S100A9 plays a key role in Clostridium perfringens beta2 toxin-induced inflammatory damage in porcine IPEC-J2 intestinal epithelial cells.

BACKGROUND: As an important regulator of autoimmune responses and inflammation, S100A9 may serve as a therapeutic target in inflammatory diseases. However, the role of S100A9 in Clostridium perfringens type C infectious diarrhea is poorly studied. The aim of our study was to screen downstream target genes regulated by S100A9 in Clostridium perfringens beta2 (CPB2) toxin-induced IPEC-J2 cell injury. We constructed IPEC-J2 cells with S100A9 knockdown and a CPB2-induced cell injury model, screened downstream genes regulated by S100A9 using RNA-Seq technique, and performed functional enrichment analysis. The function of S100A9 was verified using molecular biology techniques. RESULTS: We identified 316 differentially expressed genes (DEGs), of which 221 were upregulated and 95 were downregulated. Functional enrichment analysis revealed that the DEGs were significantly enriched in cilium movement, negative regulation of cell differentiation, immune response, protein digestion and absorption, and complement and coagulation cascades. The key genes of immune response were TNF, CCL1, CCR7, CSF2, and CXCL9. When CPB2 toxin-induced IPEC-J2 cells overexpressed S100A9, Bax expression increased, Bcl-2 expression and mitochondrial membrane potential decreased, and SOD activity was inhibited. CONCLUSION: In conclusion, S100A9 was involved in CPB2-induced inflammatory response in IPEC-J2 cells by regulating the expression of downstream target genes, namely, TNF, CCL1, CCR7, CSF2, and CXCL9; promoting apoptosis; and aggravating oxidative cell damage. This study laid the foundation for further study on the regulatory mechanism underlying piglet diarrhea.

Harmoni: A method for eliminating spurious interactions due to the harmonic components in neuronal data.

Cross-frequency synchronization (CFS) has been proposed as a mechanism for integrating spatially and spectrally distributed information in the brain. However, investigating CFS in Magneto- and Electroencephalography (MEG/EEG) is hampered by the presence of spurious neuronal interactions due to the non-sinusoidal waveshape of brain oscillations. Such waveshape gives rise to the presence of oscillatory harmonics mimicking genuine neuronal oscillations. Until recently, however, there has been no methodology for removing these harmonics from neuronal data. In order to address this long-standing challenge, we introduce a novel method (called HARMOnic miNImization - Harmoni) that removes the signal components which can be harmonics of a non-sinusoidal signal. Harmoni's working principle is based on the presence of CFS between harmonic components and the fundamental component of a non-sinusoidal signal. We extensively tested Harmoni in realistic EEG simulations. The simulated couplings between the source signals represented genuine and spurious CFS and within-frequency phase synchronization. Using diverse evaluation criteria, including ROC analyses, we showed that the within- and cross-frequency spurious interactions are suppressed significantly, while the genuine activities are not affected. Additionally, we applied Harmoni to real resting-state EEG data revealing intricate remote connectivity patterns which are usually masked by the spurious connections. Given the ubiquity of non-sinusoidal neuronal oscillations in electrophysiological recordings, Harmoni is expected to facilitate novel insights into genuine neuronal interactions in various research fields, and can also serve as a steppingstone towards the development of further signal processing methods aiming at refining within- and cross-frequency synchronization in electrophysiological recordings.

METTL3 Regulates the Inflammatory Response in CPB2 Toxin-Exposed IPEC-J2 Cells through the TLR2/NF-κB Signaling Pathway.

Clostridium perfringens beta2 (CPB2) toxin is one of the main pathogenic toxins produced by Clostridium perfringens, which causes intestinal diseases in animals and humans. The N6-methyladenosine (m6A) modification is the most common reversible modification in eukaryotic disease processes. Methyltransferase-like 3 (METTL3) regulates immunity and inflammatory responses induced by the bacterial infections in animals. However, METTL3's involvement in CPB2-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) remains unclear. In the current study, we used methylated RNA immunoprecipitation-quantitative polymerase chain reaction, Western blotting and immunofluorescence assay to determine the role of METTL3 in CPB2-exposed IPEC-J2 cells. The findings revealed that m6A and METTL3 levels were increased in CPB2 treated IPEC-J2 cells. Functionally, METTL3 overexpression promoted the release of inflammatory factors, increased cytotoxicity, decreased cell viability and disrupted tight junctions between cells, while the knockdown of METTL3 reversed these results. Furthermore, METTL3 was involved in the inflammatory response of IPEC-J2 cells by activating the TLR2/NF-κB signaling pathway through regulating TLR2 m6A levels. In conclusion, METTL3 overexpression triggered the TLR2/NF-κB signaling pathway and promoted CPB2-induced inflammatory responses in IPEC-J2 cells. These findings may provide a new strategy for the prevention and treatment of diarrhea caused by Clostridium perfringens.

Echinacoside reverses myocardial remodeling and improves heart function via regulating SIRT1/FOXO3a/MnSOD axis in HF rats induced by isoproterenol.

Myocardial remodelling is important pathological basis of HF, mitochondrial oxidative stress is a promoter to myocardial hypertrophy, fibrosis and apoptosis. ECH is the major active component of a traditional Chinese medicine Cistanches Herba, plenty of studies indicate it possesses a strong antioxidant capacity in nerve cells and tumour, it inhibits mitochondrial oxidative stress, protects mitochondrial function, but the specific mechanism is unclear. SIRT1/FOXO3a/MnSOD is an important antioxidant axis, study finds that ECH binds covalently to SIRT1 as a ligand and up-regulates the expression of SIRT1 in brain cells. We hypothesizes that ECH may reverse myocardial remodelling and improve heart function of HF via regulating SIRT1/FOXO3a/MnSOD signalling axis and inhibit mitochondrial oxidative stress in cardiomyocytes. Here, we firstly induce cellular model of oxidative stress by ISO with AC-16 cells and pre-treat with ECH, the level of mitochondrial ROS, mtDNA oxidative injury, MMP, carbonylated protein, lipid peroxidation, intracellular ROS and apoptosis are detected, confirm the effect of ECH in mitochondrial oxidative stress and function in vitro. Then, we establish a HF rat model induced by ISO and pre-treat with ECH. Indexes of heart function, myocardial remodelling, mitochondrial oxidative stress and function, expression of SIRT1/FOXO3a/MnSOD signalling axis are measured, the data indicate that ECH improves heart function, inhibits myocardial hypertrophy, fibrosis and apoptosis, increases the expression of SIRT1/FOXO3a/MnSOD signalling axis, reduces the mitochondrial oxidative damages, protects mitochondrial function. We conclude that ECH reverses myocardial remodelling and improves cardiac function via up-regulating SIRT1/FOXO3a/MnSOD axis and inhibiting mitochondrial oxidative stress in HF rats.

Neuronal biomarkers of Parkinson's disease are present in healthy aging.

The prevalence of Parkinson's disease (PD) increases with aging and both processes share similar cellular mechanisms and alterations in the dopaminergic system. Yet it remains to be investigated whether aging can also demonstrate electrophysiological neuronal signatures typically associated with PD. Previous work has shown that phase-amplitude coupling (PAC) between the phase of beta oscillations and the amplitude of gamma oscillations as well as beta bursts features can serve as electrophysiological biomarkers for PD. Here we hypothesize that these metrics are also present in apparently healthy elderly subjects. Using resting state multichannel EEG measurements, we show that PAC between beta oscillation and broadband gamma activity (50-150 Hz) is elevated in a group of elderly (59-77 years) compared to young volunteers (20-35 years) without PD. Importantly, the increase of PAC is statistically significant even after ruling out confounds relating to changes in spectral power and non-sinusoidal shape of beta oscillation. Moreover, a trend for a higher percentage of longer beta bursts (> 0.2 s) along with the increase in their incidence rate is also observed for elderly subjects. Using inverse modeling, we further show that elevated PAC and longer beta bursts are most pronounced in the sensorimotor areas. Moreover, we show that PAC and longer beta bursts might reflect distinct mechanisms, since their spatial patterns only partially overlap and the correlation between them is weak. Taken together, our findings provide novel evidence that electrophysiological biomarkers of PD may already occur in apparently healthy elderly subjects. We hypothesize that PAC and beta bursts characteristics in aging might reflect a pre-clinical state of PD and suggest their predictive value to be tested in prospective longitudinal studies.

Effects of miR-204 on apoptosis and inflammatory response of Clostridium perfringens beta2 toxin induced IPEC-J2 cells via targeting BCL2L2.

Clostridium perfringens beta2 (CPB2) toxin can cause intestinal damage and inflammatory responses in a variety of animals, which seriously endanger the healthy development of animal husbandry. Increasing evidence has demonstrated that microRNAs (miRNAs) can play an important regulatory role in the process of pathogenic infection. In our previous study, we found that miR-204 was highly expressed in the ileum tissues of the susceptible group diarrhea piglets after infection with Clostridium perfringens (C. perfringens) type C. In this study, we found that miR-204 was also up-regulated in different time points after CPB2 toxin treatment. Overexpression of miR-204 promoted apoptosis and inflammatory response of intestinal porcine epithelial cells (IPEC-J2), whereas the opposite results were displayed after transfected with miR-204 inhibitor. Furthermore, the luciferase reporter assays confirmed that BCL2L2 was a direct target gene of miR-204. Interestingly, we found that overexpression BCL2L2 attenuated the apoptosis and inflammatory response of CPB2 toxin induced IPEC-J2 cells. In conclusion, these results find that miR-204 promotes the apoptosis and intensify inflammatory response of CPB2 toxin induced IPEC-J2 cells via targeting BCL2L2. These data provide a valuable reference for the piglets resistance diarrhea at the molecular level.

[Study on Proficiency Testing of Determination Potassium in Serum].

OBJECTIVE: To evaluate the capacity of laboratories participated in the proficiency testing (PT) of determination potassium in serum and improve the quality of testing, and put forward technical suggestions for unsatisfied laboratories. METHODS: According to the requirements of CNAS related documents, the homogeneity and stability of the real PT sample were evaluated by one-way ANOVA and t test, respectively. The values of real PT samples were assigned by reference method which was used in PT results assay. It is required that the deviation of value of real PT samples (code:2, 3, 5) between the measured value and the assigned value shall be within ±15.0%. The precision of values for all samples should not be greater than 3.0%. RESULTS: All the laboratories submitted valid data according to the requirements. Only one laboratory did not meet the requirements, and the satisfaction rate was 90.9%. CONCLUSIONS: The ability of most of laboratories are accurate and reliable.

Apolipoprotein E ε4 Allele is Associated With Plasma Amyloid Beta and Amyloid Beta Transporter Levels: A Cross-sectional Study in a Rural Area of Xi'an, China.

OBJECTIVE: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aß) and Aß transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for Aß, which can prevent plasma Aß from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aß, sLRP1, sRAGE levels. DESIGN: Cross-sectional study. SETTING: The committee office of the village. PARTICIPANTS: Residents lived in the village for more than 3 years, aged 40-85 years (n = 1,119, 63.5% women). MEASUREMENTS: Plasma biomarkers include ApoE genotype, Aß, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. RESULTS: After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of Aß42 was higher and log-transformed sLRP1 was lower in ApoE ε4 carriers than that in noncarriers (ßAß42 = 1.214, 95% confidence interval: 0.105-2.316, pAß42 = 0.031; ßsLRP1 = -0.075, 95% confidence interval: -0.129 to -0.021, psLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aß40 was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (rsLRP1 = 0.116, psLRP1 <0.001; rsRAGE = 0.078, psLRP1 = 0.009, respectively). Plasma Aß42 was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). CONCLUSION: ApoE ε4 carriers had higher plasma Aß42 levels and lower sLRP1 levels. These data indicated that the ApoE ε4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aß42 and sLRP1 levels, but it needs to be further elucidated.

Alteramide B is a microtubule antagonist of inhibiting Candida albicans.

BACKGROUND: Alteramide B (ATB), isolated from Lysobacter enzymogenes C3, was a new polycyclic tetramate macrolactam (PTM). ATB exhibited potent inhibitory activity against several yeasts, particularly Candida albicans SC5314, but its antifungal mechanism is unknown. METHODS: The structure of ATB was established by extensive spectroscopic analyses, including high-resolution mass spectrometry, 1D- and 2D-NMR, and CD spectra. Flow cytometry, fluorescence microscope, transmission electron microscope, molecular modeling, overexpression and site-directed mutation studies were employed to delineate the anti-Candida molecular mechanism of ATB. RESULTS: ATB induced apoptosis in C. albicans through inducing reactive oxygen species (ROS) production by disrupting microtubules. Molecular dynamics studies revealed the binding patterns of ATB to the ß-tubulin subunit. Overexpression of the wild type and site-directed mutants of the ß-tubulin gene (TUBB) changed the sensitivity of C. albicans to ATB, confirming the binding of ATB to ß-tubulin, and indicating that the binding sites are L215, L217, L273, L274 and R282. In vivo, ATB significantly improved the survival of the candidiasis mice and reduced fungal burden. CONCLUSION: The molecular mechanism underlying the ATB-induced apoptosis in C. albicans is through inhibiting tubulin polymerization that leads to cell cycle arrest at the G2/M phase. The identification of ATB and the study of its activity provide novel mechanistic insights into the mode of action of PTMs against the human pathogen. GENERAL SIGNIFICANCE: This study shows that ATB is a new microtubule inhibitor and a promising anti-Candida lead compound. The results also support ß-tubulin as a potential target for anti-Candida drug discovery.

In vitro reconstitution of a PKS pathway for the biosynthesis of galbonolides in Streptomyces sp. LZ35.

The galbonolides are 14-membered macrolide antibiotics with a macrocyclic backbone similar to that of erythromycins. Galbonolides exhibit broad-spectrum antifungal activities. Retro-biosynthetic analysis suggests that the backbone of galbonolides is assembled by a type I modular polyketide synthase (PKS). Unexpectedly, the galbonolide biosynthetic gene cluster, gbn, in Streptomyces sp. LZ35 encodes a hybrid fatty acid synthase (FAS)-PKS pathway. In vitro reconstitution revealed the functions of GbnA (an AT-ACP didomain protein), GbnC (a FabH-like enzyme), and GbnB (a novel multidomain PKS module without AT and ACP domains) responsible for assembling the backbone of galbonolides, respectively. To our knowledge, this study is the first biochemical characterization of a hybrid FAS-PKS pathway for the biosynthesis of 14-membered macrolides. The identification of this pathway provides insights into the evolution of PKSs and could facilitate the design of modular pools for synthetic biology.

Heterologous expression of galbonolide biosynthetic genes in Streptomyces coelicolor.

The galbonolide antibiotics are non-glycosylated heptaketide 14-membered macrolides. These antibiotics exhibit broad-spectrum fungicidal activities, including against the human pathogen Cryptococcus neoformans. Previously, galbonolides B and E were isolated from the marine actinomycete Streptomyces sp. LZ35. By bioinformatics analysis, the putative galbonolide biosynthetic gene cluster, gbn, was identified in the genome of strain LZ35. In order to verify that the core genes (gbnA-E) are sufficient for synthesizing the basic structure of galbonolide as previously proposed, we performed the heterologous expression of gbnA-E in a "clean background" host Streptomyces coelicolor ZM12, in which all the native polyketide synthase genes have been deleted. As expected, the production of galbonolide B (1) was detected in the transformant. To the best of our knowledge, this is the first report that demonstrates the essential role of gbnA-E in the biosynthesis of galbonolides by heterologous expression. This heterologous expression system would be helpful to generate novel galbonolide derivatives by co-overexpression of unusual biosynthesis extender units.

Pharmacokinetic, Pharmacodynamic, and Safety Profiles of Proline Henagliflozin in Chinese Subjects with Varying Degrees of Liver Dysfunction.

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel-group, open-label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty-two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long-term safety profile and efficacy have not been specifically studied in this population.

Luteoloside inhibits Aß1-42 fibrillogenesis, disintegrates preformed fibrils, and alleviates amyloid-induced cytotoxicity.

Abnormal aggregation and fibrillogenesis of amyloid-ß protein (Aß) can cause Alzheimer's disease (AD). Thus, the discovery of effective drugs that inhibit Aß fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating Aß aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on Aß1-42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-ß-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of Aß1-42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of Aß1-42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with Aß1-42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of Aß, and promote further exploration of the therapeutic strategy against AD.

Ethanol extract of Verbena officinalis alleviates MCAO-induced ischaemic stroke by inhibiting IL17A pathway-regulated neuroinflammation.

BACKGROUND: The prevention and treatment of ischaemic stroke is a worldwide challenge, and effective clinical treatment strategies are lacking. Studies have demonstrated the efficacy of Verbena officinalis in managing cerebrovascular disorders. However, the neuroprotective bioactive components and mechanisms remain unclear. PURPOSE: To investigate the pharmacological combinatorial components and mechanism underlying the anti-ischemic stroke effect of the ethanol extract of Verbena officinalis (VO Ex). STUDY DESIGN AND METHODS: The components of VO Ex were identified by HPLC. A middle cerebral artery occlusion (MCAO) induced brain injury model was used to assess the therapeutic effect of VO Ex. The activity of the chemical components of VO Ex was evaluated using a primary astrocyte injury model induced by oxygen-glucose deprivation/reperfusion (OGD/R). RNA sequencing was used to reveal the potential targets of VO Ex against cerebral ischemia-reperfusion injury (CIRI), and the results were verified by qRT-PCR and western blotting. The key components and target binding ability were predicted by molecular docking. Finally, the mechanism of combinatorial components was verified by experiments. RESULTS: The HPLC results indicated that the main ingredients of VO Ex were hastatoside, verbenalin, acteoside, luteolin, apigenin and hispidulin. In vivo experiments showed that VO Ex improved MCAO-induced acute cerebral ischemic injury. Transcriptomic data and biological experiments suggested that VO Ex exerted therapeutic effects through IL17A signalling pathways. The in vitro experiments indicated that verbenalin, acteoside, luteolin, apigenin and hispidulin exhibited neuroprotective activities. The novel formula of VALAH, derived from the aforementioned active ingredients, exhibited superior efficacy compared to each individual component. Molecular docking and mechanistic studies have confirmed that VALAH functions in the treatment of ischaemic stroke by suppressing the activation of the IL17A signalling pathway. CONCLUSION: This work is the first to reveal that VO Ex effectively inhibits the IL17A signaling pathway and mitigates neuroinflammation following ischemic stroke. Moreover, we identified the novel formula VALAH as the bioactive combinatorial components for VO Ex. Further research suggests that the activity of VALAH is associated with IL17A-mediated regulation of neuroinflammation. This finding provides new insights into the efficacious components and mechanisms of traditional Chinese medicine.

[The performance of the microbial barrier of needleless positive pressure closed connectors].

OBJECTIVE: Analyzing the performance of microbial barrier of needleless positive pressure closed connectors. METHODS: Three kinds of brand needleless positive pressure closed connectors were chosen to do the access of microorganisms test. RESULTS: Positive results were detected in the three experimental groups. CONCLUSIONS: So far, lots of the connectors are not qualified strictly on the market, some improvement is required in the structure design and process.

Decreased S100A9 expression alleviates Clostridium perfringens beta2 toxin-induced inflammatory injury in IPEC-J2 cells.

Background: S100 calcium-binding protein A9 (S100A9) is a commonly known pro-inflammatory factor involved in various inflammatory responses. Clostridium perfringens (C. perfringens ) type C is known to cause diarrhea in piglets. However, the role of S100A9 in C. perfringens type C-induced infectious diarrhea is unclear. Methods: Here, the S100A9 gene was overexpressed and knocked down in the IPEC-J2 cells, which were treated with C. perfringens beta2 (CPB2) toxin. The role of S100A9 in CPB2 toxin-induced injury in IPEC-J2 cells was assessed by measuring the levels of inflammatory cytokines, reactive oxygen species (ROS), lactate dehydrogenase (LDH), cell proliferation, and tight junction-related proteins. Results: The results showed elevated expression of S100A9 in diarrhea-affected piglet tissues, and the elevation of S100A9 expression after CPB2 toxin treatment of IPEC-J2 was time-dependent. In CPB2 toxin-induced IPEC-J2 cells, overexpression of S100A9 had the following effects: the relative expression of inflammatory factors IL-6, IL8, TNF-α, and IL-1ß was increased; the ROS levels and LDH viability were significantly increased; cell viability and proliferation were inhibited; the G0/G1 phase cell ratio was significantly increased. Furthermore, overexpression of S100A9 reduced the expression of tight junction proteins in CPB2-induced IPEC-J2 cells. The knockdown of S100A9 had an inverse effect. In conclusion, our results confirmed that S100A9 exacerbated inflammatory injury in CPB2 toxin-induced IPEC-J2 cells, inhibited cell viability and cell proliferation, and disrupted the tight junctions between cells. Thus, decreased S100A9 expression alleviates CPB2 toxin-induced inflammatory injury in IPEC-J2 cells.

Development and validation of a three-dimensional deep learning-based system for assessing bowel preparation on colonoscopy video.

Background: The performance of existing image-based training models in evaluating bowel preparation on colonoscopy videos was relatively low, and only a few models used external data to prove their generalization. Therefore, this study attempted to develop a more precise and stable AI system for assessing bowel preparation of colonoscopy video. Methods: We proposed a system named ViENDO to assess the bowel preparation quality, including two CNNs. First, Information-Net was used to identify and filter out colonoscopy video frames unsuitable for Boston bowel preparation scale (BBPS) scoring. Second, BBPS-Net was trained and tested with 5,566 suitable short video clips through three-dimensional (3D) convolutional neural network (CNN) technology to detect BBPS-based insufficient bowel preparation. Then, ViENDO was applied to complete withdrawal colonoscopy videos from multiple centers to predict BBPS segment scores in clinical settings. We also conducted a human-machine contest to compare its performance with endoscopists. Results: In video clips, BBPS-Net for determining inadequate bowel preparation generated an area under the curve of up to 0.98 and accuracy of 95.2%. When applied to full-length withdrawal colonoscopy videos, ViENDO assessed bowel cleanliness with an accuracy of 93.8% in the internal test set and 91.7% in the external dataset. The human-machine contest demonstrated that the accuracy of ViENDO was slightly superior compared to most endoscopists, though no statistical significance was found. Conclusion: The 3D-CNN-based AI model showed good performance in evaluating full-length bowel preparation on colonoscopy video. It has the potential as a substitute for endoscopists to provide BBPS-based assessments during daily clinical practice.

[Evaluation of pulmonary arterial hypertension in chronic obstructive pulmonary disease by multislice spiral CT].

OBJECTIVE: To investigate the use of multislice spiral CT (MSCT) in the diagnosis of pulmonary arterial hypertension (PAH) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The diameters and areas of the pulmonary artery were measured in 81 cases with COPD and 100 normal adults from January to November 2011. The ratios of the diameters of the main pulmonary artery (MPA) to ascending aorta (AA), descending aorta (DA), trachea, thoracic vertebra (ThV) were also calculated. Data analysis used the t test of the 2 samples compared, multi-rate compared by χ(2) test. RESULTS: There were significant differences in the measured parameters between the COPD group and the control group. The differences were also significant among groups of COPD patients aged < 40 y, 40 - 60 y, > 60 y, and the control group, among patients with different stages of COPD (stage I, II, III, IV) and the control group, and among patients with sPAP > 50 mm Hg (1 mm Hg = 0.133 kPa), sPAP ≤ 50 mm Hg and the control group. There were positive correlations between sPAP and the measured indexes such as MPA [(3.14 ± 0.63) cm] of pulmonary artery in COPD. There were negative correlations between FEV(1)% and some of the measured indexes such as MPA/T(d) (1.81 ± 0.48). Multi-indicators was no significant difference (χ(2) = 17.76, P > 0.05). CONCLUSIONS: MSCT is very useful in diagnosis of PAH in COPD. The diameter ratio of MPA to trachea, the area of MPA, and the diameter ratio of MPA to ThV can be used as diagnostic criteria for evaluation of PAH in COPD.

Dopaminergic Modulation of Local Non-oscillatory Activity and Global-Network Properties in Parkinson's Disease: An EEG Study.

Dopaminergic medication for Parkinson's disease (PD) modulates neuronal oscillations and functional connectivity (FC) across the basal ganglia-thalamic-cortical circuit. However, the non-oscillatory component of the neuronal activity, potentially indicating a state of excitation/inhibition balance, has not yet been investigated and previous studies have shown inconsistent changes of cortico-cortical connectivity as a response to dopaminergic medication. To further elucidate changes of regional non-oscillatory component of the neuronal power spectra, FC, and to determine which aspects of network organization obtained with graph theory respond to dopaminergic medication, we analyzed a resting-state electroencephalography (EEG) dataset including 15 PD patients during OFF and ON medication conditions. We found that the spectral slope, typically used to quantify the broadband non-oscillatory component of power spectra, steepened particularly in the left central region in the ON compared to OFF condition. In addition, using lagged coherence as a FC measure, we found that the FC in the beta frequency range between centro-parietal and frontal regions was enhanced in the ON compared to the OFF condition. After applying graph theory analysis, we observed that at the lower level of topology the node degree was increased, particularly in the centro-parietal area. Yet, results showed no significant difference in global topological organization between the two conditions: either in global efficiency or clustering coefficient for measuring global and local integration, respectively. Interestingly, we found a close association between local/global spectral slope and functional network global efficiency in the OFF condition, suggesting a crucial role of local non-oscillatory dynamics in forming the functional global integration which characterizes PD. These results provide further evidence and a more complete picture for the engagement of multiple cortical regions at various levels in response to dopaminergic medication in PD.

ssc-microRNA-132 targets DACH1 to exert anti-inflammatory and anti-apoptotic effects in Clostridium perfringens beta2 toxin-treated porcine intestinal epithelial cells.

Clostridium perfringens (C. perfringens) type C (CPC) is one of the chief pathogens that causes diarrhea in piglets, and C. perfringens beta2 (CPB2) toxin is the main virulence factor of CPC. Our previous research demonstrated that ssc-microR-132 was differentially expressed in ileal tissues of CPC-mediated diarrheic piglets and healthy piglets, which implied a potential role of ssc-microR-132 in this process. Here, we found that ssc-microR-132 was notably down-regulated in CPB2-exposed intestinal porcine epithelial cells (IPEC-J2), which was consistent with the ileal tissue expression. Moreover, ssc-microR-132 upregulation alleviated CPB2-induced inflammatory damage and apoptosis in IPEC-J2, whereas ssc-microR-132 knockdown presented the opposite effects. Furthermore, the dual-luciferase reporter assay indicated that ssc-microR-132 directly targeted Dachshund homolog 1 (DACH1). Moreover, DACH1 overexpression intensified CPB2-induced inflammatory injury and apoptosis in IPEC-J2. Remarkably, the introduction of DACH1 weakened the anti-inflammatory and anti-apoptotic effects of ssc-microR-132 in CPB2-exposed IPEC-J2. Overall, the results reveal that ssc-microR-132 targeted DACH1 to alleviate CPB2-mediated inflammation and apoptosis in IPEC-J2.