Molecular Mechanism of Fusarium Fungus Inhibition by Phenazine-1-carboxamide.

Fusarium head blight caused by Fusarium graminearum is a devastating disease in wheat that seriously endangers food security and human health. Previous studies have found that the secondary metabolite phenazine-1-carboxamide produced by biocontrol bacteria inhibited F. graminearum by binding to and inhibiting the activity of histone acetyltransferase Gcn5 (FgGcn5). However, the detailed mechanism of this inhibition remains unknown. Our structural and biochemical studies revealed that phenazine-1-carboxamide (PCN) binds to the histone acetyltransferase (HAT) domain of FgGcn5 at its cosubstrate acetyl-CoA binding site, thus competitively inhibiting the histone acetylation function of the enzyme. Alanine substitution of the residues in the binding site shared by PCN and acetyl-CoA not only decreased the histone acetylation level of the enzyme but also dramatically impacted the development, mycotoxin synthesis, and virulence of the strain. Taken together, our study elucidated a competitive inhibition mechanism of Fusarium fungus by PCN and provided a structural template for designing more potent phenazine-based fungicides.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Ambient fine particulate matter and allergic symptoms in the middle-aged and elderly population: results from the PIFCOPD study.

BACKGROUND: The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. METHODS: Participants (n = 10,142; age = 40-75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0-7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. RESULTS: A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0-7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. CONCLUSIONS: Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. TRIAL REGISTRATION: Clinical trial ID: NCT03532893 (29 Mar 2018).

Insights into the role of chitosan in hydrogen production by dark fermentation of waste activated sludge.

Chitosan is widely used as a dewatering flocculant, but whether it affects hydrogen production from sludge anaerobic fermentation is unclear. This study aimed to elucidate the role of chitosan in the dark fermentation of waste activated sludge for hydrogen production. The results showed that chitosan had a negative effect on hydrogen production from sludge. Chitosan at 30 g/kg total suspended solids reduced hydrogen accumulation by 56.70 ± 1.22 % from 3.94 ± 0.12 to 1.71 ± 0.10 mL/g volatile suspended solids. Chitosan hindered the solubilization of sludge by flocculation, which reduced the available substrate for anaerobic fermentation. In addition, chitosan interfered with the electron transport system by reducing cytochrome C and caused lipid peroxidation by inducing reactive oxygen species, thereby inhibiting the activity of enzymes involved in anaerobic fermentation. Hydrogen production was reduced because hydrogen-producing processes (i.e., hydrolysis, acidification, and acetification) were inhibited more strongly than hydrogen-consuming processes (i.e., methanogenesis, sulfate reduction, and homoacetogenesis). Furthermore, chitosan enriched the abundance of Spirochaetaceae sp. and Holophagaceae sp., which occupied the survival space of hydrogen-producing microorganisms. This study reveals the potential impact of chitosan on hydrogen production in dark fermentation of sludge and provide direct evidence that chitosan triggers oxidative stress in anaerobic fermentation.

Unveiling the dual faces of chitosan in anaerobic digestion of waste activated sludge.

In this study, the roles of chitosan (CTS) in anaerobic digestion of Waste activated sludge (WAS) were investigated. The results show that the methane production potential of WAS is positively correlated with the CTS content. The presence of 30 g/kg total suspended solids CTS increased the cumulative methane production from 215 ± 1.52 to 272 ± 1.83 mL/g volatile suspended solids. The positively charged amino groups in CTS neutralize the hydroxyl and carboxyl groups of extracellular polymeric substances, which reduces the negative charge on the surface of sludge and promotes sludge agglomeration, thereby inhibiting the release of organic matter. CTS also inhibits hydrolysis and acidification by immobilizing hydrolases and acidulase enzymes. However, CTS flocculates humus to avoid its interference with electron transfer, thereby enhancing the activity of coenzyme F420 and methanogenesis. In addition, CTS increases the abundance of methanogens, which also contributes to methane production.

Triclosan facilitates the recovery of volatile fatty acids from waste activated sludge.

The emergence of triclosan (TCS) in the environment has caused extensive concern, but its role in waste activated sludge (WAS) anaerobic fermentation (AF) is still uncertain. This work investigated the impact of TCS on volatile fatty acids (VFAs) recycling from WAS. The results showed that TCS of 200 mg/kg TSS increased the maximum VFA accumulation from 7284 to 15,083 mg COD/L. The increase in total VFA production is attributed to the massive increase in acetic acid. Mechanism exploration showed that TCS promotes WAS solubilization by facilitating cell breakage and extracellular polymeric substances disruption, and stimulates AF by enhancing the activity of key enzymes among all stages. TCS promotes acidification stronger than methanogenesis, which makes VFA production faster than consumption, leading to increased VFA accumulation. These findings provide novel insights for revealing the role of TCS in WAS resource recovery, and offer thoughts for the selective production of final recycling products of TCS-containing WAS.

Rapid microwave-assisted Porter method for determination of proanthocyanidins.

INTRODUCTION: Proanthocyanidins have been widely developed and utilised in food, medicine, health care products and cosmetics. Porter-high-performance liquid chromatography (HPLC) is a quantitative method often utilised in many fields. This method uses a water bath to reflux the proanthocyanidins, but the process is cumbersome, the reagent consumption is large, and multiple batches of simultaneous treatments cannot be evaluated. OBJECTIVE: To establish a more convenient, rapid and high-batch processing method for determining the content of proanthocyanidins in functional food by HPLC. METHODS: N-Butanol-hydrochloric acid and iron salt are used as the reaction medium in the Porter method. After investigating the optimal conditions, the hydrolysis of proanthocyanidins can be performed in a microwave reactor at a power of 640 W for 75 s in the Porter reaction system. The content of proanthocyanidins was determined by HPLC with external standards. RESULTS: After the rapid pretreatment of samples, proanthocyanidins were determined by HPLC with a diode array detector at a detection wavelength of 525 nm with 0.53 µg/mL and 1.61 µg/mL limits of detection and quantification, respectively, for proanthocyanidin ions, and the linearity was 0.9999. Intra- and inter-day relative standard deviation values were between 1.5% and 3.1%, and the recovery was between 91.40% and 107.43% for the determination of different products, such as capsules, tablets and tea, which were similar to the values obtained with the conventional Porter method. CONCLUSION: This method is a time-saving and low cost approach for quantitative analysis of various proanthocyanidin health products that offers the advantages of high-batch processing and environmental friendliness.