Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

OBJECTIVE: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. METHODS: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. RESULTS: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. CONCLUSION: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

Causal relationship between several autoimmune diseases and renal malignancies: A two-sample mendelian randomization study.

OBJECTIVE: Observational studies have shown an association between systemic autoimmune disease (AD) and multiple malignancies. However, due to the difficulty indetermining the temporal nature of the order, their causal relationship remains elusive. Based on pooled data from a large population-wide genome-wide association study (GWAS), this study explores the genetic causality between systemic autoimmune disease and renal malignancy. METHODS: We took a series of quality control steps from a large-scale genome-wide association study to select single nucleotide polymorphisms (SNPs) associated with systemic autoimmune disease as instrumental variables(IVs) to analyze genetic causality with renal malignancies. Inverse variance weighting (IVW), MR- Egger, weighted median, simple model and weighted model were used for analysis. The results were mainly based on IVW (Random Effects), followed by sensitivity analysis. Inverse-Variance Weighted(IVW) and MR-Egger were used to test for heterogeneity. MR- Egger is also used for pleiotropic testing. A single SNP analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate causality, and sensitivity analysis was performed to evaluate pleiotropy and instrumental validity. RESULTS: Acute and subacute iridocylitis (P = 0.006, OR = 1.077), Ankylosing spondylitis (P = 0.002, OR = 1.051), and spondyloarthritis (P = 0.009, OR = 1.073) were positively associated with an increased risk of renal malignancy. Coxarthrosis (P = 0.008, OR = 0.483), Juvenile rheumatism (P = 0.011, OR = 0.897), and Systemic lupus erythematosus (P = 0.014, OR = 0.869) were negatively associated with an increased risk of renal malignancy. The results of sensitivity analysis were consistent without heterogeneity or pleiotropy. CONCLUSION: Our study suggests a causal relationship between different systemic autoimmune diseases and renal malignancies. These findings prompt health care providers to take seriously the potential risk of systemic autoimmune disease and provide new insights into the genetics of kidney malignancies.

Higher incidence of meibomian gland dysfunction in postmenopausal women with primary acquired nasolacrimal duct obstruction.

PURPOSE: This study aimed to investigate the incidence of meibomian gland dysfunction (MGD) in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) and enables ophthalmologists to pay attention to ocular surface damage before surgery. METHODS: 165 postmenopausal women with PANDO and 115 postmenopausal women with a normal lacrimal drainage system were enrolled in this prospective study. Based on the results of lacrimal duct irrigation and age, the participants were further subdivided. The incidence of different severities of MGD in different groups was calculated and analyzed by the chi-squared test. RESULTS: The incidence of MGD in the PANDO group was 81.21%, and in the control group, it was 46.96%, which was significantly higher in the presence of PANDO (p < 0.001). The incidence of severe MGD in the complete and incomplete PANDO groups was higher than that in the control group (all p < 0.05), and no significant differences were observed between the complete and incomplete PANDO groups. The incidence of moderate MGD was significantly higher in the complete PANDO group than in the control group (p < 0.001). When age was considered an independent variable, the results revealed a significant value for patients aged < 70 years (p < 0.001). CONCLUSIONS: Our study revealed a prodominantly high incidence of MGD in postmenopausal women with PANDO, especially in a complete PANDO or aged < 70 years. Ophthalmologists need to pay close attention to MGD in postmenopausal women with PANDO.

Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study.

BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Plasmopara viticola effector PvCRN11 induces disease resistance to downy mildew in grapevine.

The downy mildew of grapevine (Vitis vinifera L.) is caused by Plasmopara viticola and is a major production problem in most grape-growing regions. The vast majority of effectors act as virulence factors and sabotage plant immunity. Here, we describe in detail one of the putative P. viticola Crinkler (CRN) effector genes, PvCRN11, which is highly transcribed during the infection stages in the downy mildew-susceptible grapevine V. vinifera cv. 'Pinot Noir' and V. vinifera cv. 'Thompson Seedless'. Cell death-inducing activity analyses reveal that PvCRN11 was able to induce spot cell death in the leaves of Nicotiana benthamiana but did not induce cell death in the leaves of the downy mildew-resistant V. riparia accession 'Beaumont' or of the downy mildew-susceptible 'Thompson Seedless'. Unexpectedly, stable expression of PvCRN11 inhibited the colonization of P. viticola in grapevine and Phytophthora capsici in Arabidopsis. Both transgenic grapevine and Arabidopsis constitutively expressing PvCRN11 promoted plant immunity. PvCRN11 is localized in the nucleus and cytoplasm, whereas PvCRN11-induced plant immunity is nucleus-independent. The purified protein PvCRN11Opt initiated significant plant immunity extracellularly, leading to enhanced accumulations of reactive oxygen species, activation of MAPK and up-regulation of the defense-related genes PR1 and PR2. Furthermore, PvCRN11Opt induces BAK1-dependent immunity in the apoplast, whereas PvCRN11 overexpression in intracellular induces BAK1-independent immunity. In conclusion, the PvCRN11 protein triggers resistance against P. viticola in grapevine, suggesting a potential for the use of PvCRN11 in grape production as a protectant against downy mildew.

Treatment of hypertrophic scars with ablative fractional carbon dioxide laser assisted with different topical triamcinolone delivery ways.

Objectives: Ablative fractional carbon dioxide laser has been used with triamcinolone to treat hypertrophic scars, resulting in promising success rates. However, there are different topical triamcinolone delivery methods used in scar treatment. To assess the efficacy among the different triamcinolone delivery methods, this study was designed to compare the efficacy and safety of ablative fractional carbon dioxide laser followed by penetration and injection of topical triamcinolone into thicker hypertrophic scars (height score of VSS ≥2). Study design/materials and methods: We performed a retrospective study of 155 thicker hypertrophic scar patients (height score of VSS ≥2), including 88 patients in the triamcinolone external application group and 67 patients in the triamcinolone intralesional injection group. One month after the patients had 3 treatment sessions at 4-week intervals, the scars were assessed by photography, the Vancouver Scar Scale (VSS), durometry and spectrocolorimetry. Any adverse effects were also evaluated. Results: The VSS scores and the hardness of the scars in both groups improved significantly compared to baseline. Moreover, the patients in the triamcinolone intralesional injection group had higher treatment efficacy (19.77 ± 21.25 %) based on their VSS scores than the patients in the triamcinolone external application group (5.94 ± 24.07 %), especially in the improvement of scar pliability, height and hardness. Meanwhile, in the triamcinolone injection group, more patients had mild and moderate improvement than in the triamcinolone application group. However, there were no differences in the distribution of the adverse effects in either group. Conclusions: This study demonstrated that using the ablative fractional carbon dioxide laser followed by different topical triamcinolone delivery methods is effective and safe for thicker hypertrophic scar improvement. The method of using the ablative fractional carbon dioxide laser assisted with triamcinolone injection had a better therapeutic outcome in thicker hypertrophic scars, as compared with triamcinolone penetration.

Abnormal white matter along fibers by automated fiber quantification in patients undergoing hemodialysis.

BACKGROUND: Abnormal white matter has been reported in patients with end-stage renal disease (ESRD). However, few studies have investigated the relationship between specific damage segments and cognition in ESRD. This study aimed to delineate white matter alterations in ESRD and its relationship with cognition. METHODS: A total of 36 patients undergoing hemodialysis and 25 healthy controls underwent diffusion tensor imaging (DTI) and a series of neuropsychiatric tests. Automated fiber quantification was used to extract distinct DTI indices, and the relationship between the specific segment of the white matter and clinical properties was investigated. Furthermore, a support vector machine was applied to differentiate patients with ESRD from healthy controls. RESULTS: Fractional anisotropy values decreased in multiple fiber bundles, including bilateral thalamic radiata, cingulum cingulate, inferior fronto-occipital fasciculus (IFOF), uncinate, Callosum_Forceps_Major/Callosum_Forceps_Minor (CFMaj/CFMin), and left uncinate from the tract level in patients with ESRD. Specific damaged segments were detected in 8 fiber bundles, including bilateral thalamic radiation, cingulum cingulate, IFOF, CFMin, and left corticospinal tract. Few alterations in these fiber bundles were correlated with cognition impairment and hemoglobin levels. The tract profiles of the left thalamic radiata and left cingulum cingulate could be used to differentiate hemodialysis patients from healthy controls, with an accuracy of 76.9% and 67.6%, respectively. CONCLUSIONS: This study revealed white matter damage in hemodialysis patients. This damage occurred in specific segments of the tract, especially in the left thalamic radiata and left cingulum cingulate, which might become a new biomarker for patients with ESRD and cognition impairment.

Tim-3, PD-1, CD244 and Foxp3 Positive T Cells' Relation to the Prognosis of Dermatomyositis and Polymyositis Patients.

OBJECTIVE: To explore the frequency of circulating CD4+ T cells expressing PD-1+, TIM-3+ in polymyositis (PM) and dermatomyositis (DM) patients and its correlation with inflammatory factors, CD244+ and FOXP3+ T cell subtypes and prognosis. STUDY DESIGN: Observational study. Place and Duration of the Study: Ganzhou people's Hospital, Ganzhou, Jiangxi, China, from July 2019 to June 2021. METHODOLOGY: PM and DM patients were treated according to the institution's guidelines and followed up for 2 years. Fifty healthy volunteers were enrolled as controls. Serum interleukin (IL)-6, C-reactive protein (CRP), IL-17, and tumour necrosis factor α (TNF-α) levels were detected by enzyme-linked immunosorbent assay (ELISA). TIM-3+, PD-1+, CD244+, and FOXP3+ expressions were measured using flow cytometry. Inability to live normally, recurrence or death was defined as poor prognosis. RESULTS: The ESR, ALT, AST, LDH and ferritin concentration in PM/DM patients were remarkably elevated than that in healthy volunteers. The frequencies of PD-1+, TIM-3+, CD244+, and FOXP3+ were all remarkably enhanced in PM/DM patients compared with the healthy volunteers. The frequencies of PD-1+, TIM-3+, FOXP3+, and TIM-3+/PD-1+ T cells were significantly elevated in the poor prognosis group compared with the good prognosis group. The frequency of CD4+TIM-3+PD-1+ had satisfactory diagnostic value for PM/DM patients with bad prognoses. IL-17, TIM-3+, PD-1+and TIM-3+ PD-1+ were the risk factors for PM/DM patients with bad outcomes. CONCLUSION: The frequency of circulating CD4+ T cells expressing TIM-3+PD-1+ could be used to predict the prognosis of PM/DM patients. KEY WORDS: Tim-3, PD-1, Dermatomyositis, Polymyositis, Inflammatory.

Hangover headache and its behavioral changes in rats.

Objectives: The present study aims to establish and evaluate a rat model for hangover headaches caused by alcoholic drinks. Materials and Methods: Chronic migraine (CM) model rats were divided into 3 groups, and intragastrically administered alcoholic drinks (sample A, B, or C) to simulate hangover headache attacks. The withdrawal threshold for the hind paw/face and the thermal latency of hind paw withdrawal were detected after 24 hr. Serum was collected from the periorbital venous plexus of rats in each group, and enzymatic immunoassays were used to determine the serum levels of calcitonin gene-related peptide (CGRP), substance P (SP), and nitric oxide (NO). Results: Compared with the control group, the mechanical hind paw pain threshold was significantly lower in rats administered Samples A and B after 24 hr; however, no significant difference was observed across groups for the thermal pain threshold. The mechanical threshold for periorbital pain was only significantly reduced in rats administered Sample A. Immunoassays further indicated that serum levels of SP in the group administered Sample A were significantly higher than those in the control group; the serum levels of NO and CGRP were significantly higher in the group of rats receiving Sample B. Conclusion: We successfully developed an effective and safe rat model for investigating alcohol drink induced hangover headaches. This model could be used to investigate the mechanisms associated with hangover headaches for the development of novel and promising candidates for the future treatment or prophylaxis of hangover headaches.

Transcriptomic and metabolomic analysis reveals a protein module involved in preharvest apple peel browning.

Peel browning is a natural phenomenon that adversely affects the appearance of fruits. Research on the regulation of browning in apples (Malus × domestica Borkh.) has mainly focused on postharvest storage, while studies at the preharvest stage are relatively rare. Apple is an economically important horticultural crop prone to peel browning during growth, especially when the fruits are bagged (dark conditions). The present study's integrated transcriptomics and metabolomics analysis revealed that preharvest apple peel browning was primarily due to changes in phenolics and flavonoids. The detailed analysis identified MdLAC7's (laccase 7) role in the preharvest apple peel browning process. Transient injection, overexpression, and CRISPR/Cas9 knockout of the MdLAC7 gene in apple fruit and calli identified vallinic acid, anthocyanidin, tannic acid, sinapic acid, and catechinic acid as its catalytic substrates. In addition, yeast one-hybrid assay, electrophoretic mobility shift assay, luciferase reporter assay, and ChIP-PCR analysis revealed that MdWRKY31 binds to the promoter of MdLAC7 and positively regulates its activity to promote peel browning of bagged fruits (dark conditions). Interestingly, upon light exposure, the light-responsive transcription factor MdHY5 (ELONGATED HYPOCOTYL 5) bound to the promoter of MdWRKY31 and inhibited the gene's expression, thereby indirectly inhibiting the function of MdLAC7. Subsequent analysis showed that MdHY5 binds to the MdLAC7 promoter at the G-box1/2 site and directly inhibits its expression in vivo. Thus, the study revealed the MdLAC7-mediated mechanism regulating preharvest apple peel browning and demonstrated the role of light in inhibiting MdLAC7 activity and subsequently reducing peel browning. These results provide theoretical guidance for producing high-quality apple fruits.

Highly conductive copper films prepared by multilayer sintering of nanoparticles synthesized via arc discharge.

The major challenges in producing highly electrically conductive copper films are the oxide content and the porosity of the sintered films. This study developed a multilayer sintering method to remove the copper oxides and reduce copper film porosity. We used a self-built arc discharge reactor to produce copper nanoparticles. Copper nanoparticles produced by arc discharge synthesis have many advantages, such as low cost and a high production rate. Conductive inks were prepared from copper nanoparticles to obtain thin copper films on glass substrates. As demonstrated by scanning electron microscopy analyses and electrical resistivity measurements, the copper film porosity and electrical resistivity cannot be significantly reduced by prolonged sintering time or increasing single film thickness. Instead, by applying the multilayer sintering method, where the coating and sintering process was repeated up to four times in this study, the porosity of copper films could be effectively reduced from 33.6% after one-layer sintering to 3.7% after four-layer sintering. Copper films with an electrical resistivity of 3.49 ± 0.35µΩ·cm (two times of the bulk copper) have been achieved after four-layer sintering, while one-layer sintered copper films were measured to possess resistivity of 11.17 ± 2.17µΩ·cm.

Plasmopara viticola RxLR effector PvAvh77 triggers cell death and governs immunity responses in grapevine.

Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most significant production challenges for the grape and wine industry. P. viticola injects a plethora of effectors into its host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola avirulence homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger non-specific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). In addition, a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Ectopic expression of PvAvh77 in V. vinifera 'Thompson Seedless' leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immune responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defence responses in grapevine extracellularly, as evidenced by increased accumulation of salicylic acid and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as an inducer of plant immunity.

Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway.

Increased intestinal barrier permeability, leaky gut, has been reported in patients with autism. However, its contribution to the development of autism has not been determined. We selected dextran sulfate sodium (DSS) to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis. DSS treatment resulted in a decreased affinity for social proximity; however, autistic behaviors in mice were improved after the administration of metformin. We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors. The concentration of lipopolysaccharides in blood decreased after the administration of metformin. The expression levels of the key molecules in the toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-nuclear factor kappa B (NF-κB) pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed. Thus, "leaky gut" could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4-MyD88-NF-κB pathway.

Hippocampal subfield morphology in regular hemodialysis patients.

BACKGROUND: Hippocampal alterations have been implicated in the pathophysiology of cognitive impairment in hemodialysis patients. The hippocampus consists of several distinct subfields, and the molecular mechanisms underlying cognition might be associated with specific hippocampal subfield volume changes. However, this has not yet been investigated in hemodialysis patients. This study aimed to explore volumetric abnormalities in hippocampal subfields in regular hemodialysis patients. METHODS: High-resolution T1-weighted structural images were collected in 61 subjects including 36 hemodialysis patients and 25 healthy controls. A state-of-the-art hippocampal segmentation approach was adopted to segment the hippocampal subfields. Group differences in hippocampal subfield volumes were assessed in Python with a statsmodels module using an ordinary least squares regression with age and sex as nuisance effects. RESULTS: Hemodialysis patients had significantly smaller volumes in the bilateral hippocampus (P < .05/2, Bonferroni corrected), cornu ammonis 1 (CA1), CA4, granule cell and molecular layer of the dentate gyrus, hippocampus-amygdala transition area and molecular layer of the hippocampus than healthy controls (P < .05/24, Bonferroni corrected). Hemodialysis patients also had lower volumes in the left hippocampal tail and right fimbria than healthy controls (P < .05/24, Bonferroni corrected). Hippocampal subfield volumes were associated with neuropsychological test scores, the duration of disease and hemoglobin levels. CONCLUSIONS: We found smaller hippocampal subfield volumes in hemodialysis patients, which were associated with impaired cognition, supporting their role in memory disturbance in the hemodialysis population. However, multiple clinical factors may have confounded the results, and therefore, the interpretation of these results needs to be cautious.

Mapping white matter structural and network alterations in betel quid-dependent chewers using high angular resolution diffusion imaging.

Background: To evaluate brain white matter diffusion characteristics and anatomical network alterations in betel quid dependence (BQD) chewers using high angular resolution diffusion imaging (HARDI). Methods: The current study recruited 53 BQD chewers and 37 healthy controls (HC) in two groups. We explored regional diffusion metrics alternations in the BQD group compared with the HC group using automated fiber quantification (AFQ). We further employed the white matter (WM) anatomical network of HARDI to explore connectivity alterations in BQD chewers using graph theory. Results: BQD chewers presented significantly lower FA values in the left and right cingulum cingulate, the left and right thalamic radiation, and the right uncinate. The BQD has a significantly higher RD value in the right uncinate fasciculus than the HC group. At the global WM anatomical network level, global network efficiency (p = 0.008) was poorer and Lp (p = 0.016) was greater in the BQD group. At the nodal WM anatomical network level, nodal efficiency (p < 0.05) was lower in the BQD group. Conclusion: Our findings provide novel morphometric evidence that brain structural changes in BQD are characterized by white matter diffusivity and anatomical network connectivity among regions of the brain, potentially leading to the enhanced reward system and impaired inhibitory control.

The cytosolic iron-sulphur cluster assembly mechanism in grapevine is one target of a virulent Crinkler effector from Plasmopara viticola.

Grapevine downy mildew is one of the most devastating diseases in grape production worldwide, but its pathogenesis remains largely unknown. A thorough understanding of the interaction between grapevine and the causal agent, Plasmopara viticola, is helpful to develop alternative disease control measures. Effector proteins that could be secreted to the interaction interface by pathogens are responsible for the susceptibility of host plants. In this study, a Crinkler effector, named PvCRN17, which is from P. viticola and showed virulent effects towards Nicotiana benthamiana previously, was further investigated. Consistently, PvCRN17 showed a virulent effect on grapevine plants. Protein-protein interaction experiments identified grapevine VAE7L1 (Vitis protein ASYMMETRIC LEAVES 1/2 ENHANCER 7-Like 1) as one target of PvCRN17. VAE7L1 was found to interact with VvCIA1 and VvAE7, thus it may function in the cytosolic iron-sulphur cluster assembly (CIA) pathway. Transient expression of VAE7L1 in Vitis riparia and N. benthamiana leaves enhanced the host resistance to oomycete pathogens. Downstream of the CIA pathway in grapevine, three iron-sulphur (Fe-S) proteins showed an enhancing effect on the disease resistance of N. benthamiana. Competitive co-immunoprecipitation assay showed PvCRN17 could compete with VvCIA1 to bind with VAE7L1 and VvAE7. Moreover, PvCRN17 and VAE7L1 were colocalized at the plasma membrane of the plant cell. To conclude, after intruding into the grapevine cell, PvCRN17 would compete with VCIA1 to bind with VAE7L1 and VAE7, demolishing the CIA Fe-S cluster transfer complex, interrupting the maturation of Fe-S proteins, to suppress Fe-S proteins-mediated defence responses.

An RxLR effector from Plasmopara viticola suppresses plant immunity in grapevine by targeting and stabilizing VpBPA1.

Grapevine downy mildew, caused by Plasmopara viticola, is one of the most devastating diseases in viticulture. Plasmopara viticola secretes RxLR effectors to modulate immune responses in grapevine. Here, we report an RxLR effector RxLR50253 from P. viticola that can interfere with plant immune response and thus promote pathogen colonization. RxLR50253 was induced at an early stage of P. viticola infection and could suppress elicitor (INF1 and Bax)-triggered cell death. RxLR50253 promote pathogen colonization in both tobacco and grapevine leaves. VpBPA1 was found to be the host target of RxLR50253 by yeast two-hybrid screening, and interaction between RxLR50253 and VpBPA1 was confirmed by multiple in vivo and in vitro assays. Further analysis revealed that VpBPA1 promoted pathogen colonization and decreased H2 O2 accumulation in transgenic tobacco and grapevine, while there was enhanced resistance and H2 O2 accumulation in NbBPA1-silenced Nicotiana benthamiana leaves. Moreover, transient expression of VpBPA1 in NbBPA1-silenced N. benthamiana leaves could reduce the accumulation of H2 O2 . Experiments in vivo demonstrated that RxLR50253 inhibits degradation of VpBPA1. Taken together, our findings showed that RxLR50253 targets and stabilizes VpBPA1 to attenuate plant immunity through decreasing H2 O2 accumulation during pathogen infection.

Corrigendum: Altered Topological Organization of Functional Brain Networks in Betel Quid Dependence: A Resting-State Functional MRI Study.

[This corrects the article DOI: 10.3389/fpsyt.2021.779878.].

Altered Spontaneous Brain Activity in Betel Quid Dependence Chewers: A Resting-State Functional MRI Study With Percent Amplitude of Fluctuation.

Objective: This study aimed to investigate brain spontaneous neural activity changes in betel quid dependence (BQD) chewers using the percent amplitude of fluctuation (PerAF) method. Methods: This study included 48 BQD chewers. The healthy control (HC) group comprised 35 volunteers who were matched with BQD chewers in age, gender, and educational status. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological tests. The PerAF method was used to identify BQD-related regional brain activity changes. An independent samples t-test was used to evaluate the PerAF difference across two groups. The association between PerAF changes and clinical features such as BQD scores, duration of BQD, Hamilton Depression Rating Scale-24 item (HAMD-24), and Hamilton Anxiety Rating Scale-14 item (HAMA-14) was evaluated by using Spearman's correlation analysis. It assessed the ability of the PerAF method to distinguish between BQD chewers and HCs using a receiver operating characteristic (ROC) curve. Results: Compared to the control group, BQD chewers showed decreased PerAF in right anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), right insula, right precuneus, left putamen, left supramarginal gyrus (SMG), and left cerebellum and increased PerAF in right orbitofrontal and left superior temporal gyrus (STG) [P < 0.05, Gaussian random field (GRF) corrected]. PerAF values of the right MFG and right ACC had a significant negative relationship with the duration of BQD (P < 0.05). The average values of PerAF in the left putamen, left cerebellum, and left STG showed significant discriminatory power in distinguishing BQD chewers from HCs, with relatively prime area under the curve (AUC) values. Conclusion: Our findings suggested that betel quid chewing is associated with spontaneous neural activity alterations in the impulsivity areas (MFG and ACC), cognitive (MFG, ACC, precuneus, and the cerebellum), and reward (orbitofrontal, putamen, and insula) systems, which may be correlated with neuropathological mechanisms of BQD. Also, PerAF may be useful as a potential sensitive biomarker for identifying spontaneous brain activity changes in BQD chewers.

ß-defensin 118 attenuates inflammation and injury of intestinal epithelial cells upon enterotoxigenic Escherichia coli challenge.

BACKGROUND: Antimicrobial peptides including various defensins have been attracting considerable research interest worldwide, as they have potential to substitute for antibiotics. Moreover, AMPs also have immunomodulatory activity. In this study, we explored the role and its potential mechanisms of ß-defensin 118 (DEFB118) in alleviating inflammation and injury of IPEC-J2 cells (porcine jejunum epithelial cell line) upon the enterotoxigenic Escherichia coli (ETEC) challenge. RESULTS: The porcine jejunum epithelial cell line (IPEC-J2) pretreated with or without DEFB118 (25 µg/mL) were challenged by ETEC (1×106 CFU) or culture medium. We showed that DEFB118 pretreatment significantly increased the cell viability (P<0.05) and decreased the expressions of inflammatory cytokines such as the interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in IPEC-J2 cells exposure to ETEC (P<0.05). Interestingly, DEFB118 pretreatment significantly elevated the abundance of the major tight-junction protein zonula occludens-1 (ZO-1), but decreased the number of apoptotic cells upon ETEC challenge (P<0.05). The expression of caspase 3, caspase 8, and caspase 9 were downregulated by DEFB118 in the IPEC-J2 cells exposure to ETEC (P<0.05). Importantly, DEFB118 suppressed two critical inflammation-associated signaling proteins, nuclear factor-kappa-B inhibitor alpha (IκB-α) and nuclear factor-kappaB (NF-κB) in the ETEC-challenged IPEC-J2 cells. CONCLUSIONS: DEFB118 can alleviate ETEC-induced inflammation in IPEC-J2 cells through inhibition of the NF-κB signaling pathway, resulting in reduced secretion of inflammatory cytokines and decreased cell apoptosis. Therefore, DEFB118 can act as a novel anti-inflammatory agent.