3‑Hydroxy-2-oxindole Derivatives Containing Sulfonamide Motif: Synthesis, Antiviral Activity, and Modes of Action

3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides

3‑Hydroxy-2-oxindole Derivatives Containing Sulfonamide Motif: Synthesis, Antiviral Activity, and Modes of Action

3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides

Splicing Indoles and 4,5-Dihydro‑1<i>H</i>‑pyrazoline Structure Gave Birth to Novel Antiviral Agents: Design, Synthesis, and Mechanism Study

The specific conation of our research is to invent a series of indole derivatives containing a 4,5-dihydro-1H-pyrazoline motif with effective antiviral activity. The anti-potato virus Y (PVY) activities of target compounds were systematically investigated. Most target compounds exhibited good PVY activities. Compound D40, which exhibited outstanding anti-PVY activities, was sieved using a three-dimensional quantitative structure–activity relationship. Based on the anti-PVY activity assessments, the curative and protective activities of D40 were found to be 64.9 and 60.8%, respectively, which were superior to those of the commercial drug Ningnanmycin (50.2 and 50.7%, respectively). In addition, defensive enzyme activities and proteomics results indicate that D40 can increase the three crucial defense-related enzyme activities and regulate the carbon fixation pathway in photosynthetic organisms to intensify the resistance of plants to PVY. Therefore, our study suggests that compound D40 might be used as a suitable crop protection pesticide

Splicing Indoles and 4,5-Dihydro‑1<i>H</i>‑pyrazoline Structure Gave Birth to Novel Antiviral Agents: Design, Synthesis, and Mechanism Study

The specific conation of our research is to invent a series of indole derivatives containing a 4,5-dihydro-1H-pyrazoline motif with effective antiviral activity. The anti-potato virus Y (PVY) activities of target compounds were systematically investigated. Most target compounds exhibited good PVY activities. Compound D40, which exhibited outstanding anti-PVY activities, was sieved using a three-dimensional quantitative structure–activity relationship. Based on the anti-PVY activity assessments, the curative and protective activities of D40 were found to be 64.9 and 60.8%, respectively, which were superior to those of the commercial drug Ningnanmycin (50.2 and 50.7%, respectively). In addition, defensive enzyme activities and proteomics results indicate that D40 can increase the three crucial defense-related enzyme activities and regulate the carbon fixation pathway in photosynthetic organisms to intensify the resistance of plants to PVY. Therefore, our study suggests that compound D40 might be used as a suitable crop protection pesticide

Table_1_Altered Resting-State Functional Activity in Medication-Naive Patients With First-Episode Major Depression Disorder vs. Healthy Control: A Quantitative Meta-Analysis.DOC

Background: There is an urgent need for a meta-analysis that characterizes the brain states of major depression disorder (MDD) patients and potentially provides reliable biomarkers, because heterogeneity in the results of resting-state functional neuroimaging has been observed between studies, with some patients not showing the consistent changes, or even opposite patterns. Thus, we evaluated consistent regional brain activity alterations in medication-naive patients with first-episode unipolar MDD and compared the results with those in healthy controls (HCs).Methods: A systematic database search was conducted (in PubMed, Ovid, and Web of Knowledge) between January 1984 and July 2016 to select resting-state functional activity studies with a voxel-wise analysis in MDD. We used anisotropic effect size-signed differential mapping to perform a whole-brain meta-analysis, comparing functional alterations between first-episode medication-naive unipolar MDD patients and HCs by integrating the studies. In addition, subgroup meta-analysis was conducted to control for the MRI analysis method. Moreover, the meta-regression analyses were performed to examine the potential effects of mean age, education duration, illness duration, and severity of depressive symptoms.Results: A total of 12 studies were included, comparing 313 MDD patients with 283 HCs. The pooled and subgroup meta-analysis found that the MDD patients showed hyperactivity in the left parahippocampal gyrus, left supplementary motor area, left amygdala, left hippocampus, and left middle frontal gyrus (MFG; orbital part), and hypoactivity in the left lingual gyrus, left middle occipital gyrus, right cuneus cortex, right MFG (orbital part), and left cerebellum. In the meta-regression analyses, the mean illness duration was positively associated with hyper-activation in the left parahippocampal gyrus and hypoactivation in the hemispheric lobule IV/V of the left cerebellum.Conclusions: This meta-analysis indicated that MDD patients had significant and robust resting-state brain activity alteration in amygdala, left hippocampus and other regions, which implicated this finding in the pathophysiology of cognitive and emotional impairment in MDD patients.</p

Table_1_Altered Resting-State Functional Activity in Patients With Autism Spectrum Disorder: A Quantitative Meta-Analysis.DOCX

<p>Background: There is accumulating evidence showing that patients with autism spectrum disorder (ASD) have obvious changes in resting-state functional brain activity. So far, there have been no meta-analyses of the resting-state brain activity alterations in patients with ASD. We attempted to explore the resting-state functional activity changes in patients with ASD, possibly providing a new perspective for investigating the pathophysiology of patients with ASD.</p><p>Methods: We screened relevant studies published before August 2017 in PubMed, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), and the Wan-fang database. Fifteen resting-state functional neural activity datasets (including 382 patients and 348 healthy controls) were included. Through the use of the effect-size signed differential mapping (ES-SDM) method, we carried out a meta-analysis of resting-state functional activity studies of patients with ASD.</p><p>Results: Compared with healthy controls, patients with ASD showed hyperactivity in the right supplementary motor area, middle frontal gyrus, inferior frontal gyrus, the left precentral gyrus, and the bilateral cerebellum hemispheric lobule (VIII/IX), and hypoactivity in the right middle temporal gyrus, superior temporal gyrus, and the left precuneus, posterior cingulate cortex, median cingulate cortex, and bilateral cerebellum (crus I).</p><p>Conclusion: This meta-analysis indicates that patients with ASD have significant and robust resting-state brain activity alterations in the language comprehension network, inferior-posterior cerebellum, default mode network (DMN), and cerebellar crus I. These brain regions may serve as specific regions of interest for further studies of ASD, which will allow us to further clarify the neurobiological mechanisms in patients with ASD.</p

Table_4_Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice.xls

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.</p

Table_7_Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice.xls

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.</p

Table_2_Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice.xlsx

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.</p

Table_9_Comprehensive identification and characterization of lncRNAs and circRNAs reveal potential brown planthopper-responsive ceRNA networks in rice.xlsx

Brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most destructive pests of rice. Non-coding RNA plays an important regulatory role in various biological processes. However, comprehensive identification and characterization of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in BPH-infested rice have not been performed. Here, we performed a genome-wide analysis of lncRNAs and circRNAs in BPH6-transgenic (resistant, BPH6G) and Nipponbare (susceptible, NIP) rice plants before and after BPH feeding (early and late stage) via deep RNA-sequencing. A total of 310 lncRNAs and 129 circRNAs were found to be differentially expressed. To reveal the different responses of resistant and susceptible rice to BPH herbivory, the potential functions of these lncRNAs and circRNAs as competitive endogenous RNAs (ceRNAs) were predicted and investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Dual-luciferase reporter assays revealed that miR1846c and miR530 were targeted by the lncRNAs XLOC_042442 and XLOC_028297, respectively. In responsive to BPH infestation, 39 lncRNAs and 21 circRNAs were predicted to combine with 133 common miRNAs and compete for miRNA binding sites with 834 mRNAs. These mRNAs predictably participated in cell wall organization or biogenesis, developmental growth, single-organism cellular process, and the response to stress. This study comprehensively identified and characterized lncRNAs and circRNAs, and integrated their potential ceRNA functions, to reveal the rice BPH-resistance network. These results lay a foundation for further study on the functions of lncRNAs and circRNAs in the rice-BPH interaction, and enriched our understanding of the BPH-resistance response in rice.</p