Acids

  • 文章类型: Journal Article
    背景:饮食酸负荷(DAL)与几种慢性疾病密切相关。然而,DAL与慢性肾脏病(CKD)之间的联系仍然很少,并且没有来自中国人群的数据,这些人群的饮食与西方国家的人群大不相同。
    方法:本研究通过潜在的肾脏酸负荷(PRAL)和净内源性酸产生(NEAP)评估了DAL。我们基于中国健康与营养调查(CHNS)的数据,通过Logistic回归分析阐明了DAL与CKD之间的关系。
    结果:最终分析包括7699名个人,其中811例(11.44%)为CKD患者。虽然PRAL和CKD之间没有明显的联系,较高的NEAP水平与CKD独立相关。随着NEAP值的上升,CKD患病率也是如此。即使经过调整,这一趋势仍然非常重要。在亚组分析中,NEAP和CKD之间的关系在老年人和腰围小于82cm的受试者以及没有糖尿病和心脏病的受试者中更为一致。RCS剖析进一步证实CKD的OR与NEAP评分之间存在明显的线性关系。
    结论:本研究强调,较高的NEAP与CKD风险呈正相关。
    BACKGROUND: Dietary acid load (DAL) is closely related to several chronic diseases. However, the link between DAL and chronic kidney disease (CKD) remains scarce and without data from the Chinese populations whose diet is quite different from people in Western countries.
    METHODS: This study evaluated DAL by potential renal acid load (PRAL) and net endogenous acid production (NEAP). We clarified the relationship between DAL and CKD by logistic regression analysis based on data from the China Health and Nutrition Survey (CHNS).
    RESULTS: The final analysis included 7699 individuals, of whom 811 (11.44%) were CKD patients. Although there was no notable link between PRAL and CKD, higher NEAP levels were independently correlated with CKD. As NEAP values rise, so does CKD prevalence. This trend remains highly significant even after adjustments. In subgroup analyses, the relationship between NEAP and CKD was more consistent in the elderly and subjects with a waistline of less than 82 cm and those without diabetes and heart disease. RCS analysis further confirmed the clear linear relationship between the OR of CKD and NEAP score.
    CONCLUSIONS: This study highlighted that higher NEAP was positively correlated with the risk of CKD.
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  • 文章类型: Journal Article
    背景:细胞内pH(pHi)稳态的破坏,导致生理范围的偏差,会损伤肾上皮细胞。然而,是否存在使pHi恢复正常的适应性机制尚不清楚。早期研究确定H+是缺血预处理(IPC)的关键介质,导致了酸性预处理(AP)的概念。这个概念提出了短期,重复的酸性刺激可以增强细胞承受随后不利压力的能力。虽然AP在各种缺血再灌注(I/R)损伤模型中显示出保护作用,其在肾损伤中的应用仍未被探索。
    方法:通过用酸性培养基处理人肾(HK2)细胞12小时,建立了AP模型,然后用正常培养基恢复期6小时。为了诱导缺氧/复氧(H/R)损伤,HK2细胞缺氧24h,复氧1h。通过夹闭双侧肾蒂15min建立IPC小鼠模型,然后再灌注4天。相反,I/R模型包括夹闭双侧肾蒂35分钟,再灌注24小时。采用蛋白质印迹法评估cleavedcaspase3,cleavedcaspase9,NHE1,KIM1,FAK的表达水平,NOX4pH敏感的荧光探针用于测量pHi,而Hemin/CNF微电极监测肾组织pH。进行免疫荧光染色以显示NHE1,NOX4和FAK的定位,与HK2细胞中的肌动蛋白细胞骨架结构一起。进行细胞粘附和划痕测定以评估细胞运动性。
    结果:我们的研究结果表明,AP可以有效减轻HK2细胞的H/R损伤。AP的这种保护作用和维持pHi稳态涉及Na/H交换剂1(NHE1)表达和活性的上调。NHE1的活性受Y397处的粘着斑激酶(FAK)的pHi依赖性磷酸化的动态变化调节。此过程与NOX4介导的活性氧(ROS)的产生有关。此外,AP诱导FAK的共同定位,NOX4和NHE1在粘着斑中,促进细胞骨架重塑,增强细胞粘附和迁移能力。
    结论:本研究提供了令人信服的证据,表明AP通过FAK/NOX4/NHE1信号传导维持pHi稳态并促进细胞骨架重塑。该信号通路最终有助于减轻HK2细胞中的H/R损伤。
    BACKGROUND: Disruptions in intracellular pH (pHi) homeostasis, causing deviations from the physiological range, can damage renal epithelial cells. However, the existence of an adaptive mechanism to restore pHi to normalcy remains unclear. Early research identified H+ as a critical mediator of ischemic preconditioning (IPC), leading to the concept of acidic preconditioning (AP). This concept proposes that short-term, repetitive acidic stimulation can enhance a cell\'s capacity to withstand subsequent adverse stress. While AP has demonstrated protective effects in various ischemia-reperfusion (I/R) injury models, its application in kidney injury remains largely unexplored.
    METHODS: An AP model was established in human kidney (HK2) cells by treating them with an acidic medium for 12 h, followed by a recovery period with a normal medium for 6 h. To induce hypoxia/reoxygenation (H/R) injury, HK2 cells were subjected to hypoxia for 24 h and reoxygenation for 1 h. In vivo, a mouse model of IPC was established by clamping the bilateral renal pedicles for 15 min, followed by reperfusion for 4 days. Conversely, the I/R model involved clamping the bilateral renal pedicles for 35 min and reperfusion for 24 h. Western blotting was employed to evaluate the expression levels of cleaved caspase 3, cleaved caspase 9, NHE1, KIM1, FAK, and NOX4. A pH-sensitive fluorescent probe was used to measure pHi, while a Hemin/CNF microelectrode monitored kidney tissue pH. Immunofluorescence staining was performed to visualize the localization of NHE1, NOX4, and FAK, along with the actin cytoskeleton structure in HK2 cells. Cell adhesion and scratch assays were conducted to assess cell motility.
    RESULTS: Our findings demonstrated that AP could effectively mitigate H/R injury in HK2 cells. This protective effect and the maintenance of pHi homeostasis by AP involved the upregulation of Na+/H+ exchanger 1 (NHE1) expression and activity. The activity of NHE1 was regulated by dynamic changes in pHi-dependent phosphorylation of Focal Adhesion Kinase (FAK) at Y397. This process was associated with NOX4-mediated reactive oxygen species (ROS) production. Furthermore, AP induced the co-localization of FAK, NOX4, and NHE1 in focal adhesions, promoting cytoskeletal remodeling and enhancing cell adhesion and migration capabilities.
    CONCLUSIONS: This study provides compelling evidence that AP maintains pHi homeostasis and promotes cytoskeletal remodeling through FAK/NOX4/NHE1 signaling. This signaling pathway ultimately contributes to alleviated H/R injury in HK2 cells.
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  • 文章类型: Journal Article
    通过常规制剂施用的药物缺乏靶向性,并且经常扩散到各种不希望的部位。导致作用部位的亚致死浓度和不良作用的出现。因此,治疗剂应当以受控的方式在靶位点递送。目前,基于刺激的药物递送系统已经显示出用于治疗部分的位点特异性递送的显著潜力。pH是药物递送的广泛利用的刺激之一,作为几种致病条件,如肿瘤细胞,感染和炎症部位的特征在于低pH环境。这篇综述文章旨在展示酸敏感前药设计中采用的各种策略,提供市售酸敏感前药的概述。此外,我们已经汇总了目前正在进行临床试验的新的酸敏感前药的开发进展。这些前药包括白蛋白结合前药(阿霉素和DK049),聚合物胶束(NC-6300),聚合物缀合物(ProLindac™),和免疫缀合物(IMMU-110)。该文章涵盖了广泛的研究,重点是开发酸敏感的抗癌前药,抗菌,和抗炎药。最后,讨论了与酸敏感性前药策略相关的挑战,以及未来的方向。
    Drugs administered through conventional formulations are devoid of targeting and often spread to various undesired sites, leading to sub-lethal concentrations at the site of action and the emergence of undesired effects. Hence, therapeutic agents should be delivered in a controlled manner at target sites. Currently, stimuli-based drug delivery systems have demonstrated a remarkable potential for the site-specific delivery of therapeutic moieties. pH is one of the widely exploited stimuli for drug delivery as several pathogenic conditions such as tumor cells, infectious and inflammatory sites are characterized by a low pH environment. This review article aims to demonstrate various strategies employed in the design of acid-sensitive prodrugs, providing an overview of commercially available acid-sensitive prodrugs. Furthermore, we have compiled the progress made for the development of new acid-sensitive prodrugs currently undergoing clinical trials. These prodrugs include albumin-binding prodrugs (Aldoxorubicin and DK049), polymeric micelle (NC-6300), polymer conjugates (ProLindac™), and an immunoconjugate (IMMU-110). The article encompasses a broad spectrum of studies focused on the development of acid-sensitive prodrugs for anticancer, antibacterial, and anti-inflammatory agents. Finally, the challenges associated with the acid-sensitive prodrug strategy are discussed, along with future directions.
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  • 文章类型: Journal Article
    由于与环境和能源相关的问题日益严重,研究废物生物质资源再生的必要性增加了。这项研究成功地开发了一种创新的鱼骨衍生碳基固体酸催化剂,使用碳酸化-磺化方法,其随后被应用于催化纤维素的水解以产生纳米纤维素。数据分析表明,磺化处理影响催化剂的微观结构,导致其比表面积下降(134.48m2/g降至9.66m2/g)。然而,这种处理并不妨碍酸性官能团的引入。特别是,鱼骨固体酸催化剂的总酸含量为3.76mmol/g,-SO3H基团的浓度为0.48mmol/g。此外,来源于鱼骨的固体酸表现出显著的热稳定性,在高达600°C的温度下表现出<15%的质量损失。此外,催化剂在纤维素水解反应过程中表现出优异的催化性能,在优化的反应条件下实现45.7%的最佳纳米纤维素产率。另一个值得注意的特点是固体酸催化剂令人印象深刻的可回收性,即使在经历了五个连续的使用周期之后,仍保持44.87%的纳米纤维素产率。这项研究结果强调了可持续利用废弃生物质资源的创新方法。
    The necessity to look into waste biomass resource regeneration has increased due to growing environmental and energy-related problems. This study successfully developed an innovative fishbone-derived carbon-based solid acid catalyst using the carbonation-sulfonation method, which was subsequently applied to catalyze the hydrolysis of cellulose to produce nanocellulose. The data analysis reveals that the sulfonation treatment affects the microstructure of the catalyst, resulting in a decline in its specific surface area (134.48 m2/g decreased to 9.66 m2/g). However, this treatment doesn\'t hinder the introduction of acidic functional groups. In particular, the solid acid catalyst derived from fishbone exhibited a total acid content of 3.76 mmol/g, with a concentration of -SO3H groups at 0.48 mmol/g. Furthermore, the solid acids originating from fishbones manifested remarkable thermal stability, exhibiting a mass loss of <15 % at temperatures up to 600 °C. Moreover, the catalyst displayed exceptional catalytic performance during the cellulose hydrolysis reaction, achieving an optimum nanocellulose yield of 45.7 % at an optimized reaction condition. An additional noteworthy feature is the solid acid catalyst\'s impressive recyclability, maintaining a nanocellulose yield of 44.87 % even after undergoing five consecutive usage cycles. This research outcome underscores an innovative approach to for the sustainable utilization of waste biomass resources.
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  • 文章类型: Journal Article
    酸解离常数(pKa)的快速准确计算对于化学合成路线的设计至关重要。优化催化剂,并预测化学行为。尽管最近在机器学习方面取得了进展,预测溶剂化酸度,特别是在非水溶剂中,由于实验数据有限,仍然具有挑战性。这种挑战来自于将不同溶剂中的实验值作为不同的数据域处理并分别对其建模。在这项工作中,我们从分子拓扑的角度平等地对待溶质和溶剂,并提出了一个高度通用的框架,称为AttenGpKa,用于预测溶剂化酸度。使用来自iBonD数据库中的60种纯溶剂和混合溶剂的26,522个实验pKa值来训练AttenGpKa。因此,我们的模型可以同时预测化合物在各种溶剂中的pKa值,包括纯净水,纯非水,和混合溶剂。AttenGpKa通过使用图神经网络和注意力机制来学习溶质和溶剂分子内的复杂效应,从而实现了普遍性。此外,溶质和溶剂分子的编码自适应融合,以模拟溶剂对酸解离的影响。AttenGpKa在广泛的验证中证明了强大的泛化能力。可解释性研究进一步表明,我们的模型有效地学习了电子和溶剂效应。提供了免费使用的软件来促进使用AttenGpKa进行pKa预测。
    Rapid and accurate calculation of acid dissociation constant (pKa) is crucial for designing chemical synthesis routes, optimizing catalysts, and predicting chemical behavior. Despite recent progress in machine learning, predicting solvation acidity, especially in nonaqueous solvents, remains challenging due to limited experimental data. This challenge arises from treating experimental values in different solvents as distinct data domains and modeling them separately. In this work, we treat both the solutes and solvents equally from a perspective of molecular topology and propose a highly universal framework called AttenGpKa for predicting solvation acidity. AttenGpKa is trained using 26,522 experimental pKa values from 60 pure and mixed solvents in the iBonD database. As a result, our model can simultaneously predict the pKa values of a compound in various solvents, including pure water, pure nonaqueous, and mixed solvents. AttenGpKa achieves universality by using graph neural networks and attention mechanisms to learn complex effects within solute and solvent molecules. Furthermore, encodings of both solute and solvent molecules are adaptively fused to simulate the influence of the solvent on acid dissociation. AttenGpKa demonstrates robust generalization in extensive validations. The interpretability studies further indicate that our model has effectively learnt electronic and solvent effects. A free-to-use software is provided to facilitate the use of AttenGpKa for pKa prediction.
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  • 文章类型: Journal Article
    控制厌氧颗粒污泥(AnGS)中CaCO3的沉淀对于造纸废水的厌氧处理至关重要。提出了一种可行的策略,通过调节厌氧反应器中的温和酸性条件来控制钙化,而不会阻碍有机降解。结果表明,降低整体pH值(6.5至6.8)可将富钙进水(Ca21200mg/L)中的钙沉淀减少60.1%,并消除了AnGS上的CaCO3沉积。细胞外聚合物(EPS)已被证明是Ca2迁移的关键参与者。酸性溶液减弱了EPS与Ca2+之间的相互作用,然后降低了EPS的吸附能力和对Ca2+的亲和力。温和的酸性环境超出了减少废水中CaCO3形成的范围。EPS质子化降低了Ca2+粘附在AnGS表面的可能性,停止了钙从散装液体到颗粒的运输。这项工作提供了一种可行的策略,以防止高钙废水中的AnGS钙化。
    Controlling CaCO3 precipitation within anaerobic granular sludge (AnGS) is crucial for the anaerobic treatment of paper recycling wastewater. A viable strategy was proposed to control calcification by adjusting a mild acidic condition in an anaerobic reactor without hindering organic degradation. The results indicated that lowering the bulk pH (6.5 to 6.8) reduced calcium precipitation by 60.1 % in calcium-rich influent (Ca2+ 1200 mg/L) and eradicated CaCO3 deposition on AnGS. Extracellular polymeric substances (EPS) have proven to be crucial participants in Ca2+ migration. The acidic solution weakens the interactions between EPS and Ca2+ and then diminishes the EPS adsorption capacity and affinity for Ca2+. The mild acidic environment goes beyond reducing CaCO3 formation in wastewater. EPS protonation reduced the probability of Ca2+ adhering to the AnGS surface, which halted calcium transportation from bulk liquid to granule. This work offers a feasible strategy to prevent AnGS calcification in high-calcium wastewater.
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  • 文章类型: Journal Article
    近年来,随着食用菌产业的蓬勃发展,几丁质的生产越来越依赖于真菌和其他非传统来源。真菌甲壳素具有优势,包括优越的性能,更简单的分离过程,丰富的原材料,没有贝类过敏原。作为一种食用蘑菇,金针菇(F.金针菇)还具有来源广、年产量大的优点。这为几丁质的提取提供了可能性。这里,提出了从金针菇废物中提取几丁质的方法。该方法包括低浓度酸预处理以及黑曲霉的综合生物处理。通过SEM表征,FTIR,XRD,NMR,和TGA证实提取的几丁质是β-几丁质。为了实现金针菇废物(80克/升)的最佳发酵,选择硫酸铵和葡萄糖作为氮源和碳源(5g/L),发酵时间为5天。提取的几丁质可以进一步去乙酰化和纯化,以获得高纯度的壳聚糖(99.2%±1.07%)。该壳聚糖表现出广泛的脱乙酰度(50.0%±1.33%-92.1%±0.97%)和92-192kDa的分子量分布。值得注意的是,与传统的化学提取方法相比,本研究中提取的壳聚糖的收率提高了56.3%±0.47%。
    In recent years, with the booming of the edible mushroom industry, chitin production has become increasingly dependent on fungi and other non-traditional sources. Fungal chitin has advantages including superior performance, simpler separation processes, abundant raw materials, and the absence of shellfish allergens. As a kind of edible mushroom, flammulina velutipes (F. velutipes) also has the advantages of wide source and large annual yield. This provided the possibility for the extraction of chitin. Here, a procedure to extract chitin from F. velutipes waste be presented. This method comprises low-concentration acid pretreatment coupled with consolidated bioprocessing with Aspergillus niger. Characterization by SEM, FTIR, XRD, NMR, and TGA confirmed that the extracted chitin was β-chitin. To achieve optimal fermentation of F. velutipes waste (80 g/L), ammonium sulfate and glucose were selected as nitrogen and carbon sources (5 g/L), with a fermentation time of 5 days. The extracted chitin could be further deacetylated and purified to obtain high-purity chitosan (99.2 % ± 1.07 %). This chitosan exhibited a wide degree of deacetylation (50.0 % ± 1.33 % - 92.1 % ± 0.97 %) and a molecular weight distribution of 92-192 kDa. Notably, the yield of chitosan extracted in this study was increased by 56.3 % ± 0.47 % compared to the traditional chemical extraction method.
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  • 文章类型: Journal Article
    酸性矿山排水和沉积物(AMD-Sed)污染带来了严重的生态和环境问题。本研究调查了受AMD-Sed污染的荒漠草原沉积层(A)和埋藏土层(B)的地球化学参数和细菌群落,并将其与未污染的对照土壤层(CK)进行了比较。结果表明,土壤pH值显著降低,铁,硫磺,与CK相比,B层中的电导率水平明显更高。A和B以变形杆菌和放线菌为主,而CK以Firmicutes和拟杆菌为主。pH值,Fe,S,潜在有毒元素(PTE)梯度是细菌群落变异的关键影响因素,与AMD污染表征因子(pH,Fe,和S)解释了48.6%的细菌群落变异。细菌共现网络分析显示,AMD-Sed污染显著影响拓扑特性,降低了网络的复杂性和稳定性,增加了荒漠草地土壤生态系统的脆弱性。此外,AMD-Sed污染减少了B的C/N循环功能,但增加了S循环功能。研究结果强调了AMD-Sed污染对荒漠草地土壤细菌群落和生态功能的影响,为荒漠草地生态系统后期的管理和恢复提供参考依据。
    Acid mine drainage and sediments (AMD-Sed) contamination pose serious ecological and environmental problems. This study investigated the geochemical parameters and bacterial communities in the sediment layer (A) and buried soil layer (B) of desert grassland contaminated with AMD-Sed and compared them to an uncontaminated control soil layer (CK). The results showed that soil pH was significantly lower and iron, sulfur, and electroconductivity levels were significantly higher in the B layer compared to CK. A and B were dominated by Proteobacteria and Actinobacteriota, while CK was dominated by Firmicutes and Bacteroidota. The pH, Fe, S, and potentially toxic elements (PTEs) gradients were key influences on bacterial community variability, with AMD contamination characterization factors (pH, Fe, and S) explaining 48.6 % of bacterial community variation. A bacterial co-occurrence network analysis showed that AMD-Sed contamination significantly affected topological properties, reduced network complexity and stability, and increased the vulnerability of desert grassland soil ecosystems. In addition, AMD-Sed contamination reduced C/N-cycle functioning in B, but increased S-cycle functioning. The results highlight the effects of AMD-Sed contamination on soil bacterial communities and ecological functions in desert grassland and provide a reference basis for the management and restoration of desert grassland ecosystems in their later stages.
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  • 文章类型: Journal Article
    这项研究提出了一种基于酸酯交换和固相萃取(SPE)结合气相色谱-串联质谱法纯化的方法,用于定量3-和2-一氯丙二醇酯(3-MCPDE,营养食品中的2-MCPDE)和缩水甘油酯(GE)。样品用氨水水解后,用石油醚和乙醚液-液萃取法提取脂肪。然后通过填充有氨基丙基吸附剂的SPE柱纯化提取物。结果表明,3-MCPDE的最佳洗脱体积,2-MCPDE和GE很大程度上取决于样品基质,对于四种不同的食物基质,2-MCPDE和GE在6至12mL之间变化。样品溶液中的所有三种分析物可以完全收集在最初的10-12mL洗脱液中。通过这种方式,样品中通常存在的单酰基甘油被完全去除。因此,有效消除了对GE定量的高估.修改后的分析程序在单个实验室中得到了充分验证,并被推荐为中国食品安全国家标准。此外,两种衍生剂,七氟丁咪唑和苯基硼酸,被证明在定量三种分析物的方法准确性和精密度方面是等效的。
    This study presents a method based on acid transesterification and the purification by solid-phase extraction (SPE) coupled with gas chromatography-tandem mass spectrometry for quantifying 3- and 2-monochloropropanediol esters (3-MCPDE, 2-MCPDE) and glycidyl esters (GE) in nutritional foods. The fat was extracted by liquid-liquid extraction with petroleum ether and diethyl ether after the sample was hydrolysed with ammonia. Then the extract was purified by a SPE cartridge filled with the aminopropyl sorbents. It was demonstrated that the optimal elution volume for 3-MCPDE, 2-MCPDE and GE greatly depended on the sample matrix and varied from 6 to 12 mL for four different kinds of food matrices. All three analytes in the sample solution could be fully collected in the first 10-12 mL of eluate. By this way, monoacylglycerols commonly present in the samples were fully removed. Therefore, the overestimation of GE quantification was effectively eliminated. The modified analytical procedure was fully validated in a single laboratory and has been recommended as a Chinese Food Safety National Standard. In addition, two derivatisation agents, heptafluorobutyrylimidazole and phenylboronic acid, were proved to be equivalent in method accuracy and precision for the quantification of three analytes.
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  • 文章类型: Journal Article
    Mg-K稳态对于植物对非生物胁迫的反应至关重要,但它的规定在很大程度上仍然未知。从苜蓿中克隆的MsWRKY44在叶片和叶柄中高表达。它的过度表达抑制了苜蓿的生长,并促进叶片衰老和苜蓿对酸和铝胁迫的敏感性。叶尖,在pH4.5和pH4.5Al条件下,MsWRKY44-OE植物的边缘和叶间出现黄色斑点。同时,随着MsWRKY44-OE植物枝条中K积累的减少和Mg和Al积累的增加,Mg-K稳态发生了实质性变化。Further,发现MsWRKY44直接结合MsMGT7和MsCIPK23的启动子,并正激活它们的表达。烟草叶片中瞬时过表达的MsMGT7和MsCIPK23增加了Mg和Al的积累,但降低了K的积累。这些结果揭示了一个新的调控模块MsWRKY44-MsMGT7/MsCIPK23,它影响Mg和K在芽中的运输和积累,并促进苜蓿对酸和铝胁迫的敏感性。
    Mg-K homeostasis is essential for plant response to abiotic stress, but its regulation remains largely unknown. MsWRKY44 cloned from alfalfa was highly expressed in leaves and petioles. Overexpression of it inhibited alfalfa growth, and promoted leaf senescence and alfalfa sensitivities to acid and Al stresses. The leaf tips, margins and interveins of old leaves occurred yellow spots in MsWRKY44-OE plants under pH4.5 and pH4.5 +Al conditions. Meanwhile, Mg-K homeostasis was substantially changed with reduction of K accumulation and increases of Mg as well as Al accumulation in shoots of MsWRKY44-OE plants. Further, MsWRKY44 was found to directly bind to the promoters of MsMGT7 and MsCIPK23, and positively activated their expression. Transiently overexpressed MsMGT7 and MsCIPK23 in tobacco leaves increased the Mg and Al accumulations but decreased K accumulation. These results revealed a novel regulatory module MsWRKY44-MsMGT7/MsCIPK23, which affects the transport and accumulation of Mg and K in shoots, and promotes alfalfa sensitivities to acid and Al stresses.
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