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Leg compliance is required to explain the ground reaction force patterns and speed ranges in different gaits. 腿的顺应性需要解释地面反作用力模式和速度范围在不同的步态。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250527
Ali Tehrani Safa, Tirthabir Biswas, Arun Ramakrishnan, Vikas Bhandawat

Two simple models-vaulting over stiff legs and rebounding over compliant legs-are employed to describe the mechanics of legged locomotion. It is agreed that compliant legs are necessary for describing running, and that leg compliance is also present during walking. Stiff legs continue to be employed to model walking under the assumption that the compliance of the leg during walking is low enough to be considered stiff. Here we study gait choice and walk-to-run transition in a biped with compliance and show that the principles underlying gait choice and transition are completely different from stiff legs. Two findings underpin our conclusions: First, at the same speed, step length and stance duration, multiple gaits that differ in the number of times the leg expands and contracts during a single stance are possible. Among them, humans and other animals choose the (normal) gait with M-shaped vertical ground reaction forces (vGRF) not just because of energy considerations but also constraints from forces. Second, the transition from walking to running occurs because of three factors: vGRF minimum at mid-stance characteristic of normal walking, synchronization of horizontal and vertical motions during single support, and velocity redirection during the double support. The insight above required an analytical approximation of the double spring-loaded pendulum (DSLIP) model describing the intricate oscillatory dynamics that relate single and double support phases. Additionally, we also examined DSLIP as a quantitative model for locomotion and conclude that DSLIP speed range is limited. However, insights gleaned from the analytical treatment of DSLIP are general and will inform the construction of more accurate models of walking.

两个简单的模型——在僵硬的腿上跳跃和在柔顺的腿上反弹——被用来描述腿的运动力学。人们一致认为,柔顺的腿是描述跑步的必要条件,在步行时也存在腿部柔顺性。在假设腿在行走过程中的顺应性足够低而被认为是僵硬的情况下,僵硬的腿继续被用来模拟行走。本文研究了具有顺应性的两足动物的步态选择和从走到跑的过渡,发现步态选择和过渡的基本原理与僵硬腿完全不同。两个发现支持了我们的结论:首先,在相同的速度,步长和站立时间下,在单一站立期间腿部伸展和收缩的次数不同的多种步态是可能的。其中,人类和其他动物选择具有m型垂直地面反作用力(vGRF)的(正常)步态不仅是出于能量的考虑,还受到力的约束。从步行到跑步的过渡是由三个因素引起的:正常步行的中站特征的vGRF最小值、单支撑时水平和垂直运动的同步以及双支撑时速度的重定向。上述见解需要双弹簧加载摆(DSLIP)模型的解析近似,该模型描述了与单和双支撑相相关的复杂振荡动力学。此外,我们还检验了DSLIP作为运动的定量模型,并得出DSLIP速度范围有限的结论。然而,从DSLIP的分析治疗中获得的见解是一般的,并将为更准确的步行模型的构建提供信息。
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引用次数: 0
Policy principles for sustainable and just land systems. 可持续和公正的土地制度的政策原则。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250810
Rachael Garrett, Patrick Meyfroidt, Ariane de Bremond, Ariani Wartenberg, Lindsay Barbieri, Álvaro Fernández-Llamazares, Emmanuel Acheampong, Thomas Addoah, Matthew Adeleye, Peter Alexander, Joyce Brandão, David Anthony Coomes, Erle C Ellis, J Fajardo, Johanna Jacobi, Melissa Leach, Sharachchandra Lele, Aymara Llanque Zonta, Joss Lyons-White, Adrian Martin, Peter Messerli, E J Milner-Gulland, Daniel Müller, Morena Mills, Pauline Nantongo Kalunda, Unai Pascual, Ximena Rueda, Casey Ryan, Siddappa Setty, Thu Thuy Pham, Cecilia Zagaria

Land systems are the nexus of many global sustainability and justice challenges. Here we present eight guiding principles (P1-8) for improved land system policies following the heuristic stages of a policy cycle. The principles are as follows: embrace recognitional justice (P1), be politically strategic (P2), consider multiple policy goals (P3), address systemic issues (P4), take an integrative scope (P5), foster co-development (P6), adopt clear and monitorable targets (P7) and integrate diagnostic and adaptive capacities (P8). We then explore how well policies align with these principles in two globally relevant cases (land-based climate mitigation and biodiversity-friendly agriculture). In both cases, we find that when policies align poorly with the principles at the agenda-setting stage, there is further misalignment at the policy formulation stage. In the instances when recognitional justice is embraced at the onset, policies subsequently integrate more diverse goals and co-development, but they insufficiently consider political strategy and struggle to handle system complexity. Nonetheless, we identify promising policy mixes that provide benefits to multiple actors, integrate multiple goals, take an integrative scope and have strong monitoring and adaptation, aligning well with multiple principles. Further investigation of these principles could reveal promising policy pathways for land systems.

土地系统是许多全球可持续性和正义挑战的纽带。在这里,我们根据政策周期的启发式阶段提出了改善土地制度政策的八项指导原则(P1-8)。这些原则包括:承认正义(P1)、政治战略(P2)、考虑多重政策目标(P3)、解决系统性问题(P4)、统筹考虑(P5)、促进共同发展(P6)、制定明确和可监测的目标(P7)、整合诊断和适应能力(P8)。然后,我们在两个全球相关案例(陆地气候缓解和生物多样性友好型农业)中探讨政策如何与这些原则相一致。在这两种情况下,我们发现,当政策在议程设置阶段与原则不一致时,在政策制定阶段就会出现进一步的不一致。在一开始就接受承认正义的情况下,政策随后整合了更多样化的目标和共同发展,但它们没有充分考虑政治战略,难以处理系统复杂性。尽管如此,我们还是确定了有希望的政策组合,这些政策组合可以为多个参与者带来好处,整合多个目标,采取综合范围,具有强大的监测和适应能力,并与多个原则保持一致。对这些原则的进一步调查可以揭示土地制度的有希望的政策途径。
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引用次数: 0
Beyond the surface: untangling molecular complexity in organic residue analysis of coated archaeological ceramics. 表面之外:解开考古陶瓷涂层有机残留物分析中的分子复杂性。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250639
Jasmine Lundy, Julia Haas, Birgit Öhlinger, Léa Drieu

Mixed molecular and isotopic signals are readily encountered in organic residue analysis (ORA) of archaeological ceramics, which can impact our ability to identify the contents/use of the vessel. One reason for these mixed signals that is rarely considered is the mixture of organic products used to coat vessels and the organic products that were later contained in the ceramic vessel. Here, we apply a multifaceted ORA approach to experimental cooking vessels that were coated with a range of organic products during post-firing treatment and then used to cook a variety of organic contents. Our results show that the visibility of the coating agent or cooking commodity varies depending on the type of extraction or analytical method applied. We show that it is important to use a combination of extraction methods (acidified methanol and solvent extraction) and that both molecular and isotopic data must be considered. For the first time, we have also shown that thermal transformation markers could reflect the post-firing coating as opposed to cooking. We call on ORA specialists to carefully consider the impact of post-firing coating before interpreting residues from archaeological ceramics and to implement a multifaceted ORA approach to aid their detection.

在考古陶瓷有机残留物分析(ORA)中很容易遇到混合的分子和同位素信号,这会影响我们识别容器内容物/用途的能力。这些混合信号很少被考虑的一个原因是用于涂覆容器的有机产品和后来包含在陶瓷容器中的有机产品的混合物。在这里,我们将多方面的ORA方法应用于实验烹饪容器,这些容器在烧制后处理期间涂有一系列有机产品,然后用于烹饪各种有机内容物。我们的结果表明,涂层剂或蒸煮商品的可见性取决于所采用的提取类型或分析方法。我们表明,重要的是结合使用提取方法(酸化甲醇和溶剂提取),并必须考虑分子和同位素数据。我们还首次证明,热转化标记可以反映烧后涂层,而不是烹饪。我们呼吁ORA专家在解释考古陶瓷残留物之前仔细考虑烧后涂层的影响,并实施多方面的ORA方法来帮助他们的检测。
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引用次数: 0
Foundational kelp species reveal links between host traits, the environment and the associated microbial community. 基础海带物种揭示了宿主特征、环境和相关微生物群落之间的联系。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250637
Catherine A Pfister, Emma Stanfield, Maximiliana Bogan, Brooke L Weigel, Sativa Volbrecht, Kaylie Scorza

Canopy kelp are foundational species in coastal ecosystems and host diverse bacterial communities. Here, we test the association between bull kelp (Nereocystis luetkeana) host traits, blade-associated bacterial taxa and seawater environmental features across nine sites spanning more than 200 km in Washington state. Traits related to kelp fitness, environmental features and microbial community structure differed geographically. Kelp carbon fixation and tissue nitrogen content were greater at outer coast locales, compared with more inland locales in central and south Puget Sound. Geographic differences in carbon fixation rates, tissue nitrogen and bulb diameter were positively correlated with seawater nutrients and negatively correlated with sea surface temperature. Bacterial taxa showed differentiation among sites, and blade-associated bacterial densities were higher at the outer coast site compared with the most inland site. Yet, 11 bacterial genera were present in at least 80% of the samples; these taxa probably serve as core members of the N. luetkeana microbiome and show both positive and negative correlations with host health and environmental features. We show that there are strong interrelationships between kelp traits, seawater features and bacterial community composition with implications for the health of this highly productive foundational species in coastal ecosystems.

林冠海带是沿海生态系统的基础物种,是多种细菌群落的宿主。在这里,我们测试了牛海带(Nereocystis luetkeana)宿主性状、叶片相关细菌分类群与海水环境特征之间的关系,这些特征跨越了华盛顿州200多公里的9个地点。与海带适合度、环境特征和微生物群落结构相关的性状在地理上存在差异。海带固碳和组织氮含量在普吉特海湾中部和南部的外海岸地区更高,而在内陆地区则更高。固碳率、组织氮和球茎直径的地理差异与海水养分正相关,与海面温度负相关。细菌类群在各样点间呈现分化,外岸样点与叶片相关的细菌密度高于内陆样点。然而,至少80%的样本中存在11种细菌属;这些分类群可能是N. luetkeana微生物组的核心成员,并与宿主健康和环境特征呈正相关和负相关。我们表明,在海带特征、海水特征和细菌群落组成之间存在着很强的相互关系,这对沿海生态系统中这种高产基础物种的健康具有重要意义。
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引用次数: 0
Application of remote sensing and geospatial technologies in predicting vector-borne disease outbreaks. 遥感和地理空间技术在媒介传播疾病暴发预测中的应用。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250536
Ebrahim Abbasi

Vector-borne diseases (VBDs) pose significant global health threats, particularly in tropical and subtropical regions. Remote sensing (RS) and geospatial technologies offer valuable tools for monitoring environmental changes and predicting disease transmission patterns, thereby supporting proactive public health interventions. This study reviews the application of RS and geospatial methods in the prediction, monitoring and control of VBDs. A systematic approach was employed to analyse existing literature, focusing on RS platforms such as Landsat, MODIS and Sentinel-2, alongside geographical information systems and machine learning models used for predictive modelling. The review reveals that these technologies play a crucial role in identifying environmental drivers of disease dynamics, including temperature, precipitation and land-use changes. However, challenges remain in terms of data resolution, model generalizability and the integration of socio-economic factors into predictive frameworks. The integration of early warning systems and participatory surveillance is highlighted as a promising avenue for improving disease forecasting. The study emphasizes the need for enhanced data accessibility, cross-sector collaboration and the inclusion of socio-economic variables in future research to improve the scalability and accuracy of disease prediction models.

病媒传播疾病(VBDs)对全球健康构成重大威胁,特别是在热带和亚热带地区。遥感和地理空间技术为监测环境变化和预测疾病传播模式提供了宝贵的工具,从而支持主动的公共卫生干预措施。本文综述了遥感技术和地理空间技术在海洋生物多样性预测、监测和防治中的应用。采用系统方法分析现有文献,重点关注遥感平台,如Landsat、MODIS和Sentinel-2,以及用于预测建模的地理信息系统和机器学习模型。回顾表明,这些技术在确定疾病动态的环境驱动因素方面发挥着关键作用,包括温度、降水和土地利用变化。然而,在数据解析、模型通用性和将社会经济因素纳入预测框架方面仍然存在挑战。强调预警系统和参与性监测的一体化是改进疾病预报的一个有希望的途径。该研究强调需要加强数据可及性、跨部门协作和在未来研究中纳入社会经济变量,以提高疾病预测模型的可扩展性和准确性。
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引用次数: 0
Behavioural types correlate with the gut microbiome in juvenile wild and reared gilthead seabream. 野生幼鱼和饲养幼鱼的行为类型与肠道微生物群相关。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250100
Aina Pons Salom, Eneko Aspillaga, Ignacio A Catalán, Tomeu Viver, Marco Signaroli, Javier Sanllehi, Amalia Grau, Martina Martorell-Barceló, Margarida Barcelo-Serra, Josep Alós

The gut microbiome influences host behaviour through the gut-brain axis (GBA), a bidirectional network of signalling pathways. Although the GBA has been well studied in humans and other mammals, its role in shaping individual behavioural variation in fish remains largely unexplored. In this study, standardized behavioural tests were conducted on 67 juvenile gilthead seabream (Sparus aurata), consisting of 30 wild and 37 reared individuals, across five major behavioural axes-boldness, aggressiveness, sociability, activity and exploration-to determine their behavioural types using linear mixed models. High levels of repeatability of behaviour and consistent behavioural types were observed along the five studied axes. Gut samples from contrasting behavioural types were analysed for diversity, composition and structure using 16S rRNA sequencing. Statistically significant correlations and differences were found between wild and reared groups in both behavioural types and gut microbiome characteristics. These findings provide novel evidence of associations between behavioural types and the gut microbiome in juvenile marine fish, suggesting that gut microbiome may play a role in modulating fish behaviour. While this relationship could involve GBA interactions, further research is needed to confirm such mechanisms. This work could have translational significance for understanding survival, recruitment and life-history evolution in the early life stages of wild fish, as well as improving conservation management of species in both aquaculture and their natural habitats.

肠道微生物组通过肠脑轴(GBA)影响宿主行为,这是一个双向信号通路网络。尽管大湾区已在人类和其他哺乳动物中得到了很好的研究,但它在形成鱼类个体行为差异方面的作用在很大程度上仍未被探索。本研究采用线性混合模型,对67只幼金头海鲷(Sparus aurata)进行了标准化行为测试,包括30只野生和37只饲养的幼金头海鲷(Sparus aurata),从大胆性、攻击性、社会性、活动性和探索性五个主要行为轴进行了测试,以确定它们的行为类型。高水平的行为可重复性和一致的行为类型沿五个研究轴观察。使用16S rRNA测序分析不同行为类型的肠道样本的多样性、组成和结构。在行为类型和肠道微生物群特征方面,野生组和饲养组之间存在统计学上显著的相关性和差异。这些发现为幼年海鱼的行为类型和肠道微生物组之间的关联提供了新的证据,表明肠道微生物组可能在调节鱼类行为中发挥作用。虽然这种关系可能涉及大湾区的相互作用,但需要进一步的研究来证实这种机制。这项工作对了解野生鱼类生命早期阶段的生存、招募和生活史进化,以及改善水产养殖及其自然栖息地的物种保护管理具有翻译意义。
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引用次数: 0
Detecting and diagnosing faults in autonomous robot swarms with an artificial antibody population model. 基于人工抗体群体模型的自主机器人群体故障检测与诊断。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.251252
James O'Keeffe

An active approach to fault tolerance, the combined processes of fault detection, diagnosis and recovery, is essential for long-term autonomy in robots-particularly multi-robot systems and swarms. Previous efforts have primarily focused on spontaneously occurring electromechanical failures in the sensors and actuators of a minority subpopulation of robots. While the systems that enable this function are valuable, they have not yet considered that many failures arise from gradual wear and tear with continued operation, and that this may be more challenging to detect than sudden step changes in performance. This article presents the artificial antibody population dynamics (AAPD) model-an immune-inspired model for the detection and diagnosis of gradual degradation in robot swarms. The AAPD model is demonstrated to reliably detect and diagnose gradual degradation, as well as spontaneous changes in performance, among swarms of robots of varying sizes while remaining tolerant of normally behaving robots. The AAPD model is distributed, offers supervised and unsupervised configurations and demonstrates promising scalable properties. Deploying the AAPD model on a swarm of foraging robots undergoing gradual degradation enables the swarm to operate on average at between 70 and 97% of its performance in perfect conditions and is able to prevent instances of robots failing in the field during experiments in most of the cases tested.

一种主动容错方法,即故障检测、诊断和恢复的组合过程,对于机器人的长期自治至关重要,尤其是多机器人系统和群集。以前的工作主要集中在少数机器人的传感器和执行器中自发发生的机电故障。虽然实现这一功能的系统是有价值的,但他们还没有考虑到许多故障是由于持续运行的逐渐磨损引起的,这可能比检测性能的突然变化更具挑战性。本文提出了人工抗体群体动力学(AAPD)模型,这是一种用于检测和诊断机器人群体中逐渐退化的免疫启发模型。AAPD模型被证明可以可靠地检测和诊断不同大小的机器人群中的逐渐退化以及性能的自发变化,同时对正常行为的机器人保持容忍。AAPD模型是分布式的,提供有监督和无监督配置,并展示了有前景的可扩展性。在一群逐渐退化的觅食机器人上部署AAPD模型,可以使群体在完美条件下平均以70%到97%的性能运行,并且能够防止机器人在大多数测试情况下在实验过程中失败。
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引用次数: 0
Harnessing meta-analyses' insights in ecology and evolution research. 利用元分析在生态学和进化研究中的见解。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250759
Pietro Pollo, April Robin Martinig, Ayumi Mizuno, Kyle Morrison, Patrice Pottier, Lorenzo Ricolfi, Jesse Tam, Coralie Williams, Yefeng Yang, Szymek Marian Drobniak, Malgorzata Lagisz, Shinichi Nakagawa

Meta-analyses are powerful tools to synthesize the literature in several fields of study, including ecology and evolution. However, it remains uncertain whether ecologists and evolutionary biologists fully comprehend meta-analyses' findings or effectively apply them when citing these studies in their own research. Here, we first discuss key meta-analytical concepts and provide a guide to researchers in ecology and evolution on how to harness meta-analyses' insights. For instance, we clarify the meaning of effect sizes and heterogeneity to improve understanding of meta-analyses' quantitative findings. In addition, we analysed articles published in 2023 in ecology and evolution to investigate how frequently and in what context meta-analyses were cited. We found that approximately 21% of articles cited at least one meta-analysis, and that the relative number of citations of meta-analyses (0.62% of all citations analysed) was greater than the publication frequency of meta-analytical articles (0.44% of all articles). Most importantly, we found that while the direction of mean effect sizes from cited meta-analyses was often mentioned, the magnitude of effect sizes and the limitations of the data analysed were frequently overlooked. These findings underscore the need for improved citation practices of meta-analyses in ecological and evolutionary research, which our recommendations seek to promote.

荟萃分析是综合包括生态学和进化在内的几个研究领域的文献的有力工具。然而,生态学家和进化生物学家是否完全理解元分析的发现,或者在他们自己的研究中引用这些研究时是否有效地应用它们,仍然是不确定的。在这里,我们首先讨论了关键的元分析概念,并为生态学和进化论的研究人员提供了如何利用元分析的见解的指导。例如,我们澄清了效应大小和异质性的含义,以提高对meta分析定量结果的理解。此外,我们分析了2023年发表在《生态学与进化》杂志上的文章,以调查元分析被引用的频率和背景。我们发现,大约21%的文章至少引用了一项元分析,并且元分析的相对引用次数(占所有被引用次数的0.62%)大于元分析文章的发表频率(占所有被引用次数的0.44%)。最重要的是,我们发现,虽然引用元分析的平均效应量的方向经常被提及,但效应量的大小和分析数据的局限性经常被忽视。这些发现强调了在生态和进化研究中需要改进meta分析的引用实践,这是我们的建议所寻求的。
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引用次数: 0
Phosphorylation as a candidate regulatory mechanism for effector recruitment to tankyrase. 磷酸化作为一种候选的调控机制来招募储罐酶的效应物。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250824
Benjamin J Broadway, Katie Pollock, Nora Cronin, Robert Rottapel, Frank Sicheri, Sebastian Guettler

The ADP-ribosyltransferase tankyrase (with two paralogues, TNKS and TNKS2) plays pivotal roles in diverse cellular processes that encompass signal transduction, including Wnt/β-catenin, Hippo and toll-like receptor (TLR) signalling, mitotic spindle assembly, glucose homeostasis and telomere maintenance, among many other functions. Tankyrase recruits its effectors (substrates and binders) via a degenerate tankyrase-binding motif (TBM) and exerts its activities by subsequent substrate ADP-ribosylation and/or scaffolding. Variants of the TBM, found in diverse proteins, engage the ankyrin repeat cluster (ARC) domains of tankyrase. Yet, whether effector recruitment to tankyrase can be regulated has remained unknown. In this study, we propose that phosphorylation at position eight of the TBM enhances the affinity of effectors for the ARC domains of tankyrase. Using isolated TBM peptides, we demonstrate that phosphorylation of serine, but not tyrosine, strengthens ARC binding by up to an order of magnitude. Interrogation of proteome-wide phosphorylation data reveals that phosphorylation at position eight in the TBM is enriched in proteins that support centrosome function/localization. Our findings suggest that TBM phosphorylation may serve as an effector-specific mechanism for tankyrase recruitment/retention, providing an additional layer of regulation to control tankyrase.

adp核糖基转移酶储罐酶(有两个类似物,TNKS和TNKS2)在多种细胞过程中起关键作用,包括信号转导,包括Wnt/β-catenin, Hippo和toll样受体(TLR)信号传导,有丝分裂纺锤体组装,葡萄糖稳态和端粒维持,以及许多其他功能。储罐酶通过简并的储罐酶结合基序(TBM)招募其效应物(底物和结合物),并通过随后的底物adp核糖基化和/或支架发挥其活性。在不同的蛋白质中发现的TBM的变体参与了坦克酶的锚蛋白重复簇(ARC)结构域。然而,是否可以调节对坦克酶的效应募集仍然是未知的。在这项研究中,我们提出TBM第8位的磷酸化增强了效应物对坦克酶ARC结构域的亲和力。使用分离的TBM肽,我们证明了丝氨酸的磷酸化,而不是酪氨酸的磷酸化,加强了ARC的结合高达一个数量级。对蛋白质组磷酸化数据的分析显示,TBM中8号位置的磷酸化富含支持中心体功能/定位的蛋白质。我们的研究结果表明,TBM磷酸化可能是储罐酶募集/保留的一种效应特异性机制,为控制储罐酶提供了额外的调控层。
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引用次数: 0
Synthesis of a novel coumarin via the Mannich reaction: in vitro and in silico evaluation of anti-cancer, antimicrobial and antioxidant activities. 通过曼尼希反应合成一种新型香豆素:体外和计算机评价其抗癌、抗菌和抗氧化活性。
IF 2.9 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-15 eCollection Date: 2025-10-01 DOI: 10.1098/rsos.250854
Tran Nguyen Ngoc Huyen, Uyen Nguyen Ngoc Phuong, Tran Nguyen Minh An, Anh Nguyen Thi Hong

The novel coumarin derivatives (2a-2j) were synthesized via the Mannich reaction and evaluated for anti-cancer, antimicrobial and antioxidant activities. Compound (2d) exhibited the most potent cytotoxicity against MCF-7 breast cancer cells (IC50 = 2.54 ± 0.12 µM), surpassing camptothecin. Compound (2b) showed strong activity against HeLa cervical cancer cells (IC50 = 5.23 ± 0.12 µM), while compound (2a) demonstrated notable effects on HepG2 liver cancer cells (IC50 = 8.57 ± 0.42 µM). All three compounds displayed low toxicity toward normal LLCPK1 kidney cells, with IC50 values exceeding 94 µM. Antimicrobial assays revealed that compounds (2a) and (2f) effectively inhibited Bacillus subtilis, with minimum inhibitory concentration values of 25 and 75 µM, respectively. Compound (2i) showed the strongest antioxidant effect (SC50 = 7.36 ± 0.18 µM), comparable to Trolox (SC50 = 6.12 ± 0.15 µM). Molecular docking indicated that compound (2d) (pose 232) binds tightly to the 1T8I enzyme (ΔG = -9.92 kcal mol-1, Ki = 0.01 µM), forming key interactions with Arg 488 and Lys 532. Molecular dynamics simulations confirmed the complex's stability in aqueous solution over 90 ns.

通过Mannich反应合成了新的香豆素衍生物2a-2j,并对其抗癌、抗菌和抗氧化活性进行了评价。化合物(2d)对MCF-7乳腺癌细胞表现出最强的细胞毒性(IC50 = 2.54±0.12µM),超过喜树碱。化合物(2b)对HeLa宫颈癌细胞有较强的抑制作用(IC50 = 5.23±0.12µM),化合物(2a)对HepG2肝癌细胞有较强的抑制作用(IC50 = 8.57±0.42µM)。这三种化合物对正常LLCPK1肾细胞均表现出低毒性,IC50值均超过94µM。抑菌实验表明,化合物(2a)和(2f)能有效抑制枯草芽孢杆菌,最低抑菌浓度分别为25µM和75µM。化合物(2i)的抗氧化作用最强(SC50 = 7.36±0.18µM),与Trolox (SC50 = 6.12±0.15µM)相当。分子对接表明,化合物(2d) (pose 232)与1T8I酶(ΔG = -9.92 kcal mol-1, Ki = 0.01µM)紧密结合,与Arg 488和Lys 532形成关键相互作用。分子动力学模拟证实了该配合物在水溶液中超过90ns的稳定性。
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引用次数: 0
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Royal Society Open Science
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