PCA exerts dose-dependent but parameter-specific effects on frozen–thawed ram spermatozoa. Low-dose PCA, particularly 25 µg/mL, appears more suitable for preserving motility and nuclear integrity, whereas 100 µg/mL mainly improves oxidative balance. Full article

Fruit-specific promoters (FSPs) are a class of regulatory DNA sequences that direct transgene expression exclusively in fruit tissues or during specific stages of fruit development. They are indispensable molecular tools in modern agricultural biotechnology, with broad applications in fruit quality improvement, nutritional enhancement, and shelf-life extension. By functioning as precise molecular switches that regulate fruit-specific gene expression, FSPs overcome the limitations of constitutive promoters and facilitate precision molecular breeding for fruit quality improvement. This review systematically summarizes recent advances in FSP research. First, based on their spatiotemporal expression patterns, FSPs are classified into four categories: immature fruit-specific, fruit ripening-specific, whole fruit development stage-specific, and dual-stage (immature fruit/ripening) promoters. Their origins, expression characteristics, and key cis-regulatory elements are comprehensively summarized. Second, the complex transcriptional regulatory network governing FSP activity is discussed from the perspectives of cis-regulatory elements, major transcription factor families (such as MADS-box and NAC proteins), and epigenetic regulation, including DNA methylation and histone modifications. Furthermore, recent advances in key methodologies, including promoter cloning, functional characterization, and CRISPR/Cas9-mediated precise editing of cis-regulatory elements, are reviewed, together with their applications in crop genetic improvement, plant molecular farming, and fundamental molecular biology research. Finally, this review highlights the major challenges limiting the application of FSPs, including the relatively weak transcriptional activity of natural promoters, insufficient tissue specificity, and limited cross-species applicability. Future perspectives are discussed, emphasizing the integration of artificial intelligence-assisted promoter design, high-throughput screening, and single-cell omics technologies to develop finely tunable synthetic promoters. These advances are expected to provide both a theoretical foundation and technical support for precision molecular breeding in fruit crops. Full article

Background: Imidacloprid, a widely used neonicotinoid insecticide, is routinely applied to control pests in Astragalus membranaceus var. mongholicus, a crucial medicinal herb producing Astragali Radix. However, the early short-term transcriptional and metabolic responses of its seedlings under imidacloprid gradient stress remain poorly characterized. Methods: In this study, 80-day seedlings were subjected to three foliar spray treatments: blank control (CK), the recommended imidacloprid concentration (2000-fold dilution, 475 mg·L⁻¹), and an excessively high concentration (500-fold dilution, 1900 mg·L⁻¹). Leaf samples were harvested 24 h post-treatment for untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) metabolomics (6 biological replicates) and RNA-seq transcriptome sequencing (3 biological replicates). Results: The low- and high-dose treatments induced 1076 and 860 differential metabolites and 6818 and 7283 differentially expressed genes, respectively. Flavonoids, saponins, terpenoids, amino acid metabolites, and energy-related pathways were prominently affected. KEGG enrichment indicated activation of flavone/flavonol biosynthesis, phenylpropanoid metabolism, amino acid metabolism, MAPK signaling, cutin/suberin/wax biosynthesis, and ABC transporter pathways, whereas high-dose exposure was associated with stronger changes in genes related to DNA replication and cell wall remodeling. Integrated network analysis highlighted CHS, PAL, MYC2, KCS, and ABCG40 as candidate regulators linking stress signaling, secondary metabolism, and metabolite transport. Conclusions: Seedlings of A. membranaceus var. mongholicus exhibit dose-dependent acute responses to imidacloprid. Moderate pesticide exposure primarily activates defensive secondary metabolism, whereas excessive dosage triggers genome-wide transcriptional reprogramming. This work identifies key metabolic pathways and hub genes, offering candidate molecular markers for investigating pesticide stress adaptation in medicinal Astragalus and guiding standardized pesticide application in cultivation. Full article

Chemical control is the main method used to manage the oriental fruit fly (Bactrocera dorsalis) in orchards. However, the oriental fruit fly has gradually developed resistance to multiple insecticides, posing significant challenges for pest resistance management. This study investigated changes in insecticide resistance in oriental fruit flies under different selection pressures. We identified resistance-related genes and their mutation sites using cDNA probes. Our results showed that resistance to trichlorfon decreased significantly in the absence of selection pressure. However, resistance increased when selection pressures were applied every 30 or 60 days. Although the resistance ratio showed a decreasing trend at every 90 and 120 days, a risk of a rebound remained. A large number of homologous sequences were identified in the suppression subtractive hybridization library of insecticide-resistant strains. Resistance to trichlorfon and alphamethrin primarily involves detoxification and metabolic genes, which are often associated with cross-resistance. A single gene may detoxify multiple pesticides, leading to cross-resistance. The four acetylcholinesterase mutations identified in this study are consistent with previous research findings. Moreover, resistance results from the combined action of multiple genes. Based on these findings, this study recommends avoiding continuous use of trichlorfon and maintaining an interval of more than 80 days between applications. It also emphasizes the importance of incorporating pesticide application intervals into integrated pest management strategies. This study provides a theoretical foundation for delaying resistance development in the oriental fruit fly, offers guidance on proper pesticide application intervals in the field, and contributes practical insights for pest resistance management. Full article

Cereal crops including wheat, rice, maize, barley, and sorghum collectively supply most global caloric and protein requirements, yet their productivity is increasingly constrained by combined abiotic stresses that co-occur under field conditions. Simultaneous drought, heat, salinity, and cold impose yield losses that consistently exceed those caused by individual stresses and elicit molecular responses that are qualitatively distinct from single-stress reactions and cannot be inferred from them. Despite this agronomic reality, the molecular mechanisms governing combined stress responses in cereals remain poorly resolved, and no integrated framework connecting the transcriptional, epigenetic, and genome-editing dimensions of combined stress tolerance has previously been articulated for this crop group. This review proposes a three-tier integrated framework for understanding and engineering combined abiotic stress tolerance in major cereals. The first tier encompasses transcription factor networks, including bZIP, WRKY, NAC, AP2/ERF, DREB, MYB, and HSF families, that translate combined stress signals into transcriptional reprogramming through ABA-dependent and ABA-independent pathways, hormonal crosstalk, and osmoprotectant and antioxidant defence systems. The second tier addresses the epigenetic regulatory layer, encompassing DNA methylation, histone modifications, and non-coding RNA pathways that gate TF binding site accessibility and encode stress memory in cereals. The third tier examines CRISPR-based tools, including multiplexed Cas9 editing and dCas9-based epigenome editing, that engineer validated targets from both tiers, while confronting polyploid off-target effects, growth penalties, and a laboratory-to-field validation gap. The three tiers are mechanistically coupled, with TF activity shaping epigenetic landscapes, epigenetic states gating TF access, and both providing precision engineering targets. Critical gaps include the absence of combined-stress epigenomic datasets, limited characterisation in barley and sorghum, and early-stage combined-stress-specific strategies. Full article

Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionarily conserved indoleamine with potent antioxidant and cytoprotective properties. Due to its amphiphilic nature, melatonin readily accumulates in mitochondria, where it regulates redox homeostasis and bioenergetic function. Although melatonin has been implicated in cutaneous protection against ultraviolet radiation (UVR), the mitochondrial mechanisms underlying its effects in UVB-exposed keratinocytes remain insufficiently characterized. In this study, we investigated the mitochondrial-centered protective effects of melatonin in human epidermal keratinocytes (NHEKs) subjected to UVB irradiation. UVB exposure induced a dose-dependent decrease in cell viability and proliferation, accompanied by excessive reactive oxygen species (ROS) production, mitochondrial membrane depolarization (ΔΨm), ATP depletion, caspase-3 activation, and increased expression of DNA damage- and senescence-associated markers, including γH2AX, p53, and p16^INK4a. Pre-treatment with melatonin attenuated these alterations by reducing oxidative stress, preserving ΔΨm, maintaining ATP production, suppressing apoptotic signaling, and modulating DNA damage- and senescence-related pathways. Collectively, our findings suggest that mitochondria are a central target of melatonin in UVB-exposed keratinocytes and demonstrate that maintenance of mitochondrial redox balance and bioenergetic integrity is associated with reduced apoptotic and senescence-related changes. Full article

Background/Objectives: DNA-based identification of degraded human remains represents a major challenge in forensic science, particularly in cases involving burned, fragmented, or commingled bodies. Advances in forensic genetics have expanded the analytical capabilities for such samples; however, the effectiveness of different approaches and their integration within Disaster Victim Identification (DVI) workflows remain heterogeneous. This systematic review aims to critically evaluate current evidence on DNA-based identification of degraded remains, focusing on methodological strategies, emerging genomic technologies, and DVI applications, while integrating laboratory evidence and operational forensic practice into a structured analytical framework. Methods: A systematic literature search was conducted in Scopus and Web of Science from database inception to 5 June 2026, following PRISMA 2020 guidelines. Eligible studies included original research addressing DNA analysis of degraded, thermally altered, or highly compromised human remains in forensic or DVI contexts. After a multistep screening process involving title/abstract and full-text evaluation, 37 studies were included. Data were extracted and organized into three thematic categories: (i) core DNA analysis, (ii) advanced molecular technologies, and (iii) DVI case applications. Results: The findings demonstrate that DNA recovery from degraded remains is influenced by thermal exposure, tissue type, and sampling strategy. Teeth and dense cortical bone consistently provide higher DNA yield. While autosomal STR profiling remains the primary analytical approach, its limitations in highly degraded samples are mitigated through the complementary use of mitochondrial DNA (mtDNA), Y-chromosome STRs (Y-STRs), and SNP markers, together with advanced sequencing technologies such as massively parallel sequencing (MPS). Emerging technologies, including rapid DNA systems and predictive models based on macroscopic indicators, significantly enhance efficiency and success rates. DVI studies report identification rates exceeding 90–95% when multidisciplinary and structured workflows are applied. The evidence further supports a flexible triage-based analytical strategy, in which marker selection is guided by tissue preservation and degradation level. Conclusions: DNA-based identification of degraded human remains has evolved into an adaptive, multi-level forensic process. Successful outcomes rely on the integration of optimized sampling, hierarchical genetic analysis, and coordinated DVI strategies. The findings support a triage-based framework that links tissue selection, degradation assessment, and analytical methodology to maximize identification success. Future developments should focus on predictive models, advanced genomic tools, and standardized workflows to further improve identification in challenging forensic scenarios. Full article

The number of households with pets has been steadily increasing in recent years, highlighting the growing social and economic importance of companion animals. The increasing role of animals in human life and the need for biodiversity protection have contributed to growing interest in animal DNA analysis, although it still remains less developed than human forensic genetics. Current research focuses on genetic identification, parentage verification, biodiversity monitoring, and wildlife forensic investigations. DNA identification methods have evolved from restriction fragment length polymorphism (RFLP) to short tandem repeat (STR) analysis, which is currently one of the most widely used approaches due to its high sensitivity, discriminatory power, and the possibility of multiplex amplification. Recent advances include the implementation of massively parallel sequencing (MPS/NGS), sequence-based STR typing, and integrated SNPSTR systems, which significantly improve the interpretation of complex and degraded samples. Despite challenges associated with PCR artefacts, stutter formation, allelic imbalance, and interpretation of low-template DNA, STR markers remain valuable tools in forensic analyses, conservation genetics, and combating illegal wildlife trade. Continued development of new marker panels, standardized nomenclature systems, and bioinformatic approaches is essential for improving the effectiveness and reliability of animal genetic identification. Full article

Malondialdehyde (MDA) is one of the main end-products of lipid peroxidation (LPO) and represents a widely investigated marker of oxidative stress (OS) and oxidative tissue damage. Beyond its role as a measurable byproduct of polyunsaturated fatty acid peroxidation, MDA can interact with proteins and nucleic acids, generating adducts that may contribute to mutagenic, genotoxic, and cytotoxic events involved in carcinogenesis and tumor progression. This narrative review summarizes current evidence on the role of MDA in cancers, including breast, lung, head and neck, colorectal, cervical, and cutaneous tumors. Across these cancer types, increased circulating or tissue MDA levels have frequently been associated with enhanced LPO, impaired antioxidant defenses, tumor burden, advanced disease stage, aggressive histopathological features, treatment-related oxidative injury, and, in selected studies, poorer clinical outcomes. MDA-derived DNA adducts may further reflect oxidative DNA damage and provide mechanistic insight into the relationship between chronic redox imbalance, inflammation, and malignant transformation. However, MDA remains a non-specific biomarker influenced by age, smoking, diet, metabolic disorders, systemic inflammation, comorbidities, treatment exposure, and analytical methodology. Current evidence therefore supports MDA as a biologically relevant indicator of oxidative damage rather than a validated stand-alone diagnostic, prognostic, or therapeutic biomarker. Larger prospective studies using standardized and specific analytical methods are needed to clarify its clinical utility and to integrate MDA within broader redox biomarker panels. Full article

Leucoptera malifoliella (Lepidoptera: Lyonetiidae) is a quarantine pest of apple and other Rosaceae fruit trees whose range is expanding into new territories. Its minute size and morphological overlap with closely related Lyonetiidae make routine identification unreliable, especially for larvae and damaged specimens. We compared COI sequences from six common small Lepidoptera species found in orchards and designed the species-specific primer pair SXW-F/SXW-R. The resulting polymerase chain reaction (PCR) assay amplifies an ~500 base pairs (bp) fragment exclusively from L. malifoliella; no product was detected in any of five non-target species. The reaction tolerates annealing temperatures of 50–58 °C and consistently detects the target across all life stages (first- to third-instar larvae, pupae, adults) and all adult tissues tested (antennae, head-thorax, abdomen, wings, legs). Detection sensitivity reaches 0.03 ng/μL—approximately one-thousandth of the DNA content of a single adult. This is the first species-specific COI (SS-COI) method reported for L. malifoliella. It furnishes a rapid, specific, and sensitive diagnostic tool for quarantine inspection, field monitoring, and integrated pest management (IPM) programs. Full article

Microplastics (MPs) can adsorb and transport heavy metals, but their influence on cadmium (Cd)-induced hepatotoxicity in mammals remains unclear. Forty-eight male Kunming mice were assigned to control, Cd, MP, and Cd + MP groups and exposed by oral gavage for 42 days. Growth performance, liver injury, oxidative stress, and inflammation were assessed, and transcriptomic and metabolomic analyses were integrated with qPCR, mitochondrial DNA (mtDNA) copy number, and ATP measurements. Compared with Cd alone, combined exposure resulted in greater reductions in body weight gain, the liver index, and antioxidant enzyme activities, together with more severe hepatic lesions and higher levels of liver injury markers and inflammatory cytokines. Co-exposure also induced broader transcriptional and metabolic disturbances than Cd alone. Integrated omics analyses converged on the dysregulation of AMPK–FOXO signaling and related energy metabolic processes. qPCR confirmed more pronounced alterations in pathway-related genes after co-exposure, while reductions in mtDNA copy number and ATP content indicated aggravated mitochondrial dysfunction and impaired energy metabolism. Collectively, these results demonstrate that MPs exacerbate Cd-induced liver injury and suggest that disruption of AMPK–FOXO-associated energy metabolism is a key molecular feature underlying the enhanced hepatotoxicity observed under combined exposure. Full article

Research on insect biodiversity in arid and semi-arid agroecosystems of Central Asia remains limited, hindering the development of effective insect conservation strategies and integrated pest management (IPM) programs. This study examined insect community structure, diversity, and seasonal dynamics across three habitat types in Kekedala City, in the autonomous region of Ili Kazakh, Xinjiang, China. Solar-powered ultraviolet LED light traps (350–420 nm) were used for sampling from April to August 2024. A total of 63,090 individuals of 83 species, 57 families and 72 genera of insects were collected. Diversity indices calculated using the complete species dataset showed highest diversity in the riparian corridor (L3: H′ = 3.42, D = 0.962, S = 62), intermediate diversity in the agro-horticultural garden (L2: H′ = 3.18, D = 0.948, S = 54), and lowest diversity in the xerophytic shrubland (L1: H′ = 2.97, D = 0.935, S = 47). A supplementary analysis targeted a shared core assemblage of 17 species, defined as taxa captured at all three sampling sites with cumulative total abundances ranging from 50 to 100 individuals. This subset exhibited near-uniform diversity metrics across habitats (H′ = 2.83, D = 0.941, Pielou’s evenness J′ ≈ 1.0), a pattern driven by the prevalence of habitat generalists rather than capturing site-specific full community diversity. Two abundant pest species, Helicoverpa armigera (Hübner, 1808) (cotton bollworm, 5209 individuals, 8.3% of total) and Oryctes rhinoceros (Linnaeus, 1758) (rhinoceros beetle, 5206 individuals, 8.2% of total), both peaked in abundance in July–August; O. rhinoceros is associated with local ornamental and date palm plantings in the study area. In total, 15 major pest species were recorded. Mitochondrial cytochrome c oxidase subunit I (COI) DNA barcoding confirmed two new national insect records for China: Stethoconus pyri (Mella, 1861) (Hemiptera: Anthocoridae) and Pinacoplus didymogramma (Hampson, 1907) (Lepidoptera: Noctuidae). This study provides the first comprehensive baseline inventory of the insect fauna of Kekedala City. Descriptive ordination analyses suggest that habitat vegetation complexity may exert a stronger filtering effect on insect assemblage composition than the relatively small seasonal variation in temperature and humidity observed during the sampling period. As only a single trap was deployed within each habitat with no within-site replication, all cross-habitat community patterns reported herein are strictly descriptive and require validation via replicated field sampling in future research. Full article

Background: Breast cancer treatment is often based on multimodal approaches in locally advanced stages typically including neoadjuvant chemotherapy (NACT). There are limited options for the assessment of prognosis and early identification of future non-responders, which has led to the study of circulating cell-free DNA (cfDNA) and its tumor-derived subset, circulating tumor DNA (ctDNA), for potential use as non-invasive markers for prediction of response and prognosis associated with NACT. Methods: We have evaluated the literature on approaches to the use of cfDNA and/or ctDNA as potential biomarkers for NACT. Results: Out of 142 references going back to 2010, we found there were 87 original research reports, 39 reviews, 10 clinical trial reports and six case reports. A detailed analysis revealed several distinctive ways that markers were evaluated in a clinical setting. The original studies have focused on cfDNA, especially cfDNA integrity, whereby increasing integrity levels correlate with tumor shrinkage, reductions in proliferation markers, and hence indicate a better prognosis. Similarly, epigenetic alterations have shown promising results, with methylated ctDNA levels decreasing in responders. Further studies demonstrated the utility of ctDNA persistence through the NACT as strongly associated with shorter disease-free and overall survival. The most recent approaches of longitudinal ctDNA monitoring were found to be valuable for early identification of patients at high risk for post-operative recurrence. Conclusions: It should be noted that while most reports indicate the important role of circulating DNA in the assessment of prognosis and early detection of recurrence, there is currently only a limited utility in the prediction of eventual neoadjuvant therapy outcomes. Full article