171 results on '"Leong KH"'
Search Results
2. Use of graphene to reduce resin cure shrinkage
- Author
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International Conference on Composite Materials (22nd : 2019 : Melboune, VIC.), Sum, WS, Leong, KH, and Leong, AYL
- Published
- 2019
3. The Residual Tensile Strength of Stitched and Unstitched Carbon/Epoxy Laminates Impacted under Tensile Load
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Herszberg, Israel, Weller, T, Leong, KH, and Bannister, MK
- Published
- 1996
4. The Influence of Hard Points on Rib Separation in Postbuckling Stiffened Panel Design
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Sheppard, A, Kelly, D, Salmon, J, Raju, J, Leong, KH, and Tong, L
- Published
- 1996
5. An Investigation of Fracture Mechanisms of Carbon Epoxy Laminates Subjected to Impact and Compression-after-impact Loading
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Leong, KH, Herszberg, Israel, and Bannister, MK
- Published
- 1996
6. An Evaluation of the Effect of Transverse Stitching on Strength of RIM Lap Joints
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Tong, L, Jain, LK, Leong, KH, Kelly, D, and Herszberg, Israel
- Published
- 1996
7. Compression and Compression-after-impact Properties of 2-D Braided Carbon/Epoxy Composites
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Falzon, Paul J, Herszberg, Israel, Bannister, Michael K, and Leong, KH
- Published
- 1996
8. Bearing Strength of Glass/epoxy Composites Manufactured from Weft-knitted E-glass Fabric
- Author
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Australasian Congress on Applied Mechanics (1st : 1996 : Melbourne, Vic.), Herszberg, Israel, Falzon, PJ, Leong, KH, and Bannister, MK
- Published
- 1996
9. Impact Damage Resistance and Tolerance of Stitched Carbon Epoxy Laminates
- Author
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Australian Aeronautical Conference (6th : 1995 : Melbourne, Vic.), Leong, KH, Herszberg, I, and Bannister, MK
- Published
- 1995
10. An elderly couple with COVID-19 pneumonia treated in Singapore: contrasting clinical course and management
- Author
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Wong, SY, primary, Leong, KH, additional, Ng, KS, additional, Tan, SH, additional, Lo, PLC, additional, and Chan, K, additional
- Published
- 2020
- Full Text
- View/download PDF
11. Accuracy of medical record scoring of the SLICC/ACR Damage Index for systemic lupus erythematosus
- Author
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Boey Ml, Lee Hy, Leong Kh, Kok-Yong Fong, Feng Ph, Siew Pang Chan, Julian Thumboo, Chere A T Chapman, and S Thio
- Subjects
Adult ,Male ,medicine.medical_specialty ,Index (economics) ,Adolescent ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Medical Records ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,immune system diseases ,Internal medicine ,Severity of illness ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Prospective Studies ,Child ,Prospective cohort study ,030203 arthritis & rheumatology ,integumentary system ,business.industry ,Medical record ,Reproducibility of Results ,virus diseases ,Middle Aged ,Immunology ,Female ,business ,Cohort study - Abstract
Objective: To study the accuracy of medical record scoring of the SLICC/ACR Damage Index (DI) for SLE. Methods: Medical record DI (MDI) scoring of 60 SLE patients by one physician was compared with prospective direct DI (DDI) scoring a median of 2 y earlier. Agreement between DDI and MDI total and organ system scores was compared using Cohen's kappa, the degree of misclassification by MDI and the significance of differences between DDI and MDI scores. Results: The mean duration of SLE at DDI scoring was 5.2 y. The median/mean (SD) DDI and MDI total scores were 0=0.78 (1.38) and 0=0.85 (1.44). Damage was present on DDI and MDI scoring in 36.7% (22=60) and 38.3% (23=60) of patients. Qualitative MDI and DDI total scores (damage present/absent) showed good agreement (kappa ‘ 0.61, 95% CI ‘ 0.40–0.82, 18.3% misclassification). Quantitative MDI and DDI total scores (degree of damage) showed moderate agreement (kappa ‘ 0.47, 95% CI ‘ 0.28–0.66, 36.7% misclassification). 9 of 12 MDI organ system scores misclassified < 10% of subjects. There was no statistically significant difference between DDI and MDI total or organ system scores. Conclusion: MDI total scoring is a good qualitative and moderate quantitative reflection of SLE related damage. MDI organ system scores are more accurate than MDI total scores.
- Published
- 2000
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12. THE DISCOVERY OF NEW KINGIANIC ACIDS FROM ENDIANDRA KINGIANA WITH POTENTIAL ANTICANCER ACTIVITY
- Author
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Leong,KH, Mohamad, Azmi, Litaudon, Marc, Mohamad, Khalit, and Awang, Khalijah
- Subjects
Lauraceae ,Anticancer ,Kingianins Acid ,Bcl-xL ,Cancer Cell Lines ,Polyketides ,Endiandra kingiana ,Apoptosis ,Natural Products - Abstract
In our pursuit of discovering bioactive phytochemicals from the Malaysia flora, we recently reported a series of new natural pentacyclic polyketides, kingianins A-L, isolated from the ethyl acetate extract of the bark of Endiandra kingiana Gamble (Lauraceae). Several kingianins showed strong binding affinity to the anti-apoptotic protein Bcl-xL, and can therefore be considered as potential anticancer agents. In order to discover additional members of this chemical series or close analogues, we investigated the methanolic extract of the bark of this species. E. kingiana is a medium-sized evergreen tree, distributed throughout the peninsular Malaysia and Borneo. There are about 125 Endiandra species found through the tropical regions, including 10 species in Malaysia, but to our knowledge only three species i.e E. introrsa, E. anthropophagorum and E. kingiana, have been studied for their phytochemicals. The first one has been reported to produce interesting cyclic polyketides, named endiandric acids, possessing eight chiral centers, and usually isolated as racemic mixtures. It was postulated by Black and co-workers that they could be formed by non-enzymatic cyclizations (8πe and 6πe electrocyclization followed by Diels-Alder reaction) of a phenylpolyene acid precursor. The aim of this study is to isolate compounds from the methanolic extract of the E. kingiana bark, which further being subjected to MTS cell viability assays on selected human cancer cell lines and binding affinities toward antiapoptotic proteins, namely Bcl-xL and Mcl-1. This effort is to identify compounds with potential anticancer activity.
- Published
- 2013
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13. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
- Author
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Smolen, Js, Beaulieu, A, Rubbert Roth, A, Ramos Remus, C, Rovensky, J, Alecock, E, Woodworth, T, Alten, R, Tate, G, Maldonado Cocco JA, Scali, J, Taylor, A, Hanrahan, P, Nash, P, Smith, M, Smolen, J, Koeller, M, Eberl, G, Dunky, A, Zamani, O, Simon, Jc, Scheinberg, Ma, Yaneva, D, Oparanov, B, Karastatev, D, Atkins, C, Bell, M, Haraoui, B, Marin, L, Thorne, Jc, Zummer, M, Khraishi, M, Mckendry, Rj, Pandith, V, Mccarthy, T, Lau, Cs, Li, E, Mok, Cc, Kahan, A, Wendling, D, Bardin, T, Nguyen, M, Claudepierre, P, Berenbaum, F, Puechal, X, Fiehn, C, Heilig, B, Hellmich, B, Lange, U, Lorenz, Hm, Wendler, J, Czirijak, L, Hodinka, L, Szekanecz, Z, Molad, Y, Nahir, M, Rosner, I, Rubinow, A, Abu Shakra, M, Elkayam, O, Marcolongo, R, Bagnato, G, Triolo, G, Trotta, F, DE VITA, Salvatore, Lugo, Ge, Abud Mendoza, C, Pineca, C, de la Torre IG, Pacheco, C, Leong, Kh, Koh, Dr, Dudler, J, Villiger, P, Lothrenoo, W, Asavatanabodee, P, Nilganuwong, S, and Totemchokchaiyakarn, K.
- Subjects
rheumatoid arthritis ,interleukin-6 - Published
- 2008
14. Guest editorial
- Author
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Leong, KH, primary, Gibson, Professor AG, additional, and Echtermeyer, Professor AT, additional
- Published
- 2014
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15. Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region
- Author
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Xing Sun, Ru Li, Yueming Cai, Adeeba Al-Herz, Manjari Lahiri, Minhaj Rahim Choudhury, Rudy Hidayat, Bagus Putu Putra Suryana, Yuko Kaneko, Keishi Fujio, Nguyen Van Hung, Sapan Pandya, Leong Khai Pang, Wanruchada Katchamart, Keshav Raj Sigdel, Buddhi Paudyal, Pongthorn Narongroeknawin, Parawee Chevaisrakul, Feng Sun, Yu Lu, Carmen Ho, Swan Sim Yeap, and Zhanguo Li
- Subjects
Public aspects of medicine ,RA1-1270 - Abstract
Background: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region. Methods: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission. Findings: A total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission. Interpretation: Remission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.
- Published
- 2021
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16. Qualification of a composite system for pipeline repairs under dry, wet, and water-submerged conditions
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Djukic, Luke P, primary, Leong, Alan YL, additional, Falzon, Paul J, additional, and Leong, KH, additional
- Published
- 2013
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17. Numerical study of annular flaws/defects affecting the integrity of grouted composite sleeve repairs on pipelines
- Author
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Sum, WS, primary and Leong, KH, additional
- Published
- 2013
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18. Preparation and characterisation of polyamide–polyimide organoclay nanocomposites
- Author
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Varley, Russell J, primary, Groth, Andrew M, additional, and Leong, KH, additional
- Published
- 2008
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19. Central serous retinopathy complicating systemic lupus erythematosus: a case series
- Author
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Khng, CGYW, primary, Yap, EY, additional, Au-Eong, KG, additional, Lim, TH, additional, and Leong, KH, additional
- Published
- 2000
- Full Text
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20. Numerical study of annular flaws/defects affecting the integrity of grouted composite sleeve repairs on pipelines.
- Author
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Sum, WS and Leong, KH
- Subjects
- *
COMPOSITE materials , *NUMERICAL analysis , *ANNULAR flow , *PIPELINES , *FINITE element method , *FRACTURE mechanics , *MAINTENANCE - Abstract
Grouted sleeves are one of the accepted techniques used for the repair of corroded pipelines. The sleeves are attached over the region of pipe that requires repair, creating an annulus that is then filled with grout material. In this study, the repair system consists of a composite sleeve with polymeric grout. A finite element (FE) study is carried out to predict the effects of selected properties of the composite sleeve and grout on the pipe integrity, subjected to internal fluid pressure. The primary purpose is to identify the main effects and interactions between different material properties, which are useful to aid design decisions for such repairs. While structural reinforcement is provided by the sleeve, the grout plays an important role in transferring hoop pressure in the pipe to the sleeve. Since experimental observations indicate the development of cracks in the grout solely under curing conditions, it is imperative to investigate the effects of such defects. Several different repair conditions that have potential to critically influence the integrity of a repaired pipe are investigated. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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21. Heat transfer analysis and cure modelling of composite repairs for pipelines.
- Author
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Liu, Xiao Lin, Leong, Alan YL, Leong, KH, Falzon, Paul J, and Tan, Yee Chech
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HEAT transfer in composite materials ,COMPOSITE materials ,NUMERICAL analysis ,ACCELERATION (Mechanics) ,CURING ,PIPELINE maintenance & repair ,MAINTENANCE - Abstract
This paper presents work conducted to develop numerical tool for heat transfer analysis and cure modelling for the accelerated curing of a composite pipeline repair system. Experimental work was conducted to measure the cure kinetics of the composite material. The measurements were fitted into a cure kinetic model which was subsequently implemented into a FE package through a user subroutine. Applications of the numerical tool to the design and analysis of heating configuration for curing the composite repair are also presented. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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22. Qualification of a composite system for pipeline repairs under dry, wet, and water-submerged conditions.
- Author
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Djukic, Luke P, Leong, Alan YL, Falzon, Paul J, and Leong, KH
- Subjects
COMPOSITE materials ,PIPELINE maintenance & repair ,DRYING ,WETTING ,WATER ,EPOXY compounds ,CORROSION & anti-corrosives ,FRACTURE mechanics - Abstract
A new glass/epoxy prepreg system has been developed as a solution to a long-standing challenge of corrosion and other damage, such as gouging and denting, sustained by piping, pipelines, and risers. The system has been designed to be applicable in the majority of operational conditions encountered in the oil and gas sector, encompassing onshore as well as offshore environments. This paper discusses the comprehensive qualification process undertaken to enable the repair of wall-thinning defects (Type A) and through-wall defects (Type B). The results show that the composite system meets the requirements of ISO/TS 24817 and so also concurrently complies with ASME PCC-2. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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23. Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma
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Chay, OM, primary, Goh, A, additional, Lim, WH, additional, Leong, KH, additional, and Lou, J, additional
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- 1999
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24. SLE mortality in an oriental population
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Koh, ET, primary, Seow, A., additional, Leong, KH, additional, and Chng, HH, additional
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- 1997
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25. Enhancement of mucosal IgA responses by interleukins 5 and 6 encoded in recombinant vaccine vectors
- Author
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Ramsay, AJ, primary, Leong, KH, additional, Boyle, D, additional, Ruby, J, additional, and Ramshaw, IA, additional
- Published
- 1994
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26. Salivary biomarkers: Effective diagnostic tool for oral leukoplakia and oral squamous cell carcinoma.
- Author
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Liew YX, Kadir K, Phan CW, Leong KH, Kallarakkal TG, and Tilakaratne WM
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- Humans, Leukoplakia, Oral diagnosis, Leukoplakia, Oral metabolism, Saliva chemistry, Saliva metabolism, Mouth Neoplasms diagnosis, Mouth Neoplasms metabolism, Biomarkers, Tumor analysis, Carcinoma, Squamous Cell diagnosis
- Abstract
Objective: To identify potential salivary biomarkers for the diagnosis and monitoring of disease progression in oral squamous cell carcinoma and oral leukoplakia., Materials and Methods: An advance search from PubMed and Hindawi was performed with keywords; oral leukoplakia/oral squamous cell carcinoma, salivary biomarker and diagnosis/prognosis. An additional search of articles was done through a manual search from the Google Scholar database., Results: Twenty studies involving salivary biomarkers as diagnostic tools for oral squamous cell carcinoma and/or oral leukoplakia were identified. A narrative review was carried out., Conclusion: Single or multiple salivary biomarkers reported by most studies have shown great potential as diagnostic tools for oral squamous cell carcinoma and oral leukoplakia. However, the validation of sensitivity and specificity should be carried out to ensure the accuracy of the biomarkers. Furthermore, a standardised method for saliva collection should be established to prevent variability in the expression of biomarkers., (© 2023 Wiley Periodicals LLC.)
- Published
- 2024
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27. Nanobubbles improve peroxymonosulfate-based advanced oxidation: High efficiency, low toxicity/cost, and novel collaborative mechanism.
- Author
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Zhang JB, Zou JJ, Dai C, Hu J, You X, Gao MT, Li J, Fu R, Zhang Y, Leong KH, and Xu XS
- Abstract
Cl
- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl- /PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl- /PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl- /PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5 - as well as phenol and Cl- /HSO5 - , increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl- /PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl- /PMS system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
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28. A novel mycelial pellet applied to remove polycyclic aromatic hydrocarbons: High adsorption performance & its mechanisms.
- Author
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Zou JJ, Dai C, Hu J, Tong WK, Gao MT, Zhang Y, Leong KH, Fu R, and Zhou L
- Subjects
- Adsorption, Pyrenes, Mycelium, Polycyclic Aromatic Hydrocarbons analysis
- Abstract
Mycelial pellets formed by Penicillium thomii ZJJ were applied as efficient biosorbents for the removal of polycyclic aromatic hydrocarbons (PAHs), which are a type of ubiquitous harmful hydrophobic pollutants. The live mycelial pellets were able to remove 93.48 % of pyrene at a concentration of 100 mg/L within 48 h, demonstrating a maximum adsorption capacity of 285.63 mg/g. Meanwhile, the heat-killed one also achieved a removal rate of 65.01 %. Among the six typical PAHs (pyrene, phenanthrene, fluorene, anthracene, fluoranthene, benzo[a]pyrene), the mycelial pellets preferentially adsorbed the high molecular weight PAHs, which also have higher toxicity, resulting in higher removal efficiency. The experimental results showed that the biosorption of mycelial pellets was mainly a spontaneous physical adsorption process that occurred as a monolayer on a homogeneous surface, with mass transfer being the key rate-limiting step. The main adsorption sites on the surface of mycelia were carboxyl and N-containing groups. Extracellular polymeric substances (EPS) produced by mycelial pellets could enhance adsorption, and its coupling with dead mycelia could achieve basically the same removal effect to that of living one. It can be concluded that biosorption by mycelial pellets occurred due to the influence of electrostatic and hydrophobic interactions, consisting of five steps. Furthermore, the potential applicability of mycelial pellets has been investigated considering diverse factors. The mycelia showed high environmental tolerance, which could effectively remove pyrene across a wide range of pH and salt concentration. And pellets diameters and humic acid concentration had a significant effect on microbial adsorption effect. Based on a cost-effectiveness analysis, mycelium pellets were found to be a low-cost adsorbent. The research outcomes facilitate a thorough comprehension of the adsorption process of pyrene by mycelial pellets and their relevant applications, proposing a cost-effective method without potential environmental issues (heat-killed mycelial pellets plus EPS) to removal PAHs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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29. Integrated photocatalysis adsorption processes for oxytetracycline removal: using volborthite and its composite with g-C 3 N 4 .
- Author
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Wee WQ, Sim LC, Leong KH, and Aziz AA
- Abstract
The photocatalytic-adsorption performance of the composites of volborthite (CuVA) and graphitic carbon nitride (g-C
3 N4 ) was studied in this work using oxytetracycline (OTC) as model pollutant under LED light irradiation. CuVA at different weight percentages (10, 30, 50), namely, C10, C30, and C50, were loaded onto graphitic carbon nitride using wet chemical method. The physical, chemical, and optical properties were evaluated via various analytical techniques. Through integrated adsorption-photocatalytic process, no significant photocatalytic reaction occurred in g-C3 N4 and the composite even after 4 h of irradiation. The setup was modified such that each run was conducted in the presence and absence of light. Aside from photolysis and g-C3 N4 , all composites performed better under the presence of light in which CuVA improved the most from ~ 50% down to ~ 20% of initial concentration. CuVA performed almost identically (80% removal of OTC) under the presence of light irradiation at ambient temperature (22 °C) and in the dark at 32 °C, confirming that temperature was the contributing factor to the improvement instead of light. CuVA exhibited excellent adsorption capacity of 171 mg/g and adsorption rate of 90% towards the removal of highly concentrated OTC (100 mg/L) under optimized parameters of pH 5.0 and at 42 °C after 3 h of adsorption process. Life cycle assessment revealed that close to 50% of fresh 100 ppm OTC could be removed after five cycles without any desorption process., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
- Full Text
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30. D-Amino acids differentially trigger an inflammatory environment in vitro.
- Author
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Yap SH, Lee CS, Zulkifli ND, Suresh D, Hamase K, Das KT, Rajasuriar R, and Leong KH
- Subjects
- Humans, Tumor Necrosis Factor-alpha metabolism, Interleukin-8, Hydrogen Peroxide metabolism, Cytokines metabolism, Amino Acids chemistry, NF-kappa B metabolism
- Abstract
Studies in vivo have demonstrated that the accumulation of D-amino acids (D-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of D-AAs by D-amino oxidase (DAO) produces hydrogen peroxide (H
2 O2 ), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of H2 O2 contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of D-serine (D-Ser) and D-alanine (D-Ala) in human liver cancer cells, HepG2, with a focus on the production of H2 O2 the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that D-Ser decreased H2 O2 production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, D-Ala-treated cells induced H2 O2 production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both D-Ser and D-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with D-Ser. Further research is required to gain a better understanding of the mechanisms underlying D-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation., (© 2024. The Author(s).)- Published
- 2024
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31. Neural Causal Information Extractor for Unobserved Causes.
- Author
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Leong KH, Xiu Y, Chen B, and Chan WKV
- Abstract
Causal inference aims to faithfully depict the causal relationships between given variables. However, in many practical systems, variables are often partially observed, and some unobserved variables could carry significant information and induce causal effects on a target. Identifying these unobserved causes remains a challenge, and existing works have not considered extracting the unobserved causes while retaining the causes that have already been observed and included. In this work, we aim to construct the implicit variables with a generator-discriminator framework named the Neural Causal Information Extractor (NCIE), which can complement the information of unobserved causes and thus provide a complete set of causes with both observed causes and the representations of unobserved causes. By maximizing the mutual information between the targets and the union of observed causes and implicit variables, the implicit variables we generate could complement the information that the unobserved causes should have provided. The synthetic experiments show that the implicit variables preserve the information and dynamics of the unobserved causes. In addition, extensive real-world time series prediction tasks show improved precision after introducing implicit variables, thus indicating their causality to the targets.
- Published
- 2023
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32. Unveiling synergism of polymyxin B with chloramphenicol derivatives against multidrug-resistant (MDR) Klebsiella pneumoniae.
- Author
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Idris N, Leong KH, Wong EH, and Abdul Rahim N
- Subjects
- Chloramphenicol pharmacology, Klebsiella pneumoniae, Drug Synergism, Anti-Bacterial Agents pharmacology, Polymyxins pharmacology, Microbial Sensitivity Tests, Drug Resistance, Multiple, Bacterial, Polymyxin B pharmacology, Thiamphenicol pharmacology
- Abstract
Polymyxins are last-line antibiotics against multidrug-resistant Klebsiella pneumoniae but using polymyxins alone may not be effective due to emerging resistance. A previous study found that combining polymyxin B with chloramphenicol effectively kills MDR K. pneumoniae, although the bone marrow toxicity of chloramphenicol is concerning. The aim of this study is to assess the antibacterial efficacy and cytotoxicity of polymyxin B when combined with chloramphenicol and its derivatives, namely thiamphenicol and florfenicol (reported to have lesser toxicity compared to chloramphenicol). The antibacterial activity was evaluated with antimicrobial susceptibility testing using broth microdilution and time-kill assays, while the cytotoxic effect on normal bone marrow cell line, HS-5 was evaluated using the MTT assay. All bacterial isolates tested were found to be susceptible to polymyxin B, but resistant to chloramphenicol, thiamphenicol, and florfenicol when used alone. The use of polymyxin B alone showed bacterial regrowth for all isolates at 24 h. The combination of polymyxin B and florfenicol demonstrated additive and synergistic effects against all isolates (≥ 2 log
10 cfu ml-1 reduction) at 4 and 24 h, respectively, while the combination of polymyxin B and thiamphenicol resulted in synergistic killing at 24 h against ATCC BAA-2146. Furthermore, the combination of polymyxin B with florfenicol had the lowest cytotoxic effect on the HS-5 cells compared to polymyxin B combination with chloramphenicol and thiamphenicol. Overall, the combination of polymyxin B with florfenicol enhanced bacterial killing against MDR K. pneumoniae and exerted minimal cytotoxic effect on HS-5 cell line., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)- Published
- 2023
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33. Resource utilization of rice straw to prepare biochar as peroxymonosulfate activator for naphthalene removal: Performances, mechanisms, environmental impact and applicability in groundwater.
- Author
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Zhang JB, Dai C, Wang Z, You X, Duan Y, Lai X, Fu R, Zhang Y, Maimaitijiang M, Leong KH, Tu Y, and Li Z
- Subjects
- Soil, Naphthalenes, Oryza, Groundwater
- Abstract
Herein, biochar was prepared using rice straw, and it served as the peroxymonosulfate (PMS) activator to degrade naphthalene (NAP). The results showed that pyrolysis temperature has played an important role in regulating biochar structure and properties. The biochar prepared at 900°C (BC900) had the best activation capacity and could remove NAP in a wide range of initial pH (5-11). In the system of BC900/PMS, multi-reactive species were produced, in which
1 O2 and electron transfer mainly contributed to NAP degradation. In addition, the interference of complex groundwater components on the NAP removal rate must get attention. Cl- had a significant promotional effect but risked the formation of chlorinated disinfection by-products. HCO3 - , CO3 2- , and humic acid (HA) had an inhibitory effect; surfactants had compatibility problems with the BC900/PMS system, which could lead to unproductive consumption of PMS. Significantly, the BC900/PMS system showed satisfactory remediation performance in spiked natural groundwater and soil, and it could solve the problem of persistent groundwater contamination caused by NAP desorption from the soil. Besides, the degradation pathway of NAP was proposed, and the BC900/PMS system could degrade NAP into low or nontoxic products. These suggest that the BC900/PMS system has promising applications in in-situ groundwater remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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34. Recommendations for enhanced primary series (third dose) COVID-19 vaccination for people with rheumatic diseases: Chapter of Rheumatologists, College of Physicians, Singapore.
- Author
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Xu C, Lahiri M, Santosa A, Chew LC, Angkodjojo S, Sriranganathan M, Fong W, Arkachaisri T, Suresh E, Kong KO, Lateef A, Lee TH, Leong KH, Low A, Tan TC, and Leung YY
- Abstract
Introduction: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context., Methods: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel., Results: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs., Conclusion: These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs., Competing Interests: None
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- 2023
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35. An Advax-CpG55.2™ adjuvanted recombinant spike protein vaccine protects cynomolgus macaques from a homologous SARS-CoV-2 virus challenge.
- Author
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Honda-Okubo Y, Li L, André G, Leong KH, Howerth EW, Bebin-Blackwell AG, Ross TM, and Petrovsky N
- Subjects
- Animals, Female, Humans, Spike Glycoprotein, Coronavirus genetics, Adjuvants, Immunologic, Vaccines, Synthetic genetics, Macaca fascicularis, Adenoviridae, Antibodies, Neutralizing, Antibodies, Viral, SARS-CoV-2, COVID-19 prevention & control
- Abstract
Traditional protein-based vaccine approaches to COVID-19 were overshadowed by the new mRNA and adenoviral vector vaccine approaches which were first to receive marketing authorization. The current study tested for the first time in repurposed aged (median 15.4 years) cynomolgus macaques, a novel Advax-CpG55.2™ adjuvanted recombinant extracellular domain spike protein trimer antigen for immunogenicity, protection and safety. Nine animals received two intramuscular injections 10 days apart of recombinant spike protein (25 μg) with Advax-CpG55.2™ (10 mg/200 μg) and 5 controls received saline injections. Serum antibody levels were followed for 3 months and then the animals were challenged with SARS-CoV-2 virus. Clinical signs, local reactions, body weight, food consumption and antibody levels were monitored till termination on either day 3 or 7 post-infection. Two weeks after the second dose, 8/9 immunized macaques had high serum spike and receptor binding domain binding antibodies that were able to cross-neutralize Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and, to a lesser extent, Omicron variants (B.1.1.529 ). Antibody levels decayed over the subsequent 3 months, and minimal neutralizing antibody was detectable immediately prior to the challenge which used a vaccine-homologous Wuhan-like ancestral virus. Of the nine vaccinated animals, only one 18-year-old female sacrificed at d3 had low levels of lung virus, versus 100 % of the control animals. Four of 5 (80 %) control animals had positive lung staining for SARS-CoV-2 virus versus just 1 of 9 (11 %) in the immunized group. The immunized animals exhibited better maintenance of appetite post-challenge. Neutralizing antibody levels rebounded rapidly in immunized animals, post-challenge. This data supports the benefits of Advax-CpG adjuvanted recombinant spike protein vaccine in protecting against a homologous SARS-CoV-2 infection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YHO, GA and NP are affiliated with Vaxine Pty Ltd which holds the rights to COVAX-19/Spikogen vaccine and Advax™ and CpG55.2™ adjuvants., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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36. Separation of Antioxidant-Rich Alternanthera Sessilis Red Extracts by Sephadex LH-20 and Identification of Polyphenols Using HPLC-QToF-MS/MS.
- Author
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Hwong CS, Leong KH, Aziz AA, and Kong KW
- Subjects
- Tandem Mass Spectrometry, Chromatography, High Pressure Liquid, Plant Extracts chemistry, Flavonoids analysis, Ethanol, Water, Polyphenols pharmacology, Polyphenols analysis, Antioxidants chemistry
- Abstract
This study aimed to fractionate Alternanthera sessilis Red (ASR) crude extracts and determine their antioxidant activities as well as the related active components in the whole plant. ASR was extracted with water and ethanol, and further separated using a Sephadex LH-20 column. Following the assessments of the polyphenolic contents and antioxidant activities of crude extracts (H
2 OASR and EtOHASR ) and fractions, a HPLC-QToF analysis was performed on the crude extracts and selected fractions (H2 OASR FII and EtOHASR FII). Three water fractions (H2 OASR FI, FII and FIII) and four ethanolic fractions (EtOHASR FI, FII, FIII and FIV) were derived from their crude extracts, respectively. EtOHASR FII exhibited the greatest total phenolic content (120.41 mg GAE/g fraction), total flavonoid content (223.07 mg RE/g fraction), and antioxidant activities (DPPH IC50 =159.43 μg/mL; FRAP=1.93 mmol Fe2+ /g fraction; TEAC=0.90 mmol TE/g fraction). Correlation analysis showed significant (p<0.01) positive correlations between both TPC (r=0.748-0.970) and TFC (r=0.686-0.949) with antioxidant activities in the crude extracts and fractions. Flavonoids were the major compounds in the four selected samples tentatively identified using HPLC-QToF-MS/MS, with the highest number of 30 polyphenol compounds detected in the most active fraction, EtOHASR FII., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)- Published
- 2023
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37. Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.
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Hastings JF, Latham SL, Kamili A, Wheatley MS, Han JZR, Wong-Erasmus M, Phimmachanh M, Nobis M, Pantarelli C, Cadell AL, O'Donnell YEI, Leong KH, Lynn S, Geng FS, Cui L, Yan S, Achinger-Kawecka J, Stirzaker C, Norris MD, Haber M, Trahair TN, Speleman F, De Preter K, Cowley MJ, Bogdanovic O, Timpson P, Cox TR, Kolch W, Fletcher JI, Fey D, and Croucher DR
- Subjects
- Humans, Apoptosis, Signal Transduction, Histone Deacetylase Inhibitors, Drug Resistance, Neoplasm, Neuroblastoma
- Abstract
Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network. Furthermore, we reveal that the memory of this initially random state is retained following chemotherapy treatment across a series of in vitro, in vivo, and patient models. Using matched PDX models established at diagnosis and relapse from individual patients, we show that HDAC inhibitor priming cannot erase the memory of this resistant state within relapsed neuroblastomas but improves response in the first-line setting by restoring drug-induced JNK activity within the chemoresistant population of treatment-naïve tumors.
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- 2023
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38. Presence of depression and anxiety with distinct patterns of pharmacological treatments before the diagnosis of chronic fatigue syndrome: a population-based study in Taiwan.
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Chen C, Yip HT, Leong KH, Yao WC, Hung CL, Su CH, Kuo CF, and Tsai SY
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- Humans, Male, Female, Depression complications, Depression diagnosis, Depression drug therapy, Retrospective Studies, Taiwan epidemiology, Anxiety Disorders, Anxiety, Fatigue Syndrome, Chronic complications, Fatigue Syndrome, Chronic diagnosis, Fatigue Syndrome, Chronic drug therapy
- Abstract
Objective: An increased prevalence of psychiatric comorbidities (including depression and anxiety disorder) has been observed among patients with chronic fatigue syndrome (CFS). However, few studies have examined the presence of depression and anxiety disorder before the diagnosis of CFS. This study aimed to clarify the preexisting comorbidities and treatments associated with patients with subsequent CFS diagnosis in a population-based cohort in Taiwan., Methods: An analysis utilizing the National Health Insurance Research Database of Taiwan was conducted. Participants included were 6303 patients with CFS newly diagnosed between 2000 and 2010 and 6303 age-/sex-matched controls., Results: Compared with the control group, the CFS group had a higher prevalence of depression and anxiety disorder before the diagnosis of CFS. Sampled patients who took specific types of antidepressants, namely, selective serotonin reuptake inhibitors (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] 1.04-1.39), serotonin antagonists and reuptake inhibitors (SARI; aOR = 1.87, 95% CI 1.59-2.19), and tricyclic antidepressants (aOR = 1.46, 95% CI 1.09-1.95), had an increased risk of CFS. CFS risk was also higher among participants taking benzodiazepine, muscle relaxants, and analgesic drugs. A sub-group analysis revealed that SARI use was related to an increased risk of CFS in the depression, anxiety disorder, male, and female groups. In the depression and anxiety disorder groups, analgesic drug use was associated with an increased CFS risk. Nonpharmacological treatment administration differed between men and women., Conclusion: This population-based retrospective cohort study revealed an increased risk of CFS among populations with preexisting depression and anxiety disorder, especially those taking SARI and analgesic drugs., (© 2023. The Author(s).)
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- 2023
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39. Continuous Monitoring of the Hydration Behavior of Hydrophilic Matrix Tablets Using Time-Domain NMR.
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Tsuji T, Ono T, Taguchi H, Leong KH, Hayashi Y, Kumada S, Okada K, and Onuki Y
- Subjects
- Delayed-Action Preparations, Magnetic Resonance Spectroscopy, Tablets, Hypromellose Derivatives chemistry, Solubility, Methylcellulose chemistry, Polyethylene Glycols chemistry, Water
- Abstract
Time-domain NMR (TD-NMR) was used for continuous monitoring of the hydration behavior of hydrophilic matrix tablets. The model matrix tablets comprised high molecular weight polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG). The model tablets were immersed in water. Their T
2 relaxation curves were acquired by TD-NMR with solid-echo sequence. A curve-fitting analysis was conducted on the acquired T2 relaxation curves to identify the NMR signals corresponding to the nongelated core remaining in the samples. The amount of nongelated core was estimated from the NMR signal intensity. The estimated values were consistent with the experiment measurement values. Next, the model tablets immersed in water were monitored continuously using TD-NMR. The difference in hydration behaviors of the HPMC and PEO matrix tablets was then characterized fully. The nongelated core of the HPMC matrix tablets disappeared more slowly than that of the PEO matrix tablets. The behavior of HPMC was significantly affected by the PEG content in the tablets. It is suggested that the TD-NMR method has potential to be utilized to evaluate the gel layer properties, upon replacement of the immersion medium: purified (nondeuterated) water is replaced with heavy (deuterated) water. Finally, drug-containing matrix tablets were tested. Diltiazem hydrochloride (a highly water-soluble drug) was employed for this experiment. Reasonable in vitro drug dissolution profiles, which were in accordance with the results from TD-NMR experiments, were observed. We concluded that TD-NMR is a powerful tool to evaluate the hydration properties of hydrophilic matrix tablets.- Published
- 2023
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40. Accelerated sunlight photocatalysis through improved electron mobility between g-C 3 N 4 and BiPO 4 nanomaterial.
- Author
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Ng JJ, Sim LC, Oh WD, Saravanan P, Tan B, and Leong KH
- Subjects
- Sunlight, Electrons, Catalysis, Environmental Restoration and Remediation, Nanostructures
- Abstract
Herein, we report a detailed study on creating heterojunction between graphitic carbon nitride (g-C
3 N4 ) and bismuth phosphate (BiPO4 ), enhancing the unpaired free electron mobility. This leads to an accelerated photocatalysis of 2,4-dichlorophenols (2,4-DCPs) under sunlight irradiation. The heterojunction formation was efficaciously conducted via a modest thermal deposition technique. The function of g-C3 N4 plays a significant role in generating free electrons under sunlight irradiation. Together, the generated electrons at the g-C3 N4 conduction band (CB) are transferred and trapped by the BiPO4 to form active superoxide anion radicals (•O2 - ). These active radicals will be accountable for the photodegradation of 2,4-DCPs. The synthesized composite characteristics were methodically examined through several chemical and physical studies. Due to the inimitable features of both g-C3 N4 and BiPO4 , its heterojunction formation, 2.5wt% BiPO4 /g-C3 N4 achieved complete 2,4-DCP removal (100%) in 90 min under sunlight irradiation. This is due to the presence of g-C3 N4 that enhanced electron mobility through the formation of heterojunctions that lengthens the electron-hole pairs' lifetime and maximizes the entire solar spectrum absorption to generate active electrons at the g-C3 N4 conduction band. Thus, this formation significantly draws the attention for future environmental remediation, especially in enhancing the entire solar spectrum's harvesting., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2022
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41. Oxidation of sulfamethazine by peracetic acid activated with biochar: Reactive oxygen species contribution and toxicity change.
- Author
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Zhang Z, Duan Y, Dai C, Li S, Chen Y, Tu Y, Leong KH, and Zhou L
- Subjects
- Anti-Bacterial Agents, Charcoal, Humic Substances, Peracetic Acid toxicity, Reactive Oxygen Species, Singlet Oxygen, Sulfamethazine chemistry, Sulfamethazine toxicity, Water Pollutants, Chemical chemistry, Water Pollutants, Chemical toxicity
- Abstract
Peracetic acid (PAA) as an emerging oxidative has been concerned increasingly due to its high oxidation capacity and low byproducts formation potential. This study was to investigate the oxidation of sulfamethazine (SMZ) by PAA activated with activated biochar (ABC) after thermal modification. The results demonstrated that PAA could be effectively activated by ABC to degrade SMZ in a wide pH range (3-9), which followed the pseudo-second-order kinetics (R
2 > 0.99). Both non-radicals (singlet oxygen) and free radicals (alkoxy radicals, hydroxyl radicals) existed in the ABC/PAA system, and the degradation of SMZ was dominated by singlet oxygen. Humic acid (HA), SO4 2- and HCO3 - slightly inhibited the degradation of SMZ in the ABC/PAA process, while Cl- and Br- promoted the degradation of SMZ. The cleavage of S-N, S-C bond, and SO2 extraction reaction rearrangement was the main oxidation process of SMZ. Meanwhile, the results of the ECOSAR program showed that the acute toxicity of most by-products was significantly reduced compared to SMZ, which revealed the potential applicability of the ABC/PAA process in the treatment of antibiotics pollution and their detoxification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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42. Alternanthera sessilis: Uncovering the nutritional and medicinal values of an edible weed.
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Hwong CS, Leong KH, Abdul Aziz A, Mat Junit S, Mohd Noor S, and Kong KW
- Subjects
- Ethnopharmacology, Phytochemicals pharmacology, Plant Extracts pharmacology, Plant Weeds, Polyphenols, Amaranthaceae
- Abstract
Ethnopharmacological Relevance: Weeds are often considered undesirable as they interfere with the habitat of native plants, and therefore they are underestimated and underutilised. In fact, some edible weeds have beneficial nutritional and medicinal values. Alternanthera sessilis (L.) R. Br. ex DC., an edible medicinal weed is a species of the Amaranthaceae family that consists of two cultivars: green and red. Local communities in different regions have traditionally consumed the plants as food and medicine, with the green cultivar being applied to relieve pain, treat wound healing, dysentery, asthma and hypertension, while the red cultivar is applied to prevent cardiovascular and liver diseases in general., Aim of the Study: The present review intends to provide an in-depth discussion and scientific basis of A. sessilis green and red's health-promoting properties in relation to their ethnobotanical use, nutritional components and bioactive compounds., Materials and Methods: The literature search was conducted using relevant keywords on scientific search engines such as the Web of Science, Google Scholar, Medline and Scopus., Results: A. sessilis shows potent antioxidant activity as a result of its diverse phytochemical constituents, such as polyphenols, terpenes, alkaloid and carotenoids in addition to its nutritional components: vitamin C, E and unsaturated fatty acids, which contribute to its various bioactive properties: anti-microbial and anthelmintic, anti-diabetic, lipid lowering, anti-inflammatory and analgesic activities, anti-cancer and other biological activities. Toxicity evaluation revealed the absence of adverse effect of A. sesslis extracts., Conclusion: A. sessilis has a great potential to be used as complementary medicine and ingredients for pharmaceuticals, nutraceuticals and functional foods, instead of being regarded as a pest. Prospects for enhancing the development and commercialisation of this edible medicinal weed as a high value health-promoting product are suggested., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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43. Overview of the multifaceted resistances toward EGFR-TKIs and new chemotherapeutic strategies in non-small cell lung cancer.
- Author
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Dzul Keflee R, Leong KH, Ogawa S, Bignon J, Chan MC, and Kong KW
- Subjects
- Humans, ErbB Receptors genetics, Protein Kinase Inhibitors adverse effects, Mutation, Drug Resistance, Neoplasm, Neoplasm Recurrence, Local chemically induced, Neoplasm Recurrence, Local drug therapy, Tumor Microenvironment, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
The role of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) has been vastly studied over the last decade. This has led to the rapid development of many generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, patients treated with third-generation TKIs (osimertinib, avitinib and rociletinib) targeting the EGFR T790M mutation have shown emerging resistances and relapses. Therefore, further molecular understanding of NSCLC mutations, bypass signalling, tumour microenvironment and the existence of cancer stem cells to overcome such resistances is warranted. This will pave the way for designing novel and effective chemotherapies to improve patients' overall survival. In this review, we provide an overview of the multifaceted mechanisms of resistance towards EGFR-TKIs, as well as the challenges and perspectives that should be addressed in strategising chemotherapeutic treatments to overcome the ever-evolving and adaptive nature of NSCLC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leong Kok Hoong reports financial support was provided by Ministry of Higher Education, Fundamental Research Grant. Leong Kok Hoong reports financial support was provided by University of Malaya Research Programme.., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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44. The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study.
- Author
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Yao WC, Leong KH, Chiu LT, Chou PY, Wu LC, Chou CY, Kuo CF, and Tsai SY
- Abstract
Background: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database., Methods: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000-2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed., Results: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000-2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis., Conclusions: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS., (© 2022. The Author(s).)
- Published
- 2022
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45. Treatments of chronic fatigue syndrome and its debilitating comorbidities: a 12-year population-based study.
- Author
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Leong KH, Yip HT, Kuo CF, and Tsai SY
- Subjects
- Antidepressive Agents, Tricyclic pharmacology, Antidepressive Agents, Tricyclic therapeutic use, Female, Humans, Male, Norepinephrine, Selective Serotonin Reuptake Inhibitors pharmacology, Selective Serotonin Reuptake Inhibitors therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Fatigue Syndrome, Chronic drug therapy, Fatigue Syndrome, Chronic epidemiology
- Abstract
Background: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database., Methods: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed., Result: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn's disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group., Conclusion: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems., (© 2022. The Author(s).)
- Published
- 2022
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46. Plasma d-amino acids are associated with markers of immune activation and organ dysfunction in people with HIV.
- Author
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Yap SH, Lee CS, Furusho A, Ishii C, Shaharudin S, Zulhaimi NS, Kamarulzaman A, Kamaruzzaman SB, Mita M, Leong KH, Hamase K, and Rajasuriar R
- Subjects
- Alanine, Asparagine, Biomarkers, Humans, Multiple Organ Failure complications, Proline, Serine, Amino Acids, HIV Infections complications, HIV Infections drug therapy
- Abstract
Background: d-Amino acids (d-AAs) have been associated with age-associated conditions in the general population but their relevance in people with HIV (PWH), who experience accentuated/accelerated aging has not been studied. We compared d-AA levels in HIV-infected and uninfected controls and explored their association with markers of immune activation, gut permeability and organ dysfunction., Design: Case-control analysis., Method: Plasma samples from 60 antiretroviral therapy-treated HIV-infected individuals and 59 uninfected controls were analysed. A three-dimensional HPLC system was used to measure d-and l-asparagine, serine, alanine and proline and presented as %d-AA. Additionally, cell-associated and soluble markers of immune activation and senescence were characterized. Kidney and liver functions were expressed as estimated glomerular filtration rate and fibrosis-4 scores, respectively. Mann-Whitney and Spearman rank correlation coefficients were used for statistical analysis., Results: d-Asparagine, d-serine, d-alanine and d-proline were detectable in all plasma samples and correlated with age in HIV-infected and uninfected but not different between groups. Kynurenine/tryptophan ratio was positively correlated with all %d-AAs in PWH and with %d-serine and %d-proline in controls. %d-AAs were not consistently correlated with markers of gut permeability in both groups. All %d-AAs were also correlated with kidney function in both groups whereas age-associated accumulation of %d-asparagine, %d-serine and %d-proline were correlated with liver function and the VACS score in controls., Conclusion: Plasma d-AAs are associated with chronological age and correlated with markers of immune activation and organ decline, though variably, in PWH and controls. Their role in the biology of aging warrants further investigation., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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47. Mechanisms and product toxicity of activated carbon/peracetic acid for degradation of sulfamethoxazole: implications for groundwater remediation.
- Author
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Dai C, Li S, Duan Y, Leong KH, Liu S, Zhang Y, Zhou L, and Tu Y
- Subjects
- Bicarbonates, Charcoal, Chlorides, Hydrogen Peroxide, Oxidation-Reduction, Peracetic Acid, Sulfamethoxazole, Sulfates, Groundwater, Water Pollutants, Chemical analysis
- Abstract
Carbon-based materials activated peracetic acid (PAA) to repair groundwater is an environmentally friendly and low-cost technology to overcome secondary pollution problems. In this study, thermally modified activated carbon (AC600) was applied to activate PAA to degrade sulfamethoxazole (SMX). And the effect of groundwater pH, chloride ion (Cl
- ), bicarbonate (HCO3 - ), sulfate ion (SO4 2- ), and natural organic matter (NOM) on SMX removal by AC600/PAA process was studied in detail. PAA could be effectively activated by AC600. Increasing AC600 dose (10-100mg/L) or PAA dosages (0.065-0.39 mM) generally enhanced the SMX removal, the excellent performance in SMX removal was achieved at 50 mg/L AC600 and 0.26 mM PAA. The removal of SMX was well-described by second-order kinetic, with the rate constant (kobs ) of 10.79 M-1 s-1 , both much greater than the removal constants of PAA alone (0.034 M-1 s-1 ) and AC600 alone (1.774 M-1 s-1 ). R-O·(CH3 C(O)OO·, CH3 C(O)O·) and electron-transfer process were proved to be responsible for the removal of SMX while HO· and1 O2 made little to no contribution to the novel PAA/AC600 system, which differs from typical advanced oxidation processes. The SMX can be removed effectively over a wide pH range (3-9), exhibiting a remarkable pH-tolerant performance. Sulfate ion (SO4 2- ), dissolved oxygen (DO), NOM displayed negligible influence on the SMX removal. Bicarbonate (HCO3 - ) exerted an inhibitory effect on SMX abatement, while chloride ion (Cl- ) promoted the removal of SMX. This showed excellent anti-interference capacity and satisfactory decontamination performance under actual groundwater conditions. Furthermore, the degradation pathways of SMX were proposed, there was no obvious difference in the acute toxicity of the mixed products during the degradation process. It will facilitate further research of metal-free catalyst/PAA system as a new strategy for groundwater in-situ remediation technology., (Copyright © 2022. Published by Elsevier Ltd.)- Published
- 2022
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48. Review on the contamination and remediation of polycyclic aromatic hydrocarbons (PAHs) in coastal soil and sediments.
- Author
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Dai C, Han Y, Duan Y, Lai X, Fu R, Liu S, Leong KH, Tu Y, and Zhou L
- Subjects
- Biodegradation, Environmental, Cities, Environmental Monitoring, Geologic Sediments, Soil, Polycyclic Aromatic Hydrocarbons analysis, Soil Pollutants analysis
- Abstract
The rapid economic and population growth in coastal areas is causing increasingly serious polycyclic aromatic hydrocarbons (PAHs) pollution in these regions. This review compared the PAHs pollution characteristics of different coastal areas, including industrial zones, commercial ports, touristic cities, aquacultural & agricultural areas, oil & gas exploitation areas and megacities. Currently there are various treatment methods to remediate soils and sediments contaminated with PAHs. However, it is necessary to provide a comprehensive overview of all the available remediation technologies up to date, so appropriate technologies can be selected to remediate PAHs pollution. In view of that, we analyzed the characteristics of the remediation mechanism, summarized the remediation methods for soil or sediments in coastal areas, which were physical repair, chemical oxidation, bioremediation and integrated approaches. Besides, this review also reported the development of new multi-functional green and sustainable systems, namely, micro-nano bubble (MNB), biochar, reversible surfactants and peracetic acid. While physical repair, expensive but efficient, was regarded as a suitable method for the PAHs remediation in coastal areas because of land shortage, integrated approaches would produce better results. The ultimate aim of the review was to ensure the successful restructuring of PAHs contaminated soil and sediments in coastal areas. Due to the environment heterogeneity, PAHs pollution in coastal areas remains as a daunting challenge. Therefore, new and suitable technologies are still needed to address the environmental issue., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2022
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49. Giganteone A and malabaricone C as potential pharmacotherapy for diabetes mellitus.
- Author
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Sivasothy Y, Leong KH, Loo KY, Adbul Wahab SM, Othman MA, and Awang K
- Subjects
- Biphenyl Compounds, Humans, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Molecular Docking Simulation, Resorcinols, Structure-Activity Relationship, alpha-Glucosidases metabolism, Diabetes Mellitus drug therapy, Glycoside Hydrolase Inhibitors chemistry, Glycoside Hydrolase Inhibitors pharmacology
- Abstract
The use of antidiabetic agents which control glycemic levels in the blood and simultaneously inhibit oxidative stress is an important strategy in the prevention of Diabetes Mellitus and its complications. In our previous study, malabaricone C ( 3 ) and its dimer, giganteone A ( 5 ) exhibited significant DPPH free radical scavenging activities which were lower than the activity of the positive control, ascorbic acid. These compounds were evaluated for their α-glucosidase inhibitory activities at different concentrations (0.02-2.5 mM) in the present study. Compounds 3 (IC
50 59.61 µM) and 5 (IC50 39.52 µM) were identified as active alpha-glucosidase inhibitors, each respectively being 24 and 37 folds more potent than the standard inhibitor, acarbose. Based on the molecular docking studies, compounds 3 and 5 docked into the active site of the α-glucosidase enzyme, forming mainly hydrogen bonds in the active site.- Published
- 2022
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50. Characterization of the Salt and Free Base of Active Pharmaceutical Ingredients Based on NMR Relaxometry Measured by Time Domain NMR.
- Author
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Chiba Y, Okada K, Hayashi Y, Leong KH, Kumada S, and Onuki Y
- Subjects
- Calorimetry, Differential Scanning, Magnetic Resonance Spectroscopy, Salts analysis, Time Factors, X-Ray Diffraction, Pharmaceutical Preparations analysis
- Abstract
NMR relaxometry measurement by time domain NMR (TD-NMR) is a promising technique for characterizing the properties of active pharmaceutical ingredients (APIs). This study is dedicated to identifying the salt and free base of APIs by NMR relaxometry measured by the TD-NMR technique. Procaine (PC) and tetracaine (TC) were selected as model APIs to be tested. By using conventional methods including powder X-ray diffraction and differential scanning calorimetry, this study first confirmed that the salt and free base of the tested APIs differ from each other in their crystalline form. Subsequently, measurements of T
1 and T2 relaxation were performed on the tested APIs using TD-NMR. The results demonstrated that these NMR relaxometry measurements have sufficient capacity to distinguish the difference between the free base and salt of the tested APIs. Furthermore, quantification of the composition of the binary powder blends consisting of salt and free bases was conducted by analyzing the acquired T1 and T2 relaxation curves. The analysis of the T1 relaxation curves provided a partly acceptable estimation: a good estimation of the composition was observed from PC powders, whereas for TC powders the estimation accuracy changed with the free base content in the binary blends. For the analysis on T2 relaxation curves, a precise estimation of the composition was observed from all the samples. From these findings, the NMR relaxometry measurement by TD-NMR, in particular the T2 relaxation measurement, is effective for evaluating the properties of APIs having different crystalline forms.- Published
- 2022
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