Indole alkaloids isolated from the Nicotiana tabacum-derived Aspergillus fumigatus 0338 as potential inhibitors for tobacco powdery mildew and their mode of actions.

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.

C-Alkylated flavonoids from the whole plants of Desmodium caudatum and their anti-TMV activity.

BACKGROUND: Natural products are important sources of biopesticides to control plant virus, and flavonoids are identified as promising anti-tobacco mosaic virus (TMV) agents. Since Desmodium caudatum is a rich source of flavonoids, this study focuses on the discovery of the new anti-TMV active flavonoids from D. caudatum and their possible mode of action. RESULTS: Three new (compounds 1-3) and nine known (compounds 4-12) C-alkylated flavonoids were isolated from D. caudatum. To the best of our knowledge, the framework of 1-3 was reported in natural products for the first time. In addition, 1-3, 5, and 6 showed notable anti-TMV activity with inhibition rates in the range of 35.8-64.3% at a concentration of 50 µg/mL, and these rates are higher than that of positive control (with inhibition rates of 34.6% ± 2.8). In addition, the structure-activity relationship study revealed that the (pyrrol-2-yl)methyl moiety on flavone can significantly increases the activity. This result is helpful to find new anti-TMV inhibitors. CONCLUSION: C-Alkylated flavonoids showed potent activities against TMV with multiple modes of actions. The increase of defense-related enzyme activities, up-regulate the expression of defense related genes, down-regulate the expression of Hsp70 protein by inhibiting the related Hsp genes that are involved in tobacco resistance to TMV. By the actions mentioned earlier, the infection of TMV was influenced, thereby achieving the effects of control of TMV. The successful isolation of the earlier-mentioned flavonoids provide the new source of biopesticides to TMV proliferation, and also contribute to the utilization of D. caudatum. © 2023 Society of Chemical Industry.

[Retrospective and cost-effective analysis of the result of Changsha Municipal Public Welfare Program by Noninvasive Prenatal Testing].

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION: NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.

Exploiting Spatial-Temporal Locality of Tracking via Structured Dictionary Learning.

In this paper, a novel spatial-temporal locality is proposed and unified via a discriminative dictionary learning framework for visual tracking. By exploring the strong local correlations between temporally obtained target and their spatially distributed nearby background neighbors, a spatial-temporal locality is obtained. The locality is formulated as a subspace model and exploited under a unified structure of discriminative dictionary learning with a subspace structure. Using the learned dictionary, the target and its background can be described and distinguished effectively through their sparse codes. As a result, the target is localized by integrating both the descriptive and the discriminative qualities. Extensive experiments on various challenging video sequences demonstrate the superior performance of proposed algorithm over the other state-of-the-art approaches.

[Role of angiogenic T cells and EPC in the pathogenesis of preeclampsia and the relationship between angiogenic T cells and EPC].

OBJECTIVES: To investigate the role of angiogenic T cells (Tang) and endothelial progenitor cells (EPC) in the pathogenesis of preeclampsia. To explore the relationship between Tang and EPC. METHODS: From Mar 2013 to Aug 2014, 40 patients diagnosed preeclampsia (PE) and delivered in Hunan Provincial People's Hospital. A total of 20 of them were defined as the mild preeclampsia group and the other 20 cases were recruited as the severe preeclampsia group. And 24 healthy pregnant women were recruited as the control group. The percentage of Tang and EPC in peripheral blood mononuclear cells (PBMC) were determinated by flow cytometry between 28 and 40 gestational weeks. RESULTS: (1) There was no significant difference in the age, pre-pregnancy body mass index (Pre-BMI) or gestational age among the three groups (P > 0.05). The differences of blood pressure among the three groups were statistically significant (P < 0.05). The gestational week at delivery, the birthweight of the neonates and the 1 minute Apgar score in the severe preeclampsia group were lower than those in the mild preeclampsia group and the control group, with statistically significant differences (P < 0.05). The morbidity of neonatal asphyxia in the severe preeclampsia group was 35% (7/20); and in the mild preeclampsia group it was 5% (1/20), with statistically significant difference (P < 0.05). (2) The percentage of Tang in maternal peripheral blood was (52.7 ± 8.0)%, (47.5 ± 8.8)% and (45.5 ± 8.7)% in the control group, the mild preeclampsia group and the severe preeclampsia group, respectively. The difference among the three groups was significant (F = 4.248, P < 0.05), and SNK q analysis showed there was significant difference between the control group and the severe preeclampsia group (P < 0.05). While there was no statistically significant difference between the mild and the severe preeclampsia group, nor between the control group and the mild preeclampsia group(P > 0.05). (3) The percentage of EPC in maternal peripheral blood was (0.16 ± 0.07)%, (0.09 ± 0.07)% and (0.08 ± 0.05)% in the control group, the mild and the severe preeclampsia group, respectively. Analysis of variance showed that difference among the three groups was significant (F = 9.351, P < 0.05). The percentage of EPC in the mild or the severe preeclampsia group was significantly higher than that of the control group (P < 0.05). (4) There was no statistically significant correlation between the Tang level and the EPC level in the control group (r = -0.325, P > 0.05). In the preeclampsia group (including mild and severe cases), there was positive correlation between the Tang level and EPC level (r = 0.667, P < 0.01). The positive correlation between Tang level and EPC level were proved respectively in the mild preeclampsia group (r = 0.803, P < 0.01) and the severe preeclampsia group (r = 0.520, P < 0.05). CONCLUSIONS: The number of Tang had some correlation with the pathogenesis of preeclampsia. The percentage of Tang had positive correlation with the level of EPC in women with preeclampsia. Tang might have some influence on the change of EPC' level. Tang together with EPC were likely to contribute to the angiogenesis in preeclampsia.

[Correlation between the myometrial thickness in the second trimester and preterm delivery in a prospective study].

OBJECTIVE: To investigate the relationship between preterm delivery and anterior myometrial (MA) thickness measured by ultrasound in the second trimester. METHODS: The general information and pregnancy outcome of singleton pregnant women who had antenatal visit in the Hunan Provincial People's Hospital between Oct 2010 and Sep 2013 were collected prospectively. The MA thickness was measured at 20-27(+6) gestational weeks. The cases were divided into preterm delivery group and term delivery group. RESULTS: (1) A total of 1 031 pregnant women were recruited in this study. 147 pregnant women were in the preterm delivery group (14.26%, 147/1 031) and 884 women were in the term delivery group (85.74% , 884/1 031). The gestation age at delivery of the preterm delivery group was significantly earlier than the term delivery group [(34.57 ± 2.39) vs (39.23 ± 0.92) weeks, P < 0.05]. No significant difference was observed in the age, gravidity, parity, history of preterm delivery, cesarean delivery rate and gestational age at the time of MA measurement between the two groups (P > 0.05). The incidence of premature rupture of membrane (PROM) in the preterm delivery group and in the term delivery group were 49.0% (72/147) and 15.8% (140/884), respectively, with statistically significant difference (P < 0.01). (2) The mean value of MA thickness in the term delivery group was (5.49 ± 1.39) mm, while in the preterm delivery group it was (5.60 ± 0.87) mm. There was no statistically significant difference between the two groups(P > 0.05). The mean value of MA thickness in the spontaneous preterm delivery group was(5.15 ± 0.75) mm, and was (5.61 ± 1.38 ) mm in the term delivery group, with statistically significant difference (P < 0.01). The mean value of MA thickness in the preterm premature rupture of membrane (PPROM) cases was( 5.96 ± 0.78 ) mm, and in term delivery group with PROM it was (5.38 ± 1.12) mm. The difference between the two groups were statistically significant (P < 0.01). (3) Among the 1 031 pregnant women, 212 women had PROM, with the mean value of MA thickness of (5.67 ± 1.32) mm. For those who did not have PROM, the mean value of MA thickness was (5.56 ± 1.10) mm. There was no statistically significant difference between the two groups(P > 0.05). No correlation was found among PROM and MA thickness(r = 0.058, P > 0.05). However, in the preterm delivery group, the mean value of MA in PPROM was significantly thicker than the spontaneous preterm delivery cases (P < 0.01). There was a positive correlation between the MA thickness and PPROM (r = 0.457, P < 0.01). CONCLUSION: The MA thickness had some correlation with spontaneous preterm delivery and PPROM, while the MA thickness should not be considered as an independent factor of preterm delivery.

[Study of the role of nuclear factor-kappa B in preterm birth with subclinical chorioamnionitis].

OBJECTIVE: To investigate the role of nuclear factor-kappa B (NF-kappaB) in preterm birth with subclinical chorioamnionitis. METHODS: From October 2005 to October 2006, 111 cases including 36 cases of preterm birth in labor, 37 cases of full term gravida with spontaneous labor and 38 cases of full term gravida without threatened labor in the Hunan Province People's Hospital, third Xiangya Hospital of Central South University and Changsha Maternal and Child Care Service Center were enrolled in the study. After delivery, by pathology results of fetal membrane they were divided into two groups: subclinical chorioamnionitis group (subclinical infectious group) and non-infectious group. Immunohistochemical staining and RT-PCR were used to observe the change of the p65 subunit of NF-kappaB family in maternal blood and fetal membrane in subclinical infectious group and non-infectious group. RESULTS: (1) The incidence of subclinical chorioamnionitis: there were 24 cases of subclinical chorioamnionitis in the 36 cases of preterm birth in labor (67%), 7 cases in the 37 cases of full term gravida with spontaneous labor group (19%) and 3 cases in the 38 cases of full term gravida without threatened labor group (8%). There was a significant difference among the three groups (P < 0.01). In the totally 111 cases, 34 cases were classified as subclinical infectious group and 77 cases as non-infectious group. (2) In fetal membrane, the median of the average staining intensity of NF-kappaB p65 protein was higher in the subclinical chorioamnionitis group (8.0) than those in non-infectious group (4.0). Similarly, the average staining intensity of NF-kappaB p65 mRNA was higher in the subclinical infectious group (47.5 +/- 17.2) than those in non-infectious group (31.3 +/- 13.6). There was a significant difference between the two groups (P < 0.01). (3) In maternal blood, the expression of NF-kappaB p65 protein and mRNA was higher in subclinical chorioamnionitis group(8.0 and 42.6)than those in non-infectious group(4.0 and 23.6).There was a significant difference between the two groups (P < 0.01). (4) The concentration of NF-kappaB p65 protein in fetal membrane was positively correlated with that of maternal blood (r = 0.581, P < 0.01) and the concentration of NF-kappaB p65 mRNA in fetal membrane was positively correlated with that of maternal blood (r = 0.571, P < 0.01). CONCLUSION: The expression of NF-kappaB in maternal blood and fetal membrane in preterm birth with subclinical chorioamnionitis is higher and the two are correlated with each other. NF-kappaB p65 could be an accurate biochemical marker in predicting subclinical chorioamnionitis in preterm birth. NF-kappaB p65 plays an important role in the pathogenesis of subclinical chorioamnionitis in preterm birth.