Sequence Type 5 (ST5) as a Possible Predictor of Bacterial Persistence in Adult Patients with Methicillin-Resistant Staphylococcus aureus Pneumonia Treated with Vancomycin.

Vancomycin remains the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This study assessed risk factors for vancomycin failure in 63 patients with MRSA pneumonia through detailed clinical, microbiological, pharmacokinetic/pharmacodynamic, and genetic analyses of prospective multicenter studies conducted from February 2012 to July 2018. Therapeutic drug monitoring was performed during vancomycin treatment, and the 24-h area under the curve (AUC0-24) was calculated. All baseline strains were collected for MIC determination, heterogeneous vancomycin-intermediate S. aureus (hVISA) screening, and biofilm determination. Whole-genome sequencing was performed on the isolates to analyze their molecular typing and virulence and adhesion genes. Clinical signs and symptoms improved in 44 patients (44/63, 69.8%), with vancomycin daily dose (P = 0.045), peak concentration (P = 0.020), and sdrC (P = 0.047) being significant factors. Isolates were eradicated in 51 patients (51/63, 81.0%), with vancomycin daily dose (P = 0.009), cardiovascular disease (P = 0.043), sequence type 5 (ST5; P = 0.017), tst (P = 0.050), and sec gene (P = 0.044) associated with bacteriological failure. Although the AUC0-24/MIC was higher in the groups with bacterial eradication, the difference was not statistically significant (P = 0.108). Multivariate analysis showed that no variables were associated with clinical efficacy; ST5 was a risk factor for bacterial persistence (adjusted odds ratio, 4.449; 95% confidence interval, 1.103 to 17.943; P = 0.036). ST5 strains had higher frequencies of the hVISA phenotype, biofilm expression, and presence of some adhesion and virulence genes such as fnbB, tst, and sec than non-ST5 strains. Our study suggests that ST5 is a possible predictor of bacterial persistence in MRSA pneumonia treated with vancomycin. IMPORTANCE Few studies have simultaneously examined the influence of clinical characteristics of patients with pneumonia, the vancomycin pharmacokinetic/pharmacodynamic (PK/PD) index, and the phenotypic and genetic characteristics of methicillin-resistant Staphylococcus aureus (MRSA) strains. We assessed risk factors for vancomycin failure in patients with MRSA pneumonia by analyzing these influences in a prospective multicenter study. Sequence type 5 (ST5) was a possible predictor of bacterial persistence in adult patients with MRSA pneumonia (adjusted odds ratio, 4.449). We found that this may be related to ST5 strains having higher levels of vancomycin heterogeneous resistance, biofilms, and the presence of adhesion and virulence genes such as fnbB, tst, and sec.

Recent progress in minimizing the warpage and shrinkage deformations by the optimization of process parameters in plastic injection molding: a review.

The quality control of plastic products is an essential aspect of the plastic injection molding (PIM) process. However, the warpage and shrinkage deformations continue to exist because the PIM process is easily interfered with by several related or independent process parameters. Thus, great efforts have been devoted to optimizing process parameters to minimize the warpage and shrinkage deformations of products during the last decades. In this review, we begin by introducing the manufacturing process in PIM and the cause of warpage and shrinkage deformations, followed by the mechanism about how process parameters, like mold temperature, melt temperature, injection rate, injection pressure, holding pressure, holding and cooling duration, affect those defects. Then, we summarize the recent progress of the design of experiments and four advanced methods (artificial neural networks, genetic algorithm, response surface methodology, and Kriging model) on optimizing process parameters to minimize the warpage and shrinkage deformations. In the end, future perspectives of quality control in injection molding machines are discussed.

[Nontarget Screening and Ecological Risk Assessment of Polar Organic Pollutants in Surface Water on the West Bank of Taihu Lake].

Emerging pollutants occur in the environment, which has become a pressing issue for environmental research. In order to comprehensively screen potential polar organic pollutants in surface water of Wujin and Yixing in the Taihu Lake Basin, nontarget screening was carried out by high performance liquid chromatography(HPLC) and time of flight mass spectrometry(TOF-MS). Screened by accurate mass, isotope distribution, and MS/MS information, 162 organic compounds were identified, including 46 pesticides, 34 drugs, 8 personal care products, and 27 additives; 17 organic synthetic intermediates and 30 metabolites, 45 of which have been verified by reference standards. Through the quantitative analysis of 42 pollutants and ecological risk assessment of 3 trophic model species, it was found that 25 pollutants posed medium risk while 12 pollutants presented high risk. Nontarget screening can be used to identify potential pollutants with no prior information or standards. It is not only fast, accurate, and has high analytical flux, but also provides an important basis for subsequent ecological risk assessment.

Helicobacter pylori infection and risk for developing dementia: an evidence-based meta-analysis of case-control and cohort studies.

BACKGROUND: Infection with multiple pathogens may play a key role in the pathogenesis of dementia. Whether Helicobacter pylori (H. pylori) infection is associated causally with dementia is controversial. OBJECTIVE: We conduct a meta-analysis of case-control and cohort studies on the association between H. pylori infection and the risk for all-cause and Alzheimer's disease (AD) dementia. METHODS: Two independent reviewers searched the PubMed, Cochrane Library, and Embase databases with English language restrictions from the date of conception to September 18, 2020. The primary analysis was as follows: the exposure variable was H. pylori infection, and the outcome was incident all-cause and AD dementia. Pooled odds ratios (OR), relative risk (RR), and corresponding 95% confidence intervals (CI) were obtained using the fixed-or random-effect model. Forest plots were generated to summarize the results. RESULTS: Ten studies involving 96,561 participants were included in the meta-analysis: 5 case-control studies and 5 cohort studies. The overall pooled cohort studies showed a significant positive association between H. pylori infection and all-cause dementia with pooled RR of 1.36 (95% CI, 1.11-1.67). There was no association between H. pylori infection and risk for developing AD: RR of 1.33 (95% CI, 0.86-2.05) in cohort studies, and OR of 1.72 (95% CI, 0.97-3.04) in case-control studies. Significant heterogeneity was showed in each comparison group. CONCLUSION: This meta-analysis supports a positive association between H. pylori infection and the risk of all-cause dementia, but not AD dementia. Due to the interference of confounding factors, randomized controlled trials are needed to prove their causality.

[Pollution Characteristics and Risk Assessment of Nitro Polycyclic Aromatic Hydrocarbons in PM2.5 of Nanjing, China].

Nitro polycyclic aromatic hydrocarbons (NPAHs) are important pollutants with carcinogenic effects present in PM2.5. To analyze the pollution characteristics and sources of NPAHs, 14 samples of PM2.5 were collected in Nanjing from November 2017 to March 2018. The results showed that, 2,8-dinitrodibenzothiophene (743 pg·m-3), 2, 7-dinitrofluorene (331 pg·m-3), 9-nitroanthracene (326 pg·m-3), 3-nitrofluoranthene (217 pg·m-3), and 1,8-dinitropyrene (193 pg·m-3) were dominant, and the detection concentrations notably varied between seasons; the highest concentrations occurred in winter (3082 pg·m-3) followed by autumn (1553 pg·m-3) and spring (1218 pg·m-3). The ratio of nitrofluoranthene and 1-nitropyrene concentrations, and 9-nitroanthracene and 1-nitropyrene concentrations, indicated that the main sources of NPAHs in the PM2.5 of Nanjing were photooxidation of polycyclic aromatic hydrocarbons and biomass burning. NPAHs were more typically associated with smaller particles, which further indicated that secondary formation is an important source. The current carcinogenic risk of NPAHs in PM2.5 in Nanjing is controllable, and dinitro-polycyclic aromatic hydrocarbons represent the highest level of risk. The data presented in this study provide important baseline information that can inform the management of risks associated with NPAHs in PM2.5 in Nanjing.

Photodegradation of carbon dots cause cytotoxicity.

Carbon dots (CDs) are photoluminescent nanomaterials with wide-ranging applications. Despite their photoactivity, it remains unknown whether CDs degrade under illumination and whether such photodegradation poses any cytotoxic effects. Here, we show laboratory-synthesized CDs irradiated with light degrade into molecules that are toxic to both normal (HEK-293) and cancerous (HeLa and HepG2) human cells. Eight days of irradiation photolyzes 28.6-59.8% of the CDs to <3 kilo Dalton molecules, 1431 of which are detected by high-throughput, non-target high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Molecular network and community analysis further reveal 499 cytotoxicity-related molecules, 212 of which contain polyethylene glycol, glucose, or benzene-related structures. Photo-induced production of hydroxyl and alkyl radicals play important roles in CD degradation as affected by temperature, pH, light intensity and wavelength. Commercial CDs show similar photodegraded products and cytotoxicity profiles, demonstrating that photodegradation-induced cytotoxicity is likely common to CDs regardless of their chemical composition. Our results highlight the importance of light in cytocompatibility studies of CDs.

Astragaloside­IV modulates NGF­induced osteoblast differentiation via the GSK3β/β­catenin signalling pathway.

Astragaloside (AST) is derived from the Chinese herb Astragalus membranaceus, and studies have demonstrated that it promotes differentiation of bone marrow­derived mesenchymal stem cells (BMSCs). To the best of our knowledge, however, the functions of the component AST­IV in osteogenesis have not previously been elucidated. The present study aimed to verify the effects of AST­IV in osteogenesis. First, the proliferation and differentiation status of human BMSCs incubated with AST­IV were analysed and compared with a control (no AST­IV treatment). In order to determine the involvement of the glycogen synthase kinase (GSK)3ß signalling pathway in AST­IV, overexpression and inhibition of GSK3ß was induced during incubation of BMSCs with AST­IV. In order to investigate how neuronal growth factor (NGF) contributes to BMSCs differentiation, BMSCs were co­incubated with an anti­NGF antibody and AST IV, and then levels of osteogenesis markers were assessed. The results demonstrated for the first time that AST­IV contributed to BMSCs differentiation. Furthermore, the GSK3ß/ß­catenin signalling pathway was revealed to be involved in AST­IV­induced osteogenesis; moreover, AST­IV accelerated differentiation by enhancing the expression levels of NGF. In summary, the present study demonstrated that AST­IV promotes BMSCs differentiation, thus providing a potential target for the treatment of osteoporosis.

Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial.

BACKGROUND: The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI. OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC, ) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome. METHODS: This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded. DISCUSSION: The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018).

Astragalus saponin IV promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-21/NGF/BMP2/Runx2 pathway.

BACKGROUND: Astragalus saponin IV(AS- IV) extracted from tranditional Chinese medicine Radix Astragali Mongolici, which had been reported to have medicinal properties in treating several types of diseases. This study aimed at investigating the biological functions of AS-IV on bone marrow mesenchymal cells(BMSCs) differentiation, therefore, seeking for a better application of AS-IV on fracture or other orthopedic disorders. METHODS: AS-IV was co-incubated with BMSCs in vitro to testify whether it can influence the proliferation and differentiation of BMSCs. Cell proliferation activity was detected by Cell Counting Kit-8 (CCK-8), while its differentiation promoting capibility was obtained by alkaline phosphatase (ALP) activity assay and Alizarin red S staining. Besides, differentiation protein markers of preosteoblast was detected by western blots. Neuron growth factor antagonists (NGFA) and microRNA-21 (miR-21) inhibitors were co incubated with AS-IV to search the regulatory pathways it activated in BMSCs. RESULTS: AS-IV incubation boosted the proliferation of BMSCs, and accelerated the differentiating direction into preosteoblasts. Runx2, OPN, BMP2, OCN proteins were up regulated after AS- IV treatment. MiR-21/NGF/BMP2/Runx2 pathway can participate the biological effects of AS- IV on BMSCs. CONCLUSION: AS- IV might be used as a therapeutic agent for bone fracture or other orthopedic disorders.

A short review of bioaerosol emissions from gas bioreactors: Health threats, influencing factors and control technologies.

Bioaerosols have widely been a concern due to their potential harm to human health caused by the carrying and spreading of harmful microorganisms. Biofiltration has been generally used as a green and effective technology for processing VOCs. However, bioaerosols can be emitted into the atmosphere as secondary pollutants from the biofiltration process. This review presents an overview of bioaerosol emissions from gas bioreactors. The mechanism of bioaerosols production and the effect of biofiltration on bioaerosol emissions were analyzed. The results showed that the bioaerosol emission concentrations were generally exceeded 104 CFU m-3, which would damage to human health. Biomass, inlet gas velocity, moisture content, temperature, and some other factors have significant influences on bioaerosol emissions. Moreover, as a result of the analysis done herein, different inactivation technologies and microbial immobilization of bioaerosols were proposed and evaluated as a potential solution for reducing bioaerosols emissions. The purpose of this paper is to make more people realize the importance of controlling the emissions of bioaerosols in the biofiltration process and to make the treatment of VOCs by biotechnology more environmentally friendly. Additionally, the present work intends to increase people's awareness in regards to the control of bioaerosols, including microbial fragment present in bioaerosols.

Clinical Experience in Treatment of Alzheimer's Disease with Jiannao Yizhi Formula () and Routine Western Medicine.

OBJECTIVE: To investigate the long-term therapeutic effects of the Chinese medicine Jiannao Yizhi Formula (, JYF) in the treatment of Alzheimer's disease (AD). METHODS: Sixty mild-to-moderate AD participants were recruited and randomly allocated to the treatment (30 with JYF) and the control groups (30 with donepezil) for 6 months with the random numbers. The primary outcomes were scores of Alzheimer's Disease Rating Scale-Cognitive (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL). Safety assessments were conducted at baseline and the 6th month of treatment. Serum levels of acetylcholine (Ach), amyloid-ß protein 42 (Aß42), and the microtubule-associated protein tau (Tau) were also determined by enzyme-liked immunosorbent assay. RESULTS: Fifty-one participants were included in the final analyses (JYF n=27; donepezil n=24). Compared with baseline, both JYF and donepezil increased the MoCA and MMSE scores and decreased the ADAS-Cog and CM-SS scores (P<0.05 or P<0.01). Both drugs increased the serum levels of Ach and decreased the serum levels of Aß42 and Tau (all P<0.05). There was no significant difference in these variables between the two groups, which showed that JYF was not inferior to donepezil. No obviously significant changes were observed in the ADL. No severe adverse events were observed in both groups. CONCLUSION: The effect and safety of JYF for the treatment of AD were not inferior to those of donepezil.

Performance enhancement of a biofilter with pH buffering and filter bed supporting material in removal of chlorobenzene.

Acidic substances, which produced during chlorinated volatile organic compounds, will corrode the commonly used packing materials, and then affect the removal performance of biofiltration. In this study, three biofilters with different filter bed structure were established to treat gaseous chlorobenzene. CaCO3 and 3D matrix material was added in filter bed as pH buffering material and filter bed supporting material, respectively. A comprehensive investigation of removal performance, biomass accumulation, microbial community, filter bed height, voidage, pressure drops, and specific surface area of the three biofilters was compared. The biofilter with CaCO3 and 3D matrix material addition presented stable removal performance and microbial community, and greater biomass density (209.9 kg biomass/m3 filter bed) and growth rate (0.033 d-1) were obtained by using logistic equation. After 200 days operation, the height, voidage, pressure drop, specific surface area of the filter bed consisted of perlite was 27.4 cm, 0.39, 32.8 Pa/m, 974,89 m2/m3, while those of the filter bed with CaCO3 addition was 28.2 cm, 0.43, 21.3 Pa/m, and 1021.03 m2/m3, and those of the filter bed with CaCO3 and 3D matrix material addition was 28.7 cm, 0.55, 17.4 Pa/m, and 1041.60 m2/m3. All the results verified the biofilter with CaCO3 and 3D matrix material addition is capable of sustaining the long-term performance of biofilters. CaCO3 could limit the changes of removal efficiency, microbial community and filter bed structure by buffering the pH variation. And 3D matrix material could maintain the filter bed structure by supporting the filter bed, regardless of the buffering effect.

Efficacy and Safety of Guilingji Capsules () for Treating Mild-to-Moderate Cognitive Impairment: Study Protocol for A Randomized, Double-Blind, Positive-Controlled, Multicenter and Noninferiority Trial / 中国结合医学杂志

BACKGROUND@#The incidence of cognitive impairment (CI) is gradually increasing, which has attracted more attention from medical researchers worldwide. Definitive mechanisms of pathogenesis remain elusive, and there are few medications that have been proven effective for CI. The utilization of Chinese herbal medicine has shown positive therapeutic effects for a broad spectrum of diseases, including CI.@*OBJECTIVE@#The purpose of this study is to evaluate the safety and efficacy of Guilingji Capsules (GLJC, ) in treating mild-to-moderate CI with Shen (Kidney) and marrow deficiency syndrome.@*METHODS@#This is a randomized, double-blind, positive-controlled, multicenter clinical trial with a noninferiority design that included 348 participants randomly divided into an experimental arm and an active comparator arm. Individuals in the experimental arm (174 cases) took 0.6 g of GLJC once a day and 19.2 mg of Gingko biloba extract mimetic 3 times a day. Individuals in the active comparator arm (174 cases) took 0.6 g of GLJC mimetic once a day and 19.2 mg of Gingko biloba extract in tablet form 3 times a day. The intervention period included two sessions over 24 weeks. The primary outcome be the effectiveness of GLJC on cognitive improvement after 24 weeks of treatment, which was defined as an increase in the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) Scale. The secondary outcomes were improvement in independence, daily living ability, and Chinese medicine (CM) syndrome, which were measured with the Alzheimer's disease Rating Scale-Cognitive Project (ADAS-Cog), Clinical Dementia Rating (CDR) Total Score, Activities of Daily Living (ADL) Total Score and the Chinese Medicine Symptom Scale (CM-SS), respectively. Serum acetylcholine, acetylcholinesterase, bax and bcl-2 were monitored to explore the mechanism of GLJC on CI. In addition, safety measures, including vital signs, electrocardiography, laboratory indicators (full blood count, kidney and liver function tests, routine urine test and routine stool test) and adverse events, were also recorded.@*DISCUSSION@#The purpose of this trial is to evaluate the efficacy and safety of GLJC in patients with mild-to-moderate CI with kidney and marrow deficiency syndrome. If successful, the results would provide a viable treatment for patients with mild-to-moderate CI. (Clinical Trials.gov. ID: NCT03647384. Registered on 23 August 2018).

In situ measurement of perfluoroalkyl substances in aquatic systems using diffusive gradients in thin-films technique.

To better understand the environmental impact of ubiquitous perfluoroalkyl substances (PFASs) in waters, reliable and robust measurement techniques are needed. As one of the most widely used passive sampling approaches, diffusive gradients in thin-films (DGT) is not only easy to handle but also provides time-weighted analyte concentrations. Based on DGT with XAD18 as a binding agent, we developed a new methodology to measure two frequently detected PFASs in surface waters and wastewaters, i.e. perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their diffusion coefficients in the diffusive gel, measured using an independent diffusion cell, were 4.37 × 10-6 and 5.08 × 10-6 cm2 s-1 at 25 °C, respectively. DGT had a high capacity for PFOA and PFOS at 196 and 246 µg per gel disk, suggesting the DGT sampler was suitable for deployment of several weeks. Time-integrated concentrations of PFOA and PFOS in a natural lake and river, and a municipal wastewater treatment plant effluent using DGT samplers deployed in situ for 12-33 d were comparable to those measured by a solid-phase extraction method coupled with high-frequency grab sampling. This study demonstrates that DGT is an effective tool for in situ monitoring of PFASs in natural waters and wastewaters.

[Contamination Levels and Ecological Risk Assessment of Phthalate Esters (PAEs) in the Aquatic Environment of Key Areas of Taihu Lake].

To better understand phthalate esters (PAEs) pollution in key areas of Taihu Lake, water and sediment samples were collected for content analysis. The concentrations of ∑PAEs in water samples from wet, dry, and normal seasons ranged 1.6-11.2 µg·L-1 (mean:3.68 µg·L-1), nd-6.21 µg·L-1 (mean:1.3 µg·L-1), and nd-1.72 µg·L-1 (mean:0.48 µg·L-1), respectively. No differences were found between upstream and downstream samples. DEHP was the predominant component in water samples, whereas DBP exceeded the national surface water environmental quality standards. The total PAE concentration in the sediment ranged between 0.74 and 6.90 µg·g-1 (mean:2.64 µg·g-1), with DBP and DEHP the predominant PAEs. The risk quotient (RQ) results showed that DBP and DEHP contributed the most potentially adverse effects to the aquatic environment in the key areas. The contents of PAEs in sediment were all less than the ERLs, thus posing no significant threat to aquatic organisms. The overall level of PAEs in the study area was moderate compared to those in other areas, including rivers, lakes, and estuaries from cities worldwide. Industrial pollution and urban activities are the major sources of PAEs in the aquatic environment of key areas of Taihu Lake.

Heterologous Expression of the Cotton NBS-LRR Gene GbaNA1 Enhances Verticillium Wilt Resistance in Arabidopsis.

Verticillium wilt caused by Verticillium dahliae results in severe losses in cotton, and is economically the most destructive disease of this crop. Improving genetic resistance is the cleanest and least expensive option to manage Verticillium wilt. Previously, we identified the island cotton NBS-LRR-encoding gene GbaNA1 that confers resistance to the highly virulent V. dahliae isolate Vd991. In this study, we expressed cotton GbaNA1 in the heterologous system of Arabidopsis thaliana and investigated the defense response mediated by GbaNA1 following inoculations with V. dahliae. Heterologous expression of GbaNA1 conferred Verticillium wilt resistance in A. thaliana. Moreover, overexpression of GbaNA1 enabled recovery of the resistance phenotype of A. thaliana mutants that had lost the function of GbaNA1 ortholog gene. Investigations of the defense response in A. thaliana showed that the reactive oxygen species (ROS) production and the expression of genes associated with the ethylene signaling pathway were enhanced significantly following overexpression of GbaNA1. Intriguingly, overexpression of the GbaNA1 ortholog from Gossypium hirsutum (GhNA1) in A. thaliana did not induce the defense response of ROS production due to the premature termination of GhNA1, which lacks the encoded NB-ARC and LRR motifs. GbaNA1 therefore confers Verticillium wilt resistance in A. thaliana by the activation of ROS production and ethylene signaling. These results demonstrate the functional conservation of the NBS-LRR-encoding GbaNA1 in a heterologous system, and the mechanism of this resistance, both of which may prove valuable in incorporating GbaNA1-mediated resistance into other plant species.

Large animal models of traumatic brain injury.

Purpose/Aim: Animal models of traumatic brain injury (TBI) provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents. However, compared with rodents, large animals (e.g. swine, rabbit, sheep, ferret, etc.) show great advantages in modeling TBI due to the similarity of their brains to human brain. The aim of our review was to summarize the development and progress of common large animal TBI models in past 30 years. MATERIALS AND METHODS: Mixed published articles and books associated with large animal models of TBI were researched and summarized. RESULTS: We majorly sumed up current common large animal models of TBI, including discussion on the available research methodologies in previous studies, several potential therapies in large animal trials of TBI as well as advantages and disadvantages of these models. CONCLUSIONS: Large animal models of TBI play crucial role in determining the underlying mechanisms and screening putative therapeutic targets of TBI.

The island cotton NBS-LRR gene GbaNA1 confers resistance to the non-race 1 Verticillium dahliae isolate Vd991.

Wilt caused by Verticillium dahliae significantly reduces cotton yields, as host resistance in commercially cultivated Gossypium species is lacking. Understanding the molecular basis of disease resistance in non-commercial Gossypium species could galvanize the development of Verticillium wilt resistance in cultivated species. Nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins play a central role in plant defence against pathogens. In this study, we focused on the relationship between a locus enriched with eight NBS-LRR genes and Verticillium wilt resistance in G. barbadense. Independent virus-induced gene silencing of each of the eight NBS-LRR genes in G. barbadense cultivar Hai 7124 revealed that silencing of GbaNA1 alone compromised the resistance of G. barbadense to V. dahliae isolate Vd991. In cultivar Hai 7124, GbaNA1 could be induced by V. dahliae isolate Vd991 and by ethylene, jasmonic acid and salicylic acid. Nuclear protein localization of GbaNA1 was demonstrated by transient expression. Sequencing of the GbaNA1 orthologue in nine G. hirsutum accessions revealed that all carried a non-functional allele, caused by a premature peptide truncation. In addition, all 10 G. barbadense and nine G. hirsutum accessions tested carried a full-length (∼1140 amino acids) homologue of the V. dahliae race 1 resistance gene Gbve1, although some sequence polymorphisms were observed. Verticillium dahliae Vd991 is a non-race 1 isolate that lacks the Ave1 gene. Thus, the resistance imparted by GbaNA1 appears to be mediated by a mechanism distinct from recognition of the fungal effector Ave1.

A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses.

Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain-containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V. dahliae Vd991. Functional analyses demonstrated that only VdCUT11, as purified protein, induced cell death and triggered defense responses in Nicotiana benthamiana, cotton, and tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner. Furthermore, coinfiltration assays revealed that the carbohydrate-binding module family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an important secreted enzyme and virulence factor that elicits plant defense responses in the absence of VdCBM1.

Comparative genomics reveals cotton-specific virulence factors in flexible genomic regions in Verticillium dahliae and evidence of horizontal gene transfer from Fusarium.

Verticillium dahliae isolates are most virulent on the host from which they were originally isolated. Mechanisms underlying these dominant host adaptations are currently unknown. We sequenced the genome of V. dahliae Vd991, which is highly virulent on its original host, cotton, and performed comparisons with the reference genomes of JR2 (from tomato) and VdLs.17 (from lettuce). Pathogenicity-related factor prediction, orthology and multigene family classification, transcriptome analyses, phylogenetic analyses, and pathogenicity experiments were performed. The Vd991 genome harbored several exclusive, lineage-specific (LS) genes within LS regions (LSRs). Deletion mutants of the seven genes within one LSR (G-LSR2) in Vd991 were less virulent only on cotton. Integration of G-LSR2 genes individually into JR2 and VdLs.17 resulted in significantly enhanced virulence on cotton but did not affect virulence on tomato or lettuce. Transcription levels of the seven LS genes in Vd991 were higher during the early stages of cotton infection, as compared with other hosts. Phylogenetic analyses suggested that G-LSR2 was acquired from Fusarium oxysporum f. sp. vasinfectum through horizontal gene transfer. Our results provide evidence that horizontal gene transfer from Fusarium to Vd991 contributed significantly to its adaptation to cotton and may represent a significant mechanism in the evolution of an asexual plant pathogen.