Difference between revisions of "Template:Jilin China/Des C.js"

Revision as of 19:48, 21 October 2019

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//{ // type:"div", // id:"cb", // class:["pdfs","pdfcont"] // }, //newword:[{word:"vulvovaginal",mean:"The symptoms of vulvovaginal candidiasis include: [4,5]Abnormal vaginal discharge, Genital and vaginal burning, Itching and redness. Although most vulvovaginal candidiasis is mild, some women can develop severe infections that cause more serious sexual illnesses, involving AIDS, cervicitis, etc."},{word:"vulvov",mean:"The symptoms of vulvovaginal candidiasis include: [4,5]Abnormal vaginal discharge, Genital and vaginal burning, Itching and redness. Although most vulvovaginal candidiasis is mild, some women can develop severe infections that cause more serious sexual illnesses, involving AIDS, cervicitis, etc."},{word:"vvaginal",mean:"The symptoms of vulvovaginal candidiasis include: [4,5]Abnormal vaginal discharge, Genital and vaginal burning, Itching and redness. Although most vulvovaginal candidiasis is mild, some women can develop severe infections that cause more serious sexual illnesses, involving AIDS, cervicitis, etc."},{word:"vinal",mean:"The symptoms of vulvovaginal candidiasis include: [4,5]Abnormal vaginal discharge, Genital and vaginal burning, Itching and redness. Although most vulvovaginal candidiasis is mild, some women can develop severe infections that cause more serious sexual illnesses, involving AIDS, cervicitis, etc."}],

var content_alpha = { prospect:{ title:"Design" },

reference:[

"[1] Soll D R. Why does Candida albicans switch?[J]. FEMS Yeast Res, 2009, 9(7): 973-89.", "[2] Martin Lopez J E. Candidiasis (vulvovaginal)[J]. BMJ Clin Evid, 2015, 2015.", "[3] Andrade J T, Santos F R S, Lima W G, et al. Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents[J]. J Antibiot (Tokyo), 2018, 71(8): 702-712.", "[4] Prieto M A, Garcia J L. Identification of a novel positive regulator of the 4-hydroxyphenylacetate catabolic pathway of Escherichia coli[J]. Biochem Biophys Res Commun, 1997, 232(3): 759-65.", "[5] Mayer F L, Wilson D, Hube B. Candida albicans pathogenicity mechanisms[J]. Virulence, 2013, 4(2): 119-28.", "[6] Boon C, Deng Y, Wang L H, et al. A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition[J]. ISME J, 2008, 2(1): 27-36.", "[7] Cui C, Song S, Yang C, et al. Disruption of Quorum Sensing and Virulence in Burkholderia cenocepacia by a Structural Analogue of the cis-2-Dodecenoic Acid Signal[J]. Appl Environ Microbiol, 2019, 85(8).", "[8] Bi H, Christensen Q H, Feng Y, et al. The Burkholderia cenocepacia BDSF quorum sensing fatty acid is synthesized by a bifunctional crotonase homologue having both dehydratase and thioesterase activities[J]. Mol Microbiol, 2012, 83(4): 840-55.", "[9] Berman J, Sudbery P E. Candida Albicans: a molecular revolution built on lessons from budding yeast[J]. Nat Rev Genet, 2002, 3(12): 918-30.", "[10] Allonsius C N, Vandenheuvel D, Oerlemans E F M, et al. Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG[J]. Sci Rep, 2019, 9(1): 2900.", "[11]Mayer F L, Kronstad J W. Disarming Fungal Pathogens: Bacillus safensis Inhibits Virulence Factor Production and Biofilm Formation by Cryptococcus neoformans and Candida albicans[J]. MBio, 2017, 8(5).", "[12]Garcia M C, Lee J T, Ramsook C B, et al. A role for amyloid in cell aggregation and biofilm formation[J]. PLoS One, 2011, 6(3): e17632.", "[13] Gulati M, Nobile C J. Candida albicans biofilms: development, regulation, and molecular mechanisms[J]. Microbes Infect, 2016, 18(5): 310-21.", "[14]Luo X L, Li J X, Huang H R, et al. LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation[J]. Front Immunol, 2019, 10: 283.", "[15] Den Hertog A L, Van Marle J, Van Veen H A, et al. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane[J]. Biochem J, 2005, 388(Pt 2): 689-95." ],

part: [{ title: "Background", para: [

{ type: "word", cont: "As we all know, (ita)C. albicans(itaed) is a common fungal pathogen, which can transform between nonpathogenic yeast phase and pathogenic hypha phase(sup)[1](suped). The vulvovaginal candidiasis caused by (ita)C. albicans(itaed) is the second most common vaginal disease(sup)[2](suped), which brings untold suffering to women. At present, oral antifungal antibiotics are widely used. However, the widespread usage of antifungal drugs has led to the emergence of drug resistance, even the relapse to VVC of patients. So, we design a new treatment(sup)[3](suped).", class: "np5" },

]

}, { title: "Project design", para: [

{ type: "word", cont: "Our engineered bacteria are equipped with sensing system, therapeutic system and suicide system, which can inhibit and kill (ita)C. albicans(itaed).", class: "np5" }, { type: "word", cont: "Sensing system", class: "np2" }, { type: "word", cont: "In order to detect (ita)C. albicans(itaed), we first focus on 4-HPA secreted by it. ", class: "np5" }, { type: "word", cont: "(ita)E. coli(itaed) W can respond to 4-HPA(sup)[4](suped), which we use as the basis of our sensing system. The system includes a transporter (HpaX), a transcription factor (HpaA) and an inducible promoter. After imported inside by HpaX, 4-HPA can bind to HpaA, forming a complex which can activate P(sub)BC(subed) promoter and start the expression of downstream genes. ", class: "np5" }, { type: "pic", maxClass:"max7", cont: [{ num: 1, adress: "", pre: 100, }

] },

{ type: "word", cont: "Therapeutic system", class: "np2" }, { type: "word", cont: "In order to control the quantity of (ita)C. albicans(itaed) effectively, we design four parts: BDSF, Msp1, β-1,3-glucanase and LL-37. All these parts are under the control of the sensing system. Here are the details:", class: "np5" }, { type: "word", cont: "BDSF", class: "np3" }, { type: "word", cont: "For (ita)C. albicans(itaed), inhibition of hypha formation is an important factor because it can prevent the expression of filamentous specific virulence genes(sup)[5](suped). For this reason, we choose BDSF that a molecule to inhibit the two-phase transformation of (ita)C. albicans(itaed)(sup)[6](suped).", class: "np5" }, { type: "word", cont: "BDSF is a diffusible chemical produced by Burkholderia Berkeley(sup)[7](suped). The enzyme produces BDSF has been identified as Bcam0581, which has the activity of dehydratase and thioesterase(sup)[8](suped). Bcam0581 can catalyze the production of BDSF that can inhibit the phase transformation of (ita)C. albicans(itaed)(sup)[6](suped), through the intermediate substance in the fatty acid synthesis pathway of bacteria, to achieve our expectation.", class: "np5" }, { type: "word", cont: "Msp1", class: "np3" }, { type: "word", cont: "(ita)C. albicans(itaed) in hypha phase can invade human epithelial cells and cause infection(sup)[9](suped). In order to eliminate the hyphae of (ita)C. albicans(itaed), we choose the protein Msp1 with the function of destabilizing hyphae.", class: "np5" }, { type: "word", cont: "Msp1 is a protein secreted by (ita)Lactobacillus rhamnosus(itaed) GG and has chitinase activity(sup)[10](suped). There is a large amount of chitin in the hypha cell wall of (ita)C. albicans(itaed), so Msp1 can hydrolyze chitin to achieve the effect of destabilizing hyphae(sup)[11](suped). ", class: "np5" }, { type: "word", cont: "β-1,3-glucanase", class: "np3" }, { type: "word", cont: "Another major virulence factor of (ita)C. albicans(itaed) is that the cell community closely adheres to the surface, forming the biofilm(sup)[12](suped), which is an important reason for the formation of antifungal therapy. Therefore, we need an effective enzyme, β-1,3-glucanase, to degrade the biofilm.", class: "np5" }, { type: "word", cont: "β-1,3-glucan is one of the main components of EPS in (ita)C. albicans(itaed) biofilm(sup)[13](suped). β-1,3-glucanase catalyzes the hydrolysis of β-1,3-glucoside bond to decompose polysaccharide into dextrin or oligosaccharide, which leads to the destruction and morphological change of (ita)C. albicans(itaed) biofilm matrix, thus destroying the biofilm. ", class: "np5" }, { type: "word", cont: "LL-37", class: "np3" }, { type: "word", cont: "In order to ensure the ability to kill (ita)C. albicans(itaed), we select an antibacterial peptide with the function of killing (ita)C. albicans(itaed): LL-37.", class: "np5" }, { type: "word", cont: "LL-37 has a 37 amino acids sequence and it is the only antibacterial peptide in the Cathelicidin family(sup)[14](suped). LL-37 destroys the function of the membrane by interacting with the polyanionic lipopolysaccharide on the surface of the membrane(sup)[15](suped), which eventually leads to the perforation and death of (ita)C. albicans(itaed).", class: "np5" }, { type: "pic", maxClass:"max5", cont: [{ num: 1, adress: "", pre: 100, }

] }, { type: "pic", maxClass:"max5", cont: [{ num: 1, adress: "", pre: 100, }

] },

{ type: "word", cont: "Suicide system", class: "np2" }, { type: "word", cont: "Considering the safety of the project, we design a suicide system. When the P(sub)BC(subed) promoter is activated, TetR protein expression will start which inhibits the transcription of P(sub)tet(subed) and the suicide system doesn’t work. When the P(sub)BC(subed) promoter is inhibited, TetR protein expression won’t start, leaving P(sub)tet(subed) at the activated state, which makes the suicide system work.", class: "np5" },

]

},

{ title: "Experiment design", para: [

{ type: "word", cont: "In order to enable our system to be expressed in (ita)Lactobacillus(itaed) in the future, which is the dominant bacteria in vagina, (ita)Lactobacillus(itaed) vector pVE5523 is selected. Aiming to make our therapeutic factors secrete extracellularly, we fuse the secreted peptide SPusp45 with the therapeutic factors. ", class: "np5" },

{ type: "word", cont: "In order to independently verify the function of each therapeutic factor, we use P(sub)59(subed), a common promoter of (ita)Lactobacillus(itaed), which is separately connected in front of each therapeutic factor gene respectively.", class: "np5" }, { type: "word", cont: "Choice of class organism", class: "np2" }, { type: "word", cont: "(ita)Lactobacillus(itaed) is a kind of the bacteria existing in physiological environment of human vagina, so the ultimate goal of our project was to apply genetically engineered (ita)Lactobacillus(itaed) with the function of treating VVC in human body. However, considering the actual experimental situation, commonly used engineered (ita)E. coli(itaed) was used instead of (ita)Lactobacillus(itaed).", class: "np5" },

]

} ,{ title: "Conclusion", para: [

{ type: "word", cont: "In general, we combine the sensing system, therapeutic system and suicide system, which is shown in the following figure. When the high density of (ita)C. albicans(itaed) leads to a high concentration of 4-HPA, P(sub)BC(subed) will be activated, starting the expression of various factors in the therapeutic system, achieving the effect of inhibiting and killing (ita)C. albicans(itaed). And at this time, the suicide system is closed. On the contrary, when the density of (ita)C. albicans(itaed) returns to normal, the concentration of 4-HPA will decreases, which causes the close of sensing system, P(sub)BC(subed) and the activation of suicide system.", class: "np5" }, { type: "pic", maxClass:"max6", cont: [{ num: 1, adress: "", pre: 100, }

] }, { type: "pic", maxClass:"max6", cont: [{ num: 1, adress: "", pre: 100, }

] },

]

}, { title: "Reference", para: [

{ type: "word", cont: "[1] Soll D R. Why does Candida albicans switch?[J]. FEMS Yeast Res, 2009, 9(7): 973-89." }, { type: "word", cont: "[2] Martin Lopez J E. Candidiasis (vulvovaginal)[J]. BMJ Clin Evid, 2015, 2015.", class: "np5" }, { type: "word", cont: "[3] Andrade J T, Santos F R S, Lima W G, et al. Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents[J]. J Antibiot (Tokyo), 2018, 71(8): 702-712.", class: "np5" }, { type: "word", cont: "[4] Prieto M A, Garcia J L. Identification of a novel positive regulator of the 4-hydroxyphenylacetate catabolic pathway of Escherichia coli[J]. Biochem Biophys Res Commun, 1997, 232(3): 759-65.", class: "np5" }, { type: "word", cont: "[5] Mayer F L, Wilson D, Hube B. Candida albicans pathogenicity mechanisms[J]. Virulence, 2013, 4(2): 119-28.", class: "np5" },

{ type: "word", cont: "[6] Boon C, Deng Y, Wang L H, et al. A novel DSF-like signal from Burkholderia cenocepacia interferes with Candida albicans morphological transition[J]. ISME J, 2008, 2(1): 27-36.", class: "np5" }, { type: "word", cont: "[7] Cui C, Song S, Yang C, et al. Disruption of Quorum Sensing and Virulence in Burkholderia cenocepacia by a Structural Analogue of the cis-2-Dodecenoic Acid Signal[J]. Appl Environ Microbiol, 2019, 85(8).", class: "np5" }, { type: "word", cont: "[8] Bi H, Christensen Q H, Feng Y, et al. The Burkholderia cenocepacia BDSF quorum sensing fatty acid is synthesized by a bifunctional crotonase homologue having both dehydratase and thioesterase activities[J]. Mol Microbiol, 2012, 83(4): 840-55.", class: "np5" }, { type: "word", cont: "[9] Berman J, Sudbery P E. Candida Albicans: a molecular revolution built on lessons from budding yeast[J]. Nat Rev Genet, 2002, 3(12): 918-30.", class: "np5" }, { type: "word", cont: "[10] Allonsius C N, Vandenheuvel D, Oerlemans E F M, et al. Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG[J]. Sci Rep, 2019, 9(1): 2900.", class: "np5" }, { type: "word", cont: "[11] Mayer F L, Kronstad J W. Disarming Fungal Pathogens: Bacillus safensis Inhibits Virulence Factor Production and Biofilm Formation by Cryptococcus neoformans and Candida albicans[J]. MBio, 2017, 8(5).", class: "np5" }, { type: "word", cont: "[12] Garcia M C, Lee J T, Ramsook C B, et al. A role for amyloid in cell aggregation and biofilm formation[J]. PLoS One, 2011, 6(3): e17632.", class: "np5" }, { type: "word", cont: "[13] Gulati M, Nobile C J. Candida albicans biofilms: development, regulation, and molecular mechanisms[J]. Microbes Infect, 2016, 18(5): 310-21.", class: "np5" }, { type: "word", cont: "[14] Luo X L, Li J X, Huang H R, et al. LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation[J]. Front Immunol, 2019, 10: 283.", class: "np5" }, { type: "word", cont: "[15] Den Hertog A L, Van Marle J, Van Veen H A, et al. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane[J]. Biochem J, 2005, 388(Pt 2): 689-95.", class: "np5" }, ]

},

]

}