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  1. Fu X, Sévenet T, Remy F, Païs M, Hamid A, Hadi A, et al.
    J Nat Prod, 1993 Jul;56(7):1153-63.
    PMID: 8377019
    Four complex flavanones, kurziflavolactones A [2], B [3], C [4], and D [5] and a complex chalcone 6 with an unprecedented carbon side chain on the flavanone or chalcone A ring have been isolated from a Malaysian plant, Cryptocarya kurzii (Lauraceae). Their structures were determined by extensive spectroscopic analysis, especially 2D nmr experiments. Compounds 3 and 6 showed slight cytotoxicity against KB cells, with IC50 values of 4 and 15 micrograms/ml, respectively. A biosynthetic pathway for the formation of these compounds is suggested.
  2. Shi L, Fu X, Tan CP, Huang Q, Zhang B
    J Agric Food Chem, 2017 Mar 15;65(10):2189-2197.
    PMID: 28215072 DOI: 10.1021/acs.jafc.6b05749
    Ethylene gas was introduced into granular cold-water-soluble (GCWS) starches using a solid encapsulation method. The morphological and structural properties of the novel inclusion complexes (ICs) were characterized using scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy. The V-type single helix of GCWS starches was formed through controlled gelatinization and ethanol precipitation and was approved to host ethylene gas. The controlled release characteristics of ICs were also investigated at various temperature and relative humidity conditions. Avrami's equation was fitted to understand the release kinetics and showed that the release of ethylene from the ICs was accelerated by increasing temperature or RH and was decelerated by increased degree of amylose polymerization. The IC of Hylon-7 had the highest ethylene concentration (31.8%, w/w) among the five starches, and the IC of normal potato starch showed the best controlled release characteristics. As a renewable and inexpensive material, GCWS starch is a desirable solid encapsulation matrix with potential in agricultural and food applications.
  3. Ding L, Zhang B, Tan CP, Fu X, Huang Q
    Int J Biol Macromol, 2019 Sep 15;137:1068-1075.
    PMID: 31260761 DOI: 10.1016/j.ijbiomac.2019.06.226
    The objective of this study is to investigate the effects of limited moisture content and storing temperature on the retrogradation of rice starch. Starch was gelatinized in various moisture contents (30-42%) and rice paste was stored at different temperatures (4 °C, 15 °C, 30 °C, -18/30 °C and 4/30 °C). X-ray diffraction (XRD) analysis revealed that after retrogradation, the crystalline type of rice starch changed from A-type to B + V type. The B-type crystallinity of retrograded rice starch under 30 °C was the highest among the five temperature conditions, and an increase in B-type crystallinity with increasing moisture content was observed. Differential scanning calorimetry (DSC) results revealed that rice starch retrogradation consists of recrystallization of amylopectin and amylose, and is mainly attributed to amylopectin. The higher moisture content was favorable for amylopectin recrystallization, whereas the moisture content had little effect on the amylose recrystallization. The optimal temperature for amylopectin and amylose recrystallization was 4 °C and 15 °C, respectively. The amylopectin recrystallization enthalpy of rice starch stored at 4/30 °C was mediated between 4 °C and 30 °C but always higher than that at -18/30 °C. On the whole, after being heated at 42% moisture content and stored at 4 °C, rice starch showed the maximum total retrogradation enthalpy (8.44 J/g).
  4. Mohamad Zobir SZ, Mohd Fauzi F, Liggi S, Drakakis G, Fu X, Fan TP, et al.
    PMID: 26989424 DOI: 10.1155/2016/2106465
    Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, "the foundation of acquired constitution" that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications.
  5. Fu X, Song X, Li X, Wong KK, Li J, Zhang F, et al.
    PMID: 28191021 DOI: 10.1155/2017/4365715
    Traditional Chinese Marine Medicine (TCMM) represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA) displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms) via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1) Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, and Sargassum genus; (2) Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3) Holothuroidea class, Aspidochirotida order, and Holothuria genus. Our analyses showed that TCMMs with closer taxonomic relationship were more likely to possess anticancer bioactivity. We found that the cluster pattern of marine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species within Metazoa or Viridiplantae kingdom of cold nature were more likely to contain AA properties. We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources.
  6. Shao M, Li S, Tan CP, Kraithong S, Gao Q, Fu X, et al.
    Int J Biol Macromol, 2021 Mar 15;173:118-127.
    PMID: 33444656 DOI: 10.1016/j.ijbiomac.2021.01.043
    In this study, caffeine (CA) was encapsulated into food-grade starch matrices, including swelled starch (SS), porous starch (PS), and V-type starch (VS). The bitterness of the microcapsules and suppression mechanisms were investigated using an electronic tongue, molecular dynamics (MD) simulation and the in vitro release kinetics of CA. All the CA-loaded microcapsules showed a lower bitterness intensity than the control. The MD results proved that the weak interactions between starch and CA resulted in a moderate CA release rate for SS-CA microcapsules. The PS-CA microcapsule presented the longest CA release, up to 40 min, whereas the VS-CA microcapsule completely released CA in 9 min. The CA release rate was found to be related to the microcapsule structure and rehydration properties. A low CA bitterness intensity could be attributed to a delay in the CA release rate and resistance to erosion of the microcapsules. The results of this work are valuable for improving starch-based microcapsules (oral-targeted drug-delivery systems) by suppressing the bitterness of alkaloid compounds.
  7. Li S, Li C, Yang Y, He X, Zhang B, Fu X, et al.
    Food Chem, 2019 Jun 15;283:437-444.
    PMID: 30722895 DOI: 10.1016/j.foodchem.2019.01.020
    The present study aimed at investigating the effects of octenylsuccinylation and particle size on the emulsifying properties of starch granules as Pickering emulsifiers. Starch spherulites (1-5 μm), native rice starch (5-10 μm), waxy maize starch (10-20 μm) and waxy potato starch (20-30 μm) were modified with octenylsuccinic anhydride. Results showed that octenylsuccinylation caused a significant increase in the contact angle, and there was a weak positive linear correlation with the emulsifying capacity of the starch granules. After octenylsuccinylation, smaller particles of octenylsuccinate-starch granules exhibited better emulsifying properties with smaller droplet size and lower creaming index. Overall, both octenylsuccinylation and particle size have important effects on the emulsifying properties of starch granules as Pickering stabilizers. This study could be useful in the design and development of starch-based Pickering emulsifiers, and provide potential applications in the food and pharmaceutical industries.
  8. Khoo KS, Lee SY, Ooi CW, Fu X, Miao X, Ling TC, et al.
    Bioresour Technol, 2019 Sep;288:121606.
    PMID: 31178260 DOI: 10.1016/j.biortech.2019.121606
    Haematococcus pluvialis is one of the most abundant sources of natural astaxanthin as compared to others microorganism. Therefore, it is important to understand the biorefinery of astaxanthin from H. pluvialis, starting from the cultivation stage to the downstream processing of astaxanthin. The present review begins with an introduction of cellular morphologies and life cycle of H. pluvialis from green vegetative motile stage to red non-motile haematocyst stage. Subsequently, the conventional biorefinery methods (e.g., mechanical disruption, solvent extraction, direct extraction using vegetable oils, and enhanced solvent extraction) and recent advanced biorefinery techniques (e.g., supercritical CO2 extraction, magnetic-assisted extraction, ionic liquids extraction, and supramolecular solvent extraction) were presented and evaluated. Moreover, future prospect and challenges were highlighted to provide a useful guide for future development of biorefinery of astaxanthin from H. pluvialis. The review aims to serve as a present knowledge for researchers dealing with the bioproduction of astaxanthin from H. pluvialis.
  9. Wang Y, Li J, Fu X, Li J, Liu L, Alkohlani A, et al.
    Cancer Epidemiol, 2021 08;73:101958.
    PMID: 34020315 DOI: 10.1016/j.canep.2021.101958
    PURPOSE: Leptin and adiponectin are adipokines which have been commonly implicated in carcinogenesis. As such, many studies have investigated the association of circulating leptin and adiponectin levels with colorectal cancer (CRC) risk. However, the results remained inconsistent.

    METHODS: In this work, we performed a systematic review and meta-analysis to precisely examine the association between circulating levels of leptin and adiponectin and CRC risk. A systematic literature search was performed in PubMed/MEDLINE, Scopus, Web of Science, and EMBASE databases from inception until October 2020. The pooled effect size was then estimated by calculating the odds ratio (OR).

    RESULTS: A total of 23 records (comprising 26 studies) were included in the meta-analysis. The overall analysis found that circulating levels of leptin and adiponectin were not significantly associated with CRC risk (P > 0.05). Interestingly, subgroup analysis revealed that a higher level of adiponectin was significantly associated with an increased CRC risk among overweight individuals (OR = 1.16; 95 % CI: 1.02, 1.32), and a decreased CRC risk among normal weight individuals (OR = 0.76; 95 % CI: 0.62, 0.92). Besides, a higher level of adiponectin was also significantly associated with a decreased risk of CRC in men (OR = 0.76; 95 % CI: 0.59, 0.98).

    CONCLUSIONS: In conclusion, circulating leptin level was not associated with CRC risk, but that of adiponectin was associated with CRC risk only in specific subgroups.

  10. Huang L, Li S, Tan CP, Feng Y, Zhang B, Fu X, et al.
    Carbohydr Polym, 2021 Sep 01;267:118181.
    PMID: 34119149 DOI: 10.1016/j.carbpol.2021.118181
    Lauric acid was introduced into "Empty" V-type starch using a solid encapsulation method. The structural characteristics and emulsifying properties of the starch-fatty acid complex (SFAC) were explored as a function of the complexing temperature. X-ray diffraction and differential scanning calorimetry confirmed that SFAC was mainly composed of type-I amylose inclusion complexes. Contact angle measurements revealed that the hydrophobic properties of SFAC were closely related to the temperature-regulated complex index. The particle size range of SFAC gradually increased as the complexing temperature increased. The SFAC-stabilized Pickering emulsion at c of 5% and Φ of 40-60% possessed a small droplet size and long-term storage stability for up to 30 days, resulting from the formation of a gel-like network. This study provides new insight into the design of hydrophobic modified starch as a novel and multifunctional emulsifier and is of great help in the development of starch-based Pickering emulsion gels.
  11. Wang Y, Li Y, Yang Y, Peng C, Fu X, Gu X, et al.
    Exp Ther Med, 2020 Jul;20(1):543-549.
    PMID: 32537012 DOI: 10.3892/etm.2020.8728
    The aim of the present study was to analyze the sequence of the VP1 gene in enterovirus 71 (EV71) isolates and to explore their genetic evolution, so as to provide a scientific basis for the clinical prevention and treatment of hand, foot and mouth disease. The fecal samples of 590 patients with suspected hand, foot and mouth disease treated at Yan'an Hospital (Kunming, China) between January 2015 and December 2016 were collected and EV71 nucleic acid was detected by fluorescence PCR. The viral RNA of EV71-positive samples was extracted, the VP1 gene was amplified by PCR and the products were sequenced. The VP1 gene sequence was analyzed using DNAMAN and MEGA (version 4.0) software and homologous modeling was performed using Pymol software. A total of 50 EV71-positive samples were identified and the detection rate was 8.47% (50/590 cases). All of the 50 EV71 strains were of the C4 subtype. The genetic distance between the strains detected in the present study and EV71 strains detected in Beijing, Anhui and Malaysia was 0.01-0.03, while that between the strains detected in the present study and Australian strains was 2.11. Homologous modeling indicated that the amino acid sequence of the VP1 gene of the detected strains had a H144Y mutation. There was no significant genetic variation in the EV71 strain within the 2-year period. In conclusion, the EV71 strains detected in the present study was similar to that detected in Beijing, Anhui and Malaysia but different to that from Australia. A point mutation was present in the amino acid sequence of the VP1 gene.
  12. Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.
    Sci Total Environ, 2021 Jan 20;753:141904.
    PMID: 32890872 DOI: 10.1016/j.scitotenv.2020.141904
    Sick building syndrome (SBS) is a collection of nonspecific syndromes linked with the built environment. The occurrence of SBS is associated with humidity, ventilation, moulds and microbial compounds exposure. However, no study has reported the association between indoor microbiome and SBS. In this study, 308 students were surveyed for SBS symptoms from 21 classrooms of 7 junior high schools from Johor Bahru, Malaysia, and vacuum dust from floor, desks and chairs was collected. High throughput amplicon sequencing (16S rRNA gene and ITS region) and quantitative PCR were conducted to characterize the absolute concentration of bacteria and fungi taxa. In total, 326 bacterial and 255 fungal genera were detected in dust with large compositional variation among classrooms. Also, half of these samples showed low compositional similarity to microbiome data deposited in the public database. The number of observed OTUs in Gammaproteobacteria was positively associated with SBS (p = 0.004). Eight microbial genera were associated with SBS (p 
  13. Wu J, Wang HL, Liu X, Ding C, Zhou Y, Fu X, et al.
    Liver Int, 2020 02;40(2):298-307.
    PMID: 31674705 DOI: 10.1111/liv.14289
    BACKGROUND & AIMS: Trends in long-term mortality rates for viral hepatitis in East and Southeast Asia have been rarely reported. The aim of our study was to explore the long-term trends in viral hepatitis mortality rates in East and Southeast Asian countries between 1987 and 2015 and provide predictions of mortality to 2030.

    METHODS: We obtained viral hepatitis mortality data from the WHO Mortality Database for six East and Southeast Asian countries between 1987 and 2015. We produced choropleth maps of viral hepatitis mortality rates in 1987 and 2015 in East and Southeast Asia to illustrate geographic variations. We made predictions of mortality rates for each included country until the year 2030 using a series of joinpoint models.

    RESULTS: Viral hepatitis mortality rates declined in China (the average annual percent change (AAPC) = -5.1%, 95% CI: -7.5, -2.6), Singapore (AAPC = -5.4%, 95% CI: -7.5, -3.2), and the Philippines (AAPC = -3.4%, 95% CI: -4.9, -1.8). In contrast, Japan, the Republic of Korea, and Malaysia have experienced increasing trends in mortality rates, followed by decreasing trends. Our predictions indicate that all countries will experience slight to moderate downward trends until 2030.

    CONCLUSION: Favourable decreasing trends have been noted in East and Southeast Asian countries, which may not only inform the control and management of viral hepatitis in this region but also guide the prevention of viral hepatitis deaths in another region with a similar viral hepatitis epidemic.

  14. Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.
    Environ Int, 2020 05;138:105664.
    PMID: 32200316 DOI: 10.1016/j.envint.2020.105664
    Indoor microbial diversity and composition are suggested to affect the prevalence and severity of asthma by previous home microbiome studies, but no microbiome-health association study has been conducted in a school environment, especially in tropical countries. In this study, we collected floor dust and environmental characteristics from 21 classrooms, and health data related to asthma symptoms from 309 students, in junior high schools in Johor Bahru, Malaysia. The bacterial and fungal composition was characterized by sequencing 16s rRNA gene and internal transcribed spacer (ITS) region, and the absolute microbial concentration was quantified by qPCR. In total, 326 bacterial and 255 fungal genera were characterized. Five bacterial (Sphingobium, Rhodomicrobium, Shimwellia, Solirubrobacter, Pleurocapsa) and two fungal (Torulaspora and Leptosphaeriaceae) taxa were protective for asthma severity. Two bacterial taxa, Izhakiella and Robinsoniella, were positively associated with asthma severity. Several protective bacterial taxa including Rhodomicrobium, Shimwellia and Sphingobium have been reported as protective microbes in previous studies, whereas other taxa were first time reported. Environmental characteristics, such as age of building, size of textile curtain per room volume, occurrence of cockroaches, concentration of house dust mite allergens transferred from homes by the occupants, were involved in shaping the overall microbial community but not asthma-associated taxa; whereas visible dampness and mold, which did not change the overall microbial community for floor dust, was negatively associated with the concentration of protective bacteria Rhodomicrobium (β = -2.86, p = 0.021) of asthma. The result indicates complex interactions between microbes, environmental characteristics and asthma symptoms. Overall, this is the first indoor microbiome study to characterize the asthma-associated microbes and their environmental determinant in the tropical area, promoting the understanding of microbial exposure and respiratory health in this region.
  15. Khoo VPH, Ting RS, Wang X, Luo Y, Seeley J, Ong JJ, et al.
    Front Psychol, 2021;12:773510.
    PMID: 34955992 DOI: 10.3389/fpsyg.2021.773510
    Background: Though many literatures documented burnout and occupational hazard among healthcare workers and frontliners during pandemic, not many adopted a systemic approach to look at the resilience among this population. Another under-studied population was the large numbers of global healthcare workers who have been deployed to tackle the crisis of COVID-19 pandemic in the less resourceful regions. We investigated both the mental wellbeing risk and protective factors of a deployed healthcare workers (DHWs) team in Wuhan, the epicenter of the virus outbreak during 2020. Method: A consensual qualitative research approach was adopted with 25 DHWs from H province through semi-structured interviews after 3 months of deployment period. Results: Inductive-Deductive thematic coding with self-reflexivity revealed multi-layered risk and protective factors for DHWs at the COVID-19 frontline. Intensive working schedule and high-risk environment, compounded by unfamiliar work setting and colleagues; local culture adaptation; isolation from usual social circle, strained the DHWs. Meanwhile, reciprocal relationships and "familial relatedness" with patients and colleagues; organizational support to the DHWs and their immediate families back home, formed crucial wellbeing resources in sustaining the DHWs. The dynamic and dialectical relationships between risk and protective factors embedded in multiple layers of relational contexts could be mapped into a socio-ecological framework. Conclusion: Our multidisciplinary study highlights the unique social connectedness between patient-DHWs; within DHWs team; between deploying hospital and DHWs; and between DHWs and the local partners. We recommend five organizational strategies as mental health promotion and capacity building for DHWs to build a resilient network and prevent burnout at the disaster frontline.
  16. Fu X, Yuan Q, Zhu X, Li Y, Meng Y, Hashim JH, et al.
    Environ Sci Process Impacts, 2021 Aug 01;23(8):1171-1181.
    PMID: 34278392 DOI: 10.1039/d1em00115a
    Pathogens are commonly present in the human respiratory tract, but symptoms are varied among individuals. The interactions between pathogens, commensal microorganisms and host immune systems are important in shaping the susceptibility, development and severity of respiratory diseases. Compared to the extensive studies on the human microbiota, few studies reported the association between indoor microbiome exposure and respiratory infections. In this study, 308 students from 21 classrooms were randomly selected to survey the occurrence of respiratory infections in junior high schools of Johor Bahru, Malaysia. Vacuum dust was collected from the floor, chairs and desks of these classrooms, and high-throughput amplicon sequencing (16S rRNA and ITS) and quantitative PCR were conducted to characterize the absolute concentration of the indoor microorganisms. Fifteen bacterial genera in the classes Actinobacteria, Alphaproteobacteria, and Cyanobacteria were protectively associated with respiratory infections (p < 0.01), and these bacteria were mainly derived from the outdoor environment. Previous studies also reported that outdoor environmental bacteria were protectively associated with chronic respiratory diseases, such as asthma, but the genera identified were different between acute and chronic respiratory diseases. Four fungal genera from Ascomycota, including Devriesia, Endocarpon, Sarcinomyces and an unclassified genus from Herpotrichillaceae, were protectively associated with respiratory infections (p < 0.01). House dust mite (HDM) allergens and outdoor NO2 concentration were associated with respiratory infections and infection-related microorganisms. A causal mediation analysis revealed that the health effects of HDM and NO2 were partially or fully mediated by the indoor microorganisms. This is the first study to explore the association between environmental characteristics, microbiome exposure and respiratory infections in a public indoor environment, expanding our understanding of the complex interactions among these factors.
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