RG-I pectin-like polysaccharide from Rosa chinensis inhibits inflammation and fibrosis associated to HMGB1/TLR4/NF-κB signaling pathway to improve non-alcoholic steatohepatitis.

A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked ß-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg. The mechanism study suggests that the biological activity may associate to inactivating of high-mobility group box 1 protein (HMGB1)/TLR4/NF-κB and Akt signaling pathways by restraining the expression and release of HMGB1, thereby impeding the effect of NASH. The current findings outline a novel leading polysaccharide for new drug candidate development against NASH.

An Exploratory Pilot Study on the Application of Radiofrequency Ablation for Atrial Fibrillation Guided by Computed Tomography-Based 3D Printing Technology.

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation.

Long noncoding RNA LRG modulates Drosophila locomotion by sequestering Synaptotagmin 1 protein.

Apparently, the genomes of many organisms are pervasively transcribed, and long noncoding RNAs (lncRNAs) make up the majority of cellular transcripts. LncRNAs have been reported to play important roles in many biological processes; however, their effects on locomotion are poorly understood. Here, we presented a novel lncRNA, Locomotion Regulatory Gene (LRG), which participates in locomotion by sequestering Synaptotagmin 1 (SYT1). LRG deficiency resulted in higher locomotion speed which could be rescued by pan-neuronal overexpression but not by limited ellipsoid body, motoneuron or muscle-expression of LRG. At the molecular level, the synaptic vesicles (SVs) release and movement-related SYT1 protein was recognized as LRG-interacting protein candidate. Furthermore, LRG had no effects on SYT1 expression. Genetically, the behavioral defects in LRG mutant could be rescued by pan-neuronal knock-down of Syt1. Taken together, all the results suggested LRG exerts regulatory effects on locomotion via sequestering SYT1 thereby blocking its function without affecting its expression. Our work displays a new function of lncRNA and provides insights for revealing the pathogenesis of neurological diseases with motor disorders.

Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.

Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. However, we are currently unaware of any studies using selective and potent ClpP activators in lung squamous cell carcinoma. In this work, we report on such an activator, ZK53, which exhibits therapeutic effects on lung squamous cell carcinoma in vivo. The crystal structure of ZK53/ClpP complex reveals a π-π stacking effect that is essential for ligand binding selectively to the mitochondrial ClpP. ZK53 features on a simple scaffold, which is distinct from the activators with rigid scaffolds, such as acyldepsipeptides and imipridones. ZK53 treatment causes a decrease of the electron transport chain in a ClpP-dependent manner, which results in declined oxidative phosphorylation and ATP production in lung tumor cells. Mechanistically, ZK53 inhibits the adenoviral early region 2 binding factor targets and activates the ataxia-telangiectasia mutated-mediated DNA damage response, eventually triggering cell cycle arrest. Lastly, ZK53 exhibits therapeutic effects on lung squamous cell carcinoma cells in xenograft and autochthonous mouse models.

A pectic polysaccharide isolated from Achyranthes bidentata is metabolized by human gut Bacteroides spp.

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp.

The claim of primacy of human gut Bacteroides ovatus in dietary cellobiose degradation.

A demonstration of cellulose degrading bacterium from human gut changed our view that human cannot degrade the cellulose. However, investigation of cellulose degradation by human gut microbiota on molecular level has not been completed so far. We showed here, using cellobiose as a model that promoted the growth of human gut key members, such as Bacteroides ovatus (BO), to clarify the molecular mechanism. Our results showed that a new polysaccharide utilization locus (PUL) from BO was involved in the cellobiose capturing and degradation. Further, two new cellulases BACOVA_02626GH5 and BACOVA_02630GH5 on the cell surface performed the degradation of cellobiose into glucose were determined. The predicted structures of BACOVA_02626GH5 and BACOVA_02630GH5 were highly homologous with the cellulase from soil bacteria, and the catalytic residues were highly conservative with two glutamate residues. In murine experiment, we observed cellobiose reshaped the composition of gut microbiota and probably modified the metabolic function of bacteria. Taken together, our findings further highlight the evidence of cellulose can be degraded by human gut microbes and provide new insight in the field of investigation on cellulose.

Degradation of xylan by human gut Bacteroides xylanisolvens XB1A.

Although many polysaccharides utilization loci (PULs) have been investigated by genomics and transcriptomics, the detailed functional characterization lags severely behind. We hypothesize that PULs on the genome of Bacteroides xylanisolvens XB1A (BX) dictate the degradation of complex xylan. To address, xylan S32 isolated from Dendrobium officinale was employed as a sample polysaccharide. We firstly showed that xylan S32 promoted the growth of BX which might degrade xylan S32 into monosaccharides and oligosaccharides. We further showed that this degradation was performed mainly via two discrete PULs in the genome of BX. Briefly, a new surface glycan binding protein (SGBP) BX_29290SGBP was identified, and shown to be essential for the growth of BX on xylan S32. Two cell surface endo-xylanases Xyn10A and Xyn10B cooperated to deconstruct the xylan S32. Intriguingly, genes encoding Xyn10A and Xyn10B were mainly distributed in the genome of Bacteroides spp. In addition, BX metabolized xylan S32 to produce short chain fatty acids (SCFAs) and folate. Taken together, these findings provide new evidence to understand the food source of BX and the BX-directed intervention strategy by xylan.

A structure defined pectin SA02B from Semiaquilegia adoxoides is metabolized by human gut microbes.

Polysaccharide is one of the major factors for shaping the gut microbiota. However, bioactivity of polysaccharide isolated from Semiaquilegia adoxoides on human gut microbiota remains unclear. Thus, we hypothesize gut microbes may act on it. Herein, pectin SA02B from the roots of Semiaquilegia adoxoides with molecular weight 69.26 kDa was elucidated. The backbone of SA02B was composed of alternate 1, 2-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 4-, 1, 3- and 1, 3, 6-linked ß-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf and T-, 1, 4-linked-ß-Xylp substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity screening showed SA02B promoted the growth of Bacteroides spp. which deconstructed it into monosaccharide. Simultaneously, we observed competition might exist between Bacteroides spp. and probiotics. Besides, we found that both Bacteroides spp. and probiotics could generate SCFAs grown on SA02B. Our findings highlight SA02B may deserve as a prebiotic to be explored to benefit the health gut microbiota.

Is it feasible to measure pulmonary vein data using volume rendering images?

BACKGROUND: Pulmonary vein (PV) data are commonly measured on multiplanar image reformation (MPR) images and volume rendering (VR) images. PURPOSE: To compared and analyze the advantages and disadvantages of PV data based on VR images and MPR images. MATERIAL AND METHODS: A total of 94 patients with atrial fibrillation (AF) with imaging data were included in the study. The respective image postprocessing time and the three surgical interventionists' preferences for the two images were recorded. A paired t-test or chi-square test was used to compare their difference, and P < 0.05 was considered statistically significant. RESULTS: There was no statistically significant difference between the data values including the maximal and minimal ostial diameters of the left superior PV (LSPV), the left inferior PV (LIPV), the right superior PV (RSPV), and the right inferior PV (RIPV) obtained by VR and MPR images (P > 0.05). Yet, the mean postprocessing time of VR images (15.10 ± 3.05 min) was shorter compared to MPR images (16.54 ± 2.60 min) (t = 22.84, P < 0.05). All three surgical interventionists preferred VR images (accounted for 85.1%, 86.2%, and 84.0%, respectively), and there was no statistical difference in the degree of image preference among the three (chi-square = 0.596, P = 0.963). CONCLUSION: PV data measurement could be performed on both VR and MRP images; however, the data on VR images were more intuitive and more accessible for interventional surgeons.

Murine double minute 2 aggravates adipose tissue dysfunction through ubiquitin-mediated six-transmembrane epithelial antigen of prostate 4 degradation.

Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. Mdm2 adipocyte-specific knock-in (Mdm2-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in Mdm2-AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of Mdm2-AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis.

Mechanism of Fusarium graminearum Resistance to Ergosterol Biosynthesis Inhibitors: G443S Substitution of the Drug Target FgCYP51A.

Fusarium head blight (FHB), caused by the Fusarium graminearum species complex, is a devastating fungal disease resulting in substantial yield and quality losses. Ergosterol biosynthesis inhibitors (EBIs) are the most popular chemicals for controlling FHB. Recently, the resistance of F. graminearum to EBIs has emerged in the field, and an amino acid substitution (G443S) of the sterol 14α-demethylase FgCYP51A was detected in the field resistant strains. To further illustrate the resistance mechanism of F. graminearum to EBIs, site-directed mutants conferring the G443S substitution of FgCYP51A were generated from the progenitor strain PH-1 via genetic transformation with site-directed mutagenesis. We found that the FgCYP51A-G443S substitution significantly decreased the sensitivity of F. graminearum to EBIs with EC50 values ranging from 0.1190 to 0.2302 µg mL-1 and EC90 values ranging from 1.3420 to 9.1119 µg mL-1 for tebuconazole. Furthermore, the FgCYP51A-G443S substitution decreased sexual reproduction and virulence, which will reduce the initial infection source of pathogen populations in the field, while the increase of sporulation capability may enhance the frequencies of the disease cycle, thereby contributing to epidemics of FHB disease. Surprisingly, the FgCYP51A-G443S substitution accelerated DON biosynthesis by upregulating TRI5 expression and enhancing the fluorescence intensity of TRI1-GFP, the marker protein of Fusarium toxisomes. Thus, we concluded that the FgCYP51A-G443S substitution regulates EBI-fungicide resistance and DON biosynthesis, increasing the risk of fungicide resistance development in the field, thereby threatening the control efficacy of EBIs against FHB.

Cocktail polysaccharides isolated from Ecklonia kurome against the SARS-CoV-2 infection.

Previous researches suggested that polysaccharides from brown algae had anti-virus activity. We hypothesized that nature polysaccharide from marine plants might have the effect on anti-SARS-CoV-2 activity. By high throughput screening to target 3CLpro enzyme using polysaccharides library, we discover a crude polysaccharide 375 from seaweed Ecklonia kurome blocked 3CLpro enzymatic activity and shows good anti-SARS-CoV-2 infection activity in cell. Further, we show that homogeneous polysaccharide 37502 from the 375 may bind to 3CLpro well and disturb spike protein binding to ACE2 receptor. The structure characterization uncovers that 37502 is alginate. These results imply that the bioactivities of 375 on SARS-CoV-2 may target multiple key molecules implicated in the virus infection and replication. The above results suggest that 375 may be a potential drug candidate against SARS-CoV-2.

Corrigendum: Impact of Meteorological Factors and Southern Oscillation Index on Scrub Typhus Incidence in Guangzhou, Southern China, 2006-2018.

[This corrects the article DOI: 10.3389/fmed.2021.667549.].

Impact of Meteorological Factors and Southern Oscillation Index on Scrub Typhus Incidence in Guangzhou, Southern China, 2006-2018.

Background: Scrub typhus was epidemic in the western Pacific Ocean area and East Asia, scrub typhus epidemic in densely populated areas in southern China. To better understand the association between meteorological variables, Southern Oscillation Index (SOI), and scrub typhus incidence in Guangzhou was benefit to the control and prevention. Methodology/Principal Findings: We collected weekly data for scrub typhus cases and meteorological variables in Guangzhou, and Southern Oscillation Index from 2006 to 2018, and used the distributed lag non-linear models to evaluate the relationships between meteorological variables, SOI and scrub typhus. The median value of each variable was set as the reference. The high-risk occupations were farmer (51.10%), house worker (17.51%), and retiree (6.29%). The non-linear relationships were observed with different lag weeks. For example, when the mean temperature was 27.7°C with1-week lag, the relative risk (RR) was highest as 1.08 (95% CI: 1.01-1.17). The risk was the highest when the relative humidity was 92.0% with 9-week lag, with the RR of 1.10 (95% CI: 1.02-1.19). For aggregate rainfall, the highest RR was 1.06 (95% CI: 1.03-1.11), when it was 83.0 mm with 4-week lag. When the SOI was 19 with 11-week lag, the highest RR was 1.06 (95% CI: 1.01-1.12). Most of the extreme effects of SOI and meteorological factors on scrub typical cases were statistically significant. Conclusion/Significance: The high-risk occupations of scrub typhus in Guangzhou were farmer, house worker, and retiree. Meteorological factors and SOI played an important role in scrub typhus occurrence in Guangzhou. Non-linear relationships were observed in almost all the variables in our study. Approximately, mean temperature, and relative humidity positively correlated to the incidence of scrub typhus, on the contrary to atmospheric pressure and weekly temperature range (WTR). Aggregate rainfall and wind velocity showed an inverse-U curve, whereas the SOI appeared the bimodal distribution. These findings can be helpful to facilitate the development of the early warning system to prevent the scrub typhus.

Discrete genetic loci in human gut Bacteroides thetaiotaomicron confer pectin metabolism.

Although the polysaccharide utilization loci (PULs) activated by pectin have been defined, due to the complex of side-chain structure, the degradative mechanisms still remain vague. Thus, we hypothesize that there may have other specific PULs to target pectin. Here, we characterize loci-encoded proteins expressed by Bacteroides thetaiotaomicron (BT) that are involved in the pectin capturing, importation, de-branching and degradation into monosaccharides. Totally, four PULs contain ten enzymes and four glycan binding proteins which including a novel surface enzyme and a surface glycan binding protein are identified. Notably, PUL2 and PUL3 have not been reported so far. Further, we show that the degradation products support the growth of other Bacteroides spp. and probiotics. In addition, genes involved in this process are conservative in other Bacteroides spp. Our results further highlight the contribution of Bacteroides spp. to metabolism the pectic network.

Eutrophication decreased CO2 but increased CH4 emissions from lake: A case study of a shallow Lake Ulansuhai.

Eutrophic lakes, especially shallow eutrophic lakes, disproportionately contribute to greenhouse gas (GHG) emissions. To investigate the effects of eutrophication on GHG dynamics, we conducted field measurements every three months from January 2019 to October 2019 in Lake Ulansuhai, a shallow eutrophic lake (mean depth of 0.7 m) located in a semi-arid region in Northern China. We found that Lake Ulansuhai was a predominantly source of atmospheric carbon dioxide (CO2); however, it converted to a CO2 sink in July due to eutrophication. It was also a strong source of methane (CH4) with a mean CO2 emission of 35.7 ± 12.1 mmol m-2 d-1 and CH4 emission of 5.9 ± 2.9 mmol m-2 d-1. The CO2 concentrations in most sites and CH4 concentrations in all sites were supersaturated, with the average partial pressure of CO2 (pCO2) being 654±34 µatm and the partial pressure of CH4 (pCH4) being 157±37 µatm. The partial pressures and emissions of the greenhouse gases exhibited substantial seasonal and spatial variations. The correlation analysis between the trophic level index and the partial pressure of the greenhouse gases indicated that eutrophication could significantly decrease the CO2 emissions but increase the CH4 emissions from the lake, resulting in a CH4 and CO2 emission ratio of approximately 2 in terms of global warming potential. Eutrophication decreased the pCO2 in the lake and subsequently increased the pCH4 due to nutrient input, thereby enhancing primary production. The results indicated that shallow eutrophic lakes in arid regions are strong sources of CH4 and that eutrophication could alter the greenhouse gas emission patterns.

[Systematic review and Meta-analysis on chemotherapy-induced bone marrow suppression treated with acupuncture].

OBJECTIVE: To review systematically the effectiveness of acupuncture in treatment of chemotherapy-induced bone marrow suppression. METHODS: From the date of database establishment to April 1, 2020, the articles on randomized controlled trials of chemotherapy-induced bone marrow suppression were retrieved by computer from the following databases, i.e. PubMed, Cochrane central register of controlled trials (CENTRAL), EMbase, cumulative index to nursing & allied health literature (CINAHL), JBI database of systematic reviews and implementation reports, CNKI, Wanfang, VIP and SinoMed. Using RevMan5.3, Meta-analysis was conducted. With GRADEpro GDT, the evidence quality was evaluated. RESULTS: A total of 12 articles were included, 10 articles of which were analyzed by quantitative Meta-analysis. Compared with the control group, the improvements in the decrease of post-chemotherapy leukocyte (P<0.01, MD=0.88, 95%CI=[0.71, 1.05]) and platelet (P<0.01, MD=25.91, 95%CI=[16.86, 34.97]) were better in the observation group. The difference in reducing hemoglobin was not significant between the two groups (P>0.05, MD=2.19, 95%CI=[-1.22, 5.61]). Regarding the improvement in the decrease of post-chemotherapy neutrophile granulocyte (P=0.03, MD=0.40, 95%CI=[0.04, 0.77]) and erythrocyte (P=0.03，MD=0.15，95%CI=[0.01, 0.28]), Karnofsky score (P<0.01, MD=4.19, 95%CI=[3.40, 4.98]) and quality of life (QOL) score (P<0.01, MD=5.01，95%CI=[1.61, 8.42]), the effects in the observation group were better than those in the control group. CONCLUSION: Acupuncture alleviates the decrease of leukocyte, platelet, neutrophile granulocyte and erythrocyte counts and improves the survival quality of patients with chemotherapy-induced bone marrow suppression.

Crataegus pinnatifida polysaccharide alleviates colitis via modulation of gut microbiota and SCFAs metabolism.

Inflammatory bowel disease (IBD) afflicted individual and most medications have side-effects. Crataegus pinnatifida (Hawthorn), which is a safe medicine and food homolog plant, has been reported to prevent colitis in murine. Yet the bioactivity component and the underlying molecular mechanism remain unclear. Here, we established a direct link between colitis induced by dextran sulphate sodium (DSS) in mice and polysaccharide HAW1-2 isolated from hawthorn. Our results showed HAW1-2 restored the pathological lesions in colon and inhibited the expression of inflammatory cytokines including IL-1ß, IL-6 and TNF-α. Meanwhile, IKKα/ß, IκBα, NF-κB and the phosphorylation levels were inhibited significantly. These findings suggested HAW1-2 could alleviate the inflammation of colon. Further, we found the composition of gut microbiota was modified and Bacteroides including Alistipes and Odoribacter were significantly enriched. Besides, we showed Alistipes and Odoribacter were positively co-related with acetic acid and propionic acid while were negatively co-related with inflammatory cytokines. Finally, we demonstrated the anti-inflammation activity of HAW1-2 might be induced by acetic acid. Together, the present data revealed HAW1-2 could directly modify the gut microbiota, especially for Bacteroides, and generate SCFAs to inhibit colitis. It also implies microbiota-directed intervention in IBD patients should be particularly given more attention.

Nostoc sphaeroids Kütz polysaccharide and powder enrich a core bacterial community on C57BL/6j mice.

Gut microbiota is the collection of microbes that lives in the host. Glycan is the major factor to shape the composition of microbial community. Nostoc sphaeroids Kütz (NSK) has been used as food and medicine for thousands of years in Asian countries while the bioactivity on gut microbiota is unclear till now. Here, we used NSK polysaccharide and NSK powder to investigate the bioactivity on the gut microbiota of C57BL/6j mice, respectively. By 16S ribosomal RNA gene sequencing, we found the composition of gut microbiota had been changed and differed from each other. However, the abundance of Bacteroides, Parabacteroides, Escherichia-Shigella and Parasutterella on genus level were significantly increased by NSK polysaccharide and NSK powder. In addition, Akkermansia and Rikenellaceae were enriched by NSK powder. Moreover, we found the IL-1ß and IL-6 decreased significantly while TNF-α and IL-10 increased significantly especially in NSK powder group. Intriguingly, the increased microbes were significantly positively co-related with TNF-α and IL-10 while negatively co-related with IL-1ß and IL-6 by co-relation and network analysis. The above results suggested that Nostoc sphaeroids Kütz may selectively enrich a "core bacterial community" and add new evidence to discover how Nostoc sphaeroids Kütz has biological function.

Quinone outside inhibitors affect DON biosynthesis, mitochondrial structure and toxisome formation in Fusarium graminearum.

Quinone outside inhibitors (QoIs) are currently extensively used agricultural fungicides. However, the application of QoIs in controlling Fusarium graminearum was rarely reported. No information is available on pharmacological characteristics of QoIs against F. graminearum, as well as their effects on DON biosynthesis. Here, we found that six QoIs exhibited an excellent fungicidal activity against F. graminearum based on mycelial growth and spore germination. ATP production assay further confirmed that QoIs decreased ATP production via inhibiting mitochondrial respiration, which contributes their fungicidal activity. Unfortunately, QoIs can stimulate DON production and up-regulate the expression of Tri5 and Tri6 genes. Additionally, acetyl-CoA, the basic precursor of DON biosynthesis, significantly increased as affected by QoIs, furtherly indicating that QoIs indeed enhance DON biosynthesis. We also found that QoIs can accelerate the formation of toxisomes and enhance the fluorescence signals of Tri-GFP labeled toxisomes, which may be due to the effect of QoIs on toxisome-related endoplasmic reticulum-remodeling. In addition, QoIs could disrupt the homeostasis of mitochondrial dynamics, resulting in the fragmented mitochondria. Finally, the simulated inoculation assay with wheat grains further verified that QoIs can stimulate DON production relative to wheat grain weight, especially relative to mycelial biomass.