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  1. Article ; Online: Jointly Composite Feature Learning and Autism Spectrum Disorder Classification Using Deep Multi-Output Takagi-Sugeno-Kang Fuzzy Inference Systems.

    Lu, Zhaowu / Wang, Jun / Mao, Rui / Lu, Minhua / Shi, Jun

    IEEE/ACM transactions on computational biology and bioinformatics

    2023  Volume 20, Issue 1, Page(s) 476–488

    Abstract: ... classifier DeepTSK, which combines a multi-output Takagi-Sugeno-Kang (MO-TSK) fuzzy inference system (FIS ...

    Abstract Autism spectrum disorder (ASD) is characterized by poor social communication abilities and repetitive behaviors or restrictive interests, which has brought a heavy burden to families and society. In many attempts to understand ASD neurobiology, resting-state functional magnetic resonance imaging (rs-fMRI) has been an effective tool. However, current ASD diagnosis methods based on rs-fMRI have two major defects. First, the instability of rs-fMRI leads to functional connectivity (FC) uncertainty, affecting the performance of ASD diagnosis. Second, many FCs are involved in brain activity, making it difficult to determine effective features in ASD classification. In this study, we propose an interpretable ASD classifier DeepTSK, which combines a multi-output Takagi-Sugeno-Kang (MO-TSK) fuzzy inference system (FIS) for composite feature learning and a deep belief network (DBN) for ASD classification in a unified network. To avoid the suboptimal solution of DeepTSK, a joint optimization procedure is employed to simultaneously learn the parameters of MO-TSK and DBN. The proposed DeepTSK was evaluated on datasets collected from three sites of the Autism Brain Imaging Data Exchange (ABIDE) database. The experimental results showed the effectiveness of the proposed method, and the discriminant FCs are presented by analyzing the consequent parameters of Deep MO-TSK.
    MeSH term(s) Humans ; Autism Spectrum Disorder/diagnostic imaging ; Brain/diagnostic imaging ; Brain Mapping/methods ; Autistic Disorder ; Magnetic Resonance Imaging/methods
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1557-9964
    ISSN (online) 1557-9964
    DOI 10.1109/TCBB.2022.3163140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Co-existing polysaccharides affect the systemic exposure of major bioactive ingredients in Chang-Kang-Fang, a multi-herb prescription for treatment of irritable bowel syndrome.

    Zhong, Ping / Zhou, Jing / Fan, Yan-Ting / Guo, Meng-Fei / Zhu, He / Zhou, Shan-Shan / Zhu, Jin-Hao / Zhang, Huan-Huan / Zhou, Gui-Rong / Miao, Xing-Long / Li, Song-Lin / Mao, Qian

    Journal of ethnopharmacology

    2022  Volume 298, Page(s) 115601

    Abstract: Ethnopharmacological relevance: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used ...

    Abstract Ethnopharmacological relevance: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment of irritable bowel syndrome (IBS) in China. Decoction is the administration form of CKF in clinical practice. Previously, CKF has been confirmed with activities of releasing pain and reversing disorders of intestinal propulsion. And alkaloids, monoglycosides, chromones were found as the main bioactive components potentially contributing to the efficacy of CKF. Polysaccharide was also a major constituent in CKF. But if and how polysaccharides influence the systemic exposure of bioactive components in CKF is unknown.
    Aim of the study: In this study, we aimed to demonstrate the contribution of the co-existed polysaccharides on the systemic exposure of the major bioactive components from CKF in normal and IBS model rats.
    Materials and methods: An UPLC-TQ-MS with multiple reaction monitoring (MRM) scan method was developed and validated for quantifying six major small molecular bioactive ingredients of CKF in the plasma samples, including magnoflorine (MAG), berberine (BBR), albiflorin (ALB), paeoniflorin (PAE), 5-O-methylvisamminol (5-OM) and prim-O-glucosylcimifugin (POG). The rats received CKF decoction (CKF) and CKF small molecule portion (knockout of polysaccharides, CKFSM), respectively. IBS model rats were induced by daily bondage and gavage of Sennae Folium decoction (derived from the leaf of Cassia angustifolia Vahl). The effects of the co-existing polysaccharides on the pharmacokinetic parameters of six small molecular bioactive components in normal and IBS model rats were systematically evaluated. The potential gut microbiota involved mechanisms of the effects was validated by broad-spectrum antibiotic (ABX) treatment.
    Results: The selectivity, precision, accuracy, recovery and matrix effect of the established quantification method were all within acceptable limits of biological sample. In normal rats, the co-existing polysaccharides significantly reduced the AUC
    Conclusions: A reliable and sensitive UPLC-TQ-MS method was successfully developed and validated for evaluating influence of co-existing polysaccharides on pharmacokinetic behavior of six major small molecules components in CKF. The co-existing polysaccharides enhanced the systemic exposure of six bioactive small molecules in CKF under IBS pathological state potentially via gut microbiota involvement.
    MeSH term(s) Animals ; Chromatography, High Pressure Liquid/methods ; Drugs, Chinese Herbal/pharmacokinetics ; Drugs, Chinese Herbal/therapeutic use ; Irritable Bowel Syndrome/drug therapy ; Irritable Bowel Syndrome/pathology ; Polysaccharides/pharmacology ; Polysaccharides/therapeutic use ; Prescriptions ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Drugs, Chinese Herbal ; Polysaccharides ; chang-kang-fang
    Language English
    Publishing date 2022-08-10
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2022.115601
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Integrating multiple-chromatographic approaches to evaluate chemical consistency of Chang-Kang-Fang preparations from mixed-herb decoction and combined single-herb decoction.

    Fan, Yan-Ting / Zhong, Ping / Xu, Jin-Di / Zhou, Shan-Shan / Kong, Ming / Zhou, Gui-Rong / Mao, Qian / Li, Song-Lin

    Journal of pharmaceutical and biomedical analysis

    2021  Volume 203, Page(s) 114186

    Abstract: Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription ...

    Abstract Chang-Kang-Fang formula (CKF), a multi-herbs traditional Chinese medicine (TCM) prescription for treating irritable bowel syndrome (IBS), has been clinically applied in the traditional form of mixed-herb decoction (MHD), or in the modern form of combined single-herb decoction (cSHD, so called dispensing granule decoction) in the near decades, but the chemical consistency between the MHD and cSHD is still unknown. Herein, a new strategy by integrating multiple-chromatographic approaches to characterize both polysaccharides and small molecules was developed to compare the chemical consistency between MHD and cSHD. Sixteen small molecules were simultaneously qualified and quantified by UPLC-QTOF-MS/MS, the molecular weight distribution of polysaccharides was characterized by HPGPC-ELSD, while the monosaccharide composition and total saccharides content were determined by HPLC-PDA and UV-VIS, respectively. It was found that the molecular weight range and monosaccharide composition of polysaccharides, as well as the composition of small molecules, were identical between MHD and cSHD. However, the contents of berberine, epiberberine, coptisine, palmatine, albiflorin and paeoniflorin in MHD were significantly lower than those in cSHD, whereas the content of polysaccharides in MHD was higher than that in cSHD, indicating that there is a significant difference in the quality between MHD and cSHD, in particular for the relative contents of major small molecules and polysaccharides. Whether or not these quality variations affect the efficacy and safety of CKF deserves further investigation.
    MeSH term(s) Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Tandem Mass Spectrometry
    Chemical Substances Drugs, Chinese Herbal ; chang-kang-fang
    Language English
    Publishing date 2021-06-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2021.114186
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Co-existing polysaccharides affect the systemic exposure of major bioactive ingredients in Chang-Kang-Fang, a multi-herb prescription for treatment of irritable bowel syndrome

    Zhong, Ping / Zhou, Jing / Fan, Yan-Ting / Guo, Meng-Fei / Zhu, He / Zhou, Shan-Shan / Zhu, Jin-Hao / Zhang, Huan-Huan / Zhou, Gui-Rong / Miao, Xing-Long / Li, Song-Lin / Mao, Qian

    Journal of ethnopharmacology. 2022 Nov. 15, v. 298

    2022  

    Abstract: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment ...

    Abstract Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment of irritable bowel syndrome (IBS) in China. Decoction is the administration form of CKF in clinical practice. Previously, CKF has been confirmed with activities of releasing pain and reversing disorders of intestinal propulsion. And alkaloids, monoglycosides, chromones were found as the main bioactive components potentially contributing to the efficacy of CKF. Polysaccharide was also a major constituent in CKF. But if and how polysaccharides influence the systemic exposure of bioactive components in CKF is unknown. In this study, we aimed to demonstrate the contribution of the co-existed polysaccharides on the systemic exposure of the major bioactive components from CKF in normal and IBS model rats. An UPLC-TQ-MS with multiple reaction monitoring (MRM) scan method was developed and validated for quantifying six major small molecular bioactive ingredients of CKF in the plasma samples, including magnoflorine (MAG), berberine (BBR), albiflorin (ALB), paeoniflorin (PAE), 5-O-methylvisamminol (5-OM) and prim-O-glucosylcimifugin (POG). The rats received CKF decoction (CKF) and CKF small molecule portion (knockout of polysaccharides, CKFSM), respectively. IBS model rats were induced by daily bondage and gavage of Sennae Folium decoction (derived from the leaf of Cassia angustifolia Vahl). The effects of the co-existing polysaccharides on the pharmacokinetic parameters of six small molecular bioactive components in normal and IBS model rats were systematically evaluated. The potential gut microbiota involved mechanisms of the effects was validated by broad-spectrum antibiotic (ABX) treatment. The selectivity, precision, accuracy, recovery and matrix effect of the established quantification method were all within acceptable limits of biological sample. In normal rats, the co-existing polysaccharides significantly reduced the AUC₍₀₋ₜ₎ of MAG and PAE compared with CKFSM group. The Cₘₐₓ and AUC₍₀₋ₜ₎ of other four compound were not influenced by co-existing polysaccharides. However, in IBS model rats, compared with CKFSM group, the Cₘₐₓ and AUC₍₀₋ₜ₎ of the six ingredients significantly increased in CKF group. For CKF + ABX group, the Cₘₐₓ of six ingredients decreased significantly when compared with CKF group, and the AUC₍₀₋ₜ₎ of MAG, BBR, ALB, PAE also reduced with significant differences. A reliable and sensitive UPLC-TQ-MS method was successfully developed and validated for evaluating influence of co-existing polysaccharides on pharmacokinetic behavior of six major small molecules components in CKF. The co-existing polysaccharides enhanced the systemic exposure of six bioactive small molecules in CKF under IBS pathological state potentially via gut microbiota involvement.
    Keywords Senna alexandrina ; antibiotics ; berberine ; intestinal microorganisms ; intestines ; irritable bowel syndrome ; leaves ; pain ; pathological processes and conditions ; pharmacokinetics ; polysaccharides ; traditional medicine ; China
    Language English
    Dates of publication 2022-1115
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2022.115601
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome.

    Mao, Qian / Shi, Lei / Wang, Zhi-Gang / Luo, Yu-Hui / Wang, Yin-Yu / Li, Xue / Lu, Min / Ju, Jian-Min / Xu, Jin-Di / Kong, Ming / Zhou, Shan-Shan / Shen, Min-Qin / Li, Song-Lin

    Journal of ethnopharmacology

    2017  Volume 201, Page(s) 123–135

    Abstract: Ethnopharmacological relevance: Chang-Kang-Fang formula (CKF), a multi-herb ...

    Abstract Ethnopharmacological relevance: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown.
    Aim of the study: To investigate the chemical profiles and effects of CKF on IBS model.
    Materials and methods: The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated.
    Results: 80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d.
    Conclusions: CKF could alleviate the symptoms of IBS by modulating the brain-gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF.
    MeSH term(s) Acetic Acid ; Animals ; Calcitonin Gene-Related Peptide/blood ; Colon/drug effects ; Colon/metabolism ; Colon/pathology ; Drugs, Chinese Herbal/analysis ; Drugs, Chinese Herbal/pharmacology ; Drugs, Chinese Herbal/therapeutic use ; Irritable Bowel Syndrome/blood ; Irritable Bowel Syndrome/drug therapy ; Irritable Bowel Syndrome/metabolism ; Irritable Bowel Syndrome/pathology ; Male ; Mice ; Phytochemicals/analysis ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Rats, Sprague-Dawley ; Serotonin/metabolism ; Substance P/blood ; Substance P/metabolism ; Vasoactive Intestinal Peptide/metabolism ; Visceral Pain/blood ; Visceral Pain/drug therapy ; Visceral Pain/metabolism ; Visceral Pain/pathology
    Chemical Substances Drugs, Chinese Herbal ; Phytochemicals ; chang-kang-fang ; Serotonin (333DO1RDJY) ; Substance P (33507-63-0) ; Vasoactive Intestinal Peptide (37221-79-7) ; Calcitonin Gene-Related Peptide (83652-28-2) ; Acetic Acid (Q40Q9N063P)
    Language English
    Publishing date 2017-04-06
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2017.02.045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Chemical profiles and pharmacological activities of Chang-Kang-Fang, a multi-herb Chinese medicinal formula, for treating irritable bowel syndrome

    Mao, Qian / Jian-Min Ju / Jin-Di Xu / Lei Shi / Min Lu / Ming Kong / Min-Qin Shen / Shan-Shan Zhou / Song-Lin Li / Xue Li / Yin-Yu Wang / Yu-Hui Luo / Zhi-Gang Wang

    Journal of ethnopharmacology. 2017 Apr. 06, v. 201

    2017  

    Abstract: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been ...

    Abstract Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome (IBS). The mechanisms of CKF for treating IBS and the components that are responsible for the activities were still unknown.To investigate the chemical profiles and effects of CKF on IBS model.The chemical profiles of CKF were investigated by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS). On colon irritation induced rat neonates IBS model, the influence of CKF on neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and 5-hydroxytryptamine (5-HT), were measured by ELISA, and the effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores. In addition, the activities of CKF against acetic acid-induced nociceptive responses and prostigmin methylsulfate triggered intestinal propulsion in mice were also evaluated.80 components were identified or tentatively assigned from CKF, including 11 alkaloids, 20 flavanoids, 4 monoterpenoids, 9 iridoid glycoside, 9 phenylethanoid glycosides, 10 chromones, 7 organic acid, 3 coumarins, 2 triterpene and 5 other compounds. On IBS rat model, CKF was observed to reduce AWR scores and levels of SP, CGRP, VIP and 5-HT. Moreover, CKF reduced the acetic acid-induced writhing scores at all dosages and reduced the intestinal propulsion ration at dosage of 7.5 and 15.0g/kg/d.CKF could alleviate the symptoms of IBS by modulating the brain–gut axis through increasing the production of neuropeptides such as CGRP, VIP, 5-HT and SP, releasing pain and reversing disorders of intestinal propulsion. Berberine, paeoniflorin, acteoside, flavonoids and chromones may be responsible for the multi-bioactivities of CKF.
    Keywords animal models ; berberine ; calcitonin gene-related peptide ; colon ; coumarins ; enzyme-linked immunosorbent assay ; flavanoids ; iridoid glycosides ; irritable bowel syndrome ; mass spectrometry ; medicinal properties ; mice ; monoterpenoids ; pain ; serotonin ; substance P ; traditional medicine ; triterpenoids ; ultra-performance liquid chromatography ; vasoactive intestinal peptide
    Language English
    Dates of publication 2017-0406
    Size p. 123-135.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2017.02.045
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Pd-Adsorbed SiN

    Guo, Gang / Mao, Lingyun / Liu, Kang / Tan, Xiaochao

    Langmuir : the ACS journal of surfaces and colloids

    2024  Volume 40, Issue 14, Page(s) 7669–7679

    Abstract: Gas-insulated switchgear (GIS) equipment must be protected by detecting and eliminating the toxic ... ...

    Abstract Gas-insulated switchgear (GIS) equipment must be protected by detecting and eliminating the toxic SF
    Language English
    Publishing date 2024-03-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2005937-1
    ISSN 1520-5827 ; 0743-7463
    ISSN (online) 1520-5827
    ISSN 0743-7463
    DOI 10.1021/acs.langmuir.4c00370
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Improvement of wheat drought tolerance through editing of TaATX4 by CRISPR/Cas9.

    Wang, Zhongxue / Zhang, Yifang / Kang, Zhensheng / Mao, Hude

    Journal of genetics and genomics = Yi chuan xue bao

    2023  Volume 50, Issue 11, Page(s) 913–916

    MeSH term(s) CRISPR-Cas Systems/genetics ; Triticum/genetics ; Drought Resistance ; Gene Editing ; Genome, Plant
    Language English
    Publishing date 2023-10-16
    Publishing country China
    Document type Letter
    ZDB-ID 2374568-X
    ISSN 1873-5533 ; 1673-8527
    ISSN (online) 1873-5533
    ISSN 1673-8527
    DOI 10.1016/j.jgg.2023.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: CM-YOLOv8: Lightweight YOLO for Coal Mine Fully Mechanized Mining Face.

    Fan, Yingbo / Mao, Shanjun / Li, Mei / Wu, Zheng / Kang, Jitong

    Sensors (Basel, Switzerland)

    2024  Volume 24, Issue 6

    Abstract: With the continuous development of deep learning, the application of object detection based on deep neural networks in the coal mine has been expanding. Simultaneously, as the production applications demand higher recognition accuracy, most research ... ...

    Abstract With the continuous development of deep learning, the application of object detection based on deep neural networks in the coal mine has been expanding. Simultaneously, as the production applications demand higher recognition accuracy, most research chooses to enlarge the depth and parameters of the network to improve accuracy. However, due to the limited computing resources in the coal mining face, it is challenging to meet the computation demands of a large number of hardware resources. Therefore, this paper proposes a lightweight object detection algorithm designed specifically for the coal mining face, referred to as CM-YOLOv8. The algorithm introduces adaptive predefined anchor boxes tailored to the coal mining face dataset to enhance the detection performance of various targets. Simultaneously, a pruning method based on the L1 norm is designed, significantly compressing the model's computation and parameter volume without compromising accuracy. The proposed algorithm is validated on the coal mining dataset DsLMF+, achieving a compression rate of 40% on the model volume with less than a 1% drop in accuracy. Comparative analysis with other existing algorithms demonstrates its efficiency and practicality in coal mining scenarios. The experiments confirm that CM-YOLOv8 significantly reduces the model's computational requirements and volume while maintaining high accuracy.
    Language English
    Publishing date 2024-03-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2052857-7
    ISSN 1424-8220 ; 1424-8220
    ISSN (online) 1424-8220
    ISSN 1424-8220
    DOI 10.3390/s24061866
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Facilitated OH¯ diffusion via bubble motion and water flow in a novel electrochemical reactor for enhancing homogeneous nucleation of CaCO

    Mao, Wei / Gu, Yuwei / Kang, Wenda / Yu, Hongtao

    Water research

    2023  Volume 242, Page(s) 120195

    Abstract: Electrochemistry is a potential method for water softening. An essential disadvantage is OH¯ ions from water electrolysis accumulate on cathode surface, inducing the generation of the insulating ... ...

    Abstract Electrochemistry is a potential method for water softening. An essential disadvantage is OH¯ ions from water electrolysis accumulate on cathode surface, inducing the generation of the insulating CaCO
    MeSH term(s) Electrolysis ; Electrochemistry ; Ions ; Diffusion ; Electrodes
    Chemical Substances hydroxide ion (9159UV381P) ; Ions
    Language English
    Publishing date 2023-06-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 202613-2
    ISSN 1879-2448 ; 0043-1354
    ISSN (online) 1879-2448
    ISSN 0043-1354
    DOI 10.1016/j.watres.2023.120195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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