A Potential Fungicide against Pseudoperonospora Cubensis: Design, Synthesis and 3D-QSAR of New Pyrazole-5-Carboxamide Derivatives.

BACKGROUND: Downy mildew is one of the major fungi causing significant economic losses to crops. The resistance of this fungus to current fungicides is increasing and new fungicides with a unique mode of action are needed. OBJECTIVE: To find a novel pyrazole amide derivative as a potential fungicide. METHODS: A series of pyrazole-5-carboxamide derivatives containing a diaryl ether were designed and synthesized by the Intermediate derivatization method (IDM). Their fungicidal activities against Pseudoperonospora cubensis (P. cubensis, cucumber downy mildew) were evaluated in the greenhouse. RESULTS: Bioassays indicated that several compounds exhibited excellent fungicidal activity against P. cubensis in vivo. In particular, T24 (EC50 = 0.88 mg L-1) had the highest activity compared with Dimethomorph and Fluazinam and other analogues. The relationship between the activity and the structure of these derivatives was analyzed, and an accurate and reliable three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established to determine that electrostatic and steric fields had important effects on the improvement of fungicidal activity. CONCLUSION: The novel pyrazole-5-carboxamide derivative T24 can be considered a potential fungicide for P. cubensis control.

Preparation and characterization of astaxanthin-loaded microcapsules and its application in effervescent tablets.

BACKGROUND: Astaxanthin is a type of keto-carotene with potential health benefits. However, astaxanthin has poor solubility and stability, resulting in its low oral bio-availability. Microcapsules can be used to improve the water solubility, stability and oral bio-availability of lipophilic bioactive compounds. Effervescent tablets can further improve the stability, smell and taste of microcapsules, and are more easily accepted by consumers. RESULTS: Astaxanthin-loaded microcapsules were prepared by layer-by-layer assembly and freeze-drying technologies. Sodium caseinate and κ-carrageenan were applied as wall materials. The prepared microcapsules had good flow properties and encapsulation efficiencies (> 85%). Fourier transform infrared spectroscopy demonstrated that the mechanisms of layer-by-layer self-assembly between sodium caseinate and κ-carrageenan might be electrostatic adsorption and hydrogen bonding. The preparation process and excipients did not affect the antioxidant effect of astaxanthin. The in vitro simulated digestion study showed that microcapsules were mainly dissolved and digested in the simulated intestinal solution. Compared with its raw material, microencapsulation could improve the bio-accessibility of astaxanthin greatly. Then, astaxanthin-loaded microcapsules were incorporated into effervescent tablets by wet granulation and tablet-pressing methods. The dissolution of astaxanthin from effervescent tablets was over 90% in 2 h, which indicated a good dissolution effect. A cytotoxicity study revealed that astaxanthin loaded effervescent tablets had a good biocompatibility. Encapsulating astaxanthin-loaded microcapsules in effervescent tablets can improve its chemical stability. CONCLUSION: Effervescent tablets containing microcapsules could be used to improve the solubility, stability and bio-accessibility of lipophilic bioactive compounds. © 2022 Society of Chemical Industry.

Plasma miR-125a and miR-125b in sepsis: Correlation with disease risk, inflammation, severity, and prognosis.

OBJECTIVE: This study aimed to explore the predictive value of microRNA (miR)-125a and miR-125b for sepsis risk, and their correlations with inflammation, disease severity, and 28-day mortality in sepsis patients. METHODS: Totally, 150 sepsis patients and 150 healthy controls (HCs) were enrolled. Plasma samples were separated from blood samples obtained from sepsis patients and HCs to detect miR-125a and miR-125b expressions by real-time quantitative polymerase chain reaction. Besides, the 28-day mortality of sepsis patients was assessed. MiR-125a and miR-125b expressions were elevated in sepsis patients compared with HCs, and further receiver operating characteristics (ROC) curve analysis displayed that miR-125a (area under the curve (AUC): 0.749, 95% CI: 0.695-0.803) and miR-125b (AUC: 0.839, 95% CI: 0.795-0.882) could predict sepsis risk. As for inflammation, no correlation of miR-125a with C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-17, and IL-23 was observed in sepsis patients, while miR-125b was positively associated with CRP, TNF-α, IL-6, IL-17, and IL-23. Regarding disease severity, miR-125a and miR-125b were positively correlated with acute physiology and chronic health care evaluation II and sequential organ failure assessment score in sepsis patients. Besides, ROC curve analysis exhibited that miR-125a failed to predict 28-day mortality risk (AUC: 0.588, 95% CI: 0.491-0.685) in sepsis patients, while miR-125b had a potential value in predicting elevated 28-day mortality risk (AUC: 0.699, 95% CI: 0.603-0.795). CONCLUSION: Both miR-125a and miR-125b predict sepsis risk, while only miR-125b exhibits the potency for disease management and prognosis prediction in sepsis patients.

Correlation of microRNA-125a/b with acute respiratory distress syndrome risk and prognosis in sepsis patients.

OBJECTIVE: This study was conducted to explore the association of microRNA (miR)-125a and miR-125b with acute respiratory distress syndrome (ARDS) risk and to investigate their correlation with clinical characteristics and prognosis in sepsis patients. METHODS: Totally 150 sepsis patients admitted to our hospital were consecutively enrolled and another 150 healthy subjects were enrolled as healthy controls (HCs). Their blood samples were collected for miR-125a and miR-125b detection by real-time quantitative polymerase chain reaction. Besides, ARDS occurrence and 28-day mortality were documented in all sepsis patients. RESULTS: MiR-125a and miR-125b relative expressions were increased in ARDS-sepsis patients/non-ARDS-sepsis patients compared with HCs, while only miR-125b but not miR-125a was elevated in ARDS-sepsis patients compared with non-ARDS-sepsis patients. Receiver operating characteristic (ROC) curve presented that miR-125a (AUC: 0.650, 95%CI: 0.549-0.750) and miR-125b (AUC: 0.739, 95%CI: 0.653-0.823) could differentiate ARDS-sepsis patients from non-ARDS-sepsis patients, and miR-125b was of increased predictive value compared with miR-125a numerically. In sepsis patients, miR-125a relative expression was positively associated with serum creatinine (Scr), chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and miR-125b was positively associated with Scr, C-reactive protein (CRP), APACHE II score, SOFA score, and chronic obstructive pulmonary disease. All sepsis patients were categorized into survivors and deaths according to 28-day mortality, and miR-125b but not miR-125a was upregulated in deaths compared with survivors. CONCLUSION: Both of miR-125a and miR-125b predict ARDS risk, while only miR-125b is of value in prognosis prediction in sepsis patients.

Discovery of a New Fungicide Candidate through Lead Optimization of Pyrimidinamine Derivatives and Its Activity against Cucumber Downy Mildew.

Downy mildew is one of the most highly destructive of the diseases that cause damage to fruits and vegetables. Because of the continual development of resistance, it is important to discover new fungicides with different modes of action from existing fungicides for the control of downy mildew. This study is a continuation of our previous work on the novel pyrimidinamine lead compound, 9, and includes field trials for the identification of the optimal candidate. A new compound, 1c, was obtained, which gave a lower EC50 value (0.10 mg/L) against downy mildew than lead compound 9 (0.19 mg/L) and the commercial fungicides diflumetorim, dimethomorph, and cyazofamid (1.01-23.06 mg/L). Compound 1c displayed similar broad-spectrum fungicidal activity to compound 9 but better field efficacy than compound 9, cyazofamid, and flumorph. The present work indicates that pyrimidinamine compound 1c is a candidate for further development as a commercial fungicide for the control of downy mildew.