Integration of Metabolomics and Transcriptomics to Explore Dynamic Alterations in Fruit Color and Quality in 'Comte de Paris' Pineapples during Ripening Processes.

Pineapple color yellowing and quality promotion gradually manifest as pineapple fruit ripening progresses. To understand the molecular mechanism underlying yellowing in pineapples during ripening, coupled with alterations in fruit quality, comprehensive metabolome and transcriptome investigations were carried out. These investigations were conducted using pulp samples collected at three distinct stages of maturity: young fruit (YF), mature fruit (MF), and fully mature fruit (FMF). This study revealed a noteworthy increase in the levels of total phenols and flavones, coupled with a concurrent decline in lignin and total acid contents as the fruit transitioned from YF to FMF. Furthermore, the analysis yielded 167 differentially accumulated metabolites (DAMs) and 2194 differentially expressed genes (DEGs). Integration analysis based on DAMs and DEGs revealed that the biosynthesis of plant secondary metabolites, particularly the flavonol, flavonoid, and phenypropanoid pathways, plays a pivotal role in fruit yellowing. Additionally, RNA-seq analysis showed that structural genes, such as FLS, FNS, F3H, DFR, ANR, and GST, in the flavonoid biosynthetic pathway were upregulated, whereas the COMT, CCR, and CAD genes involved in lignin metabolism were downregulated as fruit ripening progressed. APX as well as PPO, and ACO genes related to the organic acid accumulations were upregulated and downregulated, respectively. Importantly, a comprehensive regulatory network encompassing genes that contribute to the metabolism of flavones, flavonols, lignin, and organic acids was proposed. This network sheds light on the intricate processes that underlie fruit yellowing and quality alterations. These findings enhance our understanding of the regulatory pathways governing pineapple ripening and offer valuable scientific insight into the molecular breeding of pineapples.

In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection.

Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-ß given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes 4 days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Molecular characterization of fast-growing melanomas.

BACKGROUND: The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied. OBJECTIVE: To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth. METHODS: Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma samples. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month). RESULTS: Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth. LIMITATIONS: Single-center study, cohort size, potential memory bias, number of investigated genes. CONCLUSION: Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies.

Biosynthesis and Metabolism of Garlic Odor Compounds in Cultivated Chinese Chives (Allium tuberosum) and Wild Chinese Chives (Allium hookeri).

Chinese chives is a popular herb vegetable and medicine in Asian countries. Southwest China is one of the centers of origin, and the mountainous areas in this region are rich in wild germplasm. In this study, we collected four samples of germplasm from different altitudes: a land race of cultivated Chinese chives (Allium tuberosum), wide-leaf chives and extra-wide-leaf chives (Allium hookeri), and ovoid-leaf chives (Allium funckiaefolium). Leaf metabolites were detected and compared between A. tuberosum and A. hookeri. A total of 158 differentially accumulated metabolites (DAM) were identified by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), among which there was a wide range of garlic odor compounds, free amino acids, and sugars. A. hookeri contains a higher content of fructose, garlic odor compounds, and amino acids than A. tuberosum, which is supported by the higher expression level of biosynthetic genes revealed by transcriptome analysis. A. hookeri accumulates the same garlic odor compound precursors that A. tuberosum does (mainly methiin and alliin). We isolated full-length gene sequences of phytochelatin synthase (PCS), γ-glutamyltranspeptidases (GGT), flavin-containing monooxygenase (FMO), and alliinase (ALN). These sequences showed closer relations in phylogenetic analysis between A. hookeri and A. tuberosum (with sequence identities ranging from 86% to 90%) than with Allium cepa or Allium sativum (which had a lower sequence identity ranging from 76% to 88%). Among these assayed genes, ALN, the critical gene controlling the conversion of odorless precursors into odor compounds, was undetected in leaves, bulbs, and roots of A. tuberosum, which could account for its weaker garlic smell. Moreover, we identified a distinct FMO1 gene in extra-wide-leaf A. hookeri that is due to a CDS-deletion and frameshift mutation. These results above reveal the molecular and metabolomic basis of impressive strong odor in wild Chinese chives.

Analysis of Lipids in Green Coffee by Ultra-Performance Liquid Chromatography-Time-of-Flight Tandem Mass Spectrometry.

Lipid components in green coffee were clarified to provide essential data support for green coffee processing. The types, components, and relative contents of lipids in green coffee were first analyzed by ultra-performance liquid chromatography-time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS). The results showed that the main fatty acids in green coffee were linoleic acid (43.39%), palmitic acid (36.57%), oleic acid (8.22%), and stearic acid (7.37%). Proportionally, the ratio of saturated fatty acids/unsaturated fatty acids/polyunsaturated fatty acids was close to 5.5:1:5.2. A total of 214 lipids were identified, including 15 sterols, 39 sphingosines, 12 free fatty acids, 127 glycerides, and 21 phospholipids. The main components of sterols, sphingosines, free fatty acids, glycerides, and phospholipids were acylhexosyl sitosterol, ceramide esterified omega-hydroxy fatty acid sphingosine, linoleic acid, and triglyceride, respectively. UPLC-TOF-MS/MS furnished high-quality and accurate information on TOF MS and TOF MS/MS spectra, providing a reliable analytical technology platform for analyzing lipid components in green coffee.

Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.

RATIONALE: Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, and lower respiratory tract infections, are poorly understood. OBJECTIVES: We characterized multiple cytokine responses of peripheral blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes. METHODS: In a population-based birth cohort, we measured 28 cytokines after stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes, using longitudinal models. We also ascertained phytohemagglutinin-induced T-helper cell type 2 (Th2)-cytokine responses (PHA-Th2). MEASUREMENTS AND MAIN RESULTS: We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related (IFN), proinflammatory (Inflam), Th2-chemokine (Th2-chem), and regulatory (Reg). Clusters differed in their clinical characteristics. Children with an IFNmodInflamhighestTh2-chemhighestReghighest rhinovirus-16-induced pattern had a PHA-Th2low response, and a very low asthma risk (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01-0.81; P = 0.03). Two clusters had a high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowestInflamhighTh2-chemlowRegmod cluster exhibited a PHA-Th2lowest response and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (OR, 1.37; 95% CI, 1.07-1.76; P = 0.014) and lower respiratory tract infection hospitalizations (OR, 2.40; 95% CI, 1.26-4.58; P = 0.008) throughout childhood. In contrast, the IFNhighestInflammodTh2-chemmodReghigh cluster with a rhinovirus-16-cytokine pattern was characterized by a PHA-Th2highest response, and a low prevalence of asthma/sensitization in infancy that increased sharply to become the highest among all clusters by adolescence (but with a low risk of asthma exacerbations). CONCLUSIONS: Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.

[Performance of FibroScan in evaluating the curative effects of traditional Chinese medicine on liver fibrosis].

OBJECTIVE: To assess the performance of FibroScan in evaluating the curative effects of traditional Chinese medicine (TCM) on liver fibrosis, and to analyze factors influencing the diagnostic accuracy. METHODS: Data of FibroScan values, types of disease, use of drug, liver function indexes, prothrombin time (PT) and international normalized ratio (INR) were collected at both pre- (1 month prior) and post-FibroScan for 102 patients who underwent at least two FibroScan procedures. Patients were subgrouped according to presence of fibrosis, presence of cirrhosis, and TCM formulation and statistically analyzed. RESULTS: The pre- and post-FibroScan mean liver stiffness measurements (LSMs) were significantly different when the variation of LSM was more than or equal to2 kPa for the non-fibrotic group (vs. the fibrotic group), or when the variation wasmore than or equal to4 kPa for the cirrhotic group (vs. the non-cirrhotic group). In addition, the three TCM formulation groups showed significant differences, with the most robust difference exhibited between the FuZheng HuaYu formulation group and the other treatment groups (P = 0.010). No significant differences were observed for the liver function indexes, PT, or INR. However, the post-FibroScan levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) was significantly reduced in patients with reduced LSM. CONCLUSION: FibroScan may be a useful non-invasive clinical tool for evaluating the comprehensive curative effect of treatments for chronic liver diseases, and its performance is not obviously impacted by ALT, AST, GGT, PT, and INR. The criteria for efficacy established by FibroScan are 2 kPa for the patients without liver fibrosis and 4 kPa for patients with liver cirrhosis.

[Chemical constituents from Canarium pimela fruits].

OBJECTIVE: To investigate the chemical constituents from Canarium pimela fruits. METHODS: Compounds were obtained after separation and purification by silica gel and Sephadex LH-20. The structures were identified on the basis of physico-chemical properties and spectrum data. RESULTS: Eight compounds were isolated from Canarium pimela fruits. The structures were identified as amentoflavone (1), kaempferol-3-O-ß-D-galactopyranoside (2), shikimic acid (3), quercetin (4), kaempferol (5), 3,3'-di-O-methylellagic acid (6), 3,3',4-tri-O-methylellagic acid (7) and stigmasterol (8). CONCLUSION: Compounds 1-8 are isolated from Canarium pimela fruits for the first time.

Preparation and characterization of tea tree essential oil microcapsule-coated packaging paper with bacteriostatic effect.

We prepared tea tree essential oil microcapsules, and the microcapsules and pullulan were coated on kraft paper to prepare an antibacterial paper. The antibacterial activity, structural characterization, and thermal stability of the prepared microcapsules and packaging paper were then tested. We found that the retention rate of microcapsules reached 87.1% after a 70 min of high-temperature treatment. The minimum inhibitory concentrations of microcapsules to S. aureus and E. coli were 112 mg/mL and 224 mg/mL, and the bacteriostatic zones of the packaging paper to E. coli and S. aureus were 17.49 mm and 22.75 mm, respectively. The prepared microcapsules were irregular. The paper coating was formed via hydrogen bonding, which filled the pores of paper fibers. When compared with the base paper, the roughness of the paper was reduced to 7.16 nm (Rq) and 5.61 nm (Ra), and no thermal decomposition occurred at <288 °C, which together implies a good application prospect.

Making predictions under interventions: a case study from the PREDICT-CVD cohort in New Zealand primary care.

Background: Most existing clinical prediction models do not allow predictions under interventions. Such predictions allow predicted risk under different proposed strategies to be compared and are therefore useful to support clinical decision making. We aimed to compare methodological approaches for predicting individual level cardiovascular risk under three interventions: smoking cessation, reducing blood pressure, and reducing cholesterol. Methods: We used data from the PREDICT prospective cohort study in New Zealand to calculate cardiovascular risk in a primary care setting. We compared three strategies to estimate absolute risk under intervention: (a) conditioning on hypothetical interventions in non-causal models; (b) combining existing prediction models with causal effects estimated using observational causal inference methods; and (c) combining existing prediction models with causal effects reported in published literature. Results: The median absolute cardiovascular risk among smokers was 3.9%; our approaches predicted that smoking cessation reduced this to a median between a non-causal estimate of 2.5% and a causal estimate of 2.8%, depending on estimation methods. For reducing blood pressure, the proposed approaches estimated a reduction of absolute risk from a median of 4.9% to a median between 3.2% and 4.5% (both derived from causal estimation). Reducing cholesterol was estimated to reduce median absolute risk from 3.1% to between 2.2% (non-causal estimate) and 2.8% (causal estimate). Conclusions: Estimated absolute risk reductions based on non-causal methods were different to those based on causal methods, and there was substantial variation in estimates within the causal methods. Researchers wishing to estimate risk under intervention should be explicit about their causal modelling assumptions and conduct sensitivity analysis by considering a range of possible approaches.

Analysis of Physicochemical Properties, Lipid Composition, and Oxidative Stability of Cashew Nut Kernel Oil.

Cashew nut kernel oil (CNKO) is an important oil source from tropical crops. The lipid species, composition, and relative content of CNKO were revealed using ultra high performance liquid chromatography time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS), and the physicochemical properties, functional group structure, and oxidation stability of CNKO at different pressing temperatures were characterized using a near infrared analyzer and other methods. The results showed that CNKO mainly consisted of oleic acid (60.87 ± 0.06%), linoleic acid (17.33 ± 0.28%), stearic acid (10.93 ± 0.31%), and palmitic acid (9.85 ± 0.04%), and a highly unsaturated fatty acid (78.46 ± 0.35%). In addition, 141 lipids, including 102 glycerides and 39 phospholipids, were identified in CNKO. The pressing temperature had a significant effect on the physicochemical properties of cashew kernels, such as acid value, iodine value, and peroxide value, but the change in value was small. The increase in pressing temperature did not lead to changes in the functional group structure of CNKO, but decreased the induction time of CNKO, resulting in a decrease in their oxidative stability. It provided basic data support to guide subsequent cashew kernel processing, quality evaluation, and functional studies.

Effects of Three Extraction Methods on Avocado Oil Lipid Compounds Analyzed via UPLC-TOF-MS/MS with OPLS-DA.

Avocado oil is excellent functional oil. Effects of three extraction methods (squeezing extraction, supercritical carbon dioxide extraction, and aqueous extraction) on the species, composition, and contents of lipids in avocado oil were analyzed via ultra-performance liquid chromatography-time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS), and the differential components of lipids were revealed by OrthogonalPartialLeast Squares-DiscriminantAnalysis (OPLS-DA), S-plot combined with variable importance in the projection (VIP). The results showed that the fatty acid composition of avocado oil mainly consisted of oleic acid (36-42%), palmitic acid (25-26%), linoleic acid (14-18%), and palmitoleic acid (10-12%). A total of 134 lipids were identified first from avocado oil, including 122 glycerides and 12 phospholipids, and the total number of carbon atoms contained in the fatty acid side chains of the lipids was 32-68, and the number of double bonds was 0-9. Forty-eight differential lipid compounds with significant effects of the three extraction methods on the lipid composition of avocado oil were excavated, among which the differences in triglycerides (TG), phosphatidylethanol (PEtOH), and phosphatidylmethanol (PMeOH) contents were highly significant, which provided basic data to support the subsequent guidance of avocado oil processing, quality evaluation, and functional studies.

Study of the Metabolite Changes in Ganoderma lucidum under Pineapple Leaf Residue Stress via LC-MS/MS Coupled with a Non-Targeted Metabolomics Approach.

The effects of fermentation metabolites of G. lucidum under different pineapple leaf residue additions were separated and identified using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The mass spectra showed that the metabolites had good response values only in the positive ion mode, and 3019 metabolites with significant differences, mainly distributed in 95 metabolic pathways, were identified. The multivariate analyses, including the principal component analysis (PCA), orthogonal least squares discriminant analysis (OPLS-DA), and volcano plots (VP), revealed that the G. lucidum metabolites exhibited significant differences (p < 0.05) and were well clustered under various pineapple leaf residue additions, featuring 494-545 upregulated and 998-1043 downregulated metabolites. The differential metabolic pathway analysis proved that two metabolic pathways related to the biosynthesis of amino acids and ABC transporters were particularly significant under the addition of pineapple leaf residue, where amino acids such as histidine and lysine were upregulated in contrast to downregulated tyrosine, valine, L-alanine, and L-asparagine. These study results are considered instrumental in substantiating the application of pineapple leaf residue in the cultivation of G. lucidum and improving its utilization rate and added value.

Study on the Structure and Bioactivity of Ganoderma lucidum Polysaccharides under Cassava Stalk Stress.

Various carbon sources affect the growth of the G. lucidum fruiting body, and the cassava stalk is considered a promising carbon source for G. lucidum. The composition, functional group characteristics, molecular weight distribution, antioxidant activity in vitro, and growth effect of L. rhamnosus LGG of G. lucidum polysaccharides (GLPs) under cassava stalk stress were investigated by gas chromatography-mass spectrometry, near-infrared spectroscopy, and gel chromatography. The results showed that GLPs consisted of D-glucose, D-galactose, and seven other monosaccharides. The end of the sugar chain had ß-D-Glc and ß-D-Gal configurations. The total sugar content in GLP1 was the highest (4.07%), and GLP1, GLP2, GLP3, and GLP5 had the ß-D-Gal configuration, while GLP4 and GLP6 had the ß-D-Glc configuration. The greater the proportion of cassava stalk, the greater the maximum molecular weight of GLPs. The total antioxidant capacities of GLPs obtained from different cassava stalks significantly varied, as well as their stimulating effects on the L. rhamnosus LGG growth. Higher concentrations of GLPs corresponded to the more intensive growth of L. rhamnosus LGG. This study provided essential data support for cassava stalk as a carbon source in G. lucidum cultivation.

Physiological and transcriptomic analysis of IAA-induced antioxidant defense and cell wall metabolism in postharvest mango fruit.

Mango fruit tend to oxidize and senescence rapidly after harvesting, significantly reducing their commercial value. This study investigated the effect of exogenous auxin indole-3-acetic acid (IAA) on fruit quality, antioxidant system, and cell wall metabolism of mango fruit during storage. The results showed that the 1.0 mM IAA treatment delayed weight loss and maintained the firmness, pH and contents of total soluble solids (TSS) and titratable acidity (TA) of the mango fruit. The 1.0 mM IAA treatment increased the peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities and the ascorbic acid (AsA) and total phenols (TP) contents but decreased the polyphenol oxidase (PPO) activity in postharvest mango fruit. Moreover, beta-galactosidase (ß-Gal) and polygalacturonase (PG) activities were increased, but the pectinesterase (PME) activity was decreased in the IAA-treated fruit. Transcriptome analysis showed that the differentially expressed genes (DEGs) in the IAA vs. control groups were mainly associated with oxidative stress responses, cell wall metabolism, and transcription factors (TFs). The IAA treatment upregulated the antioxidant-related genes (SOD, CAT1, PODs, GSTs, Prxs, and Trxs) and MYB TFs, and downregulated cell wall metabolism-related genes (PG, PME31 and two PME63) and 11 ethylene-responsive transcription factors (ERFs). These results suggested that exogenous IAA could improve the antioxidant system and maintain the storage quality of mango fruit by regulating gene expression and metabolic pathways. The results provide insights into the mechanisms involved in IAA-mediated delayed ripening and senescence of mango fruit.

Exogenous glutathione maintains the postharvest quality of mango fruit by modulating the ascorbate-glutathione cycle.

Background: Mango fruit is prone to decay after harvest and premature senescence, which significantly lowers its quality and commercial value. Methods: The mango fruit (Mangifera indica L.cv. Guixiang) was treated with 0 (control), 2, 5, and 8 mM of reduced glutathione (GSH) after harvest. The fruit was stored at 25 ± 1 °C for 12 days to observe the changes in the antioxidant capacity and postharvest quality. Results: Compared with the control, the 5 mM GSH treatment significantly decreased the weight loss by 44.0% and 24.4%, total soluble solids content by 25.1% and 4.5%, and soluble sugar content by 19.0% and 27.0%. Conversely, the 5 mM GSH treatment increased the firmness by 25.9% and 30.7% on days 4 and 8, respectively, and the titratable acidity content by 115.1% on day 8. Additionally, the 5 mM GSH treatment decreased the malondialdehyde and hydrogen peroxide contents and improved the antioxidant capacity of mango fruit by increasing the superoxide dismutase and peroxidase activities and upregulating the expression of the encoding genes. Meanwhile, the higher levels of monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase enzyme activities and gene expressions accelerated the AsA-GSH cycle, thereby increasing the accumulation of AsA and GSH and maintaining the redox balance. Conclusions: Overall, the experimental results suggest that 5 mM GSH maintains high antioxidant capacity and postharvest quality of mangoes and can use as an effective preservation technique for postharvest mangoes.

Influence of highly effective modulator therapy on the sputum proteome in cystic fibrosis.

BACKGROUND: There have been dramatic clinical improvements in people with cystic fibrosis (PwCF) commenced on the cystic fibrosis conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI). Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms. Using this technique, we evaluated how ETI changes the sputum proteome in PwCF. METHODS: Sputum samples from 21 CF subjects pre- and post- ETI, 6 CF controls ineligible for ETI, and 15 healthy controls were analysed by liquid chromatography mass spectrometry. RESULTS: Post-ETI, mean FEV1 % increased by 13.7 % (SD 7.9). Principal component and hierarchical clustering analysis revealed that the post-ETI proteome shifted to an intermediate state that was distinct from pre-ETI and healthy controls, even for those achieving normal lung function. Functional analysis showed incomplete resolution of neutrophilic inflammation. The CF control sputum proteome did not alter. At the protein-level many more proteins increased in abundance than decreased following ETI therapy (80 vs 30; adjusted p value <0.05), including many that have anti-inflammatory properties. Of those proteins that reduced in abundance many were pro-inflammatory neutrophil-derived proteins. Several important respiratory proteases were unchanged. CONCLUSIONS: Sputum proteomics can provide insights into CF lung disease mechanisms and how they are modified by therapeutic intervention, in this case ETI. This study identifies imbalances in pro- and anti- inflammatory proteins in sputum that partially resolve with ETI even in those achieving normal spirometry values. This post-ETI intermediate state could contribute to ongoing airway damage and therefore its relevance to clinical outcomes needs to be established.

[Response of Topsoil Fungal Community Structure to Soil Improvement Measures in Degraded Forest of Red Soil Region].

Soil fungal community structure and diversity are highly sensitive to variations in the external environment, as well as soil improvement measures. In order to clarify the effects of soil improvement measures on topsoil fertility or quality, a field experiment was conducted in eroded forest of a red soil region. Organic fertilizer, biochar, and lime+microbial fertilizer were added to the topsoil, respectively. After four years, the chemistry properties and nutrients in the topsoil were measured, and the diversity and composition of fungi were analyzed. The results showed that the additions of organic fertilizer, biochar, and lime+microbial fertilizer reduced fungal richness in topsoil, compared to that with no fertilizer addition (CK). Among them, lime+microbial fertilizer had the most negative effect on fungal richness. The three soil improvement measures also affected the diversity of topsoil fungi, but the impacts were not significant. The dominant fungal phyla in the topsoil were Ascomycota (31.29%-46.55%) and Basidiomycota (30.07%-70.71%), and the dominant fungal genera were Amphinema and Archaeorhizomyces. The effects of soil improvement measures on fungal community structure in the topsoil were different; organic fertilizer increased the relative abundance of Ascomycetes and Archaeopteroides, and biochar enhanced the relative abundance of Basidiomycetes and Archaeopteroides, whereas lime+microbial fertilizer improved the relative abundance of Basidiomycetes and Archaeopteroides. Fungal diversity and community structure in the topsoil was affected by edaphic factors, and fungal richness was regulated by pH value, whereas fungal community structure was influenced by pH, total nitrogen, and organic carbon. This study provides scientific guidance for soil improvement and ecological restoration below the canopy in eroded forests of red soil regions.

Profiling the expression of interleukin (IL)-28 and IL-28 receptor α in systemic lupus erythematosus patients.

BACKGROUND: Interleukin (IL)-28 is an interferon-λ-family member involved in immunity against viral infection and tumour. We here determined the expression profiles of IL-28 and IL-28 receptor α (IL-28RA) in patients with systemic lupus erythematosus (SLE) to evaluate the possibility that IL-28 is linked to the pathogenesis of SLE. MATERIALS AND METHODS: The serum IL-28 protein levels were determined by ELISA, and the IL-28 and IL-28RA transcript levels in peripheral blood mononuclear cells (PBMCs) and peripheral blood T cells were determined by RT-PCR. The levels in patients with SLE with the active disease activity were statistically compared with those in normal controls. RESULTS: IL-28 protein in sera and IL-28 transcripts in PBMCs and unactivated T cells were detectable only in some individuals, and IL-28 transcripts in T cells were induced by cell activation with anti-CD2, anti-CD3 and anti-CD28 antibodies. However, compared with normal controls, patients with SLE more frequently had detectable IL-28 protein in serum and had the higher IL-28 transcript levels in activated CD4(+) T cells, but not activated CD8(+) T cells. Two IL-28RA transcripts isoforms were detected in PBMCs and T cells, and their levels in patients with SLE were comparable with those in normal controls. CONCLUSIONS: The expression of IL-28, a T-cell autocrine factor, is dysregulated in patients with SLE, supporting the possibility that IL-28 may contribute to some of the SLE pathogenesis.