deacetylation

脱乙酰化
  • 文章类型: Journal Article
    背景:透明细胞肾细胞癌(ccRCC)仍然是最致命的泌尿系统恶性肿瘤之一,尽管在过去的几十年中在诊断和治疗方面取得了很大的进步。越来越多的证据表明,组蛋白脱乙酰酶(HDACs)在细胞增殖中起着至关重要的作用,分化和凋亡。然而,ccRCC中组蛋白去乙酰化修饰相关基因的生物学功能尚不清楚。
    方法:ccRCC患者的大量转录组数据和临床信息来自TCGA数据库,并从中国人民解放军总医院收集。在我们的研究中总共选择并研究了36个组蛋白去乙酰化基因。单变量cox回归分析,最小绝对收缩和选择算子(LASSO)回归,随机森林(RF)分析,应用蛋白质-蛋白质相互作用(PPI)网络分析来确定影响ccRCC预后的关键基因。“oncoPredict”算法用于药物敏感性分析。使用基因集富集分析(GSEA)和京都基因和基因组百科全书(KEGG)富集分析来探索潜在的生物学功能。ssGSEA算法用于肿瘤免疫微环境分析。通过RT-PCR和免疫组织化学(IHC)验证HDAC10的表达水平。5-乙炔基-2'-脱氧尿苷(EdU测定),CCK-8测定,采用细胞transwell迁移侵袭实验和集落形成实验检测ccRCC细胞的增殖和侵袭能力。建立了包含HDAC10和临床病理特征的列线图来预测ccRCC患者的预后。
    结果:两种机器学习算法和PPI分析确定了四种与ccRCC预后有显著关联的组蛋白去乙酰化基因,HDAC10是其中的关键基因。HDAC10在ccRCC中高表达,其高表达与ccRCC患者预后不良有关。途径富集和EdU染色实验,CCK-8测定,细胞迁移和侵袭实验以及集落形成实验表明,HDAC10介导了ccRCC细胞的增殖和转移,并参与重塑ccRCC的肿瘤微环境(TME)。通过结合HDAC10和其他临床病理特征(https://nomogramhdac10,建立了临床上可靠的预后预测模型。shinyapps.io/HDAC10_列线图/)。
    结论:我们的研究发现HDAC10的表达增加与ccRCC患者的不良预后密切相关。HDAC10对ccRCC有促瘤作用,促进ccRCC的增殖和转移,这可能为ccRCC的靶向治疗提供新的思路。
    BACKGROUND: Clear cell renal cell carcinoma (ccRCC) remains one of the most lethal urological malignancies even though a great number of improvements in diagnosis and management have achieved over the past few decades. Accumulated evidence revealed that histone deacetylases (HDACs) play vital role in cell proliferation, differentiation and apoptosis. Nevertheless, the biological functions of histone deacetylation modification related genes in ccRCC remains poorly understood.
    METHODS: Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and collected from the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were selected and studied in our research. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were applied to identify key genes affecting the prognosis of ccRCC. The \'oncoPredict\' algorithm was utilized for drug-sensitive analysis. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). 5-ethynyl-2\'-deoxyuridine (EdU assay), CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients.
    RESULTS: Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis for ccRCC patients. Pathway enrichment and the experiments of EdU staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay demonstrated that HDAC10 mediated the proliferation and metastasis of ccRCC cells and involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ).
    CONCLUSIONS: Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 showed a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.
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  • 文章类型: Journal Article
    使用魔芋葡甘聚糖(KGM)/高酰基结冷胶(HAGG)可食用膜具有单面不饱和水溶胀,指定为水梯度膜(WGF),已被证明有效地提高了冷冻鱼片的保存质量。这项研究调查了使用部分脱乙酰的魔芋葡甘露聚糖(DKGM)/HAGGWGFs增强冷冻鱼片保存的潜力。KGM的部分脱乙酰作用改善了冷冻KGM/HAGGWGF的水蒸气和氧气阻隔性能,表现出薄膜和冰的结构特性的组合。这种改善归因于DKGM和HAGG之间加强的相互作用,导致更结构化的膜基质表现出对水蒸气和氧气两者的降低的渗透性。此外,DKGM和HAGG之间相互作用的改善导致形成较小的多糖冰晶,这反过来又增加了沿着晶间边界的氧扩散路径,进一步降低氧气渗透率。超过90天的冷冻期,DKGM/HAGGWGF的表现明显优于传统的KGM/HAGGWGF,冰玻璃,和聚乙烯薄膜包装在保持冷冻鱼片的质量。这项研究为设计和开发基于DKGM的用于冷冻鱼片保存应用的WGFs提供了有希望的策略。
    The use of konjac glucomannan (KGM)/high acyl gellan gum (HAGG) edible film with single-sided unsaturated water swelling, designated as a water gradient film (WGF), has been shown to effectively enhance the preservation quality of frozen fish fillets. This study investigates the potential of using partially deacetylated konjac glucomannan (DKGM)/HAGG WGFs to enhance the preservation of frozen fish fillets. The partial deacetylation of KGM improved the water vapour and oxygen barrier properties of the frozen KGM/HAGG WGF, which exhibited a combination of film and ice structural characteristics. This improvement is attributed to strengthened interactions between DKGM and HAGG, resulting in a more structured film matrix that exhibited reduced permeability to both water vapour and oxygen. Furthermore, the improved interactions between DKGM and HAGG led to the formation of smaller polysaccharide ice crystals, which in turn increased the oxygen diffusion path along the intercrystalline boundaries, further decreasing oxygen permeability. Over a 90-day freezing period, the DKGM/HAGG WGF significantly outperformed traditional KGM/HAGG WGF, ice glazing, and polyethylene film packaging in preserving the quality of frozen fish fillets. This study provides a promising strategy for the design and development of DKGM-based WGFs for frozen fish fillet preservation applications.
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  • 文章类型: Journal Article
    Sirtuins,作为NAD+依赖性脱乙酰酶,广泛存在于真细菌中,古细菌,和真核生物,它们在调节细胞功能中起关键作用。其中,SIRT7作为成员发现相对较晚且研究较少的成员而脱颖而出。它位于细胞核内,并显示作为NAD依赖性脱乙酰酶的酶活性,靶向各种各样的酰基。SIRT7在基因转录等重要细胞过程中的作用,细胞代谢,细胞应激反应,和DNA损伤修复已在最近进行的许多研究中被证明。这些研究还强调了SIRT7与衰老等人类疾病的强烈相关性,癌症,神经系统疾病,和心血管疾病。此外,已经报道了多种针对SIRT7的抑制剂,这表明靶向SIRT7可能是抑制肿瘤生长的有希望的策略。这篇综述的目的是深入研究SIRT7的结构和功能,并探讨其在临床应用中的潜在价值。为相关领域的研究提供必要的参考。
    Sirtuins, as NAD+-dependent deacetylases, are widely found in eubacteria, archaea, and eukaryotes, and they play key roles in regulating cellular functions. Among these, SIRT7 stands out as a member discovered relatively late and studied less extensively. It is localized within the nucleus and displays enzymatic activity as an NAD+-dependent deacetylase, targeting a diverse array of acyl groups. The role of SIRT7 in important cellular processes like gene transcription, cellular metabolism, cellular stress responses, and DNA damage repair has been documented in a number of studies conducted recently. These studies have also highlighted SIRT7\'s strong correlation with human diseases like aging, cancer, neurological disorders, and cardiovascular diseases. In addition, a variety of inhibitors against SIRT7 have been reported, indicating that targeting SIRT7 may be a promising strategy for inhibiting tumor growth. The purpose of this review is to thoroughly look into the structure and function of SIRT7 and to explore its potential value in clinical applications, offering an essential reference for research in related domains.
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  • 文章类型: Journal Article
    受自然启发的壳聚糖(CS)材料在设计/制造具有非凡结构/物理特征的可持续异质(纳米)材料方面具有很高的潜力,如优越的生物降解性/生物相容性,化学修饰的简单性,环境安全,高可用性,成本效益,高电化学活性,良好的成膜能力,和抗氧化剂,抗菌/抗菌,和抗凝血活性。工业化和工业废物或副产品的增长导致对清洁发展的需求不断增加,低成本,和可再生的自然系统,以尽量减少或消除对环境有毒化合物的利用。通过对天然CS进行化学修饰以改善其物理化学/生化特性,制备新型异质功能化多糖启发的生物(纳米)材料最近对许多研究人员具有极大的吸引力。在(纳米)催化剂生产的经济方面,最丰富和具有成本效益的官能化CS启发(纳米)材料非常有价值,(纳米)水凝胶,(纳米)复合/共混膜,因此,他们的商业化。在这方面,含有-SO3H基团的功能化CS启发(纳米)材料的制备已被认为是用于各种应用的均质未改性生物材料的有效替代品。CS启发(纳米)材料的磺化衍生物可能具有巨大的表面积,催化活性,吸附,和生物/生物医学特性。本文旨在研究磺化CS(纳米)材料在催化中的不同方法和潜在应用。燃料电池,离子的吸附,膜,和生物应用。
    Nature-inspired chitosan (CS) materials show a high potential for the design/fabrication of sustainable heterogeneous (nano)materials with extraordinary structural/physical features, such as superior biodegradability/biocompatibility, simplicity of chemical modification, environmental safety, high availability, cost-effectiveness, high electrochemical activity, good film-forming ability, and antioxidant, antimicrobial/antibacterial, and anticoagulant activities. Industrialization and growth of industrial wastes or by-products induce an increasing demand for the development of clean, low-cost, and renewable natural systems to minimize or eliminate the utilization of environmentally toxic compounds. The preparation of novel heterogeneous functionalized polysaccharide-inspired bio(nano)materials via chemical modifications of natural CS to improve its physicochemical/biochemical properties has recently become tremendously attractive for many researchers. The most abundantly available and cost-effective functionalized CS-inspired (nano)materials are considerably valuable in terms of the economic aspects of production of (nano)catalysts, (nano)hydrogels, (nano)composite/blend membranes, and thus their commercialization. In this respect, the preparation of functionalized CS-inspired (nano)materials containing -SO3H groups has been represented as a valid alternative to the homogenous unmodified biomaterials for various applications. Sulfonated derivatives of CS-inspired (nano)materials may possess huge surface areas, catalytic activity, adsorption, and biological/biomedical properties. This review article is aimed at the investigation of different methods and potential applications of sulfonated CS-inspired (nano)materials in catalysis, fuel cells, adsorption of ions, membranes, and biological applications.
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  • 文章类型: Journal Article
    背景:由SARS-CoV-2引起的COVID-19的全球爆发已导致数百万人死亡。这种意想不到的紧急情况促使全球病毒学家更深入地研究宿主-病毒界面的复杂动态性,旨在识别抗病毒靶标并阐明严重疾病的宿主和病毒决定因素。
    目的:本研究旨在分析组蛋白去乙酰化酶6(HDAC6)在调节SARS-CoV-2感染中的作用。
    结果:在SARS-CoV-2感染后,在不同的SARS-CoV-2允许细胞系中观察到HDAC6表达逐渐增加。SARS-CoV-2核衣壳蛋白(N蛋白)被鉴定为负责上调HDAC6表达的主要病毒因子。使用shRNA或特异性抑制剂tubacin下调HDAC6导致病毒复制减少,表明其脱乙酰酶活性的前病毒作用。进一步的研究揭示了HDAC6与应激颗粒蛋白G3BP1和N蛋白在感染过程中的相互作用。发现HDAC6介导的SARS-CoV-2N蛋白的去乙酰化对其与G3BP1的关联至关重要。
    结论:这项研究为SARS-CoV-2感染过程中细胞质应激颗粒破坏的分子机制提供了有价值的见解,并强调了HDAC6在此过程中的重要性。
    BACKGROUND: The global outbreak of COVID-19 caused by the SARS-CoV-2 has led to millions of deaths. This unanticipated emergency has prompted virologists across the globe to delve deeper into the intricate dynamicity of the host-virus interface with an aim to identify antiviral targets and elucidate host and viral determinants of severe disease.
    OBJECTIVE: The present study was undertaken to analyse the role of histone deacetylase 6 (HDAC6) in regulating SARS-CoV-2 infection.
    RESULTS: Gradual increase in HDAC6 expression was observed in different SARS-CoV-2-permissive cell lines following SARS-CoV-2 infection. The SARS-CoV-2 nucleocapsid protein (N protein) was identified as the primary viral factor responsible for upregulating HDAC6 expression. Downregulation of HDAC6 using shRNA or a specific inhibitor tubacin resulted in reduced viral replication suggesting proviral role of its deacetylase activity. Further investigations uncovered the interaction of HDAC6 with stress granule protein G3BP1 and N protein during infection. HDAC6-mediated deacetylation of SARS-CoV-2 N protein was found to be crucial for its association with G3BP1.
    CONCLUSIONS: This study provides valuable insights into the molecular mechanisms underlying the disruption of cytoplasmic stress granules during SARS-CoV-2 infection and highlights the significance of HDAC6 in the process.
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  • 文章类型: Journal Article
    高迁移率族蛋白B1(HMGB1)作为致病性炎症反应,介导各种疾病,如癫痫,感染性休克,缺血,创伤性脑损伤,帕金森病,阿尔茨海默病和质谱。HMGB1在无菌和感染性损伤期间促进炎症,并在疾病发展中起关键作用。从细胞核动员到细胞质是活化免疫细胞释放HMGB1的第一步重要步骤。这里,我们证明了Sirtuin2(SIRT2)在43个赖氨酸残基的核定位信号位置与HMGB1物理相互作用并去乙酰化,加强其与HMGB1的相互作用并使HMGB1定位于细胞质中。这些发现是第一个揭示SIRT2核质穿梭的发现,影响HMGB1及其降解,因此揭示了神经炎症治疗的新治疗靶点和途径。
    High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson\'s disease, Alzheimer\'s disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.
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  • 文章类型: Journal Article
    多糖广泛用于改善基于植物的肉类似物(PMA)的质量。在这项研究中,制备了四种不同脱乙酰度(DD)的魔芋葡甘聚糖(KG),即KG1(原生KG,DD=0.00%),KG2(DD=41.40%),KG3(DD=80.01%)和KG4(DD=89.07%),研究了它们对PMA质量的影响。结果表明,KG3在不降低P21的情况下提高了PMA的硬度(从3017.16g提高到3307.16g)和蛋白质消化率(从49.65%提高到53.01%),KG2和KG4的效果不如KG3,而KG1导致PMA的硬度和蛋白质消化率显着下降。流变学性质和分子间力分析表明,部分脱乙酰KG更有利于提高加热过程中蛋白质体系的G\'和PMA中共价键的比例。这些发现表明,在PMA中,部分脱乙酰的KG比天然或高度脱乙酰的KG更有前途。此外,扫描电镜显示,KG的形态从细丝逐渐改变,粗丝,短丝和颗粒随DD增加。本研究为部分脱乙酰KG在PMA中的应用提供了理论依据。
    Polysaccharides are widely used to improve the quality of plant-based meat analogue (PMA). In this study, four kinds of konjac glucomannan (KG) with different deacetylation degrees (DD) were prepared, namely KG1 (native KG, DD = 0.00 %), KG2 (DD = 41.40 %), KG3 (DD = 80.01 %) and KG4 (DD = 89.07 %), and their effects on the quality of PMA were studied. Results manifested that KG3 improved the hardness (from 3017.16 g to 3307.16 g) and protein digestibility (from 49.65 % to 53.01 %) of PMA without reducing the P21, KG2 and KG4 were less effective than KG3, while KG1 led to a significant decline in the hardness and protein digestibility of PMA. The rheological properties and intermolecular force analysis showed that the partially deacetylated KG was more conducive to improving the G\' of the protein system during heating and the proportion of covalent bonds in PMA. These findings suggested that partially deacetylated KG was more promising than native or highly deacetylated KG in PMA. Furthermore, scanning electron microscopy revealed that the morphology of KG gradually changed from fine filaments, to coarse filaments, short filaments and granules as DD increased. This study provides a theoretical basis for the application of partially deacetylated KG in PMA.
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  • 文章类型: Journal Article
    与天然大豆皂甙及其在人体肠道中通过酶促水解形成的苷元不同,体内中间大豆皂甙代谢物很难制备。因此,体内中间大豆皂甙的药理活性仍未研究。在这里,通过制备型高效液相色谱法对天然大豆皂甙进行体外脱乙酰(碱处理)和脱葡糖基化(β-葡萄糖苷酶处理),制备纯度>90%的体内中间大豆皂甙。这些化合物在体外生物测定中表现出比天然大豆皂甙更高的抗炎和抗氧化活性,这表明中间大豆皂甙可以用作改进的生物活性食品补充剂。据我们所知,这是首次报道人体肠道中形成的体内大豆皂甙代谢产物的体外制备和生物分析。
    Unlike natural soyasaponins and their aglycones formed by enzymatic hydrolysis in the human intestine, in vivo intermediate soyasaponin metabolites are difficult to prepare. Therefore, the pharmacological activities of in vivo intermediate soyasaponins remain uninvestigated. Herein, in vivo intermediate soyasaponins with purities of >90% were prepared by in vitro deacetylation (alkaline treatment) and deglucosylation (β-glucosidase treatment) of natural soyasaponins using preparative high-performance liquid chromatography. These compounds exhibited higher anti-inflammatory and antioxidant activities than natural soyasaponins in in vitro bioassays, suggesting that the intermediate soyasaponins can be used as improved bioactive food supplements. To the best of our knowledge, this is the first study reporting the in vitro preparation and bioassays of in vivo intermediate soyasaponin metabolites formed in the human intestine.
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  • 文章类型: Journal Article
    由于其乳化和增稠性能,魔芋葡甘聚糖(KGM)广泛应用于食品中,医学,和材料工业。然而,其高粘度和显著的吸水性限制了其应用范围。因此,为了提高KGM的脱乙酰效率,进行了电子束辐照预处理,并对KGM的理化性质和凝胶性质进行了研究。结果表明,电子束辐照和脱乙酰作用降低了吸水率,溶解度,透明度,分子量,和KGM的粘度。相反,水分含量,热稳定性,和水结合能力增加。FTIR和X射线衍射分析表明,改性前后KGM的化学和晶体结构没有显着变化。然而,改性削弱了KGM水溶胶的分子间相互作用,这影响了它们的流变学。此外,脱乙酰提高了KGM凝胶的机械性能和保水能力。总的来说,电子束辐照预处理提供了一种提高KGM脱乙酰效率和改善KGM理化性能的方法,从而扩大其在食品和化学工业中的潜在应用,在其他人中。
    Due to its emulsifying and thickening properties, konjac glucomannan (KGM) is widely used in the food, medicine, and materials industries. Nevertheless, its high viscosity and significant water absorption limit its application range. Therefore, electron beam (e-beam) irradiation pretreatment was carried out to improve the deacetylation efficiency of KGM, and the physicochemical and gel properties of KGM were investigated. The results show that e-beam irradiation and deacetylation decrease the water absorption, solubility, transparency, molecular weight, and viscosity of KGM. Conversely, the moisture content, thermal stability, and water-binding capacity increase. FTIR and X-ray diffraction analysis revealed no significant changes in the chemical and crystalline structure of KGM before and after modification. However, modification weakens the intermolecular interaction of KGM hydrosols, which affects their rheology. Furthermore, deacetylation improves the mechanical properties and water retention capacity of KGM gels. Overall, the e-beam irradiation pretreatment provides a method to increase the efficiency of KGM deacetylation and improve the physical and chemical properties of KGM, thus expanding its potential applications in the food and chemical industries, among others.
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  • 文章类型: Journal Article
    酸性矿山排水(AMD)是与采矿活动有关的环境问题,导致矿区释放有毒水。聚醚砜(PES)膜用于AMD治疗,但是它们有限的亲水性阻碍了它们的性能。壳聚糖增强亲水性,解决这个问题。然而,有效性取决于壳聚糖的脱乙酰度(DD),在壳聚糖生产的脱乙酰过程中确定。本研究优化了甲壳素脱乙酰温度,碱性(NaOH)浓度,和反应时间,对于PES/壳聚糖膜应用,壳聚糖脱乙酰度(DD)最高。先前的研究表明,高DD壳聚糖增强膜的防污和亲水性,增加污染物截留率和渗透通量。根据温度(80、100、120°C)评估最佳脱乙酰条件,NaOH浓度(20、40、60wt。%),和时间(2,4,6小时)进行。在80°C下获得的最高壳聚糖DD为87.11%,40wt。%NaOH在4小时的甲壳素脱乙酰。与原始PES膜(72.83°接触角)相比,PES/0.75壳聚糖膜(87.11%DD)显示表面亲水性(63.62°接触角)增加。这表明了膜性能的改善。因此,推测在AMD治疗背景下导致高污染物排斥和渗透通量,对文学的假设。
    Acid mine drainage (AMD) is an environmental issue linked with mining activities, causing the release of toxic water from mining areas. Polyethersulphone (PES) membranes are explored for AMD treatment, but their limited hydrophilicity hinders their performance. Chitosan enhances hydrophilicity, addressing this issue. However, the effectiveness depends on chitosan\'s degree of deacetylation (DD), determined during the deacetylation process for chitosan production. This study optimized the chitin deacetylation temperature, alkaline (NaOH) concentration, and reaction time, yielding the highest chitosan degree of deacetylation (DD) for PES/chitosan membrane applications. Prior research has shown that high DD chitosan enhances membrane antifouling and hydrophilicity, increasing contaminant rejection and permeate flux. Evaluation of the best deacetylation conditions in terms of temperature (80, 100, 120 °C), NaOH concentration (20, 40, 60 wt.%), and time (2, 4, 6 h) was performed. The highest chitosan DD obtained was 87.11% at 80 °C, 40 wt. %NaOH at 4 h of chitin deacetylation. The PES/0.75 chitosan membrane (87.11%DD) showed an increase in surface hydrophilicity (63.62° contact angle) as compared to the pristine PES membrane (72.83° contact angle). This was an indicated improvement in membrane performance. Thus, presumably leading to high contaminant rejection and permeate flux in the AMD treatment context, postulate to literature.
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