Pub Date : 2024-05-22DOI: 10.1080/10286020.2024.2355479
A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7–9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 μM and compounds 1, 9–11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.
{"title":"Chemical constituents from the leaves and branches of Wikstroemia chamaedaphne with their activation of latent HIV activities","authors":"","doi":"10.1080/10286020.2024.2355479","DOIUrl":"10.1080/10286020.2024.2355479","url":null,"abstract":"<div><p>A new compound, named coniferin B (<strong>1</strong>), and fourteen known compounds were purified and identified from the leaves and branches of <em>Wikstroemia chamaedaphne</em> Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds <strong>2</strong>, <strong>3</strong>, <strong>5</strong>, <strong>7</strong>–<strong>9</strong>, <strong>11,</strong> and <strong>13</strong> were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 μM and compounds <strong>1</strong>, <strong>9</strong>–<strong>11</strong> showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1080/10286020.2024.2355132
In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3.
{"title":"Regulation of Fuzheng Huayu capsule on inhibiting the fibrosis-associated hepatocellular carcinogenesis","authors":"","doi":"10.1080/10286020.2024.2355132","DOIUrl":"10.1080/10286020.2024.2355132","url":null,"abstract":"<div><p>In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and <em>tanshinone IIA</em>, <em>arachidonic acid</em>, and <em>quercetin</em>, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of <em>PLAU</em> and <em>IGFBP3</em>. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression <em>via</em> regulating the expression of PLAU and IGFBP3.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1080/10286020.2024.2347521
Using various chromatographic separations, six glycoside derivatives (1–6), including one new ent-labdane glucoside named cayratioside (1), were isolated from the methanol extract of Cayratia geniculata stems and leaves. Their structures were elucidated by detailed analysis of the 1D, 2D NMR, and HRESIQTOF mass spectra. The inhibitory effect of 1–6 on LPS-induced NO production in RAW264.7 cells was also evaluated. Among isolated compounds, 1 exhibited moderate activity with an IC50 value of 59.65 ± 1.85 µM.
{"title":"Glycoside constituents from Cayratia geniculata","authors":"","doi":"10.1080/10286020.2024.2347521","DOIUrl":"10.1080/10286020.2024.2347521","url":null,"abstract":"<div><p>Using various chromatographic separations, six glycoside derivatives (<strong>1–6</strong>), including one new <em>ent</em>-labdane glucoside named cayratioside (<strong>1</strong>), were isolated from the methanol extract of <em>Cayratia geniculata</em> stems and leaves. Their structures were elucidated by detailed analysis of the 1D, 2D NMR, and HRESIQTOF mass spectra. The inhibitory effect of <strong>1–6</strong> on LPS-induced NO production in RAW264.7 cells was also evaluated. Among isolated compounds, <strong>1</strong> exhibited moderate activity with an IC<sub>50</sub> value of 59.65 ± 1.85 µM.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-16DOI: 10.1080/10286020.2024.2347530
Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.
{"title":"Macrophorins H and L, two new HMG-conjugate macrophorins from rihzospheric Penicillium sp. NX-05-G-3","authors":"","doi":"10.1080/10286020.2024.2347530","DOIUrl":"10.1080/10286020.2024.2347530","url":null,"abstract":"<div><p>Macrophorins H (<strong>4</strong>) and L (<strong>5</strong>), two rare HMG-conjugate macrophorins along with three known macrophorins (<strong>1</strong>-<strong>3</strong>), three DMOA-derived meroterpenoids (<strong>6</strong>-<strong>8</strong>) and two ergosterol derivates (<strong>9</strong>-<strong>10</strong>) were isolated from sterilized rice medium cultured <em>Penicillium</em> sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds <strong>1</strong> and <strong>2</strong> showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC<sub>50</sub> values ranging from 17.6 to 32.8 µM.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1080/10286020.2024.2346297
Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter required for excitation/inhibition balance is synthesized by the glutamic acid decarboxylases (GADs) in GABAergic neurons. The levels and activity of GADs are strongly correlated with GABA and neural transmission. Dysregulation of GADs and GABA is associated with various neurological disorders. The study used psoralidin, found in the seeds of Psoralea corylifolia, to investigate its effect on GAD levels and regulatory mechanisms in primary cortical neurons. Psoralidin reduced GAD67 through transcriptional regulation. The reduction was not mediated by the N-methyl-D-aspartate receptor. Additionally, psoralidin attenuated the formation of inhibitory synapses in primary hippocampal neurons.
{"title":"Effects of psoralidin on the expression of glutamate decarboxylases and inhibitory synapse development","authors":"","doi":"10.1080/10286020.2024.2346297","DOIUrl":"10.1080/10286020.2024.2346297","url":null,"abstract":"<div><p>Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter required for excitation/inhibition balance is synthesized by the glutamic acid decarboxylases (GADs) in GABAergic neurons. The levels and activity of GADs are strongly correlated with GABA and neural transmission. Dysregulation of GADs and GABA is associated with various neurological disorders. The study used psoralidin, found in the seeds of <em>Psoralea corylifolia</em>, to investigate its effect on GAD levels and regulatory mechanisms in primary cortical neurons. Psoralidin reduced GAD67 through transcriptional regulation. The reduction was not mediated by the N-methyl-D-aspartate receptor. Additionally, psoralidin attenuated the formation of inhibitory synapses in primary hippocampal neurons.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1080/10286020.2024.2345181
Ming-You Peng , Xiong Zhang , Qin-Dan Li , En-Ming Feng , Lu Chen , Hu-Cheng Yang , Bing Guo , Ying-Tong Di , Lei Tang , Rong-Can Luo , Ying Yan
Nine jatrophane diterpenoids were isolated from the whole plant Euphorbia helioscopia, including two new ones, helioscopnins A (1) and B (2). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds 1, 3, 4, 5, 8, and 9 significantly increased autophagic flux.
{"title":"Two new jatrophane diterpenoids from Euphorbia helioscopia with activity towards autophagic flux","authors":"Ming-You Peng , Xiong Zhang , Qin-Dan Li , En-Ming Feng , Lu Chen , Hu-Cheng Yang , Bing Guo , Ying-Tong Di , Lei Tang , Rong-Can Luo , Ying Yan","doi":"10.1080/10286020.2024.2345181","DOIUrl":"10.1080/10286020.2024.2345181","url":null,"abstract":"<div><p>Nine jatrophane diterpenoids were isolated from the whole plant <em>Euphorbia helioscopia</em>, including two new ones, helioscopnins A (<strong>1</strong>) and B (<strong>2</strong>). Comprehensive spectroscopic data analysis and ECD calculations elucidated their structures, including absolute configurations. All compounds were evaluated for bioactivity towards autophagic flux by flow cytometry using HM mCherry-GFP-LC3 cells. Compounds <strong>1</strong>, <strong>3</strong>, <strong>4</strong>, <strong>5</strong>, <strong>8</strong>, and <strong>9</strong> significantly increased autophagic flux.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1080/10286020.2024.2346636
Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 μg/ml) and 7a (38.15 μg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 μg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 μg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.
{"title":"Development of natural perfume as potential fungicide candidates: construction and biological evaluation of vanillin analogs bearing the 1,3,4-oxadiazole/1,3-thiazolidin-4-one fragments","authors":"","doi":"10.1080/10286020.2024.2346636","DOIUrl":"10.1080/10286020.2024.2346636","url":null,"abstract":"<div><p>Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds <strong>6j</strong> (29.73 μg/ml) and <strong>7a</strong> (38.15 μg/ml) displayed excellent inhibitory activity against the spore of <em>Fusarium solani</em>. The inhibitory activity of compound <strong>7d</strong> (10.53 μg/ml) against the spore of <em>Alternaria solani</em> was more than 42-fold that of vanillin. Compound <strong>7a</strong> (37.54 μg/ml) showed better antifungal activity against the spore of <em>B. cinerea</em> than positive controls. The cytotoxicity assay confirmed that compounds <strong>6k</strong>, <strong>7a</strong>, and <strong>7d</strong> showed good selectivity and less toxicity to normal mammalian cells.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-15DOI: 10.1080/10286020.2024.2349664
A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.
{"title":"Secofumitremorgins C and D, a pair of atropisomers from saltern-derived fungus Aspergillus fumigatus GXIMD00544","authors":"","doi":"10.1080/10286020.2024.2349664","DOIUrl":"10.1080/10286020.2024.2349664","url":null,"abstract":"<div><p>A pair of atropisomers secofumitremorgins C (<strong>1a</strong>) and D (<strong>1b</strong>), together with fifteen known alkaloids (<strong>2-16</strong>), were isolated from a saltern-derived fungus <em>Aspergillus fumigatus</em> GXIMD00544. The structures of atropisomers <strong>1a</strong> and <strong>1b</strong> were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds <strong>1</strong> and <strong>8</strong> displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane <em>Fusarium</em> sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers <strong>1</strong> also exhibited antifouling potential against <em>Balanus amphitrite</em> larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.1080/10286020.2024.2340073
Quan-Yu Yang , Song-Xue Yang , Qiong Wei , Yan-Zi Ma , Bo Li , Xue-Wen Wu , Rui-Han Zhang , Xing-Jie Zhang , Xiao-Li Li , Wei-Lie Xiao
Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36–3.44 μM.
{"title":"Two new oleanane triterpenes from Maytenus hookeri","authors":"Quan-Yu Yang , Song-Xue Yang , Qiong Wei , Yan-Zi Ma , Bo Li , Xue-Wen Wu , Rui-Han Zhang , Xing-Jie Zhang , Xiao-Li Li , Wei-Lie Xiao","doi":"10.1080/10286020.2024.2340073","DOIUrl":"10.1080/10286020.2024.2340073","url":null,"abstract":"<div><p>Two new triterpenes mayteneri A (<strong>1</strong>), mayteneri B (<strong>2</strong>), and seven known compounds (<strong>3-9</strong>) were isolated from stems of <em>Maytenus hookeri</em> Loes. The chemical structures of compounds <strong>1</strong> and <strong>2</strong> were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds <strong>3</strong>-<strong>9</strong> were determined by comparison of their spectral with those reported. Compounds <strong>4</strong>-<strong>7</strong> showed significant inhibitory activity for NLRP3 inflammasome, with the IC<sub>50</sub> values of 2.36–3.44 <em>μ</em>M.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1080/10286020.2023.2269528
Samy K. El-Desouky
A new quinochalcone C-glycoside featuring a unique quinonoid moiety, named celochalcoside (1), was isolated from the n-butanol extract of the aerial parts of Celosia trigyna L. The structure was determined by extensive spectroscopic analysis as well as mass spectrometric data. Compound 1 showed moderate cytotoxic activities against breast cancer cell lines (MCF-7), colon cancer cell lines (HT-29) and hepatocellular carcinoma cell lines (HepG2) with IC50 values of 23.16, 37.05 and 18.35 μg/ml, respectively.
{"title":"Celochalcoside, a new quinochalcone C-glycoside from Celosia trigyna","authors":"Samy K. El-Desouky","doi":"10.1080/10286020.2023.2269528","DOIUrl":"10.1080/10286020.2023.2269528","url":null,"abstract":"<div><p>A new quinochalcone <em>C</em>-glycoside featuring a unique quinonoid moiety, named celochalcoside (<strong>1</strong>), was isolated from the <em>n</em>-butanol extract of the aerial parts of <em>Celosia trigyna</em> L. The structure was determined by extensive spectroscopic analysis as well as mass spectrometric data. Compound <strong>1</strong> showed moderate cytotoxic activities against breast cancer cell lines (MCF-7), colon cancer cell lines (HT-29) and hepatocellular carcinoma cell lines (HepG2) with IC<sub>50</sub> values of 23.16, 37.05 and 18.35 μg/ml, respectively.</p></div>","PeriodicalId":15180,"journal":{"name":"Journal of Asian Natural Products Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}