Study on the mechanism of SND in the treatment of anxiety disorders based on network pharmacology, molecular docking and experiment validation

Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.

Single-cell transcriptomic analysis identifies a highly replicating Cd168+ þskeletal stem/progenitor cell population in mouse long bones

Skeletal stem/progenitor cells(SSPCs)are tissue-specific stem/progenitor cells localized within skeletons and contribute to bone development,homeostasis,and regeneration.However,the heterogeneity of SSPC populations in mouse long bones and their respective regenerative capacity remain to be further clarified.In this study,we perform integrated analysis using single-cell RNA sequencing(scRNA-seq)datasets of mouse hindlimb buds,postnatal long bones,and fractured long bones.Our analyses reveal the heterogeneity of osteochondrogenic lineage cells and recapitulate the developmental trajectories during mouse long bone growth.In addition,we identify a novel Cd168þSSPC population with highly replicating capacity and osteochondrogenic potential in embryonic and postnatal long bones.Moreover,the Cd168þSSPCs can contribute to newly formed skeletal tissues during fracture healing.Furthermore,the results of multicolor immunofluorescence show that Cd168þSSPCs reside in the superficial zone of articular cartilage as well as in growth plates of postnatal mouse long bones.In summary,we identify a novel Cd168þSSPC population with regenerative potential in mouse long bones,which adds to the knowledge of the tissuespecific stem cells in skeletons.

N-Fluorinated phenyl-N'-pyrimidyl urea derivatives: Synthesis,biological evaluation and 3D-QSAR study

With the increase of herbicide-resistant weeds, novel, more selective and even more potent herbicides to control weeds are needed. In this paper, a series of N-fluorinated phenyl-N＇-pyrimidyl urea derivatives were synthesized and screened for their herbicidal activities against Amaranthus retroflexus （AR） and Setaria viridis （ SV）. Compound 2S （N-（3-trifluoromethylphenyl）-N＇-（2-amino-4-chloro-6-methylpyr- imidyl） urea） exhibited marked herbicidal activity against SV（IC50 =11.67 mg/L） and is more potent than bensulfuron （IC50= 27.45 mg/L）, a commercially available herbicide. A statistically significant CoMFA model with high prediction abilities （q2 = 0.869, r2 = 0.989） was obtained.

Emerging role of long non-coding RNAs in normal and malignant hematopoiesis

Long noncoding RNAs(lncRNAs)have recently been discovered and are increasingly recognized as vital components of modern molecular biology.Accumulating evidence shows that lncRNAs have emerged as important mediators in diverse biological processes such as cell differentiation,pluripotency,and tumorigenesis,while the function of lncRNAs in the field of normal and malignant hematopoiesis remains to be further elucidated.Here,we widely reviewed recent advances and summarize the characteristics and basic mechanisms of lncRNAs and keep abreast of developments of lncRNAs within the field of normal and malignant hematopoiesis.Based on gene regulatory networks at different levels of lncRNAs participation,lncRNAs have been shown to regulate gene expression from epigenetics,transcription and post transcription.The expression of lncRNAs is highly cell-specific and critical for the development and activation of hematopoiesis.Moreover,we also summarized the role of lncRNAs involved in hematological malignancies in recent years.LncRNAs have been found to play an emerging role in normal and malignant hematopoiesis,which may provide novel ideas for the diagnosis and therapeutic targets of hematological diseases in the foreseeable future.

Spermidine affects the transcriptome responses to high temperature stress in ripening tomato fruit

Objective:High temperature adversely affects quality and yield of tomato fruit.Polyamine can alleviate heat injury in plants.This study is aimed to investigate the effects of polyamine and high temperature on transcriptional profiles in ripening tomato fruit.Methods:An Affymetrix tomato microarray was used to evaluate changes in gene expression in response to exogenous spermidine(Spd,1 mmol/L) and high temperature(33/27 °C) treatments in tomato fruits at mature green stage.Results:Of the 10 101 tomato probe sets represented on the array,127 loci were differentially expressed in high temperature-treated fruits,compared with those under normal conditions,functionally characterized by their involvement in signal transduction,defense responses,oxidation reduction,and hormone re-sponses.However,only 34 genes were up-regulated in Spd-treated fruits as compared with non-treated fruits,which were involved in primary metabolism,signal transduction,hormone responses,transcription factors,and stress re-sponses.Meanwhile,55 genes involved in energy metabolism,cell wall metabolism,and photosynthesis were down-regulated in Spd-treated fruits.Conclusions:Our results demonstrated that Spd might play an important role in regulation of tomato fruit response to high temperature during ripening stage.