Antibacterial insights into alternariol and its derivative alternariol monomethyl ether produced by a marine fungus.

Alternaria alternata FB1 is a marine fungus identified as a candidate for plastic degradation in our previous study. This fungus has been recently shown to produce secondary metabolites with significant antimicrobial activity against various pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and the notorious aquaculture pathogen Vibrio anguillarum. The antibacterial compounds were purified and identified as alternariol (AOH) and its derivative, alternariol monomethyl ether (AME). We found that AOH and AME primarily inhibited pathogenic bacteria (MRSA or V. anguillarum) by disordering cell division and some other key physiological and biochemical processes. We further demonstrated that AOH could effectively inhibit the unwinding activity of MRSA topoisomerases, which are closely related to cell division and are the potential action target of AOH. The antibacterial activities of AOH and AME were verified by using zebrafish as the in vivo model. Notably, AOH and AME did not significantly affect the viability of normal human liver cells at concentrations that effectively inhibited MRSA or V. anguillarum. Finally, we developed the genetic operation system of A. alternata FB1 and blocked the biosynthesis of AME by knocking out omtI (encoding an O-methyl transferase), which facilitated A. alternata FB1 to only produce AOH. The development of this system in the marine fungus will accelerate the discovery of novel natural products and further bioactivity study.IMPORTANCEMore and more scientific reports indicate that alternariol (AOH) and its derivative alternariol monomethyl ether (AME) exhibit antibacterial activities. However, limited exploration of their detailed antibacterial mechanisms has been performed. In the present study, the antibacterial mechanisms of AOH and AME produced by the marine fungus Alternaria alternata FB1 were disclosed in vitro and in vivo. Given their low toxicity on the normal human liver cell line under the concentrations exhibiting significant antibacterial activity against different pathogens, AOH and AME are proposed to be good candidates for developing promising antibiotics against methicillin-resistant Staphylococcus aureus and Vibrio anguillarum. We also succeeded in blocking the biosynthesis of AME, which facilitated us to easily obtain pure AOH. Moreover, based on our previous results, A. alternata FB1 was shown to enable polyethylene degradation.

Clinical characteristics of inpatients with coronavirus disease 2019 (COVID-19) in Sichuan province.

BACKGROUND: The outbreak of COVID-19 has resulted in serious concerns in China and abroad. To investigate clinical features of confirmed and suspected patients with COVID-19 in west China, and to examine differences between severe versus non-severe patients. METHODS: Patients admitted for COVID-19 between January 21 and February 11 from fifteen hospitals in Sichuan Province, China were included. Experienced clinicians trained with methods abstracted data from medical records using pre-defined, pilot-tested forms. Clinical characteristics between severe and non-severe patients were compared. RESULTS: Of the 169 patients included, 147 were laboratory-confirmed, 22 were suspected. For confirmed cases, the most common symptoms from onset to admission were cough (70·7%), fever (70·5%) and sputum (33·3%), and the most common chest CT patterns were patchy or stripes shadowing (78·0%); throughout the course of disease, 19·0% had no fever, and 12·4% had no radiologic abnormality; twelve (8·2%) received mechanical ventilation, four (2·7%) were transferred to ICU, and no death occurred. Compared to non-severe cases, severe ones were more likely to have underlying comorbidities (62·5% vs 26·2%, P = 0·001), to present with cough (92·0% vs 66·4%, P = 0·02), sputum (60·0% vs 27·9%, P = 0·004) and shortness of breath (40·0% vs 8·2%, P <  0·0001), and to have more frequent lymphopenia (79·2% vs 43·7%, P = 0·003) and eosinopenia (84·2% vs 57·0%, P = 0·046). CONCLUSIONS: The symptoms of patients in west China were relatively mild, and an appreciable proportion of infected cases had no fever, warranting special attention.

The effect of different flushing and locking techniques on catheter occlusion rates in central venous catheters: protocol for a multicentre, randomized controlled, parallel-group, open-label, superiority clinical trial.

BACKGROUND: Maintaining venous access is of great clinical importance. Running a slow continuous infusion to keep the vein open (KVO) is often used in peripheral intravenous catheters (PIVCs). Previous studies have compared the effects of intermittent flushing and continuous infusion via peripherally inserted central catheters (PICCs). In this study, we applied KVO to central venous catheters (CVCs) and compared the occlusion rate of this technique with that of the intermittent flushing technique. METHOD: This is a randomized controlled trial of 14 hospitals in China. A total of 250 patients will be recruited in this study, and they will be randomized at a 1:1 ratio. After study inclusion, patients who will undergo CVC insertion will receive intermittent flushing with prefilled saline syringes (control group) or KVO infusion with elastic pumps (test group). All the catheters will be checked for patency by scoping Catheter Injection and Aspiration (CINAS) Classification on Days 3 and 7. The primary outcome is the rate of catheter occlusion in 7 days. Patients will be followed up until 9 days after CVC insertion, catheter occlusion, or catheter removal. The secondary outcomes are the rate of catheter occlusion in 3 days, nurse satisfaction, cost-effectiveness, adverse event rate, catheter-related bloodstream infection rate, catheter-related thrombosis rate, extravasation rate, phlebitis rate, and catheter migration. DISCUSSION: We expect that the trial will generate findings that can provide an evidence-based basis for the improvement and optimization of clinical catheter flushing techniques. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200064007. Registered on 23 September 2022. https://www.chictr.org.cn/showproj.html?proj=177311 .

The impact of different drying methods on the physical properties, bioactive components, antioxidant capacity, volatile components and industrial application of coffee peel.

This study evaluated the effects of hot air drying (HAD), microwave drying (MD), vacuum drying (VD), sun drying (SD) and vacuum freeze drying (VFD) on the physical properties, bioactive components, antioxidant capacity, volatile components and industrial application of coffee peel. The results showed VFD could retain the appearance color, total phenolics (19.49 mg GAE/g DW), total flavonoids (9.65 mg CE/g DW), caffeine (3.15 mg/g DW), trigonelline (2.71 mg/g DW), and antioxidant capacities of fresh sample to the greatest extent, but its operating cost was significantly higher than other treatments and total volatile components were in the minimum levels. HAD and SD exhibited the highest loss rates of total phenols and antioxidant capacities, exceeding 50%. MD offered the lowest operating cost, superior retention of bioactive components, and the richest variety and quantity of volatile compounds. Therefore, it is recommended to use MD to dehydrate the coffee peel in actual production.

Optimizing drip fertigation at different periods to improve yield, volatile compounds and cup quality of Arabica coffee.

How to improve and regulate coffee bean yield and quality through split fertilization in the whole life cycle of coffee is still unclear and deserves further study. A field experiment of 5-year-old Arabica coffee trees was conducted for 2 consecutive years from 2020 to 2022. The fertilizer (750 kg ha-1 year-1, N-P2O5-K2O:20%-20%-20%) was split in three times at early flowering (FL), the berry expansion (BE), and the berry ripening (BR). Taking equal fertilization throughout the growth cycle (FL250BE250BR250) as the control check, variable fertilizations including FL150BE250BR350, FL150BE350BR250, FL250BE150BR350, FL250BE350BR150, FL350BE150BR250, and FL350BE250BR150. Leaf net photosynthetic rate (A net), stomatal conductance (g s), transpiration rate (T r), leaf water use efficiency (LWUE), carboxylation efficiency (CE), partial factor productivity of fertilizer (PFP), bean yield, crop water use efficiency (WUE), bean nutrients, volatile compounds and cup quality, and the correlation of nutrients with volatile compounds and cup quality was evaluated. FL350BE250BR150 had the maximum A net and g s, followed by FL250BE350BR150. The highest dry bean yield and WUE were obtained from FL250BE350BR150, which increased by 8.86% and 8.47% compared with FL250BE250BR250 in two-year average. The ash, total sugar, fat, protein, caffeine and chlorogenic acid in FL250BE350BR150 were 6.47%, 9.48%, 3.60%, 14.02%, 4.85% and 15.42% higher than FL250BE250BR250. Cluster analysis indicated FL150BE350BR250, FL250BE350BR150, FL350BE150BR250 and FL350BE250BR150 under medium roasted degree increased pyrazines, esters, ketones and furans, FL150BE350BR250 and FL250BE350BR150 under dark roasted degree increased ketones and furans. The aroma, flavor, acidity and overall score of medium roasted coffee were higher than dark roasted coffee, while the body score of dark roasted coffee was higher than medium roasted coffee. The nutrient contents were correlated with the volatile compounds and cup quality. TOPSIS indicated that FL250BE350BR150 was the optimal fertilization mode in the xerothermic regions. The obtained optimum fertilization mode can provide a scientific basis for coffee fertilization optimization and management.

The diagnostic value of intracavitary electrocardiogram for verifying tip position of peripherally inserted central catheters in cancer patients: A retrospective multicenter study.

PURPOSE: To evaluate the feasibility and accuracy of intracavitary electrocardiogram for verifying tip position of peripherally inserted central catheters in cancer patients during follow-up period. METHODS: From March 2015 to October 2015, 126 patients involved in eight hospitals who underwent peripherally inserted central catheter placement received intracavitary electrocardiogram and chest X-ray to verify position of the catheter tip during follow-up period. Their intracavitary electrocardiogram was compared with surface electrocardiogram to judge catheter tip landing zone in one of three different anatomical zones. The amplitude of intracavitary electrocardiogram P wave and the ratio of intracavitary electrocardiogram P wave/surface electrocardiogram P wave were measured and showed correlation with catheter tip position confirmed by chest X-ray. Based on chest X-ray principle, all the cases were assigned into three intracavitary electrocardiogram groups to explore the optimal cut-off values for intracavitary electrocardiogram P wave and intracavitary electrocardiogram P wave/surface electrocardiogram P wave by analyzing the receiver operating characteristic. RESULTS: No technique-related complications or adverse events occurred in this study. The matching rate between intracavitary electrocardiogram and chest X-ray method was 93.7%. The optimal cut-off values for intracavitary electrocardiogram P wave were set from 3.15 to 3.75 mV, and intracavitary electrocardiogram P wave/surface electrocardiogram P wave from 1.65 to 3.25. CONCLUSIONS: It is demonstrated in this retrospective multicenter study that the intracavitary electrocardiogram method for verifying tip position of peripherally inserted central catheter during follow-up period is feasible and accurate in all adult patients with cancer.

Xanthomonas oryzae pv. oryzae type III effector PthXo3JXOV suppresses innate immunity, induces susceptibility and binds to multiple targets in rice.

Transcription activator-like (TAL) effectors encoded by tal genes were recognized as a key virulence strategy used by Xanthomonas oryzae pv. oryzae (Xoo) to cause bacterial leaf blight of rice. TAL effector PthXo3 is a major virulence factor identified in a Philippine Xoo strain PXO61, and it can induce the expression of susceptibility gene OsSWEET14 by binding to the effector-binding element (EBE) in the promoter region. In this study, pthXo3 homologous genes were also identified and isolated from Xoo Chinese strain OS198 and Japanese strain JXOV, which were named as pthXo3OS198 and pthXo3JXOV, respectively. When pthXo3JXOV was delivered into PXO99A, the resulting strain PXO99A/pthXo3JXOV significantly increased virulence in 18 out of 23 rice varieties tested, with the most prominent increase in lesion length and bacteria propagation in rice IRBB13. PthXo3JXOV suppresses the plant's innate immunity by inhibiting hypersensitive response (HR) and callose deposition. The Agrobacterium tumefaciens-mediated transient expression assays showed that, besides OsSWEET14, PthXo3JXOV also interacts with other targets by binding to the EBEs in their promoter regions. Our results suggest that PthXo3JXOV may interact with multiple targets to execute its virulence functions.

Superior success rate of intracavitary electrocardiogram guidance for peripherally inserted central catheter placement in patients with cancer: A randomized open-label controlled multicenter study.

BACKGROUND: Intracavitary electrocardiogram (IC ECG) guidance emerges as a new technique for peripherally inserted central catheters (PICCs) placement and demonstrates many potential advantages in recent observational studies. AIMS: To determine whether IC ECG-guided PICCs provide more accurate positioning of catheter tips compared to conventional anatomical landmarks in patients with cancer undergoing chemotherapy. METHODS: In this multicenter, open-label, randomized controlled study (ClinicalTrials.gov number, NCT02409589), a total of 1,007 adult patients were assigned to receive either IC ECG guidance (n = 500) or anatomical landmark guidance (n = 507) for PICC positioning. The confirmative catheter tip positioning x-ray data were centrally interpreted by independent radiologists. All reported analyses in the overall population were performed on an intention-to-treat basis. Analyses of pre-specified subgroups and a selected large subpopulation were conducted to explore consistency and accuracy. RESULTS: In the IC ECG-guided group, the first-attempt success rate was 89.2% (95% confidence interval [CI], 86.5% to 91.9%), which was significantly higher than 77.4% (95% CI, 73.7% to 81.0%) in the anatomical landmark group (P < 0.0001). This trend of superiority of IC ECG guidance was consistently noted in almost all prespecified patient subgroups and two selected large subpopulations, even when using optimal target rates for measurement. In contrast, the superiority nearly disappeared when PICCs were used via the left instead of right arms (interaction P-value = 0.021). No catheter-related adverse events were reported during the PICC intra-procedures in either group. CONCLUSIONS: Our findings indicated that the IC ECG-guided method had a more favorable positioning accuracy versus traditional anatomical landmarks for PICC placement in adult patients with cancer undergoing chemotherapy. Furthermore, there were no significant safety concerns reported for catheterization using the two techniques.