Sacral neuromodulation for Organophosphate-induced delayed neuropathy neurogenic lower urinary tract dysfunction: a case report.

BACKGROUND: Organophosphate-Induced Delayed Neuropathy (OPIDN) is a rare neurological disorder triggered by exposure to organophosphorus compounds. These compounds exert their neurotoxic effects by impacting the nervous system, leading to systemic manifestations. Urinary system symptoms are infrequently observed in clinical settings. Currently, effective therapeutic interventions for OPIDN-related urinary symptoms are lacking. Sacral nerve modulation therapy, an FDA-approved approach for managing lower urinary tract symptoms, presents as a promising option. Herein, we present a case of OPIDN-induced lower urinary tract obstruction successfully treated with sacral nerve modulation therapy, resulting in substantial symptom relief. CASE REPORT: A 27-year-old male patient presented with severe bilateral hydronephrosis, attributed to low bladder compliance and accompanied by a fever persisting for 6 days. The patient's medical history revealed accidental ingestion of organophosphate pesticide (Dimethoate) with no concomitant underlying diseases. In consideration of the potential for OPIDN, surgical intervention in the form of sacral neuromodulation (phase I) was undertaken. Subsequent evaluation one month post-surgery revealed notable improvements in both bladder compliance and bilateral hydronephrosis, necessitating sacral neuromodulation (phase II). Presently, following a 5-month follow-up period, the patient remains asymptomatic and in favorable health. CONCLUSION: This patient achieved long-term relief using sacral neuromodulation.

Integrative analysis of the immunological significances of guanylate binding protein family genes in microsatellite stability colorectal cancer.

Background: Microsatellite stability (MSS) colorectal cancer (CRC) has poor sensitivity to immunotherapy and its underlying mechanisms are still unclear. Guanylate binding proteins (GBPs) are a family of GTPase involving innate immune responses by providing defense against invading microbes and pathogens. However, the immunological significances of GBPs in MSS CRC remain unknown. Methods: We utilized bioinformatic tools to comprehensively analysis the expression pattern, clinical relevance, prognostic value, biological function, and immunoregulation effect of distinct GBP members in MSS CRC. Results: The expression of all seven GBPs in MSS samples are remarkably decreased compared to microsatellite instability-high (MSI-H) samples. Among them, GBP1/2/4/5 are obviously correlated with distant metastasis status. High expression of GBP1/4/5/6 was remarkably related to favorable overall survival (OS) and progression-free survival (PFS) in CRC patients with MSS tumor. Subsequent enrichment analysis revealed that Interferon-gamma (IFN-γ) and NOD-like receptor signaling are the most relevant functions. Besides, the expression patterns of GBPs are remarkably associated with several tumor infiltrated immune cells (e.g. regulatory T cells, CD4+ T cells, and macrophages) and diverse immunoregulatory molecules (e.g. immune checkpoint biomarkers (ICBs) and major histocompatibility complex (MHC) molecules). Moreover, high GBP1/2/4/5 expression predicted better immunotherapy responsiveness in immunotherapy cohorts. Conclusion: These findings might provide novel insights for the identification of therapeutic targets and potential prognostic biomarkers of GBP family in CRC with MSS samples.

ASReml-based estimation of early genetic parameters in hybrid mutton sheep populations.

The aim of this study was to analyze the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid mutton sheep using ASReml software, in order to provide theoretical basis for screening the optimal hybriding combinations and accelerating the breeding process of new breeds of specialized housed-feeding mutton sheep. We selected the wellgrown hybrid Southhu (Southdown × Hu sheep) and Dorhu (Dorset × Hu sheep) sheep as the research objects, constructed weight correction formulae for SH and DH sheep at 60 and 180 days; and used ASReml software to investigate the effects of non-genetic factors on the estimation of genetic parameters of early growth traits in hybrid sheep. The results showed that the birth month and birth type were found significant for all traits (p < 0.001); the heritability of maternal effects ranged from 0.0709 to 0.1859. It was found that both SH and DH sheep emerged the potential for rapid early growth and development, early growth traits are significantly affected by maternal genetic effects, thereby the maternal effect should be taken into consideration for the purpose of improving accuracy in parameter estimations and therefore increasing the success of breeding programs.

Identification of immunotherapy-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognostic signature in gastric carcinoma.

BACKGROUND: Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types, the present study aimed to explore the immunotherapy-related genes (IRGs) and develop a prognostic risk signature in gastric carcinoma (GC) based on these genes. METHODS: IRGs were identified by comparing immunotherapy responders and non-responders in GC. Then, GC patients were divided into distinct subtypes by unsupervised clustering method based on IRGs, and the differences in immune characteristics and prognostic stratification between these subtypes were analyzed. An immunotherapy-related risk score (IRRS) signature was developed and validated for risk classification and prognosis prediction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Besides, the predictive ability of the IRRS in immunotherapy response was also determined. RESULTS: A total of 63 IRGs were identified, and 371 GC patients were stratified into two molecular subgroups with significantly different prognosis and immune characteristics. Then, an IRRS signature comprised of three IRGs (CENP8, NRP1, and SERPINE1) was constructed to predict the prognosis of GC patients in TCGA cohort. Importantly, external validation in multiple GEO cohorts further confirmed the universal applicability of the IRRS in distinct populations. Furthermore, we found that the IRRS was significantly correlated with patient's responsiveness to immunotherapy, GC patients with low IRRS are more likely to benefit from existing immunotherapy. CONCLUSIONS: The risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for immunotherapy and may be helpful for clinical decision making in GC patients.

Development of a CD8+ T cell associated signature for predicting the prognosis and immunological characteristics of gastric cancer by integrating single-cell and bulk RNA-sequencing.

The universally poor clinical outcome makes gastric cancer (GC) still a significant public health threat, the main goal of our research is to develop a prognostic signature that can forecast the outcomes and immunological characteristics of GC via integrating single-cell and bulk RNA-sequencing. The CD8+ T cell feature genes were screened out by exploring single-cell RNA-sequencing (scRNA-seq) profiles retrieved from the TISCH2 database. Then, Cox and LASSO regressions were exploited for constructing a prognostic model in TCGA cohort based on these CD8+ T cell feature genes. Survival analysis was conducted to investigate the predictive capability of the signature for the clinical outcome of GC patients in TCGA and GEO cohorts. Additionally, we further examined the correlations between the risk signature and tumor immunotherapeutic response from the perspectives of immune infiltration, tumor mutation burden (TMB), immune checkpoint biomarker (ICB) expression, tumor microenvironment (TME), microsatellite instability (MSI), TIDE, and TCIA scores. In total, 703 CD8+ T cell feature genes were identified, eight of which were selected for constructing a prognostic signature. GC patients who possess high-risk score had significantly poorer survival outcomes than those who possess low-risk score in TCGA and GEO cohorts. Immune infiltration analysis proved that the risk score was negatively connected with the infiltration abundance of CD8+ T cells. Then, our findings demonstrated that GC patients in the high-risk subgroup possess a higher proportion of MSI-L/MSS, lower immune checkpoint biomarker expression, lower TMB, higher TIDE scores and lower TCIA scores compared to those in the low-risk subgroup. What's more, immunotherapy cohort analysis confirmed that patients who possess high-risk score are not sensitive to anti-cancer immunotherapy. Our study developed a reliable prognostic signature for GC that was significantly correlated with the immune landscape and immunotherapeutic responsiveness. The risk signature may guide clinicians to adopt more accurate and personalized treatment strategies for GC patients.

circAGTPBP1 promotes the progression of papillary thyroid cancer through the notch pathway via the miR-34a-5p/notch1 axis.

The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq. We conducted in vitro and in vivo experiments to investigate the biological functions of circAGTPBP1 in PTC progression. We found that circAGTPBP1 was upregulated in PTC tissues and cell lines, and its expression was positively correlated with tumor size, lymph node metastasis, and clinical stage. Using RNA-seq and bioinformatic analysis, we identified miR-34a-5p and NOTCH1 as downstream targets of circAGTPBP1. Functionally, circAGTPBP1 knockdown significantly inhibited the migration, invasion, and metastasis of PTC cell lines in vitro, while the miR-34a-5p inhibitor reversed these effects. Additionally, circAGTPBP1 knockdown inhibited tumor growth in vivo. Our findings suggest that circAGTPBP1 may act as a tumor promoter and could be a potential therapeutic target for PTC.

Identification of prognostic immune-related lncRNA signature predicting the overall survival for colorectal cancer.

Long non-coding RNA (lncRNA) is an important regulator of gene expression and serves a fundamental role in immune regulation. The present study aimed to develop a novel immune-related lncRNA signature to assess the prognosis of patients with colorectal cancer (CRC). Transcriptome data and clinical information of patients with CRC were downloaded from The Cancer Genome Atlas (TCGA) and UCSC Xena platforms. Immune-related mRNAs were extracted from the Molecular Signatures Database (MSigDB), and the immune-related lncRNAs were identified based on correlation analysis. Then, univariate, Lasso and multivariate Cox regression were applied to construct an immune-related lncRNA signature, and CRC patients were divided into high- and low-risk groups according to the median risk score. Finally, we evaluated the signature from the perspectives of clinical outcome, clinicopathological parameters, tumor-infiltrating immune cells (TIICs), immune status, tumor mutation burden (TMB) and immunotherapy responsiveness. In total, 272 immune-related lncRNAs were identified, five of which were applied to construct an immune-related lncRNA signature. The signature divided patients with CRC into low- and high-risk groups, the prognosis of patients in the high-risk group were significantly poorer than those in low-risk group, and the results were further confirmed in external validation cohort. Furthermore, the high-risk group showed aggressive clinicopathological characteristics, specific TIIC and immune function status, and low sensitivity to immunotherapy. The immune-related lncRNA signature could be exploited as a promising biomarker for predicting the prognosis and immune status of patients with CRC.

H19 may regulate the immune cell infiltration in carcinogenesis of gastric cancer through miR-378a-5p/SERPINH1 signaling.

BACKGROUND: Increasing studies have indicated that noncoding RNA (ncRNA)-mediated competing endogenous RNA (ceRNA) network serves as a significant role in cancer progression, but the underlying regulatory mechanisms of which in gastric cancer (GC) remain largely unclear. METHODS: Based on Gene Expression Omnibus and The Cancer Genome Atlas datasets, potential biomarkers for GC were screened and validated by machine learning. Then, upstream regulatory ncRNA of potential biomarkers was identified to construct a novel ceRNA network in GC through means of stepwise reverse prediction and validation. Ultimately, tumor immune cell infiltration analysis was performed based on the EPIC algorithm. RESULTS: A total of 188 differentially expressed genes (DEGs) were screened, and three candidate diagnostic biomarkers (FAP, PSAPL1, and SERPINH1) for GC were identified and validated. Subsequently, H19 and miR-378a-5p were identified as upstream regulatory ncRNAs that could potentially bind SERPINH1 in GC. Moreover, Immune infiltration analysis revealed that each component in the ceRNA network (H19/miR-378a-5p/SERPINH1) was significantly correlated with the infiltration abundances of diverse tumor-infiltrating immune cells. CONCLUSIONS: H19 may regulate the immune cell infiltration in carcinogenesis of GC through miR-378a-5p/SERPINH1 signaling.

Effects of 6-Week Betaine Supplementation on Muscular Performance in Male Collegiate Athletes.

The purpose of this study was to investigate the effects of 6-week betaine supplementation during a preparatory period of collegiate athletes on muscular power and strength. Sixteen male collegiate athletes received 5 g/day of betaine (betaine group, n = 9) or carboxymethyl cellulose (placebo group, n = 7) for 6 weeks. All participants engaged in their regular training during the experimental period. The overhead medicine-ball throw (OMBT), countermovement jump, and maximal strength (one repetition maximum, 1-RM) on the bench press, overhead press, half squat, and sumo dead lift by the participants were assessed before and after betaine supplementation. Blood lipids were also analyzed before and after betaine supplementation. After supplementation, there were no significant differences between betaine and placebo groups on any variables. Compared to presupplementation, the performance of OMBT and 1-RM of overhead press and half squat in the betaine group had significantly improved (p < 0.05). By contrast, no significant differences were observed in the placebo group before and after supplementation. Blood analysis revealed no negative effect on blood lipid profiles. Betaine seems to be a useful nutritional strategy to improve and maintain performance during 6-week preparatory periods in collegiate athletes.

Construction of a Novel Immune-Related mRNA Signature to Predict the Prognosis and Immune Characteristics of Human Colorectal Cancer.

Background: Anti-cancer immunotherapeutic approaches have gained significant efficacy in multiple cancer types. However, not all patients with colorectal cancer (CRC) could benefit from immunotherapy due to tumor heterogeneity. The purpose of this study was to construct an immune-related signature for predicting the immune characteristics and prognosis of CRC. Methods: RNA-sequencing data and corresponding clinical information of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and immune-related genes (IRGs) were downloaded from the Immunology Database and Analysis Portal (ImmPort). Then, we utilized univariate, lasso regression, and multivariate cox regression to identify prognostic IRGs and develop the immune-related signature. Subsequently, a nomogram was established based on the signature and other prognostic factors, and its predictive capacity was assessed by receiver operating characteristic (ROC) and decision curve analysis (DCA). Finally, associations between the signature and the immune characteristics of CRC were assessed. Results: In total, 472 samples downloaded from TCGA were divided into the training cohort (236 samples) and internal validation cohort (236 samples), and the GEO cohort was downloaded as an external validation cohort (122 samples). A total of 476 differently expressed IRGs were identified, 17 of which were significantly correlated to the prognosis of CRC patients. Finally, 10 IRGs were filtered out to construct the risk score signature, and patients were divided into low- and high-risk groups according to the median of risk scores in the training cohort. The high-risk score was significantly correlated with unfavorable survival outcomes and aggressive clinicopathological characteristics in CRC patients, and the results were further confirmed in the internal validation cohort, entire TCGA cohort, and external validation cohort. Immune infiltration analysis revealed that patients in the low-risk group infiltrated with high tumor-infiltrating immune cell (TIIC) abundances compared to the high-risk group. Moreover, we also found that the immune checkpoint biomarkers were significantly overexpressed in the low-risk group. Conclusion: The prognostic signature established by IRGs showed a promising clinical value for predicting the prognosis and immune characteristics of human CRC, which contribute to individualized treatment decisions.

Identification of novel survival-related lncRNA-miRNA-mRNA competing endogenous RNA network associated with immune infiltration in colorectal cancer.

Increasing studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of carcinogenesis. However, the underlying regulatory mechanisms of lncRNA-related competing endogenous RNA (ceRNA) network in colorectal cancer (CRC) are not fully understood. In the present study, we systematically analyzed the expression levels and prognostic values of dysregulated microRNAs (miRNAs) in human CRC to identify novel survival-related lncRNA-miRNA-mRNA ceRNA regulatory network. As a result, 28 dysregulated miRNAs were obtained, and hsa-miR-195-5p was identified as a key oncogene in human CRC based on analyses of expression levels and prognostic values. By means of stepwise prediction and validation, two upstream lncRNAs (NEAT1, XIST) and eight downstream mRNAs (ACOX1, CYP26B1, IRF4, ITPR1, LITAF, PHLPP2, RECK, and TPM2) were identified as key genes that interact with hsa-miR-195-5p. A ceRNA regulatory network consisted of these key genes was constructed, and Gene Set Enrichment Analysis (GSEA) indicated the possible association of key mRNAs with CRC onset and progression. Importantly, immune infiltration analysis revealed that the ceRNA network was remarkably associated with infiltration abundance of multiple immune cells and expression levels of immune checkpoints. These findings indicate that NEAT1 and XIST are potential prognostic factors that affect CRC onset and progression by targeting miR-195-5p.

Study on the Effect of Antiplatelet and Gastric Mucosal Protection of Traditional Chinese Medicine Invigorating Qi and Hemostasis.

BACKGROUND: To investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model. METHODS: A pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested. RESULTS: The area under the curve (AUC; 0-T, 300.342 ± 35.832 mg/L* h; AUC 0-∞, 320.462 ± 40.213 mg/L* h), the plasma peak concentration (30.622 ± 9.917 mg/L*), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05). CONCLUSION: TCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.

The membrane mucin Msb2 regulates aflatoxin biosynthesis and pathogenicity in fungus Aspergillus flavus.

As a pathogenic fungus, Aspergillus flavus can produce carcinogenic aflatoxins (AFs), which poses a great threat to crops and animals. Msb2, the signalling mucin protein, is a part of mitogen-activated protein kinase (MAPK) pathway which contributes to a range of physiological processes. In this study, the roles of membrane mucin Msb2 were explored in A. flavus by the application of gene disruption. The deletion of msb2 gene (Δmsb2) caused defects in vegetative growth, sporulation and sclerotia formation when compared to WT and complement strain (Δmsb2C ) in A. flavus. Using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis, it was found that deletion of msb2 down-regulated aflatoxin B1 (AFB1 ) synthesis and decreased the infection capacity of A. flavus. Consistently, Msb2 responds to cell wall stress and osmotic stress by positively regulating the phosphorylation of MAP kinase. Notably, Δmsb2 mutant exhibited cell wall defect, and it was more sensitive to inhibitor caspofungin when compared to WT and Δmsb2C . Taking together, these results revealed that Msb2 plays key roles in morphological development process, stresses adaptation, secondary metabolism and pathogenicity in fungus A. flavus.

Rapid Fabrication of Protein Microarrays via Autogeneration and on-Chip Purification of Biotinylated Probes.

A streamlined approach toward the rapid fabrication of streptavidin-biotin-based protein microarrays was investigated. First, using our engineered versatile plasmid (pBADcM-tBirA) and an optimal coexpression strategy for biotin ligase and biotin acceptor peptide (BAP) chimeric recombinant protein, an autogeneration system for biotinylated probes was developed. This system permitted an advantageous biotinylation of BAP chimeric recombinant proteins, providing a strategy for the high-throughput synthesis of biotinylated probes. Then, to bypass the conventional rate-limiting steps, we employed an on-chip purification process to immobilize the biotinylated probes with high-throughput recombinant lysates. The integration of the autogeneration of probes and on-chip purification not only contributed to the effective and reliable fabrication of the protein microarray, but also enabled simplification of the process and an automated throughput format. This labor- and cost-effective approach may facilitate the use of protein microarrays for diagnosis, pharmacology, proteomics, and other laboratory initiatives.

H19 promotes the gastric carcinogenesis by sponging miR-29a-3p: evidence from lncRNA-miRNA-mRNA network analysis.

Aim: To identify novel competing endogenous RNA (ceRNA) network correlated with the prognosis of gastric cancer (GC) patients. Materials & methods: We systematically analyzed the aberrantly expressed genes in human GC to construct a ceRNA network by using multiple bioinformatic tools. Results: Aberrantly expressed mRNAs in GC were identified. By means of stepwise reverse prediction and validation from mRNA to lncRNA, a ceRNA network comprised of H19, miR-29a-3p, COL3A1, COL5A2, COL1A2 and COL4A1 was constructed, and all genes in the network are significantly correlated with the prognosis of GC patients. Conclusion: The present study successfully constructed a GC related ceRNA network, and provided potential targets for GC clinical treatment.

CDK1 and CDC20 overexpression in patients with colorectal cancer are associated with poor prognosis: evidence from integrated bioinformatics analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system, which causes severe financial burden worldwide. However, the specific mechanisms involved in CRC are still unclear. METHODS: To identify the significant genes and pathways involved in the initiation and progression of CRC, the microarray dataset GSE126092 was downloaded from Gene Expression Omnibus (GEO) database, and then, the data was analyzed to identify differentially expressed genes (DEGs). Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on these DEGs using the DAVID database, and the protein-protein interaction (PPI) network was constructed using the STRING database and analyzed using the Cytoscape software. Finally, hub genes were screened, and the survival analysis was performed on these hub genes using the Kaplan-Meier curves in the cBioPortal database. RESULTS: In total, 937 DEGs were obtained, including 316 upregulated genes and 621 downregulated genes. GO analysis revealed that the DEGs were mostly enriched in terms of nuclear division, organelle fission, cell division, and cell cycle process. KEGG pathway analysis showed that the DEGs were mostly enriched in cell cycle, oocyte meiosis, cytokine-cytokine receptor interaction, and cGMP-PKG signaling pathway. The PPI network comprised 608 nodes and 3100 edges, and 4 significant modules and 10 hub genes with the highest degree were identified using the Cytoscape software. Finally, survival analysis showed that overexpression of CDK1 and CDC20 in patients with CRC were statistically associated with worse overall survival. CONCLUSIONS: This bioinformatics analysis revealed that CDK1 and CDC20 might be candidate targets for diagnosis and treatment of CRC, which provided valuable clues for CRC.

AflSte20 Regulates Morphogenesis, Stress Response, and Aflatoxin Biosynthesis of Aspergillus flavus.

Various signaling pathways in filamentous fungi help cells receive and respond to environmental information. Previous studies have shown that the mitogen-activated protein kinase (MAPK) pathway is phosphorylation-dependent and activated by different kinase proteins. Serine/threonine kinase plays a very important role in the MAPK pathway. In this study, we selected the serine/threonine kinase AflSte20 in Aspergillus flavus for functional study. By constructing Aflste20 knockout mutants and complemented strains, it was proven that the Aflste20 knockout mutant (ΔAflste20) showed a significant decrease in growth, sporogenesis, sclerotinogenesis, virulence, and infection compared to the WT (wild type) and complemented strain (ΔAflste20C). Further research indicated that ΔAflste20 has more sensitivity characteristics than WT and ΔAflste20C under various stimuli such as osmotic stress and other types of environmental stresses. Above all, our study showed that the mitogen-activated kinase AflSte20 plays an important role in the growth, conidia production, stress response and sclerotia formation, as well as aflatoxin biosynthesis, in A. flavus.

Lysine acetylation contributes to development, aflatoxin biosynthesis and pathogenicity in Aspergillus flavus.

Aspergillus flavus is a pathogenic fungus that produces carcinogenic aflatoxins, posing a great threat to crops, animals and humans. Lysine acetylation is one of the most important reversible post-translational modifications and plays a vital regulatory role in various cellular processes. However, current information on the extent and function of lysine acetylation and aflatoxin biosynthesis in A. flavus is limited. Here, a global acetylome analysis of A. flavus was performed by peptide pre-fractionation, pan-acetylation antibody enrichment and liquid chromatography-mass spectrometry. A total of 1313 high-confidence acetylation sites in 727 acetylated proteins were identified in A. flavus. These acetylation proteins are widely involved in glycolysis/gluconeogenesis, pentose phosphate pathway, citric acid cycle and aflatoxin biosynthesis. AflO (O-methyltransferase), a key enzyme in aflatoxin biosynthesis, was found to be acetylated at K241 and K384. Deletion of aflO not only impaired conidial and sclerotial developments, but also dramatically suppressed aflatoxin production and pathogenicity of A. flavus. Further site-specific mutations showed that lysine acetylation of AflO could also result in defects in development, aflatoxin production and pathogenicity, suggesting that acetylation plays a vital role in the regulation of the enzymatic activity of AflO in A. flavus. Our findings provide evidence for the involvement of lysine acetylation in various biological processes in A. flavus and facilitating in the elucidation of metabolic networks.

Receiver operating characteristics of impulse oscillometry parameters for predicting obstructive sleep apnea in preobese and obese snorers.

BACKGROUND: Inability to maintain upper-airway patency during sleep is a cause of obstructive sleep apnea (OSA) and its sequelae. The associated syndrome (OSAS) is common in obese populations, currently, nocturnal polysomnography is the gold standard for diagnosing this conditions, but the diagnostic procedures are expensive and time-consuming. Therefore, identification of new markers of OSAS would be useful. This study aims to examine the receiver operating characteristics of impulse oscillometry (IOS) parameters for the prediction of OSAS in preobese and obese snoring patients. METHODS: In total, 230 patients with normal spirometric values were included in this cross-sectional study. Full laboratory polysomnography was performed and IOS measurements were determined in sitting and supine positions to obtain respiratory impedance (Zrs), resistance (Rrs), and reactance (Xrs) parameters. The respiratory resistance at zero-frequency (Rrs0) was extrapolated by linear regression analysis of Rrs versus low-oscillatory-frequencies and its inverse, respiratory conductance (Grs), was calculated. RESULTS: In both the sitting and supine positions Rrs0, Zrs, and Rrs at five oscillatory-frequencies (Hz) and Grs, the reciprocal of Zrs5 (Gz), and Xrs at 5 Hz all had significant positive or negative correlations with OSAS severity as defined by the Respiratory disturbance index (RDI). The correlation coefficients between Rrs0, Zrs5, Rrs5, Grs, Gz, Xrs5 measured in the supine and RDI were 0.425, 0.395, 0.378, -0.425, -0.395, and -0.517, respectively (all p < 0.001). The receiver operating characteristics curves showed that Xrs at 5 Hz (reactance) in the supine position was the best for predicting OSAS with a sensitivity of 73 % and specificity of 84 % at the optimal cut-off point of -0.23 (kPa s L(-1)). The other parameters also showed acceptable discriminating power. A logistic-regression model based on respiratory function abnormalities revealed that reactance combined with patient sex and lung volume yielded a specificity of 83.3 % with a sensitivity of 76.8 % for indicating OSAS. CONCLUSION: Respiratory resistance and reactance measured by IOS are abnormal in preobese and obese OSAS patients, and these parameters are moderate to closely correlated with OSAS severity. IOS might be a useful screening tool for detecting OSAS in clinic based populations.

Impact of obstructive sleep apnea on lung volumes and mechanical properties of the respiratory system in overweight and obese individuals.

BACKGROUND: Even through narrowing of the upper-airway plays an important role in the generation of obstructive sleep apnea (OSA), the peripheral airways is implicated in pre-obese and obese OSA patients, as a result of decreased lung volume and increased lung elastic recoil pressure, which, in turn, may aggravate upper-airway collapsibility. METHODS: A total of 263 male (n = 193) and female (n = 70) subjects who were obese to various degrees without a history of lung diseases and an expiratory flow limitation, but troubled with snoring or suspicion of OSA were included in this cross-sectional study. According to nocturnal-polysomnography the subjects were distributed into OSA and non-OSA groups, and were further sub-grouped by gender because of differences between males and females, in term of, lung volume size, airway resistance, and the prevalence of OSA among genders. Lung volume and respiratory mechanical properties at different-frequencies were evaluated by plethysmograph and an impulse oscillation system, respectively. RESULTS: Functional residual capacity (FRC) and expiratory reserve volume were significantly decreased in the OSA group compared to the non-OSA group among males and females. As weight and BMI in males in the OSA group were greater than in the non-OSA group (90 ± 14.8 kg vs. 82 ± 10.4 kg, p < 0.001; 30.5 ± 4.2 kg/m(2) vs. 28.0 ± 3.0 kg/m(2), p < 0.001), multiple regression analysis was required to adjust for BMI or weight and demonstrated that these lung volumes decreases were independent from BMI and associated with the severity of OSA. This result was further confirmed by the female cohort. Significant increases in total respiratory resistance and decreases in respiratory conductance (Grs) were observed with increasing severity of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The specific Grs (sGrs) stayed relatively constant between the two groups in woman, and there was only a weak association between AHI and sGrs among man. Multiple-stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI in males and females or hypopnea index in females, independently-highly correlated with peripheral-airway resistance and significantly associated with decreasing FRC. CONCLUSIONS: Total respiratory resistance and peripheral airway resistance significantly increase, and its inverse Grs decrease, in obese patients with OSA in comparison with those without OSA, and are independently associated with OSA severity. These results might be attributed to the abnormally increased lung elasticity recoil pressure on exhalation, due to increase in lung elasticity and decreased lung volume in obese OSA.