{"title":"Structural characteristics of phenylboronic acid-modified astaxanthin ester and its effect on DSS-induced ulcerative colitis by blocking reactive oxygen species and maintaining intestinal homeostasis","authors":"","doi":"10.26599/FSHW.2022.9250223","DOIUrl":"10.26599/FSHW.2022.9250223","url":null,"abstract":"<div><div>A novel and reactive oxygen species (ROS) responsive astaxanthin phenylboronic acid derivative (AstaD-PBA) was constructed by grafting phenylboronic acid (PBA) onto astaxanthin succinate diester (AstaD), and its chemical structure and physicochemical property were identified. AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model. Then, the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive inflammatory models induced by LPS, copper (Cu<sup>2+</sup>), high-fat diet, and dextran sodium sulfate (DSS). The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis (UC) induced by DSS. Furtherly, AstaD-PBA significantly alleviated and treated weight loss and colonic shrinkage, inhibited inflammatory cytokines, and maintained microbiota homeostasis to improve UC in C57BL/6J mice. <em>Alistipes</em> and <em>Oscillibacter</em> were expected to be considered UC marker flora according to the Metastats analysis and Pearson correlation Mantel test (<em>P</em> < 0.01) of 16S rRNA gene sequencing data. In conclusion, AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2754-2764"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135372444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcriptomic analysis of molecular mechanisms underlying the biodegradation of organophosphorus pesticide chlorpyrifos by Lactobacillus delbrueckii ssp. bulgaricus in skimmed milk","authors":"","doi":"10.26599/FSHW.2022.9250244","DOIUrl":"10.26599/FSHW.2022.9250244","url":null,"abstract":"<div><div>Bioremediation of organophosphorus pesticides in contaminated foodstuffs using probiotics has been increasingly under the spotlight in recent years, though the biodegradation mechanism and derived intermediate products remain unclear. This study aimed to help fill this knowledge gap and examined the degradation mechanism of organophosphorus pesticide, chlorpyrifos, in milk by <em>Lactobacillus delbrueckii</em> ssp. <em>bulgaricus</em> using gas chromatography- tandem mass spectrometry (GC-MS/MS) combined with transcriptome analysis. After the strain was cultured for 20 h in the presence of chlorpyrifos, differential expressions of 383 genes were detected, including genes probably implicated during chlorpyrifos degradation such as those related to hydrolase, phosphoesterase, diphosphatase, oxidoreductase, dehydratase, as well as membrane transporters. GC-MS/MS analysis revealed the changes of secondary metabolites in <em>L. bulgaricus</em> during milk fermentation due to chlorpyrifos stress. 6-Methylhexahydro-2<em>H</em>-azepin-2-one, 2,6-dihydroxypyridine and methyl 2-aminooxy-4-methylpentanoate as intermediates, along with the proposed pathways, might be involved in chlorpyrifos biodegradation by <em>L. bulgaricus</em>.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 3018-3030"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135373416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Curcumin delivery nanoparticles based on Maillard reaction of Haematococcus pluvialis protein/galactose for alleviating acute alcoholic liver damage","authors":"","doi":"10.26599/FSHW.2022.9250211","DOIUrl":"10.26599/FSHW.2022.9250211","url":null,"abstract":"<div><div>The aim of this study is to investigate the feasibility of Maillard reaction products of <em>Haematococcus pluvialis</em> protein and galactose (HPP-GAL) for improving the bioactivities of curcumin (CUR) for alleviating alcoholic liver damage. CUR was embedded into HPP-GAL nanoparticles by the self-assembly of hydrogen bonding and hydrophobic interaction with the particle size around 200 nm. HPP-GAL enhanced the encapsulation efficiency and loading amount of CUR with the value of (89.21 ± 0.33)% and (0.500 ± 0.004)%, respectively. The stabilities of CUR under strong acid, salt ion stability and ultraviolet irradiation conditions were improved by the encapsulation. HPP-GAL-CUR nanoparticles exhibited excellent concentration-dependent <em>in vitro</em> antioxidant activities including DPPH and ABTS scavenging rates, and better protective effect on CUR against gastric acid environment as well as longer release of CUR in simulated intestinal fluid. In addition, the HPP-GAL-CUR delivery system possessed liver targeting property due to the existence of GAL, which could effectively alleviate the alcohol-induced liver damage and the inflammation indexes by inhibiting the oxidative stress. Therefore, HPP-GAL-CUR nanoparticles might be a potential candidate system for the prevention of alcoholic liver damage in the future.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2629-2641"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135373423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yunli Xiao , Junfeng Shen , Jianfeng Zhan , Limin Guo , Chi-Tang Ho , Shiming Li
{"title":"Antiglycating effects of citrus flavonoids and associated mechanisms","authors":"Yunli Xiao , Junfeng Shen , Jianfeng Zhan , Limin Guo , Chi-Tang Ho , Shiming Li","doi":"10.26599/FSHW.2022.9250247","DOIUrl":"10.26599/FSHW.2022.9250247","url":null,"abstract":"<div><div>Glycation of proteins and DNA forms advanced glycation end products (AGEs) causing cell and tissue dysfunction and subsequent various chronic diseases, in particular, metabolic and age-related diseases. Targeted AGE inhibition includes scavengers of reactive carbonyl species (RCS) such as methylglyoxal (MG), glyoxalase-1 enhancers, Nrf2/ARE pathway activators, AGE/RAGE formation inhibitors and other antiglycatng agents. Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents. Herein, we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms. Major citrus flavonoids, hesperedin and its aglycone, hesperetin, inhibited glycation by scavenging MG forming mono- or di-flavonoid adducts with MG, enhanced the activity of glyoxase-1, activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway, reduced the formation of <em>N</em><sup>ε</sup>-(carboxylmethyl)lysine (CML) and pentosidine, inhibited aldol reductase activity and decreased the levels of fructosamine. The antiglycating activity and mechanisms of other flavonoids was also summarized in this review. In conclusion, citrus flavonoids possess effective antiglycating activity via different mechanisms, yet there are many challenging questions remaining to be studied in the near future such as <em>in vivo</em> testing and human study of citrus flavonoids for efficacy, effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases, diabetic complications in particular.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2363-2372"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fufang E’jiao Jiang’s effect on immunity, hematopoiesis, and angiogenesis via a systematic “compound-effect-target” analysis","authors":"","doi":"10.26599/FSHW.2022.9250228","DOIUrl":"10.26599/FSHW.2022.9250228","url":null,"abstract":"<div><div><em>Fufang E</em>’<em>jiao Jiang</em> (FEJ) as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish <em>qi</em> and nourish blood, and it has a positive impact on women’s health. To find out the material basis and mechanism of FEJ, a systematic “compound-effect-target” analysis including chemical composition resolution, zebrafish, network pharmacology, molecular docking, transcriptome, and bibliometric analysis was adopted. 124 chemical components including ginsenosides, and phenylethanoid glycosides in FEJ were discovered, and effects of FEJ on promoting the generation of immune cells, erythropoiesis and angiogenesis in zebrafish were exhibited. Based on network pharmacology, molecular docking and <em>in vivo</em> activity assay, 6 compounds including jionoside A1, isoacteoside, echinacoside, acteoside, lobetyolin, and rehmannioside D were identified as active components of FEJ. Transcriptome data showed that several pathways such as complement and coagulation cascades, ECM-receptor interaction, and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ. 19 common targets were obtained through combined analysis of network pharmacology and transcriptomics, and 5 targets of them were verified by PCR. The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism, pathway in cancer, etc., which was consistent with the results of network pharmacology and transcriptome. The studies suggested that FEJ could replenish <em>qi</em> and nourish blood through multi-compound and multi-targets.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2813-2832"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135372281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Facile SERS screening of melamine in bovine milk with 2D printed AgNPs/glass fabric filter paper as the flexible substrate","authors":"","doi":"10.26599/FSHW.2022.9250208","DOIUrl":"10.26599/FSHW.2022.9250208","url":null,"abstract":"<div><div>Melamine is one of the most frequently detected adulterants in dairy products. The current study proposes a surface-enhanced Raman spectroscopy (SERS)-based analytical tool for fast and reliable screening of melamine in bovine milk. A hand-held Raman spectrometer was used in conjunction with a substrate composed of silver nanoparticles (AgNPs) that was 2D printed onto glass fiber (GF) filter paper. Under optimized conditions, a sensitive and fingerprint-like signal at 674 cm<sup>−1</sup> was obtained. The AgNPs/GF substrate exhibited high sensitivity to melamine in milk down to 1.9498 × 10<sup>−5</sup> mg/mL, which is well below the USA and EU safety limits (2.5 × 10<sup>−3</sup> mg/mL). Remarkably, the proposed technology was also highly reproducible, showing spot-to-spot and block-to-block variations below 3.3 % and 4.9 % at 674 cm<sup>−1</sup> in Raman intensity, respectively. The characteristic peak intensity and concentration of melamine showed an acceptable linear relationship (<em>R</em><sup>2</sup> = 0.9909) within the range of 0.0001–1 mg/mL. Overall, the method established in this study can provide an efficient and effective method for the quantitative target screening and detection of melamine in dairy products.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2595-2600"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135372291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of phytoconstituents on oral health practices: a post COVID-19 observation","authors":"","doi":"10.26599/FSHW.2022.9250197","DOIUrl":"10.26599/FSHW.2022.9250197","url":null,"abstract":"<div><div>Appropriate oral hygiene significantly reduces the possibility of oral infections. However, dental caries and periodontal diseases are major oral health issues causing chronic diseases due to poor oral health. Recently, herbal compounds have gained interest in maintaining oral health. Extracts of burdock root (<em>Arctium)</em>, noni fruit (<em>Morinda citrifolia)</em>, and neem leaf (<em>Azadirachta indica</em>) are now used as intracanal medicaments in endodontics and periodontics. <em>Plectranthus amboinicus</em> species and other plants produces essential oil like <em>β</em>-caryophyllene, <em>p</em>-cymene, and <em>γ</em>-terpinene can exhibit antibacterial activity; highlighting phytoconstituents plays a vital role in oral health. The COVID-19 pandemic highlighted the importance of hygiene and sanitization, to curb SARS-CoV-2. Oral cavity is among the gateways for virus entry into saliva. Saliva is a potential reservoir of SARS-CoV-2, and there is an increased risk of infection if there is any fissure in the mouth. This enables entry of virus into the vascular system through gingival or periodontal pocket, possibly reaching lung periphery then to lung vessels by interacting with endothelial surface receptors triggering pulmonary vasoconstriction and lung damage due to endothelial dysfunction. This review aims to draw attention to the possible route of SARS-CoV-2 infection via the oral cavity and the importance of oral hygiene against COVID-19.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2386-2400"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135372441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oligomeric procyanidins combined with Parabacteroides distasonis ameliorate high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and bile acid metabolism in ApoE−/− mice","authors":"","doi":"10.26599/FSHW.2022.9250230","DOIUrl":"10.26599/FSHW.2022.9250230","url":null,"abstract":"<div><div>Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases. Hence, the prevention and treatment strategies of AS have attracted great research attention. As a potential probiotic, <em>Pararabacteroides distasonis</em> has a positive regulatory effect on lipid metabolism and bile acids (BAs) profile. Oligomeric procyanidins have been confirmed to be conducive to the prevention and treatment of AS, whose anti-atherosclerotic effect may be associated with the promotion of gut probiotics. However, it remains unclear whether and how oligomeric procyanidins and <em>P. distasonis</em> combined (PPC) treatment can effectively alleviate high-fat diet (HFD)-induced AS. In this study, PPC treatment was found to significantly decrease atherosclerotic lesion, as well as alleviate the lipid metabolism disorder, inflammation and oxidative stress injury in ApoE<sup><strong>−/−</strong></sup> mice. Surprisingly, targeted metabolomics demonstrated that PPC intervention altered the BA profile in mice by regulating the ratio of secondary BAs to primary BAs, and increased fecal BAs excretion. Further, quantitative polymerase chain reaction (qPCR) analysis showed that PPC intervention facilitated reverse cholesterol transport by upregulating <em>Srb1</em> expression; In addition, PPC intervention promoted BA synthesis from cholesterol in liver by upregulating <em>Cyp7a1</em> expression via suppression of the farnesoid X receptor (FXR) pathway, thus exhibiting a significant serum cholesterol-lowering effect. In summary, PPC attenuated HFD-induced AS in ApoE<sup><strong>−/−</strong></sup> mice, which provides new insights into the design of novel and efficient anti-atherosclerotic strategies to prevent AS based on probiotics and prebiotics.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2847-2856"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135373296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model","authors":"","doi":"10.26599/FSHW.2022.9250238","DOIUrl":"10.26599/FSHW.2022.9250238","url":null,"abstract":"<div><div>As the body’s internal clock, the circadian rhythm regulates the energy expenditure, appetite, and sleep. There exists a close relationship between the host circadian rhythm and gut microbiota. In this work, a circadian disorder mouse model induced by constant darkness (CD) was constructed to investigate the regulating effects of capsaicin (CAP) on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms. Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue. The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP. Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness, diversity and composition, and restored diurnal oscillations of gut microbes at the phylum and family level. These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice, providing theoretical basis for CAP to be used as a muti-functional ingredient with great health-promoting effects.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 2947-2958"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135373418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural characterization and anti-inflammatory activities of novel polysaccharides obtained from Pleurotus eryngii","authors":"","doi":"10.26599/FSHW.2022.9250245","DOIUrl":"10.26599/FSHW.2022.9250245","url":null,"abstract":"<div><div>Natural polysaccharides named PEP-0.1-1, PEP-0-1 and PEP-0-2 from edible mushroom species <em>Pleurotus eryngii</em> were obtained in the present study. Results showed that molecular weights of these polysaccharides were 3235, 2041 and 23933 Da, respectively. Further, structural characterization revealed that PEP-0.1-1 had a →4-<em>α</em>-<em>D</em>-Glc<em>p</em>-1→ backbone and contained →4)-<em>α</em>-<em>D</em>-Glc<em>p</em> and →4)-<em>β</em>-<em>D</em>-Glc<em>p</em> reducing end groups. PEP-0-1 backbone contained →4-<em>α</em>-<em>D</em>-Glc<em>p</em>-1→ and →6-<em>α</em>-3-<em>O</em>-Me-<em>D</em>-Gal<em>p</em>-1→, and the side chains contained <em>α</em>-<em>D</em>-Glc<em>p</em>, <em>β</em>-<em>D</em>-Man<em>p</em>-1→ and <em>α</em>-<em>D</em>-Glc<em>p</em>-3→. However, PEP-0-2 backbone consisted of →4-<em>α</em>-<em>D</em>-Glc<em>p</em>-1→ and →6-<em>α</em>-3-<em>O</em>-Me-<em>D</em>-Gal<em>p</em>-(1→6)-<em>α</em>-<em>D</em>-Gal<em>p</em>-1→ while the side chains contained <em>α</em>-<em>D</em>-Glc<em>p</em> and <em>β</em>-<em>D</em>-Man<em>p</em>-1→. Biological activity analysis was then carried out and found that all these polysaccharides could significantly suppress the relative mRNA expression of toll-like receptor 4, nitric oxide, tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-induced inflammation of RAW264.7 cells, as well as the over secretion of the above cell cytokines. Moreover, Western blotting analysis revealed that all these purified fractions displayed significant inhibition effects on the expression of c-Jun N-terminal kinases protein protein induced by LPS in mitogen activated protein kinase pathway, along with the relieving on the inhibition effect of LPS on IκB-α protein expression. In summary, the information generated by the present study could provide a theoretical basis for the exploration of novel healthy food materials from edible mushroom with anti-inflammation activities.</div></div>","PeriodicalId":12406,"journal":{"name":"Food Science and Human Wellness","volume":"13 5","pages":"Pages 3031-3042"},"PeriodicalIF":5.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135373426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}