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Decadal Meta‐Analysis Confirms Bacillus spp. Optimizes Fish Intestinal Microbiota 年代际元分析证实芽孢杆菌可优化鱼类肠道微生物群
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-13 DOI: 10.1111/nyas.70154
Qing Yang, Yi Jin, Lei Yang, Renge Hu, Junyang Ma, Zongxiu Wu, Tao Yang, Bintong Yang, Shu Li, Wei Cong, Yuanhuan Kang
Against the backdrop of reducing the use of antibiotics in aquaculture, the application of Bacillus spp. as probiotics has gained attention. Probiotics exert a beneficial impact on health by modulating the intestinal microbiota, consequently influencing the growth and overall health status of fish. However, the effectiveness of Bacillus spp. supplementation as well as the specific changes of fish intestinal microbiota following variations in the species, amounts, and feeding forms of Bacillus spp. remain unanalyzed. We collected publicly available 16S rRNA gene sequence data (2012−2022) and used meta‐analysis to combine and summarize the studies that met the inclusion criteria. The results indicated that Bacillus spp. supplementation significantly increased the α‐diversity indices, including the Shannon index ( p = 0.041), Simpson index ( p = 0.002), and Pielou evenness index ( p = 0.004), but did not affect the β‐diversity index ( p = 0.44). The Chao1 index was significantly influenced by different Bacillus spp., forms, treatment duration, and amounts ( p < 0.01). Bacillus spp. supplementation also increased the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of candidate probiotics, while reducing the relative abundance of potential pathogenic genera. These findings confirm Bacillus spp. positively regulate fish intestinal microbiota, offering evidence for their probiotic application in aquaculture.
在减少水产养殖中抗生素使用的背景下,芽孢杆菌作为益生菌的应用备受关注。益生菌通过调节肠道菌群对健康产生有益影响,从而影响鱼类的生长和整体健康状况。然而,补充芽孢杆菌的效果以及随着芽孢杆菌种类、数量和饲养方式的变化,鱼类肠道微生物群的具体变化尚未得到分析。我们收集了公开可用的16S rRNA基因序列数据(2012 - 2022年),并使用meta分析来合并和总结符合纳入标准的研究。结果表明,添加芽孢杆菌显著提高了α‐多样性指数,包括Shannon指数(p = 0.041)、Simpson指数(p = 0.002)和Pielou均匀度指数(p = 0.004),但对β‐多样性指数没有影响(p = 0.44)。不同芽孢杆菌种类、形态、处理时间和用量对Chao1指数有显著影响(p < 0.01)。添加芽孢杆菌还增加了厚壁菌门/拟杆菌门的比例,提高了候选益生菌的相对丰度,同时降低了潜在致病菌属的相对丰度。这些发现证实了芽孢杆菌对鱼类肠道菌群具有正向调节作用,为其益生菌在水产养殖中的应用提供了依据。
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引用次数: 0
An Active Inference Model of Meter Perception and the Urge to Move to Music. 节拍感知与音乐移动冲动的主动推理模型。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-09 DOI: 10.1111/nyas.70129
Tomas E Matthews,Peter Vuust,Jonathan Cannon
Why do some rhythms make us want to move and not others? A predictive processing account suggests that prediction errors drive this phenomenon, but this hypothesis remains underspecified. Here, we operationalized this account as a Bayesian model that infers whether a rhythmic sequence is caused by a metered or unmetered template, coupled with an active inference rule in which movement occurs if the sensory feedback from movement would reduce the prediction errors generated by this inference process. Surprisal, as an index of prediction error, was calculated for each rhythm with and without a metronome (a proxy for the feedback from moving along), with delta surprisal as the difference. Surprisal increased linearly as a function of rhythmic complexity, while delta surprisal showed a similar pattern with urge to move ratings shown in previous studies, and this relation was confirmed in an online study. These results suggest that the urge to move to music is driven by the potential to reduce meter-based prediction errors via the expected feedback from moving along to the beat. This work provides a crucial update to the predictive processing account and highlights a key role of active inference and prediction-based learning in our musical experiences.
为什么有些节奏让我们想动,而另一些却不想动?一种预测处理解释表明,预测误差驱动了这一现象,但这一假设仍未得到充分说明。在这里,我们将这一解释操作为贝叶斯模型,该模型推断节奏序列是由计量模板还是非计量模板引起的,再加上一个主动推理规则,如果运动的感觉反馈会减少这种推理过程产生的预测误差,则运动就会发生。惊喜,作为预测误差的指标,计算了每个节奏有节拍器和没有节拍器(代表移动反馈)的情况,惊喜作为差异。惊喜作为节奏复杂性的函数线性增加,而delta惊喜与之前的研究中显示的移动冲动评级的模式相似,这一关系在一项在线研究中得到了证实。这些结果表明,随着音乐移动的冲动是由减少基于节拍的预测误差的潜力驱动的,这种预测误差是通过随着节拍移动的预期反馈来实现的。这项工作为预测处理提供了重要的更新,并强调了主动推理和基于预测的学习在我们的音乐体验中的关键作用。
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引用次数: 0
Global Arts Engagement Inequalities in and Outside School: Analyses of 441,183 15-Year-Olds Across 73 Countries. 全球艺术参与在学校内外的不平等:对73个国家441183名15岁学生的分析。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-09 DOI: 10.1111/nyas.70151
Hei Wan Mak,Nisha Sajnani,Nils Fietje,Daisy Fancourt
Participation in and enjoying arts and creative activities is a United Nations human right, offering significant benefits, particularly for young people. However, past research, predominantly from Western countries, has shown that many young people do not engage in the arts and that such engagement is socially patterned, yet research gaps remain. It is unclear whether this pattern is also observed in other parts of the world and whether it is persistent across both in-school and out-of-school contexts in different countries. We analyzed data from the OECD Programme for International Study Assessment (PISA), which surveyed 441,183 15-year-olds across 73 countries and found substantial variation in engagement rates. Three key engagement patterns were identified. (1) Countries with higher in-school engagement rates also had higher out-of-school engagement rates. (2) Most students engaged more in the arts in school than out of school. (3) Individual-, school-, and country-related factors may influence engagement, with a strong social gradient, especially for out-of-school engagement. Schools hold the potential to equalize engagement in and outside school and thus reduce cultural, health, and academic inequalities. This aligns with Sustainable Development Goal 3: promoting wellbeing for all, and is relevant across multiple sectors and countries worldwide.
参加并享受艺术和创造性活动是联合国的一项人权,它带来了巨大的好处,特别是对年轻人而言。然而,过去主要来自西方国家的研究表明,许多年轻人不参与艺术活动,这种参与是社会模式,但研究差距仍然存在。目前尚不清楚这一模式是否在世界其他地区也被观察到,以及它是否在不同国家的校内和校外环境中持续存在。我们分析了经合组织国际学习评估项目(PISA)的数据,该项目对73个国家的441183名15岁学生进行了调查,发现他们的参与度存在很大差异。确定了三种关键的参与模式。(1)校内参与率较高的国家,校外参与率也较高。大多数学生在学校比在校外更多地参与艺术活动。(3)与个人、学校和国家相关的因素可能影响敬业度,且具有较强的社会梯度,尤其是校外敬业度。学校有可能使学校内外的参与平等,从而减少文化、健康和学术上的不平等。这符合可持续发展目标3:促进所有人的福祉,并与全球多个部门和国家相关。
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引用次数: 0
Cost-Efficiency and Cost-Effectiveness of Alternative Bouillon Fortification Programs: Evidence for Burkina Faso, Nigeria, and Senegal. 替代肉汤强化项目的成本效率和成本效益:布基纳法索、尼日利亚和塞内加尔的证据。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-09 DOI: 10.1111/nyas.70137
Stephen A Vosti,Michael Jarvis,Lauren Thompson,Emily Becher,Maguette Beye,Faith Ishaya,Karim Koudougou,Reina Engle-Stone,Katherine P Adams
Cost-efficiency and cost-effectiveness of fortification programs are not single, fixed numbers, but rather depend on dietary intake patterns and choices regarding the numbers and amounts of fortificants in premixes. We modeled the cost-efficiency and cost-effectiveness of alternative bouillon fortification formulations with vitamins A, B9, and B12, iron, and zinc in Burkina Faso, Nigeria, and Senegal. Cost per consumer reached varied by nutrient and context; for example, cost-efficiency for vitamin A (96 µg/g) ranged from ∼$0.05 (Burkina Faso) to ∼$0.12 (Nigeria). In Nigeria, the cost per woman effectively covered by vitamin A-fortified bouillon delivering 40-250 µg/g ranged from ∼$2.00 to ∼$6.50; in Burkina Faso, this metric fell from ∼$3.25 to ∼$1.25 for the same programs. Cost per child-life saved by bouillon co-fortified with vitamin A (96 µg/g), zinc (1.68 mg/g), and folic acid (28.8 µg/g) ranged from ∼$1272 (Burkina Faso) to ∼$3234 (Senegal). Cost functions tended to be linear in the amounts of fortificants in premixes; nutritional and child mortality benefit curves tended to be nonlinear, with context-specific shapes. Identifying fortification levels at which marginal benefits become small could help inform the design of efficient programs; design should also consider technical issues, program objectives, affordability, and sustainability.
强化计划的成本效益和成本效益不是单一的固定数字,而是取决于饮食摄入模式以及预混料中强化剂的数量和数量的选择。我们在布基纳法索、尼日利亚和塞内加尔模拟了维生素A、维生素B9和维生素B12、铁和锌的替代肉汤强化配方的成本效率和成本效益。每个消费者的成本因营养和环境而异;例如,维生素A(96微克/克)的成本效益从0.05美元(布基纳法索)到0.12美元(尼日利亚)不等。在尼日利亚,维生素a强化肉汤(40-250µg/g)能有效覆盖每位妇女的成本,从约2美元到约6.5美元不等;在布基纳法索,同样的项目,这一指标从3.25美元下降到1.25美元。加维生素A(96微克/克)、锌(1.68毫克/克)和叶酸(28.8微克/克)的肉汤挽救每个儿童生命的成本从约1272美元(布基纳法索)到约3234美元(塞内加尔)不等。预混料中加强剂用量的成本函数趋于线性;营养和儿童死亡率效益曲线往往是非线性的,具有具体情况的形状。确定边际效益变小的强化水平有助于为有效方案的设计提供信息;设计还应考虑技术问题、项目目标、可负担性和可持续性。
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引用次数: 0
tRF-30-FP18LPMBQ4NK in Systemic Juvenile Idiopathic Arthritis: A Promising Diagnostic and Disease Activity Biomarker. tRF-30-FP18LPMBQ4NK在系统性幼年特发性关节炎中的应用:一种有前景的诊断和疾病活性生物标志物。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-09 DOI: 10.1111/nyas.70148
Jiqian Huang,Yuting Pan,Jing Jin,Xiaoyan Shao,Wenjie Zheng,Zhidan Fan,Haiguo Yu
Diagnosing systemic juvenile idiopathic arthritis (sJIA) poses significant challenges. Accumulating evidence has indicated that tRNA-derived fragments (tRFs) play integral roles in the pathogenesis of numerous diseases. Plasma samples were collected from individuals diagnosed with sJIA and healthy controls (HCs) from two medical centers and divided into training and validation cohorts. Small-RNA high-throughput sequencing was employed to investigate the expression profiles of tRFs in the plasma of patients. Aberrantly expressed tRFs in sJIA were validated using quantitative reverse-transcription PCR (qRT-PCR). A total of 245 tRFs were differentially expressed in sJIA samples than in HC samples. Through qRT-PCR validation, tRF-30-FP18LPMBQ4NK was identified as a potential biomarker. In the training cohort, plasma levels of tRF-30-FP18LPMBQ4NK were significantly higher in patients with sJIA than in HCs. Furthermore, the tRF-30-FP18LPMBQ4NK levels in patients in the active disease group were substantially higher than those in the inactive disease group. Additionally, the positive and negative predictive values of the selected tRF in the validation cohort reached 100% and 85%, respectively. Our results suggest that tRF-30-FP18LPMBQ4NK can be used as a promising biomarker candidate for sJIA and has the potential to aid in determining disease activity among patients with sJIA.
诊断系统性青少年特发性关节炎(sJIA)提出了重大挑战。越来越多的证据表明,trna衍生片段(tRFs)在许多疾病的发病机制中起着不可或缺的作用。血浆样本采集自两个医疗中心诊断为sJIA的个体和健康对照(hc),并分为培训组和验证组。采用小rna高通量测序法研究患者血浆中tRFs的表达谱。使用定量反转录PCR (qRT-PCR)对sJIA中异常表达的trf进行验证。sJIA样本与HC样本中共有245个tRFs差异表达。通过qRT-PCR验证,tRF-30-FP18LPMBQ4NK被确定为潜在的生物标志物。在训练队列中,sJIA患者血浆中tRF-30-FP18LPMBQ4NK水平显著高于hcc患者。此外,活动性疾病组患者的tRF-30-FP18LPMBQ4NK水平显著高于非活动性疾病组。此外,在验证队列中选择的tRF的阳性预测值和阴性预测值分别达到100%和85%。我们的研究结果表明,tRF-30-FP18LPMBQ4NK可以作为sJIA的一种有希望的生物标志物候选物,并有可能帮助确定sJIA患者的疾病活动性。
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引用次数: 0
An Improved Aerodynamic Model for Quasi-Steady Simulations of Animal Flight at Moderate Reynolds Numbers. 中等雷诺数下动物飞行准稳态模拟的改进气动模型。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-09 DOI: 10.1111/nyas.70142
Yunxing Su,Xiaozhou Fan,Kyohei Onoue,Hamid Vejdani,Kenneth S Breuer
We present experimental and numerical studies aimed at improving models of animal flight at moderate Reynolds numbers ( 20 k $20k$ - 50 k $50k$ ). Quasi-steady aerodynamic force and moment data were collected using a rectangular wing across various angles of attack, α $alpha$ . The drag coefficient, C D ( α ) $C_D(alpha)$ , is well described by a simple trigonometric function, while the lift coefficient, C L ( α ) $C_L(alpha)$ , combines trigonometric and exponential terms-the latter capturing the linear behavior at small α $alpha$ predicted by inviscid theory. We also derive an empirical relation for the center of pressure as a function of α $alpha$ , allowing evaluation of the pitching moment coefficient, C M ( α ) $C_M(alpha)$ , about any axis. These formulas are integrated into a dynamic flapping wing model to simulate forward flight of a pigeon and a bat at different speeds. Compared to prior models, our approach yields better agreement with wingbeat frequency data, particularly at high speeds. The small α $alpha$ angle regime proves especially beneficial, offering higher C L / C D $C_L/C_D$ , which translates to reduced power demands and smaller body pitch variation-key considerations for the design of flapping wing robots.
我们提出了实验和数值研究,旨在改进中等雷诺数(20k$ 20k$ - 50k$ 50k$)下动物飞行模型。采用不同迎角(α $ α $)的矩形机翼收集准定常气动力和力矩数据。阻力系数C D(α)$ C_D(alpha)$可以用一个简单的三角函数很好地描述,而升力系数C L(α)$ C_L(alpha)$结合了三角函数和指数项,后者捕捉了由无粘理论预测的小α $alpha$时的线性行为。我们还推导了压力中心作为α $ α $函数的经验关系,允许评估俯仰力矩系数,cm (α)$ C_M( α)$,关于任何轴。将这些公式整合到一个动态扑翼模型中,模拟了鸽子和蝙蝠在不同速度下的前飞。与之前的模型相比,我们的方法与翼拍频率数据的一致性更好,特别是在高速飞行时。小的α $ α $角度被证明是特别有益的,提供更高的C L/C D$ C_L/C_D$,这意味着更低的功率需求和更小的机身俯仰变化——这是扑翼机器人设计的关键考虑因素。
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引用次数: 0
Inconsistent Reporting and Suicidality Prevalence: A 30-Year Analysis of the Youth Risk Behavior Survey (1993-2023). 不一致的报告与自杀流行:青少年危险行为调查(1993-2023)的30年分析。
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-08 DOI: 10.1111/nyas.70157
Romain Brisson
Inconsistent reporting can bias suicidality research findings. This study focused on an overlooked pattern-endorsing suicide plans while denying suicidal ideation-and estimated its impact on suicidality prevalence in the Youth Risk Behavior Survey. Publicly available Youth Risk Behavior Survey data from 1993 to 2023 (n = 242,403) were analyzed. Four suicidality indicators were examined: active suicidal ideation, suicide plans, suicide attempts, and post-attempt medical treatment. Statistical analyses included proportion tests and Cohen's h. Overall, 3.1% of respondents reported suicide plans while denying suicidal ideation. Screening out inconsistent reporters systematically impacted the prevalence of suicide plans. By contrast, the prevalence of active suicidal ideation, suicide attempts, and post-attempt medical treatment was only marginally affected. Decisions to include or exclude participants who endorsed suicide plans while denying suicidal ideation should be explicitly justified. Findings underscore the importance of addressing inconsistent reporting and suggest that the suicide plan item may require wording revision to enhance its validity.
不一致的报告可能会使自杀研究结果产生偏差。这项研究聚焦于一个被忽视的模式——认可自杀计划而否认自杀想法——并在青少年风险行为调查中估计了它对自杀流行率的影响。对1993 - 2023年公开获得的青少年危险行为调查数据(n = 242,403)进行分析。调查了四项自杀指标:主动自杀意念、自杀计划、自杀未遂和自杀未遂后的医疗。统计分析包括比例测试和科恩的h。总体而言,3.1%的受访者表示有自杀计划,但否认有自杀念头。筛选不一致的报告系统地影响了自杀计划的流行。相比之下,主动自杀意念、自杀企图和自杀未遂后的医疗治疗的流行率只受到轻微影响。决定包括或排除那些支持自杀计划而否认自杀意念的参与者应该明确地证明是合理的。调查结果强调了解决不一致报告的重要性,并建议自杀计划项目可能需要修改措辞以提高其有效性。
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引用次数: 0
InCHORRRuS: Infant‐Directed Communication Highlights and Organizes Repetition and Redundancy Through Rhythmic Structure InCHORRRuS:婴儿导向的沟通通过节奏结构突出和组织重复和冗余
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-07 DOI: 10.1111/nyas.70147
Camila Alviar, Warren Jones, Miriam Lense
Learning to successfully participate in social interactions is a monumental task for infants, whose perceptual systems are immature and communicative signals complex and hard to parse. To support their infants, caregivers naturally modify their communicative behaviors to be more repetitive, redundant, and rhythmic, thus engaging infants’ perceptual biases. In this paper, we present the InCHORRRuS framework: which considers the role of rhythm in organizing caregivers’ communicative behaviors across modalities to scaffold communication and dyadic coordination in early social interactions. We argue rhythm's role in infant‐directed (ID) communication is particularly highlighted in ID singing, in which metrically structured beat‐based rhythms make the multimodal redundancy and repetition in ID communication also temporally predictable, thus “supercharging” the cues’ communicative value. Additionally, the repetition in songs, across verses and over time, offers caregivers a natural way of leveraging predictability and familiarity at the local level and at longer interactional timescales alike, increasing the impact of the enriched communicative signal. We review the current literature on timing and rhythm, redundancy, and repetition in ID signals; discuss the evidence on the confluence of redundancy and repetition in rhythmic contexts; and consider open questions and future directions our framework inspires.
学习成功地参与社会互动对婴儿来说是一项艰巨的任务,他们的感知系统不成熟,沟通信号复杂且难以解析。为了支持他们的婴儿,照顾者自然地修改他们的交流行为,使其更加重复,冗余和有节奏,从而吸引婴儿的感知偏见。在本文中,我们提出了InCHORRRuS框架:该框架考虑了节奏在组织照顾者跨模式的沟通行为中的作用,以支持早期社会互动中的沟通和二元协调。我们认为节奏在婴儿定向(ID)交流中的作用在婴儿定向歌唱中尤为突出,其中以节拍为基础的韵律结构使得ID交流中的多模态冗余和重复在时间上也是可预测的,从而“强化”了线索的交流价值。此外,歌曲中的重复,跨诗和随时间的重复,为照顾者提供了一种自然的方式,可以在当地层面和更长的互动时间尺度上利用可预测性和熟悉性,从而增加了丰富的交流信号的影响。我们回顾了当前关于ID信号的时间和节奏、冗余和重复的文献;讨论冗余和重复在节奏语境中合流的证据;并考虑我们的框架所激发的开放性问题和未来方向。
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引用次数: 0
Immersive Virtual Nature Environments for Stress Reduction: A Between‐Subjects Experimental Study 沉浸式虚拟自然环境减压:受试者间实验研究
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-07 DOI: 10.1111/nyas.70145
Lin Ma, Jing Chen, Qiyuan An, Xinggang Hou, Yidan Qiao, Jiahui Wu, Qiuyuan Zhu, Yizhou Li, Yuan Feng, Dengkai Chen
Immersive virtual nature (IVN) is an effective strategy for mitigating anxiety and stress associated with prolonged indoor lifestyles. This study evaluated stress recovery differences across various IVN scenes that incorporate different combinations of natural elements. Initial identification of key elements for creating relaxing digital environments was conducted through an online survey. Subsequently, a between‐subjects experiment involving six distinct scenario configurations was implemented with a participant pool of 61 individuals. Following stress induction, recovery was assessed, measuring physiological indices such as heart rate, the root mean square of successive differences (RMSSD), skin conductance level (SCL), and the electroencephalography alpha/beta power ratio. Psychological responses were evaluated using the State‐Trait Anxiety Inventory–State form and Subjective Coordinate Scale. The results indicated that IVN scenes featuring both water and plants significantly improved RMSSD and SCL recovery compared to scenarios devoid of any elements. Each element uniquely influenced the alpha/beta ratio, with notable variations in recovery rates across different scenarios. Participants reported enhanced emotional relaxation following exposure to IVN settings. This study substantiates the differential restorative effects of various element combinations and underscores the pivotal roles of water, plants, sunlight, and color–material–finish in the optimized design and development of digital nature scenes.
沉浸式虚拟自然(IVN)是缓解长时间室内生活方式带来的焦虑和压力的有效策略。本研究评估了不同IVN场景中包含不同自然元素组合的应力恢复差异。通过在线调查,初步确定了创造轻松数字环境的关键要素。随后,涉及六种不同场景配置的受试者间实验在61个人的参与者池中实施。应激诱导后,评估恢复情况,测量心率、连续差均方根(RMSSD)、皮肤电导水平(SCL)和脑电图α / β功率比等生理指标。使用状态-特质焦虑量表和主观坐标量表评估心理反应。结果表明,与不含任何元素的情景相比,含水和植物的IVN情景显著提高了RMSSD和SCL的回收率。每个因素都对α / β比值有独特的影响,在不同的情况下,采收率有显著的变化。参与者报告了暴露于IVN环境后情绪放松的增强。本研究证实了不同元素组合的不同修复效果,并强调了水、植物、阳光和色彩材料在数字自然场景优化设计和开发中的关键作用。
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引用次数: 0
tRF‐M2–Regulated Dopamine Receptor D2 Expression Attenuates Methamphetamine Reinstatement Behavior in Rats tRF‐m2调节多巴胺受体D2表达减弱大鼠甲基苯丙胺恢复行为
IF 5.2 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-07 DOI: 10.1111/nyas.70127
Yun Zhou, Qingxiao Hong, Wenjin Xu, Shanshan Chen, Han Du, Xiaohu Xie, Miaojun Lai, Weisheng Chen, Wenhua Zhou, Zizhen Si, Huifen Liu
Methamphetamine addiction is a chronic disorder characterized by compulsive drug‐seeking and high relapse rates, driven by dopamine‐mediated neuroadaptations in reward circuits that induce persistent behavioral and synaptic changes that endure despite abstinence, making treatment challenging. In this study, we demonstrated significant downregulation of the tRNA‐derived small RNA (tsRNA) tRF‐M2 (tRF‐1:32‐Gly‐GCC‐2‐M2) in the nucleus accumbens (NAc) of rats exposed to methamphetamine self‐administration (METH SA). Through bioinformatic prediction and experimental validation via dual‐luciferase reporter assays, we identified that dopamine receptor D2 ( Drd2 ) mRNA is a direct molecular target of tRF‐M2. We found that NAc‐specific tRF‐M2 delivery attenuated reinstatement behaviors in METH SA rats, potentially mediated through downstream Akt‐Gsk3β signaling cascade and the transcriptional regulator CREB. The antireinstatement effect mirrored the behavioral outcomes observed following Drd2 knockdown in the NAc, which similarly showed concomitant changes in phosphorylated Akt (p‐Akt) and Gsk3β (p‐Gsk3β). These findings show that tRF‐M2 regulates Drd2 expression via Akt‐Gsk3β‐CREB signaling, thereby inhibiting drug‐seeking behavior in addiction models. These results provide valuable mechanistic insights into neuroepigenetic regulation of psychostimulant addiction and identify promising candidates for therapeutic intervention against methamphetamine relapse.
甲基苯丙胺成瘾是一种慢性疾病,其特征是强迫性药物寻求和高复发率,由多巴胺介导的奖赏回路中的神经适应驱动,诱导持续的行为和突触变化,尽管戒断,但仍能持续,使治疗具有挑战性。在这项研究中,我们证明了暴露于甲基苯丙胺(METH SA)的大鼠伏隔核(NAc)中tRNA衍生的小RNA (tsRNA) tRF‐M2 (tRF‐1:32‐Gly‐GCC‐2‐M2)的显著下调。通过生物信息学预测和双荧光素酶报告基因检测的实验验证,我们发现多巴胺受体D2 (Drd2) mRNA是tRF‐M2的直接分子靶点。我们发现,NAc特异性tRF - M2递送可能通过下游Akt - Gsk3β信号级联和转录调节因子CREB介导,减弱了甲基苯丙胺SA大鼠的恢复行为。抗恢复效应反映了Drd2在NAc中下调后观察到的行为结果,这同样显示了磷酸化Akt (p‐Akt)和Gsk3β (p‐Gsk3β)的变化。这些发现表明,tRF‐M2通过Akt‐Gsk3β‐CREB信号通路调节Drd2的表达,从而抑制成瘾模型中的药物寻求行为。这些结果为精神兴奋剂成瘾的神经表观遗传调控提供了有价值的机制见解,并确定了有希望的治疗干预甲基苯丙胺复发的候选药物。
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