Biology-Basel最新文献

{"title":"Breeding in the City: Non-Linear Associations of Urbanization, Tree Cover, and Human Disturbance with Eurasian Tree Sparrows (<i>Passer montanus</i>) Breeding Performance.","authors":"Igor Irazusta-Peco, Beatriz Martínez-Miranzo, José I Aguirre, Eva Banda","doi":"10.3390/biology15191746","DOIUrl":"10.3390/biology15191746","url":null,"abstract":"<p><p>Urbanization can alter habitat structure and disturbance regimes, with consequences for bird reproduction. We used 13 years of nest-box monitoring data from 15 urban green spaces in Madrid, Spain, with an average of 866 nest boxes monitored annually, to assess how urbanization, tree cover, building height, road infrastructure, noise, and pedestrian intensity were associated with Eurasian Tree Sparrow (<i>Passer montanus</i>) breeding performance. Nest-box occupancy, eggs and hatched chicks per box, nestlings reaching ringing age, and mean number of clutches showed non-linear associations with urbanization, with the highest values generally recorded in partially urbanized areas. Occupancy was 66.9% in these areas, compared with 17.5% in urbanized areas. Tree cover was positively associated with productivity in highly urbanized areas, suggesting that vegetation may be particularly relevant to productivity under highly urbanized conditions. In contrast, greater building height was associated with lower occupancy and reproductive performance. Pedestrian intensity was negatively related to nest-box use and reproductive output, whereas road infrastructure and noise mainly affected later reproductive stages. Overall, breeding performance was associated with the combined characteristics of vegetation, urban structure, and human disturbance. Maintaining partially urbanized green spaces and increasing tree cover in densely built areas may be associated with more favourable breeding conditions for Eurasian Tree Sparrows.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197344","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":"Wheat Rust Diseases: Global Impact, Integrated Disease Management, and Emerging Biotechnological Innovations for Sustainable Crop Protection.","authors":"Mingzheng Duan, Muhammad Asif Shabbir, Mustansar Mubeen, Yasir Iftikhar, Naureen Anwar, Shiping Jiang, Zhifang He, Sirui Han, Ahmed Mahmoud Ismail, Khalid M Alsyaad, Ahmed Ezzat Ahmed, Muhammad Umer","doi":"10.3390/biology15191756","DOIUrl":"10.3390/biology15191756","url":null,"abstract":"<p><p>Wheat (<i>Triticum aestivum</i> L.) remains one of the most important staple crops worldwide and serves as a primary source of calories and protein for billions of people. Global wheat production, however, continues to be threatened by rust diseases caused by <i>Puccinia triticina, Puccinia striiformis</i> f. sp. <i>tritici</i> and <i>Puccinia graminis</i> f. sp. <i>tritici</i>. These pathogens are highly adaptive and frequently give rise to new virulent races, causing resistance in wheat cultivars to breakdown. Under favorable environmental conditions, severe epidemics can develop and substantial yield losses may occur. In response to these challenges, traditional management approaches such as resistant cultivars, crop rotation, sanitation and fungicide application have long been employed in wheat production systems. Yet these strategies have increasingly been constrained by resistance breakdown, genetic uniformity in modern cultivars, and climate-driven changes in pathogen distribution. Conventional management practices are evaluated alongside emerging technological solutions including genomic-assisted breeding, gene pyramiding, CRISPR-based genome editing, biological control agents and precision agriculture tools. In addition, nanotechnology has emerged as a promising tool in plant disease management, where nanoparticles such as silver, copper and zinc oxide exhibit strong antifungal activity and enable targeted delivery of agrochemicals. Nano-enabled formulations can enhance fungicide efficiency, reduce chemical inputs and improve plant defense responses, offering a sustainable complement to existing wheat rust management strategies. Particular attention is given to integrated disease management strategies, which combine traditional agronomic practices with modern surveillance technologies such as remote sensing, artificial intelligence-based forecasting models, and pathogen genomics. These combined approaches can improve resistance durability and build more resilient wheat production systems. Future directions emphasize climate adaptation, global surveillance and collaborative breeding. In an era of increasing climatic uncertainty and evolving pathogen populations, durable rust management will depend on coordinated global efforts that align scientific innovation, farmer adoption, and policy support to safeguard wheat productivity and global food security.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197345","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":"Zinc Homeostasis in <i>Brucella ovis</i> Under Zinc Scarcity: Characterization of the ZnuABC Zinc Import System and of a Newly Identified Gene of the Zur Regulon.","authors":"Beatriz Tartilán-Choya, Ian S Barton, R Martin Roop, Nieves Vizcaíno","doi":"10.3390/biology15191753","DOIUrl":"10.3390/biology15191753","url":null,"abstract":"<p><p>The zinc import system ZnuABC is essential for the virulence of smooth (bearing O-polysaccharide chains) zoonotic <i>Brucella</i> species but remains uncharacterized in the non-zoonotic rough (lacking O-chains) species <i>Brucella ovis</i>, the causative agent of a type of ovine brucellosis of veterinary and economic importance. In this study, we constructed a panel of <i>B. ovis</i> mutants for genes of the <i>znuACB</i> locus that were characterized by evaluating growth, gene expression, protein abundance, metal content, and virulence in mice. We identified a ZigA ortholog (uncharacterized in the genus <i>Brucella</i> but linked to zinc homeostasis and histidine metabolism in other bacteria) that belongs to the Zur regulon and is transcriptionally modulated in a zinc-dependent manner as the ZnuABC system. A potential link of <i>B. ovis</i> ZigA with histidine catabolism and a crosstalk between the homeostasis of zinc and other metals have been identified as areas for further exploration. Remarkably, the <i>znuA</i>, <i>zigAznuA</i> and <i>znuACB</i> mutants of <i>B. ovis</i> displayed wild-type virulence in mice, which contrasts with the reported attenuation for the <i>znuA</i> mutant of smooth zoonotic <i>Brucella</i> species sharing a high degree of DNA homology. These results significantly enlarge the knowledge about the metallobiology of the genus <i>Brucella</i>, providing new perspectives for related research.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197364","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":"Calmodulin: The Essential Biological Regulator Self-Regulates Its Activity, Structure and Function.","authors":"Danton H O'Day","doi":"10.3390/biology15191750","DOIUrl":"10.3390/biology15191750","url":null,"abstract":"<p><p>Calmodulin is an evolutionarily conserved critical controller protein found in animals, plants, fungi, and microbes. As the primary calcium sensor and effector in eukaryotes, calmodulin translates calcium signals into vital biological responses by binding to and regulating calmodulin-binding proteins. While it was previously shown to control several hundred proteins, evidence now indicates it binds to over 100 in its calcium-free state and more than 500 when activated by calcium ions. While calmodulin function is modulated by calcium levels, the final cytosolic levels of calcium are often under calmodulin's control. Human calmodulin is encoded by three unique genes (<i>CALM1-3</i>), each of which produces an identical functional protein. The <i>CALM</i> genes are among the most mutation-intolerant sequences in the human genome. They are under the control of two calmodulin-binding transcription activators (CAMTAs) that are also ancient, highly conserved, and, as their name implies, under the control of calmodulin. Thus, calmodulin controls the transcription of the genes that encode it. Finally, two primary post-translational events that affect the function and stability of calmodulin are also regulated by it: methylation, which stabilizes the functional protein, and phosphorylation, which regulates its activity as needed. This review covers those topics to reveal that calmodulin controls its own expression, structure, and function, reflecting its unique position as an essential major regulator of cell function.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197304","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":"Elevated Atmospheric CO₂ Modifies Symbiont-Associated Dispersal Behavior Under a Standardized Assay in an Aphid Clone.","authors":"Edward Mondor, Tyler Follman, Kerry M Oliver","doi":"10.3390/biology15191748","DOIUrl":"10.3390/biology15191748","url":null,"abstract":"<p><p>Rising atmospheric CO₂ levels may alter behavioral dynamics that mediate species interactions, a largely overlooked dimension of ecosystem functioning. Aphids offer a tractable model for examining these modifications, as their primary protection from natural enemies relies on the alarm pheromone (E)-β-farnesene (Eβf). Facultative aphid endosymbionts like Candidatus <i>Hamiltonella defensa</i> complicate this dynamic by modifying parasitoid resistance and associated behaviors, yet their interaction with elevated CO₂ remains largely unexplored. Using a single clone of the pea aphid <i>Acyrthosiphon pisum</i> (Harris), we investigated how CO₂ levels and <i>H. defensa</i> D3 status, independently and interactively, altered <i>Vicia faba</i> L. plant size, aphid fecundity, and aphid dispersal responses to Eβf. Here we show that dry shoot weights of bean plants grown under elevated CO₂ increased, compared to those grown under ambient conditions. Irrespective of CO₂ level, however, aphids harboring <i>H. defensa</i> produced significantly more offspring, and dispersed at significantly higher rates in response to Eβf than symbiont-free individuals. Under the standardized Eβf assay, the difference in dispersal between <i>H. defensa</i>-harboring aphids and those that were symbiont-free was large under ambient CO₂ (59% vs. 9%) and smaller under elevated CO₂ (23% vs. 12%). Thus, elevated CO₂ reduced symbiont-associated differences in dispersal under standard assay conditions in this aphid clone with implications for tri-trophic interactions, biological control efficacy, and symbiont prevalence under future atmospheric conditions.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196988","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":"Habitat Quality, Conservation Gaps, and Environmental Suitability of Siberian Cranes (<i>Leucogeranus leucogeranus</i>) in the Erlongtao River Basin, Songnen Plain.","authors":"Yang Wen, Haibo Jiang, Shiying Zhu, Junqi You, Huiyun Yue, Hanbo Teng, Chunguang He","doi":"10.3390/biology15191759","DOIUrl":"10.3390/biology15191759","url":null,"abstract":"<p><p>Wetland degradation induced by climate change and human disturbance poses severe threats to migratory waterbirds, particularly the critically endangered Siberian crane (<i>Leucogeranus leucogeranus</i>). The Erlongtao River Basin, a key stopover wetland complex on the Songnen Plain, exhibits prominent mismatches between general waterbird habitat quality and species-specific habitat suitability, together with widespread conservation gaps. In this study, line-transect and point-sampling field surveys were conducted during spring and autumn migration (2020-2024). The eight phases of land use datasets (1990-2023), the InVEST Habitat Quality module, and the MaxEnt habitat suitability model were used to quantify 33-year spatiotemporal dynamics of habitat quality and contributions from land use transitions, map spatial patterns of Siberian crane suitable habitats, and identify conservation gaps within and outside two national nature reserves. Wetland shrinkage and swamp fragmentation degraded regional foraging and habitat conditions for waterbirds. Transitions from unused and construction land to water bodies, shallows, and swamps increased habitat quality, whereas cropland expansion and soil salinization drove habitat degradation. In 2020, high-, moderate, and low-suitability habitats for Siberian cranes occupied merely 0.18%, 1.37%, and 3.55% of the total watershed area, respectively. Dry farmland constituted 47.97% of high-suitability habitats, 44% of which belonged to the poor-quality land cover class grade. Meanwhile, 66% of highly suitable habitats and 68% of moderate-suitability habitats occurred outside protected area boundaries. Targeted restoration of water body and swamp patches with high habitat quality contributions is needed to maintain Siberian crane populations. This work offers quantitative conservation strategies for this flagship species and provides theoretical support for spatial planning of the proposed Songnen Crane National Park.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197332","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":"Distinct Evolutionary Trajectories of Major Intracellular Proteolytic Systems in Gilthead Seabream and European Seabass.","authors":"Rafael Angelakopoulos, Andreas Tsipourlianos, Themistoklis Giannoulis, Katerina A Moutou","doi":"10.3390/biology15191755","DOIUrl":"10.3390/biology15191755","url":null,"abstract":"<p><p>Intracellular proteolysis is essential for protein turnover, cellular homeostasis, stress responses, immune function, development and tissue remodeling. In teleost fishes, ancient vertebrate and teleost-specific whole-genome duplication events (1R, 2R, Ts3R) increased gene copy number, followed by lineage-specific patterns of gene retention, loss and regulatory divergence. We investigated three major intracellular proteolytic systems, the ubiquitin-proteasome system (UPS), calpains and cathepsins, in gilthead seabream (<i>Sparus aurata</i>) and European seabass (<i>Dicentrarchus labrax</i>). Using comparative genomic, phylogenetic, syntenic and transcriptomic approaches, we identified and curated gene repertoires, inferred duplication histories and examined developmental and tissue-specific expression patterns. We identified 29 and 22 calpain genes, 23 and 17 cathepsin genes and 61 and 53 UPS genes in gilthead seabream and European seabass, respectively. Phylogenetic and synteny analyses indicated that retained paralogs were inferred to derive from a combination of ancient vertebrate duplications, teleost-specific whole-genome duplication and lineage- or species-specific events. Single copy genes predominated the UPS and only selected duplicated components showed patterns compatible with retention following the Ts3R. In contrast, calpains and cathepsins showed broader paralog retention, mixed duplication origins and greater diversity in developmental and tissue-specific expression patterns. Expression profiling indicated that most UPS genes were broadly expressed, whereas several calpain and cathepsin paralogs displayed stage- or tissue-dependent expression patterns. Overall, these results suggest that intracellular proteolytic systems in teleosts followed partly distinct evolutionary trajectories, with comparatively greater conservation of the multi-subunit UPS and expression patterns consistent with greater regulatory divergence among calpain and cathepsin paralogs. Retained proteolytic paralogs therefore displayed divergent expression patterns consistent with possible regulatory divergence which could reflect subfunctionalization following genome duplication.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196547","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":"Harnessing Ratoon Cropping for Mitigating Greenhouse Gas Emissions.","authors":"Xin Zhang, Hai Huang, Zengqiang Li, Xiangjun Kong, Aziz Khan, Yanbo Zhang","doi":"10.3390/biology15191751","DOIUrl":"10.3390/biology15191751","url":null,"abstract":"<p><p>Ratoon cropping systems have gained increasing attention for their potential to mitigate greenhouse gas (GHG) emissions, including carbon dioxide (CO₂), methane (CH₄), and nitrous oxide (N₂O). Building on the well-established root system of the previous crop, ratoon crops require no land preparation, sowing, or transplanting and need less fertilizer, water, and pesticides than annual crops while achieving earlier harvests, thereby reducing GHG emission intensity (GHGI) by 7.9-17.3% and N₂O emissions by 40.4-78.1%. Reduced fertilization, efficient water management, and integrated pest management can further curtail GHG emissions, while improved soil fertility, sustainable land management, and cover crop integration enhance soil carbon sequestration. Genetic improvement of ratoon crops can additionally enhance stress tolerance and resource use efficiency, reducing fertilizer requirements and ultimately lowering GHG emissions. This review also addresses ratoon cropping in dryland systems, including sugarcane, sorghum, cotton, and pigeon pea, highlighting their distinct GHG emission profiles and mitigation potential. Its innovative contribution is an integrated framework-synthesizing crop physiology, soil carbon processes, agronomic management, and genetic improvement-that evaluates GHG mitigation opportunities across both ratoon rice and dryland ratoon crops while explicitly addressing trade-offs, context-dependency, and evidence gaps.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197366","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":"Mitochondrial Genome of the Korean Endemic <i>Arabis takesimana</i> (Brassicaceae): Addition to the Genomic Resources and Evolutionary Insights.","authors":"Asif S Tamboli, Jin-Suk Youn, Suhas K Kadam, Manoj M Lekhak, Jan Bocianowski","doi":"10.3390/biology15191762","DOIUrl":"10.3390/biology15191762","url":null,"abstract":"<p><p>Brassicaceae is a major model system for studies of plant evolution, systematics, comparative genomics, and speciation; however, mitochondrial genomic resources remain limited compared to plastid genomic resources, constraining investigations of mitochondrial genome evolution. Here, we report the mitogenome of the Korean endemic species <i>Arabis takesimana</i>, representing only the third available mitogenome for the genus <i>Arabis</i>. The mitogenome is 291,633 bp in length with a GC content of 45.3%. It was assembled with an average sequencing depth of 298.9×. It contains 58 annotated genes, including 34 protein-coding genes, three rRNA genes, and 21 tRNA genes. A 5.15 kb mitochondrial plastid DNA insertion (MIPT) region contributes four intact plastid-derived tRNA genes (<i>trn</i>A, <i>trn</i>L-CAA, <i>trn</i>S-GGA, and <i>trn</i>N-GUU) and a partial <i>rrn18</i> gene. The mitogenome also contains 21.83 kb of transposable element (TE) sequences and 44.03 kb of repetitive DNA, representing 7.48% and 15.09% of the genome, respectively. Comparative analysis of 32 Brassicaceae mitogenomes revealed 30 conserved mitochondrial protein-coding genes shared across the sampled taxa, whereas <i>rpl2</i>, <i>rpl10</i>, <i>rps1</i>, <i>rps10</i>, <i>rps13</i>, <i>rps14</i>, <i>rps19</i>, <i>sdh3</i>, and <i>sdh4</i> exhibited lineage-specific patterns of truncation, pseudogenization, or loss. Linear regression revealed a strong positive association between mitogenome size and TE content (<i>R</i>² = 0.7245), whereas MIPT content (<i>R</i>² = 0.09146) and repetitive DNA (<i>R</i>² = 0.1896) showed weaker associations with mitogenome size. Nucleotide diversity analyses identified highly variable mitochondrial loci with potential as molecular markers. Phylogenetic analyses based on conserved mitochondrial protein-coding genes resolved sampled Brassicaceae species with strong support and established the phylogenetic placement of <i>A. takesimana</i>, highlighting the utility of mitogenomic data for evolutionary, phylogenetic, and comparative genomic studies within the family.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197222","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":"In Silico Evaluation via Virtual Screening, ADMET Profiling and Molecular Dynamics Simulations: Synthesis and Biological Activity Analysis of a Novel Antitumor PI3K Inhibitor.","authors":"Wenqing Jia, Yukui Ma, Zhe Zhang","doi":"10.3390/biology15191742","DOIUrl":"10.3390/biology15191742","url":null,"abstract":"<p><p>The PI3K plays a crucial role in cancer progression, and the development of PI3K inhibitors has always been a hot research direction in oncology. Through virtual screening and docking, potential lead compounds were identified. ADMET prediction revealed that KTC101 possesses superior pharmacokinetic profile. Molecular dynamics simulations indicated that compound KTC101 could stably bind to PI3Kδ, with a binding free energy of -374.627 kJ/mol. Analysis of the metabolism of KTC101 revealed that this compound could undergo diverse phase I metabolic reactions catalyzed by hepatic CYP450 enzymes to form highly polar metabolites, indicating its strong metabolic potential and easy metabolic clearance in vivo. Then it was synthesized and evaluated for kinase inhibitory activity and antiproliferative effects in HNSCC cell lines. KTC101 was first reported as a PI3K inhibitor, with IC₅₀ values of 191.23 ± 40.84 nM, 23.30 ± 5.68 nM, and 146.20 ± 21.82 nM for PI3Kα, PI3Kδ and PI3Kγ, respectively, and demonstrated dose-dependent inhibition of cancer cell growth in vitro, with IC₅₀ values of 4.1 ± 0.73 μM for HSC3 cells and 2.2 ± 0.11 μM for HSC4 cells. It exhibited inhibitory activity against PI3K, showing greater inhibitory potency toward PI3Kδ. This study demonstrates the anti-tumor potential of KTC101.</p>","PeriodicalId":48624,"journal":{"name":"Biology-Basel","volume":"15 19","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149196578","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}