Biology-BaselPub Date : 2025-09-18DOI: 10.3390/biology14091290
Paul Medina-González
{"title":"Morphofunctional Spaces from the Astragalus: Exploring Angular Excursions and Mechanical Efficiency in <i>Caraguatypotherium munozi</i> (Notoungulata, Mesotheriidae).","authors":"Paul Medina-González","doi":"10.3390/biology14091290","DOIUrl":"10.3390/biology14091290","url":null,"abstract":"<p><p>The astragalus is a key biomechanical link between the autopodium and limb in mammals, modulating stability and mobility during stance. Its morphology provides reliable proxies for inferring posture, body mass, and locomotor behavior in extinct taxa. Mesotheriids (Notoungulata, Mesotheriidae) have traditionally been regarded as fossorial generalists, yet their functional diversity remains poorly tested. The astragali of <i>Caraguatypotherium munozi</i> (Miocene, Chile) and <i>Trachytherus spegazzinianus</i> (early Miocene, Argentina) were analyzed, integrating osteological measurements and functional indices to explore their locomotor ecology. Principal component analyses were performed to compare their morphofunctional spaces with those of 38 extant terrestrial mammals grouped by posture, body mass, top speed, and locomotor habit. Total Angular Excursion (TAE) and Angular Efficiency Index (AEI) were estimated using a comparative dataset of 182 terrestrial mammals spanning 15 taxonomic orders, focused on stance-phase mechanics during comfortable locomotion. <i>C. munozi</i> shows a deeper trochlea and moderately expanded navicular facets, whereas <i>T. spegazzinianus</i> presents a shallower trochlea and narrower articular proportions. Despite these morphological differences, both species share broadly overlapping stance-phase kinematic ranges, reflecting a conserved plantigrade locomotor module optimized for stability and energy-efficient weight support. These findings challenge the view of mesotheriids as functionally uniform and highlight ecological diversification through subtle morphological adjustments within a constrained locomotor framework.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-18DOI: 10.3390/biology14091291
Cuixia Zhang, Haiming Li, Mengdi Li, Sihui Su, Han Xiao, Xiaodong Zhang, Qian Zhang
{"title":"Contrasting Assembly and Network Roles of Abundant and Rare Bacteria in Reservoir and Soil Habitats.","authors":"Cuixia Zhang, Haiming Li, Mengdi Li, Sihui Su, Han Xiao, Xiaodong Zhang, Qian Zhang","doi":"10.3390/biology14091291","DOIUrl":"10.3390/biology14091291","url":null,"abstract":"<p><p>Reservoir water and the adjacent soil are ecologically interconnected yet distinct microhabitats in saline coastal wetland ecosystems, but direct comparisons of their bacterial community composition and assembly remain limited. Here, we integrated high-throughput 16S rRNA gene sequencing with statistical, null model, and network analyses to compare diversity patterns, assembly mechanisms, and interactions of abundant and rare bacterial taxa in both habitats. Soil communities exhibited greater taxonomic diversity but a lower overall abundance, while reservoir communities displayed a pronounced vertical stratification, in contrast to the more spatially uniform soil communities at the sampled scale. Key environmental drivers differed: salinity (reflecting the harsh saline context) and nutrient levels structured reservoir communities, whereas the nutrient availability and cation exchange capacity predominated in soils. Stochastic processes mainly governed the assembly of abundant taxa in both habitats, whereas deterministic selection more strongly structured rare taxa, especially in soils subject to harsh saline conditions. The co-occurrence network analysis revealed higher connectivity and modularity in soils, with moderate taxa acting as critical connectors between modules. In contrast, rare taxa played a pivotal role in sustaining network stability in the reservoir. Together, these findings demonstrate distinct, habitat-dependent assembly mechanisms and ecological roles of abundant and rare bacterial taxa in saline coastal wetland microhabitats, providing insights that can inform wetland conservation and ecosystem management.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-18DOI: 10.3390/biology14091287
Yue Liang, Timothy P Topper, Baopeng Song, Caibin Zhang, Oluwatoosin B A Agbaje, Lars E Holmer, Zhifei Zhang
{"title":"Branched Setae or Attached Macroalgae: A Case Study of an Exceptionally Preserved Brachiopod from the Early Cambrian Chengjiang Lagerstätte.","authors":"Yue Liang, Timothy P Topper, Baopeng Song, Caibin Zhang, Oluwatoosin B A Agbaje, Lars E Holmer, Zhifei Zhang","doi":"10.3390/biology14091287","DOIUrl":"10.3390/biology14091287","url":null,"abstract":"<p><p>The remarkable conservation of soft tissues within Cambrian fossils has significantly enhanced our comprehension of the origins and evolutionary trajectories of animals, in addition to the progression of ecological intricacy. Here, we report an exceptionally preserved specimen of the lingulid brachiopod <i>Xianshanella haikouensis</i> from the lower Cambrian Chengjiang Lagerstätte, exhibiting branched fringes along the distal ends of its marginal setae. These structures may represent either branched setae or attached macroalgae. The diameter of the branched fringes is slightly larger than that of the marginal setae, and they exhibit third- or fourth-order bifurcations, forming a complex structure comparable in length to the shell. Both the branched fringes and marginal setae are preserved as iron oxides, as revealed by SEM and Micro-XRF analyses, a characteristic preservation mode in Chengjiang fossils. The results of Micro-CT scanning suggest that these branched fringes are preserved along almost the entire distal end of marginal setae. Comparable branched fringes are reminiscent of those found in annelids, and such structural analogs between annelid and brachiopod setae support the homology of brachiopod and annelid setae, representing a lophotrochozoan synapomorphy. An alternative explanation involving attached macroalgae is proposed, given that branched setae have never been documented in either extinct or extant brachiopod taxa. If these structures represent macroalgae, this association could represent a mimicry strategy to deceive predators, although comparable macroalgal fossils remain undocumented in the Chengjiang Lagerstätte. Our research highlights the potential for brachiopod setae to serve roles in sensory function or ecological interactions, offering a new perspective on early animal adaptation and community dynamics.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091282
Claudia Cosentino, Antonio Caruso
{"title":"The Progressive Colonization of the Invasive Species <i>Amphistegina lobifera</i> on Pantelleria Island (Central Mediterranean, Sicily Channel).","authors":"Claudia Cosentino, Antonio Caruso","doi":"10.3390/biology14091282","DOIUrl":"10.3390/biology14091282","url":null,"abstract":"<p><p><i>Amphistegina lobifera</i>, a symbiont-bearing benthic foraminifera native to the Indo-Pacific, is expanding its distribution range in the Mediterranean Sea due to <i>ysian</i> migration through the Suez Canal. This study investigates the colonization dynamics and ecological impact of <i>A. lobifera</i> on Pantelleria Island, which is located in the Central Mediterranean. Nine samples were collected from various substrates at different depths (-4 to -20 m) and analysed for composition, abundance, and ecological diversity. Results reveal a significant dominance of <i>A. lobifera</i>, especially in shallow unvegetated substrates, with relative abundances exceeding 50%. Conversely, more vegetated substrates host more diverse and balanced assemblages. Diversity indices are consistently lower where <i>A. lobifera</i> is dominant, indicating reduced biodiversity. Comparison with similar studies in Malta, Linosa, and Corfu confirms a 20% relative abundance threshold for <i>A. lobifera</i> as indicative of potential ecological imbalance. The results suggest that it represents a growing threat to native microbenthic biodiversity and reinforce its usefulness as a bioindicator species. Pantelleria represents a key transition zone for monitoring the dynamics of invasive species in the Mediterranean, and this study highlights the urgent need for long-term surveillance of benthic biodiversity.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091278
Natalia Zeber-Lubecka, Maria Kulecka, Aneta Balabas, Pawel Czarnowski, Kazimiera Pyśniak, Michalina Dąbrowska, Jerzy Ostrowski, Ewa E Hennig
{"title":"Lifetime Changes in Gut Microbiota and Metabolite Composition in High-Fat Diet-Induced Obesity in Apolipoprotein A-IV Gene Knockout Mice.","authors":"Natalia Zeber-Lubecka, Maria Kulecka, Aneta Balabas, Pawel Czarnowski, Kazimiera Pyśniak, Michalina Dąbrowska, Jerzy Ostrowski, Ewa E Hennig","doi":"10.3390/biology14091278","DOIUrl":"10.3390/biology14091278","url":null,"abstract":"<p><p>Apolipoprotein A-IV (ApoA-IV) has been implicated in modulating the gut microbiota. However, chronic high-fat diet (HFD) consumption impairs ApoA-IV signaling and disrupts gut microbial balance, contributing to obesity and insulin resistance. This study aimed to investigate the role of ApoA-IV in shaping the gut microbiota and associated metabolic profiles throughout the lifespan of mice exposed to an HFD. Fecal samples were collected from ApoA-IV knockout (KO) and wild-type mice at five time points for microbiota and metabolite profiling using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. Lifespan was longest in ApoA-IV-KO mice on a normal diet, while the HFD reduced survival across genotypes. Microbiota analysis revealed diet- and age-dependent shifts, including an elevated Firmicutes/Bacteroidota ratio, altered abundance of <i>Akkermansia</i> and reduced <i>Monoglobus</i> in ApoA-IV-KO mice on the HFD. Metabolic profiling showed a stronger impact of diet than genotype, with early and persistent increases in branched-chain amino acids and reductions in short-chain fatty acids (SCFAs). ApoA-IV deficiency modulated lifespan microbial and metabolic changes and shaped distinct responses to dietary stress. Despite age-related convergence in microbiota structure, genotype-specific differences in metabolite profiles and SCFA-producing bacteria correlations persisted into old age, demonstrating the lasting impact of ApoA-IV on host metabolic adaptation.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of Variation in Abdominal Adipose Color Among Male Kazakh Horses Through Non-Coding RNA Sequencing.","authors":"Yuhe Zhou, Xinkui Yao, Jun Meng, Jianwen Wang, Yaqi Zeng, Linling Li, Wanlu Ren","doi":"10.3390/biology14091285","DOIUrl":"10.3390/biology14091285","url":null,"abstract":"<p><p>The Kazakh horse is a highly valuable indigenous Chinese breed known for its use in both milk and meat production. However, the mechanisms underlying color variation in the abdominal adipose tissue of this breed remain poorly understood. In this study, the sequencing of non-coding RNAs (ncRNAs) was conducted on abdominal adipose tissue of different colors from Kazakh horses, with the aim of investigating the molecular mechanisms responsible for this variation. A total of 205 differentially expressed long non-coding RNAs (DELncRNAs) including <i>ENSECAG00000003836</i>, <i>ENSECAG00000017858</i>, and <i>ENSECAG00000035167</i>; 52 differentially expressed microRNAs (DEmiRNAs) including <i>miR-200-y</i> and <i>eca-miR-9a</i>; and 559 differentially expressed circular RNAs (DEcircRNAs) including <i>ZNF226</i> and <i>ITPKC</i>, were identified between Group W and Group Y. GO annotation and KEGG enrichment analyses of the DEGs revealed that these genes were primarily involved in biological processes such as chemical homeostasis (biological process, BP), intracellular components (cellular component, CC), and iron-sulfur cluster binding (molecular function, MF) as well as in metabolic pathways related to lipid biosynthesis and metabolism including vitamin B6 metabolism, tryptophan metabolism, and glycerolipid metabolism. The sequencing accuracy was further validated using reverse transcription quantitative PCR (RT-qPCR). This study identified key DEGs and signaling pathways associated with the color variation in adipose tissue of Kazakh horses and sheds light on the regulatory genes and biological processes involved. These findings provide a theoretical basis and research foundation for future studies on color variations in the adipose tissue of equine species.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091281
Adelaide Carista, Melania Ionelia Gratie, Francesco Cappello, Stefano Burgio
{"title":"HSP60 and SARS-CoV-2: Les Liaisons Dangereuses.","authors":"Adelaide Carista, Melania Ionelia Gratie, Francesco Cappello, Stefano Burgio","doi":"10.3390/biology14091281","DOIUrl":"10.3390/biology14091281","url":null,"abstract":"<p><p>Heat shock protein 60 (Hsp60) plays a crucial role in cellular homeostasis and stress responses. Recent evidence highlights its involvement in COVID-19 pathophysiology, particularly in immune modulation, inflammation, and endothelial dysfunction. Extracellular Hsp60 can interact with Toll-like receptors, amplifying inflammatory responses and contributing to cytokine storm and tissue damage. Additionally, since the presence of several common epitopes with SARS-CoV-2 proteins, its role in molecular mimicry suggests a potential link also to post-infectious autoimmune disorders. Hsp60 has also been implicated in endothelial damage and thromboembolic complications observed in severe COVID-19 cases. Beyond its pathogenic roles, Hsp60 could emerge as a potential biomarker for disease severity as well as a target for therapeutic strategies aimed at modulating immune responses. Finally, the structural similarity with SARS-CoV-2 proteins raises important considerations regarding both vaccine safety and the unexpected potential for anti-tumor immunity. This review critically examines the multifaceted roles of Hsp60 in COVID-19, specifically from a morpho-functional point of view, highlighting its implications in disease progression, post-viral complications, and therapeutic opportunities.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091279
Surajit Hansda, Hiranmoy Das
{"title":"Unraveling the Bone-Brain Communication Network.","authors":"Surajit Hansda, Hiranmoy Das","doi":"10.3390/biology14091279","DOIUrl":"10.3390/biology14091279","url":null,"abstract":"<p><p>The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone-brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone-brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091286
Cynthia Philibert, Joana Ferrolho, Mark S Gibson, Sérgio Ramalho de Sousa, Hugo Vilhena, Sofia Anastácio
{"title":"The Challenge of Lyme Borreliosis: Knowledge, Attitudes, and Practices in France.","authors":"Cynthia Philibert, Joana Ferrolho, Mark S Gibson, Sérgio Ramalho de Sousa, Hugo Vilhena, Sofia Anastácio","doi":"10.3390/biology14091286","DOIUrl":"10.3390/biology14091286","url":null,"abstract":"<p><p>Lyme borreliosis (LB), a zoonotic disease caused by <i>Borrelia burgdorferi</i> sensu lato and transmitted by <i>Ixodes ricinus</i>, is increasingly relevant in France, yet data on public awareness and prevention are limited. This cross-sectional study assessed the knowledge, attitudes, and practices (KAP) of companion-animal owners (CAOs) and veterinarians regarding LB. Online questionnaires were distributed between January and April 2023, yielding 159 valid CAO responses and 48 responses from veterinarians. Among owners, 95% reported outdoor access for their pets, 73.9% had observed ticks, and 88.8% used ectoparasiticides. However, only 16.4% reported LB vaccination, and just 38% recognized key canine clinical signs. Veterinarians frequently suspected LB (70%) but confirmed diagnoses less often (39.6%), relying mainly on clinical signs and the results of rapid tests. While prevention through antiparasitic use was common, communication between veterinarians and owners regarding LB was inconsistent. Despite this, most owners reported compliance with veterinary guidance. These findings reveal good preventive habits but identify knowledge gaps and underdiagnosis. Enhancing veterinary-client communication and promoting a One Health approach could improve LB prevention and control in France.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology-BaselPub Date : 2025-09-17DOI: 10.3390/biology14091280
Faris Alrumaihi
{"title":"Ferroptosis-Linked Six-Gene Panel Enables Machine Learning-Assisted Diagnosis and Therapeutic Guidance in Lung Adenocarcinoma.","authors":"Faris Alrumaihi","doi":"10.3390/biology14091280","DOIUrl":"10.3390/biology14091280","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) remains the most common subtype of non-small-cell lung cancer and a major cause of cancer mortality, with many patients lacking actionable mutations or durable responses to targeted or immune therapies. Here, we report an integrative analysis of TCGA LUAD transcriptomes (n = 598) seeded from a curated ferroptosis gene catalogue, yielding a compact six-gene signature (AQP4, CDCA3, HJURP, KIF20A, PLK1, UHRF1) with diagnostic, prognostic, and therapeutic relevance. The signature was consistently dysregulated in tumours versus normal lung and stratified patients into high- and low-risk groups with distinct survival outcomes (log-rank <i>p</i> < 0.0001), outperforming conventional staging when incorporated into multivariable models. Across ten machine learning algorithms, the panel achieved near-perfect tumour-normal classification (AUC 0.99-1.00), highlighting its translational potential for early detection. Functional analyses linked the signature to cell-cycle, angiogenic, and immune modulation, while exploratory drug-gene correlations identified PLK1 and other candidates as potential therapeutic targets. Together, these findings establish a biologically anchored six-gene panel that complements existing mutation-based classifiers and provides a framework for advancing diagnostic precision, prognostic refinement, and biomarker-guided therapeutic strategies in LUAD.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"14 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}