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  • Publication
    Chemiluminescence-Guided Cancer Therapy Using a Chemiexcited Photosensitizer
    (Elsevier Inc., 2017-12-14) MAO DUO; WU WENBO; Ji, Shenglu; Chen, Chao; Hu, Fang; Kong, Deling; Ding, Dan; LIU BIN; Dr Mao Duo; MATERIALS SCIENCE AND ENGINEERING; CHEMICAL & BIOMOLECULAR ENGINEERING
    Image-guided therapy is one of the most promising strategies for efficiently curing a tumor. Here, a novel nanomaterial with chemiexcited far-red/near-infrared (FR/NIR) emission and singlet oxygen (1O2) generation is reported for precise diagnosis and treatment of tumors. Bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate (CPPO) and a specially designed photosensitizer TBD with aggregation-induced FR/NIR emission were co-encapsulated by pluronic F-127 and soybean oil to form C-TBD nanoparticles (C-TBD NPs). These NPs serve as a specific H2O2 probe to precisely track tumors in vivo through chemiluminescence imaging. In addition, effective 1O2 generation by C-TBD NPs in response to tumor H2O2 was observed, which could efficiently induce tumor cell apoptosis and inhibit tumor growth. Both the chemiluminescence response and the therapeutic function were further enhanced when β-phenylethyl isothiocyanate was used to enhance the H2O2 production at the tumor site. Our results prove that C-TBD NPs provide a new strategy for intelligent, accurate, and non-invasive tumor therapy. Precise image-guided therapy is key to eradicating tumors in clinical practice. Here, we report a new nanomaterial based on a chemiexcited photosensitizer, which can be specifically activated by H2O2 within the tumor environment to produce far-red/near-infrared luminescence and singlet oxygen. Using such a nanoparticle, primary and metastatic breast tumors can be clearly identified through chemiluminescence imaging with a very high signal-to-noise ratio. Accompanied by the use of an anti-tumor drug, FEITC, the signal of the tumor could be further enhanced as a result of elevated H2O2 production at the tumor site. More importantly, specific tumor killing can be achieved through chemiexcited singlet oxygen production, and the effect of therapy is also increased in the presence of FEITC. Considering the multiple advantages of simultaneous tumor theranostics, our nanoparticle design represents a promising strategy for future clinical tumor therapy. Organic nanoparticles exhibiting intense FR/NIR chemiluminescence and strong chemiexcited singlet oxygen generation in the presence of H2O2 have been successfully used for selective tumor imaging and therapy. Both tumor chemiluminescent signals and singlet oxygen production can be further enhanced in the presence of an anti-tumor drug, FEITC, which could increase the amount of H2O2 at the tumor site for effective tumor treatment. Our design represents a new strategy for light-source-free image-guided tumor therapy.
  • Publication
    Searching for shortest and least programs
    (Elsevier B.V., 2020) Calude C.S.; Jain S.; Merkle W.; Stephan F.; MATHEMATICS; DEPARTMENT OF COMPUTER SCIENCE
    The Kolmogorov complexity of a string x is defined as the length of a shortest program p of x for some appropriate universal machine U, that is, U(p)=x and p is a shortest string with this property. Neither the plain nor the prefix-free version of Kolmogorov complexity are recursive but for both versions it is well-known that there are recursive exact Solovay functions, that is, recursive upper bounds for Kolmogorov complexity that are infinitely often tight. Let a coding function for a machine M be a function f such that f(x) is always a program of x for M. From the existence of exact Solovay functions it follows easily that for every universal machine there is a recursive coding function that maps infinitely many strings to a shortest program. Extending a recent line of research, in what follows it is investigated in which situations there is a coding function for some universal machine that maps infinitely many strings to the length-lexicographically least program. The main results which hold in the plain as well as in the prefix-free setting are the following. For every universal machine there is a recursive coding function that maps infinitely many strings to their least programs. There is a partial recursive coding function (defined in the natural way) for some universal machine that for every set maps infinitely many prefixes of the set to their least programs. Exactly for every set that is Bennett shallow (not deep), there is a recursive coding function for some universal machine that maps all prefixes of the set to their least programs. Differences between the plain and the prefix-free frameworks are obtained by considering effective sequences I1,I2,… of mutually disjoint finite sets and asking for a recursive coding function for some universal machine that maps at least one string in each set In to its least code. Such coding functions do not exist in the prefix-free setting but exist in the plain setting in case the sets In are not too small. © 2019 Elsevier B.V.
  • Publication
    Metal-Organic Framework as a Simple and General Inert Nanocarrier for Photosensitizers to Implement Activatable Photodynamic Therapy
    (Wiley-VCH Verlag, 2018-05-09) Hu, Fang; MAO DUO; KENRY; WANG YUXIANG; Wu, Wenbo; Zhao Dan; Kong, Deling; LIU BIN; Dr Mao Duo; CHEMICAL & BIOMOLECULAR ENGINEERING
    There has been a surging interest in the synthesis of activatable photosensitizers (PSs) as they can be selectively activated with minimum nonspecific phototoxic damages for photodynamic therapy (PDT). Conventional strategies to realize activatable PSs are only applicable to a limited number of molecules. Herein, a simple and general strategy to yield activatable PSs by coupling MIL-100 (Fe) (MIL: Materials Institute Lavoisier) with different kinds of PSs is presented. Specifically, when PSs are encapsulated into MIL-100 (Fe), the photosensitization capability is suppressed due to their isolation from O2. After the reaction between iron(III) in MIL-100 (Fe) and H2O2 occurs, the framework of MIL-100 (Fe) collapses and the encapsulated PSs regain contact with O2, leading to activation of photosensitization. In addition, the decomposition of H2O2 can generate O2 to relieve tumor hypoxia and enhance PDT effect. As O2 is an indispensable factor for PDT, the activation strategy should be generally applicable to different PSs for activatable PDT.
  • Publication
    Expression of macrophage colony-stimulating factor and its receptor in microglia activation is linked to teratogen-induced neuronal damage
    (Elsevier, 2002-01-01) Hao, AJ; Dheen, ST; Ling, EA; Assoc Prof Dheen, Shaikali Thameem; ANATOMY
    Prenatal exposure to teratogen agents is linked to the pathogenesis of neurodevelopment disorders, but the mechanisms leading to the neurodevelopmental disturbance are poorly understood. To elucidate this, an in vitro model of microglial activation induced by neuronal injury has been characterized. In this connection, exposure of primary microglial cells to the conditioned medium from the neuronal damage induced by teratogen, cyclophosphamide, is accompanied by a reactive microgliosis as assessed by reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, lectin histochemistry, double labeling immunohistochemistry and in situ hybridization. Our results showed that reactive microglia were capable of releasing various cytokines such as tumor necrosis factor-α, interleukin-1, interleukin-6, transforming growth factor-β and nitric oxide. Also, we have shown that macrophage colony-stimulating factor (M-CSF) was in fact produced by the reactive microglia. Concomitant to this was the increased expression of M-CSF receptor in these cells following the teratogen-induced neuronal injury. The up-regulation of M-CSF receptor suggests that the cells are capable of responding to self-derived M-CSF in an autocrine fashion. Results with antibody neutralization further suggest that microglial proinflammatory response, as manifested by cytokine expression in culture, is mediated by M-CSF, which acts as a molecular signal that initiates a microglial reaction. We therefore suggest that microglial activation following cyclophosphamide treatment is not only a response to the neuronal damage, but is also a cause of the damage during pathogenesis of neurodevelopment disorders. To this end, the increased expression of M-CSF and its receptor on microglia would be directly linked to the active cell proliferation and proinflammatory response in the teratogen-induced injury. © 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
  • Publication
    Spatial variation of fouling behavior in high recovery nanofiltration for industrial reverse osmosis brine treatment towards zero liquid discharge
    (Elsevier, 2020-08-15) SONG WEILONG; LEE LAI YOKE; LIU ENYU; SHI XUEQING; ONG SAY LEONG; NG HOW YONG; CIVIL AND ENVIRONMENTAL ENGINEERING
    Nanofiltration (NF), as a cost-efficient pre-concentrating process, has been incorporated into Zero Liquid Discharge (ZLD) treatment system to improve economic feasibility. However, NF is required to operate with an extremely high recovery rate to achieve ZLD, which could cause severe and complex membrane fouling. Understanding the variation of fouling behavior with increase in recovery rate is crucial for the development of effective fouling control strategy. Spatial variation of fouling behavior in a 3-stage NF used for industrial RO brine treatment towards ZLD was investigated in present study. Distinctive fouling characteristics were observed in each operation stage. Membrane fouling was dominated by organics at lead stage, which could be completely removed via simple base cleaning. Scaling by deposition of bulk crystallization occurred on fouling layer at middle stage, which required a combination of acid and base cleaning for its removal. At the tail stage, more refractory scaling by surface crystallization accompanied by irreversible silica and ferric fouling led to the formation of fouling layer that was resistant to conventional chemical cleaning. Significant humics in preformed fouling layer could have facilitated the occurrence of surface crystallization. Minor elements present in the feed such as silica, humics and iron could cause significant fouling and alter preformed fouling layer that induced more complex and refractory fouling/scaling as recovery rate increased.
  • Publication
    Economic evaluations in the treatment and evaluation of patients with periodontal disease: A critical review
    (John Wiley & Sons Ltd, 2021-03-25) John Rong Hao TAY; Ethan NG; Rahul NAIR; TAN Zhe Sheng; Sharon Hui Xuan TAN; DENTISTRY; DEAN'S OFFICE (DENTISTRY); DEAN'S OFFICE (SSH SCH OF PUBLIC HEALTH); SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
    Aim: To evaluate the types and quality of reporting of economic evaluations carried out in the clinical management of periodontal disease over 32 years from 1987 to 2019. Material and Methods: A systematic search of articles from 1987 to 2019 was conducted using PubMed, Web of Science, The Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and Embase. The quality of the economic evaluations was assessed based on the Consolidated Health Economic Evaluation Reporting Standard checklist. Due to considerable between-study heterogeneity, a meta-analysis was not performed. Results: 21 publications were included. 11 studies used cost-effectiveness analysis, five used cost-minimisation analysis, four used cost-utility analysis, and two used cost-benefit analysis. Comparators, choice of health outcomes, estimating resources and costs were fully reported in all studies. Many studies had inadequate reporting in terms of characterising heterogeneity, study perspective, currency, and discount rates. Conclusions: There has been an increase in health economics studies in the field of clinical periodontology over the past decade. Several studies did not report study perspective. Future studies should follow an economic evaluation checklist for high quality reporting and consistency. lacking. Future reviews are required to assess the conduct and design of cost-effectiveness and cost-utility studies.
  • Publication
    Precise Two-Photon Photodynamic Therapy using an Efficient Photosensitizer with Aggregation-Induced Emission Characteristics
    (Wiley-VCH Verlag, 2017-07-26) Gu, Bobo; Wu, Wenbo; Xu, Gaixia; FENG GUANGXUE; Yin, Feng; Chong, Peter Han Joo; Qu, Junle; Yong, Ken-Tye; LIU BIN; Prof Liu Bin; CHEMICAL & BIOMOLECULAR ENGINEERING
    Two-photon photodynamic therapy (PDT) is able to offer precise 3D manipulation of treatment volumes, providing a target level that is unattainable with current therapeutic techniques. The advancement of this technique is greatly hampered by the availability of photosensitizers with large two-photon absorption (TPA) cross section, high reactive-oxygen-species (ROS) generation efficiency, and bright two-photon fluorescence. Here, an effective photosensitizer with aggregation-induced emission (AIE) characteristics is synthesized, characterized, and encapsulated into an amphiphilic block copolymer to form organic dots for two-photon PDT applications. The AIE dots possess large TPA cross section, high ROS generation efficiency, and excellent photostability and biocompatibility, which overcomes the limitations of many conventional two-photon photosensitizers. Outstanding therapeutic performance of the AIE dots in two-photon PDT is demonstrated using in vitro cancer cell ablation and in vivo brain-blood-vessel closure as examples. This shows therapy precision up to 5 µm under two-photon excitation.
  • Publication
    Homologous SV40 RNA trans-splicing: Special case or prime example of viral RNA trans-splicing?
    (Elsevier, 2014) Sushmita Poddar; Volker Patzel; Joachim Eul; MICROBIOLOGY AND IMMUNOLOGY
  • Publication
    Zeolitic-imidazolate framework membranes for organic solvent nanofiltration: a molecular simulation exploration
    (2018-08) Wan Wei; Krishna M. Gupta; Jie Liu; Jianwen Jiang; CHEMICAL & BIOMOLECULAR ENGINEERING
  • Publication
    Decoding capsule synthesis in Streptococcuspneumoniae
    (Oxford University Press, 2020-12-18) Tong Su; Rei Nakamot; Ye-Yu Chun; Wan-Zhen Chua; Jia-Hui Chen; JustinJ. Zik; Lok-To Sham; MICROBIOLOGY AND IMMUNOLOGY
    Streptococcus pneumoniae synthesizes >100 types of capsular polysaccharides (CPSs). While the diversity of the enzymes and transporters involved is enormous, it is not limitless. In this review, we summarized the recent progress on elucidating the structure�function relationships of CPSs, the mechanisms by which they are synthesized, how their synthesis is regulated, the host immune response against them and the development of novel pneumococcal vaccines. Based on the genetic and structural information available, we generated provisional models of the CPS repeating units that remain unsolved. In addition, to facilitate cross-species comparisons and assignment of glycosyltransferases, we illustrated the biosynthetic pathways of the known CPSs in a standardized format. Studying the intricate steps of pneumococcal CPS assembly promises to provide novel insights for drug and vaccine development as well as improve our understanding of related pathways in other species.