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JOURNAL OF MOLECULAR STRUCTURE · 2021 · IF 3.196

Emodin derivatives with multi-factor anti-AD activities: AChE inhibitor, anti-oxidant and metal chelator

Xiaodi Kou,Juanjuan Liu,Yuhong Chen,Aihong Yang,Rui Shen

Four new emodin derivatives which inhibit Alzheimer's disease were designed and the related activities such as cholinesterase inhibitor, anti-oxidant and metal chelator were evaluated. Among them, compounds a and b had comparable inhibitory activities of acetylcholinesterase to control drug tacrine. In particular, compound a had the strongest inhibitory effect on acetylcholinesterase with IC 50 value of 0.067 μM. Kinetic analysis of a and b indicated the mixed-type inhibition. Molecular simulation studies showed that they could bind both the catalytically active site and the peripheral anion site of acetylcholinesterase. The antioxidant activities were determined using the superoxide radical ( . O 2 – ) and hydroxyl radical ( . OH) assays. All derivatives showed high anti-oxidative activities. The mechanisms of electrochemical oxidation of emodin and its derivations were studied by cyclic voltammetry. In addition, compounds a-d exhibited obvious chelating abilities with Cu 2+ , Fe 3+ , Zn 2+ and Al 3+ ions. Interestingly, complexes chelated with Cu 2+ and Zn 2+ showed better acetylcholinesterase inhibitory activities and antioxidative activities. Taken together, emodin derivatives have multi-factor anti-Alzheimer's disease activities, and they are worthy of further study as potential candidate drugs for Alzheimer's disease.

研究领域: 药理学 · 神经科学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2016 · IF 3.994

Xanthoceraside hollow gold nanoparticles, green pharmaceutics preparation for poorly water-soluble natural anti-AD medicine

Da-li Meng,Lei Shang,Xiao-he Feng,Xing-fei Huang,Xin Che

In order to increase the solubility of poorly water-soluble natural product, xanthoceraside, an effective anti-AD compound from Xanthoceras sorbifolia Bunge , and maintain its natural property, the xanthoceraside hollow gold nanoparticles were successively prepared by green ultrasonic method with silica spheres as templates and HF solution as selective etching solvent. Hollow gold nanoparticles and drug-loaded hollow gold nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The solubilities of xanthoceraside loaded on hollow gold nanoparticles were increased obviously from 3.0   μg/ml and 2.5   μg/ml to 12.7   μg/ml and 10.7   μg/ml at 25   °C and 37   °C, respectively. The results of XRD and DSC indicated that the reason for this increase was mainly due to the amorphous state of xanthoceraside loaded on the hollow gold nanoparticles. In summary, the method of loading xanthoceraside onto hollow gold nanoparticles was a green and useful strategy to improve the solubility and dissolution of poorly water-soluble natural products and worth to applying to other natural products.

CAS / MDL: 919-30-2
研究领域: 药剂学 · 纳米医学 · 绿色制药
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Frontiers in Microbiology · 2018 · IF 4.019

Purification and Initial Characterization of 3-Hydroxybenzoate 6-Hydroxylase From a Halophilic Martelella Strain AD-3

Chen Xin,Tang Hongzhi,Liu Yongdi,Xu Ping,Xue Yong,Lin Kuangfei,Cui Changzheng

3-Hydroxybenzoate 6-hydroxylase, an NADH-dependent flavoprotein, can convert 3-hydroxybenzoate which is an important intermediate in the biodegradation of many aromatic hydrocarbons. 3-Hydroxybenzoate is metabolized by entering the TCA cycle through the gentisate pathway. We found a putative 3HB6H gene from a cluster that potentially encodes for gentisic acid degradation from a halophilic Martelella sp. strain AD-3. The corresponding protein was expressed with an N-terminal His-tag and purified by Ni2+-nitrilotriacetic acid affinity chromatography. The protein showed an overexpressed band of about 46 kDa by SDS–PAGE, and it was also proven that the enzyme contains FAD by absorption spectroscopy and HPLC analysis. The optimal activity of 3HB6H from strain AD-3 was observed in phosphate buffer (pH 8.0) at 37∘C without salinity (NaCl) and metal salts. The Km values of 3-hydroxybenzoate 6-hydroxylase were determined to be 72.6 ± 10.1 μM and 104.1 ± 18.2 μM for 400 μM NADH and 3-hydroxybenzoate, respectively. Site-directed mutagenesis showed that residues 305, 306 and 308 are important for FAD binding. In addition, we found that Tyr221 and Gln305 of 3HB6H from strain AD-3 are involved in substrate binding.

研究领域: 微生物学 · 酶学
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ACS Sustainable Chemistry & Engineering · 2020 · IF 7.632

Effect of Cholinium Amino Acids Ionic Liquids As Cosolvents on the Bioconversion of Phytosterols by Mycobacterium sp. Resting Cells

Xia Xiao,Jing-Kai He,Yi-Xin Guan,Shan-Jing Yao

Androst-4-ene-3,17-dione (AD) is an important intermediate of steroid drugs, and the microbial side-chain cleavage of sterols to produce AD by Mycobacterium sp. has attracted much attention. Unfortunately, a low yield of this reaction due to the extremely poor solubility of sterols in aqueous medium is a critical problem. Ionic liquid (IL) as a promising alternative to organic solvents is deemed to increase the solubility of hydrophobic substrates; however, the tolerance of microorganisms to ILs is limited and biocompatible ILs are desperately needed. In this work, cholinium amino acids ([Ch][AA]) ILs were first introduced as cosolvents for the whole-cell bioconversion of phytosterols to produce AD. The physicochemical properties of these novel ILs were investigated on the basis of their structures, and the solubility of phytosterols and AD in [Ch][AA] ILs aqueous solution was determined. The results indicated that moderate cell membrane permeability was obtained by [Ch][AA] ILs, and [Ch][Asp], [Ch][Glu], and [Ch][Gln] showed proper biocompatibility to Mycobacterium sp. MB 3683 cells among 18 kinds of [Ch][AA] ILs. The highest production of AD was achieved in 1% (v/v) [Ch][Asp], which was about twice as high as that in the buffer. Therefore, [Ch][AA] ILs are potential cosolvents in steroid biotransformation to promote medium engineering for a sustainable environment.

研究领域: 生物化学 · 环境科学 · 微生物学
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CHEMOSPHERE · 2023 · IF 8.8

Enhancing sludge methanogenesis with changed micro-environment of anaerobic microorganisms by Fenton iron mud

Ming Wu,Zhen-Hu Yang,Tong-Bao Jiang,Wen-Wen Zhang,Zhi-Wei Wang,Qing-Xi Hou

Conductive materials have been demonstrated to enhance sludge methanogenesis , but few researches have concentrated on the interaction among conductive materials, microorganisms and their immediate living environment. In this study, Fenton iron mud with a high abundance of Fe(III) was recycled and applied in anaerobic reactors to promote anaerobic digestion (AD) process. The results show that the primary content of extracellular polymeric substances (EPS) such as polysaccharides and proteins increased significantly, possibly promoting microbial aggregation. Furthermore, with the increment of redox mediators including humic substances in EPS and Fe(III) introduced by Fenton iron mud, the direct interspecies electron transfer (DIET) between methanogens and interacting bacteria could be accelerated, which enhanced the rate of methanogenesis in anaerobic digestion (35.21 ± 4.53% increase compared to the control). The further analysis of the anaerobic microbial community confirmed the fact that Fenton iron mud enriched functional microorganisms, such as the abundance of CO 2 -reducing (e.g. Chloroflexi) and Fe(III)-reducing bacteria (e.g., Tepidimicrobium ), thereby expediting the electron transfer reaction in the AD process via microbial DIET and dissimilatory iron reduction (DIR). This work will make it possible for using the recycled hazardous material – Fenton iron mud to improve the performance of anaerobic granular sludge during methanogenesis.

研究领域: 环境工程 · 微生物学 · 废物管理
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FREE RADICAL BIOLOGY AND MEDICINE · 2025 · IF 8.2

Eleutheroside B ameliorates AD-like pathological features in Caenorhabditis elegans by inducing autophagy and combating oxidative stress

Xiaoyu Fu,Jing Han,Yu Xia,Wei Wang,Ya Wen,Boning Zhang,Xue Zhang,Xinyu Wang,Shengnan Han,Chenggang Zhang

Alzheimer's disease (AD) incidence is rising with no effective treatments. Eleutheroside B (EB) has neuroprotective potential, but its therapeutic effects and mechanisms in AD are unclear. This study investigated EB's effects on AD pathologies and elucidated its underlying mechanisms using a transgenic Caenorhabditis elegans ( C. elegans ) model. We found that EB could ameliorate cognitive impairment, locomotor dysfunction, and shortened lifespan induced by amyloid-β(Aβ) and Tau aggregation in C. elegans , and reduce the relative expression levels of Aβ, Tau, and phosphorylated Tau (p-Tau) proteins. EB significantly improved the health status and anti-aging capacity of the worms, as evidenced by prolonged healthspan, elevated pharyngeal pumping rate and body bend frequency, and increased body length and width. Notably, EB exhibited no observable toxicity even at high-dose administration. Furthermore, EB activated key antioxidant transcription factors skn-1 , daf-16 , and hsf-1 ; it also increased the expression levels of antioxidant enzymes superoxide dismutase-3(SOD-3) and glutathione S-transferase 4(GST-4), decreased reactive oxygen species (ROS) levels, and elevated the expression of heat shock proteins Hsp-4 and Hsp-6. EB also reduced the accumulation of p62/SQST-1 protein, promoted the colocalization of lgg-1::GFP with lysosomes, and increased the relative mRNA expression of autophagy-related genes aak-2 , unc-51 , bec-1 , vps-34 , and lgg-1 . After targeted knockdown of these genes, the protective effects of EB against AD-related pathologies were abolished. Our findings demonstrate that EB exhibits anti-aging properties and potential for ameliorating AD, which is likely mediated via antioxidative activities and autophagy induction.

CAS / MDL: 50-67-9
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Science China-Chemistry · 2021 ·Vol. 65 ·期 2 ·339-352 · IF 9.445

Visualizing Aβ deposits in live young AD model mice with a simple red/near-infrared-fluorescent AIEgen

Wang Yipu,Mei Dong,Zhang Xinyi,Qu Da-Hui,Mei Ju

Precise and early detection of β -amyloid (A β ) deposits in situ and in real time is pivotal to the diagnosis and early intervention of Alzheimer’s disease (AD). Optical imaging stands out to be a promising technique for such a task; however, it still remains a big challenge, due to the lack of high-performance imaging contrast agent. Restricted by poor blood-brain barrier (BBB) penetrability, short-wavelength excitation and emission, as well as the aggregation-caused quenching effect, the widely used gold-standard probes cannot be used for early in-vivo imaging of A β deposits. Herein, we integrate the A β deposits-favored geometry, amphiphilic and zwitterionic molecular structure, extended D-π-A electronic structure, and 3D conformation into one molecule, facilely establishing a simple and economic imaging contrast agent that enjoys high specificity and affinity to A β deposits, good BBB penetrability, bright red/near-infrared fluorescence, low interference from autofluorescence, aggregation-induced emission (AIE) feature, high signal-to-noise ratio (SNR), and high contrast. In-vitro, ex-vivo , and in-vivo experiments with different strains of mice indicate that AIE-CNPy-AD holds the universality to A β deposits identification. Noteworthily, AIE-CNPy-AD is even able to precisely trace the small and sparsely-distributed A β deposits in AD model mice as young as 4-month-old APP/PS1 mice, the youngest having A β deposits. Moreover, the present probe could clearly reveal the increase and enlargement of A β deposits as the mice grow. Therefore, AIE-CNPy-AD might be an ideal alternative for early AD diagnosis and highly reliable monitoring of AD progression.

研究领域: 神经生物学 · 医学影像学 · 分子探针设计
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SEPARATION AND PURIFICATION TECHNOLOGY · 2018 · IF 3.927

Enhanced fouling and wetting resistance of composite Hyflon AD/poly(vinylidene fluoride) membrane in vacuum membrane distillation

Xue Li,Yongxing Zhang,Jingyi Cao,Xiaozu Wang,Zhaoliang Cui,Shouyong Zhou,Meisheng Li,Enrico Drioli,Zhaohui Wang,Shuaifei Zhao

Membrane fouling and pore wetting are the key problems affecting the separation performance of membrane distillation (MD). They can become more severe with increasing the operation time, which will have a negative impact on heat and mass transfers. In this paper, solutions containing CaCO 3 , humid acid (HA), and/or silica sols (SiO 2 ) were used as the feed with different Hyflon AD/polyvinylidene fluoride (PVDF) composite membranes for vacuum membrane distillation (VMD). The evolutions of flux and salt rejection during the concentration process were examined, and the membranes with different properties were compared. The results showed that the original membrane was more prone to be fouled and wetted even at low concentration factors. In the single-component systems, CaCO 3 impacts the membrane performance most severely. With the hybrid component solutions, the flux declines for the composite membranes were lower than that of the original membrane. Compared with the single-component systems, the practical situation is more likely close to the hybrid-component system where fouling and wetting were easier to happen. Overall, the composite membranes showed enhanced fouling and wetting resistance and maintained stable salt rejections. Particularly, the composite membrane with smaller pore sizes (M-40L) performed best among all the membranes, suggesting its high potential for practical VMD applications.

CAS / MDL: 1415-93-6
研究领域: 环境科学 · 材料科学
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APPLIED SURFACE SCIENCE · 2018 · IF 4.439

The enhanced performance of Sb-modified Cu/TiO2 catalyst for selective catalytic reduction of NOx with NH3

Zhong-yi Wang,Rui-tang Guo,Xu Shi,Wei-guo Pan,Jian Liu,Xiao Sun,Shuai-wei Liu,Xing-yu Liu,Hao Qin

The Cu/TiO 2 catalysts modified by Sb were compounded through the sol-gel way and put into use for the selective catalytic reduction (SCR) of NOx with NH 3 . Experimental results suggested that CuSb/TiO 2 -0.4 exhibited the excellent NOx conversion and SO 2 tolerance. Subsequently, the relationship between surface physicochemical properties and catalytic performance was also investigated by different characterization methods. From characterizations, the introduction of Sb for Cu/TiO 2 could promote the generation of more Cu 2+ , surface adsorbed oxygen species and surface acid sites on CuSb/TiO 2 -0.4 catalyst. Furthermore, Sb species on CuSb/TiO 2 -0.4 could contribute to the formation of more surface ad-NOx and ad-NH 3 species, which would enhance the NH 3 -SCR process effectively through both the Langmuir-Hinshelwood (L-H) and Eley-Rideal (E-R) mechanisms.

研究领域: 催化 · 环境科学 · 材料科学
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JOURNAL OF ENVIRONMENTAL MANAGEMENT · 2025 · IF 8.4

Quorum sensing signaling molecules enhance the treatment performance of the HN-AD bacteria-Chlorella symbiotic system in MABR

Shumin Qin,Lin Deng,Yan Lin,Lang Jiang,Xilong Liu,Qian Zhang

To enhance the stability of membrane aerated biofilm reactor (MABR) and accelerate the formation of biofilm, this study introduced a symbiotic system composed of heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria and Chlorella into the MABR, and compared it with a control system inoculated with HN-AD bacteria and activated sludge. The effects of adding 0.8 μM exogenous C8-HSL on biofilm formation and the efficiency of nitrogen and phosphorus removal were investigated by comparing systems with and without the signaling molecule. Results showed that 0.8 μM C8-HSL enhanced the removal efficiencies of ammonia nitrogen, total nitrogen (TN), and total phosphorus (TP) by 25.17 %, 36.22 %, and 38.74 %, respectively, and increased extracellular polymeric substances (EPS) production by 68.62 %. High-throughput sequencing identified Desulfomicrobium and Aliidiomarina as the dominant microorganisms involved in nitrogen and phosphorus removal. The nirB gene played a key role in the denitrification process, and phoBR gene was essential for phosphorus removal. This study provides theoretical support for the application of quorum sensing in MABR systems, offering a novel strategy to improve the efficiency and stability of high ammonia wastewater treatment.

CAS / MDL: 147852-84-4
研究领域: 环境工程 · 微生物学 · 生物技术 · 废水处理 · 分子生物学
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Biomaterials Science · 2019 ·Vol. 7 ·期 10 ·4248-4259 · IF 5.251

The topography of fibrous scaffolds modulates the paracrine function of Ad-MSCs in the regeneration of skin tissues

Ruiying Huang,Jian Wang,Haoxiang Chen,Xuelei Shi,Xiaocheng Wang,Yonghua Zhu,Zhikai Tan

Injuries to the skin are common in daily life, and a certain type or size of defect is not easily restored using conventional dressings or naturally. The repair of these defects requires restoration of function in regenerated tissues. In this study, a tissue engineered skin was designed and fabricated using a bio-3D printing system. Polycaprolactone and bacterial cellulose comprised the scaffold, due to their excellent biocompatibility and multifunctionality. Adipose-derived mesenchymal stem cells (Ad-MSCs) were seeded onto the scaffold to functionalize it as an artificial skin. The finished artificial skin had mechanical properties similar to that of natural skin, and its fibrous structure providing a unique micro-environment that could regulate the paracrine function of the Ad-MSCs. This effect could be greatly increased by changes in the characteristics of the biomaterials. The artificial skin exhibited high biological activity, strong induction of cell recruitment, migration, growth and up-regulation of gene expression of relevant factors, resulting in excellent wound healing characteristics. This study clarified novel design aspects of cell-material interactions in which the topographical characteristics of materials can be further developed to establish cell signaling or communication networks that take advantage of the paracrine actions of Ad-MSCs to promote specific tissue regeneration or repair characteristics.

CAS / MDL: 67-68-5
研究领域: 组织工程 · 生物医学工程 · 再生医学 · 细胞生物学 · 材料科学
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CHEMISTRY & BIODIVERSITY · 2022 ·Vol. 20 ·期 1 ·e202200867 · IF 2.745

Design, Synthesis, Calculation and Biological Activity Studies Based on Privileged Coumarin Derivatives as Multifunctional Anti-AD Lead Compound

Huiyan Wang,Mengyang Su,Xuli Shi,Xiangyu Li,Xinyu Zhang,Aihong Yang,Rui Shen

Coumarins and their derivatives possessed a variety of biological activities and some of coumarin-based drugs have been approved by the US Food and Drug Administration. Alzheimer's disease (AD) has caused great losses to human society. However, due to its complex pathogenesis, the ideal therapeutic approach has not been found yet. Free radical scavenging activity which is one of the main activities of coumarin core structure is closely related to other anti-AD activities. Therefore, in this work coumarins were chosen as privileged lead compounds for the development of anti-AD drugs based on strategy of multi-target directed ligands (MTDLs). Derivatives 1 – 3 which could modulate multiple targets simultaneously, including ROS, cholinesterase, βamyloid (Aβ) aggregation, and metal dyshomeostasis were designed and for the first time synthesized. Their anti-AD activities were studied both in vitro and in silico . Results showed that 1 – 3 possessed potent antioxidant activities and 7-OH group did change the electron distribution of the molecule and enhance the antioxidant activities. They also have good inhibition activities on acetylcholinesterase (AChE) and Aβ aggregation and compound 1 had the strongest AChE inhibitory effect among the three compounds (AChE IC 50 =11.15 μM). Compound 1 – 3 could also selectively chelate with Cu 2+ and Al 3+ to regulate the metal homeostasis. In silico simulations, including molecular docking and prediction of ADMET performance, indicated that 1 – 3 could interact with target proteins and cross the blood brain barrier. In conclusion, 1 – 3 could be promising MTDLs applied as anti-AD candidate drugs. Graphical

研究领域: 药物化学 · 神经科学 · 有机合成
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