The experience of shared decision-making for people with asthma: A systematic review and metasynthesis of qualitative studies.

OBJECTIVES: To identify, describe and synthesise the views and experiences of adults living with asthma regarding shared decision-making (SDM) in the existing qualitative literature METHODS: We conducted a comprehensive search of 10 databases (list databases) from inception until September 2023. Screening was performed according to inclusion criteria. Tools from the Joanna Briggs lnstitute were utilised for the purposes of data extraction and synthesis in this study. The data extraction process in this study employed the Capability, Opportunity and Motivation Model of Behaviour (COM-B model) as a framework, and a pragmatic meta-aggregative approach was employed to synthesise the collected results. RESULTS: Nineteen studies were included in the metasynthesis. Three synthesised themes were identified: the capability of people living with asthma, the opportunities of people living with asthma in SDM, and the motivation of the people living with asthma in SDM. CONCLUSIONS: We have identified specific factors influencing people living with asthma engaging in SDM. The findings of this study can serve as a basis for the implementation of SDM in people living with asthma and provide insights for the development of their SDM training programs. The ConQual score for the synthesised findings was rated as low. To enhance confidence, future studies should address dependability and credibility factors. PRACTICE IMPLICATIONS: This review contemplates the implementation of SDM from the perspective of people living with asthma, with the aim of providing patient-centred services for them. The results of this review can benefit the implementation of SDM and facilitate information sharing. It offers guidance for SDM skills training among adults living with asthma, fosters a better doctor-patient relationship and facilitates consensus in treatment decisions, thereby enabling personalised and tailored medical care. PATIENT OR PUBLIC CONTRIBUTION: Three nursing graduate students participated in the data extraction and integration process, with two students having extensive clinical experience that provided valuable insights for the integration.

Ethylene-responsive factor ERF114 mediates fungal pathogen effector PevD1-induced disease resistance in Arabidopsis thaliana.

APETALA2/ethylene-responsive factor (AP2/ERF) family transcription factors are well-documented in plant responses to a wide range of biotic and abiotic stresses, but their roles in mediating elicitor-induced disease resistance remains largely unexplored. PevD1 is a Verticillium dahliae secretory effector that can induce disease resistance in cotton and tobacco plants. In our previous work, Nicotiana benthamiana ERF114 (NbERF114) was identified in a screen of genes differentially expressed in response to PevD1 infiltration. Here, we found that the ortholog of NbERF114 in Arabidopsis thaliana (ERF114) also strongly responded to PevD1 treatment and transcripts were induced by Pseudomonas syringae pv. tomato (Pst) DC3000 infection. Loss of ERF114 function caused impaired disease resistance, while overexpressing ERF114 (OE-ERF114) enhanced resistance to Pst DC3000. Moreover, ERF114 mediated PevD1-induced disease resistance. RNA-sequencing analysis revealed that the transcript level of phenylalanine ammonia-lyase1 (PAL1) and its downstream genes were significantly suppressed in erf114 mutants compared with A. thaliana Col-0. Reverse transcription-quantitative PCR (RT-qPCR) analysis further confirmed that the PAL1 mRNA level was significantly elevated in overexpressing OE-ERF114 plants but reduced in erf114 mutants compared with Col-0. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and electrophoretic mobility shift assay verified that ERF114 directly bound to the promoter of PAL1. The gene expression profiles of ERF114 and PAL1 in oestradiol-inducible transgenic plants confirmed ERF114 could activate PAL1 transcriptional expression. Further investigation revealed that ERF114 positively modulated PevD1-induced lignin and salicylic acid accumulation, probably by activating PAL1 transcription.

DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images. METHODS: A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts. RESULTS: On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971-0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis. CONCLUSION: The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.

Verticillium dahliae secretory effector PevD1 induces leaf senescence by promoting ORE1-mediated ethylene biosynthesis.

Leaf senescence, the final stage of leaf development, is influenced by numerous internal and environmental signals. However, how biotic stresses such as pathogen infection regulate leaf senescence remains largely unclear. In this study, we found that the premature leaf senescence in Arabidopsis caused by the soil-borne vascular fungus Verticillium dahliae was impaired by disruption of a protein elicitor from V. dahliae 1 named PevD1. Constitutive or inducible overexpression of PevD1 accelerated Arabidopsis leaf senescence. Interestingly, a senescence-associated NAC transcription factor, ORE1, was targeted by PevD1. PevD1 could interact with and stabilize ORE1 protein by disrupting its interaction with the RING-type ubiquitin E3 ligase NLA. Mutation of ORE1 suppressed the premature senescence caused by overexpressing PevD1, whereas overexpression of ORE1 or PevD1 led to enhanced ethylene production and thereby leaf senescence. We showed that ORE1 directly binds the promoter of ACS6 and promotes its expression for mediating PevD1-induced ethylene biosynthesis. Loss-of-function of ACSs could suppress V. dahliae-induced leaf senescence in ORE1-overexpressing plants. Furthermore, we found thatPevD1 also interacts with Gossypium hirsutum ORE1 (GhORE1) and that virus-induced gene silencing of GhORE1 delays V. dahliae-triggered leaf senescence in cotton, indicating a possibly conserved mechanism in plants. Taken together, these results suggest that V. dahliae induces leaf senescence by secreting the effector PevD1 to manipulate the ORE1-ACS6 cascade, providing new insights into biotic stress-induced senescence in plants.

FoEG1, a secreted glycoside hydrolase family 12 protein from Fusarium oxysporum, triggers cell death and modulates plant immunity.

Fusarium oxysporum is an important soilborne fungal pathogen with many different formae speciales that can colonize the plant vascular system and cause serious crop wilt disease worldwide. We found a glycoside hydrolase family 12 protein FoEG1, secreted by F. oxysporum, that acted as a pathogen-associated molecular pattern (PAMP) targeting the apoplast of plants to induce cell death. Purified FoEG1 protein triggered cell death in different plants and induced the plant defence response to enhance the disease resistance of plants. The ability of FoEG1 to induce cell death was mediated by leucine-rich repeat (LRR) receptor-like kinases BAK1 and SOBIR1, and this ability was independent of its hydrolase activity. The mutants of cysteine residues did not affect the ability of FoEG1 to induce cell death, and an 86 amino acid fragment from amino acid positions 144 to 229 of FoEG1 was sufficient to induce cell death in Nicotiana benthamiana. In addition, the expression of FoEG1 was strongly induced in the early stage of F. oxysporum infection of host plants, and FoEG1 deletion or loss of enzyme activity reduced the virulence of F. oxysporum. Therefore, our results suggest that FoEG1 can contribute to the virulence of F. oxysporum depending on its enzyme activity and can also act as a PAMP to induce plant defence responses.

Multimodal Retinal Imaging for Detection of Ischemic Stroke.

Background: This study aims to evaluate ocular changes in patients with ischemic stroke using multimodal imaging and explore the predictive value of ocular abnormalities for ischemic stroke. Methods: A total of 203 patients (ischemic stroke group, 62; control group, 141) were enrolled in this study. Basic data from patients, including age; gender; height; weight; history of hypertension, hyperlipidemia, diabetes, alcohol use, and coronary heart disease; and smoking status, were collected. Consequently, Doppler color ultrasound, color fundus photography, and optical coherence tomography (OCT) examinations were conducted. Differences in traditional risk factors and ocular parameters between the two groups were compared, and binary logistic regression was used for multivariate analysis. Results: The central retinal artery equivalent (CRAE) in the ischemic stroke group was 150.72 ± 20.15 µm and that in the control group was 159.68 ± 20.05 µm. The difference was statistically significant (P = 0.004). Moreover, the subfoveal choroidal thickness (SFChT) in the ischemic stroke group was 199.90 ± 69.27 µm and that in the control group was 227.40 ± 62.20 µm. The difference was statistically significant (P = 0.006). Logistic regression results showed that smoking [odds ratio (OR) = 2.823; 95% confidence interval (95% CI) = 1.477-5.395], CRAE (OR = 0.980; 95% CI = 0.965-0.996), and SFChT (OR = 0.994; 95% CI = 0.989-0.999) are associated with increased risk of ischemic stroke when ocular parameters were combined with traditional risk factors. The area under the receiver operating characteristic (ROC) curve was 0.726, which shows good diagnostic accuracy. Conclusion: SFChT may be a diagnostic marker for early detection and monitoring of ischemic stroke. Combined with traditional risks, retinal artery diameter, and choroidal thickness, the prediction model can improve ischemic stroke prediction.

Association between dietary antioxidants and risk for diabetic retinopathy in a Chinese population.

BACKGROUND: Diabetic retinopathy (DR) is related to oxidative stress and insufficient intake of dietary antioxidants may be associated with the onset and progression of DR. This study aimed to detect the association between main dietary antioxidants intake and the risk for DR. METHODS: This is a cross-sectional study of a Chinese urban population. Four hundred and fifty-five subjects with type 2 diabetes were recruited and divided into diabetic patients without retinopathy (DWR) group and DR group based on their retinal status. CSMO (clinically significant macular oedema) was diagnosed by stereoscopic photography. Demographic and lifestyle characteristics were ascertained by questionnaire. General physical and ophthalmic examinations were completed for all subjects. Dietary antioxidants were assessed by 3-day food records. Subjects who have taken any type of vitamin supplements were excluded from the study. The association of dietary antioxidants with the risk for DR was analysed by logistic regression with adjustment of other factors. The dietary antioxidants levels of the CSMO subjects and non-CSMO subjects were compared using the Wilcoxon rank sum test. RESULTS: One hundred and nineteen subjects in DR group and 336 subjects in DWR group participated in the study. Only ten DR subjects had CSMO. The results showed that higher vitamin E (OR (95% CI):0.97 (0.95, 1.00), P = 0.036) and selenium (OR (95% CI):0.98 (0.96, 1.00), P = 0.017) intake appear to be the protective factors of DR. The dietary antioxidants levels of CSMO and non-CSMO subjects had no statistical differences (P > 0.05). CONCLUSIONS: Dietary antioxidants intake, particularly vitamin E and selenium, were observed to have protective effects on DR.

Nbnrp1 mediates Verticillium dahliae effector PevD1-triggered defense responses by regulating sesquiterpenoid phytoalexins biosynthesis pathway in Nicotiana benthamiana.

PevD1, a fungal effector secreted by Verticillium dahliae, could induce hypersensitive responses-like necrosis and systemic acquired resistance (SAR) in cotton and tobacco plants. PevD1 could drastically induce the expression of Nbnrp1, which is an asparagine-rich protein (NRP) of Nicotiana benthamiana. Our previous research indicated that Nbnrp1 positively regulated PevD1-induced cell necrosis and disease resistance. In this study, we further investigated PevD1-induced immune responses in both wild-type (WT) and Nbnrp1-RNAi lines through RNA-seq, in order to reveal the underlying mechanism of Nbnrp1-modulated PevD1-induced disease resistance in N. benthamiana. Results showed that Nbnrp1-RNAi lines exhibited reduced PevD1-induced immune responses, like inhibiting H2O2 accumulation and MAPK phosphorylation. To silence Nbnrp1 inhibited the expression of PevD1-induced differential expression genes (DEGs) involved in pathways associated with sesquiterpenoid and triterpenoid biosynthesis, flavone and flavonol biosynthesis, plant-pathogen interaction and phenylpropanoid biosynthesis, etc. It is worth noting that sesquiterpene phytoalexin capsidiol accumulation were obviously decreased in Nbnrp1-RNAi plants after PevD1 treatment, accompanied with the down-expression of EAS and EAH, which were two key genes related to capsidiol biosynthesis. These results suggested that Nbnrp1 mediates PevD1-induced defense responses by regulating sesquiterpenoid phytoalexins biosynthesis pathway.

[Research progress on anti-atherosclerosis effect and mechanism of flavonoids compounds mediated by macrophages].

Flavonoids are important active ingredients of traditional Chinese medicine, mainly with cardiovascular, anti-liver injury, antioxidant, antispasmodic, and estrogen-like effects. These compounds have obvious effects on the cardiovascular and cerebrovascular diseases. Macrophage-derived foam cells are the key medium in the process of atherosclerosis(AS). In plaque, allserum lipids, serum lipoproteins, and various pro-or anti-inflammatory stimulating factors, chemokines, and small bioactive molecules can significantly affect the macrophage phenotype and induce stronger pro-inflammatory or anti-inflammatory properties. Studies have shown that some flavonoids can be used for macrophages through different pathways and mechanisms, playing an anti-atherosclerosis effect to different degrees, including promotion of cholesterol efflux from macrophages, anti-foaming of macrophages, inhibition of secretion of inflammatory factors, and antioxidant modified low density lipoprotein(ox-LDL)-induced apoptosis of macrophages. Related gene regulation inclu-ded ATP-binding cassette transporter A1(ABCA1), ATP-binding cassette transporter G1(ABCG1), Toll-like receptor(TLR), and scavenger receptor(SR). In this article, we would review the recent research progress of flavonoids on anti-atherosclerosis effect me-diated by macrophage. It is expected to provide new treatment strategies for AS-related cardiovascular and cerebrovascular diseases, and provide research ideas and development directions for the use of related natural medicines and design of new products.

Association of candidate gene polymorphisms with diabetic retinopathy in Chinese patients with type 2 diabetes.

AIM: To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system. RESULTS: Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs. CONCLUSION: The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

The Novel Cerato-Platanin-Like Protein FocCP1 from Fusarium oxysporum Triggers an Immune Response in Plants.

Panama disease, or Fusarium wilt, the most serious disease in banana cultivation, is caused by Fusarium oxysporum f. sp. cubense (FOC) and has led to great economic losses worldwide. One effective way to combat this disease is by enhancing host plant resistance. The cerato-platanin protein (CPP) family is a group of small secreted cysteine-rich proteins in filamentous fungi. CPPs as elicitors can trigger the immune system resulting in defense responses in plants. In this study, we characterized a novel cerato-platanin-like protein in the secretome of Fusarium oxysporum f. sp. cubense race 4 (FOC4), named FocCP1. In tobacco, the purified recombinant FocCP1 protein caused accumulation of reactive oxygen species (ROS), formation of necrotic reaction, deposition of callose, expression of defense-related genes, and accumulation of salicylic acid (SA) and jasmonic acid (JA) in tobacco. These results indicated that FocCP1 triggered a hypersensitive response (HR) and systemic acquired resistance (SAR) in tobacco. Furthermore, FocCP1 enhanced resistance tobacco mosaic virus (TMV) disease and Pseudomonas syringae pv. tabaci 6605 (Pst. 6605) infection in tobacco and improved banana seedling resistance to FOC4. All results provide the possibility of further research on immune mechanisms of plant and pathogen interactions, and lay a foundation for a new biological strategy of banana wilt control in the future.

Estrogen receptor alpha activates MAPK signaling pathway to promote the development of endometrial cancer.

Endometrial cancer (EC) is a common malignant tumor of the female reproductive system in the world. For most of the treated patients, although the survival rate is improved, most patients still have a poor prognosis. The pathogenesis of EC has always been a strong scientific focus, but there is no clear conclusion. Therefore, in view of modularization, this study is to conduct an in-depth analysis on the effects of estrogen receptor alpha (ERα) regarding EC. The purpose is to identify the molecular course of EC. We obtained 10 co-expression modules, in which ANO2, EMP3, and other genes are significantly differentially expressed in patients with EC. Additionally, there are active regulatory effects in dysfunction modules, thus genes such as ANO2 and EMP3 would be identified as key genes, which are associated with the development of EC. Enrichment results showed that the module genes were significantly involved in RNA splicing, covalent chromatin modification, histone modification, and organelle fission, and other biological processes, as well as significantly regulated mitogen-activated protein kinases (MAPK) signaling pathway, Endocytosis, Rap1 signaling pathway, and viral carcinogenesis, and other signaling pathways. Finally, we identified noncoding RNA pivot including FENDRR, miR-520c-3p. Besides, transcription factors pivot including NFKB1, E2F1, and RELA which significantly regulate dysfunction module genes. Overall, our work deciphered a co-expression network involving differential gene regulation in ERα-associated EC. It helps reveal the core modules and potential regulatory factors of the diseases and enhances our understanding of the pathogenesis. More importantly, we revealed that ERα activates the MAPK signaling pathway to promote the development of EC. It helps to provide a new reference for later research.

Verticillium dahliae PevD1, an Alt a 1-like protein, targets cotton PR5-like protein and promotes fungal infection.

Alt a 1 family proteins (AA1s) have only been observed in the Dothideomycetes and Sordariomycetes classes of fungi, and their biological functions have remained poorly understood. Verticillium dahliae, a soil-borne pathogen that causes plant wilt disease, secretes hundreds of proteins during the process of pathogenic infection, including the AA1 member PevD1. In this study, we found that the pevd1 transcript was present in all of the hosts studied (cotton, Arabidopsis, tomato, and tobacco) and showed elevated expression throughout the infection process. Furthermore, pevd1 knockout mutants displayed attenuated pathogenicity compared with the wild-type (WT) strain and complemented strains in hosts. A partner protein of PevD1, pathogenesis-related protein 5 (PR5)-like protein GhPR5, was isolated from cotton (Gossypium hirsutum) plants by co-purification assays, and the PevD1-GhPR5 interaction was determined to be localized in the C-terminus (PevD1b, amino acids residues 113-155) by pull-down and yeast two-hybrid techniques. Re-introduction of the pevd1b gene into a pevd1 knockout mutant resulted in restoration of the virulence phenotype to WT levels. In addition, PevD1b, which is similar to PevD1, decreased the antifungal activity of GhPR5 in vitro. Our findings reveal an infection strategy in which V. dahliae secretes PevD1 to inhibit GhPR5 antifungal activity in order to overcome the host defence system.

The Botrytis cinerea Xylanase BcXyl1 Modulates Plant Immunity.

Botrytis cinerea is one of the most notorious pathogenic species that causes serious plant diseases and substantial losses in agriculture throughout the world. We identified BcXyl1 from B. cinerea that exhibited xylanase activity. Expression of the BcXyl1 gene was strongly induced in B. cinerea infecting Nicotiana benthamiana and tomato plants, and BcXyl1 deletion strains severely compromised the virulence of B. cinerea. BcXyl1 induced strong cell death in several plants, and cell death activity of BcXyl1 was independent of its xylanase activity. Purified BcXyl1 triggered typically PAMP-triggered immunity (PTI) responses and conferred resistance to B. cinerea and TMV in tobacco and tomato plants. A 26-amino acid peptide of BcXyl1 was sufficient for elicitor function. Furthermore, the BcXyl1 death-inducing signal was mediated by the plant LRR receptor-like kinases (RLKs) BAK1 and SOBIR1. Our data suggested that BcXyl1 contributed to B. cinerea virulence and induced plant defense responses.

A Verticillium dahliae Pectate Lyase Induces Plant Immune Responses and Contributes to Virulence.

Verticillium dahliae is a wide-host-range fungal pathogen that causes soil-borne disease in hundreds of dicotyledonous hosts. In search of V. dahliae Vd991 cell death-inducing proteins, we identified a pectate lyase (VdPEL1) that exhibited pectin hydrolytic activity, which could induce strong cell death in several plants. Purified VdPEL1 triggered defense responses and conferred resistance to Botrytis cinerea and V. dahliae in tobacco and cotton plants. Our results demonstrated that the mutant VdPEL1rec lacking the enzymatic activity lacked functions to induce both cell death and plant resistance, implying that the enzymatic activity was necessary. In addition, VdPEL1 was strongly induced in V. dahliae infected Nicotiana benthamiana and cotton roots, and VdPEL1 deletion strains severely compromised the virulence of V. dahliae. Our data suggested that VdPEL1 contributed to V. dahliae virulence and induced plant defense responses. These findings provide a new insight for the function of pectate lyase in the host-pathogen interaction.

A DREPP protein interacted with PeaT1 from Alternaria tenuissima and is involved in elicitor-induced disease resistance in Nicotiana plants.

PeaT1 is a proteinaceous elicitor from fungal pathogen Alternaria tenuissima. Our previous research revealed that this elicitor could induce defense response and enhance disease resistance in various plants including Nicotiana plants. However, immune activation mechanisms whereby PeaT1 elicits defense response remain unclear. In this study, the association between elicitor protein PeaT1 and the plasma membrane was assessed using the FITC (Fluorescein isothiocyanate) labeling method. A PeaT1-interacting protein was isolated via 125I-PeaT1 cross-linking and Far Western blot analyses, and designated PtBP1 (PeaT1 Binding Protein 1). From the data of Mass spectrometry (MS) and bioinformatics analysis, the 22 kDa plasma membrane protein PtBP1 was inferred to be a member of DREPP (developmentally regulated plasma membrane polypeptide) family that is induced in plants under stress conditions and might get involved in downstream signaling. For further verification of this association, Far Western blot, co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) analyses were performed, showing PtBP1 could bind with PeaT1 in vitro and in vivo. Virus-induced gene silencing (VIGS) analysis exhibited that PtBP1 silencing in Nicotiana benthamiana attenuated tobacco mosaic virus (TMV) resistance compared to the tobacco rattle virus (TRV) control after PeaT1 treatment.

An Asparagine-Rich Protein Nbnrp1 Modulate Verticillium dahliae Protein PevD1-Induced Cell Death and Disease Resistance in Nicotiana benthamiana.

PevD1 is a fungal protein secreted by Verticillium dahliae. Our previous researches showed that this protein could induce hypersensitive responses-like necrosis and systemic acquired resistance (SAR) in cotton and tobacco. To understand immune activation mechanisms whereby PevD1 elicits defense response, the yeast two-hybrid (Y2H) assay was performed to explore interacting protein of PevD1 in Arabidopsis thaliana, and a partner AtNRP (At5g42050) was identified. Here, AtNRP homolog in Nicotiana benthamiana was identified and designated as Nbnrp1. The Nbnrp1 could interact with PevD1 via Y2H and bimolecular fluorescence complementation (BiFC) analyses. Moreover, truncated protein binding assays demonstrated that the C-terminal 132 amino acid (development and cell death, DCD domain) of Nbnrp1 is required for PevD1-Nbnrp1 interaction. To further investigate the roles of Nbnrp1 in PevD1-induced defense response, Nbnrp1-overexpressing and Nbnrp1-silence transgenic plants were generated. The overexpression of Nbnrp1 conferred enhancement of PevD1-induced necrosis activity and disease resistance against tobacco mosaic virus (TMV), bacterial pathogen Pseudomonas syringae pv. tabaci and fungal pathogen V. dahliae. By contrast, Nbnrp1-silence lines displayed attenuated defense response compared with the wild-type. It is the first report that an asparagine-rich protein Nbnrp1 positively regulated V. dahliae secretory protein PevD1-induced cell death response and disease resistance in N. benthamiana.

Protective Effects of Leukemia Inhibitory Factor on Retinal Vasculature and Cells in Streptozotocin-induced Diabetic Mice.

BACKGROUND: Leukemia inhibitory factor (LIF) has been reported to possess various pharmacological effects, including displaying vascular and neuroprotective properties, during retinal disease. The aim of this study was to investigate the vascular and structural changes in the retina of diabetic mice and to explore whether LIF prevents experimental diabetes-induced retinal injury in the early stages. METHODS: Diabetes was induced in C57Bl/6J mice with streptozotocin (STZ) injections. Successful diabetic animal models were randomly separated into two groups: the diabetic group (n = 15) and the LIF-treated group (n = 15). Normal C57BL/6 mice served as the normal control group (n = 14). Recombinant human LIF was intravitreally injected 8 weeks after the diabetic model was successfully established. Retinas were collected and evaluated using histological and immunohistochemical techniques, and flat-mounted retinas and Western blotting were performed at 18 weeks after the induction of diabetes and 2 days after the intravitreal injection of LIF. The analysis of variance test were used. RESULTS: Histological analysis showed that there were fewer retinal ganglion cells (RGCs) and the inner nuclear layer (INL) became thinner in the diabetic model group (RGC 21.8 ± 4.0 and INL 120.2 ± 4.6 µm) compared with the normal control group (RGC 29.0 ± 6.7, t = -3.02, P = 0.007; INL 150.7 ± 10.6 µm, t = -8.88, P < 0.001, respectively). After LIF treatment, the number of RGCs (26.9 ± 5.3) was significantly increased (t = 3.39, P = 0.030) and the INL (134.5 ± 14.2 µm) was thicker compared to the diabetic group (t = 2.75, P = 0.013). In the anti-Brn-3a-labeled retinas, the number of RGCs in the LIF-treated group (3926.0 ± 143.9) was obviously increased compared to the diabetic group (3507.7 ± 286.1, t = 2.38, P = 0.030), while no significance was found between the LIF-treated group and the control group (4188.3 ± 114.7, t = -2.47, P = 0.069). Flat-mounted retinas demonstrated that a disorganized, dense distribution of the vessel was prominent in the diabetic model group. Vessel distribution in the LIF-treated mouse group was typical and the thickness was uniform. The levels of phosphosignal transducer and activator of transcription 3 activation were obviously higher in the LIF-injected retinas than those in the diabetic control group (t = 3.85, P = 0.019) and the normal control (t = -3.20, P = 0.019). CONCLUSION: The present study provides evidence that LIF treatment protects the integrity of the vasculature and prevents retinal injury in the early stages of diabetic retinopathy in STZ-induced diabetic models.

The Verticillium dahliae SnodProt1-Like Protein VdCP1 Contributes to Virulence and Triggers the Plant Immune System.

During pathogenic infection, hundreds of proteins that play vital roles in the Verticillium dahliae-host interaction are secreted. In this study, an integrated proteomic analysis of secreted V. dahliae proteins was performed, and a conserved secretory protein, designated VdCP1, was identified as a member of the SnodProt1 phytotoxin family. An expression analysis of the vdcp1 gene revealed that the transcript is present in every condition studied and displays elevated expression throughout the infection process. To investigate the natural role of VdCP1 in V. dahliae, two vdcp1 knockout mutants and their complementation strains were generated. Bioassays of these mutants revealed no obvious phenotypic differences from the wild-type (WT) in terms of mycelial growth, conidial production or mycelial/spore morphology. However, compared with the WT, the vdcp1 knockout mutants displayed attenuated pathogenicity in cotton plants. Furthermore, treating plants with purified recombinant VdCP1 protein expressed in Pichia pastoris induced the accumulation of reactive oxygen species (ROS), expression of several defense-related genes, leakage of ion electrolytes, enhancement of defense-related enzyme activity and production of salicylic acid. Moreover, VdCP1 conferred resistance to Botrytis cinerea and Pseudomonas syringae pv. tabaci in tobacco and to V. dahliae in cotton. Further research revealed that VdCP1 possesses chitin-binding properties and that the growth of vdcp1 knockout mutants was more affected by treatments with chitinase, indicating that VdCP1 could protect V. dahliae cell wall from enzymatic degradation, which suggests an effector role of VdCP1 in infecting hosts.

Internal limiting membrane peeling and gas tamponade for myopic foveoschisis: a systematic review and meta-analysis.

BACKGROUND: Myopic foveoschisis (MF) is among the leading causes of visual loss in high myopia. However, it remains controversial whether internal limiting membrane (ILM) peeling or gas tamponade is necessary treatment option for MF. METHODS: PubMed, EMBASE, CBM, CNKI, WANFANG DATA and VIP databases were systematically reviewed. Outcome indicators were myopic foveoschisis resolution rate, visual acuity improvement and postoperative complications. RESULTS: Nine studies that included 239 eyes were selected. The proportion of resolution of foveoschisis was higher in ILM peeling group than non-ILM peeling group (OR = 2.15, 95% CI: 1.06-4.35; P = 0.03). The proportion of postoperative complications was higher in Tamponade group than non-Tamponade group (OR = 10.81, 95% CI: 1.26-93.02; P = 0.03). However, the proportion of visual acuity improvement (OR = 1.63, 95% CI: 0.56-4.80; P = 0.37) between ILM peeling group and non-ILM peeling group and the proportion of resolution of foveoschisis (OR = 1.80, 95% CI: 0.76-4.28; P = 0.18) between Tamponade group and non-Tamponade group were similar. CONCLUSIONS: Vitrectomy with internal limiting membrane peeling could contribute to better resolution of myopic foveoschisis than non-peeling, however it does not significantly influence the proportion of visual acuity improvement and postoperative complications. Vitrectomy with gas tamponade is associated with more complications than non-tamponade and does not significantly influence the proportion of visual acuity improvement and resolution of myopic foveoschisis.