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The trunk canker caused by Botryosphaeria dothidea is a devastating disease for Chinese hickory (Carya cathayensis) in China. Chemical fungicides are commonly and repeatedly applied to control the disease; however, fungicide application raises major environmental and food safety issues. Ecofriendly biocontrol alternatives were urgently needed. Herein, the antifungal activity of a natural secondary metabolite, rapamycin, against B. dothidea and the effect of a rapamycin-producing Streptomyces hygroscopicus on C. cathayensis canker were investigated.

The 50% effective concentrations (EC

) of rapamycin against mycelial growth and spore germination on the potato dextrose agar were 5.1 × 10

and 5.5× 10

μg mL

, respectively, which were much lower than the EC

values of thiophanate-methyl. The hyphae of B. dothidea exhibited premature aging and wrinkling after treatment with rapamycin at 5.0 × 10

μg mL

. A rapamycin-producing bacterium S. LY 3200882 chemical structure hygroscopicus LYJ637 was batch produced and formulated in a carboxymethylcellulose/poly (vinyl alcohol) (CMC/PVA) blend and used for testing the efficiency of the bacterium in controlling Botryosphaeria canker in C. cathayensis. S. hygroscopicus exhibited high stability in the CMC/PVA blend. Results of a 3-year field experiment suggested that rapamycin formation reduced the occurrence of both developed cankers and new cankers, with an efficacy comparable to the treatment with thiophanate-methyl.

The rapamycin-producing S. hygroscopicus LYJ637 carried in a CMC/PVA blend prevented effectively Botryosphaeria canker on Chinese hickory, which provides an alternative approach to chemical control strategies.

The rapamycin-producing S. hygroscopicus LYJ637 carried in a CMC/PVA blend prevented effectively Botryosphaeria canker on Chinese hickory, which provides an alternative approach to chemical control strategies.

To determine the accuracy of, and agreement among, EEG and aEEG readers' estimation of maturity and a novel computational measure of functional brain age (FBA) in preterm infants.

Seven experts estimated the postmenstrual ages (PMA) in a cohort of recordings from preterm infants using cloud-based review software. The FBA was calculated using a machine learning-based algorithm. Error analysis was used to determine the accuracy of PMA assessments and intraclass correlation (ICC) was used to assess agreement between experts.

EEG recordings from a PMA range 25 to 38weeks were successfully interpreted. In 179 recordings from 62 infants interpreted by all human readers, there was moderate agreement between experts (aEEG ICC=0.724; 95%CI0.658-0.781 and EEG ICC=0.517; 95%CI0.311-0.664). In 149 recordings from 61 infants interpreted by all human readers and the FBA algorithm, random and systematic errors in visual interpretation of PMA were significantly higher than the computational FBA estimate. Tracking of maturation in individual infants showed stable FBA trajectories, but the trajectories of the experts' PMA estimate were more likely to be obscured by random errors. The accuracy of visual interpretation of PMA estimation was compromised by neurodevelopmental outcome for both aEEG and EEG review.

Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.

Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.The chronopharmacology refers to the utilization of physiological circadian rhythms to optimize the administration time of drugs, thus increasing their efficacy and safety, or reducing adverse effects. Simvastatin is one of the most widely prescribed drugs for the treatment of hypercholesterolaemia, hyperlipidemia and coronary artery disease. There are conflicting statements regarding the timing of simvastatin administration, and convincing experimental evidence remains unavailable. Thus, we aimed to examine whether different administration times would influence the efficacy of simvastatin. High-fat diet-fed mice were treated with simvastatin at zeitgeber time 1 (ZT1) or ZT13, respectively, for nine weeks. Simvastatin showed robust anti-hypercholesterolaemia and anti-hyperlipidemia effects on these obese mice, regardless of administration time. However, simvastatin administrated at ZT13, compared to ZT1, was more functional for decreasing serum levels of total cholesterol, triglycerides, non-esterified free fatty acids and LDL cholesterol, as well as improving liver pathological characteristics. In terms of possible mechanisms, we found that simvastatin did not alter the expression of hepatic circadian clock gene in vivo, although it failed to change the period, phase and amplitude of oscillation patterns in Per2Luc U2OS and Bmal1Luc U2OS cells in vitro. In contrast, simvastatin regulated the expression of Hmgcr, Mdr1 and Slco2b1 in a circadian manner, which potentially contributed to the chronopharmacological function of the drug. Taken together, we provide solid evidence to suggest that different administration times affect the lipid-lowering effects of simvastatin.

Conduction defects requiring permanent pacemaker (PPM) implantation are frequent complications occurring after surgical (SAVR) and transcatheter aortic valve replacement (TAVR).

Patients who underwent TAVR or SAVR with a bioprosthesis from the nationwide FinnValve registry were the subjects of this study. Patients with prior PPM, who received a sutureless prosthesis, or required cardiac resynchronization therapy or implantable cardioverter defibrillator were excluded from this analysis.

Four thousand and ten patients underwent SAVR and 1,897 underwent TAVR. TAVR had an increased risk of PPM implantation at 30-day (10.1% vs. 3.5%, unadjusted OR 3.11, 95%CI 2.56-3.87) and 5-year (15.7% vs. 8.6%, unadjusted SHR, 2.12, 95%CI 1.81-2.48) compared to SAVR. PPM implantation within 30 days from the index procedure did not increase the risk of 5-year mortality after either SAVR or TAVR. Among 1,042 propensity score matched pairs, TAVR had an increased risk of PPM implantation at 30-day (9.9% vs. 4.7%, p < .0001) and 5-year (14.

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