Scientific Reports最新文献

{"title":"Computational screening identifies selective aldose reductase inhibitors with strong efficacy and limited off target interactions.","authors":"Jicli Jose Rojas, Roberto Pestana-Nobles, Leonardo C Pacheco-Londono, Jesús Utria-Munive, Nataly J Galan-Freyle","doi":"10.1038/s41598-025-12859-x","DOIUrl":"https://doi.org/10.1038/s41598-025-12859-x","url":null,"abstract":"<p><p>Diabetes mellitus is characterized by persistent hyperglycemia that triggers micro-vascular complications in organs such as the eyes and kidneys; a pivotal enzymatic driver is aldose reductase (AR), which reduces glucose to sorbitol. Because existing AR inhibitors often cause off-target toxicity, we implemented an integrative in-silico workflow to discover selective, safer compounds. A library of 4 975 small molecules was docked against AR and, in parallel, against five clinically relevant antitarget proteins or proteins whose unintended inhibition is associated with adverse pharmacological or toxicological effects (CYP2A6, CYP2C9, CYP3A4, SULT1A3 and the pregnane X receptor), retaining 236 ligands whose binding energies to every antitarget were weaker than those of the reference drug tolrestat. These survivors were redocked to five high-resolution human AR crystal structures, and the ten best-scoring ligands underwent 100 ns molecular-dynamics simulations followed by MM-PBSA free-energy calculations to refine affinity estimates and probe complex stability. Ligand 4934, a benzo[a]anthracene-pyrene polyphenol, displayed the strongest predicted affinity for while showing poor affinity for the antitarget panel, outperforming tolrestat by more than 2 kcal mol⁻¹ and adopting a stable plug-like pose that occludes the catalytic pocket through extensive π-π and hydrophobic contacts with Trp111, Phe123 and Lys22. These findings highlight ligand 4934 as a promising scaffold for selective AR inhibition and demonstrate the effectiveness of the stepwise computational strategy in prioritizing lead compounds with reduced off-target liabilities.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28111"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Epstein Barr virus biosensor by mimicking its infection mechanism for early detection of multiple sclerosis.","authors":"Ülkü Anik, Nil Su Çaylayik","doi":"10.1038/s41598-025-13030-2","DOIUrl":"https://doi.org/10.1038/s41598-025-13030-2","url":null,"abstract":"<p><p>Given the established link between Epstein-Barr virus (EBV) and multiple sclerosis, the early and asymptomatic detection of EBV has become increasingly important. In this study, we developed an impedimetric EBV biosensor designed for practical and early screening, based on mimicking the virus's natural infection mechanism. To achieve this, the B cell surface protein CD21-serving as the host receptor-was immobilized onto a carbon screen-printed electrode. The interaction between CD21 and the EBV surface glycoprotein gp350 was monitored using electrochemical impedance spectroscopy. Following the optimization of experimental parameters, the biosensor's analytical performance was evaluated. It exhibited a linear detection range from 5 to 100 ng/mL, with a limit of detection of 0.0074 ng/mL, a limit of quantification of 0.022 ng/mL, and a relative standard deviation of 1.34%. The optimized biosensor was then tested using 1:100 diluted saliva samples collected from healthy individuals, yielding highly promising results that support its potential for real-world applications.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28089"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flow regime transitions in flow blurring injection through a CFD parametric study.","authors":"S Amirreza S Madani, Erfan Vaezi, Mohammad Reza Morad, Amir Keshmiri","doi":"10.1038/s41598-025-13047-7","DOIUrl":"https://doi.org/10.1038/s41598-025-13047-7","url":null,"abstract":"<p><p>Flow-blurring (FB) is a twin-fluid atomization technique that generates fine sprays through internal turbulent mixing. This study presents a parametric computational investigation of an FB injector operating with air and various liquids at ambient pressure. A validated unsteady two-phase solver based on the Volume of Fluid (VOF) method is used to model the injector at different air-to-liquid mass flow rate ratios (ALRs). Parameters such as penetration length, volume fraction, static pressure, vorticity magnitude, and turbulent kinetic energy are analyzed to understand flow dynamics. The results identify three distinct flow regimes: air-dominant, liquid-dominant, and bubbly flow. Screening analysis of a full factorial design of 32 cases shows that liquid mass flow rate and dynamic viscosity are the most influential factors in penetration length. The resulting penetration length varies between 2 [mm] and 8.5 [mm] across the design space. A correlation analysis confirms these findings and reveals important two-way interactions between parameters, such as the positive effect of combined liquid and air mass flow rates. This insight offers a promising pathway for optimizing flow-blurring injectors in various applications.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28178"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrogen-doped mesoporous carbon as an efficient metal-free catalyst for biodiesel production.","authors":"Zahra Taherinia, Arash Ghorbani-Choghamarani, Amir Ghanbarpour","doi":"10.1038/s41598-025-11802-4","DOIUrl":"https://doi.org/10.1038/s41598-025-11802-4","url":null,"abstract":"<p><p>MOF@COF hybrid materials are precursors for producing metal-free N-doped carbon materials-based catalysts. This work is allocated to the production of nitrogen-doped mesoporous carbon from a metal-organic framework (MOF, named Zn-MOF-74), with modification of triazine-based covalent-organic frameworks (TriCF) via high-temperature pyrolysis. The obtained porous N-rich carbon materials provided rich active sites for the esterification of purslane oil. The maximum biodiesel production yield reached 95% for the following parameters: catalyst concentration of 900 mg, methanol: Oil ratio of (10:1), reaction time of 10 h, and temperature of 65 °C. Furthermore, all the measured physicochemical properties are according to the ASTM standard. Therefore, it is found that purslane is an appropriate crop to use for biodiesel production.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28066"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved conservation of callus and rhizome microcuttings of Podophyllum hexandrum germplasm using the slow growth storage approach.","authors":"Zahoor Khan, Bushra Khan, Syed Tanveer Shah, Javaid Iqbal, Abdul Basit, Monsif Ur Rehman, Mian Afaq Ahmad, Muhammad Fahim, Muhammad Farhan Saeed, Árpád Székely, Aftab Jamal","doi":"10.1038/s41598-025-13729-2","DOIUrl":"https://doi.org/10.1038/s41598-025-13729-2","url":null,"abstract":"<p><p>Podophyllum hexandrum Royle (syn. Podophyllum emodi Wall.), commonly known as Himalayan mayapple, is an endangered medicinal plant recognized as the primary natural source of podophyllotoxin, a potent compound with anticancer and antiviral properties. In this study, we developed an optimized protocol for the long-term preservation of P. hexandrum germplasm using a slow growth storage (SGS) technique, successfully preserving the viability and genetic stability of both callus and rhizome cuttings. In vitro cultured callus and rhizome microcuttings of P. hexandrum were conserved using the slow growth storage (SGS) technique in Murashige and Skoog (MS) medium under cold conditions (5 °C), supplemented with different concentrations of sucrose, mannitol, and sorbitol in combination with calcium pantothenate and spermidine, to induce slow growth and maintain tissue viability. It was observed that sorbitol (5.5%) combined with spermidine (2 mg L^-1), calcium pantothenate (3 mg L^-1), and 6-benzylaminopurine (BA) (1.5 mg L^-1) showed better efficacy than the mannitol (6.5%) combination in preserving and regenerating callus and rhizome microcuttings. In contrast, the combination with sucrose (6.5%) was the least effective. This study developed an effective in vitro protocol for conserving P. hexandrum, an endangered medicinal plant, through slow growth storage. A medium containing sorbitol, mannitol, spermidine (2 mg L^-1), and calcium pantothenate (2 mg L^-1) enhanced tissue viability, stress tolerance, and long-term survival of callus and rhizome explants while maintaining genetic stability during cold storage. These findings suggest that this protocol provides a reliable approach for the ex-situ conservation of P. hexandrum, ensuring the availability of genetically stable plant material for future research and medicinal use. This is the first report on the germplasm conservation of callus and rhizome microcuttings of P. hexandrum grown in Pakistan using the slow growth technique.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28173"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel feature-based method for multi-modal biomedical image registration compared to intensity-based technique.","authors":"Mohammad Javad Shojaei, Lichen Yang, Kazem Shojaei, Jeerapat Doungchawee, Richard W Vachet","doi":"10.1038/s41598-025-12862-2","DOIUrl":"https://doi.org/10.1038/s41598-025-12862-2","url":null,"abstract":"<p><p>Multimodal image registration plays a crucial role in biomedical research, enabling the integration of complementary information from different imaging techniques. We present a novel feature-based approach for multimodal image registration, alongside traditional intensity-based methods. Our method, inspired by SPP-net architecture, employs multi-level feature extraction for robust image alignment. Additionally, we perform t-SNE dimensionality reduction on the MALDI-MSI dataset to enhance feature discrimination and visualization. We evaluated both approaches using datasets from the ANHIR Grand Challenge and mass spectrometry imaging modalities (LA-ICP-MS and MALDI-MSI). The proposed feature-based method achieved comparable accuracy to optimized intensity-based approaches, with Dice Coefficients of 0.95 for ANHIR samples (e.g., COAD_05) and 0.97 for mass spectrometry data, while requiring approximately 50% less computational time. Quantitative evaluation through Mutual Information metrics and Hausdorff Distance demonstrated high registration accuracy across different tissue types and imaging modalities. These results establish our feature-based approach as an efficient alternative to traditional intensity-based methods for multimodal image registration in biomedical applications.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28183"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ratcheting fatigue behaviour of advanced structural materials at their service temperatures.","authors":"Prerna Mishra, Vivek Gupta, Prateek Deoman Malwe, Ashish Urade, Venushree Khanke, Md Irfanul Haque Siddiqui, Saurav Dixit, Choon Kit Chan, Chandrakant Sonawane, Ghanshyam G Tejani","doi":"10.1038/s41598-025-09147-z","DOIUrl":"https://doi.org/10.1038/s41598-025-09147-z","url":null,"abstract":"<p><p>Ratcheting fatigue behavior is a critical phenomenon in structural materials undergoing cyclic loading, particularly when combined with nonzero mean stress or multiaxial stress states. This manifests as the progressive buildup of plastic strain in one direction with each loading cycle, ultimately leading to material degradation and failure. This behavior is highly relevant in industries such as automotive, aerospace, nuclear, and civil engineering, where components frequently experience complex loading conditions. Structural materials exposed to ratcheting fatigue often exhibit changes in their mechanical properties, such as cyclic hardening or softening, which influence their ability to withstand cyclic stresses. Factors such as the mean stress, stress amplitude, loading path, material microstructure, and environmental conditions play crucial roles in governing the ratcheting response. Understanding the ratcheting fatigue behavior is essential for the design and life prediction of critical components. Comprehensive investigations through experimental testing and computational modelling are required. This investigation presents the asymmetrical stress-controlled (ratcheting) behaviour of 9 C-1Mo modified steel and IN-617 superalloy at service temperatures of 600 and 800^oC respectively at different tensile mean stresses. When there was change in the mean stress, the amplitude of stress as well as the rate of stress was not changed. The fatigue life of these alloys decreased with an increase in tensile mean stress. The maximum stress increases with the mean stress and leads to a higher inducement of the plastic strain, which results in a lower fatigue life. At elevated temperatures, the fatigue life was found to be higher than that at room temperature (RT) owing to dynamic-strain aging.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28115"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of annual cycle stages and life-history traits on feather abrasion.","authors":"Yosef Kiat, Quentin Dupriez, Gina Pyo, Oliver J L Fox, Rafi Paz, Hans-Jürgen Eilts, Carlos Talabante, Nir Sapir","doi":"10.1038/s41598-025-13458-6","DOIUrl":"https://doi.org/10.1038/s41598-025-13458-6","url":null,"abstract":"<p><p>Tissue wear in animals occurs consistently and can impair their functionality. In birds, abrasion - which reduces the feathered surface area - is caused by various factors. However, little is known about the underlying mechanisms, patterns and immediate consequences of feather abrasion. Given the lack of reliable and widely accepted methods for quantifying feather abrasion, we present the Minimum Convex Abrasion Area (MCAA), a novel approach for its measurement. This method facilitates the estimation of feather abrasion in both museum specimens and living birds, enabling an exploration of the factors influencing abrasion across different phases of the avian annual- and life-cycle. We analysed 283 feathers from 21 passerine species, revealing that the highest rate of feather abrasion occurs during the breeding season, with a significant reduction in feather surface area compared to other periods of the annual cycle. Surprisingly, migration periods, despite their high metabolic demands and long-distance movement, do not significantly contribute to feather abrasion. The timing of feather moult plays a pivotal role in influencing abrasion rates during the breeding season, with species that undergo moult nearer to the breeding season, during winter (pre-breeding moult), showing significantly lower abrasion rates than those moulting before the autumn migration (post-breeding moult), likely a result of the weakening of the feather structure over time. These findings highlight the importance of moult timing for feather abrasion rate and maintaining plumage integrity during the reproduction season. The application of the proposed abrasion measurement method is expected to facilitate better understanding of plumage function and properties, as well as bird moult strategies, thereby enhancing our comprehension of avian ecology, biomechanics, life-history traits and sexual selection, as well as their evolution.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28067"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associated factors and clinical outcomes of feeding intolerance in preterm extremely low birthweight infants.","authors":"Stav Soffer, Dror Mandel, Jacky Herzlich, Rafael Mendelsohn, Ronit Lubetzky, Hadar Moran-Lev","doi":"10.1038/s41598-025-14386-1","DOIUrl":"https://doi.org/10.1038/s41598-025-14386-1","url":null,"abstract":"<p><p>Feeding intolerance (FI) is a major challenge among extremely low birthweight (ELBW) preterm infants, impacting their growth, development, and overall clinical outcomes. We aimed to identify factors associated with FI in ELBW preterm infants and examine the relationship between FI and respiratory support modalities. Our retrospective review of medical records of all ELBW preterm infants between 12/2016 and 12/2021 revealed that 78 (58%) of the 133 ELBW infants (median gestational age 26.5 weeks, median birth weight 809 g) had FI. FI was more common in infants with bronchopulmonary dysplasia and periventricular leukomalacia (n = 69 vs. n = 24 and n = 11 vs. n = 2, respectively, p < 0.001). Non-invasive positive pressure ventilation (NIPPV) had the highest FI rate (7.8 per 100 device-days) compared with other noninvasive ventilation modes (p < 0.001). Infants with FI required longer to achieve full enteral feeding (median 18 vs. 14 days for infants without FI, p < 0.001) and had longer neonatal intensive care unit (NICU) stays (median 89.5 vs. 47 days, respectively, p < 0.001). We conclude that provision of NIPPV support was associated with higher FI rates and longer NICU stays in preterm ELBW infants.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28189"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination chemotherapy and hormone therapy in patients with hormone receptor positive and HER2 negative metastatic breast cancer.","authors":"Kripa Bajaj, Sushmita Rath, Deep Vora, Pallavi Parab, Seema Gulia, Swapnil Rane, Tanuja Shet, Jaya Ghosh, Palak Popat, Prabhat Bhargava, Anbarasan Sekar, Anuradha Mehta, Yogesh Kembhavi, Dinesh Jethwa, Rajiv Sarin, Tabassum Wadasadawala, Shalaka Joshi, Rajendra Badwe, Sudeep Gupta","doi":"10.1038/s41598-025-12419-3","DOIUrl":"https://doi.org/10.1038/s41598-025-12419-3","url":null,"abstract":"<p><p>There is sparse data on the outcomes of combined chemotherapy and hormonal therapy (CHT) in patients with metastatic breast cancer (MBC). This retrospective analysis of HR-positive, HER2-negative MBC patients treated between January 2015 and December 2020 with a combination of chemotherapy (capecitabine or oral cyclophosphamide) and hormonal therapy evaluated their progression-free survival (PFS) and overall survival (OS).The study included 224 patients with a median age of 53 (26-91) years, a median of 3 (0-12) prior treatment lines and a median follow-up of 21.2 (1.7-87.0) months. There were 195 (87.1%) PFS events and 154 (68.8%) deaths, with a median PFS of 8.8 (95% CI 7.0-10.6) months and a median OS of 16.7 (95% CI 13.5-19.9) months. In univariable analyses, ECOG PS (≤ 1 vs. ≥ 2, PFS 14.9 vs. 6.0 months, HR 0.32, 95% CI 0.23-0.44, p < 0.001; OS 36.2 vs. 11.0 months, HR 0.29, 95% CI 0.20-0.42, p < 0.001) and duration of most recent endocrine therapy (> 12 vs. ≤ 12 months, PFS 11.7 vs. 6.9 months, HR 0.32, 95% CI 0.23-0.44, p = 0.023; OS 21.9 vs. 15.0 months, HR 0.70, 95% CI 0.49-0.99, p = 0.047) were significantly associated with survival. In multivariable Cox analyses, better ECOG PS (HR 0.29, 95% CI 0.19-0.43, p<0.001) and capecitabine-based chemotherapy (HR 0.60, 95% CI 0.37-0.99, p=0.043) were significantly associated with higher OS. The chemo-hormonal therapy regimens were well tolerated, with 21 (9.4%) patients experiencing any grade ≥3 toxicity. Chemo-hormonal therapy is an effective treatment in heavily pre-treated MBC patients, including those with visceral metastases. Trial registration: CTRI/2022/01/039242.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"28172"},"PeriodicalIF":3.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}