Network pharmacology prediction and experiment validation of anti-liver cancer activity of Curcumae Rhizoma and Hedyotis diffusa Willd.

Objective: This study aims to elucidate anti-liver cancer components and potential mechanisms of Curcumae Rhizoma and Hedyotis diffusa Willd (CR-HDW). Methods: Effective components and targets of CR-HDW were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Liver cancer-related genes were collected from GeneCards, Gene-Disease Association (DisGeNET), and National Center for Biotechnology Information (NCBI). Protein-protein interaction networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted to analyze the identified genes. Molecular docking was used to simulate binding of the active components and their target proteins. Cell activity assay, western blot, and senescence-associated ß-galactosidase (SA-ß-gal) experiments were conducted to validate core targets identified from molecular docking. Results: Ten active compounds of CR-HDW were identified including quercetin, 3-epioleanic acid and hederagenin. The primary core proteins comprised Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Protein Kinase B(AKT1), etc. The pathways for Phosphoinositide 3-kinase (PI3K)/ AKT, cellular senescence, Fork head boxO (FOXO) were revealed as important for anti-cancer activity of CR-HDW. Molecular docking demonstrated strong binding between liver cancer target proteins and major active components of CR-HDW. In-vitro experiments confirmed that hederagenin and 3-epioleolic acid inhibited HuH-7 cell growth, reduced expression of PI3K, AKT, and mechanistic target of rapamycin (mTOR) proteins. Hederagenin also induced HuH-7 senescence. Conclusions: In summary, The authors' results suggest that the CR-HDW component (Hederagenin, 3-epoxy-olanolic acid) can inhibit the proliferation of HuH-7 cells by decreasing PI3K, AKT, and mTOR. Hederagenin also induced HuH-7 senescence.

Exploring Acori Tatarinowii Rhizoma and Polygalae Radix in Alzheimer's: Network pharmacology and molecular docking analysis.

Explore Acori Tatarinowii Rhizoma (ATR) and Polygalae Radix (PR) mechanisms in Alzheimer's disease (AD) treatment through network pharmacology. ATR-PR was investigated in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, Batman, and Traditional Chinese Medicines Integrated Database (TCMID) to gather information on its chemical components and target proteins. Target genes associated with AD were retrieved from the GeneCards and National Center for Biotechnology Information (NCBI) databases. The integration of these datasets with potential targets facilitated the construction of an AD and ATR-PR protein-protein interaction (PPI) network using the STRING database. The resulting network identified the core active ingredients and main targets of ATR-PR in AD treatment. Cluster analysis of the PPI network was performed using Cytoscape 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape database. Molecular docking simulations revealed potential interactions between the main active ingredients and core targets. Our analysis identified 8 putative components and 455 targets of ATR-PR. We systematically searched for 1306 genes associated with AD, conducted Venn diagram analysis resulting in 156 common targets, and constructed a PPI network with 57 key targets. GO functional analysis highlighted the primary biological processes associated with oxidative stress. KEGG pathway enrichment analysis revealed the involvement of 64 signaling pathways, with the PI3K/Akt signaling pathway playing a key role. Molecular docking analysis indicated a high affinity between the potential targets of ATR-PR and the main compounds of AD. This study sheds light on the complex network of interactions involving ATR-PR in the context of AD. The identified targets, pathways, and interactions provide a foundation for understanding the potential therapeutic mechanisms. The involvement of oxidative stress-related processes and the crucial role of the PI3K/Akt signaling pathway suggest avenues for targeted therapeutic interventions in Alzheimer's disease treatment. Our proposition of the combined use of ATR-PR has emerged as a potential treatment strategy for AD, supported by a network pharmacology approach. This framework provides a robust foundation for future clinical applications and experimental research in the pursuit of effective Alzheimer's disease treatments.

Exploring the mechanism of Epimedii folium and notoginseng radix against vascular dementia based on network pharmacology and molecular docking analysis: pharmacological mechanisms of EH-PN for VD.

To explore the mechanism of Epimedii Folium (HF) and Notoginseng Radix (NR) intervention in vascular dementia (VD). This study used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database to collect the active ingredients and potential drug targets of HF and NR, the Uniprot database to convert drug target names into gene names, GeneCards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man database to collect the potential disease targets of VD, and then combined them with the drug targets to construct the HF-NR-VD protein-protein interaction (PPI) network by Search Tool for the Retrieval of Interacting (STRING). Cytoscape (version 3.7.1) was used to perform cluster analysis of the PPI network. Metascape database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The potential interaction of the main components of the HF-NR couplet medicine with core disease targets was revealed by molecular docking simulations. There were 23 predicted active ingredients in HF and NR, and 109 common drug targets that may be involved in the treatment of VD. Through PPI network analysis, 30 proteins were identified as core proteins owing to their topological importance. GO functional analysis revealed that the primary biological processes were mainly related to inflammation, apoptosis, and the response to oxidative stress. KEGG pathway enrichment analysis revealed that TNF and PI3K/Akt signaling pathways may occupy the core status in the anti-VD system. Molecular docking results confirmed that the core targets of VD had a high affinity for the main compounds of the HF-NR couplet medicine. We demonstrated the multi-component, multi-target, and multi-pathway characteristics of HF-NR couplet medicine for the treatment of VD and provided a foundation for further clinical application and experimental research.

Digital in-service relative time delay estimation for SDM self-homodyne coherent systems.

For space division multiplexing self-homodyne coherent systems, we propose a novel digital in-service relative time delay (RTD) estimation method without any additional optoelectronic device. Taking advantage of the frequency-domain periodicity of the colored frequency modulation noise, we manage to find the peak with location reflecting the RTD in its autocorrelation function (ACF). The peak to average ratio is further enhanced by leveraging a low-pass differential finite impulse response filter for robust identification. By simulations, the method is validated to be feasible for various linewidths, formats (16QAM, 32QAM and 64QAM), and links up to 80 km. Particularly, it is proved to be inherently compatible with large-linewidth low-cost lasers for the 10-km link. Also, for a low-complexity implementation, we discuss the way to reduce the number of points used to calculate the ACF while maintaining the same dynamic range. Furthermore, we demonstrate a 50-GBaud 16-QAM experiment to investigate its performances. With received optical power varying from -11 dBm to -17 dBm, 216 points are sufficient to provide an estimation accuracy of standard deviation (STD) less than 0.089 ns for the RTD range of [2.6, 491.0 ns]. The STD can be lowered to 0.036 ns by adopting 218 points. Especially, at -11-dBm ROP, the highest performance has been achieved with an accuracy smaller than the symbol period (0.018-ns STD) and a RTD range of [1.5, 491.0 ns].

Geometric shaping optimization of 64-APSK constellation in discrete nonlinear frequency division multiplexing systems.

We experimentally demonstrated a geometric shaped (GS) 64-ary amplitude phase shift keying (64-APSK) eigenvalue transmission. The signal is modulated on the scatter coefficient of a single eigenvalue and linear minimum mean square error (LMMSE) estimator is used to reduce the noise. The channel response is estimated by transmitting a normally distributed 64-APSK constellation through a communication link. Based on the polar coordinates distribution of the received constellation, the diameter distributions for each circle can be obtained so that circles with larger noise can obtain larger judgment width. After optimization, the experimental results show that the Q-factor gain is 1.13 dB under 22 dB received optical signal to noise ratio (OSNR) configuration and 0.88 dB after 900 km transmission compared with normally distributed APSK configuration.

In-service crosstalk monitoring in multicore fibers based on precoded DMT system.

In-service crosstalk monitoring based on the precoding technique in a discrete multitone (DMT) system is proposed and validated experimentally. The method relies on the ability of time-frequency domain equalization of precoded DMT. Experiments on a 20 GBaud 16 quadrature amplitude modulation DMT system over seven-core weakly coupled multicore fibers (MCFs) are conducted. The inter-core instantaneous average crosstalk (IAXT) is gathered and evaluated in a period as short as 10 µm without disturbing the signal transmission. Such IAXT has a high correlation with the bit error ratio (BER), and a transmission performance evaluation strategy of the MCF transmitting system is developed according to the relationship between IAXT and BER.