Novel nitroxoline derivative combating resistant bacterial infections through outer membrane disruption and competitive NDM-1 inhibition.

ABSTRACTNew Delhi metallo-ß-lactamase-1 (NDM-1) has rapidly disseminated worldwide, leading to multidrug resistance and worse clinical prognosis. Designing and developing effective NDM-1 inhibitors is a critical and urgent challenge. In this study, we constructed a library of long-lasting nitroxoline derivatives and identified ASN-1733 as a promising dual-functional antibiotic. ASN-1733 can effectively compete for Ca2+ on the bacterial surface, causing the detachment of lipopolysaccharides (LPS), thereby compromising the outer membrane integrity and permeability and exhibiting broad-spectrum bactericidal activity. Moreover, ASN-1733 demonstrated wider therapeutic applications than nitroxoline in mouse sepsis, thigh and mild abdominal infections. Furthermore, ASN-1733 can effectively inhibit the hydrolytic capability of NDM-1 and exhibits synergistic killing effects in combination with meropenem against NDM-1 positive bacteria. Mechanistic studies using enzymatic experiments and computer simulations revealed that ASN-1733 can bind to key residues on Loop10 of NDM-1, hindering substrate entry into the enzyme's active site and achieving potent inhibitory activity (Ki = 0.22 µM), even in the presence of excessive Zn2+. These findings elucidate the antibacterial mechanism of nitroxoline and its derivatives, expand their potential application in the field of antibacterial agents and provide new insights into the development of novel NDM-1 inhibitors.

The Interaction between Collagen 1 and High Mannose Type CD133 Up-Regulates Glutamine Transporter SLC1A5 to Promote the Tumorigenesis of Glioblastoma Stem Cells.

Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs. COL1, mainly secreted by cancer-associated fibroblasts, is a niche component for GSCs. COL1 enhances the interaction between CD133 and p85 and activates Akt phosphorylation. Activation of Akt pathway increases transcription factor ATF4 protein level, subsequently enhances SLC1A5-dependent glutamine uptake and glutathione synthesis. The inhibition of CD133-COL1 interaction or down-regulation of SLC1A5 reduces COL1-accelerated GSCs self-renewal and tumorigenesis. Analysis of glioma samples reveals that the level of COL1 is correlated with histopathological grade of glioma and the expression of SLC1A5. Collectively, COL1, a niche component for GSCs, enhances the tumorigenesis of GSCs partially through CD133-Akt-SLC1A5 signaling axis, providing a new mechanism underlying the cross-talk between GSCs and extracellular matrix (ECM) microenvironment.

Loss of α-1,2-mannosidase MAN1C1 promotes tumorigenesis of intrahepatic cholangiocarcinoma through enhancing CD133-FIP200 interaction.

CD133 is widely used as a marker to isolate tumor-initiating cells in many types of cancers. The structure of N-glycan on CD133 is altered during the differentiation of tumor-initiating cells. However, the relationship between CD133 N-glycosylation and stem cell characteristics remains elusive. Here, we found that the level of α-1,2-mannosylated CD133 was associated with the level of stemness genes in intrahepatic cholangiocarcinoma (iCCA) tissues. α-1,2-mannosylated CD133+ cells possessed the characteristics of tumor-initiating cells. The loss of the Golgi α-mannosidase I coding gene MAN1C1 resulted in the formation of α-1,2-mannosylated CD133 in iCCA-initiating cells. Mechanistically, α-1,2-mannosylation promoted the cytoplasmic distribution of CD133 and enhanced the interaction between CD133 and the autophagy gene FIP200, subsequently promoting the tumorigenesis of α-1,2-mannosylated CD133+ cells. Analysis of iCCA samples showed that the level of cytoplasmic CD133 was associated with poor iCCA prognosis. Collectively, α-1,2-mannosylated CD133 is a functional marker of iCCA-initiating cells.

Noncovalent composites of meso-substituted A2B2-porphyrins and carbon nanotubes for enhanced electrocatalytic oxygen reduction.

Exploring highly active oxygen reduction electrocatalysts with low precious metals content is imperative but remains a considerable challenge. Herein, a series of heterobimetallic multi-walled carbon nanotubes (MWCNTs) electrocatalysts based on metal complexes are presented. These electrocatalysts feature diverse transition metals (M=Mn, Fe, Co, Ni) 5,15-bromophenyl-10, 20-methoxyphenyl porphyrin (MBMP) and tetrakis(triphenylphosphine)palladium (0) (Pd[P(Ph3)4]) anchored non-covalently on its surface. The resulting NiBMP-based MWCNTs with Pd[P(Ph3)4] (PdNiN4/MWCNTs) display outstanding electrocatalytic oxygen reduction activity (onset potential, 0.941 V; half wave potential, 0.830 V) and robust long-term durability in alkaline electrolyte. While in neutral condition, the MnBMP-based MWCNTs with Pd[P(Ph3)4] (PdMnN4/MWCNTs) are the most active heterobimetallic ORR catalyst and produce ultra-low concentration hydrogen peroxide (H2O2yield, 1.2%-1.3%). Synergistically tuning the ORR electrocatalytic activity and electron transfer pathway is achieved by the formation of NiBMP/MnBMP-Pd[P(Ph3)4] active sites. This work indicates such metalloporphyrin-Pd[P(Ph3)4] active sites on MWCNTs have significantly positive influence on electrocatalytic ORR systems and provides facile and mild strategy for designing highly efficient ORR electrocatalysts with ultra-low loading precious metal.

Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.

PURPOSE: Sialic acid-bound immunoglobulin-like lectin 15 (Siglec15) has emerged as a novel therapeutic target in tumor immunotherapy. This study is designed to investigate the function and mechanism of Siglec15 in thyroid carcinoma (THCA). MATERIALS AND METHODS: The information on patients with THCA from TGCA and GEO database were used to analyze the expression of Siglec15 in THCA. THCA cells were treated with Siglec15-mFc, a recombinant fusion protein consisting of the extracellular domain of human Siglec15 and murine IgG Fc. THP-1 cells expressing human Siglec15 and its mutant were co-cultured with THCA cells to mimic the contact between Siglec15-expressing tumor-associated macrophages and THCA cells. Wound-healing assay and transwell migration assay were used to examine the migration abilities of BCPAP and C643 cells. Pull-down assay was performed to examine the interaction between Siglec15 and epidermal growth factor receptor (EGFR) on the cancer cells. Cycloheximide (CHX) assay was used to evaluate the stability of the protein. RESULTS: The expression of Siglec15 in thyroid carcinoma tissues is higher than in normal tissues. Siglec15 promotes the migration of THCA cells by binding to EGFR in a sialic acid-dependent manner and increases EGFR protein expression. Inhibition of the EGFR pathway blocks the effect of Siglec15 on the migration of THCA cells. CONCLUSIONS: Our findings reveals that Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.

Pharmacokinetics and Pharmacodynamics of a Novel Vancomycin Derivative LYSC98 in a Murine Thigh Infection Model Against Staphylococcus aureus.

Introduction: LYSC98 is a novel vancomycin derivative used for gram-positive bacterial infections. Here we compared the antibacterial activity of LYSC98 with vancomycin and linezolid in vitro and in vivo. Besides, we also reported the pharmacokinetic/pharmacodynamic (PK/PD) index and efficacy-target values of LYSC98. Methods: The MIC values of LYSC98 were identified through broth microdilution method. A mice sepsis model was established to investigate the protective effect of LYSC98 in vivo. Single-dose pharmacokinetics of LYSC98 was studied in thigh-infected mice and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to determine LYSC98 concentration in plasma. Dose fractionation studies were performed to evaluate different PK/PD indices. Two methicillin-resistant Staphylococcus aureus (MRSA) clinical strains were used in the dose ranging studies to determine the efficacy-target values. Results: LYSC98 showed a universal antibacterial effect in Staphylococcus aureus with a MIC range of 2-4 µg/mL. In vivo, LYSC98 demonstrated distinctive mortality protection in mice sepsis model with an ED50 value of 0.41-1.86 mg/kg. The pharmacokinetics results displayed maximum plasma concentration (Cmax) 11,466.67-48,866.67 ng/mL, area under the concentration-time curve from 0 to 24 h (AUC0-24) 14,788.42-91,885.93 ng/mL·h, and elimination half-life (T1/2) 1.70-2.64 h, respectively. Cmax/MIC (R 2 0.8941) was proved to be the most suitable PK/PD index for LYSC98 to predict its antibacterial efficacy. The magnitude of LYSC98 Cmax/MIC associated with net stasis, 1, 2, 3 and 4 - log 10 kill were 5.78, 8.17, 11.14, 15.85 and 30.58, respectively. Conclusion: Our study demonstrates that LYSC98 is more effective than vancomycin either in killing vancomycin-resistant Staphylococcus aureus (VRSA) in vitro or treating S. aureus infections in vivo, making it a novel and promising antibiotic. The PK/PD analysis will also contribute to the LYSC98 Phase I dose design.

Sialylation-dependent interaction between PD-L1 and CD169 promotes monocyte adhesion to endothelial cells.

The monocyte adhesion to endothelial cells is an early step in chronic inflammation. Interferon-γ (IFN-γ) is regarded as a master regulator of inflammation development. However, the significance and mechanisms of IFN-γ in the monocyte adhesion to endothelial cells remains largely unknown. IFN-γ up-regulates PD-L1 on various types of cells. Here, we performed flow cytometry to examine the contribution of IFN-γ-induced PD-L1 expression on monocyte adhesion to endothelial cells. Up-regulation of PD-L1 by IFN-γ enhanced the adhesion of monocytes to endothelial cells. By immunoprecipitation and lectin blot, PD-L1 in endothelial cells interacted with CD169/Siglec 1 in monocytes depending on the α2,3-sialylation of PD-L1. ST3Gal family (ST3ß-galactoside α-2,3-sialyltransferase) was the major glycosyltransferase responsible for the α2,3-sialylation of membrane proteins. Down-regulation of ST3Gal4 by RNAinterference partially reduced the α2,3-sialylation of PD-L1 and the PD-L1-CD169 interaction. Finally, purified PD-L1 protein with α2,3-sialylation, but not PD-L1 protein without α2,3-sialylation, partially reduced IFN-γ-induced monocyte adhesion to endothelial cells. These findings provide evidence that the interaction between PD-L1 and CD169 promoted monocyte adhesion to endothelial cells and might elucidate a new mechanism of monocyte adhesion to endothelial cells.

Removing microplastics from aquatic environments: A critical review.

As one of the typical emerging contaminants, microplastics exist widely in the environment because of their small size and recalcitrance, which has caused various ecological problems. This paper summarizes current adsorption and removal technologies of microplastics in typical aquatic environments, including natural freshwater, marine, drinking water treatment plants (DWTPs), and wastewater treatment plants (WWTPs), and includes abiotic and biotic degradation technologies as one of the removal technologies. Recently, numerous studies have shown that enrichment technologies have been widely used to remove microplastics in natural freshwater environments, DWTPs, and WWTPs. Efficient removal of microplastics via WWTPs is critical to reduce the release to the natural environment as a key connection point to prevent the transfer of microplastics from society to natural water systems. Photocatalytic technology has outstanding pre-degradation effects on microplastics, and the isolated microbial strains or enriched communities can degrade up to 50% or more of pre-processed microplastics. Thus, more research focusing on microplastic degradation could be carried out by combining physical and chemical pretreatment with subsequent microbial biodegradation. In addition, the current recovery technologies of microplastics are introduced in this review. This is incredibly challenging because of the small size and dispersibility of microplastics, and the related technologies still need further development. This paper will provide theoretical support and advice for preventing and controlling the ecological risks mediated by microplastics in the aquatic environment and share recommendations for future research on the removal and recovery of microplastics in various aquatic environments, including natural aquatic environments, DWTPs, and WWTPs.

Feasibility of using AI to auto-catch responsible frames in ultrasound screening for breast cancer diagnosis.

The research of AI-assisted breast diagnosis has primarily been based on static images. It is unclear whether it represents the best diagnosis image.To explore the method of capturing complementary responsible frames from breast ultrasound screening by using artificial intelligence. We used feature entropy breast network (FEBrNet) to select responsible frames from breast ultrasound screenings and compared the diagnostic performance of AI models based on FEBrNet-recommended frames, physician-selected frames, 5-frame interval-selected frames, all frames of video, as well as that of ultrasound and mammography specialists. The AUROC of AI model based on FEBrNet-recommended frames outperformed other frame set based AI models, as well as ultrasound and mammography physicians, indicating that FEBrNet can reach level of medical specialists in frame selection.FEBrNet model can extract video responsible frames for breast nodule diagnosis, whose performance is equivalent to the doctors selected responsible frames.

The Interaction between DNMT1 and High-Mannose CD133 Maintains the Slow-Cycling State and Tumorigenic Potential of Glioma Stem Cell.

The quiescent/slow-cycling state preserves the self-renewal capacity of cancer stem cells (CSCs) and leads to the therapy resistance of CSCs. The mechanisms maintaining CSCs quiescence remain largely unknown. Here, it is demonstrated that lower expression of MAN1A1 in glioma stem cell (GSC) resulted in the formation of high-mannose type N-glycan on CD133. Furthermore, the high-mannose type N-glycan of CD133 is necessary for its interaction with DNMT1. Activation of p21 and p27 by the CD133-DNMT1 interaction maintains the slow-cycling state of GSC, and promotes chemotherapy resistance and tumorigenesis of GSCs. Elimination of the CD133-DNMT1 interaction by a cell-penetrating peptide or MAN1A1 overexpression inhibits the tumorigenesis of GSCs and increases the sensitivity of GSCs to temozolomide. Analysis of glioma samples reveals that the levels of high-mannose type N-glycan are correlated with glioma recurrence. Collectively, the high mannose CD133-DNMT1 interaction maintains the slow-cycling state and tumorigenic potential of GSC, providing a potential strategy to eliminate quiescent GSCs.

A Comparative Study of Multiple Deep Learning Models Based on Multi-Input Resolution for Breast Ultrasound Images.

Purpose: The purpose of this study was to explore the performance of different parameter combinations of deep learning (DL) models (Xception, DenseNet121, MobileNet, ResNet50 and EfficientNetB0) and input image resolutions (REZs) (224 × 224, 320 × 320 and 488 × 488 pixels) for breast cancer diagnosis. Methods: This multicenter study retrospectively studied gray-scale ultrasound breast images enrolled from two Chinese hospitals. The data are divided into training, validation, internal testing and external testing set. Three-hundreds images were randomly selected for the physician-AI comparison. The Wilcoxon test was used to compare the diagnose error of physicians and models under P=0.05 and 0.10 significance level. The specificity, sensitivity, accuracy, area under the curve (AUC) were used as primary evaluation metrics. Results: A total of 13,684 images of 3447 female patients are finally included. In external test the 224 and 320 REZ achieve the best performance in MobileNet and EfficientNetB0 respectively (AUC: 0.893 and 0.907). Meanwhile, 448 REZ achieve the best performance in Xception, DenseNet121 and ResNet50 (AUC: 0.900, 0.883 and 0.871 respectively). In physician-AI test set, the 320 REZ for EfficientNetB0 (AUC: 0.896, P < 0.1) is better than senior physicians. Besides, the 224 REZ for MobileNet (AUC: 0.878, P < 0.1), 448 REZ for Xception (AUC: 0.895, P < 0.1) are better than junior physicians. While the 448 REZ for DenseNet121 (AUC: 0.880, P < 0.05) and ResNet50 (AUC: 0.838, P < 0.05) are only better than entry physicians. Conclusion: Based on the gray-scale ultrasound breast images, we obtained the best DL combination which was better than the physicians.

Zygomaticomaxillary suture maturation evaluation in patients with and without cleft lip and palate.

INTRODUCTION: The zygomaticomaxillary suture (ZMS) maturation evaluation is a reliable method for predicting the optimal timing of maxillary protraction. The objective of this study was to compare age distribution patterns of ZMS maturation stages between cleft lip and palate (CLP) patients and non-cleft lip and palate (non-CLP) patients to aid our comprehension in choosing the optimal timing of maxillary protraction. METHODS: Samples of 216 non-CLP and 220 CLP Asian patients without orthodontic and orthognathic treatment aged 5-25 years were scanned to evaluate the ZMS maturation stage by 2 evaluators blindly. Evaluators' agreements and bilateral ZMS maturation consistency were assessed by weighted kappa tests. Age distribution patterns of each ZMS maturation stage were described. Gender effect and age distribution differences between groups were analyzed using an independent t-test. RESULTS: Evaluators' agreements and bilateral ZMS maturation consistency were satisfying (weighted kappa coefficient >0.90). At stages A and B, patients with CLP were 1.3 and 0.4 years older than patients in the non-CLP group (P <0.001 and P = 0.01). In contrast, at stage C, patients with CLP were approximately 1.2 years younger (P = 0.004). Gender barely played a role in the divergence of ZMS maturation (P >0.05). No statistically significant difference was observed between ZMS maturation of patients with unilateral or bilateral cleft lip and palate (UBCLP) and patients with unilateral or bilateral cleft lip (UBCL) (P >0.05). CONCLUSIONS: The ZMS development of patients with CLP was premature at stage C, whereas delayed at stages A and B.

The significance of dual-mode elastography in the diagnosis of breast lesions by physicians with different levels of experience.

BACKGROUND: This study aimed to assess the diagnostic value of dual-mode elastography for benign and malignant breast lesions and determine whether this technique can improve the diagnostic ability of physicians with different levels of experience. METHODS: One hundred and eighty-three breast lesions were analyzed retrospectively, and the following values were calculated for the lesions with various shells: shear modulus (G), Young's modulus (E), shear wave velocity (Cs), and strain ratio (SR). A random forest algorithm was used to select the optimal modes for elastography. A receiver operating characteristic curve was used to assess the diagnostic efficacy for benign and malignant breast lesions. Sensitivity and specificity values were calculated to evaluate any improvements in the diagnostic efficacy of physicians with different levels of experience (junior, intermediate-level, and senior) in the evaluation of malignant breast lesions using dual-mode elastography. RESULTS: The best-performing mode of shear wave elastography (SWE) in the diagnosis of breast lesions was the A'min 1.0 (Cs) mode (minimum shear wave velocity of the area of interest and 1.0 mm around the area of interest), and the best-performing mode of strain elastography (SE) was the B/A' 0.5 (ratio of fat to the elasticity of the area of interest and 0.5 mm around the area of interest). When the two methods were used in series, results showed high specificity (98%), positive likelihood ratio (PLR) (21.2), and positive predictive value (PPV) (95%). Series means that if SE and SWE were malignant, the result in series was malignant, and that if either SE or SWE was benign, the result in series was benign. When the methods were used in parallel, the results showed high sensitivity (91%), negative likelihood ratio (NLR) (0.15), and negative predictive value (NPV) (89%). Parallel means that if SE and SWE were benign, the result in parallel was benign, and that if either SE or SWE was malignant, the result in parallel was malignant. When conventional ultrasound was combined with dual-mode elastography, the intermediate-level and junior physicians' diagnoses of breast lesions showed a higher sensitivity, specificity, and area under the curve than conventional ultrasound diagnosis alone. CONCLUSIONS: Dual-mode elastography is effective in the diagnosis of breast lesions. The sensitivity and specificity values in this study show that diagnoses made by junior and intermediate-level physicians improve when dual-mode elastography is used, although diagnoses made by senior physicians do not improve significantly.

Psychometric properties of the metacognitions about smartphone use questionnaire (MSUQ) in Chinese college students.

AIMS: Over the last ten years, several studies investigating the role of metacognitions in addictive behaviors, including technological addictions, have been published. Problematic Smartphone use has been conceptualized as a behavioural addiction and a psychometrically sound self-report measure to assess metacognitions about PSU has been recently published. The objective of this study was to evaluate some psychometric properties (e.g., factor structure, reliability, and validity) of the Chinese Metacognitions about Smartphone Use Questionnaire (Chinese MSUQ). METHODS: A sample of 698 undergraduates (F = 54.70%, mean age = 19.89 ±â€¯1.38 years) were enrolled in China. An exploratory factor analysis was first performed in a randomly allocated subsample of 349 participants. A confirmatory factor analysis was then computed on a second subsample of 349 participants to test its fitting with the identified factor structure. Internal consistency and predictive validity were verified. RESULTS: The result of exploratory factor analysis showed a 2-factor structure, which consists of positive metacognitions concerning emotional and cognitive regulation and social advantages of smartphone use (MSUQ-PM) and negative metacognitions about uncontrollability and cognitive harm of smartphone use (MSUQ-NM). The confirmatory factor analysis indicated that the 2-factor structure of Chinese MSUQ had appropriate fit. Cronbach's Alphas ranged from 0.90 to 0.92. Additionally, regression analysis showed that MSUQ-PM and MSUQ-NM positively predicted PSU. Notably, MSUQ-NM is a stronger predictor of PSU compared with MSUQ-PM, with a rescaled importance of 86.36%. CONCLUSIONS: The Chinese MSUQ has appropriate psychometric properties, suggesting it is a reliable instrument to assess metacognitions about smartphone use in the Chinese context.

Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as a novel potential target for cancer immunotherapy. Here, we explored the role of Siglec-15 in human hepatoma cells. In this study, we found that the expression of Siglec-15 is substantially upregulated in liver cancer tissues in comparison with the nontumor tissues. Functionally, in vitro experiments show that Siglec-15 promotes the migration of hepatoma cells. Furthermore, the data demonstrated an interaction between Siglec-15 and CD44, a transmembrane glycoprotein that mediates tumor progression and metastasis. In addition, we show that CD44 is modified by α2,6-linked sialic acids on N-glycans in hepatoma cells and that CD44 sialylation affects its interaction with Siglec-15. Removal of the sialic acid residues from CD44 resulted in suppressed interaction between Siglec-15 and CD44. We further demonstrate that Siglec-15 interacts and promotes the stability of CD44 by preventing its lysosomal-mediated degradation. Taken together, our findings demonstrate that Siglec-15 promotes the migration of hepatoma cells by regulating the CD44 protein stability.

Relationship Between Crown to Root Ratio and Alveolar Bone Support in Patients With Unilateral Cleft Lip and Alveolus.

OBJECTIVES: To evaluate the tooth lengths, crown to root ratios (CRRs), and alveolar bone support (ABS) around cleft-adjacent maxillary central incisors (U1s) in patients with unilateral cleft lip and alveolus (UCLA) and to investigate the relationships between CRR and ABS. DESIGN: This is a retrospective study. SETTING: Cleft Lip and Palate Care Center of Shanghai Ninth People's Hospital, Shanghai, China. PATIENTS: Fifty-eight Chinese patients with UCLA. MAIN OUTCOME MEASURE: Cone beam computed tomography data from 58 nonsyndromic patients with UCLA (36 males, 22 females; mean age = 12.65 ± 3.64 years) were evaluated. Crown length and root length, alveolar bone thickness (ABT), and the distances between the cementoenamel junction and alveolar bone crest on 4 surfaces of cleft-adjacent U1 were measured and compared with those of noncleft side in the same patients. Crown to root ratio and frequency of dehiscence were calculated and comparisons were also made between cleft and noncleft sides. Regression analysis was performed to explore the association between CRR and ABS. RESULTS: The CRR of cleft-adjacent U1 and alveolar bone crest heights (ACHs) on the 4 surfaces were significantly greater than those of noncleft side (P < .01). A 3 mm labial, all lingual, and apico-distal ABTs decreased on the cleft side (P < .01). A positive correlation was found between lingual ACH and CRR (R = 0.316, P < .05), between the 3 mm (R = 0.417, P < .05) and 6 mm labial (R = 0.448, P < .05) ABT and CRR. A negative correlation was found between the 3 mm and 6 mm labial ABTs and the root length. CONCLUSIONS: It can be suggested that the CRR is related to ACH and ABT. The lingual ACH, the 3 mm, and 6 mm labial ABTs tend to increase with the increasing CRR.

Effect of PM characterization on PM oxidative potential by acellular assays: a review.

The health risks brought by particles cannot be present via a sole parameter. Instead, the particulate matter oxidative potential (PM OP), which expresses combined redox properties of particles, is used as an integrated metric to assess associated hazards and particle-induced health effects. OP definition provides the capacity of PM toward target oxidation. The latest technologies of a cellular OP measurement has been growing in relevant studies. In this review, OP measurement techniques are focused on discussing along with PM characterization because of many related studies via OP measurements investigating relationship with human health. Many OP measurement methods, such as dithiothreitol (DTT), ascorbic acid (AA), glutathione (GSH) assay and other a cellular assays, are used to study the association between PM toxicity and PM characterization that make different responses, including PM components, size and sources. Briefly, AA and DTT assays are sensitive to metals (such as copper, manganese and iron etc.) and organics (quinones, VOCs and PAH). Measured OP have significant association with certain PM-related end points, for example, lung cancer, COPD and asthma. Literature has found that exposure to measured OP has higher risk ratios than sole PM mass, which may be containing the PM health-relevant fraction. PM characterization effect on health via OP measurement display a promising method.

Acute Effects of Exposure to Ambient Air Pollutants on Preterm Birth in Xiamen City (2015-2018), China.

Backgrounds: Urban energy consumption is one of the important causes of air pollution. The epidemiological risk assessment guided by air pollution is of great significance to the promotion of urban environmental protection. Objectives: The work researched the acute impact of exposure to air pollution on preterm birth (PTB) in Xiamen city from 2015 to 2018. Furthermore, the economic losses were assessed as well. Methods: Association of air pollution and PTB with economic losses were assessed using the generalized additive model. Results: A total of 1991 PTB visits, who are inhabitant in Xiamen, have been investigated. An interquartile range (IQR) (10 µg/m3) increase of PM10, NO2, and SO2 in the current day corresponded to the increase of 0.64% [95% CI: -1.22, 2.54%], 0.52% [95% CI: -5.21, 6.61%], and 2.33% [95% CI: -6.41, 11.58%] in daily PTB visits. Especially, PTB visits were significantly related with PM10 and NO2 in Lag 1 and NO2 and SO2 in Lag 2. Furthermore, for multipollutants, an IQR increase in PM2.5, O3, and CO, after adjustment with SO2, was related with 5.04% [95% CI: -5.90, 17.24], 2.49% [95% CI: -6.07, 11.81], and 7.10% [95% CI: -2.79, 18.00] increase of PTB morbidity, respectively. The estimates of the number of excess PTBs attributed to typical pollutants PM10 and SO2 were ∼2400 and 1200 people, respectively, every year. The highest excess PTBs was estimated to occur as a result of PM10 and SO2 effects. Conclusions: Although Xiamen has a relatively low level of air pollution, short-term exposure to NO2, SO2, and PM10 was linked to the increase of PTB visits.

Quantification of synergistic, additive and antagonistic effects of aerosol components on total oxidative potential.

The interaction-based oxidative potential (OPint) represents the prediction of binary mixture effects distinguishing from linear additivity by including information on binary mixtures among PM components. The objective of this work is to develope a reliable estimate on the possible synergistic or antagonistic possibility of binary PM components and to quantify the combined effect. We firstly assessed the interactions among PM components in generating the OP based on DTT consumption rate and AA depletion. We started with the standard solution sequence (from 0.005 to 10 µM), including quinones (PQ, 1,2-NQ, and 1,4-NQ) and metals (Cu, Mn, and Fe). The interactions between metals were antagonistic interactions in DTT consumption. Cu showed antagonistic interaction with PQ, but additive with 1,2-NQ and 1,4-NQ. Mn interacted synergistically with 1,4-NQ in DTT consumption but antagonistically with PQ (where CPQ < 2.5 µM) and 1,4-NQ (where CPQ < 2 µM). Fe showed synergistic with quinones in investigated concentration range (from 0.01 to 5 µM). Finally, applying a moderate approach, on the basis of interaction magnitude (M = 5), resulted in 1-17% higher environmental risks, compared with the classical calculation method using simple addition. This work highlights a new approach to quantify the interaction effects between metals and quinones in PM components, and apportioning the components' contributions for PM OP.

Difference and Commonness Among CLP, NON-CLP Patients and Their Parents Seeking for Orthodontic Treatment: A Questionnaire Applying Q Methodology to Investigate Motives.

PURPOSE: Based on Q methodology, this study investigated the motivation of orthodontic treatment for patients and their parents. Through investigation, this paper attempts to explore the motivational factors of CLP and NON-CLP children and their parents, which are different or general. PATIENTS AND METHODS: Q methodology involves 4 phases. (1) Interviews of CLP (N=5), NON-CLP (N=5) patients generated 30 statements (Q-set 1) and CLP (N=5), NON-CLP (N=5) patients' parents produced 36 statements (Q-set 2) about different reasons to pursue orthodontic care. (2) P-set: recruitment participants. The sample comprised 40 CLP patients (G1) and 40 NON-CLP patients (G2) aged 9-16 years, 40 CLP patients' parents (G3) and 40 NON-CLP patients' parents (G4) wanting their children to have orthodontic treatment. (3) Q-sort: 4 groups ranked statements in order of comparative significance using enforced distribution grids (G1, G2 ranked Q-set 1; G3, G4 ranked Q-set 2). (4) Analysis: using the PQMehtod 2.35 vision to analyze data. RESULTS: Three factors in each group were identified as representing the most widespread views of the majority of the participants, described as G1: (1) aesthetics, (2) preparation for other oral treatments, (3) timely. G2: (1) admiration of others, aesthetics, (2) oral function, (3) oral hygiene and improvement of smile. G3: (1) worrying about the future of children, parents' responsibilities, children's feelings; (2) mental health, timely; (3) parents' responsibilities, ready for treatment. G4: (1) aesthetics, children's will; (2) future problems, timely; (3) timely, parents' responsibility and no need to worry about physical problems. CONCLUSION: CLP and NON-CLP patients and parents have different orthodontic treatment motives, yet, they still shared 3 global motivation themes, respectively. Consideration of these motives may help clinicians develop their treatment discussions with patients and parents, which could consequently improve their cooperation and may achieve a more satisfactory outcome.