CT whole lung radiomic nomogram: a potential biomarker for lung function evaluation and identification of COPD.

BACKGROUND: Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients. METHODS: This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts. RESULTS: Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869-0.906], 0.874 (95%CI 0.844-0.904) and 0.846 (95%CI 0.822-0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P < 0.001). DCA demonstrated that the nomogram constructed by combining radiomic score, age, sex, height, and smoking status was superior to the clinical factor model. CONCLUSIONS: The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.

Bio-Inspired FeMo2S4 Microspheres as Bifunctional Electrocatalysts for Boosting Hydrogen Oxidation/Evolution Reactions in Alkaline Solution.

Developing robust and effectual nonprecious electrocatalysts for the bifunctional hydrogen oxidation and evolution reactions (HOR and HER) in alkaline electrolyte is of critical significance for the realization of future hydrogen economy but challenging. Herein, this work demonstrates a new routine for the preparation of bio-inspired FeMo2S4 microspheres via the one-step sulfuration of Keplerate-type polyoxometalate {Mo72Fe30}. The bio-inspired FeMo2S4 microspheres feature potential-abundant structural defects and atomically precise iron doping and act as an effective bifunctional electrocatalyst for hydrogen oxidation/reduction reactions. The FeMo2S4 catalyst presents an impressive alkaline HOR activity compared to FeS2 and MoS2 with the high mass activity of 1.85 mA·mg-1 and high specific activity as well as excellent tolerance to carbon monoxide poisoning. Meanwhile, FeMo2S4 electrocatalyst also displayed prominent alkaline HER activity with a low overpotential of 78 mV at a current density of 10 mA·cm-2 and robust long-term durableness. Density functional theory (DFT) calculations indicate that the bio-inspired FeMo2S4 with a unique electron structure possesses the optimal hydrogen adsorption energy and enhanced adsorption of hydroxyl intermediates, which accelerates the potential-determining Volmer step, thus promoting the HOR and HER performance. This work provides a new pathway for designing efficient noble-metal-free electrocatalysts for the hydrogen economy.

Three-Dimensional Silver-Containing Polyoxotungstate Frameworks for Photocatalytic Aerobic Oxidation of Benzyl Alcohol.

Photocatalytic organic transformation derived by functionalized polyoxometalate (POM)-based metal-organic frameworks provides a feasible route for fine chemical synthesis. Herein, three kinds of photoactive three-dimensional silver-containing polyoxotungstate frameworks are synthesized with the formulas [Ag3L2(OH)][Na(H2O)0.5][PW12O40]·H2O (1), [Ag4L3][SiW12O40] (2), and [Ag(H2O)][Ag4L3][BW12O40]·9H2O (3) (L = 1,4-di(4H-1,2,4-triazol-4-yl)benzene). In compounds 1-3, the cationic Ag-triazole clusters with diverse nuclei serve as nodes to assemble with rigid bridging ligands (L) and polyoxoanions to extend into stable three-dimensional frameworks, in which Keggin-type anions act as guests or pendants. When using them as heterogeneous photocatalysts, compounds 1-3 show high catalytic activity and selectivity for the photocatalytic aerobic oxidation of benzyl alcohol to benzoic acid under 10 W 365 nm light irradiation. Among them, compound 1 exhibits the highest performance with ca. 99% benzyl alcohol conversion and 99% selectivity of benzoic acid in 9 h. Compounds 2 and 3 show ca. 79 and 88% conversions of benzyl alcohol, respectively, which are higher than those of the individual Keggin-type precursors. Moreover, mechanism investigation suggests that the synergistic cooperation occurring between cationic Ag-triazole clusters and Keggin-type polyoxoanions modulates the energy band structures of compounds 1-3, resulting in the efficient separation of photogenerated carriers and accelerating the aerobic oxidation of benzyl alcohol. This work provides some important guidance for the design and development of efficient POM-based photocatalysts for practical organic transformation.

Production of generic monoclonal antibody and development of chemiluminescence immunoassay for determination of 32 sulfonamides in chicken muscle.

A hapten of sulfabenzamide was first synthesized to generate a monoclonal antibody that simultaneously recognized 32 sulfonamides. The computational simulation showed that the 3D conformation, molecular bend angle, molecular volume, electronic charge of core structure of these drugs all showed influences on the antibody binding. The antibody was combined with a heterologous enzyme-labeled hapten to develop a direct competitive chemiluminescence enzyme linked immunosorbent assay for determination of the 32 sulfonamides in chicken muscle sample. The CRs of the optimized method for these drugs were in the range of 7.3%-1778%, and the IC50 values were in the range of 0.038-11.2 ng/g. The limits of detection for detection of these drugs in chicken were in the range of 0.03-26 ng/g. Their recoveries from the standards fortified blank chicken samples were in the range of 60.8%-97.1%. Therefore, this method could be used as a useful tool for routine screening sulfonamides residues in meat.

Determination of sulfonamides in meat with dummy-template molecularly imprinted polymer-based chemiluminescence sensor.

In this study, a molecularly imprinted polymer capable of recognizing 15 sulfonamides was first synthesized with sulfabenz as the dummy template. The calculation results from computation simulation showed that the specific 3D conformation of the template had an important influence on the polymer's recognition ability. Then, the polymer was used as recognition reagent to prepare a chemiluminescence sensor on a conventional 96-well microplate for the determination of the residues of 15 sulfonamides in meat (chicken and pork). Due to the 4-(imidazol-1-yl)phenol-enhanced luminol-H2O2 system, the limits of detection for the 15 analytes were in the range of 1.0-12 pg/mL. The recoveries from the standard fortified blank samples were in the range of 72.7-99%. Furthermore, one assay could be finished within 30 min, and the sensor could be reused 4 times. Therefore, this sensor could be used as a very useful tool for routine screening of residues of sulfonamides in meat samples. Graphical abstract Assay procedures of the molecularly imprinted polymer-based chemiluminescence sensor for determination of sulfonamides.

Preparation of a chemiluminescence sensor for multi-detection of benzimidazoles in meat based on molecularly imprinted polymer.

In this study, a molecularly imprinted polymer capable of recognizing 8 benzimidazoles was first synthesized. The computation simulation showed that the shape and size of used template were the main factors influencing its recognition ability. Then the polymer was used as recognition reagent to prepare a chemiluminescence sensor on conventional 96-well microplate. The sample solution and a HRP-labeled hapten were added into the microplate wells to perform competitive binding, and the light signal was initiated with 4-(imidazol-1-yl)phenol enhanced luminol-H2O2 system. The optimized sensor was used to determine the residues of 8 benzimidazoles in mutton and beef. Result showed that the sensor achieved ultrahigh sensitivity (limits of detection of 1.5-21 pg/mL), rapid assay process (18 min) and satisfactory recovery (65.8%-91.2%). Furthermore, this sensor could be reused for 4 times. Therefore, this sensor could be used as a rapid, simple, sensitive and durable tool for screening the residual benzimidazoles in meat.

Co-inhibition of epidermal growth factor receptor and insulin-like growth factor receptor 1 enhances radiosensitivity in human breast cancer cells.

BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) or insulin-like growth factor-1 receptor (IGF-1R) have been shown to closely correlate with radioresistance of breast cancer cells. This study aimed to investigate the impact of co-inhibition of EGFR and IGF-1R on the radiosensitivity of two breast cancer cells with different profiles of EGFR and IGF-1R expression. METHODS: The MCF-7 (EGFR +/-, IGF-1R +++) and MDA-MB-468 (EGFR +++, IGF-1R +++) breast cancer cell lines were used. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle distribution were measured by flow cytometry. Phospho-Akt and phospho-Erk1/2 were quantified by western blot. In vivo studies were conducted using MDA-MB-468 cells xenografted in nu/nu mice. RESULTS: In MDA-MB-468 cells, the inhibition of IGF-1R upregulated the p-EGFR expression. Either EGFR (AG1478) or IGF-1R inhibitor (AG1024) radiosensitized MDA-MB-468 cells. In MCF-7 cells, radiosensitivity was enhanced by AG1024, but not by AG1478. Synergistical radiosensitizing effect was observed by co-inhibition of EGFR and IGF-1R only in MDA-MB-468 cells with a DMF10% of 1.90. The co-inhibition plus irradiation significantly induced more apoptosis and arrested the cells at G0/G1 phase in MDA-MB-468 cells. Only co-inhibition of EGFR and IGF-1R synergistically diminished the expression of p-Akt and p-Erk1/2 in MDA-MB-468 cells. In vivo studies further verified the radiosensitizing effects by co-inhibition of both pathways in a MDA-MB-468 xenograft model. CONCLUSION: Our data suggested that co-inhibition of EGFR and IGF-1R synergistically radiosensitized breast cancer cells with both EGFR and IGF-1R high expression. The approach may have an important therapeutic implication in the treatment of breast cancer patients with high expression of EGFR and IGF-1R.

Correlation of dynamic changes in γ-H2AX expression in peripheral blood lymphocytes from head and neck cancer patients with radiation-induced oral mucositis.

BACKGROUND: To evaluate the role of γ-H2AX in peripheral blood lymphocytes (PBLs) as a predictive biomarker of the severity of oral mucositis (OM) in head and neck cancer (HNC) patients with receiving radiotherapy. METHODS: In vitro assays for evaluating DNA damage and repair kinetics were performed on blood samples withdrawn from 25 HNC patients undergoing radiotherapy or chemoradiotherapy before radiotherapy. As for the in vivo study, blood samples were also withdrawn before radiotherapy, and 1 hour after radiotherapy on the fourth and last days. Flow cytometry was used to assess the expression of γ-H2AX in PBLs. OM was assessed using the World Health Organization (WHO) scores twice a week and correlated with the expression of γ-H2AX. RESULTS: The in vitro assay results showed that patients with severe OM had higher γ-H2AX-specific relative fluorescence at various irradiation doses in the damage kinetics assay, with significantly higher γ-H2AX expression at 8 Gy (p = 0.039), and also at 24 hours after irradiation at a dose of 2 Gy in the repair kinetics assay, compared to the patients with mild OM (p = 0.008). The optimal cutoff value for relative fluorescence of γ-H2AX was 0.960, 24 hours post-irradiation. However, there were no significant differences in γ-H2AX expression at different times between the two groups, as assessed with the in vivo assay. CONCLUSIONS: These results suggest that the damage and repair kinetics of γ-H2AX from PBLs in the in vitro study may have predictive value for identifying the grades of OM among HNC patients prior to radiotherapy.

Simultaneous inhibition of EGFR and PI3K enhances radiosensitivity in human breast cancer.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling transduction pathway are common in cancer. This pathway is imperative to the radiosensitivity of cancer cells. We aimed to investigate the radiosensitizing effects of the simultaneous inhibition of EGFR and PI3K in breast cancer cells. METHODS AND MATERIALS: MCF-7 cell lines with low expression of EGFR and wild-type PTEN and MDA-MB-468 cell lines with high expression of EGFR and mutant PTEN were used. The radiosensitizing effects by the inhibition of EGFR with AG1478 and/or PI3K with Ly294002 were determined by colony formation assay, Western blot was used to investigate the effects on downstream signaling. Flow cytometry was used for apoptosis and cell cycle analysis. Mice-bearing xenografts of MDA-MB-468 breast cancer cells were also used to observe the radiosensitizing effect. RESULTS: Simultaneous inhibition of EGFR and PI3K greatly enhanced radiosensitizing effect in MDA-MB-468 in terms of apoptosis and mitotic death, either inhibition of EGFR or PI3K alone could enhance radiosensitivity with a dose-modifying factor (DMF(SF2)) of 1.311 and 1.437, radiosensitizing effect was further enhanced by simultaneous inhibition of EGFR and PI3K with a DMF(SF2) at 2.698. DNA flow cytometric analysis indicated that dual inhibition combined with irradiation significantly induced G0/G1 phase arrest in MDA-MB-468 cells. The expression of phosphor-Akt and phosphor-Erk1/2 (induced by irradiation and PI3K inhibitor) were fully attenuated by simultaneous treatment with both inhibitors in combination with irradiation. In addition, dual inhibition combined with irradiation induced dramatic tumor growth delay in MDA-MB-468 xenografts. CONCLUSIONS: Our study indicated that simultaneous inhibition of EGFR and PI3K could further sensitize the cancer cells to irradiation compared to the single inhibitor with irradiation in vitro and in vivo. The approach may have important therapeutic implication in the treatment of a subset of breast cancer patients with high expression of EGFR and deficient function of PTEN.

[Tumor necrosis factor alpha-308 polymorphism and asthenospermia].

OBJECTIVE: To investigate the relationship between -308 genotype polymorphism in the promoter region of the tumor necrosis factor alpha (TNFalpha) gene and asthenospermia in infertile men. METHODS: Allele-specific polymerase chain reaction (ASPCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to analyze the genotype at position -308 in the promoter region of the TNFalpha gene in 187 infertile male patients, who were divided into Groups A (asthenospermia, n = 60), B (oligoasthenozoospermia, n = 65) and C (infertile patients with normal sperm, n = 62). The levels of TNFalpha in the seminal plasma from these patients were measured by radioimmunoassay, and all the data were statistically analyzed by SPSS16.0. RESULTS: Groups A and B exhibited significant differences from C in the frequency of GA/AA at position 308 in the promoter region of the TNFalpha gene (21.67% and 26.15% versus 8.06%, P < 0.05). Spearman analysis showed a negative correlation between the GA + AA type of the TNFalpha-308 allele and the percentage of grade a + b sperm (r = -0.690, P < 0.05). The level of TNFalpha in the seminal plasma was significantly elevated in Groups A ([4.23 +/- 0.45] ng/ml) and B ([4.29 +/- 0.47] ng/ml) as compared with C ([4.03 +/- 0.66] ng/ml, P < 0.05), but with no significant differences between Groups A and B (P > 0.05). It was also significantly higher in the GA+AA ([4.61 +/- 0.29] ng/ml) than in the GGtype ([4.06 +/- 0.45] ng/ml, P < 0.05). CONCLUSION: Regardless of sperm density, the frequently of TNFalpha-308 GA/AA is negatively correlated with the percentage of grade a + b sperm, which may be associated with the level of TNFalpha in the seminal plasma. Accordingly, anti-TNFalpha therapy might be effective for asthenospermia, and the measurement of the TNFalpha level in the seminal plasma can be an auxiliary diagnostic marker for male infertility.