Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

Rose long noncoding RNA lncWD83 promotes flowering by modulating ubiquitination of the floral repressor RcMYC2L.

Long noncoding RNAs (lncRNAs) play important roles in various signaling pathways in vascular plants. However, the crosstalk between lncRNAs and E3 ubiquitin ligases has been barely reported. In this study, we demonstrate that the lncRNA lncWD83 from rose (Rosa chinensis) 'Old blush' activates flowering by modulating the ubiquitination of the floral repressor MYC2 LIKE (RcMYC2L). Flowering was substantially delayed in rose by virus-induced gene silencing of lncWD83. In an in vitro pull-down assay, lncWD83 associated with PLANT U-BOX PROTEIN 11 (PUB11), a U-box-containing E3 ubiquitin ligase. Seedlings with knocked down RcPUB11 transcripts phenocopied the later-flowering phenotype of lncWD83-silenced seedlings. RcMYC2L physically interacted with RcPUB11 and was ubiquitinated in an RcPUB11-dependent manner in vitro. Accordingly, silencing RcMYC2L fully reversed the later-flowering phenotype resulting from RcPUB11 knockdown. Furthermore, RcMYC2L bound to G-box-related motifs in the FLOWERING LOCUS T (RcFT) promoter and repressed its transcription. However, RcPUB11 alleviated this repression of RcFT expression via proteasomal degradation of RcMYC2L, and lncWD83 enhanced this degradation by associating with RcPUB11. Therefore, lncWD83 promotes flowering by modulating the ubiquitination of the floral repressor RcMYC2L in rose plants. These findings reveal a distinct regulatory mechanism for an lncRNA in facilitating ubiquitin-mediated proteolysis to regulate rose flowering.

Lake warming intensifies the seasonal pattern of internal nutrient cycling in the eutrophic lake and potential impacts on algal blooms.

Lake warming induced by climate change has constituted a particular challenge for the restoration of eutrophic lakes. However, a quantitative analysis about impacts of lake warming on the internal nutrient cycling in eutrophic lakes is limited. In this study, monthly nutrient monitoring data set in 2015-2016 in eutrophic Lake Chaohu, China, revealed a regular seasonal pattern of nutrient concentration. A process-based water quality model was established to quantify contributions from internal loadings on seasonal nutrient variations and predict responses under climate change scenarios. Results indicated that internal nutrient loading was responsible for the intra-annual variations of nutrient concentrations in the lake, and the internal loadings fluctuated much more between different seasons than the external nutrient inputs. We predicted that lake warming might probably result in stronger seasonal fluctuations of internal loading and create conditions beneficial for longer duration of cyanobacteria blooms in the year. Evidence derived from this study could help water managers to rethink the existing mitigation strategies in the restoration of eutrophic lakes and emphasize the potential interactions among lake warming, eutrophication and internal nutrient cycling in the future.

Factors related to antibiotic-associated diarrhea in patients in the intensive care unit receiving antifungals: a single-center retrospective study.

OBJECTIVE: To analyze factors related to antibiotic-associated diarrhea (AAD) in patients in the intensive care unit (ICU) receiving antifungals with the aim of informing rational antibiotic use. METHODS: Sex, age, medical history, use of proton pump inhibitors, administration of parenteral nutrition, albumin level, occurrence of AAD, type of antibiotics, duration of ICU admission, and prognosis were retrospectively analyzed. The associations of age, sex, medical history, and other factors with AAD were associated by logistic regression. RESULTS: In total, 284 patients were enrolled (antifungals, n = 110; no antifungals, n = 174). The total incidence of AAD was 32.39%. The incidence of AAD was significantly different between the groups (52.73% vs. 19.54%). The duration of proton pump inhibitor therapy, duration of antifungal therapy, enzyme inhibitor antibiotic use, and azithromycin use were associated with AAD in ICU patients receiving antifungal therapy. The mean duration of ICU admission was higher in patients receiving antifungal therapy (20.14 ± 11.50 vs. 14.48 ± 8.54 days). There was no significant difference in ICU mortality rates. CONCLUSION: The duration of proton pump inhibitor therapy, duration of antifungal therapy, use of enzyme inhibitor antibiotics, and use of azithromycins were associated with AAD in ICU patients receiving antifungal therapy.

Risk Factors for Antibiotic-Associated Diarrhea in Critically Ill Patients.

BACKGROUND We analyzed the factors related to AAD to inform the rational use of antibiotics in critically ill patients and to reduce the incidence of AAD by providing a reference for antibiotic use in the clinical setting. MATERIAL AND METHODS This study was a retrospective analysis of the clinical data of patients who were hospitalized in the ICU of the First Teaching Hospital of Xi'an Jiaotong University from January 1, 2015 to December 31, 2016. Patients with AAD were assigned to the case group, and all others were assigned to the control group. Basic data were collected for all the selected patients. All the relevant data were analyzed with univariate or multivariate regression analyses, and P<0.05 was considered statistical significance. RESULTS A total of 293 patients were enrolled. Statistical analyses showed that gender (OR 1.915; 95% [CI] 1.061-3.455; P=0.031), parenteral nutrition (OR 1.877; 95% [CI] 1.043-3.377; P=0.036), preventive use of probiotics (OR 0.497; 95% [CI] 0.285-0.866; P=0.014), APACHE II score upon admission to the ICU (OR 0.961; 95% [CI] 0.927-0.998; P=0.037) and use of enzyme-inhibitor antibiotics (OR 1.899; 95% [CI] 1.044-3.420; P=0.016) were associated with AAD. Further subgroup analysis by gender showed that parenteral nutrition (OR 2.144; 95% [CI] 1.064-4.322; P=0.033), preventive use of probiotics (OR 0.367; 95% [CI] 0.186-0.722; P=0.004), and APACHE II score upon admission to the ICU (OR 1.055; 95% [CI] 1.011-1.101; P=0.014) were associated with AAD in critically ill male patients. Age (OR 0.975; 95% [CI] 0.951-0.999; P=0.041) and use of carbapenem antibiotics (OR 4.826; 95% [CI] 1.011-23.030; P=0.048) were associated with AAD in critically ill female patients. CONCLUSIONS Parenteral nutrition, prophylactic use of probiotics, use of enzyme-inhibitor antibiotics, and use of combinations of antibiotics were associated with AAD in critically ill patients. The prophylactic use of probiotics may be a protective factor in AAD.

[Treated dentin matrix enhances proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells].

OBJECTIVE: The effect of treated dentin matrix (TDM) to the proliferation and osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) is evaluated in vitro. METHODS: TDM leaching solution was prepared by dentine particles suffering from gradient demineralization. Human BMSCs were isolated and cultivated, and subsequently cultivated in the TDM leaching solution. The proliferation of BMSCs was detected by CCK-8. The osteogenesis-related proteins, including collagen type I (Col I) and runt-related transcription factor-2 (Runx2), were extracted and detected by Western blot after a 7-day culture. RESULTS: Compared with the control group and hydroxyapatite (HA)/ß-tricalcium phosphate (ßTCP) group, the proliferation of BMSCs cultivated in TDM leaching solution was significantly improved. The expression of Col I and Runx2 obviously increased after the 7-day cultivation in TDM leaching solution. CONCLUSION: TDM can promote the proliferation and osteogenesis differentiation of BMSCs, implying the feasibility of the application in bone tissue engineering.