Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

( Yaodong Liu ),( Sibtain Ahmed ),( Yaowei Fang ),( Meng Chen ),( Jia An ),( Guang Yang ),( Xiaoyue Hou ),( Jing Lu ),( Qinwen Ye ),( Rongjun Zhu ),( Qitong Liu ),( Shu Liu ) 한국미생물생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.4

Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soil-borne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 μM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 μg/ml and minimum fungicidal concentration (MFC) at 520 μg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.

A key ABA hydrolase gene, OsABA8ox3 is involved in rice resistance to Nilaparvata lugens by affecting callose deposition

Yaodong Zhou,Litong Sun,Shuang Wang,Pengfei Xie,Jing-Lan Liu 한국응용곤충학회 2019 Journal of Asia-Pacific Entomology Vol.22 No.2

Abscisic acid (ABA) is an important plant hormone in regulating abiotic and biotic stresses. OsABA8ox3 is the key gene in ABA hydrolase genes, and plays an important role in controlling ABA level, but little is known in rice resistance to insects. We used rice osaba8ox3 T-DNA insertion mutant (knocking down the OsABA8ox3 gene) to elucidate rice resistance to the insect. There were obvious phenotype differences between the osaba8ox3 T-DNA insertion mutant and wild-type (WT), and the relative expression of synthetase genes in the osaba8ox3 mutant was higher, while the relative expression of hydrolase genes was lower than that of WT, respectively. The electrical penetration graph (EPG) recording indicated that the osaba8ox3 mutant had the less sucking phloem sap duration compared with WT, which indicated a significant increase in rice resistance to brown planthopper (Nilaparvata lugens; BPH). The callose deposition in the osaba8ox3 mutant increased by 60.39%, 52.2%, 26.6% and 31.7% than that of WT after BPH feeding for 0, 24, 48, and 72 h, respectively. These results showed OsABA8ox3 gene played an important role in rice resistance to BPH, and also provided new insights into the mechanism of callose deposition regulation in response to the piercing-sucking pest.

Research Progress on Non-coding RNAs in Cholesteatoma of the Middle Ear

Dongliang Liu,Hang Zhang,Xiulan Ma,Yaodong Dong 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.2

Cholesteatoma of the middle ear is a common disease in otolaryngology that is receiving increasing attention. It is estimat-ed that over five million people around the world have suffered from middle ear cholesteatoma. The annual incidence ofmiddle ear cholesteatoma has been reported to be 9.2 per 100,000 in adults and 3 per 100,000 in children. Without timelydiscovery and intervention, cholesteatomas can become perilously large and damage intratemporal structures, causing vari-ous intracranial and extracranial complications. No practical nonsurgical treatments are currently available. Although multi-ple hypotheses exist, research directions have consistently focused on cell proliferation, apoptosis, and bone destruction. Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs),have recently received increasing attention because of their key roles in gene expression, cell cycle regulation, and the de-velopment of many diseases. Although ncRNAs are not involved in protein translation, they are abundant in the genome,with only approximately 2% of genes encoding proteins and the remaining approximately 98% encoding ncRNAs. Thepurpose of this review is to summarize the current state of knowledge regarding the specific role of ncRNAs in middle earcholesteatoma.

Comparative study of the sublethal effects of indoxacarb on juvenile hormone titer and juvenile hormone esterase mRNA expression of Nilaparvata lugens and Chilo suppressalis in rice

Jing-Lan Liu,Zhenghui Li,Hong-Mei Zhang,Haitao Du,Xu Ding,Yaodong Zhou,Jin-Cai Wu,AndrewWong 한국응용곤충학회 2017 Journal of Asia-Pacific Entomology Vol.20 No.2

Both the rice stem borer, Chilo suppressalis, and the brown planthopper, Nilaparvata lugens are important rice pests. The study is a comparative analysis on the effects of indoxacarb on the pest's juvenile hormone (JH) titer and juvenile hormone esterase (JHE) mRNA expression. RT-PCR and RACE were used to amplify the full length Csjhe (JHE of C. suppressalis) cDNA fromC. suppressalis. The full length cDNA is 1841 bp in length and contains a 1734 bp open reading encoding 577 amino acid residues. An amino acid sequence alignment shows that Csjhe shares high identity with other three other lepidopterans homologues including Manduca sexta, Bombyx mori, and Choristoneura fumiferana. JH III titer in 4th instar larvae of C. suppressalis was significantly reduced with 0.1, 0.2, 0.4 and 0.8 g/L indoxacarb, which were decreased by 11.0%, 22.3%, 32.0% and 37.7% respectively, the expression levels of Csjhe mRNA were 1.38, 1.92 and 5.25 times the control levels in 4th instar larvae with 0.2, 0.4 and 0.8 g/L indoxacarb. Similarly, all of the tested concentrations of indoxacarb caused a significant decrease in JH III titer of N. lugens adult females after indoxacarb treatments, Nljhe (JHE of N. lugens)mRNAaverage expression levels were 4.8, 5.0 and 4.4 times before mating and 6.5, 7.6 and 5.3 times after mating compared to the control at 1, 3 and 5 days, respectively. The comparative studies of the effects of indoxacarb on JH III titer and JHE mRNA further have a significance to a guided integrated pest management.

Frost Resistance of Thermoinsulating Recycled-Aggregate Concretes Containing Glazed Hollow Beads

Zhaoxu Wang,Yuanzhen Liu,Yaodong Guo,Yu Zhao,Lucen Hao 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.2

Glazed hollow bead (GHB) is an innovative material that gives concrete very good thermal-insulation properties and improves concrete frost resistance, when used as a partial replacement of ordinary fine aggregate. The improvement in frost resistance under freeze-thaw cycles and the deterioration mechanisms of recycled aggregate thermoinsulating concretes (RATICs) is the objective of this study, after adding GHBs to the mix. Fifteen cubes and ninety prisms made of five RATIC mixes (GHB content = 0, 40, 65, 90 and 130 kg/m3) were tested in compression, to identify the optimum content of GHB. The degradation mechanisms of RATIC were identified based on mass loss, dynamic elastic modulus and uniaxial compressive strength. In addition, RATIC mesostructure was investigated by means of Computed Tomography Scanning, and the deterioration mechanisms by analyzing pore amount, average and maximum pore area and porosity. The experimental results demonstrate that adding glazed hollow beads to recycled aggregate concrete (RAC) moderately changes the mesostructure of the concrete, to the advantage of frost resistance, and that the optimum content of GHB is around 90 kg/m3.

PFP@PLGA/Cu12Sb4S13-mediated PTT ablates hepatocellular carcinoma by inhibiting the RAS/MAPK/MT-CO1 signaling pathway

Dong Tianxiu,Jiang Jian,Zhang Hao,Liu Hongyuan,Zou Xiaomeng,Niu Jiamei,Mao Yingxuan,Zhu Mingwei,Chen Xi,Li Zizhuo,Chen Yaodong,Shi Chunying,Yang Xiuhua 나노기술연구협의회 2021 Nano Convergence Vol.8 No.29

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world, and patients with HCC face a poor prognosis. The conventional therapeutic strategies for HCC have undergone a challenge-riddled evolution owing to side effects and unsatisfactory efficacy. Here, aiming to provide a new method of HCC elimination, we formulated a novel multifunctional nanocapsule (PFP@PLGA/Cu 12 Sb 4 S 13 , PPCu) with applications in contrast-enhanced ultrasound imaging (CEUS) and photothermal therapy (PTT). These PPCu were successfully constructed with an average diameter of 346 nm (polydispersity index, PDI = 0.276). The reinforced contrast ratio of these PPCu was determined by CEUS, revealing their promising applications in image-guided monitoring of HCC treatment. Furthermore, the excellent photoabsorption and biocompatibility indicated by organ H&E staining indicated that PPCu meet quality expectations for use as photothermal transduction agent (PTA). PPCu treatment at 50 °C and higher temperatures efficiently repressed the proliferation, induced the apoptosis and decreased the motility of HCC cells. These effects might have been results of RAS/MAPK/MT-CO1 signaling pathway inhibition. In summary, PPCu were constructed to integrate CEUS and PTT successfully into therapy, which can lead to HCC elimination through RAS/MAPK/MT-CO1 signaling pathway repression.

Characterization and functional study of juvenile hormone diol kinase gene in Nilaparvata lugens (Stål) (Hemiptera: Delphacidae)

Pengfei Xie,Zhenghui Li,Xu Ding,Yaodong Zhou,Jing-Lan Liu 한국응용곤충학회 2018 Journal of Asia-Pacific Entomology Vol.21 No.4

The brown planthopper, Nilaparvata lugens (Stål) is an important pest in rice. It has been widely recognized that the juvenile hormone (JH) is regulated by its hydrolase, which includes juvenile hormone esterase (JHE), juvenile hormone epoxide hydrolase (JHEH) and juvenile hormone diol kinase (JHDK). In this paper, we cloned the gene of Jhdk and the gene expression at different stages of N. lugens was analysed, and the relationship with Jhe and Jheh was studied after silencing the jhdk gene of N. lugens (Nljhdk) through double-stranded RNA (dsRNA) feeding. We also explored the expression of the three JH hydrolase after indoxacarb treatments. RT-PCR was used to amplify the full length Jhdk cDNA, and the Nljhdk gene was expressed throughout all the development periods tested and showed the lowest level at the 4th instar and the highest in the 5th instar. The expression level of Nljhdk in male adults was higher than that of female adults. Through feeding, dsRNA against Nljhdk successfully knocked down the target gene, which had no significant effect on the expression of the jhe gene of N. lugens (Nljhe), while the expression of Nljheh was upregulated. Indoxacarb could inhibit N. lugens reproduction, and the expression level of Nljhe and Nljhdk increased with the increasing of indoxacarb concentration, but the expression of the jheh gene of N. lugens (Nljheh) was reduced. These studies provide a line of experimental evidence in N. lugens to support that Nljhdk encodes the functional protein involved in JH degradation and further showed the relationship of the three hydrolases and the mechanism of indoxacarb inhibition of the fecundity of N. lugens.