New indole derivatives from endophytic fungus Colletotruchum sp. HK-08 originated from leaves of Nerium indicum

Objective:To study secondary metabolites from endophytic fungus Colletotruchum sp.HK-08 originated from the leaves of Nerium indicum.Methods:The compounds were isolated by various column chromatographic techniques,and their structures were elucidated by spectroscopic techniques[high resolution electrospray ionization mass spectroscopy(HRESIMS),one-dimensional(1D)and two-dimensional(2D)nuclear magnetic resonance spectroscopy(NMR)],as well as comparison with literature data.The Ellman method was used to determine the acetylcholinesterase(AChE)inhibitory activity.Results:Four indole derivatives were identified from Colletotruchum sp.HK-08,including 60-hydroxymonaspiloindole(1),2-(2-oxoindolin-3-yl)ethyl 2-(4-hydroxyphenyl)acetate(2),2-(2-oxoindolin-3-yl)ethyl 2-(2-hydroxyphenyl)acetate(3),and monaspiloindole(4).Compound 4 presented weak AChE inhibitory activity with IC50 value of(69.30±6.27)lmol/L[tacrine as the positive control,with IC50 value of(0.61±0.07)lmol/L].Conclusion:Compounds 1–3 were new compounds,and compound 4 had weak AChE inhibitory activity。

A novel inhibitor of N^(6)-methyladenosine demethylase FTO induces m RNA methylation and shows anti-cancer activities

N^(6)-methyladenosine(m^(6)A)modification is critical for m RNA splicing,nuclear export,stability and translation.Fat mass and obesity-associated protein(FTO),the first identified m^(6)A demethylase,is critical for cancer progression.Herein,we developed small-molecule inhibitors of FTO by virtual screening,structural optimization,and bioassay.As a result,two FTO inhibitors namely 18077 and 18097 were identified,which can selectively inhibit demethylase activity of FTO.Specifically,18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells.In addition,18097 reprogrammed the epi-transcriptome of breast cancer cells,particularly for genes related to P53 pathway.18097 increased the abundance of m^(6)A modification of suppressor of cytokine signaling1(SOCS1)m RNA,which recruited IGF2 BP1 to increase m RNA stability of SOCS1 and subsequently activated the P53 signaling pathway.Further,18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma(PPARγ),CCAAT/enhancer-binding protein alpha(C/EBPa),and C/EBPβ.Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells.Collectively,we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Integrated analysis reveals an association between the rhizosphere microbiome and root rot of arecanut palm

The rhizosphere microbial community is crucial to plant health.Many studies have explored the association between the rhizosphere microbiome and plant disease.However,few studies have focused on root rot in arecanut palm,a disease causing devastating effects and thus resulting in economic losses that considerably affect the development of the arecanut industry.Here,rhizosphere samples were collected from both healthy arecanut palm plants and root-rotted arecanut palm plants,and the microbial communities were analyzed using high-throughput sequencing.The root-rotted samples exhibited distinct microbial community richness,diversity,and composition compared with the healthy samples,which was associated with p H according to the Mantel test.Identified potential plant pathogens,including Proteobacteria,Bacteroidetes,Chytridiomycota,and Mortierellomycota,were significantly enriched in the root-rotted samples.In contrast,potentially beneficial plant microbes,such as Acidobacteria and Gemmatimonadetes,were significantly depleted in the root-rotted samples.Co-occurrence networks were constructed to further identify microbial relationships in the root-rotted samples.These findings revealed ecological imbalance among beneficial bacteria in the root-rotted samples.The present study therefore provides an integrated view of the association between the microbial community and root rot in arecanut palm.

Physalin B reduces Aβ secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation

Physalin B(PB),one of the major active steroidal constituents of Solanaceae Physalis plants,has a wide variety of biological activities.We found that PB significantly down-regulatedβ-amyloid(Aβ)secretion in N2a/APPsw cells.However,the underlying mechanisms are not well understood.In the current study,we investigated the changes in key enzymes involved inβ-amyloid precursor protein(APP)metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations.The results indicated that PB reduced Aβ secretion,which was caused by down-regulation of β-secretase(BACE1)expression,as indicated at both the protein and mRNA levels.Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1(FoxO1)and inhibiting the phosphorylation of signal transducer and activator of transcription 3(STAT3).In addition,the effect of PB on BACE1 expression and Aβsecretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201.In conclusion,these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aβsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.

Gas Chromatography–Mass Spectrometry for Quantitative and Qualitative Analysis of Essential Oil from Curcuma wenyujin Rhizomes

Objectives:A rapid and sensitive gas chromatography–mass spectrometry(GC–MS)method for quantitative and qualitative analysis of essential oil from Curcuma wenyujin rhizomes was established.Methods:The essential oil of C.wenyujin rhizomes was extracted by supercritical CO2 extraction(SFE).Six main bioactive compounds(eucalyptol,β-elemene,curzerene,germacrone,curdione,and curcumol)were analyzed in selected ion monitoring mode(SIM).Results:Curzerene is not originally present in C.wenyujin rhizomes,but is a product of the transformation of furanodiene at high temperature.The six target components demonstrated good linearity(R2>0.9979)over a relatively wide concentration range.The interday and intraday variations had relative standard deviation values less than 5%and the average recovery ranged from 96.95%to 100.04%.The limit of quantitation ranged from 0.032 to 0.235μg/mL.The developed method was successfully used to analyze the six compounds in 17 samples collected from different origins.Significant variation was observed for the concentrations of the six compounds.In addition,51 constituents were identified in C.wenyujin rhizome essential oil,consisting of 87.66%of the total essential oil,including curdione,curzerene,dehydrocurdione,germacrone,1,4-bis(2-benzimidazoyl)benzene,neocurdione,curcumenone,andβ-elemene.Conclusions:The proposed method will be useful in the quality control of C.wenyujin rhizome essential oil production.

Arylalkalamine N-acetyltransferase-1 functions on cuticle pigmentation in the yellow fever mosquito,Aedes aegypti

Arylalkylamine N-acetyltransferase(aaNAT)catalyzes the acetylation of dopamine,5-hydroxy-tryptamine,tryptamine,octopamine,norepinephrine and other ary-lalkylamines to form respective N-acetyl-arylalkylamines.Depending on the products formed,aaNATs are involved in a variety of physiological functions.In the yellow fever mosquito,Aedes aegypti,a number of aaNATs and aaNAT-like proteins have been reported.However,the primary function of each individual aaNAT is yet to be identified.In this study we investigated the function of Ae.aegypti aaNAT 1(Ae-aaNATl)in cuticle pigmentation and development of morphology.Ae-aaNAT1 transcripts were detected at all stages of development with highest expressions after pupation and right before adult eclosion.Ae-aaNATl mutant mosquitoes generated using clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated protein 9 had no obvious effect on larval and pupal development.However,the mutant mosquitoes exhibited a roughened ex-oskeletal surface,darker cuticles,and color pattern changes suggesting that Ae-aaNAT1 plays a role in development of the morphology and pigmentation of Ae.aegypti adult cuticles.The mutant also showed less blood feeding efficiency and lower fecundity when compared with the wild-type.The mutation of Ae-aaNAT1 influenced expression of genes involved in cuticle formation.In summary,Ae-aaNAT1 mainly functions on cuticular pigmentation and also affects blood feeding efficiency and fecundity.