Organic fertilizer application promotes the soil nitrogen cycle and plant starch and sucrose metabolism to improve the yield of Pinellia ternata.

Pinellia ternata (Thunb.) Breit is a traditional Chinese medicine with important pharmacological effects. However, its cultivation is challenged by soil degradation following excessive use of chemical fertilizer. We conducted an experiment exploring the effects of replacing chemical fertilizers with organic fertilizers (OF) on the growth and yield of P. ternata, as well as on the soil physicochemical properties and microbial community composition using containerized plants. Six fertilization treatments were evaluated, including control (CK), chemical fertilizer (CF), different proportions of replacing chemical fertilizer with organic fertilizer (OM1-4). Containerized P. ternata plants in each OF treatment had greater growth and yield than the CK and CF treatments while maintaining alkaloid content. The OM3 treatment had the greatest yield among all treatments, with an increase of 42.35% and 44.93% compared to the CK and CF treatments, respectively. OF treatments improved soil quality and fertility by enhancing the activities of soil urease (S-UE) and sucrase (S-SC) enzymes while increasing soil organic matter and trace mineral elements. OF treatments increased bacterial abundance and changed soil community structure. In comparison to the CK microbial groups enriched in OM3 were OLB13, Vicinamibacteraceae, and Blrii41. There were also changes in the abundance of gene transcripts among treatments. The abundance of genes involved in the nitrogen cycle in the OM3 has increased, specifically promoting the transformation of N-NO3- into N-NH4+, a type of nitrogen more easily absorbed by P. ternata. Also, genes involved in "starch and sucrose metabolism" and "plant hormone signal transduction" pathways were positively correlated to P. ternata yield and were upregulated in the OM3 treatment. Overall, OF in P. ternata cultivation is a feasible practice in advancing sustainable agriculture and is potentially profitable in commercial production.

Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17.

BACKGROUND: Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. METHODS: In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. RESULTS: TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1ß (p < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). CONCLUSION: Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

Binding specificities of estrogen receptor with perfluorinated compounds: A cross species comparison.

BACKGROUND: Perfluorinated compounds (PFCs) were reported to result in the endocrine disruption by activating the estrogen receptor (ER) and inducing ER-mediated transcriptions. OBJECTIVE: The aim of the present work was to perform cross-species comparisons on the characteristics of eight PFCs binding to humans ERα and to rats ERα. METHODS: In the present work, in vivo tests, including serum estradiol level assay and immunohistochemical staining, fluorescence assay and molecular models were applied. RESULTS: Based on the in vivo experiments, the exposure of PFOA and PFOS to female rats was proved to increase the ERα expression in the terus, suggesting that PFCs may act as estrogenic compounds to activate ERα in vivo. The further fluorescence assay presented that these eight PFCs have stronger binding abilities to human ERα than to rat ERα. In addition, the differences in binding specificities between human ERα and rat ERα were identified in the process of molecular dynamics modeling with the term of helix position and the ability of coregulator recruitment. It can be found that more and stronger charge clamps could form between PFCs with human ERα than with rat ERα. Also, the eight PFCs presented lower binding energies in human ERα systems, which proved that eight PFCs presented much stronger binding abilities with human ERα. DISCUSSION: In all, it can be concluded that PFCs might be more sensitive to human ERα than to that of rats, which also suggested the greater susceptibility to adverse effects on humans. The present work was a beginning assessment of a cross-species comparison, providing important information on health impacts of PFCs in humans.

Perfluorinated compounds binding to estrogen receptor of different species: a molecular dynamic modeling.

Perfluorinated compounds (PFCs) were widely utilized in commercial and industrial applications, which could interfere with the endocrine systems of experimental animals and humans by interacting with estrogen receptors (ERs). Considering the possible differential binding preferences and relative binding affinities of PFCs to ERs of humans and other species, a cross-species comparison is necessary to effectively assess the health risk of PFCs to humans. In the present work, the species-specific binding characterizations between two PFCs, including perfluorooctane sulfonate (PFOS) and PFOS(4m, 5m), and the different ERαs from Rattus norvegicus, rainbow trout, and humans were explored based on a molecular dynamic modeling. The results proved that linear perfluorinated compound PFOS could make a much stronger binding to ERαs than the branched perfluorinated compounds PFOS(4m, 5m). In addition, PFOS and PFOS(4m, 5m) presented species-difference among human, Rattus norvegicus, and rainbow trout. The binding affinity with ERα presented an order of human >Rattus norvegicus > rainbow trout. This suggested that PFOS and PFOS(4m, 5m) have the strongest effects on human ERα over the other two species. As a consequence, the PFCs were more sensitive to human ERα than to those of Rattus norvegicus and rainbow trout. This resulted in greater susceptibility to adverse effects, which suggested a possible underestimation of the endocrine-disrupting effects of PFCs in humans. The cross-species comparison represents the first and necessary step to identify species-specific binding mechanisms and to accurately evaluate the potential health risks of PFCs in humans.

Bisphenol A (BPA) binding on full-length architectures of estrogen receptor.

Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full-length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen-like toxicity of BPA. In the present work, the consequence of BPA on full-length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi-domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full-length ER structure was dependent on long-range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue-residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full-size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen-like toxicity upon BPA binding with full-length ER.

SNP mutations occurring in thyroid hormone receptor influenced individual susceptibility to triiodothyronine: Molecular dynamics and site-directed mutagenesis approaches.

The increasing evidences have suggested that expression of single nucleotide polymorphisms (SNP) coded thyroid hormone receptors (THR) generally are associated with individual susceptibility to chemicals. In the present research, multiple molecular dynamics simulations on four SNP mutants (G332R, T337Δ, G345R, and G347E) were performed to investigate the structural and dynamical altering, which could lead to a binding capability variation to triiodothyronine (T3). It proved the structures of two SNP mutants (G345R and T337Δ) occurring in the THR proteins had experienced conformational change to a great extend, which also led to a significant decreasing in binding ability with T3. In addition, two mutates (G345R and G347E) and wild type THR proteins were expressed and purified based on site-directed mutagenesis technology to test their binding abilities with T3 by fluorescence experiments. The fluorescence quenching efficiencies of two mutates displayed that the conjugation with T3 decreased with a significant rate in G345R system and a little rate in G347E system compared with its wild type. It was consistent with the molecular dynamic research that the SNP mutations did change structures of THR protein, and thereby decreased the binding behavior of T3 at different extent. The overall molecular-level look at the protein structure may provide the structural basis to explain how one amino acid change can create a ripple effect on the protein structures and eventually affect the binding affinity of the ligands, which maybe the first stage to understand how SNP mutation results in individual difference in susceptibility to variant chemicals.