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Abstract Background The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. Methods House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. Results Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. Conclusion Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation. Graphical Abstract

Abstract Background Central nervous system (CNS) disorders, such as stroke, often lead to spasticity, which result in limb deformities and significant reduction in quality of life. Spasticity arises from disruptions in the normal functioning of cortical and descending inhibitory pathways in the brainstem, leading to abnormal muscle contractions. Contralateral seventh cervical nerve cross transfer (CC7) surgery has been proven to effectively reduce spasticity, but the specific mechanism for its effectiveness is unclear. Methods This study aimed to investigate the changes in the dorsal root ganglia (DRG) following CC7 surgery. A comprehensive anatomical analysis was conducted through cadaveric study and magnetic resonance imaging (MRI) study, to accurately measure the regional anatomy of the C7 DRG. DRG perfusion changes were quantitatively assessed by comparing pre‐ and postoperative dynamic contrast‐enhanced (DCE) MRI. Results In CC7 surgery, the C7 nerve root on the affected side is cut close to the DRG (3.6 ± 1.0 mm), while the C7 nerve root on the healthy side is cut further away from the DRG (65.0 ± 10.0 mm). MRI studies revealed that after C7 proximal neurotomy on the affected side, there was an increase in DRG volume, vascular permeability, and perfusion; after C7 distal neurotomy on the healthy side, there was a decrease in DRG volume, with no significant changes in vascular permeability and perfusion. Conclusion This study provides preliminary insights into the mechanisms of spasticity reduction following CC7 surgery, indicating that changes in the DRG, such as increased vascular permeability and perfusion, could disrupt abnormal spinal γ‐circuits. The resulting high‐perfusion state of DRG, possibly due to heightened neuronal activity and metabolic demands, necessitating further research to verify this hypothesis.

Abstract Objective This study aimed to assess the effectiveness of Mersilene tape versus alternative suture types in prolonging singleton pregnancies as well as other pregnancy and neonatal outcomes, in cases of history-, ultrasound-, and exam-indicated cervical cerclage. Methods A systematic review was conducted to identify relevant studies comparing different suture types in cervical cerclage procedures. The primary outcome of interest was preterm birth (PTB) rate

BackgroundCough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. ObjectiveThe aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. MethodsIn this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. ResultsThere were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). ConclusionsCough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Background: Due to the complexity of airways and the limitation of experiments, the production mechanism of the lung sounds in airways has not been fully understood, which often confuses diagnosis. Method: A 3D geometrical model of human airways (G5-G8) has been developed based on Weibel's model. Simulation on transient airflow and the noise production during exhalation under different breathing intensities (Q = 15, 30, 45, 60, 75, 90 L/min) has been carried out with Direct Noise Computation (DNC) and Ffowcs Williams-Hawkings (FW-H) method. Results: (1) The junctions between airways are most likely to produce lung sounds, and the peak value is located in the junction between G7 and G6 at the middle of exhalation (about 0.75 s). (2) With the increase in breathing intensity, the average sound pressure level first increases, reaches the peak value at 70–75 L/min, and then drops. (3) Higher breathing intensity is helpful to produce the feature of wheezing, namely a comparatively higher sound pressure level in the range of 200–500 Hz. Moreover, this feature is prominent with the increase in breathing intensity.

Background. The activation of complement is involved in monocyte recruitment in tuberculous pleural effusion (TPE), while the role of the cleavage product of complement C3 in this process needs further research. Methods. The expression of complement components in pleural biopsy specimens of TPE patients was measured. The concentration of cleavage products of complement was tested in TPE by ELISA. Moreover, the colocalizations of C3b and CR1, C3d and CR3, and CXCL12 and CXCR4 in monocytes and pleural mesothelial cells (PMCs) isolated from TPE were determined by an immunofluorescent assay. Monocyte chemotaxis assay was analyzed via transwell chambers. Results. Three pathways of the complement system were activated in tuberculous pleurisy. In patients with TPE, C3 lysis was more active than peripheral blood in pleural cavity. Tuberculous protein Mpt64 and anaphylatoxin C3a could significantly promote CXCL12 production in human PMCs isolated from TPE. C3b-CR1, C3d-CR3, and CXCL12-CXCR4 were colocalized in PMCs and monocytes from TPE. The recruitment of monocytes into TPE mediated by PMCs could be inhibited by anti-CR1, anti-CR3, and anti-CXCL12 monoclonal antibodies (mAbs). Conclusions. Complement activates strongly in TPE, and PMCs induced monocytes to the pleural cavity through C3a, C3b, and C3d.

Inhalation represents a significant route of cadmium (Cd) exposure, which is associated with an elevated risk of lung diseases. This research study aims to evaluate the impact of repeated low-dose cadmium inhalation on exacerbating airway inflammation induced by ovalbumin (OVA) in asthma-afflicted mice. Mice were grouped into four categories: control (Ctrl), OVA, cadmium chloride (CdCl2), and OVA + cadmium chloride (OVA + CdCl2). Mice in the OVA group displayed increased airway mucus secretion and peribronchial and airway inflammation characterized by eosinophil cell infiltration, along with elevated levels of Th2 cytokines (IL-4, IL-5, IL-13) in bronchoalveolar lavage fluids (BALFs). These parameters were further exacerbated in the OVA + CdCl2 group. Additionally, the OVA + CdCl2 group exhibited higher levels of the oxidative stress marker malondialdehyde (MDA), greater activity of glutathione peroxidase (GSH-Px), and higher phosphorylation of extracellular regulated kinase (ERK) in lung tissue. Treatment with U0126 (an ERK inhibitor) and α-tocopherol (an antioxidant) in the OVA + CdCl2 group resulted in reduced peribronchial and airway inflammation as well as decreased airway mucus secretion. These findings indicate that CdCl2 exacerbates airway inflammation in OVA-induced allergic asthma mice following airway exposure. ERK and oxidative stress are integral to this process, and the inhibition of these pathways significantly alleviates the adverse effects of CdCl2 on asthma exacerbation.

Introduction Aphasia affects many stroke survivors; therefore, effective treatments are urgently needed. Preliminary clinical findings have suggested an association between contralateral C7–C7 cross nerve transfer and recovery from chronic aphasia. Randomised controlled trials supporting the efficacy of C7 neurotomy (NC7) are lacking. This study will explore the efficacy of NC7 at the intervertebral foramen for improving chronic poststroke aphasia.Methods and analysis This study protocol reports a multicentre, randomised, assessor-blinded active-controlled trial. A total of 50 patients with chronic poststroke aphasia for over 1 year and with a aphasia quotient calculated by Western Aphasia Battery Aphasia Quotient (WAB-AQ) score below 93.8 will be recruited. Participants will be randomly assigned to 1 of 2 groups (25 individuals each) to receive NC7 plus intensive speech and language therapy (iSLT), or iSLT alone programme. The primary outcome is the change in Boston Naming Test score from baseline to the first follow-up after NC7 plus 3 weeks of iSLT or iSLT alone. The secondary outcomes include the changes in the WAB-AQ, Communication Activities of Daily Living-3, International Classification of Functioning, Disability and Health (ICF) speech language function, Barthel Index, Stroke Aphasic Depression Questionnaire-hospital version and sensorimotor assessments. The study will also collect functional imaging outcomes of naming and semantic violation tasks through functional MRI and electroencephalogram to evaluate the intervention-induced neuroplasticity.Ethics and dissemination This study was approved by the institutional review boards of Huashan Hospital, Fudan University, and all participating institutions. The study findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration number ChiCTR2200057180.

Background and aimsComplement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis.Materials and methodsNinety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values.ResultsThe ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy.ConclusionsComplement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.

Abstract Background Monocytes are involved in tumor growth and metastasis, but the distribution of monocyte phenotypes and their role in the development of malignant pleural effusion (MPE) remains unknown. Methods A total of 94 MPE patients (76 diagnosed with adenocarcinoma lung cancer and 18 with squamous cell lung cancer) and 102 volunteers for health examination in Xiangya Hospital from December 2016 to December 2019 were included in the study. Results The distribution of monocyte subtypes identified by the expression of CD14 and CD16 were analyzed by flow cytometry. The proportion of CD14++CD16+ intermediate monocytes were significantly increased in pleural effusion of MPE patients. The complement system components were assayed by immunohistochemistry and ELISA, and higher expression of the classical and alternative pathways were detected in malignant pleural tissue. Transwell assay further revealed that C5a enhanced the infiltration of intermediate monocytes into the pleural cavity by promoting CCL2 production in pleural mesothelial cells (PMCs). In addition, C5a promoted the secretion of IL‐1β by intermediate monocytes. Furthermore, C5a activated in intermediate monocytes and IL‐1β released after C5a stimulation by monocytes promoted the proliferation, migration, adhesion, and epithelial‐to‐mesenchymal transition (EMT) of tumor cells, and attenuated tumor cell apoptosis. Conclusions C5a, activated by the classical and alternative pathways of the complement system, not only mediated the infiltration of intermediate monocytes by enhancing CCL2 production in PMCs but also induced IL‐1β release from the recruited monocytes in MPE. The consequence of C5a activation and the subsequent IL‐1β overexpression in intermediate monocytes contributed to MPE progression.

ObjectiveIn the treatment of cervical spondylotic radiculopathy (CSR), spinal endoscopy has been developed vigorously in the past 30 years. However, its effectiveness and subsequent problem of cervical spine stability have always been the controversial hotspots. This study aims to conduct a retrospective study using posterior cervical full-endoscopic technique for the treatment of CSR with foraminal bony stenosis, and evaluate its clinical effect and application value.MethodsAll 22 patients treated for CSR with foraminal bony stenosis using posterior cervical full-endoscopic technique were analyzed since Dec 1, 2016, to Apr 30, 2020. The data collection included operation time, length of stay, wound healing, surgical complications, visual analog scale (VAS), Japanese Orthopaedic Association (JOA) scores, intervertebral foramen diameter, intervertebral foramen area and cervical instability. The relevant indicators were observed on admission, at postoperative 1 week and 3 months, and at the last follow-up.ResultsThe operation time was 141.6 ± 13.7 min. The length of stay was 6.0 ± 2.5 days. VAS and JOA at different time points after operation were decreased compared with before operation (p 0.05). The height, anteroposterior diameter and area of intervertebral foramen after operation were significantly increased compared with before operation (p

Background and purposeWeight loss and muscle mass loss are common in patients with chronic obstructive pulmonary disease (COPD). Muscle density and fat infiltration based on CT images may be more sensitive than muscle mass by DXA in the assessment of sarcopenia for COPD patients. However, the age-related changes of cross-sectional trunk muscle compositions based on lung CT scans are still unknown. Thus, we aimed to investigate over time the change in muscle density, size, and fat deposition of L1-level trunk muscles in patients with COPD.Materials and methods129 male COPD patients with a second chest CT scan (from 2013-2019 to 2014-2020) were enrolled. The CT images at first and second CT scans are analyzed by OsiriX software. Trunk muscles at the level of the 1st lumbar vertebrae were selected for analysis. Attenuation of lumbar vertebrae 1 was also measured from chest CT images. The pulmonary function values were calculated based on forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).ResultsThe mean age of the 129 patients with COPD was 69.7 years. The durations of COPD of this cohort were from 8-17 years. The mean area and density of L1 trunk muscles were 85.5 cm2 and 36.4 HU. At baseline, muscle area and density and vertebral density were negatively associated with age (p0.05). The per-year loss of trunk muscle area was 2.83 cm2 (p

BackgroundMonocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.Methods30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16+ monocytes was observed. The effect of MPO-ANCA on the migration of CD16+ monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.ResultsCompared with controls, CD16+ monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16+ monocytes. Finally, the percentage of CD16+ monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14+ and CD16+ cells in the kidneys.ConclusionEnhanced extravasation of CD16+ monocytes to the kidney via the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.

Abstract Background Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV. Methods Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA. Results We observed decreased percentages of CD4+ and CD8+ T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3+ T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the TEM17 cell frequency, with concomitant increases in the frequencies of CD4+ TEM1 and CD4+ TEM17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8+ T cells and CD4+ TEM subsets were correlated with renal prognosis and inflammatory markers. Conclusions Our data indicate that dysregulated chemokine receptor expression on CD4+ and CD8+ effector memory T cells and aberrant distribution of functional CD4+ T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.

Summary: Background: A previous randomized controlled trial showed contralateral seventh cervical nerve (CC7) cross transfer to be safe and effective in restoring the arm function of spastic arm paralysis patients in a specified population. Guidance on indications, safety and expected long-term improvements of the surgery are needed for clinical practice. Methods: This is a retrospective, multicenter, propensity score-matched cohort study. All patients registered between 2013 and 2019 with unilateral spastic arm paralysis over 1 year who were registered at one of five centers in China and South Korea were included. Patients received CC7 cross transfer or rehabilitation treatment in each center. Primary outcome was the change in the upper-extremity Fugl–Meyer (UEFM) score from baseline to 2-year follow-up; larger increase indicated better functional improvements. Findings: The analysis included 425 eligible patients. After propensity score matching, 336 patients who were 1:1 matched into surgery and rehabilitation groups. Compared to previous trial, patient population was expanded on age ( 45 years old), duration of disease (

BackgroundDespite long-standing recognition in the significance of mucus overproduction in asthma, its etiology remains poorly understood. Muc5ac is a secretory mucin that has been associated with reduced pulmonary function and asthma exacerbations.ObjectivesWe sought to investigate the immunological pathway that controls Muc5ac expression and allergic airway inflammation in asthma.MethodsCockroach allergen-induced Muc5ac expression and aryl hydrocarbon receptor (AhR) signaling activation was examined in the human bronchial epithelial cells (HBECs) and mouse model of asthma. AhR regulation of Muc5ac expression, mitochondrial ROS (Mito-ROS) generation, and NLRP3 inflammasome was determined by AhR knockdown, the antagonist CH223191, and AhR-/- mice. The role of NLRP3 inflammasome in Muc5ac expression and airway inflammation was also investigated.ResultsCockroach allergen induced Muc5ac overexpression in HBECs and airways of asthma mouse model. Increased expression of AhR and its downstream genes CYP1A1 and CYP1B1 was also observed. Mice with AhR deletion showed increased allergic airway inflammation and MUC5AC expression. Moreover, cockroach allergen induced epithelial NLRP3 inflammasome activation (e.g., NLRP3, Caspase-1, and IL-1β), which was enhanced by AhR knockdown or the antagonist CH223191. Furthermore, AhR deletion in HBECs led to enhanced ROS generation, particularly Mito-ROS, and inhibition of ROS or Mito-ROS subsequently suppressed the inflammasome activation. Importantly, inhibition of the inflammasome with MCC950, a NLRP3-specifc inhibitor, attenuated allergic airway inflammation and Muc5ac expression. IL-1β generated by the activated inflammasomes mediated cockroach allergen-induced Muc5ac expression in HBECs.ConclusionsThese results reveal a previously unidentified functional axis of AhR-ROS-NLRP3 inflammasome in regulating Muc5ac expression and airway inflammation.

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1−/− asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1−/− Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

The complement system is activated in tuberculous pleural effusion (TPE), with increased levels of the anaphylatoxins stimulating pleural mesothelial cells (PMCs) to secrete chemokines, which recruit nonclassical monocytes to the pleural cavity. The differentiation and recruitment of naive CD4+ T cells are induced by pleural cytokines and PMC-produced chemokines in TPE. However, it is unclear whether anaphylatoxins orchestrate CD4+ T cell response via interactions between PMCs and monocytes in TPE. In this study, CD16+ and CD16- monocytes isolated from TPE patients were cocultured with PMCs pretreated with anaphylatoxins. After removing the PMCs, the conditioned monocytes were cocultured with CD4+ T cells. The levels of the cytokines were measured in PMCs and monocyte subsets treated separately with anaphylatoxins. The costimulatory molecules were assessed in conditioned monocyte subsets. Furthermore, CD4+ T cell response was evaluated in different coculture systems. The results indicated that anaphylatoxins induced PMCs and CD16+ monocytes to secrete abundant cytokines capable of only inducing Th17 expansion, but Th1 was feeble. In addition, costimulatory molecules were more highly expressed in CD16+ than in CD16- monocytes isolated from TPE. The interactions between monocytes and PMCs enhanced the ability of PMCs and monocytes to produce cytokines and that of monocytes to express HLA-DR, CD40, CD80 and CD86, which synergistically induced Th17 expansion. In the above process, anaphylatoxins enhanced the interactions between monocytes and PMCs by increasing the level of the cytokines IL-1β, IL-6, IL-23 and upregulating the phenotype of CD40 and CD80 in CD16+ monocytes. Collectively, these data indicate that anaphylatoxins play a central role in orchestrating Th17 response mainly via interactions between CD16+ monocytes and PMCs in TPE.

Background: Asthma is a complex pulmonary inflammatory disease which is common among older adults. Aging-related alterations have also been found in structural cells and immune cells of asthma patients. Nonetheless, the underlying mechanism by which differenced aging-related gene contributes to asthma pathology remains unclear. Of note, DNA methylation (DNAm) has been proven to play a critical mechanism for age-related gene expression changes. However, the methylation changes of aging-related genes in asthma patients are still obscure.Methods: First, changes in DNAm and gene expression were detected with multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients. Second, the correlation between the DNAm levels of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Last, the receiver operator characteristic (ROC) curve and principal component analysis (PCA) were used to identify the feasibility of the candidate CpG sites as biomarkers for asthma.Results: Compared with HCs, there was a differential mRNA expression for nine aging-related genes in peripheral blood of asthma patients. Besides, the methylation levels of the nine aging-related genes were also altered in asthma patients, and a total of 68 CpG sites were associated with the severity of asthma. Notably, 9 of the 68 CpG sites were significantly associated with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma.Conclusions: In summary, this study confirmed the differentially expressed mRNA and aberrant DNAm level of aging-related genes in asthma patients. DMSs are associated with the clinical evaluation indicators of asthma, which indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarkers for asthma.

Abstract Background Restoration of hand function after total brachial plexus root avulsion (tBPRA) is a difficult problem in surgical management. A new modified approach in repairing tBPRA is to use a subcutaneous tunnel across the anterior surface of the chest and neck, and then transfer the contralateral C7 root (cC7) to the lower trunk. However, the anatomical details of this method have not yet been fully described and assessed. The objective of this study was to quantitatively describe the nerve transfer using a cadaveric surgical simulation. Materials and methods Brachial plexuses were dissected from 12 adult cadavers, producing 24 sides of brachial plexuses for nerve transfer experiments. We performed simulated cC7 transfers to the lower trunk via a subcutaneous tunnel across the anterior surface of the chest and neck. Measurements of the nerves were made and transfers quantitatively documented. Results With the affected shoulder and arm in a neutral position, cC7 and C8-T1 could be sutured directly together in 75% of the cadavers. A nerve graft length of 4.6 ± 1.18 cm was needed to bridge the gap in the remaining cadavers. For cadavers where distal cC7 was directly connected with the lower trunk, 54.17% could be sutured, and an average nerve graft length of 3.9 cm was needed in the remains. Conclusions For surgical management of total tBPRA, transfer of the cC7 nerve to the C8-T1 or lower trunk via a subcutaneous tunnel across the chest and neck will likely be superior to a conventional cC7 root transfer in the clinic. This approach shortens the nerve graft needed and nerve regeneration distance, decreases the number of neurorrhaphy sites, and makes full use of the donor nerves, which may benefit hand flexion restoration.

Abstract Backgrounds Contralateral cervical seventh (C7) nerve transfer aids motor and sensory recovery in total brachial plexus avulsion injuries (TBPI), but synchronous sensation often persists postoperatively. The mechanism underlying synchronous sensory phenomena remain largely unknown. Objective To investigate the role of central plasticity in sensory recovery after contralateral C7 nerve transfer. Methods Sixteen right TBPI patients who received contralateral C7 nerve transfer for more than 2 years were included. Sensory evaluations included Semmes–Weinstein monofilament assessment (SWM), synchronous sensation test, and sensory evoked action potential (SNAP) test. Smaller value in the SWM assessment and larger amplitude of SNAP indicates better tactile sensory. Functional magnetic resonance imaging was performed while stimulations delivered to each hand separately in block‐design trials for central plasticity analysis. Results The SWM value of the injured right hand was increased compared with the healthy left side (difference: 1.76, 95% confidence interval: 1.37–2.15, p

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidiummonnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

ObjectivesIn December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19.MethodsData on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed.ResultsIn this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0-20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough.ConclusionThe symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.

BackgroundSurgical site infections (SSIs) are common postoperative complications. Whether the use of staples or sutures makes a difference in abdominal surgery's infection rate remains elusive.MethodsA systematic review was performed to identify randomized clinical trials comparing staples and sutures after abdominal surgeries. Eligibility criteria involved the SSI occurrence as the primary outcome and the incidence of wound dehiscence, closure time, cosmesis, and patient satisfaction as the secondary outcomes.ResultsOf the 278 studies identified, seven randomized controlled trials representing 3705 patients were included in this review. There was no significant difference in SSI rates between sutures and staples in general (OR = 0.98, 95% CI = 0.79-1.22, I2 = 44%, P = 0.1) or in a subgroup of gastrointestinal surgery, where subcuticular suturing was found with a comparable SSI risk with skin stapling (OR = 0.85, 95% CI = 0.66-1.09). Staple closure was associated with a shorter surgery duration, whereas sutures appeared to provide better cosmesis and patient satisfaction. Sutures and staples achieved a comparable incidence of dehiscence. There was no significant between-study publication bias.ConclusionOur study demonstrated similar outcomes in SSI rate between subcuticular sutures and staples for skin closure in patients undergoing abdominal surgery.

The Valsa canker caused by Valsa mali seriously harmed the production of East Asian apples and caused very significant economic losses. Considering the chemical residues and the improvement of people’s awareness of environmental protection, there is a need for screening new green pesticides for the control of Valsa canker. Therefore, we conducted systematic evaluations on the antifungal activity of wood tar. In this research, the effective concentration (EC50) of six strains of V. mali to wood tar was determined, and the EC50 ranged from 69.54 to 92.81 μg/mL. After treatment with wood tar, the hyphae of V. mali broke, swelled, and deformed; the permeability of the cell membrane increased; and the activity of pectinase reduced. Moreover, the expression levels of five genes related to pectinase also decreased significantly. In addition, the activities of phenylalanine ammonia lyase (PAL) and peroxidase (POD) of apple leaves treated with wood tar also increased. On detached apple branches, wood tar also showed therapeutic and protective activities. In the 2016–2019 field experiments, wood tar also showed good efficacy against Valsa canker and promoted the formation of callus. (In the experiments from 2016 to 2019, it can be seen that the control effect of 50% wood tar and 100% wood tar in the field is above 75% and promoted the formation of callus.) This study is the first to report the bidirectional efficacy of wood tar against Valsa mali and for trunk wound healing. The above results evidenced that wood tar has great potential to be developed as a natural alternative to commercial fungicides for the management of apple Valsa canker.

Abstract Background Myoelectric control of multifunctional prostheses is challenging for individuals with high-level amputations due to insufficient surface electromyography (sEMG) signals. A surgical technique called targeted muscle reinnervation (TMR) has achieved impressive improvements in myoelectric control by providing more sEMG control signals. In this case, some channels of sEMG signals are coupled after TMR, which limits the performance of conventional amplitude-based control for upper-limb prostheses. Methods In this paper, two different ways (training and algorithms) were attempted to solve the problem in a transhumeral amputee after TMR. Firstly, effect of rehabilitation training on generating independent sEMG signals was investigated. The results indicated that some sEMG signals recorded were still coupled over the targeted muscles after rehabilitation training for about two months. Secondly, pattern recognition (PR) algorithm was then applied to classify the sEMG signals. In the second way, to further improve the real-time performance of prosthetic control, a post-processing method named as mean absolute value-based (MAV-based) threshold switches was utilized. Results Using the improved algorithms, substantial improvement was shown in a subset of the modified Action Research Arm Test (ARAT). Compared with common PR control without post-processing method, the total scores increased more than 18% with majority vote and more than 58% with MAV-based threshold switches. The amputee was able to finish all the tasks within the allotted time with the standard MAV-based threshold switches. Subjectively the amputee preferred the PR control with MAV-based threshold switches and reported it to be more accurate and much smoother both in experiment and practical use. Conclusions Although the sEMG signals were still coupled after rehabilitation training on the TMR patient, the online performance of the prosthetic operation was improved through application of PR control with combination of the MAV-based threshold switches. Trial registration Retrospectively registered http://www.chictr.org.cn/showproj.aspx?proj=22058.

To avoid the widespread resistance of commercial fungicides, new broad-spectrum botanical fungicides need to be developed. In previous bioactive screening assays, extracts of Artemisia ordosica Krasch. (A. ordosica) had highly antifungal activities, but the responsible phytochemicals were unidentified. In this study, active compounds of A. ordosica extracts were identified using a bioassay-guided method, and antifungal assays were performed in vitro and in vivo. The bioactive compounds were dissolved in petroleum ether, and the best antifungal fraction contained four compounds: trans-dehydromatricaria ester (TDDE), 7, 4-demetylnringenin, capillarin, and stearic acid. Among them, TDDE exhibited the highest antifungal activity against six pathogenic fungi and five bacteria. It exhibited significant fungicidal activity against Thanatephorus cucumeris and Botrytis cinerea with EC50 values of 0.464 μg/mL and 1.4 μg/mL, respectively. The living tissue bioassay results showed that the relative protection effects (RPE) of TDDE on tomato leaves, tomato fruit, and strawberry leaves infected with B. cinerea reached 76.78%, 86.2%, and 80.89%, respectively. In pot experiments, the RPE on tomato and strawberry plants infected with B. cinerea reached 84.11% and 96.37%, respectively. Morphological and physiological examination showed that TDDE had significant inhibitory effects on mycelial growth, including increased top offshoot, contorted hyphal tips, and extravasated cytochylema. Meanwhile, bactericidal activities of TDDE were significantly higher than kanamycin and streptomycin in five bacteria, and the plant tissue experiments further demonstrated that it had an 88.31% RPE on walnut leaves infected with Xanthomonas campestris pv. jugiandis, 72.18% RPE on potato infected with Erwinia carotovora subsp. carotovora, and 82.50% RPE on kiwifruit branches infected with Pseudomonas syringae pv. actinidiae. The active compounds isolated from A. ordosica in this study show great potential value for developing broad-spectrum fungicides, and also provide an important way to identify and isolate new bioactive products from medicinal plants.

Abstract Background Unstable pelvic ring injuries often involve high mortality and morbidity. This study was aimed to evaluate the modified minimally invasive pedicle screw–rod fixation for anterior pelvic ring injuries, in the respects of its feasibility, merits, and limitations. Methods Twenty-three patients with unstable pelvic ring injuries underwent the modified anterior pedicle screw–rod fixation, with or without posterior fixation. The clinical outcomes were assessed using Majeed scores, and the quality of reduction was evaluated according to the criteria of Matta. Results Majeed scores showed that the clinical outcomes at postoperatively 1 year were excellent in 14 patients, good in 7, and fair in 2. One woman complained of persistent pain at the pubic tubercle during sexual intercourse. Iatrogenic neuropraxia of the unilateral lateral femoral cutaneous nerve occurred in 3 patients. Unilateral femoral nerve palsy occurred in 1 patient. The reduction was found to be excellent in 12 patients, good in 8, and fair in 3. Heterotopic ossification occurred in 8 patients, all being asymptomatic. Conclusions The modified pedicle screw–rod fixation with the minimally invasive technique offered an effective alternative for unstable anterior pelvic ring injuries.

Respiratory viral infections can directly lead to kidney damage such as IgA nephropathy (IgAN), partly due to mucosal immune system dysfunction. Although the activated C5a-C5aR1 axis results in increased Th1 and Th17 frequencies but reduced Treg frequencies in Respiratory syncytial virus (RSV) infection, how this axis affects Th cell disorders in RSV-induced IgAN exacerbation remains unknown. Here, we used a mouse model to dissect the activation of C5a-C5aR1 by RSV and the consequences on the regulation of Th1, Th17, and Treg immune responses in IgA nephropathy. RSV fusion protein was clearly deposited not only in the pulmonary interstitium but also in the glomerulus in RSV-IgAN mice, and RSV infection led to more severe pathological changes in the kidneys in IgAN mice. Blocking the C5a-C5aR1 axis resulted in a decrease in the albumin-to-creatinine ratio, and the attenuation of kidney damage in IgAN and RSV-IgAN mice might be partly attributed to the inhibition of Th cell and cytokine dysfunction. Th1, Th17 and Treg immune responses and their corelative cytokines were disrupted by RSV infection and rescued by C5aR1 inhibition. Moreover, we constructed a coculture system of human mesangial cells and CD4+ T cells and found that RSV infection might lead to CD4+ T cell production via human mesangial cells-enhanced CD4+ T cell proliferation, consequently increasing IL-17 levels. These pathological behaviors were augmented by C5a stimulation and decreased by C5aR1 inhibition. Thus, C5aR1 inhibition alters both kidney damage and Th1, Th17, and Treg cell dysfunction in RSV-induced IgAN exacerbation and locally regulates HMC antigen presentation function in the kidney. Taken together, our data offer profound evidence that blocking the C5a-C5aR1 axis might be a potential therapy for RSV-induced IgAN.

Background: Previous studies have demonstrated that glucocorticoid-induced transcript 1 gene (GLCCI1) rs37973 mutant genotype is associated with poor inhaled corticosteroid (ICS) response in asthmatics. As human airway relaxation is regulated by circulation epinephrine, which can be enhanced by corticosteroid. It is unknown whether or not GLCCI1 rs37973 is associated with circulation epinephrine and cortisol concentrations in asthma. The aim of this study is to evaluate these relationships. Methods: A total of 182 asthmatics and 180 healthy controls were recruited for the study. 30 mild-to-moderate asthmatics received fluticasone propionate (125 μg, bid) treatment for 12 weeks. GLCCI1 rs37973 genotyping was performed with the iPlex MassARRAY genotyping platform. The plasma concentrations of cortisol and epinephrine of each participant were detected by enzyme linked immunosorbent assay (ELISA) kits. Results: GLCCI1 rs37973 homozygotes mutant genotype GG had a higher plasma epinephrine concentration (median concentration 27.032 pg/ml, nGG = 36; median concentration 23.149 pg/ml, nAA+AG = 146; P = 0.015) and cortisol concentration (median concentration 1.141 ng/ml, nGG = 36; median concentration 0.921 ng/ml, nAA+AG = 146; P = 0.013). Both epinephrine concentration and cortisol concentration in plasma were positively correlated with FEV1 (r = 0.889 and r = 0.821, respectively. nasthma = 182). For asthmatics treated with ICS, rs37973 was associated with change in plasma epinephrine and cortisol concentration in a recessive model (AA + AG vs GG), with GG had less improvement in epinephrine concentration [ΔEPIAA+AG = 6.843 (9.26) pg/ml, nAA+AG = 26; ΔEPIGG = −1.666 (6.52) pg/ml, nGG = 4; P = 0.018] and cortisol concentration [ΔCORAA+AG = 0.3040 (0.21) ng/ml, nAA+AG = 26; ΔCORGG = −0.066 (0.24) ng/ml, nGG = 4; P = 0.009]. Conclusions: Our study suggested that the poor ICS response in GLCCI1 rs37973 mutant genotype might be related to the less increased amplitudes of plasma epinephrine and cortisol in asthmatic patients. Trial registration: ChiCTR-RCC-13003634 www.chictr.org.cn. Active since September 27, 2013. Keywords: GLCCI1, Adrenal hormone, Inhaled corticosteroids, Asthma

Take-all, caused by Gaeumannomyces tritici, is one of the most important wheat root diseases worldwide, as it results in serious yield losses. In this study, G. tritici was transformed to express the hygromycin B phosphotransferase using a combined protoplast and polyethylene glycol (PEG)-mediated transformation technique. Based on a series of single-factor experimental results, three major factors—temperature, enzyme lysis time, and concentration of the lysing enzyme—were selected as the independent variables, which were optimized using the response surface methodology. A higher protoplast yield of 9.83 × 107 protoplasts/mL was observed, and the protoplast vitality was also high, reaching 96.27% after optimization. Protoplasts were isolated under the optimal conditions, with the highest transformation frequency (46–54 transformants/μg DNA). Polymerase chain reaction and Southern blotting detection indicated that the genes of hygromycin phosphotransferase were successfully inserted into the genome of G. tritici. An optimised PEG-mediated protoplast transformation system for G. tritici was established. The techniques and procedures described will lay the foundation for establishing a good mutation library of G. tritici and could be used to transform other fungi.

Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs. To obtain soluble protein, the truncated TwSQS without the last 28 amino acids of the carboxy terminus was inductively expressed in Escherichia coli Transetta (DE3). The purified protein was detected by SDS-PAGE and Western blot analysis. Squalene was detected in the product of in vitro reactions by gas chromatograph-mass spectrometry, which meant that TwSQS did have catalytic activity. Organ-specific and inducible expression levels of TwSQS were detected by quantitative real-time PCR. The results indicated that TwSQS was highly expressed in roots, followed by the stems and leaves, and was significantly up-regulated upon MeJA treatment. The identification of TwSQS is important for further studies of celastrol biosynthesis in T. wilfordii.

Fusarium wilt and anthracnose are two major diseases which limit the yield and quality of cucumber worldwide. Cuminic acid was extracted from the seed of Cuminum cyminum L. The mean EC50 values of cuminic acid for inhibiting mycelial growth and zoospore germination of five Fusarium oxysporum f. sp. cucumerinum strains were 25.66 ± 3.02 μg/mL and 15.99 ± 2.19 μg/mL, and of four Colletotrichum lagenarium (Pass.) Ellis and Halsted strains were 29.53 ± 3.18 μg/mL and 18.41 ± 2.78 μg/mL, respectively. In greenhouse experiments, cuminic acid at 2000 μg/mL exhibited 70.77% protective and 62.63% curative efficacies against F. oxysporum, and 65.43% protective and 55.46% curative efficacies against C. lagenarium. Moreover, the translocation behavior of cuminic acid, determined by high performance liquid chromatography (HPLC), showed that it could be readily absorbed and transported upward and downward in cucumber. Importantly, superoxide dismutase (SOD) and pyphenol oxidase (PPO) activities of cucumber leaves treated with cuminic acid increased significantly. All results indicated that cuminic acid showed antifungal activity, and could be used as a botanical fungicide in disease management. This study encourages further investigation on the mechanism of action of cuminic acid and the development of alternative antifungal drugs.

Background and objective Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. Methods Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H＆E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. Results No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (χ2=8.12, P0.05). However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P

Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P. capsici to cuminic acid was determined. The mean EC50 (50% effective concentration) values for cuminic acid in inhibiting mycelial growth and zoospore germination of the 54 studied P. capsici isolates were 14.54 ± 5.23 μg/mL and 6.97 ± 2.82 μg/mL, respectively. After treatment with cuminic acid, mycelial morphology, sporangium formation and mycelial respiration were significantly influenced; cell membrane permeability and DNA content increased markedly, but pyruvic acid content, adenosine triphosphate (ATP) content, and ATPase activity decreased compared with the untreated control. In pot experiments, cuminic acid exhibited both protective and curative activity. Importantly, POD and PAL activity of the pepper leaves increased after being treated with cuminic acid. These indicated that cuminic acid not only showed antifungal activity, but also could improve the defense capacity of the plants. All the results suggested that cuminic acid exhibits the potential to be developed as a new phytochemical fungicide, and this information increases our understanding of the mechanism of action of cuminic acid against Phytophthora capsici.

In consideration of the fact that the α-methylene-γ-butyrolactone moiety is a major bio-functional group in the structure of carabrone and possesses some agricultural biological activity, forty-six new ester and six new ether derivatives containing α-methylene-γ-butyrolactone moieties were synthesized, and their fungicidal activities against Colletotrichum lagenarium and Botrytis cinerea were investigated. Most of the synthesized compounds showed moderate to significant fungicidal activity. Among them, halogen atom-containing derivatives showed better activity than others, especially compounds 6a,d which exhibited excellent fungicidal activity against C. lagenarium, with IC50 values of 7.68 and 8.17 μM. The structure-activity relationship (SAR) analysis indicated that ester derivatives with electron-withdrawing groups on the benzene ring showed better fungicidal activity than those with electron-donating groups. A quantitative structure-activity relationship (QSAR) model (R2 = 0.9824, F = 203.01, S2 = 0.0083) was obtained through the heuristic method. The built model revealed a strong correlation of fungicidal activity against C. lagenarium with the molecular structures of these compounds. These results are expected to prove helpful in the design and exploration of low toxicity and high efficiency α-methylene-γ-butyrolactone-based fungicides.