Nitric oxide mediates positive regulation of Nostoc flagelliforme polysaccharide yield via potential S-nitrosylation of G6PDH and UGDH.

Based on our previous findings that salicylic acid and jasmonic acid increased Nostoc flagelliforme polysaccharide yield by regulating intracellular nitric oxide (NO) levels, the mechanism through which NO affects polysaccharide biosynthesis in Nostoc flagelliforme was explored from the perspective of S-nitrosylation (SNO). The addition of NO donor and scavenger showed that intracellular NO had a significant positive effect on the polysaccharide yield of N. flagelliforme. To explore the mechanism, we investigated the relationship between NO levels and the activity of several key enzymes involved in polysaccharide biosynthesis, including fructose 1,6-bisphosphate aldolase (FBA), glucokinase (GK), glucose 6-phosphate dehydrogenase (G6PDH), mitochondrial isocitrate dehydrogenase (ICDH), and UDP-glucose dehydrogenase (UGDH). The enzymatic activities of G6PDH, ICDH, and UGDH were shown to be significantly correlated with the shifts in intracellular NO levels. For further validation, G6PDH, ICDH, and UGDH were heterologously expressed in Escherichia coli and purified via Ni+-NAT affinity chromatography, and subjected to a biotin switch assay and western blot analysis, which revealed that UGDH and G6PDH were susceptible to SNO. Furthermore, mass spectrometry analysis of proteins treated with S-nitrosoglutathione (GSNO) identified the SNO modification sites for UGDH and G6PDH as cysteine 423 and cysteine 249, respectively. These findings suggest that NO modulates polysaccharide biosynthesis in N. flagelliforme through SNO of UGDH and G6PDH. This reveals a potential mechanism through which NO promotes polysaccharide synthesis in N. flagelliforme, while also providing a new strategy for improving the industrial production of polysaccharides.

Influence of left ventricular ejection fraction in patients undergoing contemporary pLVAD-supported high-risk PCI.

BACKGROUND: Left ventricular (LV) systolic dysfunction worsens outcomes in patients undergoing percutaneous coronary intervention (PCI). The objective of this study, therefore, was to evaluate outcomes of pLVAD-supported high-risk PCI (HRPCI) patients according to LV ejection fraction (LVEF). METHODS: Patients from the PROTECT III study undergoing pLVAD-supported HRPCI were stratified according to baseline LVEF: severe LV dysfunction (LVEF <30%), mild and moderate LV dysfunction (LVEF ≥30% to <50%), or preserved LV function (LVEF ≥50%). Major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization), and PCI-related complications were assessed at 90 days and mortality was assessed at 1-year. RESULTS: From March 2017 to March 2020, 940 patients had evaluable baseline LVEF recorded in the study database. Patients with preserved LV function were older, more frequently presented with myocardial infarction, and underwent more left main PCI and atherectomy. Immediate PCI-related coronary complications were infrequent (2.7%, overall), similar between groups (P = 0.98), and not associated with LVEF. Unadjusted 90-day MACCE rates were similar among LVEF groups; however, as a continuous variable, LVEF was associated with both 90-day MACCE (adj.HR per 5% 0.89, 95% CI [0.80, 0.98], P = 0.018) and 1-year mortality (adj.HR per 5% 0.84 [0.78, 0.90], P <0.0001). CONCLUSIONS: Patients who underwent pLVAD-supported HRPCI exhibited low incidence of PCI-related complications, regardless of baseline LVEF. However, LVEF was associated with 90-day MACCE and 1-year mortality.

Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen hepatotoxicity by promoting hepatic Cry1 expression.

Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.

Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts.

Sustained or chronic inflammation in the placenta can result in placental insufficiency, leading to adverse reproductive outcomes such as pregnancy loss. Branched-chain amino acid transaminase 1 (BCAT1) expresses in the placenta and is involved in the pathological inflammatory response, but its role in recurrent miscarriage (RM) has not been fully investigated. In the present study, we delved into the effects of BCAT1 on trophoblast inflammation induced by lipopolysaccharide (LPS) and a mouse model of pregnancy loss induced by LPS. In vitro, after the HTR-8/SVneo cells were treated with LPS and BCATc inhibitor 2 (a selective BCAT inhibitor), the cell apoptosis was verified by TUNEL assay, and the activity of caspase-3 and caspase-9 was detected. Real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF) were used to determine the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and inflammasomes (NLRP3 and ASC) in LPS-treated trophoblast cells. Western blot analysis was performed to verify the expression of phospho-IκBα (p-IκBα) in cells and NF-κB p65 in the nuclei. IF staining was used to detect the nuclear translocation of NF-κB p65. The DNA binding activity of NF-κB was detected by an electrophoretic mobility shift assay (EMSA). The results demonstrated that inhibition of BCAT1 reduced trophoblast apoptosis, suppressed the release of proinflammatory cytokines, and prevented NLRP3 inflammasome activation in response to LPS. Additionally, BCAT1 inhibition blocked the activation of the NF-κB pathway in trophoblasts. This study highlights the potential therapeutic role of targeting BCAT1 in preventing adverse reproductive outcomes associated with chronic placental inflammation.

Super-resolution radial fluctuations microscopy for optimal resolution and fidelity.

Fluorescence fluctuation super-resolution microscopy (FF-SRM) has emerged as a promising method for the fast, low-cost, and uncomplicated imaging of biological specimens beyond the diffraction limit. Among FF-SRM techniques, super-resolution radial fluctuation (SRRF) microscopy is a popular technique but is prone to artifacts, resulting in low fidelity, especially under conditions of high-density fluorophores. In this Letter, we developed a novel, to the best of our knowledge, combinatory computational super-resolution microscopy method, namely VeSRRF, that demonstrated superior performance in SRRF microscopy. VeSRRF combined intensity and gradient variance reweighted radial fluctuations (VRRF) and enhanced-SRRF (eSRRF) algorithms, leveraging the enhanced resolution achieved through intensity and gradient variance analysis in VRRF and the improved fidelity obtained from the radial gradient convergence transform in eSRRF. Our method was validated using microtubules in mammalian cells as a standard biological model system. Our results demonstrated that VeSRRF consistently achieved the highest resolution and exceptional fidelity compared to those obtained from other algorithms in both single-molecule localization microscopy (SMLM) and FF-SRM. Moreover, we developed the VeSRRF software package that is freely available on the open-source ImageJ/Fiji software platform to facilitate the use of VeSRRF in the broader community of biomedical researchers. VeSRRF is an exemplary method in which complementary microscopy techniques are integrated holistically, creating superior imaging performance and capabilities.

Analysis of the cell wall binding domain in bacteriocin-like lysin LysL from Lactococcus lactis LAC460.

Wild-type Lactococcus lactis strain LAC460 secretes prophage-encoded bacteriocin-like lysin LysL, which kills some Lactococcus strains, but has no lytic effect on the producer. LysL carries two N-terminal enzymatic active domains (EAD), and an unknown C-terminus without homology to known domains. This study aimed to determine whether the C-terminus of LysL carries a cell wall binding domain (CBD) for target specificity of LysL. The C-terminal putative CBD region of LysL was fused with His-tagged green fluorescent protein (HGFPuv). The HGFPuv_CBDlysL gene fusion was ligated into the pASG-IBA4 vector, and introduced into Escherichia coli. The fusion protein was produced and purified with affinity chromatography. To analyse the binding of HGFPuv_CBDLysL to Lactococcus cells, the protein was mixed with LysL-sensitive and LysL-resistant strains, including the LysL-producer LAC460, and the fluorescence of the cells was analysed. As seen in fluorescence microscope, HGFPuv_CBDLysL decorated the cell surface of LysL-sensitive L. cremoris MG1614 with green fluorescence, whereas the resistant L. lactis strains LM0230 and LAC460 remained unfluorescent. The fluorescence plate reader confirmed the microscopy results detecting fluorescence only from four tested LysL-sensitive strains but not from 11 tested LysL-resistant strains. Specific binding of HGFPuv_CBDLysL onto the LysL-sensitive cells but not onto the LysL-resistant strains indicates that the C-terminus of LysL contains specific CBD. In conclusion, this report presents experimental evidence of the presence of a CBD in a lactococcal phage lysin. Moreover, the inability of HGFPuv_CBDLysL to bind to the LysL producer LAC460 may partly explain the host's resistance to its own prophage lysin.

Development and validation of a novel colonoscopy withdrawal time indicator based on YOLOv5.

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

A newly discovered glycosyltransferase gene UGT88A1 affects growth and polysaccharide synthesis of Grifola frondosa.

Grifola frodosa polysaccharides, especially ß-D-glucans, possess significant anti-tumor, antioxidant and immunostimulatory activities. However, the synthesis mechanism remains to be elucidated. A newly discovered glycosyltransferase UGT88A1 was found to extend glucan chains in vitro. However, the role of UGT88A1 in the growth and polysaccharide synthesis of G. frondosa in vivo remains unclear. In this study, the overexpression of UGT88A1 improved mycelial growth, increased polysaccharide production, and decreased cell wall pressure sensitivity. Biomass and polysaccharide production decreased in the silenced strain, and the pressure sensitivity of the cell wall increased. Overexpression and silencing of UGT88A1 both affected the monosaccharide composition and surface morphology of G. frondosa polysaccharides and influenced the antioxidant activity of polysaccharides from different strains. The messenger RNA expression of glucan synthase (GLS), UTP-glucose-1-phosphate uridylyltransferase (UGP), and UDP-xylose-4-epimerase (UXE) related to polysaccharide synthesis, and genes related to cell wall integrity increased in the overexpression strain. Overall, our study indicates that UGT88A1 plays an important role in the growth, stress, and polysaccharide synthesis of G. frondosa, providing a reference for exploring the pathway of polysaccharide synthesis and metabolic regulation. KEY POINTS: •UGT88A1 plays an important role in the growth, stress response, and polysaccharide synthesis in G. frondosa. •UGT88A1 affected the monosaccharide composition, surface morphology and antioxidant activity of G. frondosa polysaccharides. •UGT88A1 regulated the mRNA expression of genes related to polysaccharide synthesis and cell wall integrity.

Association between overnight repetitive respiratory events and the accumulation of genioglossus fatigue in male patients with severe obstructive sleep apnea.

PURPOSE: To evaluate the correlation between median frequency (MF) as a measure of genioglossus (GG) fatigue and overnight repetitive respiratory events in male patients with severe obstructive sleep apnea (OSA). METHODS: GG electromyography (EMG) data were collected synchronously with polysomnography (PSG). Overnight respiratory events were divided based on whether they occurred during the first or second halves of the total number of overnight respiratory events, and differences in MF in the respiratory phase were compared in the same segments. Events were then sampled in pairs to compare MF. The correlation between MF and the order of respiratory events, as well as interindividual differences, were analyzed. RESULTS: Twenty-two male patients were enrolled in this study and 2210 respiratory events were recorded. Before and during respiratory events, MF decreased significantly in the second half, especially during the inspiratory phase (segments 1-4: P = 0.014, P < 0.001, P < 0.001, P < 0.001, respectively). This trend was observed in non-rapid eye movement sleep and lateral position, but not in rapid eye movement sleep or the supine position, and remained after pairing for duration, stage, and position. MF correlated negatively with the order of respiratory events during the inspiratory phase. The trend of decrease in MF only existed in patients with apnea-hypopnea index > 30 events/h. CONCLUSION: Overnight repetitive respiratory events were associated with increased GG fatigue, influenced by sleep stage and body position in male patients with severe OSA. GG fatigue depends on the order and frequency of respiratory events.

Clinical characteristics and prognosis of laryngeal tuberculosis combined with respiratory tuberculosis.

PURPOSE: To investigate the clinical characteristics, diagnosis and prognosis of patients with laryngeal tuberculosis (LTB) combined with respiratory tuberculosis. MATERIALS AND METHODS: A retrospective analysis was conducted on 134 patients who underwent endoscopy and were eventually diagnosed with LTB. The patients' demographic characteristics, clinical manifestations, endoscopic features, auxiliary examination, imaging examination and prognostic characteristics were analyzed. RESULTS: LTB patients had a median age of 45.5 years (range from 12 to 87 years) and a median course of 3.0 months (range from 0.1 to 72 months). The patients' symptoms mainly presented as hoarseness (97.0 %), abnormal sensation of pharyngeal (49.3 %), cough and sputum (41.0 %), pharyngalgia (39.6 %), dysphagia (10.4 %) and dyspnea (8.2 %). The positive rate of tuberculous symptoms was 25.4 %. Endoscopic features showed that the lesions mainly involved the glottis (87.3 %), presenting as unilateral lesions (66.7 %), near-full-length involvement (88.0 %), with mucosal waves significantly reduced (86.3 %), followed by supraglottis (43.3 %), subglottis (24.6 %) and the pharynx (15.7 %). The lesions may present as granulomatous proliferation (66.4 %), ulceration (65.7 %) or swelling and exudation (51.5 %). A total of 75 patients (56.0 %) were finally diagnosed with combined pulmonary tuberculosis (PTB), with a positive chest X-ray rate of 25.6 % and a positive chest CT rate of 71.2 %. A total of 42 patients who received anti-tuberculosis treatment were followed up, and 73.8 % of patients had significant improvement in symptoms. The morphology of the pharyngeal and laryngeal mucosa returned to basically normal (59.4 %) or scar-like (34.4 %). CONCLUSIONS: LTB is usually found in middle-aged men, and patients' symptoms are mainly hoarseness, abnormal sensation of pharyngeal, pharyngalgia, cough and sputum, and can be combined with tuberculous symptoms. These lesions mainly involve multiple subregions, mainly in the glottis, and can be combined with pharyngeal involvement. There were various types of lesions. Half of the patients were complicated with PTB, and chest CT was superior to X-ray in the detection of pulmonary lesions. After regular anti-tuberculosis treatment, the symptoms and morphology of the pharyngeal and laryngeal mucosa of most patients were significantly improved.

Insights on the Roles of Nitrogen Configuration in Enhancing the Performance of Electrocatalytic Methanol Oxidation over Pt Nanoparticles.

Stabilization of the Pt in N-doped carbon materials is an effective method to improve the performance of electrocatalytic methanol oxidation reaction (MOR). Nevertheless, the roles of different N configurations (pyridinic N, pyrrolic N, and graphitic N) toward the electrochemical performance of Pt-based catalysts remain unclear. Herein, Density Functional Theory calculations are adopted to elucidate the synergistic promotion of MOR by different N-configurations with Pt nanoparticles (NPs). Guided by the theoretical study, a series of MOR electrocatalysts with different ratios of pyridinic N and pyrrolic N (denoted as Pt/N-CNT-X (500, 600, 700, 800, and 900)) are designed and synthesized. Surprisingly, the electrocatalytic activity of Pt/N-CNT-600 with a suitable ratio of pyrrolic-N and pyridinic-N for MOR reaches 2394.7 mA mg-1 Pt and 5515.8 mA mg-1 Pt in acidic and alkaline media, respectively, which are superior to the Pt/CNTs, commercial Pt/C, and the ever-reported Pt-based electrocatalysts. The strong metal-support interaction induced by the N-doping is the crucial reason for the superior electrocatalytic performance. More importantly, the ability of pyrrolic-N and pyridinic-N in promoting the adsorption and oxidation of CH3 OH and the oxidation of CO* is substantiated for the first time in methanol oxidation. This work provides new insights on the design of efficient electrocatalysts for MOR.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

Highly Efficient and Reusable PI/TiO2 Organic-Inorganic Microfibers for Sustainable Photocatalytic Degradation of Multiple Organic Pollutants under Simulated Sunlight.

Herein, a series of polyimide (PI)/titanium dioxide (TiO2) organic-inorganic flexible composite microfibers with high photocatalytic performance and good reusability were prepared by combining electrospinning technology and a hydrothermal method. Under simulated sunlight, the photocatalytic characteristics of the as-prepared PI nanofibers, TiO2 nanorods, and PI/TiO2 microfibers were evaluated with photocatalytic degradation of Rhodamine B (RhB) solution. Among the tested samples, PI/TiO2-3 mL hydrochloric acid-160 °C-14 h (PI/TiO-3-160-14) (100%) exhibited a superior photocatalytic degradation rate compared to pure PI (84.0%) and TiO2 (62.2%). The enhancement of the photocatalytic performance was attributed to the Z-scheme heterojunction mechanism. When the interface was irradiated by simulated sunlight, the band edge bending, built-in electric field, and Coulomb interaction synergistically facilitated the separation and transport of electron-hole pairs in the heterojunction. This enhanced the oxidation and reduction abilities of the valence and conduction bands of PI/TiO2. These results were adequately verified by X-ray photoelectron spectroscopy (XPS) analyses and radical trapping experiments. Additionally, PI/TiO2 microfibers also demonstrated excellent photocatalytic activity toward methylene blue (MB, 81.4%), methyl orange (MO, 95.9%), and malachite green (KG, 98.9%), underscoring the versatile applicability of PI/TiO2. Further supplementary investigations illustrated that PI/TiO2 microfibers also possess excellent photostability during our extensive recycling photocatalytic experiments.

Evaluation of obstructive sleep apnea: an analysis based on aberrant genes.

BACKGROUND: Obstructive sleep apnea (OSA) is an upstream disorder that frequently causes multisystem disorders. Much research has revealed the pathogenesis of OSA, but there is still a lack of research on the complications caused by OSA. METHODS: The mRNA expression and methylation dataset based on peripheral blood mononuclear cells (PBMCs) were downloaded from the Gene Expression Omnibus (GEO) database. All differential expressed genes (DEGs) were ranked using the Robust Rank Aggregation (RRA) algorithm. A weighted gene co-expression network analysis (WGCNA) was constructed. Subsequently, we used immune infiltration, enrichment analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis for apnea and hypopnea index (AHI) and hypertension and excessive daytime sleepiness (EDS) and constructed diagnostic model using random forest algorithm. RESULTS: In the present study, we identified 318 DEGs in PBMCs involved in pathogenesis or continuous positive airway pressure (CPAP) therapy. Pathway enrichment identified DEGs associated with protein regulation and metabolism. Notably, through intra group analysis, we found that the immune disorder was more significant for OSA in males, non-daytime sleepy, or non-hypertensive OSA. The area under the ROC curve of model for EDS prediction is 0.889 and 0.852 for hypertension. Notably, we found that the diagnostic model had a high linear predictive value for AHI. CONCLUSIONS: Our results indicate that PBMCs are a significant component of alterations in OSA and are expected to explain the mechanism of multisystem diseases caused by OSA. The present study provides new insights for symptom evaluation, classification and treatment of OSA from the molecular level.

Influence of postural changes on nasal resistance in patients with obstructive sleep apnea.

OBJECTIVE: Increased nasal resistance (NR) can augment upper airway collapse in patients with obstructive sleep apnea (OSA). Posture change can lead to altered nasal resistance. Our study aimed to investigate the influence of posture changes on NR in patients with OSA. METHODS: Healthy controls without subjective nasal obstruction (apnea-hypopnea index (AHI) < 5 events/h), patients with OSA and subjective nasal obstruction, and patients with OSA and no subjective nasal obstruction were recruited. NR was measured by active anterior rhinomanometry in sitting, supine, left-lateral, and right-lateral postural positions. Total NR and postural change-related NR increments were calculated and compared among groups. RESULTS: In total, 26 healthy controls and 72 patients with OSA (mean AHI 39.7 ± 24.8 events/h) were recruited. Of patients with OSA, 38/72 (53%) had subjective nasal obstruction. Compared with controls, patients with OSA and no subjective nasal obstruction had lower total NR (inspiration, p = 0.037; expiration, p = 0.020) in the supine postural position. There was no difference in sitting, left-lateral, and right-lateral total NR among groups. Total NR was higher in lateral compared to sitting posture in both patients with OSA and in controls. The NR increment for sitting to supine postural change was significantly lower in patients with OSA (inspiration, p = 0.003; expiration, p = 0.005) compared with controls. The change in NR showed no statistically significant difference among groups in supine-left or supine-right postural change. CONCLUSION: Patients with OSA had lower supine total NR and lower total NR increment in the sitting to supine postural change, which may be related to a different posture-related NR regulatory mechanism. This study provides a new exploratory direction for the compensatory mechanism of the upper airway to collapse during sleep.

Exposure to ambient particulate matter and hyperuricemia: An eight-year prospective cohort study on male traffic officers in China.

BACKGROUND AND OBJECTIVES: Studies on the effects of airborne particulates of diameter ≤ 1 µm (PM1), airborne particulates of diameter ≤ 2.5 µm (PM2.5) and airborne particulates of diameter ranges from 1 to 2.5 µm (PM1-2.5) on incidence of hyperuricemia are limited. We aimed to investigate the associations between PM1, PM2.5, and PM1-2.5 and hyperuricemia among male traffic officers. METHODS: We conducted a prospective cohort study of 1460 traffic officers without hyperuricemia in Guangzhou, China from 2009 to 2016. Exposures of PM1 and PM2.5 were estimated with a spatiotemporal model. PM1-2.5 concentrations were calculated by subtracting PM1 from PM2.5 concentrations. Cox's proportional hazards regressions models were used to examine the association between PM1, PM2.5, and PM1-2.5 and hyperuricemia, adjusted for potential confounders. Associations between PM1, PM2.5, and PM1-2.5 and serum uric acid (SUA) levels were evaluated with multiple linear regression models. RESULTS: Hazard ratios (HRs) and 95% confidence intervals (CIs) of hyperuricemia associated with 10 µg/m3 increment in PM1, PM2.5, and PM1-2.5 were 1.67 (95% CI:1.30-2.36), 1.49 (95% CI: 1.27-1.75), and 2.18 (95% CI: 1.58-3.02), respectively. The SUA concentrations increased by 12.23 µmol/L (95% CI: 5.91-18.56), 6.93 µmol/L (95% CI: 3.02-10.84), and 8.72 µmol/L (95% CI: 0.76-16.68) per 10 µg/m3 increase in PM1, PM2.5, and PM1-2.5, respectively. Stratified analyses indicated the positive associations of PM2.5 and PM1-2.5 with SUA levels were stronger in non-smokers, and PM1, PM2.5, and PM1-2.5 with SUA levels were stronger in non-drinkers. CONCLUSION: Long-term PM1, PM2.5, and PM1-2.5 exposures may increase the risk of hyperuricemia and elevate SUA levels among male traffic officers, especially in non-smokers and non-drinkers.

Facial Contour Features Measured on CT Reflects Upper Airway Morphology in Patients With OSA.

OBJECTIVE: To determine facial contour features, measured on computed tomography (CT), related to upper airway morphology in patients with obstructive sleep apnea (OSA); certain phenotype of facial abnormalities implying restriction of craniofacial skeleton and adipose tissue nimiety has predicted the value of the severity of OSA. MATERIALS AND METHOD: Sixty-four male patients with OSA [apnea-hypopnea index (AHI) ≥10/h] who had upper airway CT were randomly selected to quantitatively measure indicators of facial contour and upper airway structures. Pearson correlation analyses were performed. Partial correlation procedure was used to examine correlations while controlling body mass index (BMI). RESULTS: Upper airway anatomy can nearly all be reflected in the face, except retroglossal airway. Upper face width can be measured to assess the overall skeletal structures of the airway. Lower face width can be used to represent how much adipose tissue deposited. Hard palate, retropalatal, and hypopharyngeal airways have corresponding face indicators respectively. Midface width is a better predictor of AHI severity and minimum blood oxygen even than neck circumference because it contains the most anatomical information about the airway, including RP airway condition, soft palate length, tongue volume, etc. These correlations persisted even after correction for BMI. CONCLUSIONS: All anatomical features of the upper airway except retroglossal airway can be reflected in the face, and midface width is the best predictor of AHI severity and minimum blood oxygen, even better than neck circumference and BMI.

Detecting obstructive sleep apnea by craniofacial image-based deep learning.

STUDY OBJECTIVES: This study aimed to develop a deep learning-based model to detect obstructive sleep apnea (OSA) using craniofacial photographs. METHODS: Participants referred for polysomnography (PSG) were recruited consecutively and randomly divided into the training, validation, and test groups for model development and evaluation. Craniofacial photographs were taken from five different angles (front, right 90° profile, left 90° profile, right 45° profile, and left 45° profile) and inputted to the convolutional neural networks. The neural networks extracted features from photographs and outputted the probabilities of the presence of the disease. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using PSG diagnosis as the reference standard. These analyses were repeated using two apnea-hypopnea index thresholds (≥ 5 and ≥ 15events/h). RESULTS: A total of 393 participants were enrolled. Using the operating point with maximum sum of sensitivity and specificity, the model of the photographs exhibited an AUC of 0.916 (95% confidence interval [CI], 0.847-0.960) with a sensitivity of 0.95 and a specificity of 0.80 at an AHI threshold of 5 events/h; an AUC of 0.812 (95% CI, 0.729-0.878) with a sensitivity of 0.91 and a specificity of 0.73 at an AHI threshold of 15 events/h. CONCLUSIONS: The results suggest that combining craniofacial photographs and deep learning techniques can help detect OSA automatically. The model may have potential utility as a tool to assess OSA probability in clinics or screen for OSA in the community.

Chitosan Oligosaccharides Alleviate Colitis by Regulating Intestinal Microbiota and PPARγ/SIRT1-Mediated NF-κB Pathway.

Chitosan oligosaccharides (COS) have been shown to have potential protective effects against colitis, but the mechanism underlying this effect has not been fully elucidated. In this study, COS were found to significantly attenuate dextran sodium sulfate-induced colitis in mice by decreasing disease activity index scores, downregulating pro-inflammatory cytokines, and upregulating Mucin-2 levels. COS also significantly inhibited the levels of nitric oxide (NO) and IL-6 in lipopolysaccharide-stimulated RAW 264.7 cells. Importantly, COS inhibited the activation of the NF-κB signaling pathway via activating PPARγ and SIRT1, thus reducing the production of NO and IL-6. The antagonist of PPARγ could abolish the anti-inflammatory effects of COS in LPS-treated cells. COS also activated SIRT1 to reduce the acetylation of p65 protein at lysine 310, which was reversed by silencing SIRT1 by siRNA. Moreover, COS treatment increased the diversity of intestinal microbiota and partly restored the Firmicutes/Bacteroidetes ratio. COS administration could optimize intestinal microbiota composition by increasing the abundance of norank_f_Muribaculaceae, Lactobacillus and Alistipes, while decreasing the abundance of Turicibacte. Furthermore, COS could also increase the levels of propionate and butyrate. Overall, COS can improve colitis by regulating intestinal microbiota and the PPARγ/SIRT1-mediated NF-κB pathway.

LncRNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) promotes the migration, invasion and epithelial-mesenchymal transition (EMT) through targeting miR-147a/insulin-like growth factor 1 receptor (IGF1R) pathway in cervical cancer tissues and cell model.

BACKGROUND: Two factors involved in regulation, long noncoding RNA Opa interacting protein 5-antisense RNA 1 (lncRNA OIP5-AS1) and microRNA-147a, were found in cervical cancer. Therefore, the investigation of the specific regulation of miR-147a by OIP5-AS1 was performed in cervical cancer. METHOD: The cervical cancer tissues were collected from patients with cervical cancer (n = 50). The expression of OIP5-AS1, miR-147a, proteins in epithelial-mesenchymal transition (EMT) process and insulin-like growth factor 1 receptor (IGF1R) were measured by quantitative real-time polymerase chain reaction (qRT-PCT) or western blotting. Cell motility and the relationship between OIP5-AS1 and miR-147a were detected or analyzed by wound healing test, Transwell assay, dual-luciferase reporter assay, RNA binding protein immunoprecipitation assay or Pearson correlation in OIP5-AS1, or miR-147a over-expressed and/or suppressed cervical cancer cells. RESULTS: OIP5-AS1 showed the high-expression and miR-147a showed the low-expression in tumor tissues collected from patients with cervical cancer and cell lines Hela, CaSki, Siha, and ME-180. The low-expression of OIP5-AS1 suppressed the motility of Caski cells, as well as up-regulated the level of E-cadherin, which a key protein in EMT. There were targeting sites between miR-147a and OIP5-AS1. OIP5-AS1 induced the down-regulation of miR-147a, so miR-147a was inversely correlated with OIP5-AS1. The down-regulation of miR-147a increased IGF1R and E-cadherin, and these increases were alleviated by OIP5-AS1 knockdown. CONCLUSION: LncRNA OIP5-AS1 promotes the migration, invasion and EMT of cervical cancer cells via targeting miR-147a/IGF1R pathway.