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PubMed2026

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results↗

PubMed2026

Recent advances in electrode materials for electrochemical detection of zearalenone.

Zearalenone (ZEN) is an estrogenic mycotoxin commonly found in cereals, animal feed, and processed foods, making it an important concern for food safety and public health. Conventional chromatographic and immunological methods can detect ZEN; however, they often require expensive instruments, lengthy sample preparation, and skilled personnel, which restrict their use for rapid and on-site testing. Electrochemical sensors have attracted enormous interest of the scientific community because of their high sensitivity, rapid response, low cost, miniaturization potential, and compatibility with portable systems. The analytical performance of the electrochemical sensors is strongly influenced by electrode materials, morphology, conductivity, porosity, surface functionality, and the efficiency of bioreceptor immobilization. Despite several reviews on mycotoxin detection, a systematic assessment connecting electrode-material design, modification strategies, sensing mechanisms, and electroanalytical performance specifically for ZEN sensing remain limited. This review critically evaluates recent advances in metal oxides, carbon-based materials, metal-organic- and covalent organic frameworks, MXenes, polymers, and hybrid composites for electrochemical ZEN detection. Particular attention has been given to their roles in electron transfer, analyte enrichment, selectivity, and real-sample analysis. The review also compares the major limitations of current sensing systems, including complex fabrication, matrix interference, insufficient long-term stability, poor inter-electrode reproducibility, and limited scalability. Finally, future directions for developing robust, cost-effective, portable, and commercially viable ZEN sensors are discussed.

Journal Article↗

PubMed2026

Biological characterization of Candida parapsilosis haploids induced by voriconazole.

OBJECTIVES: Candida parapsilosis is an important opportunistic fungal pathogen causing serious human infections in nosocomial settings. It has long been thought that C. parapsilosis has a diploid genome with a high homozygosity between chromosome homologs. METHODS: In this study, we report the discovery of C. parapsilosis haploids induced by voriconazole, a triazole with broad antifungal activity against fungal pathogens, in an experimental evolutionary assay. RESULTS: The haploid strains were able to undergo auto-diploidization under in vitro culture conditions or during systemic infection at a low frequency. Compared to the progenitor diploid strain, C. parapsilosis haploid and auto-diploid strains exhibited a reduced ability of invasive growth and biofilm formation. Global transcriptional expression analysis indicated that haploid and auto-diploid strains had a similar transcriptomic profile, which showed a remarkable difference from the progenitor diploid strain perhaps due to the loss of chromosome heterozygosity. Moreover, the haploid and diploid strains had distinct fungal burdens in different animal tissues, suggesting the haploid state could have a colonization advantage over the diploids in certain tissues such as the brain and spleen. CONCLUSIONS: The discovery of C. parapsilosis haploids not only sheds lights on the biology of this important fungal pathogen, but also provides a tool for genetic modifications for the field.

Voriconazole↗

PubMed2026

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence↗

PubMed2026

Ensemble DNA methylation clock demonstrates Immune-metabolic aging signatures associated with mortality.

Aging is a multifactorial process that is best described in terms of the progressive acquisition of multiple layers of phenotypic changes, such as epigenetic modifications, inflammation, and metabolic dysregulation. DNA methylation clocks have been extensively used to construct epigenetic clocks based on the DNAm profiles that can be used to estimate biological age and predict age-associated outcomes. Nevertheless, the vast majority of clocks constructed so far have been based on linear models, which are unlikely to fully account for the heterogeneity and non-linearity of survival-related DNAm signatures. In this work, we constructed a heterogeneous stacked ensemble survival model based on DNAm data obtained from the Framingham Heart Study. We first identified 190 CpG loci using elastic net Cox regression and subsequently constructed a survival prediction model based on the fusion of five complementary survival models by means of a neural network meta-learner. The prediction power of the survival model was evaluated in an external validation cohort, where we observed strong performance for predicting all-cause mortality that significantly exceeded PhenoAge and was statistically comparable to GrimAge. These performance estimates were derived in cohorts of European ancestry and externally validated in postmenopausal women aged 50-79 years, and should therefore be interpreted as applicable only to demographically similar populations.

Humans↗

PubMed2026

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P = 0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans↗

PubMed2026

Multiscale Modeling Primer: Focus on Chromatin and Epigenetics.

A central challenge in modern biology is to understand how molecular interactions produce cellular and organismal functions across vast spatiotemporal scales. Nowhere is this challenge more apparent than in the study of chromatin, where meters of DNA compact into a micron-sized nucleus. How this polymer folds is a dynamic process, regulated by epigenetic modifications-chemical changes to DNA and histones that involve only a handful of atoms. These small changes cooperate to produce emergent, higher-order structures that define cellular identity and function. To explain this system, we must integrate static, high-resolution snapshots from techniques like cryo-EM with dynamic, lower-resolution data from microscopy and genomics. Multiscale computational models are essential tools that bridge these experimental gaps and reveal the mechanisms of emergent behavior. However, the communication divide between experimental biologists and quantitative modelers often hampers progress. This primer addresses that gap. It first introduces the fundamental biology of chromatin and epigenetics at an introductory level for non-biologists audiences. We then survey the landscape of computational approaches, from atomistic to systems-level models, and connect them to the experimental data that inform and validate them at an introductory level for non-computationalists. We argue that the next frontier will require us to build integrative models that can predict how molecular perturbations mechanistically alter cellular phenotypes, which will open a new era of chromatin-targeted therapeutics.

Chromatin Dynamics↗

PubMed2026

Chalcone-indole hybrid scaffolds as promising anticancer drug candidates: a mini-review.

Cancer treatment is hampered by severe systemic side effects, poor tumor selectivity, and multidrug resistance (MDR). Molecular hybridization integrates chalcone and indole, two privileged antitumor pharmacophores, into one scaffold to generate chalcone-indole hybrids that synergistically enhance antitumor potency, improve tumor targeting, and reverse MDR. This mini-review analyzes literature from 2020 to 2026 on chalcone-indole anticancer hybrids. Based on structural modification patterns, the reported hybrids are categorized into four subgroups: simple substituted, α/β-position modified, N-1 fatty acid-substituted, and multi-pharmacophore fused hybrids. For each category, we summarize structure-activity relationships (SARs), antiproliferative activity, selective toxicity, molecular mechanisms, and in vivo xenograft performance. Most lead compounds exert tumor-suppressive effects via tubulin polymerization inhibition, G2/M cell cycle arrest, ROS overaccumulation, and mitochondrial-dependent apoptosis. Representative hybrids 10a, 12a, 21a, and 25a exhibit remarkable efficacy against drug-resistant colorectal, lung, and breast tumors with favorable in vivo safety. We highlight the application potential of different subtypes for specific malignancies, including α/β-modified analogues for resistant colorectal cancer, N-1 fatty acid-platinum conjugates for platinum-resistant lung cancer, NLRP3 inhibitor 7a for oral cancer, and multi-pharmacophore fused derivatives for broad-spectrum activity. Current bottlenecks limiting clinical transformation are discussed. This review provides structural design rules for developing novel chalcone-indole targeted anticancer agents.

Humans↗

PubMed2026

Cre-loaded integrase-defective lentiviral vectors for targeted cassette exchange in CHO cells.

Genome-modifying enzymes, such as recombinases and CRISPR-associated nucleases, enable targeted gene insertion when delivered transiently to minimize off-target effects. Precise genome engineering requires controlled enzyme activity, as well as efficient donor DNA transfer. Integrase-defective lentiviral vectors (IDLVs) provide a promising platform for transient episomal DNA transfer; however, their integration efficiency depends on complementary genome-targeting strategies. Here, we engineered Cre-loaded IDLVs (Cre-IDLVs) that co-package lentiviral vector genomes together with bioactive Cre recombinase. Cre was inserted into the Gag region of an integrase-defective gag-pol construct, allowing for efficient encapsidation and protease-mediated release during virion maturation without compromising the viral titer. The resulting particles carried donor cassettes flanked by heterospecific loxP sites. When applied to CHO founder cells harboring compatible genomic loxP landing pads, Cre-IDLVs efficiently mediated recombination-mediated cassette exchange, producing the highest number of G418-resistant colonies among the plasmid ratios tested. Genomic PCR and sequencing confirmed precise locus-specific insertion without detectable random integration in the analyzed clones. These findings establish Cre-IDLVs as a streamlined dual-delivery platform that couples transient recombinase activity with episomal donor DNA transfer. This hybrid lentiviral strategy provides a programmable approach for controlled and site-specific genome modification in mammalian cells.

Integrases↗

PubMed2026

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans↗

PubMed2026

Innovations in microbial physical mutagenesis for food fermentation: An overview from traditional to emerging technologies.

Microbial strains serve as an important factor affecting fermentation efficiency and product quality. To obtain superior strains, mutation breeding is a classic strategy. Compared to chemical mutagenesis, physical mutagenesis directly induces genomic changes, providing notable advantages such as the elimination of chemical residues and environmental sustainability, hence rendering it a favored method for enhancing food-grade microorganisms. Conventional physical mutagenesis mostly depends on UV, rays, high pressure, or space radiation. As physical technologies advance, emerging methods such as ion implantation, plasma, microwave, ultrasound, and pulsed light are widely utilized for genetic modification. Mutagenesis technologies are progressively transitioning from single-effect to multi-effect synergy. Recent evaluations indicate that emerging technologies can enhance microbial mutation efficiency at the application level relative to established technologies. Nonetheless, the systematic clarification and comparative analysis at the mechanistic level remain inadequate, hindering intuitive comprehension of the qualities and distinctions across techniques. Furthermore, physical mutagenesis encounters several significant obstacles, such as cellular damage, limited rates of advantageous mutations, and laborious screening processes. This review carefully elucidates the mechanisms and properties of physical mutagenesis technology and delineates the distinctions among approaches through comparative analysis. Simultaneously, solutions for optimizing mutagenesis are presented to tackle the principal challenges mentioned above. This review aims to offer a theoretical foundation and practical guidance for the enhanced application of physical mutagenesis technologies in microbial breeding.

Mutagenesis↗

PubMed2026

A cooperative regulatory module between TAGL2 and JMJC1 activates specific defense genes against root-knot nematodes in tomato.

Plant-parasitic nematodes (PPNs) threaten global food security. Although epigenetic modifications are crucial for plant immunity, how histone modifiers contribute to root-knot nematodes (RKNs, Meloidogyne incognita) resistance remains unclear. Here, using genetic, molecular and biochemical approaches, we investigated the epigenetic and transcriptional mechanisms underlying RKN resistance mediated by the histone demethylase (HDM) JMJC1 and the MADS-box transcription factor TAGL2 in tomato (Solanum lycopersicum). We identified JMJC1 as an RKN-induced positive defense regulator targeting H3K9me3 and H3K27me3 histone marks. JMJC1 physically interacts with TAGL2, which also positively regulates RKN resistance. Transcriptomic analysis indicated that TAGL2 regulates multiple layers of the plant defense network, transcriptionally activating representative genes from distinct pathways (including PUB10, bHLH98, CCaMK, and SAUR3), which we validated as positive regulators of RKN resistance via virus-induced gene silencing (VIGS). At the chromatin level, TAGL2 and JMJC1 co-regulate these loci, associating with localized H3K9me3 and H3K27me3 reduction. Furthermore, TAGL2 directly activates JMJC1 transcription, establishing a positive feedback loop that amplifies immune signaling. Our findings reveal a cooperative model wherein a HDM and a transcription factor coordinate at specific loci to fine-tune multiple defense layers at both epigenetic and transcriptional levels, providing insights for breeding durable nematode-resistant plants.

Solanum lycopersicum↗

PubMed2025

Technology-Facilitated Gender-Based Violence Against Politically Active Women: A Systematic Review of Psychological and Political Consequences and Women's Coping Behaviors.

Technology-facilitated gender-based violence presents critical challenges for politically active women, whose professional roles often expose them to elevated levels of online abuse with far-reaching impacts on their emotional well-being, professional engagement, and participation in public life. This systematic review synthesizes findings from 48 studies employing qualitative, quantitative, and mixed-methods research to examine the psychological and political consequences and coping mechanisms associated with online harassment. Eighty-one percent of the included studies (39/48) report psychological distress, anxiety, and fear among targeted women, with 31% of the studies (15/48) identifying online harassment as a trigger for (re-) traumatization. The political consequences are equally significant, with 62% of the studies (30/48) documenting modifications in political messaging, 39% (19/48) noting reduced engagement with online platforms, and 29% (14/48) showing that women abandon their online presence altogether. Additionally, 20% (10/48) of the studies report cases of women withdrawing from their political roles. In terms of coping strategies, 66% (32/48) report women blocking or muting harassers, while 37% (18/48) document women reporting abuse to authorities or platforms. This study highlights the pervasive impact of technology-facilitated violence on women's emotional well-being, and their political participation and underscores its broader implications for democratic discourse and social equity.

Humans↗

PubMed2026

Integrated analysis uncovers exogenous induction and molecular regulation of erinacine A accumulation in Hericium erinaceus.

Erinacine A, a cyathane-type diterpenoid mainly from Hericium erinaceus mycelia, exhibits prominent neurotrophic and neuroprotective activities, making it a promising candidate for managing neurodegenerative diseases. However, its low abundance and unclear genetic regulatory mechanisms hinder its application as a nutraceutical. This study aimed to decipher its regulatory mechanisms and enhance production. Four exogenous inducers were screened, with salicylic acid (SA) and ergosterol (ERG) significantly increasing erinacine A content by 62.21% and 146.70% at 20 days, respectively. Transcriptome and WGCNA of inducer-treated sample identified darkorange and magenta modules associated with erinacine A biosynthesis, with the eri gene cluster enriched in the darkorange module and eriG and eriF as hub genes. Forward genetic analysis via QTL mapping of the HeD127 dikaryon population revealed significant phenotypic variation in erinacine A content (0.341-13.085 mg/g) and identified two loci (erA-1 and erA-2) explaining 18.63% of phenotypic variation. Integrating these forward and reverse genetic analyses revealed that salicylic acid and ergosterol synergistically regulate core carbon metabolic pathways to augment acetyl-CoA supply for the mevalonate pathway, suppressed competitive metabolism, enhanced diterpene skeleton construction and structural modification. These results deepen our understanding of the genetic and molecular basis governing accumulation of erinacine A, and facilitate its application in neuroprotective pharmaceuticals.

Diterpenes↗

PubMed2026

Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy that accounts for about 15%-20% of childhood leukemias. Despite therapeutic advances, relapses remain common, and survival for high-risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3-ITD, NPM1, KMT2A rearrangements, and core-binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non-coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances in silico transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA-seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi-omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of in silico transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision-based epigenetic therapies aimed at improving long-term outcomes in children with AML.

Humans↗

PubMed2026

Physiologic age modifies the association between visceral fat predominance and urinary calcium excretion in adults with nephrolithiasis.

Although adiposity is associated with kidney stone disease, the relationship between abdominal fat distribution and urinary calcium excretion remains unclear. We investigated whether the CT-derived visceral-to-subcutaneous fat ratio (VSR) was associated with 24-hour urinary calcium excretion and whether physiologic age modified this association. This retrospective cross-sectional study included 308 adults with nephrolithiasis who underwent preoperative CT, stone removal, and postoperative metabolic evaluation. Participants were stratified into prespecified younger (men aged < 50 years and premenopausal women) and older (men aged ≥ 50 years and postmenopausal women) physiologic-age groups. Multivariable linear regression assessed the association between VSR and urinary calcium excretion and its modification by physiologic age. Results showed that VSR was not associated with urinary calcium excretion in the overall cohort, but its association differed significantly by physiologic age (P for interaction < 0.001). Among younger participants, each 1-unit higher VSR was associated with 2.07 mmol/day greater urinary calcium excretion (95% CI, 1.23-2.90), whereas no significant association was observed in the older group. These findings suggest that the metabolic relevance of visceral fat predominance differs by physiologic age, with a significant association observed only in younger adults. Prospective studies are needed to confirm these findings and determine their clinical implications.

Humans↗

PubMed2026

Beyond predictive performance: A systematic review and critical methodological appraisal of AI/ML and conventional modelling strategies in breast, colorectal, and pancreatic Cancer.

BACKGROUND: Predictive modelling for cancer risk, treatment-related complications, and survival is central to precision oncology. Conventional logistic regression (LR) and Cox proportional hazards (CoxPH) regression remain widely used but are limited when modelling nonlinear interactions, high-dimensional imaging features, and multimodal clinical-metabolic predictors. Artificial intelligence (AI) and machine learning (ML) methods offer expanded capability through automated feature extraction, ensemble learning, and flexible survival modelling, but the evidence on when AI/ML adds value over conventional models across cancer sites and predictive tasks remains fragmented. OBJECTIVE: To systematically evaluate the methodological performance, validation strategies, and translational limitations of AI/ML models compared with conventional statistical models in published predictive-modelling studies for breast, colorectal, or pancreatic cancer. METHODS: PubMed, Scopus, and Web of Science were searched for studies published between January 2019 and March 2025. Two reviewers independently conducted title-and-abstract screening, full-text eligibility assessment, and PROBAST risk-of-bias assessment. Sixty-five studies (n = 907,567 participants) were narratively synthesised by cancer site, predictive task, model family, comparator, validation strategy, predictor modality, and calibration or explainability reporting. RESULTS: The 65 studies comprised breast cancer (n = 35), colorectal cancer (n = 21), and pancreatic cancer (n = 9). AI/ML superiority over LR and CoxPH was task- and data-dependent. CNN- and U-Net-based models predominated in imaging and body-composition tasks, tree-based ensembles consistently outperformed LR for tabular perioperative complication prediction, and CoxPH remained competitive, and in the largest pancreatic risk study, superior to XGBoost (C-index 0.802 vs 0.723) in well-structured datasets. PROBAST analysis-domain risk was moderate in 54 of 65 studies (83%), driven by limited external validation, sparse calibration reporting (11/65), and few decision-curve analyses (7/65). CONCLUSION: AI/ML adds the most methodological value in imaging-derived feature extraction and nonlinear perioperative prediction, while conventional regression remains preferable in large, structured datasets with linear predictors. Clinical translation requires standardised body-composition definitions, external validation, calibration assessment, decision-curve analysis, and explainability, in line with TRIPOD+AI and CLAIM standards.

Humans↗

PubMed2026

Morphological changes and transcriptomic insights into skeletal development of embryos and larvae of the sea urchin Strongylocentrotus intermedius.

To explore morphological features and molecular dynamics underlying skeletogenesis in the sea urchin Strongylocentrotus intermedius, we conducted combined morphological observation and comparative transcriptome analyses across representative embryonic and larval developmental stages. Morphological results showed that triradiate spicules first emerged at the gastrula stage. The 8-arm pluteus stage was identified as a key phase for skeletal remodeling, during which new three-radiate crystals transformed into complex stereoscopic ossicles including tube feet, spines and test plates. Transcriptomic data indicated that most differentially expressed genes (DEGs) were downregulated from the blastula to gastrula. The altered expression of basal metabolic genes and extracellular matrix genes including Colp2α and calm may be correlated with the linear mineralization of early spicules, which potentially reflects an energy adjustment pattern in developing larvae. During the transition from 6-arm to 8-arm pluteus, expression changes of calmodulin-like, Colp2α and SISin18G001660 suggest potential associations with regional calcium deposition and modifications of skeletal matrix properties. This work systematically characterizes morphological traits and transcriptional dynamics of skeletogenesis in S. intermedius. Its early spiculogenesis follows the conserved developmental pattern of echinoderms, while massive formation of stereoscopic ossicles occurs at the 8-arm pluteus stage. Stage-specific transcriptional changes across key larval skeletogenic stages are uncovered, offering transcriptomic resources for functional verification of skeletal regulatory genes.

Animals↗