Development and identification of KASP-SNP markers correlated with Aeromonas hydrophila resistance traits in blunt snout bream (Megalobrama amblycephala).

BACKGROUNDIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with limited therapeutic options and poor prognosis. Recent evidence indicates that lactate metabolism (LM) plays a pivotal role in tumor metabolic reprogramming, immune evasion, and disease progression; however, the heterogeneity and regulatory mechanisms of LM activity within ICC remain largely undefined.AIMTo systematically characterize LM-driven heterogeneity and its molecular and functional implications in ICC.METHODSSingle-cell RNA sequencing and bulk transcriptomic datasets were integrated to characterize LM heterogeneity in ICC. High-dimensional weighted gene co-expression network analysis and multiple machine-learning algorithms (least absolute shrinkage and selection operator, random forest, gradient boosting machine, adaptive best subset selection, and decision tree) were employed to identify LM-associated feature genes. CytoTRACE and CellChat analyses were used to assess differentiation potential and intercellular communication among malignant epithelial subpopulations. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed to elucidate biological functions. A random forest model combined with SHapley Additive exPlanation (SHAP) interpretability analysis identified the most predictive LM-related gene. Functional assays, including quantitative polymerase chain reaction, cell counting kit-8, colony formation, wound-healing, and transwell experiments, were conducted to validate CYC1 in ICC cell lines.RESULTSMalignant ICC cells were stratified into three LM-activity subtypes (high, intermediate, and low) exhibiting distinct transcriptional programs and differentiation trajectories. Twelve LM-associated feature genes GPX3, CYC1, NME1, GSTP1, MGST1, ALDH3A1, TALDO1, SNRPB, TKT, NAA20, G6PD, and RPL13A were identified as key molecular markers linked to aggressive phenotypes and poor prognosis. Among them, CYC1 showed the highest predictive accuracy (area under the curve = 0.844) and strongest model contribution (SHAP = 0.091), marking it as the principal LM-related driver gene. Functional experiments confirmed that CYC1 knockdown significantly suppressed ICC cell proliferation, migration, and invasion, validating its oncogenic role in promoting malignant progression.CONCLUSIONThis integrative single-cell and machine-learning study delineates the molecular heterogeneity of LM in ICC and identifies twelve feature genes linking LM with tumor aggressiveness. These findings provide novel insight into LM-driven oncogenic mechanisms and propose CYC1 and other LM-associated genes as potential biomarkers and therapeutic targets for ICC.

Tomato (Solanum lycopersicum), one of the world's most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience.

While ferroptosis is implicated in alcoholic liver disease, its precise mechanisms of action are not fully defined. This study aims to investigate the protective role of the ferroptosis inhibitor Ferrostatin-1 (Fer-1) against alcoholic liver injury, exploring its underlying mechanisms. Using mice models of acute and chronic ethanol exposure, we assessed the effects of Fer-1. We evaluated liver function, histopathological damage, and key molecular markers related to ferroptosis, metabolism, and inflammation. Fer-1 significantly improved liver function and alleviated tissue damage, including lipid accumulation and fibrosis. It enhanced antioxidant capacity and reduced iron overload, oxidative stress, and lipid peroxidation. Furthermore, Fer-1 improved dysregulated iron and lipid metabolism and attenuated inflammation. Notably, these protective effects appear to be independent of the Nrf2/HO-1 pathway, autophagy, and NLRP3 inflammasome. Fer-1 exerts multi-faceted protection against alcoholic liver injury by specifically inhibiting ferroptosis. It blocks the vicious cycle of alcohol-induced metabolic imbalances, oxidative stress, and inflammation, offering new potential strategies for treating alcoholic liver disease.

Herpes simplex keratitis (HSK) is classically described as an immunopathological disease driven by recurrent herpes simplex virus type 1 (HSV-1) infection and chronic inflammation. So far, immune-mediated tissue damage has not fully explained the molecular mechanisms governing disease progression toward corneal neovascularization (CNV), a major cause of corneal blindness and vision loss worldwide. Increasing evidence indicates that CNV results from complex interactions that extend beyond leukocyte-driven inflammation, as the host cell machinery, including key pathways and molecular markers, is hijacked by the invading virus to establish and perpetuate replication and lifelong latency. These host-cell interactions regulate angiogenic imbalance, vascular privilege, and tissue remodeling, which collectively promote pathological vascular invasion. This review re-examines HSK by focusing on molecular mechanistic pathways and drivers that regulate disease progression towards CNV, upstream of immune response drivers. Specifically, we discuss the roles of endothelial growth factors, matrix metalloproteinases, Heparanase, and Syndecan-1 signaling, as well as microRNA-mediated regulation, and key signaling axes, including JAK2/STAT3, PI3K/AKT/mTOR, and hypoxia signaling. By integrating these pathways and molecular markers, we propose an updated mechanistic framework, including a conceptual model for the underexplored role of heparanase, and identify pathway-level targets with potential therapeutic relevance for HSK-associated CNV.

Predicting short-term recurrence and identifying key risk factors in elderly glioma patients: Insights from a retrospective cohort study.

Diabetes-linked metabolic dysfunction relates with distinct tau phosphorylation patterns, neuroinflammation and cognitive impairment in mouse models of Alzheimer's disease.

Reveal a risk and potential mechanism for keratoconus progression with isotretinoin: Toxicogenomic, transcriptomics and real-world evidence insights.

Susceptibility to the larvicide pyriproxyfen and genotyping of kdr mutations in two Aedes aegypti populations from Maranhão State, Brazil.

The wet gluten content (WGC) of wheat is a key indicator of wheat-processing quality, and its genetic basis is extremely critical in breeding. This study evaluated the WGC of 207 wheat accessions under three growing seasons from a natural population. Nine quantitative trait loci (QTLs) explained 7.61–15.18% of phenotypic variation in a genome-wide association study (GWAS) using a 660K SNP array. Among them, qWGC6B.2 on chromosome 6BL was consistently detected across multiple environments, accounting for 10.08–12.27% of variation. Incorporating grain transcriptome data led to the identification of TaWGC6B.1 (TraesCS6B02G386700), which is highly expressed in developing endosperm and strongly correlated with WGC. A competitive allele specific PCR (KASP) marker development and validation indicated that the Whaas68366_GG allele significantly enhanced gene expression and WGC. This study identified key genes and molecular markers, providing theoretical and technical support for WGC genetic improvement in wheat (Triticum aestivum L.).

Changes in the gut microbiota (GM) are closely linked to colorectal cancer (CRC) development, influencing tumor cell proliferation and apoptosis. Prebiotics, probiotics, and synbiotics have been proposed as modulators of GM and potential regulators of tumor progression through key molecular markers, such as p53 and Ki-67. In this sense, a scoping review was performed following PRISMA-ScR guidelines to map available evidence on the impact of prebiotics, probiotics, and synbiotics on p53 and Ki-67 expression in CRC. Search was conducted in PubMed, SciELo, BVS/Lilacs, Embase, and Web of Science databases without date or language restrictions. Nineteen studies were included (18 preclinical and one randomized clinical trial). Ten studies assessed p53, seven evaluates Ki-67, and two examined both markers. Most preclinical studies suggested that biotic supplementation modulates apoptosis and proliferation-related pathways, often through p53 activation or Ki-67 suppression, although directionality varied across strains and models. Biotic interventions appear to influence tumor proliferation markers in CRC with strain- and model-dependent manner. Nevertheless, the evidence remains limited by heterogeneity of the study design, dosage, exposure time, and biomarker assessment. Well-designed and strain-resolved clinical trials are required to clarify whether these findings have translational and therapeutic relevance in CRC management.

Background: In melanoma diagnostics key molecular markers, such as BRAF, NRAS, and KIT mutations also paved the way for targeted therapies. Immunotherapies, including immune checkpoint inhibitors like anti-CTLA-4 and anti-PD-1/PD-L1, have revolutionized treatment, improving survival outcomes for advanced-stage melanoma patients. Despite these advances, challenges such as resistance to targeted therapies and variability in patient responses to immunotherapy remain critical issues. The purpose of the project is to characterize the molecular landscape of a set of 28 malignant melanomas using next-generation sequencing, identify the prevalence and nature of class 3-5 variants (e.g., NRAS, BRAF, KIT, TP53), assess the genetic complexity and molecular patterns, and use these insights to inform personalized therapies and optimize patient stratification for potential combination strategies (targeted therapy followed by immunotherapy). Methods: We analyzed a set of malignant melanoma of the skin of 17 women (61%) and 11 men (39%) at the age of 23 to 85 years (median: 63 years) by tumor-only next generation sequencing. Results: 22/28 cases (79%) present a pathogenic or likely pathogenic variant with an allelic frequency of ≥5%. In total 42 distinct somatic pathogenic or likely pathogenic variants with an allelic frequency of ≥5% could be detected. The most frequent pathogenic molecular alteration in these melanomas were found in NRAS (25%) and BRAF (25%). The most frequent molecular alteration of unknown significance was found in FANDC2 (46%), NOTCH3 (39%), ARID1A (32%), PMS2 (32%), POLE (29%), NOTCH1 (29%), TSC2 (25%), SMARCA4 (25%), ATR (25%) and TERT (21%). Conclusions: While NRAS and BRAF were the most frequent actionable alterations (each 25%), a broad spectrum of variants of unknown significance (e.g., FANDC2, NOTCH3, ARID1A, PMS2, POLE, NOTCH1, TSC2, SMARCA4, ATR and TERT) also predominates, underscoring the genetic complexity of melanoma. These variants complicate clinical decision-making because their contribution to tumorigenesis, therapeutic response, and prognosis remains uncertain. Nevertheless, these variants also offer a valuable resource for future research, as they may uncover novel pathogenic mechanisms or therapeutic targets once their significance is elucidated. Integrating comprehensive genetic profiling with immunologic markers can enhance patient stratification and support rational, potentially synergistic strategies, such as combining targeted therapies with immunotherapy, to optimize clinical outcomes. This study is limited due to a small cohort and limited available clinical data. Larger cohort studies and prospective clinical trials are necessary to validate and explore the interplay between molecular and immune biomarkers as well as general biological mechanism in paving therapeutic way in melanoma.

Background Cancer is a complex condition defined by the uncontrolled growth and proliferation of cells. Brain neoplasms, both primary and secondary, present a rising global health burden. Newer classification integrates key molecular markers; IDH mutation, 1p/19q co-deletion, and methylation promoter, enhancing diagnostic precision and guiding therapeutic targeted therapies. Purpose This review provides comprehensive molecular insights into the multistep pathophysiology of brain tumours, highlighting early genomic and epigenomic alterations that drive malignancy and metastasis. Materials and Methods Advancements in neuroimaging, such as magnetic resonance imaging (MRI) and computed tomography (CT) scans, have significantly improved the early detection and precise localization of brain tumors. Moreover, molecular and genetic profiling has revolutionized the classification and prognostication of these tumors, enabling more personalized therapeutic strategies. Results Treatment modalities for brain tumors include surgical resection, radiotherapy, and chemotherapy, often employed in combination to maximize efficacy. Innovations in surgical techniques and radiotherapy, such as stereotactic radiosurgery, have enhanced the precision of tumor removal and minimized damage to surrounding healthy tissue. Despite these advancements, the prognosis for many brain tumor patients remains challenging, with high-grade gliomas, like glioblastoma multiforme, having particularly poor outcomes. Conclusion Comprehensive literature collection was conducted using various scientific databases, including PubMed, ScienceDirect, and Google Scholar, focusing on the molecular mechanisms underlying tumorigenesis and therapeutic resistance, with the objective of identifying molecular therapeutic targets. Emerging diagnostic and therapeutic innovations, including liquid biopsy, MR-guided blood–brain barrier modulation, and nanotechnology-based drug delivery, are providing novel, targeted, and minimally invasive strategies for the effective management of central nervous system malignancies.

ABSTRACT Diffuse astrocytomas represent the most prevalent primary brain tumors. Despite advances in molecular classification, their clinical behavior remains heterogeneous. This study aimed to evaluate the immunohistochemical expression of PD-L1 in adult diffuse astrocytomas and to investigate its association with key molecular markers, clinicopathological features, and survival outcomes. A retrospective cohort of 80 adult astrocytoma cases diagnosed between 2015 and 2021 was analyzed. Clinicopathological and survival data were reviewed, tissue microarrays were constructed, and immunohistochemical staining for PD-L1, ATRX, IDH1/2, and p53 was performed. Clinicopathological correlation was done using appropriate statistical methods. PD-L1 expression was detected in 50% of cases and was more frequently observed in high-grade astrocytomas compared to low-grade tumors. A statistically significant association was identified between PD-L1 expression and microvascular proliferation (p = 0.007), as well as IDH-wild type status (p = 0.01). However, PD-L1 expression was not significantly associated with overall or disease-free survival. These findings indicate that PD-L1 expression is relatively prevalent in diffuse astrocytoma and is linked to adverse pathological features, particularly in tumors with aggressive molecular profiles. Integrating immunohistochemical and molecular data may enhance tumor characterization and support the rational selection of patients for future PD-1/PD-L1-targeted therapeutic strategies.

Aging is associated with progressive synaptic deterioration and cognitive decline; however, therapeutic strategies capable of restoring both structural and functional deficits remain limited. This study evaluated the effects of aging on dendritic spine dynamics and recognition memory across multiple brain regions, and evaluated whether chronic treatment with cerebrolysin (CBL) could ameliorate age-related alterations (3, 6, 12 and 18 months of age). We additionally assessed the effects of CBL on key molecular markers of synaptic plasticity in aged (18-month) C57BL6 mice. Aging impaired locomotor activity (12- and 18-month groups) and produced deficits in short- and long-term recognition memory relative to young controls. Notably, CBL selectively enhanced locomotion in 18-month group and improved short-term memory in the 12-month group. At the structural level, aging reduced spine density and decreased the proportion of thin and mushroom spines in the prefrontal cortex and dorsal hippocampus, whereas CBL treatment increased spine density in the dorsal hippocampus and basolateral amygdala, and promoted the formation of mature mushroom spines in a region and age-dependent manner. Importantly, CBL elevated β-actin, synaptophysin and brain-derived nerve factor expression across multiple regions in the 18-month group. This study provides the first integrated demonstration that CBL enhances dendritic spine maturation and dendritic structural remodeling while concurrently improving cognitive outcomes within the same cohort of aged animals. Collectively, our findings position CBL as a promising therapeutic candidate to counteract age-related synaptic loss and cognitive decline, advancing current understanding of neuroprotective interventions in aging.

This study presents the phenotypic characterization and genomic mining of uric acid catabolism genes in Lactiplantibacillus plantarum YC, a novel food-grade lactic acid bacterium isolated from traditional fermented vegetables with potent uric acid-lowering activity. YC is non-hemolytic, catalase- and gelatinase-negative, exhibits strong adhesion and broad antibacterial activity, and degrades 29.22% of uric acid in vitro, along with complete (100%) degradation of inosine and guanosine. Whole-genome sequencing revealed a 3,214,448 bp chromosome encoding 3026 protein-coding genes. Comparative genomics-based functional annotation highlighted abundant CAZy-related genes and antimicrobial factors, including lysozyme and monooxygenase. Crucially, genomic mining identified a complete uric acid degradation gene cluster, comprising pucK (uric acid permease), hpxO (uric acid hydroxylase), eight copies of hiuH (5-hydroxyisourate hydrolase), allB (allantoinase), and purine nucleoside transport/metabolism genes (rihA, rihB, rihC, pbuG). This work provides the first comparative genomic insight into the genetic architecture and distribution of uric acid metabolism in L. plantarum, elucidating YC's dual urate-lowering mechanism and delivering key molecular markers for developing enzyme-based functional foods and microbial therapeutics against hyperuricemia.

The 5th edition of the World Health Organization Classification of Tumors of the CNS introduced a subclassification of tumors based on key molecular markers. In adult-type diffuse gliomas, isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter mutations play pivotal roles in the molecular classification. This study developed a rapid genotyping system using GeneSoC, a real-time PCR platform with microfluidic thermal cycling capable of completing 50 cycles of PCR within 20min. To establish optimal analytical conditions, frozen tumor tissues from 67 patients and artificial DNA vectors were analyzed using this system. This system demonstrated a detection limit of at least 5% variant allele frequency for the IDH1 R132H and TERT promoter C228T/C250T mutations. Subsequently, intraoperative testing was performed in 120 cases using this system. The sensitivity and specificity of IDH1 R132H mutation were 0.985 and 0.982, respectively, whereas those of TERT promoter C228T/C250T mutation were 1.000 and 1.000, respectively. These mutations were detected intraoperatively within approximately 25min after tumor tissue collection. Furthermore, this assay identified tumor boundaries in an IDH-mutated glioma case, where IDH1 R132H mutations could not be detected. The GeneSoC®︎-based rapid genotyping system may be effective not only for intraoperative diagnosis of diffuse glioma but also for detecting tumor boundaries.

Employing genome-wide association studies and machine learning to accurately identify Eastern and Western migratory pathways of Spodoptera frugiperda in China via key molecular markers

Development of solenoidal assembly for probing static magnetic field-induced physiological and behavioral disruptions in zebrafish.

Underreporting of molecular targets in surgically treated patients with peritoneal metastasis of gastric cancer.