Isolation, identification, and evaluation of the biocontrol potential of a Bacillus velezensis strain against tobacco root rot caused by Fusarium oxysporum.

AIMS: Tobacco (Nicotiana tabacum) is an economically important crop. Root rot caused by Fusarium oxysporum has become a damaging disease in N. tabacum crops grown in Henan province of China. Therefore, the objectives of this study were to screen bacterial isolates against F. oxysporum from rhizosphere soils of tobacco growing areas and to evaluate their antifungal activities, biocontrol effects, and effects on plant growth. METHODS AND RESULTS: Nineteen strains with antifungal inhibition effects of >60% against F. oxysporum were obtained using the method of flat confrontation; the strain Ba-0321 was the strongest, with an antifungal effect of 75%. Moreover, this strain had broad spectrum antimicrobial activity to eight additional tobacco pathogens. The strain was identified as Bacillus velezensis by morphology and the 16S rDNA sequence. The B. velezensis strain Ba-0321 had strong UV resistance as well as tolerance to high temperatures and low nutrition. The bacteria inhibited spore germination and mycelial growth of F. oxysporum under in vitro co-culture conditions. In vivo assays demonstrated that the Ba-0321 strain significantly reduced the pathogenicity of F. oxysporum, resulting in a control effect on tobacco root rot of 81.00%. Simultaneously, the bacteria significantly promoted root development and the growth of tobacco plants. CONCLUSION: Our results confirmed that the B. velezensis strain Ba-0321 has a strong antifungal effect and stress resistance that enable it to be used as a biological control agent for tobacco root rot caused by F. oxysporum. SIGNIFICANCE AND IMPACT OF THE STUDY: Tobacco root rot caused by F. oxysporum has become a damaging disease in China. The B. velezensis strain Ba-0321 has promising application value for controlling tobacco root rot diseases, and it could provide a new biocontrol agent against root rot caused by F. oxysporum in other plant species.

Age-related adiposity and beta-cell function: impact on prediabetes and diabetes prevalence in middle-aged and older Han Chinese adults.

PURPOSE: To investigate the effect of aging on the prevalence of prediabetes and diabetes, and the influence of aging on the associations among adipose mass, redistribution, ß cell function, and the prevalence of hyperglycaemia. METHOD: This urban-based cross-sectional study included 1033 Chinese Han people, aged 40-65 years. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were determined by magnetic resonance imaging. The prevalence rates of prediabetes and diabetes were analyzed according to age group (40-49, 50-59, and 60-65 years). The effects of aging on abdominal fat mass, adipose distribution, insulin action indexes were also assessed. RESULTS: Prediabetes and diabetes prevalence gradually increased with age. Both SFA and VFA increased, while SFA/VFA decreased, in the 50-59 and 60-65 years age groups compared to the 40-49 years group. Homeostatic model assessment of insulin resistance (HOMA-IR) increased with fat mass. Homeostatic model assessment of beta-cell function (HOMA-ß) and early-phase insulin secretion (∆I30/∆G30) were decreased in the 60-65 years group compared to the younger age groups. Increased age, VFA, and HOMA-IR, as well as decreased HOMA-ß, were risk factors for the development of prediabetes and diabetes. The associations between central obesity and the development of prediabetes and diabetes, but not the associations of SFA/VFA, HOMA-IR, and HOMA-ß with hyperglycaemia prevalence, weakened with age. CONCLUSIONS: The prevalence of prediabetes and diabetes increased with age. Central obesity may be related stronger to the development of hyperglycaemia in younger people.

Choline induced cardiac dysfunction by inhibiting the production of endogenous hydrogen sulfide in spontaneously hypertensive rats.

To investigate the exact effects of dietary choline on hypertensive heart disease (HHD) and explore the potential mechanisms, male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into five groups as follows: WKY group, WKY + Choline group, SHR group, SHR + Choline group, and SHR + Choline + NaHS group. In choline treatment groups, rats were fed with 1.3% (w/v) choline in the drinking water for 3 months. The rats in the SHR + Choline + NaHS group were intraperitoneally injected with NaHS (100 micromol/kg/day, a hydrogen sulfide (H2S) donor) for 3 months. After 3 months, left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), the indicators of cardiac function measured by echocardiography, were increased significantly in SHR as compared to WKY, although there was no significant difference in collagen volumes and Bax/Bcl-2 ratio between the two groups, indicating the early stage of cardiac hypertrophy. There was a significant decrease in LVEF and LVFS and an increase in collagen volumes and Bax/Bcl-2 ratio in SHR fed with choline, meanwhile, plasma H2S levels were significantly decreased significantly in SHR fed with choline accompanying by the decrease of cystathionine-gamma-lyase (CSE) activity. Three months of NaHS significantly increased plasma H2S levels, ameliorated cardiac dysfunction and inhibited cardiac fibrosis and apoptosis in SHR fed with choline. In conclusion, choline aggravated cardiac dysfunction in HHD through inhibiting the production of endogenous H2S, which was reversed by supplementation of exogenous H2S donor.

Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury.

The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor ß1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. We hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.

Consistency checks of results from a Monte Carlo code intercomparison for emitted electron spectra and energy deposition around a single gold nanoparticle irradiated by X-rays.

Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed.

Efficacy of utidelone plus capecitabine versus capecitabine for heavily pretreated, anthracycline- and taxane-refractory metastatic breast cancer: final analysis of overall survival in a phase III randomised controlled trial.

BACKGROUND: Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints. PATIENTS AND METHODS: In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan-Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug. RESULTS: At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group [hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142]. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred. CONCLUSIONS: For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.

Intercomparison of dose enhancement ratio and secondary electron spectra for gold nanoparticles irradiated by X-rays calculated using multiple Monte Carlo simulation codes.

PURPOSE: Targeted radiation therapy has seen an increased interest in the past decade. In vitro and in vivo experiments showed enhanced radiation doses due to gold nanoparticles (GNPs) to tumors in mice and demonstrated a high potential for clinical application. However, finding a functionalized molecular formulation for actively targeting GNPs in tumor cells is challenging. Furthermore, the enhanced energy deposition by secondary electrons around GNPs, particularly by short-ranged Auger electrons is difficult to measure. Computational models, such as Monte Carlo (MC) radiation transport codes, have been used to estimate the physical quantities and effects of GNPs. However, as these codes differ from one to another, the reliability of physical and dosimetric quantities needs to be established at cellular and molecular levels, so that the subsequent biological effects can be assessed quantitatively. METHODS: In this work, irradiation of single GNPs of 50 nm and 100 nm diameter by X-ray spectra generated by 50 and 100 peak kilovoltages was simulated for a defined geometry setup, by applying multiple MC codes in the EURADOS framework. RESULTS: The mean dose enhancement ratio of the first 10 nm-thick water shell around a 100 nm GNP ranges from 400 for 100 kVp X-rays to 600 for 50 kVp X-rays with large uncertainty factors up to 2.3. CONCLUSIONS: It is concluded that the absolute dose enhancement effects have large uncertainties and need an inter-code intercomparison for a high quality assurance; relative properties may be a better measure until more experimental data is available to constrain the models.

Practitioners' knowledge and acceptance of paediatric dental procedures under general anaesthesia.

AIM: As paediatric treatment under dental general anaesthesia (DGA) in China is a fairly new technique that was first applied at the beginning of the 21st century, the purpose of this study was to explore practitioners' understanding and acceptance of paediatric dental procedures under general anaesthesia (GA). MATERIALS AND METHODS: This cross-sectional study was conducted among 300 practitioners at the Hospital of Stomatology, Guangxi Medical University, and Guangxi China. A questionnaire was used to collect information about the practitioners' knowledge and acceptance of DGA, and multiple logistic regression analysis was used to test the relationship between the practitioners' knowledge and their acceptance of DGA. RESULTS: The average scores for the practitioners' knowledge of DGA was 4.45 ±1.49. Also, 77.0% of them were willing to refer children for DGA. Practitioners who accepted DGA had higher DGA knowledge scores than those who did not accept it [(4.63 ± 1.38) vs. (3.82 ±1.48), p <0.001]. After controlling for demographic factors, the practitioners' knowledge of DGA was significantly related to their acceptance of DGA (OR=1.47, 95% CI=1.21 -1.79). CONCLUSION: Practitioners' knowledge of DGA is a significant indicator for their acceptance of DGA for children.

(CAG)n loci as genetic modifiers of age at onset in patients with spinocerebellar ataxia type 1 from mainland China.

BACKGROUND AND PURPOSE: The expanded repeat length in ATXN1 negatively correlates with age at onset (AAO) of spinocerebellar ataxia type 1 (SCA1) but can explain only part of it, indicating that other factors affect AAO. Some studies have explored the influence of non-causative CAG repeats on the AAO of SCA patients. However, studies on Chinese SCA1 patients regarding candidate modifier factors involved in the variability in AAO are rare. METHODS: In all, 152 Chinese SCA1 patients who were genotyped for ATXN1 and nine other (CAG)n -containing genes were enrolled. Regression analysis was performed to determine the effect of the expanded allele of ATXN1 (linear and quadratic effects) on AAO. Then, different models were used to explore the modulatory effect of nine other (CAG)n -containing genes. RESULTS: Our results verified the negative effect of the expanded allele in ATXN1 by regression analysis. Some (CAG)n -containing genes including TBP, ATN1 and HTT modified AAO with variance ranging from 0.8% to 3.8% and tended to decrease or delay AAO. However, no modifier effects of ATXN2, ATXN3, CACNA1A, ATXN7, KCNN3, RAI1 and normal ATXN1 alleles in trans were detected. CONCLUSION: By using interaction analyses, TBP, ATN1 and HTT were determined to have modifying effects. Our study revealed that differences in modulation may be due to ethnic and geographic diversity across different populations. Furthermore, the variability of AAO was not completely explained by the genetic modifiers examined here, suggesting that other genetic or environmental factors are involved in these diseases.

Universal intracellular biomolecule delivery with precise dosage control.

Intracellular delivery of mRNA, DNA, and other large macromolecules into cells plays an essential role in an array of biological research and clinical therapies. However, current methods yield a wide variation in the amount of material delivered, as well as limitations on the cell types and cargoes possible. Here, we demonstrate quantitatively controlled delivery into a range of primary cells and cell lines with a tight dosage distribution using a nanostraw-electroporation system (NES). In NES, cells are cultured onto track-etched membranes with protruding nanostraws that connect to the fluidic environment beneath the membrane. The tight cell-nanostraw interface focuses applied electric fields to the cell membrane, enabling low-voltage and nondamaging local poration of the cell membrane. Concurrently, the field electrophoretically injects biomolecular cargoes through the nanostraws and into the cell at the same location. We show that the amount of material delivered is precisely controlled by the applied voltage, delivery duration, and reagent concentration. NES is highly effective even for primary cell types or different cell densities, is largely cargo agnostic, and can simultaneously deliver specific ratios of different molecules. Using a simple cell culture well format, the NES delivers into >100,000 cells within 20 s with >95% cell viability, enabling facile, dosage-controlled intracellular delivery for a wide variety of biological applications.

[Clinical analysis of 3 cases of eosinophilic granulomatosis with polyangiitis].

Objective: To improve the clinical recognition of eosinophilic granulomatosis with polyangiitis(EGPA) in clinical manifestations, diagnosis and treatment. Methods: The clinical manifestations, pathological characteristic, imaging manifestations, diagnosis and the therapy of three patients with EGPA were presented. Results: These 3 patients had asthma-like symptoms and extrapulmonary manifestations of systemic vasculitis. They were 20, 40 and 44 years old. All of them were female.They denied exposure or contact. Chest radiographic examination showed that the most common features were nodule shadow and tree-in-bud in the lung. The pathological manifestation was characterized by hypereosinophilia, high total IgE(over 300 KU/L) and high CRP(over 14.1mg/L). The FeNO of 2 patients was over 100ppb. The ANCA of these 3 patients was negative. The pulmonary pathology was observed had eosinophil infiltration in the alveolar, interstitial and vessel for 3 cases. The clinical manifestations were nonspecific. All patients were treated by glucocorticoid and immune-inhibitor(alkylating agents or purine synthesis inhibitors) therapy. Because patients were complicated with other organs involved, they needed long-time treatment. Conclusions: This disease is diverse and complex, with a lack of pathognomonic symptoms. We should highly suspect eosinophilic granulomatosis with polyangiitis, when the patients present severe asthma and eosinophilia. Early detection, early treatment, and the prognosis could be better.

New levels of high angular resolution EBSD performance via inverse compositional Gauss-Newton based digital image correlation.

Conventional high angular resolution electron backscatter diffraction (HREBSD) uses cross-correlation to track features between diffraction patterns, which are then related to the relative elastic strain and misorientation between the diffracting volumes of material. This paper adapts inverse compositional Gauss Newton (ICGN) digital image correlation (DIC) to be compatible with HREBSD. ICGN-based works by efficiently tracking not just the shift in features, but also the change in their shape. Modeling a shape change as well as a shift results in greater accuracy. This method, ICGN-based HREBSD, is applied to a simulated data set, and its performance is compared to conventional cross-correlation HREBSD, and cross-correlation HREBSD with remapping. ICGN-based HREBSD is shown to have about half the strain error of the best cross-correlation method with a comparable computation time.

[Effect of long-term asthma management on asthma patients from China-Japan Friendship Hospital].

Objective: To investigate the outcome of long-term asthma management of China-Japan Friendship Hospital. Methods: A face-to-face, questionnaire-based survey was carried out in outpatient department in 30 general hospital (including China-Japan Friendship Hospital) from Oct 2015 to May 2016. Data of demographic characteristics, asthma control, asthma management, asthma attacks and self-management, disease perception was collected. Results from China-Japan Friendship Hospital were compared to the national mean level within the same period. Results: Altogether 150 asthmatic outpatients were recruited from China-Japan Friendship Hospital. Asthma control level was significantly higher than the national asthma control level[56.7% (85/150) vs 28.5% (1 099/3 854), P<0.001]. The rate of hospitalizations due to asthma exacerbations was significantly lower than the national hospitalization rate[13.3% (20/150) vs 26.4% (1 017/3 858), P<0.001]. The rate of peak flow meter (PFM) usage was significantly higher than the national PFM usage rate[50.7% (76/150) vs 10.1% (388/3 837), P<0.001]. For reasons of not using PFM, the proportion of doctors never introduced was lower than the national level[43.3% (65/150) vs 65.2% (2 518/3 860), P<0.001]. As to the choice of anti-asthmatics when symptoms deteriorated, the proportion of inhaled corticosteroid (ICS)+ formoterol was significantly higher than the national level[70.0% (105/150) vs 45.8% (1 776/3 875), P<0.001]. The proportion of the patients that had right perception on disease nature was significantly higher than the national level[78.7% (118/150) vs 69.0% (2 660/3 857), P=0.011]. The proportion of the patients that had right perception on medication choice on daily-used first-line medication for chronic asthma was significantly higher than the national level[70.7% (106/150) vs 60.2% (2 321/3 857), P=0.010]. Conclusion: The level of asthma control, disease management and disease perception in China-Japan Friendship Hospital are much higher than national level due to the conduction of long-term asthma management.

[Influence on compliance of subcutaneous immunotherapy in patients with allergic rhinitis by We-Media management].

Objective:To investigate the influence on compliance of sublingual immunotherapy (SLIT) in patients with allergic rhinitis by We-Media management.Method:One hundred and eighty patients of allergic rhinitis were randomly divided into We-Media management group (Group A 90 cases) and telephone management group (Group B 90 cases). All of patients were treated with SLIT. In the group A, the doctor-patient WeChat and/or QQ group were formed. The specific duty doctor acted as group leader, made monthly plans, sent SLIT related knowledge more than 3 times a week and assessed patient reported outcomes. In the group B, the patients were conductd on-the-spot demonstration and explanation and followed up by telephone once three month. The statistical analysises were made on the rates and reason of dropouts on the first, third, sixth, ninth, twelfth post-treatment months in two groups.Result:The rates of dropouts in group A and group B were 13.3%(12/90) and 32.2%(29/90) respectively in the first year. The statistical difference were noticeable between group A and group B(P=0.003). Most dropouts were happened in the first 3 months, group A 41.7%(5/12) and group B 51.7%(15/29) respectively. It had no statistically significant(P=0.558). Two major reasons of dropouts were no improvement of symptoms and lack of confidence.Conclusion:Percentage of dropouts in SLIT patients through telephone management was comparatively high, which can be significantly improved by We-Media management. We-Media management has more advantage,especially during long-term follow-up.

New mesh-type phantoms and their dosimetric applications, including emergencies.

Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8-40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.

Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome.

The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Using Hi-C in edited mouse cells with allelic deletions or inversions within the hinge, here we show that the conserved Dxz4 locus is necessary to maintain this bipartite structure. Dxz4 orientation controls the distribution of contacts on the Xi, as shown by a massive reversal in long-range contacts after Dxz4 inversion. Despite an increase in CTCF binding and chromatin accessibility on the Xi in Dxz4-edited cells, only minor changes in TAD structure and gene expression were detected, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of its bank of CTCF motifs, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.

Analysis of (CAG)n expansion in ATXN1, ATXN2 and ATXN3 in Chinese patients with multiple system atrophy.

Multiple system atrophy (MSA) is a complex and multifactorial neurodegenerative disease, and its pathogenesis remains uncertain. Patients with MSA or spinocerebellar ataxia (SCA) show overlapping clinical phenotypes. Previous studies have reported that intermediate or long CAG expansions in SCA genes have been associated with other neurodegenerative disease. In this study, we screened for the number of CAG repeats in ATXN1, 2 and 3 in 200 patients with MSA and 314 healthy controls to evaluate possible associations between (CAG)n in these three polyQ-related genes and MSA. Our findings indicated that longer repeat lengths in ATXN2 were associated with increased risk for MSA in Chinese individuals. No relationship was observed between CAG repeat length in the three examined genes and age at onset (AO) of MSA.