Evaluation of three prevalent global riverine nutrient transport models.

Global riverine nitrogen (N) and phosphorus (P) transport models offer important insights into basin nutrient cycling. However, appropriate model selection for a given research objective remains ambiguous. This study conducted a meta-analysis to evaluate the performance and applicability of three prevalent global riverine nutrient transport models: Global NEWS, IMAGE-GNM, and WorldQual. According to performance criteria (satisfactory: R2 > 0.50 and NSE > 0.50), the Global NEWS model performs satisfactorily in simulating dissolved organic nitrogen (DON; n = 101, R2 = 0.58, NSE = 0.57) and dissolved organic phosphorus loads (DOP; n = 80, R2 = 0.59, NSE = 0.59). The model falls short in simulating dissolved inorganic nitrogen (DIN; n = 644, R2 = 0.56, NSE = - 0.80) and dissolved inorganic phosphorus loads (DIP; n = 450, R2 = 0.33, NSE = - 0.12). The IMAGE-GNM model shows satisfactory accuracies in simulating riverine total nitrogen (TN; n = 831, R2 = 0.56, NSE = 0.53) and total phosphorus (TP; n = 902, R2 = 0.59, NSE = 0.48) concentrations, particularly in European basins. The WorldQual model presented unsatisfactory performance in simulating riverine TN (n = 11, R2 = 0.76, NSE = 0.34) and TP (n = 13, R2 = 0.71, NSE = - 0.25) concentrations. Using a two-segment linear model, we recommend the Global NEWS model for basins larger than 2.2 × 104 km2 for DIN and 3.2 × 104 km2 for DIP. The IMAGE-GNM model is best suited for basins with long-term datasets and high latitudes (TN > 21 years and > 53.8 °N; TP > 22 years and > 54.5 °N). For model improvements, both the Global NEWS and WorldQual models could benefit from enhanced in-stream nutrient retention/release modules. The Global NEWS model could be further improved with a better chemical weathering module. For the IMAGE-GNM model, refining the soil erosion module is warranted to enhance model performance. Addressing legacy nutrient effects is crucial for all three models. This study provides valuable guidance for selecting and improving nutrient transport models based on specific research needs.

Nano-composite system of traditional Chinese medicine for ocular applications: molecular docking and three-dimensional modeling insight for intelligent drug evaluation.

The absorption of drugs was impeded in the posterior part of the eye due to the special structure. In addition, it was crucial to comprehend transport laws of molecules in ocular drug delivery for designing effective strategies. However, the current quality evaluation methods of the eye were backward and lack of dynamic monitoring of drug processes in vivo. Herein, nano-drug delivery system and three-dimensional (3D) model were combined to overcome the problems of low bioavailability and diffusion law. The model drugs were screened by molecular docking. The flexible nano-liposome (FNL) and temperature-sensitive gel (TSG) composite formulation was characterized through comprehensive evaluation. COMSOL software was utilized to build 3D eyeball to predict the bioavailability of drugs. The size of the preparation was about 98.34 nm which is relatively optimal for the enhanced permeability of the eyes. The formulation showed a stronger safety and non-irritant. The pharmacokinetics results of aqueous humor showed that the AUC of two drugs in this system increased by 3.79 and 3.94 times, respectively. The results of 3D calculation model proved that the concentrations of drugs reaching the retina were 1.90×10-5 mol/m3 and 6.37×10-6 mol/m3. In conclusion, the FNL-TSG markedly improved the bioavailability of multiple components in the eye. More importantly, a simplified 3D model was developed to preliminarily forecast the bioavailability of the retina after drug infusion, providing technical support for the accurate evaluation of ocular drug delivery. It provided new pattern for the development of intelligent versatile ophthalmic preparations.

An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

A Comprehensive Review of Pharmacokinetics and Pharmacodynamics in Animals: Exploration of Interaction with Antibiotics of Shuang-Huang- Lian Preparations.

As a traditional Chinese medicine (TCM), Shuang-Huang-Lian (SHL) has been widely used for treating infectious diseases of the respiratory tract such as encephalitis, pneumonia, and asthma. During the past few decades, considerable research has focused on pharmacological action, pharmacokinetic interaction with antibiotics, and clinical applications of SHL. A huge and more recent body of pharmacokinetic studies support the combination of SHL and antibiotics have different effects such as antagonism and synergism. SHL has been one of the best-selling TCM products. However, there is no systematic review of SHL preparations, ranging from protection against respiratory tract infections to interaction with antibiotics. Since their important significance in clinical therapy, the pharmacodynamics, pharmacokinetics, and interactions with antibiotics of SHL were reviewed and discussed. In addition, this review attempts to explore the possible potential mechanism of SHL preparations in the prevention and treatment of COVID-19. We are concerned about the effects of SHL against viruses and bacteria, as well as its interactions with antibiotics in an attempt to provide a new strategy for expanding the clinical research and medication of SHL preparations.

A strategy based on gene sequencing and molecular docking for analysis and prediction of bioactive peptides in Shuxuetong injection.

Peptides are a class of protein fragments with relatively high biological activity and intense specificity, which play crucial role in the treatment of Shuxuetong injection (SXT). However, the extraordinary complexity of Chinese medicinal formulates and the lack of systematic identification methods are primary challenges for study of pharmacodynamic peptides. In addition, infinitesimal peptides contents further hinder the identification and structural characterization of polypeptide by traditional means. In this paper, we described a strategy that LC-MS combined with molecular docking to systematically illustrate the peptide components of SXT. The key to this research was used of gene sequencing to establish a SXT protein database to further achieve the separation and enrichment of chemical methods. Moreover, the ADRA2A, PAR4 and DRD3 were precisely docked with the identified peptides. The result indicated that 12 compounds had stable binding ability and were speculated to be the latent bioactive monomers for the treatment of stroke. Additionally, 12 peptides were verified by cell-based experiment. The results showed that only YLKTT could indeed protect astrocytes from oxygen glucose deprivation/reoxygenation (OGD/R). The YLKTT showed higher activity than the others in vitro. It might be a completely new compound that has never been reported before, providing the basis for further research and a new paradigm for stroke.

Study on the Mechanism of Prunella Vulgaris L on Diabetes Mellitus Complicated with Hypertension Based on Network Pharmacology and Molecular Docking Analyses.

The role of traditional Chinese medicine Prunella vulagaris L in the treatment of tumors and inflammation has been widely confirmed. We found that some signaling pathways of Prunella vulgaris L action can also regulate diabetes and hypertension, so we decided to study the active ingredients, potential targets and signaling pathway of Prunrlla vulgaris L, and explore the "multi-target, multi-pathway" molecular mechanism of Prunella vulgaris L on diabetes mellitus complicated with hypertension(DH). Methods. Based on TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and CNKI(China National Knowledge Infrastructure), the components and action targets related to Prunella vulgaris L were screened. The OMIM(Online Mendelian Inheritance in Man) and GeneCards (The human gene database) were used to search for targets related to DH. The "gene - drug - disease" relationship map was drawn by Cytoscape_v3.7.2 plug-in. The target was amplified by the STRING platform, and the "protein - protein" interaction relationship (PPI) network of the interacting target was obtained by the STRING online analysis platform and the Cytoscape_v3.7.2 plug-in. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were conducted on David and Metascape platform to study the co-acting targets. Results. 11 active components, 41 key targets and 16 significant signaling pathways were identified from Prunella vulgaris L. The main active components of Prunella vulgaris L against DH were quercetin and kaumferol, etc, and potential action targets were IL-6 and INS, etc and signaling pathways were AGE-RAGE signaling pathway, TNF signaling pathway, MAPK signaling pathway, PI3K-AKT signaling pathway, etc. It involves in biological processes such as cell proliferation, apoptosis and inflammatory response. Conclusions. The main molecular mechanism of Prunella vulgaris L against DH is that sterols and flavonoids play an active role by affecting TNF signaling pathway, AGE-RAGE signaling pathway, MAPK pathway, PI3K-Akt pathway related targets such as IL-6 and INS.

A comprehensive application: Molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine.

Traditional Chinese medicine (TCM) has been used for more than 2000 years in China. TCM has received wide attention recently due to its unique charm. At the same time, its main obstacles have attracted wide attention, including vagueness of drug composition and treatment mechanism. With the development of virtual screening technology, more and more Chinese medicine compounds have been studied to discover the potential active components and mechanisms of action. Molecular docking is a computer technology based on structural design. Network pharmacology establishes powerful and comprehensive databases to understand the relationship between TCM and disease network. In this review, emergent uses and applications of two techniques and further superiorities of the two techniques when embarked to boil down into a tidy system were illustrated. A combination of the two provides a theoretical basis and technical support for the construction of modern TCM based on the compatibility of components and accelerates the realization of two basic elements as well, including the clearness of the pharmacodynamic substances and explanation of the effect of TCM.

Advances in Pharmacological Actions and Mechanisms of Flavonoids from Traditional Chinese Medicine in Treating Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high morbidity and mortality. The conventional therapies remain palliative and have various undesired effects. Flavonoids from traditional Chinese medicine (TCM) have been proved to exert protective effects on COPD. This review aims to illuminate the poly-pharmacological properties of flavonoids in treating COPD based on laboratory evidences and clinical data and points out possible molecular mechanisms. Animal/laboratory studies and randomised clinical trials about administration of flavonoids from TCM for treating COPD from January 2010 to October 2020 were identified and collected, with the following terms: chronic obstructive pulmonary disease or chronic respiratory disease or inflammatory lung disease, and flavonoid or nature product or traditional Chinese medicine. Pharmacokinetic studies and external application treatment were excluded. A total of 15 flavonoid compounds were listed. Flavonoids could inhibit inflammation, oxidative stress, and cellular senescence, restore corticosteroid sensitivity, improve pulmonary histology, and boost pulmonary function through regulating multiple targets and signaling pathways, which manifest that flavonoids are a group of promising natural products for COPD. Nevertheless, most studies remain in the research phase of animal testing, and further clinical applications should be carried out.