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Innovations and strategies for sustainable wastewater-integrated microalgal biodiesel production 可持续废水集成微藻生物柴油生产的创新和战略
IF 4 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-09-16 DOI: 10.1016/j.crbiot.2025.100335
Sonali Biswas , L. Muruganandam , I. Ganesh Moorthy
The increasing need for developing a sustainable and renewable fuel has been one of the prime concerns in the world over the past few decades. This review proposes that microalgae have the ability to be scalable, cost efficient, eco-friendly and sustainable for biodiesel production simultaneous contributing to the treatment of wastewater. This integrated framework highlights new business opportunities for energy, wastewater, and bioproduct industries, where cost reductions from the current US $4–6 per liter to projected values near US $1.5 per liter could make microalgal biodiesel increasingly competitive with fossil fuels that can be sufficient for large scale industrial application. This review synthesizes progress in cultivation strategies, lipid extraction methods, and scale-up innovations, while outlining future directions such as wastewater-driven strain optimization, development of hybrid cultivation systems, and resolution of techno-economic and policy barriers essential for industrial deployment. Ultimately this review focuses on an array of approaches to accomplish reasonably priced, eco-friendly and sustainable way to produce biodiesel from microalgae and reduce the greenhouse effect based on critical analysis.
在过去的几十年里,开发可持续和可再生燃料的需求日益增长,一直是世界上最关注的问题之一。本文综述了微藻在生物柴油生产中具有可扩展性、成本效益、生态友好性和可持续性的特点,同时也有助于废水的处理。这一综合框架突出了能源、废水和生物制品行业的新商机,这些行业的成本从目前的每升4-6美元降低到每升1.5美元左右的预计价值,这可能使微藻生物柴油与化石燃料相比更具竞争力,足以进行大规模工业应用。本文综述了栽培策略、脂质提取方法和规模化创新方面的进展,并概述了未来的发展方向,如废水驱动菌株优化、杂交栽培系统的开发以及解决产业化部署所必需的技术经济和政策障碍。最后,本文在分析的基础上,重点介绍了利用微藻生产生物柴油、降低温室效应、实现价格合理、生态友好和可持续的方法。
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引用次数: 0
Characterization and kinetic analysis of Vc1509, a NAD+ dependent deacetylase from Vibrio cholerae 霍乱弧菌NAD+依赖性脱乙酰酶Vc1509的表征及动力学分析
IF 4 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-07-26 DOI: 10.1016/j.crbiot.2025.100320
Arindam Jana , Pragyan Mishra , Ritu Ghosh , Ajit Kumar Dhal , Shibangini Beura , Amrita Mishra , Rahul Modak
Protein lysine acetyltransferase and deacetylases play crucial role in the regulation of bacterial metabolism, stress response and virulence. Among deacetylases, sirtuin-type NAD+ dependent deacetylases, CobB, play central role in bacterial homeostasis. CobB has been extensively studied in several bacterial species like E. coli, Salmonella spp., Vibrio parahaemolyticus, Mycobacterium etc. A CobB homolog, Vc1509, has been identified among the multiple putative deacetylases present in Vibrio cholerae genome. Knockout of Vc1509 led to global hyperacetylation, but there was no further biochemical characterization of enzyme activity. Our previous study reported the involvement of Vibrio parahaemolyticus CobB in the deacetylation of mammalian histones during host-pathogen interactions. In this study, we present the first comprehensive functional and kinetic analysis of Vc1509. We established a scalable expression system for high-yield production of recombinant Vc1509 required for detailed characterization. Vc1509 is a monomeric protein and harbours conserved secondary structure features of CobB. Our data show that Vc1509 is an active NAD+ dependent lysine de-acylase capable of targeting a broad range of acylated substrates, providing new insights into the enzymatic properties and substrate specificity of CobB bacterial deacetylases.
蛋白质赖氨酸乙酰转移酶和去乙酰化酶在细菌代谢、应激反应和毒力调控中起重要作用。在去乙酰化酶中,sirtuin型NAD+依赖性去乙酰化酶CobB在细菌稳态中起着核心作用。CobB在大肠杆菌、沙门氏菌、副溶血性弧菌、分枝杆菌等细菌中得到了广泛的研究。在霍乱弧菌基因组中存在的多个假定的去乙酰化酶中,已鉴定出CobB同源物Vc1509。敲除Vc1509导致全局超乙酰化,但没有进一步的酶活性生化表征。我们之前的研究报道了在宿主-病原体相互作用过程中,副溶血性弧菌CobB参与哺乳动物组蛋白的去乙酰化。在这项研究中,我们首次对Vc1509进行了全面的功能和动力学分析。我们建立了一个可扩展的表达系统,用于详细表征所需的重组Vc1509的高产生产。Vc1509是一种单体蛋白,具有CobB的保守二级结构特征。我们的数据表明,Vc1509是一种活性的NAD+依赖赖氨酸去乙酰化酶,能够靶向广泛的酰化底物,这为CobB细菌去乙酰化酶的酶学性质和底物特异性提供了新的见解。
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引用次数: 0
Unraveling the role of perineural invasion in cancer-associated pain: Insights and treatment strategies 揭示神经周围浸润在癌症相关疼痛中的作用:见解和治疗策略
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-06-18 DOI: 10.1016/j.crbiot.2025.100305
Martina Catalano , Lorenzo Landini , Filippo Nozzoli , Romina Nassini , Giandomenico Roviello , Francesco De Logu
Perineural invasion (PNI) occurs when cancer cells infiltrate the space around nerves, commonly seen in head and neck, pancreatic, prostate, and colorectal cancers. PNI is clinically significant as it promotes metastasis, recurrence, and reduced survival. Mechanistically, it involves tumor-neural microenvironment interactions mediated by neurotrophic factors, inflammatory signals, and immune responses. PNI also causes severe neuropathic pain due to nerve compression, plasticity, and inflammation, resulting in sensory abnormalities from neuronal hyperexcitability, demyelination, and upregulated ion channels. This pain significantly impacts quality of life and complicates cancer management. Cells like macrophages and Schwann cells amplify pain via paracrine signaling and pro-inflammatory mediators. Standard pain management, including NSAIDs and opioids, often fails due to toxicity. Emerging therapies target PNI-specific mechanisms to limit tumor-nerve interactions and relieve pain. Research focuses on improving PNI models, dissecting tumor neuroimmune networks, and translating targeted therapies for effective pain relief.
当癌细胞浸润到神经周围的间隙时,会发生围神经浸润(PNI),常见于头颈部、胰腺癌、前列腺癌和结直肠癌。PNI在临床上具有重要意义,因为它促进转移、复发和降低生存率。从机制上讲,它涉及肿瘤-神经微环境相互作用,由神经营养因子、炎症信号和免疫反应介导。PNI还会由于神经压迫、可塑性和炎症引起严重的神经性疼痛,导致神经元过度兴奋、脱髓鞘和离子通道上调引起的感觉异常。这种疼痛严重影响生活质量,并使癌症治疗复杂化。巨噬细胞和雪旺细胞等细胞通过旁分泌信号和促炎介质放大疼痛。标准的疼痛管理,包括非甾体抗炎药和阿片类药物,往往因毒性而失败。新兴疗法针对pni特异性机制,以限制肿瘤-神经相互作用和缓解疼痛。研究重点是改进PNI模型,解剖肿瘤神经免疫网络,转化靶向治疗以有效缓解疼痛。
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引用次数: 0
A systematic review on Indian Acacia species 文章题目印度金合欢种的系统综述
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-01-28 DOI: 10.1016/j.crbiot.2025.100274
Bharat Singh , Jagdish Prasad , Ram Avtar Sharma
Acacia plants are evergreen, perennial, short, flat-crowned to long and straight-bole trees. A total of 34 species of Acacia genus are distributed in different states of India. Acacia plants are used in the treatment of chronic dysentery, diarrhoea, throat troubles, conjunctivitis and stomatitis. The critical data of ethnopharmacological properties, phytochemical and pharmacological attributes of 27 species were obtained through extensive review of relevant reference books, M. Sc./M. Tech dissertations, PhD theses, Web of Science, PubMed, Google Scholar, ScienceDirect, Wiley, Taylors & Francis, Bentham, Thieme, Springer, and eFloras. The flavone glycosides, flavonoids, lignans, anthraquinones, monoterpenes, and alkaloids have been identified from 20 species of Indian Acacia species. Indian Acacia species possess antimicrobial, antidiabetic, antiarthritic, antistress, anti-inflammatory, antioxidant, anticancer, and wound healing properties. However, various reports are available in literature on phytochemistry and biological properties of 27 Indian Acacia species but, still 7 species have not been evaluated for their pharmacological studies. The review discusses updated knowledge of ethnopharmacological applications, phytochemical and pharmacological attributes, and pharmacokinetic profiles of Indian Acacia species.
金合欢植物是常绿,多年生,短,平冠到长和直孔树。共有34种金合欢属分布在印度的不同邦。金合欢植物被用于治疗慢性痢疾、腹泻、咽喉疾患、结膜炎和口炎。通过查阅相关文献,获得了27种植物的民族药理学、植物化学和药理特性的关键数据。科技论文、博士论文、Web of Science、PubMed、b谷歌Scholar、ScienceDirect、Wiley、Taylors &;Francis, Bentham, Thieme, b施普林格和eFloras。从20种印度金合欢中鉴定出黄酮类苷、类黄酮、木脂素、蒽醌类、单萜和生物碱。印度金合欢具有抗菌、抗糖尿病、抗关节炎、抗应激、抗炎、抗氧化、抗癌和伤口愈合的特性。然而,文献对27种印度金合欢的植物化学和生物学特性有各种报道,但仍有7种尚未进行药理研究。综述了印度金合欢的民族药理学应用、植物化学和药理学特性以及药代动力学特征等方面的最新知识。
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引用次数: 0
Implementation of Dunaliella tertiolecta and Desmodesmus communis in a photobioreactor prototype for treatment of wastewater in a recirculating aquaculture system 在光生物反应器原型中处理循循环水产养殖系统中的废水
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-07-13 DOI: 10.1016/j.crbiot.2025.100314
Kathleen P. Nolan, Jordan Roszell, Robert H. Hanner, Andreas Heyland
Inline photobioreactors (PBRs) are a promising tool for nutrient removal from aquacultural wastewater and production of valuable algal biomass, yet few PBR systems have been rigorously tested. Optimization of algal growth screening across species and strains of interest under specific water conditions is crucial but time-consuming, limiting PBR implementation. Here, we developed a high-throughput screening system to efficiently test algal growth under various nutrient treatments, with the goal of informing implementation in a PBR designed for wastewater treatment in recirculating aquaculture systems (RAS). We assessed growth of the marine alga Dunaliella tertiolecta and the freshwater alga Desmodesmus communis under a matrix of inorganic nitrogen (N) treatments in 96-well plates. We then tested ammonium transfer within a prototype PBR for RAS wastewater treatment and evaluated the batch growth response of D. tertiolecta to ammonium treatments in the PBR. Both species grew on the provided inorganic N sources, showing significant differences in response to N treatments due to species-driven variations in nitrogen uptake and storage mechanisms. D. tertiolecta thrived when grown individually on either nitrate or ammonium, while D. communis favored a combination of N sources. D. tertiolecta showed a 5.4% higher growth rate in nitrate than ammonium. Both species grew in nutrient-free controls, suggesting potential use of internal nutrient reserves. D. tertiolecta grew within the PBR, serving as proof-of-concept for algal cultivation in the prototype. This study supports PBR technology for enhancing food production systems and protecting food security through RAS wastewater treatment.
嵌入式光生物反应器(PBR)是一种很有前途的从水产养殖废水中去除营养物质和生产有价值的藻类生物质的工具,但很少有PBR系统经过严格的测试。在特定的水条件下,跨物种和菌株的藻类生长筛选优化是至关重要的,但耗时,限制了PBR的实施。在这里,我们开发了一个高通量筛选系统,以有效地测试各种营养处理下的藻类生长,目的是为循环水养殖系统(RAS)废水处理设计的PBR的实施提供信息。研究了96孔板中无机氮(N)基质下海洋藻类Dunaliella terolecta和淡水藻类Desmodesmus communis的生长情况。然后,我们在一个原型PBR中测试了氨转移,用于RAS废水处理,并评估了PBR中氨处理对D. tertiolecta的批量生长响应。两个物种在提供的无机氮源上生长,由于物种驱动的氮素吸收和储存机制的差异,对氮素处理的响应存在显著差异。在硝酸盐或铵源上单独生长时,三叶蓟马都能茁壮成长,而群落蓟马则更倾向于组合氮源。在硝态氮中的生长速率比铵态氮的生长速率高5.4%。这两个物种都生长在无营养的环境中,这表明它们可能利用体内的营养储备。D. tertiolecta在PBR内生长,作为原型中藻类培养的概念证明。本研究支持PBR技术通过RAS废水处理加强粮食生产系统和保护粮食安全。
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引用次数: 0
Innovative chemical biology tools for monitoring activity in complex microbiomes 用于监测复杂微生物组活性的创新化学生物学工具
IF 4 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-09-11 DOI: 10.1016/j.crbiot.2025.100334
Yumechris Amekan , Kelly R. Redeker , James P.J. Chong
The functional analysis of complex microbiomes is hindered by their cellular heterogeneity and dynamic interactions. Conventional approaches often lack the resolution to resolve the metabolic activity of individual cells in situ. Recent advances in chemical biology have introduced powerful tools—such as bioorthogonal chemistry, stable isotope probing (SIP), and single-cell phenotyping—that enable non-destructive, high-resolution profiling of microbial activity across diverse ecosystems. These techniques bridge the gap between genotype and phenotype by targeting translational and metabolic functions in live cells, including uncultured or low-abundance taxa. This review outlines the principles, applications, and current limitations of these tools, including challenges in probe biocompatibility, throughput, and spectral or isotopic data analysis. We highlight recent innovations, including BONCAT-FACS integration, automated SIP platforms, and microfluidic Raman-activated cell sorting (RACS), which enhance analytical scalability. Emphasis is placed on the integration of chemical biology tools with multi-omics workflows to generate causal insights into microbial function. By addressing key technical and analytical barriers, these tools promise to expand our capacity to monitor and manipulate microbiomes for applications in ecology, biotechnology, and health. Their continued development will be critical for unlocking the functional potential of microbial communities across environmental and engineered systems.
复杂微生物组的功能分析受到其细胞异质性和动态相互作用的阻碍。传统的方法往往缺乏解决单个细胞的代谢活动原位。化学生物学的最新进展引入了强大的工具,如生物正交化学、稳定同位素探测(SIP)和单细胞表型,这些工具可以对不同生态系统中的微生物活动进行非破坏性的高分辨率分析。这些技术通过靶向活细胞(包括未培养或低丰度的分类群)的翻译和代谢功能,弥合了基因型和表型之间的差距。本文概述了这些工具的原理、应用和当前的局限性,包括探针生物相容性、通量和光谱或同位素数据分析方面的挑战。我们重点介绍了最近的创新,包括boncats - facs集成、自动化SIP平台和微流控拉曼激活细胞分选(RACS),这些都提高了分析的可扩展性。重点放在化学生物学工具与多组学工作流程的整合上,以产生对微生物功能的因果见解。通过解决关键的技术和分析障碍,这些工具有望扩大我们监测和操纵微生物组的能力,以应用于生态学、生物技术和健康。它们的持续发展对于释放环境和工程系统中微生物群落的功能潜力至关重要。
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引用次数: 0
Curcumin dietary supplementation enhances serum carbohydrate-degrading enzyme activities in buffaloes 饲粮中添加姜黄素可提高水牛血清碳水化合物降解酶的活性
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-01-29 DOI: 10.1016/j.crbiot.2025.100276
Maima Matin , Natalia Ksepka , Kamil Wysocki , Michel-Edwar Mickael , Alpana Pande , Jarosław Olav Horbańczuk , Artur Jóźwik , Olga Adamska , Artur Stolarczyk , Laszlo Barna Iantovics , Yordanka Ilieva , Pencho Penchev , Atanas G. Atanasov
Curcumin, the major bioactive compound found in turmeric (Curcuma longa) is a subject of intensive research, due to its multiple bioactivities. Previous studies have investigated metabolic effects of curcumin in humans or established animal research models such as mice, but studies with farm animals have been scarce. In this work, we aimed to study the effects of curcumin supplementation in Bulgarian Murrah buffaloes (Bubalus bubalis), on the serum activities of seven important carbohydrate-metabolizing enzymes, β-glucuronidase, α-galactosidase, α-glucosidase, β-glucosidase, β-galactosidase, N-acetyl-hexosaminidase, and mannosidase. Curcumin was supplemented at a dose of 50 g per animal, per day, and serum activities of the studied enzymes were determined at the start (day 0), middle (day 14), and end (day 28) of the supplementation period. A tendency for increased activity of all studied enzymes was observed upon supplementation with curcumin, with the activity levels of five of the enzymes displaying statistically significant upregulation at day 28 (β-glucuronidase, α-galactosidase, β-galactosidase, N-acetyl-hexosaminidase, and mannosidase). These upregulated activities are in general indicative of increased carbohydrates turnover and detoxification processes, and might provide clues for a better understanding of the mechanisms of action of curcumin in vivo, as well as for novel approaches to rationally impact animal or human health and wellbeing through targeted supplementation.
姜黄素是姜黄(Curcuma longa)中发现的主要生物活性化合物,因其具有多种生物活性而受到广泛研究。以前的研究已经调查了姜黄素在人类或建立动物研究模型(如小鼠)中的代谢作用,但对农场动物的研究很少。本研究旨在研究在保加利亚穆拉水牛(Bubalus bubalis)中添加姜黄素对7种重要糖代谢酶(β-葡萄糖苷酶、α-半乳糖苷酶、α-葡萄糖苷酶、β-葡萄糖苷酶、β-半乳糖苷酶、n -乙酰己糖苷酶和甘露糖苷酶)血清活性的影响。以每只动物每天50 g的剂量添加姜黄素,并在添加期开始(第0天)、中期(第14天)和结束(第28天)测定所研究酶的血清活性。在补充姜黄素后,观察到所有研究酶的活性都有增加的趋势,其中5种酶的活性水平在第28天显示出统计学上显著的上调(β-葡萄糖醛酸酶、α-半乳糖苷酶、β-半乳糖苷酶、n -乙酰己糖苷酶和甘露糖苷酶)。这些上调的活性通常表明碳水化合物转换和解毒过程增加,并可能为更好地了解姜黄素在体内的作用机制提供线索,以及通过有针对性的补充合理影响动物或人类健康和福祉的新方法。
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引用次数: 0
Modern and traditional strategies for controlling microbial contamination in plant micropropagation: Current insights and future perspectives 控制植物微繁殖中微生物污染的现代和传统策略:当前的见解和未来的展望
IF 4 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-09-27 DOI: 10.1016/j.crbiot.2025.100337
Nandang Permadi , Dedat Prismantoro , Pramesthi Reitza Navisya Vasall , Farah Aprisza Sheelmarevaa , Sarifah Nurjanah , Mohamad Nurzaman , Arshad Naji Alhasnawi , Febri Doni , Euis Julaeha
Plant tissue culture is an essential technique widely utilized in agriculture, horticulture, scientific research, and biodiversity preservation, offering controlled methods for plant multiplication and genetic modification. This approach contributes to increased agricultural productivity, enhanced disease resistance, and the protection of rare or threatened plant species. However, microbial contamination—originating from microorganisms in the phyllosphere, rhizosphere, and endosphere—remains a major challenge in plant micropropagation. Without effective management, contamination can inhibit regeneration, callus formation, adventitious shoot development, and may even lead to tissue death. Various strategies, including thermotherapy, chemotherapy, and cryotherapy, have been employed to combat contamination in plant micropropagation. Moreover, emerging approaches such as the application of nanotechnology and natural products offer promising, eco-friendly alternatives. This review examines the sources of contamination and highlights the strategies used to mitigate it, offering insights into innovative solutions that support sustainable agricultural practices and conservation efforts.
植物组织培养是一项广泛应用于农业、园艺、科学研究和生物多样性保护的重要技术,为植物增殖和基因改造提供了有控制的方法。这种方法有助于提高农业生产力,增强抗病能力,保护稀有或受威胁的植物物种。然而,来自根层、根际和内球层的微生物污染仍然是植物微繁殖的主要挑战。如果没有有效的管理,污染会抑制再生、愈伤组织形成、不定芽的发育,甚至可能导致组织死亡。热疗、化学疗法和冷冻疗法等多种方法已被用于植物微繁过程中的污染防治。此外,诸如纳米技术和天然产品的应用等新兴方法提供了有希望的、环保的替代方案。本综述审查了污染源,重点介绍了用于减轻污染的战略,为支持可持续农业实践和保护工作的创新解决方案提供了见解。
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引用次数: 0
Sustainable remediation of persistent organic Pollutants: A review on Recent innovative technologies 持久性有机污染物的可持续修复:最新创新技术综述
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-04-22 DOI: 10.1016/j.crbiot.2025.100293
Fatihu Kabir Sadiq , Abdulalim Ahovi Sadiq , Tiroyaone Albertinah Matsika , Barikisu Ahuoyiza Momoh
Persistent organic pollutants (POPs) are harmful chemicals that remain in the environment for a long time due to their resistance to degradation. They represent a significant challenge to sustainable development due to their enduring presence and potential for bioaccumulation in the environment. This review examines emerging technologies for POP remediation, assessing conventional methods while emphasizing the potential of innovative approaches. Advanced technologies, including nanotechnology and advanced oxidation processes (AOPs), show potential for effective, cost-efficient and environmentally friendly POP degradation. Among AOPs, methods such as UV/H2O2, Fenton’s reaction, photo-Fenton, UV/Ozone, and photocatalysis with semiconductors like TiO2 are particularly effective in breaking down POPs into less harmful substances. Nanotechnology-based methods provide high efficiency, selectivity, and reduced environmental impact, while photocatalysis offers a sustainable and eco-friendly approach to POP degradation. To enhance remediation effectiveness, integrating innovative materials, optimized processes, and artificial intelligence (AI) is crucial. Advancements in eco-friendly nanomaterials, hybrid AOPs, and AI-driven process optimization can significantly improve degradation efficiency, selectivity, and sustainability. Future research should focus on scaling up these technologies, improving cost-effectiveness, and incorporating AI-powered smart monitoring systems for long-term environmental management. A holistic and sustainable remediation strategy must also align with circular economy principles, promote eco-friendly innovations, and address the influence of climate change on POP behavior. By fostering interdisciplinary research, policy support, and international collaboration, the development of accessible and sustainable remediation solutions can be accelerated, contributing to a cleaner environment and a healthier future for all.
持久性有机污染物(POPs)是一种有害化学品,因其难降解而长期存在于环境中。由于它们在环境中的持久存在和生物累积潜力,它们对可持续发展构成了重大挑战。本综述探讨了持久性有机污染物修复方面的新兴技术,在评估传统方法的同时强调了创新方法的潜力。包括纳米技术和高级氧化工艺 (AOP) 在内的先进技术显示出了有效、经济、环保地降解持久性有机污染物的潜力。在 AOPs 中,紫外线/H2O2、芬顿反应、光-芬顿、紫外线/臭氧以及使用 TiO2 等半导体的光催化等方法在将持久性有机污染物分解为危害较小的物质方面尤为有效。基于纳米技术的方法具有效率高、选择性强和对环境影响小的特点,而光催化则为持久性有机污染物的降解提供了一种可持续的生态友好型方法。要提高修复效果,整合创新材料、优化工艺和人工智能(AI)至关重要。生态友好型纳米材料、混合 AOP 和人工智能驱动的工艺优化等方面的进步可以显著提高降解效率、选择性和可持续性。未来研究的重点应是扩大这些技术的规模,提高成本效益,并将人工智能驱动的智能监测系统纳入长期环境管理。全面、可持续的修复战略还必须符合循环经济原则,促进生态友好型创新,并应对气候变化对持久性有机污染物行为的影响。通过促进跨学科研究、政策支持和国际合作,可以加快开发可获得和可持续的修复解决方案,为更清洁的环境和更健康的未来做出贡献。
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引用次数: 0
Neurotensin(8-13) analogs targeting NTS1 and NTS2 receptors: A comparative in vitro and molecular modeling study 靶向NTS1和NTS2受体的神经紧张素(8-13)类似物:体外和分子模型的比较研究
IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-01-01 Epub Date: 2025-05-14 DOI: 10.1016/j.crbiot.2025.100298
Kiril Kirilov , Maria Ponticelli , Toni Kühl , Harald Hübner , Maya G. Georgieva , Matthias Vogel , Aneliya A. Balacheva , Bodo Haas , Tamara I. Pajpanova , Maima Matin , Luigi Milella , Peter Gmeiner , Diana Imhof , Nikolay T. Tzvetkov
The simultaneous activation of both neurotensin type 1 and 2 receptors (NTS1R and NTS2R) through the neuronal peptide neurotensin (NT), activating the dopamine (DA) release and DA signaling within the dopaminergic system in the brain, suggest that NTS1R/NTS2R dual-specific NT analogs may represent an attractive tool in the treatment of Parkinson’s disease (PD) and/or other related conditions. Herein, we report in silico exploration of NTS1R and NTS2R driven by in vitro pharmacological evaluation of the linear hexapeptide NT analogs 3 (sequence Lys8-Cav9-Pro10-Tyr11-Ile12-Leu13) and 6 (Arg8-Cav9-Pro10-Tyr11-Ile12-Leu13), both active towards the human NTS1R and NTS2R. Compared to the parent peptide NT(8–13) (2), compounds 3 and 6 showed improved in vitro human plasma stability and BBB permeability. Moreover, in silico ADMET evaluation indicated that both NT-analogs have strong pharmacological properties combined with good safety profiles, highlighting their potential for further structural improvements. Furthermore, we applied an AI-based approach to generate the homology models of hNTS1R and hNTS2R, followed by MD simulations of their ligand-free state and molecular docking in order to estimate the most probable protein–ligand complexes of peptides 3 and 6. Binding interaction/affinity analysis of the best-ranked docking modes, obtained with selected time-frames from the respective MD trajectories, suggest that the receptor activation occurs via a ligand-receptor binding into the initial “entry” conformation of hNTS1R and hNTS2R. This assumption is supported by additional HYDE analysis confirming the binding affinities of peptides 3 and 6 towards hNTS1R and hNTS2R obtained by radioligand binding experiments. The reported study may serve as a ready-to-use in silico approach for further development of therapeutic options against PD and potentially other neurological disorders.
通过神经元肽神经紧张素(NT)同时激活神经紧张素1型和2型受体(NTS1R和NTS2R),激活多巴胺(DA)释放和大脑多巴胺能系统内的DA信号,表明NTS1R/NTS2R双特异性NT类似物可能是治疗帕金森病(PD)和/或其他相关疾病的有吸引力的工具。本文通过对线状六肽NT类似物3(序列Lys8-Cav9-Pro10-Tyr11-Ile12-Leu13)和6(序列Arg8-Cav9-Pro10-Tyr11-Ile12-Leu13)的体外药理学评价,对NTS1R和NTS2R进行了芯片探索,这两个类似物都对人类NTS1R和NTS2R有活性。与母体肽NT(8-13)(2)相比,化合物3和6显示出体外人血浆稳定性和血脑屏障通透性的改善。此外,计算机ADMET评估表明,这两种nt -类似物具有强大的药理特性和良好的安全性,突出了它们进一步结构改进的潜力。此外,我们应用基于人工智能的方法生成hNTS1R和hNTS2R的同源性模型,然后对它们的无配体状态和分子对接进行MD模拟,以估计肽3和肽6最可能的蛋白质-配体复合物。结合相互作用/亲和分析的最佳对接模式,从各自的MD轨迹中选择的时间框架中获得,表明受体激活是通过配体-受体结合到hNTS1R和hNTS2R的初始“进入”构象中发生的。另外的HYDE分析证实了肽3和6对hNTS1R和hNTS2R的结合亲和力,这一假设得到了支持。该报告的研究可以作为一种现成的计算机方法,用于进一步开发针对PD和潜在的其他神经系统疾病的治疗选择。
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Current Research in Biotechnology
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