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Innovative light sources for phototherapy 用于光疗的创新光源
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0020
G. Romano, G. Insero, Santiago Nonell Marrugat, F. Fusi
Abstract The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advancement in medical sciences have produced newer and more sophisticated solutions for light-emitting sources and their applications in medicine. Starting from a brief historical introduction, the concept of innovation in light sources is discussed and analysed, first from a technical point of view and then in the light of their fitness to improve existing therapeutic protocols or propose new ones. If it is true that a “pure” technical advancement is a good reason for innovation, only a sub-system of those advancements is innovative for phototherapy. To illustrate this concept, the most representative examples of innovative light sources are presented and discussed, both from a technical point of view and from the perspective of their diffusion and applications in the clinical field.
摘要光用于治疗目的可以追溯到古埃及,那里的太阳本身就是一种创新的来源,可能是第一次用于治疗皮肤病。从那时起,医学科学的技术创新和进步为发光源及其在医学中的应用提供了更新、更复杂的解决方案。从一个简短的历史介绍开始,首先从技术角度讨论和分析了光源创新的概念,然后根据它们是否适合改进现有的治疗方案或提出新的治疗方案。如果“纯粹”的技术进步确实是创新的好理由,那么只有这些进步中的一个子系统才是光疗的创新。为了说明这一概念,从技术角度以及从其在临床领域的扩散和应用角度,介绍和讨论了创新光源的最具代表性的例子。
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引用次数: 1
Low-temperature librations and dynamical transition in proteins at differing hydration levels 蛋白质在不同水合水平下的低温振动和动力学转变
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0007
Erika Aloi, R. Bartucci, R. Guzzi
Abstract Hydration of water affects the dynamics and in turn the activity of biomacromolecules. We investigated the dependence of the librational oscillations and the dynamical transition on the hydrating conditions of two globular proteins with different structure and size, namely β-lactoglobulin (βLG) and human serum albumin (HSA), by spin-label electron paramagnetic resonance (EPR) in the temperature range of 120–270 K. The proteins were spin-labeled with 5-maleimide spin-label on free cysteins and prepared in the lyophilized state, at low (h = 0.12) and full (h = 2) hydration levels in buffer. The angular amplitudes of librations are small and almost temperature independent for both lyophilized proteins. Therefore, in these samples, the librational dynamics is restricted and the dynamical transition is absent. In the small and compact beta-structured βLG, the angular librational amplitudes increase with temperature and hydrating conditions, whereas hydration-independent librational oscillations whose amplitudes rise with temperature are recorded in the large and flexible alpha-structured HSA. Both βLG and HSA at low and fully hydration levels undergo the dynamical transition at about 230 K. The overall results indicate that protein librational dynamics is activated at the low hydration level h = 0.12 and highlight biophysical properties that are common to other biosamples at cryogenic temperatures.
摘要水的水合作用影响生物大分子的动力学,进而影响其活性。在120–270的温度范围内,我们用自旋标记电子顺磁共振(EPR)研究了两种不同结构和大小的球状蛋白,即β-乳球蛋白(βLG)和人血清白蛋白(HSA)的平动振荡和动力学转变对水合条件的依赖性 K.用游离半胱氨酸上的5-马来酰亚胺自旋标记物对蛋白质进行自旋标记,并在缓冲液中以低(h=0.12)和完全(h=2)水合水平在冻干状态下制备蛋白质。两种冻干蛋白质的平动角振幅都很小,几乎与温度无关。因此,在这些样品中,平动动力学是受限制的,并且不存在动力学跃迁。在小而紧凑的β结构βLG中,角振动振幅随着温度和水合条件而增加,而振幅随着温度而增加的与水合无关的振动振荡记录在大而灵活的α结构HSA中。βLG和HSA在低水化和完全水化水平下都在230左右发生动力学转变 K.总体结果表明,蛋白质库动力学在低水合水平h=0.12下被激活,并突出了在低温下其他生物样品常见的生物物理特性。
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引用次数: 0
Supercomplex supercomplexes: Raison d’etre and functional significance of supramolecular organization in oxidative phosphorylation 超复合物超复合物:Raison d’etre和超分子组织在氧化磷酸化中的功能意义
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0021
S. Nath
Abstract Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I–IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in the respirasome. Nonetheless, the reason for the existence of the OXPHOS supercomplexes and their functional role remains an enigma. Several hypotheses have been proposed for the existence of these supercomplex supercomplexes. A commonly-held view asserts that they enhance catalysis by substrate channeling. However, this – and other views – has been challenged based on structural and biophysical information. Hence, new ideas, concepts, and frameworks are needed. Here, a new model of energy transfer in OXPHOS is developed on the basis of biochemical data on the pure competitive inhibition of anionic substrates like succinate by the classical anionic uncouplers of OXPHOS (2,4-dinitrophenol, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and dicoumarol), and pharmacological data on the unique site-selective, energy-linked inhibition of energy conservation pathways in mitochondria induced by the guanidine derivatives. It is further found that uncouplers themselves are site-specific and exhibit differential selectivity and efficacy in reversing the inhibition caused by the Site 1/Complex I or Site 2/Complexes II–III-selective guanidine derivatives. These results lead to new vistas and sufficient complexity in the network of energy conservation pathways in the mitochondrial respiratory chain that necessitate discrete points of interaction with two classes of guanidine derivatives and uncoupling agents and thereby separate and distinct energy transfer pathways between Site 1 and Site 2 and the intermediate that energizes adenosine triphosphate (ATP) synthesis by Complex V. Interpretation based on Mitchell’s single-ion chemiosmotic theory that postulates only a single energy pool is inadequate to rationalize the data and account for the required complexity. The above results and available information are shown to be explained by Nath’s two-ion theory of energy coupling and ATP synthesis, involving coupled movement of succinate anions and protons, along with the requirement postulated by the theory for maintenance of homeostasis and ion translocation across the energy-transducing membrane of both succinate monoanions and succinate dianions by Complexes I–V in the OXPHOS supercomplexes. The new model of energy transfer in mitochondria is mapped onto the solved structures of the supercomplexes and integrated into a consistent model with the three-dimensional electron microscope computer tomography visualization of the internal structure of the cristae membranes in mammalian mitochondria. The model also offers valuable insights into diseased states induced in type 2 diabetes and especially in Alzheimer’s and other neurodegenerative diseases that involve mitochondrial dysfunction.
摘要:在电子低温显微镜的最新进展下,现在已经确定氧化磷酸化(OXPHOS)中的呼吸复合物I-IV在呼吸小体中被组织成超复合物。尽管如此,OXPHOS超复合体存在的原因及其功能作用仍然是一个谜。对于这些超复合体的存在,已经提出了几个假设。一种普遍持有的观点认为,它们通过底物通道增强催化作用。然而,基于结构和生物物理信息,这一观点和其他观点受到了挑战。因此,需要新的想法、概念和框架。本研究基于OXPHOS经典阴离子解耦剂(2,4-二硝基苯酚、羰基氰化物4-(三氟甲氧基)苯腙和二oumarol)对琥珀酸盐等阴离子底物的纯竞争性抑制的生化数据,以及胍衍生物诱导的线粒体能量守恒途径的独特位点选择性、能量连锁抑制的药理学数据,建立了OXPHOS中新的能量传递模型。进一步发现解偶联剂本身具有位点特异性,在逆转由Site 1/Complex I或Site 2/Complexes ii - iii选择性胍衍生物引起的抑制方面表现出不同的选择性和有效性。这些结果为线粒体呼吸链中的能量守恒途径网络带来了新的前景和足够的复杂性,这需要与两类胍衍生物和解偶联剂相互作用的离散点,从而在Site 1和Site 2以及激活三磷酸腺苷(ATP)合成的中间体之间分离和不同的能量转移途径假设只有一个能量池不足以使数据合理化并解释所需的复杂性。上述结果和现有信息可以用Nath的能量耦合和ATP合成双离子理论来解释,该理论涉及琥珀酸阴离子和质子的耦合运动,以及OXPHOS超配合物中配合物I-V在琥珀酸单阴离子和琥珀酸双阴离子的能量传导膜上维持稳态和离子转运的理论假设。线粒体能量传递的新模型被映射到超复合体的已解结构上,并与哺乳动物线粒体嵴膜内部结构的三维电子显微镜计算机断层扫描可视化集成到一个一致的模型中。该模型还为2型糖尿病,特别是阿尔茨海默氏症和其他涉及线粒体功能障碍的神经退行性疾病诱导的疾病状态提供了有价值的见解。
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引用次数: 6
A photosensitizing fusion protein with targeting capabilities 一种具有靶向能力的光敏融合蛋白
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0014
S. Bruno, Marilena Margiotta, Marco Cozzolino, P. Bianchini, A. Diaspro, L. Cavanna, M. Tognolini, S. Abbruzzetti, C. Viappiani
Abstract The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed.
摘要用于抗菌应用或抗癌治疗的光动力治疗依赖于光敏分子在吸收可见光或近红外光后产生的活性氧。如果光敏分子靠近微生物或恶性细胞,则产生光细胞毒性作用。因此,光敏化合物的有效性在很大程度上取决于它们靶向微生物或癌症特异性蛋白质的能力。在本研究中,我们报道了与血管活性肠肽融合的人重组肌红蛋白的制备和初步表征,以靶向血管活性肠肽受体(VPAC)受体。用光敏化合物Zn-protopophyrin IX代替Fe-protopopharphirin IX。利用Zn-protoporphirin IX的荧光发射,我们表明该构建体可以结合表达VPAC受体的前列腺癌症细胞。
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引用次数: 3
Diffusion of molecules through nanopores under confinement: Time-scale bridging and crowding effects via Markov state model 约束下分子通过纳米孔的扩散:基于马尔可夫状态模型的时间尺度桥接和拥挤效应
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0019
I. Bodrenko, S. Milenkovic, M. Ceccarelli
Abstract Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits the presence of molecules in its interior. The molecule–pore interaction is treated within the diffusion approximation by introducing the potential of mean force and the local diffusion coefficient for a correct statistical description. The crowding effect can be handled within the Markov state model approximation. By combining the two methods, one can deal with complex free energy surfaces taking into account crowding effects. We recapitulate the equations bridging the two models to calculate passive currents assuming a limited occupancy of the nanopore in a wide range of molecular concentrations. Several simple models are analyzed to clarify the consequences of the model. Eventually, a biologically relevant case of transport of an antibiotic molecule through a bacterial porin is used to draw conclusions (i) on the effects of crowding on transport of small molecules through biological channels, and (ii) to demonstrate its importance for modelling of cellular transport.
分子通过纳米孔的被动运输的特点是分子与孔内壁的相互作用,以及由于纳米孔本身的缩小而产生的一般拥挤效应,这限制了分子在其内部的存在。为了得到正确的统计描述,在扩散近似中引入了平均力势和局部扩散系数来处理分子-孔隙相互作用。拥挤效应可以在马尔可夫状态模型近似内处理。通过结合这两种方法,可以处理考虑拥挤效应的复杂自由能表面。我们总结了连接两个模型的方程,以计算在广泛的分子浓度范围内假设纳米孔的有限占用的无源电流。分析了几个简单的模型,以阐明该模型的后果。最后,一个抗生素分子通过细菌孔蛋白运输的生物学相关案例被用来得出结论:(i)拥挤对小分子通过生物通道运输的影响,以及(ii)证明其对细胞运输建模的重要性。
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引用次数: 3
Is styrene competitive for dopamine receptor binding? 苯乙烯对多巴胺受体结合有竞争力吗?
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0016
E. De Santis, V. Minicozzi, G. Rossi, F. Stellato, S. Morante
Abstract The potential role of styrene oxide in altering the dopaminergic pathway in the ear is investigated by means of molecular docking and molecular dynamics simulations. We estimate the binding affinity of both styrene oxide and dopamine to the dopaminergic receptor DrD2 by computing the free-energy difference, ∆G, between the configuration where the ligand is bound to the receptor and the situation in which it is “infinitely” far away from it. The results show that the styrene oxide has a somewhat lower affinity for binding with respect to dopamine, which, however, may not be enough to prevent exogenous high concentration styrene oxide to compete with endogenous dopamine for DrD2 binding.
摘要通过分子对接和分子动力学模拟研究了氧化苯乙烯在改变耳朵多巴胺能通路中的潜在作用。我们通过计算配体与受体结合的构型与配体“无限”远离受体的情况之间的自由能差∆G来估计氧化苯乙烯和多巴胺与多巴胺能受体DrD2的结合亲和力。结果表明,氧化苯乙烯与多巴胺的结合亲和力略低,然而可能不足以阻止外源性高浓度氧化苯乙烯与内源性多巴胺竞争DrD2结合。
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引用次数: 0
Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases 聚谷氨酰胺神经退行性疾病的离子通道与神经元兴奋性
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0018
Vladimir A. Martínez-Rojas, L. J. Juárez-Hernández, C. Musio
Abstract Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.
摘要多聚谷氨酰胺(polyQ)疾病是一个由9种神经退行性遗传性疾病(NDD)组成的家族,由胞嘧啶腺嘌呤鸟嘌呤(CAG)三核苷酸重复序列的病理性扩增引起,这些重复序列在相应的蛋白质中编码多聚Q通道。CAG polyQ重复序列扩增通过多种下游机制产生神经退行性变;其中,离子通道下的神经元活动直接受到特定通道疾病的影响,或间接受到继发性失调的影响。在这两种情况下,兴奋性的改变是获得或丧失功能的病理影响的基础。在这里,我们总结了polyQ-NDD中离子通道的种类,强调了神经元兴奋性的生物物理特征及其致病作用。这篇综述的目的是指出深入了解这些功能机制和过程的价值,这些机制和过程是设计和靶向新的治疗途径的关键要素。
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引用次数: 0
Subcellular elements responsive to the biomechanical activity of triple-negative breast cancer-derived small extracellular vesicles. 亚细胞因子对三阴性乳腺癌来源的细胞外小泡的生物力学活性的响应。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2022-01-01 DOI: 10.1515/bmc-2022-0024
Beatrice Senigagliesi, Diana E Bedolla, Giovanni Birarda, Michele Zanetti, Marco Lazzarino, Lisa Vaccari, Pietro Parisse, Loredana Casalis
Abstract Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognosis and limited treatment options. Among the mechanisms that contribute to TNBC spreading, attention has been recently paid to small extracellular vesicles (sEVs), nano-sized vesicles that by transferring bioactive molecules to recipient cells play a crucial role in the intercellular communication among cancer, healthy cells, and tumor microenvironment. In particular, TNBC-derived sEVs have been shown to alter proliferation, metastasis, drug resistance, and biomechanical properties of target cells. To shed light on the molecular mechanisms involved in sEVs mediation of cell biomechanics, we investigated the effects of sEVs on the main subcellular players, i.e., cell membrane, cytoskeleton, and nuclear chromatin organization. Our results unveiled that TNBC-derived sEVs are able to promote the formation and elongation of cellular protrusions, soften the cell body, and induce chromatin decondensation in recipient cells. In particular, our data suggest that chromatin decondensation is the main cause of the global cell softening. The present study added new details and unveiled a novel mechanism of activity of the TNBC-derived sEVs, providing information for the efficient translation of sEVs to cancer theranostics.
三阴性乳腺癌(TNBC)具有侵袭性、快速扩散和高度转移性,并且对传统的激素治疗无反应。它被认为是一种预后不良且治疗选择有限的疾病。在促进TNBC扩散的机制中,最近关注的是细胞外小泡(sev),纳米级小泡通过将生物活性分子转移到受体细胞,在癌症、健康细胞和肿瘤微环境之间的细胞间通讯中起着至关重要的作用。特别是,tnbc衍生的sev已被证明可以改变靶细胞的增殖、转移、耐药性和生物力学特性。为了阐明sev介导细胞生物力学的分子机制,我们研究了sev对主要亚细胞参与者(即细胞膜、细胞骨架和核染色质组织)的影响。我们的研究结果揭示了tnbc衍生的sev能够促进细胞突起的形成和伸长,软化细胞体,并诱导受体细胞的染色质去浓缩。特别是,我们的数据表明,染色质去浓缩是整体细胞软化的主要原因。本研究增加了新的细节,揭示了tnbc衍生的sev的新的活性机制,为sev有效转化为癌症治疗提供了信息。
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引用次数: 2
Antibodies targeting enzyme inhibition as potential tools for research and drug development. 靶向酶抑制的抗体是研究和药物开发的潜在工具。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-12-31 DOI: 10.1515/bmc-2021-0021
José Manuel Pérez de la Lastra, Victoria Baca-González, Sergio González-Acosta, Patricia Asensio-Calavia, Andrea Otazo-Pérez, Antonio Morales-delaNuez

Antibodies have transformed biomedical research and are now being used for different experimental applications. Generally, the interaction of enzymes with their specific antibodies can lead to a reduction in their enzymatic activity. The effect of the antibody is dependent on its narrow i.e. the regions of the enzyme to which it is directed. The mechanism of this inhibition is rarely a direct combination of the antibodies with the catalytic site, but is rather due to steric hindrance, barring the substrate access to the active site. In several systems, however, the interaction with the antibody induces conformational changes on the enzyme that can either inhibit or enhance its catalytic activity. The extent of enzyme inhibition or enhancement is, therefore, a reflection of the nature and distribution of the various antigenic determinants on the enzyme molecule. Currently, the mode of action of many enzymes has been elucidated at the molecular level. We here review the molecular mechanisms and recent trends by which antibodies inhibit the catalytic activity of enzymes and provide examples of how specific antibodies can be useful for the neutralization of biologically active molecules.

抗体已经改变了生物医学研究,现在正被用于不同的实验应用。一般来说,酶与其特异性抗体的相互作用会导致酶活性的降低。抗体的作用取决于它的狭窄区域,即它所指向的酶的区域。这种抑制的机制很少是抗体与催化位点的直接结合,而是由于位阻,阻止底物进入活性位点。然而,在一些系统中,与抗体的相互作用会引起酶的构象变化,从而抑制或增强其催化活性。因此,酶抑制或增强的程度反映了酶分子上各种抗原决定因子的性质和分布。目前,许多酶的作用方式已经在分子水平上得到了阐明。我们在这里回顾了抗体抑制酶催化活性的分子机制和最新趋势,并提供了特异性抗体如何用于中和生物活性分子的例子。
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引用次数: 3
Implication of plant growth-promoting rhizobacteria of Bacillus spp. as biocontrol agents against wilt disease caused by Fusarium oxysporum Schlecht. in Vicia faba L. 促进植物生长的芽孢杆菌属根瘤菌防治枯萎病的意义。在维州faba L。
Q2 Biochemistry, Genetics and Molecular Biology Pub Date : 2021-12-31 DOI: 10.1515/bmc-2021-0020
Mostafa Mohamed El-Sersawy, Saad El-Din Hassan, Abbas A El-Ghamry, Amr Mahmoud Abd El-Gwad, Amr Fouda

Out of seven Fusarium spp. isolated from infected faba bean roots, two Fusarium oxysporum were selected and showed faba bean-wilt disease severity with percentages of 68% and 47% under greenhouse conditions. The F. oxysporum showed the highest wilt disease was selected to complete the current study. Three rhizobacterial strains were isolated and identified as Bacillus velezensis Vb1, B. paramycoides Vb3, and B. paramycoides Vb6. These strains showed the highest in-vitro antagonistic activity by the dual-culture method against selected F. oxysporum with inhibition percentages of 59±0.2, 46±0.3, and 52±0.3% for Vb1, Vb3, and Vb6, respectively. These rhizobacterial strains exhibit varied activity for nitrogen-fixing and phosphate-solubilizing. Moreover, these strains showed positive results for ammonia, HCN, and siderophores production. The phytohormones production (indole-3-acetic acid, ABA, benzyl, kinten, ziaten, and GA3) and secretion of various lytic enzymes were recorded by these strains with varying degrees. Under greenhouse conditions, the rhizobacterial strains Vb1, Vb3, Vb6, and their consortium can protect faba bean from wilt caused by F. oxysporum with percentages of 70, 60, 65, and 82%, respectively. Under field conditions, the inoculation with the rhizobacterial consortium (Vb1+Vb3+Vb6) significantly increases the growth performance of the F. oxysporum-infected faba bean plant and recorded the highest wilt protection (83.3%).

从侵染蚕豆根中分离到7株枯萎菌,其中2株尖孢枯萎菌在温室条件下表现出蚕豆枯萎病的严重程度,分别为68%和47%。选择枯萎病发病率最高的尖孢镰刀菌来完成本研究。分离得到3株根瘤菌,分别为velezensis Vb1、B. parycoides Vb3和B. parycoides Vb6。双培养法对所选尖孢镰刀菌Vb1、Vb3和Vb6的抑菌率分别为59±0.2、46±0.3和52±0.3%,体外抑菌活性最高。这些根杆菌菌株表现出不同的固氮和溶磷活性。此外,这些菌株在氨、HCN和铁载体生产方面显示出阳性结果。不同程度地记录了这些菌株的植物激素(吲哚-3-乙酸、ABA、苄基、kinten、ziaten和GA3)的产生和各种裂解酶的分泌。在温室条件下,根瘤菌Vb1、Vb3、Vb6及其组合对蚕豆枯萎病的防效率分别为70%、60%、65%和82%。在田间条件下,接种Vb1+Vb3+Vb6的根瘤菌联合体显著提高了尖孢镰刀菌侵染蚕豆植株的生长性能,并取得了最高的防枯萎率(83.3%)。
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引用次数: 10
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