Search

Herein, we developed a convenient and efficient method via protonation of p-toluenesulfonic acid promoted cyclocondensation of o-phenylenediamine and aldehydes for selectively synthesizing 1,2-disubstituted benzimidazoles. This method displayed broad substrate adaptability and afforded the desired products in moderate to excellent yield in short reaction time. The effect of different substituents on the yield was investigated by extending optimum reaction conditions, which was further confirmed by theoretical calculations. It suggested that the surface electrostatic potential of oxygen atom and nitrogen atom on the substrates played important role in the synthesis of 1,2-disubstituted benzimidazoles. Besides, the crystal structure of compound 2t in the orthorhombic space group P2(1)/c was presented. Also, the anti-mycolicibacterium smegmatis (MC2155) activity was evaluated using rifampicin as a positive control. The products (2a, 2b, 2c, 2i, 2j, 2k, 2m) showed good antibacterial activities which were comparable to rifampicin. [ABSTRACT FROM AUTHOR]

Background: Obesity not only affects physical and mental conditions, but also influences cognitive function. Endocrine hormones may influence the risk of obesity and severe obesity. Our study investigated the influences of changes in levels of endocrine hormones on cognitive function in patients with obesity and severe obesity. Methods: We used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in the groups of healthy control (HC), obesity (OB), and severe obesity (SOB). We detected the levels of endocrine hormones and cortisol at 8:00 am in the three groups. We statistically analyzed differences in cognitive function and levels of endocrine hormones among the three groups, and performed linear correlation analysis of cortisol level and cognitive function. Using mediation analysis, we assessed the influences of body mass index (BMI) on endocrine levels and cognitive function. Results: Our findings revealed that OB and SOB groups exhibited a lower level of cortisol than HC group. Among the three groups, we found significant differences in verbal learning (F = 4.433, P = 0.014), social cognition (F = 4.778, P = 0.010), and total cognition (F = 2.989, P = 0.008). After post hoc Bonferroni correction, we noted that SOB group had worse scores in the above-mentioned three areas than OB and HC groups. Moreover, except for working memory and visual cognition, we identified that the degree of cognitive impairment in SOB group was more severe than that in OB group. In our study, mediation analysis showed a mediating effect of BMI on cortisol level and verbal learning. We also found correlations between cortisol level and attention/alertness (r = 0.277, P = 0.003), between cortisol level and verbal learning (r = 0.205, P = 0.030), and between BMI and verbal learning (r = − 0.192, P = 0.043). Conclusion: In our study, patients in both OB and SOB groups experienced a widespread cognitive impairment. We also found that patients with severe obesity had more severe cognitive impairment. Cognitive impairment could be mediated by abnormal cortisol metabolism, and BMI could be a mediating factor in regulation of cortisol level. [ABSTRACT FROM AUTHOR]

Laser shock hole-clinching is a high–strain rate mechanical joining process in which the metal foils are joined together based on plastic deformation generated by a laser-induced shock wave. In the process, fracture is a typical defect and seriously influences the clinching quality and production efficiency of joints. However, the classification and variation of fracture modes in laser shock hole-clinching are of less concern. In this study, the fracture mode of Cu-Fe joints in laser shock hole-clinching was experimentally investigated. Both optical microscopy and scanning electron microscopy were adopted to analyze the fracture surface morphology of clinched joints. The influence of laser power density, laser spot diameter, the initial grain size and thickness of metal foil, and spacer height on the fracture mode of joints was evaluated. It is revealed that the temperature increase caused by high–strain rate plastic deformation has no impact on the fracture behavior of the joining partners. Fracture always occurs on joining partner I, and it can be divided into four modes, including bottom surface fracture, bottom corner fracture, neck fracture, and mixed fracture. It is found that fracture on the bottom surface is seldom seen but mixed fracture accounts for most of the cracked specimens. Neck tensile fracture rarely appears alone, and it usually exists accompanied by fracture on the bottom corner. The fracture mode varies from a tensile fracture mode on the bottom corner to a mixed fracture mode and then to a shear fracture mode on the neck with the enhancement of laser power density. In addition, the initial grain size of joining partner I has a significant impact on the fracture mode of clinched joints. The fracture mode varies from bottom corner fracture to mixed fracture in relation to the change of mechanical properties of metal foil with an enlarged grain size. However, the mixed fracture mode always appears with the enlargement of both laser spot diameter and spacer height. [ABSTRACT FROM AUTHOR]

Laser shock hole-clinching is a novel mechanical joining process in which the shock wave pressure induced by a high-energy pulsed laser is employed as a punch. This process is quite suitable for the joining of two dissimilar materials with significant differences in plasticity and strength. However, the effect of key process parameters on the forming quality of joints by laser shock hole-clinching is less concerned. In this study, the influence of laser power density, spacer height, number of laser pulse, and initial grain size of metal foils on the forming quality of Cu-Fe joints was experimentally investigated. The characteristics of interlock value and thinning rate distribution under various process parameters were systematically examined. It is revealed that laser shock hole-clinching process can be divided into the confined bulging and interlock formation stages. Based upon the examination of substandard joints, the defects in laser shock hole-clinching process are classified which contains no interlock, nonuniform interlock, bottom and neck fracture. It is found that the thinnest position of joints locates at the region in contact with the upper corner of the joining partner II in which extensive plastic deformation occurs related to the force acting during clinching process. The interlock value increases significantly as the enlargement of initial grain size, whereas the deviation also becomes larger due to the inhomogeneous plastic deformation for the metal foil with coarse grains. Moreover, the ratio of spacer height to the thickness of the joining partner II affects the thinning rate distribution and interlock value of joints. The spacer height equaling to the thickness of the joining partner II is recommended within the given parameters. [ABSTRACT FROM AUTHOR]

Background: The tumor-node-metastasis classification system has proposed that lung cancers presenting as multifocal ground-glass nodules (multi-GGN) on computed tomography scan should be staged as multiple primaries instead of intrapulmonary metastases. However, the problem still exists for those synchronous multiple lung adenocarcinomas (SMLA) involving solid lesions. This study aimed to explore the distinct features of SMLA to better define the diagnosis and staging of this disease. Methods: Between 2008 and 2016, consecutive patients with complete resection of SMLA were prospectively enrolled in the study. The patients were divided into three groups based on CT images as follows: multi-GGN, one solid nodule plus one or more GGNs (solid-GGN), and multiple solid lesions with or without GGN (multi-solid). Clinicopathologic features and survival outcomes were compared between these groups. Multivariate Cox proportional hazards analyses using bootstrap internal validation were performed to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS). Results: Of the 695 patients who met the inclusion criteria, 486 (69.9%) presented with multi-GGN tumor, 124 (17.9%) with solid-GGN tumor, and 85 (12.2%) with multi-solid tumor. The three groups had distinguished clinicopathologic features of gender, smoking history, nodal metastases, tumor size, subtype, and location (all P < 0.001). Multivariate analyses demonstrated that multi-solid tumor was an independent predictor for both decreased RFS [hazard ratio (HR) 2.941; 95% confidence interval (CI) 1.07–8.08; P = 0.036] and poor OS (HR 6.13; 95% CI 1.15–32.63; P = 0.034), but neither RFS (P = 0.384) nor OS (P = 0.811) differed between solid-GGN and multi-GGN tumors. Conclusions: Both multi-GGN and solid-GGN tumors should be staged as multiple primaries, whereas multi-solid tumor was indicated to be advanced disease. [ABSTRACT FROM AUTHOR]

Recently, based on the tremendous progresses in performance of perovskite solar cells (PSCs), the inverted planar PSCs have attracted attentions for future applications. Since the traditional poly(3,4-ethylenedioxythiophene) hole transport layer could cause a loss of open-circuit voltage (Voc), some organic and inorganic alternatives have been widely investigated. However, the Voc is still below for the demand of optimized value. Here, we demonstrate that the reduced graphene oxide (RGO) doping is a facile and effective method to make molybdenum oxide (MoOx) as a promising hole transport layer (HTL) for high-performance PSCs. The conductive MoOx:RGO HTL can facilitate perovskite crystallization and reduce the potential losses of Voc in devices. Thus, a high PCE of up to 18.15% is achieved which simultaneously possesses a high Voc of 1.12 V. With this strategy, the MoOx:RGO provides a novel hole transport layer for high performance and decently stable optoelectronic devices. More importantly, it opens up the research significance of doping in inorganic buffer interlayers for the perovskite solar cells. [ABSTRACT FROM AUTHOR]

Introduction: Mutated tumor suppressor genes (TSG) such as TP53, STK11, and MGA are widely-reported. We hypothesized the presence of single mutation or co-occurring mutations in these specific genes may represent a significant therapeutic target for lung adenocarcinoma.Methods: We sequenced lung adenocarcinoma samples from 677 East-Asian patients, combined them with those from cBioPortal public database (including TCGA) and performed a comparative analysis between Asian and Caucasian populations.Results: East-Asian lung adenocarcinomas presented distinct driver-mutational distribution compared to that of Caucasians (79% vs 56%, p < 0.001). Similar results were observed in TSG mutations of TP53 (35% vs 46%, p = 0.150), STK11 (4% vs 17%, p = 0.006) and MGA (10% vs 4%, p = 0.166). Compared with none-mutational cases, the patients harboring TSG mutations are more likely to be male (p = 0.009), smokers (p < 0.001), and more advanced disease (p = 0.004). In addition, the TSG-mutated tumors had poorer differentiation (p < 0.001), and more likely to be solid or micropapillary-predominant adenocarcinomas (p < 0.001). Survival analysis showed that both overall survival (OS, p < 0.001) and post-recurrence survival (PRS, p < 0.001) became worse with the accumulation of TSG mutations. However, the prognostic variety was not found in Caucasian patients. Moreover, multivariate analysis proved the accumulation of TSG mutations independently predicts both unfavorable OS (HR = 0.435, 95% CI 0.245-0.774, p = 0.005) and PRS (HR = 0.491, 95% CI 0.269-0.894, p = 0.020) in East-Asian patients, adjusting all other survival-associated factors.Conclusions: Co-occurring mutations of specific TSGs define unfavorable subgroups of lung adenocarcinoma, implying that the tumor promotion mechanisms contribute to the heterogeneity in tumor evolution. However, the Caucasian population did not show the same results, providing insights into the molecular basis underlying the striking racial disparities of this disease and evidence for different gene-panel designs for different population in the purpose of targeted therapy. [ABSTRACT FROM AUTHOR]

Introduction: Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown. Methods: We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes. Results: Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858R patients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R ( p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p < 0.001) were independent predictors of PRS. The 19del and L858R patients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007). Conclusions: Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS. [ABSTRACT FROM AUTHOR]

Purpose: To define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor ( EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients. Methods: A total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated. Results: EGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis ( P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [ P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR ( P < 0.001) and HER3 ( P = 0.016). In addition, higher expression of p-Akt ( P = 0.007) and lower expression of p-Erk ( P = 0.009) were observed in tumors with exon 20 insertion mutations. Conclusions: Lung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations. [ABSTRACT FROM AUTHOR]

Purpose: Current criteria for identification of synchronous non-small cell lung cancers (NSCLCs) may be confusing in patients with lymphatic metastases. This study was aimed at investigating the strategy using both the new histologic classification and driver-mutational testing to define multiple primary lung cancers. Methods: Prospectively collected data of surgical patients with synchronous NSCLCs were retrospectively analyzed. Cases were defined using the Martini-Melamed criteria, and validated by histologic subtyping based on the new classification and driver mutation of selected genes. Survival was estimated between patients with multiple primary and metastatic disease controlling by nodal (N) stage. Factors associated with prolonged survival were evaluated using the Cox proportional hazards mode. Results: A total of 131 patients followed for at least 12 months were included in this study. Controlling by N0 stage, patients who were diagnosed with multiple primary NSCLCs showed better relapse-free survival (RFS) than those with intrapulmonary metastases categorized either by the Martini-Melamed criteria or by histologic-mutational methods (both p < 0.0001). However, at N+ stage, patients stratified by Martini-Melamed criteria showed no difference in survival ( p = 0.517), while those defined by histologic-mutational methods maintained superior survival compared with the control group ( p = 0.042). On multivariate analysis, only N0 and diagnosis of independent lung lesions by histologic-mutational methods were significant predictors of better RFS ( p = 0.031 and 0.001, respectively) Conclusions: The histologic-mutational strategy may be an option for identification of synchronous NSCLC when traditional criteria were not applicable, especially in cases with positive lymphatics. N0 stage and the diagnosis of independent pulmonary tumors were associated with better RFS. [ABSTRACT FROM AUTHOR]