Dissection of action mechanisms of Zuogui Pill in the treatment of liver cancer based on machine learning and network pharmacology: A review.

This study aimed to investigate the underlying mechanism of Zuogui Pill in its efficacy against liver cancer, employing a combination of data mining approaches and network pharmacology methods. A novel clustering analysis algorithm was proposed to identify the core gene modules of Zuogui Pill. This algorithm successfully identified 5 core modules, with the first large module comprised of twelve proteins forming a 12-clique, representing the strongest connections among them. By utilizing GEO platform, ten key target proteins were detected, including FOS, PTGS2, and MYC. According to the GO annotation and KEGG analysis, desired target proteins were significantly enriched in various biological processes (BP). The analysis showed that ten key targets were strongly associated with signaling pathways mainly centered on MAPK and PI3K-Akt pathway. Additionally, molecular docking revealed strong binding affinities between core active ingredients of Zuogui Pill and these key targets, and the best affinity modes were observed for PTGS2-Sesamin, PRKCA-Sesamin, FOS-delta-Carotene. In order to establish the relationships between clinical symptoms and drug targets, a heterogeneous targets-related network was constructed. A total of 60 key target-symptom association pairs were detected, exemplified by the strongly association between fever and PTGS2 through the intermediary of Shu Di Huang. In summary, symptom-target associations are valuable in uncovering the underlying molecular mechanisms of Zuogui Pill. Our work reinforced the notion that Zuogui pill exhibits therapeutic potential on liver cancer through network targets, as well as synergistic effects of multi-component and multi-pathway. This study provided specific references for future experiments at the cost of less time.

CRISPR/Cas9-Based Knock-Out of the PMR4 Gene Reduces Susceptibility to Late Blight in Two Tomato Cultivars.

Phytophthora infestans, the causal agent of late blight (LB) in tomato (Solanum lycopersicum L.), is a devastating disease and a serious concern for plant productivity. The presence of susceptibility (S) genes in plants facilitates pathogen proliferation; thus, disabling these genes may help provide a broad-spectrum and durable type of tolerance/resistance. Previous studies on Arabidopsis and tomato have highlighted that knock-out mutants of the PMR4 susceptibility gene are tolerant to powdery mildew. Moreover, PMR4 knock-down in potato has been shown to confer tolerance to LB. To verify the same effect in tomato in the present study, a CRISPR-Cas9 vector containing four single guide RNAs (sgRNAs: sgRNA1, sgRNA6, sgRNA7, and sgRNA8), targeting as many SlPMR4 regions, was introduced via Agrobacterium-tumefaciens-mediated transformation into two widely grown Italian tomato cultivars: 'San Marzano' (SM) and 'Oxheart' (OX). Thirty-five plants (twenty-six SM and nine OX) were selected and screened to identify the CRISPR/Cas9-induced mutations. The different sgRNAs caused mutation frequencies ranging from 22.1 to 100% and alternatively precise insertions (sgRNA6) or deletions (sgRNA7, sgRNA1, and sgRNA8). Notably, sgRNA7 induced in seven SM genotypes a -7 bp deletion in the homozygous status, whereas sgRNA8 led to the production of fifteen SM genotypes with a biallelic mutation (-7 bp and -2 bp). Selected edited lines were inoculated with P. infestans, and four of them, fully knocked out at the PMR4 locus, showed reduced disease symptoms (reduction in susceptibility from 55 to 80%) compared to control plants. The four SM lines were sequenced using Illumina whole-genome sequencing for deeper characterization without exhibiting any evidence of mutations in the candidate off-target regions. Our results showed, for the first time, a reduced susceptibility to Phytophtora infestans in pmr4 tomato mutants confirming the role of KO PMR4 in providing broad-spectrum protection against pathogens.

Improvement of gel properties and digestibility of the water-soluble polymer of tea polyphenol-egg white under thermal treatment.

In this study, the improvement of gel properties and digestibility of the water-soluble polymer of tea polyphenol (TP)-egg white protein (TEP) under heat induction (HTEP), was studied. Results indicated that the particle size and turbidity of TEP increased with TP concentration, and the absolute value of ζ-potential decreased. After heat induction, the surface hydrophobicity of HTEP decreased with TP concentration, and the degree of protein aggregation increased. Microstructure and T2 showed that the gel structure became compact and stable, and HTEP had a strong water-binding ability. The ionic and disulfide bonds were the main chemical bonds in HTEP. The hardness and disulfide bond increased, but the digestion of HTEP increased initially and then decreased (caused by the change of gel structure). Infrared spectroscopy indicated the mutual conversion of intermolecular and intramolecular ß-sheets. In short, TP could modify egg white gel through forming stable disulfide bonds and dense gel network structures.

The roles of phosphorus species formed in activated biochar from rice husk in the treatment of landfill leachate.

Untreated landfill leachate is a threat to the environment. Here, the phosphoric acid activated biochars prepared from rice husk were successfully used for leachate treatment to achieve a high removal of color (100%), pollutants (>90%), chemical oxygen demand (∼80%) and NH4+-N (100%). The leachate treatment process on phosphoric acid activated biochar could be well described by the pseudo-second order and Langmuir isotherm model, and it was controlled by external mass transfer followed by intra-particle diffusion. The phosphorus species formed in activated biochar could adjust and control the textural properties and structures of biochar, while the phosphorus species of activated biochar could attract humic acid-like organics in the leachate via hydrogen bond and π-π interactions, which were found to significantly enhance the treatment of leachate. The findings provided important insights for efficient treatment of wastewater using agricultural waste residues on an industrial scale.

[Rainfall intensity effects on nutrients transport in surface runoff from farmlands in gentle slope hilly area of Taihu Lake Basin].

To investigate the effect of rainfall on agricultural nonpoint source pollution, watershed scale experiments were conducted to study the characteristics of nutrients in surface runoff under different rainfall intensities from farmlands in gentle slope hilly areas around Taihu Lake. Rainfall intensity significantly affected N and P concentrations in runoff. Rainfall intensity was positively related to TP, PO4(3-) -P and NH4+ -N event mean concentrations(EMC). However, this study have found the EMC of TN and NO3- -N to be positively related to rainfall intensity under light rain and negatively related to rainfall intensity under heavy rain. TN and TP site mean amounts (SMA) in runoff were positively related to rainfall intensity and were 1.91, 311.83, 127.65, 731.69 g/hm2 and 0.04, 7.77, 2.99, 32.02 g/hm2 with rainfall applied under light rain, moderate rain, heavy rain and rainstorm respectively. N in runoff was mainly NO3- -N and NH4+ -N and was primarily in dissolved form from Meilin soils. Dissolved P (DP) was the dominant form of TP under light rain, but particulate P (PP) mass loss increased with the increase of rainfall intensity and to be the dominant form when the rainfall intensity reaches rainstorm. Single relationships were used to describe the dependence of TN and TP mass losses in runoff on rainfall, maximum rainfall intensity, average rainfall intensity and rainfall duration respectively. The results showed a significant positive correlation between TN mass loss and rainfall, maximum rainfall intensity respectively (p < 0.01) and also TP mass loss and rainfall, maximum rainfall intensity respectively (p < 0.01).

Angelica injection improves functional recovery and motoneuron maintenance with increased expression of brain derived neurotrophic factor and nerve growth factor.

This study assessed the neuroprotective effects of angelica injection in the rat sciatic nerve crush injury (SCI). Forty eight male Sprague Dawley rats were randomly divided into 4 groups: one was the sham group (S), which received sham surgery and given saline injection and the others were received SCI surgery and given saline injection, high and low dose angelica injection for 4 weeks, respectively. The sciatic functional index (SFI) in walking-track analysis, conductive velocity (CV), the number of fluorogold labeled motoneurons, and the expression patterns of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the sciatic nerve and spine were examined. The results showed that SFI descended gradually on day 7, and dropped more quickly on day 28 in treatment groups (Low and High dose group). The CV in treatment groups was higher than control group (C). The numbers of motoneurons in treatment groups were larger than C group (P<0.05), but less than that in S group (P<0.01). The expressions of BDNF and NGF protein in the groups received SCI surgery were significantly lower than in S group, but the protein expressions in the groups received angelica injections were significantly higher than that in C group (P<0.01). These findings suggested that angelica injection can improve the sciatic nerve crush injury, and the mechanism might be through the increase of BDNF and NGF protein expression.