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Synopsis: Laparoscopy combined with retrieval bag is an effective method for disseminated peritoneal leiomyomatosis that can prevent the spreading of tumor fragments. [ABSTRACT FROM AUTHOR]

Based on the magnetohydrodynamics model, this study numerically investigated the influence of a transverse non-uniform magnetic field on the flow and heat transfer characteristics of molten salt in a conductive pipe. The magnetic field was constructed with three sections including gradient and uniform regions, which was fitting to real application of the magnetic field. The flow and heat transfer of molten salt were studied within the ranges of 0 ≤ Ha ≤ 200 and 3000 ≤ Re ≤ 12 000. The results indicated that variation of magnetic field had significant effects on the flow velocity, turbulent intensity, and Joule heat, thus influencing the temperature and the Nusselt number of molten salt. Although the flow in core region was suppressed by the magnetic field, the flow velocity was enhanced and turbulence was reduced near the pipe wall, which was shown obviously different within three regions of the magnetic field. An interesting phenomenon of local heat transfer enhancement with increasing magnetic intensity was observed in the first section of the magnetic field, which was from the complex effects of flow velocity and turbulence. In addition, the Joule heat was calculated and analyzed to determine its influence on heat transfer under the magnetic field. A detailed analyzation of magnetic fluid flow in this study was provided to hopefully promote the molten salt in real application of flow and heat transfer. [ABSTRACT FROM AUTHOR]

The layered Li2MnO3 is investigated by using the first-principles calculations within the GGA and GGA+U scheme, respectively. Within the GGA+U approach, the calculated intercalation voltage (ranges from 4.5 V to 4.9 V) is found to be in good agreement with experiments. From the analysis of electronic structure, the pure phase Li2MnO3 is insulating, which is indicative of poor electronic-conduction properties. However, further studies of lithium ion diffusion in bulk Li2MnO3 show that unlike the two-dimensional diffusion pathways in rock salt structure layered cathode materials, lithium can diffuse in a three-dimensional pathway in Li2MnO3, with moderate lithium migration energy barrier ranges from 0.57 to 0.63 eV. [ABSTRACT FROM AUTHOR]

Purpose: Cisplatin can cause a variety of DNA crosslink lesions including intra-strand and inter-strand crosslinks (ICLs), which are associated with the sensitivity of cancer cells to cisplatin. Here, we aimed to assess the contribution of the Fanconi anemia (FA), homologous recombination (HR) and nucleotide excision repair (NER) pathways to cisplatin resistance in non-small cell lung cancer (NSCLC)-derived cells. Methods: The expression of FA, HR and NER pathway-associated genes was assessed by RT-qPCR and Western blotting. siRNAs were used to knock down the expression of these genes. CCK-8 and flow cytometry assays were used to assess the viability and apoptotic rate of NSCLC-derived cells, respectively. Immunofluorescence and alkaline comet assays were used to assess the repair of ICLs. Results: We found that acquired cisplatin-resistant NSCLC-derived A549/DR cells exhibited markedly enhanced FA and HR repair pathway capacities compared to its parental A549 cells and another independent NSCLC-derived cell line, Calu-1, which possesses a moderate innate resistance to cisplatin. siRNA-mediated silencing of the FA-associated genes FANCL and RAD18 and the HR-associated genes BRCA1 and BRCA2 significantly potentiated the sensitivity of A549/DR cells to cisplatin compared to A549 and Calu-1 cells, suggesting that the acquired cisplatin resistance in A549/DR cells may be attributed to enhanced FA and HR pathway capacities responsible for ICL repair. Although we found that expression knockdown of the NER-associated genes XPA and ERCC1 sensitized the three NSCLC-derived cell lines to cisplatin, the sensitization effect was more significant in Calu-1 cells than in A549 and A549/DR cells, implying that the innate cisplatin resistance in Calu-1 cells may result from an increased NER activity. Conclusions: Our results indicate that the functional status of DNA repair pathways determine the sensitivity of NSCLC cells to cisplatin. Direct targeting of the pathway that is involved in cisplatin resistance may be an effective strategy to surmount cisplatin resistance in NSCLC. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer (NSCLC) with wild‐type epidermal growth factor receptor (EGFR) is intrinsic resistance to EGFR‐tyrosine kinase inhibitors (TKIs), such as afatinib. Celastrol, a natural compound with antitumor activity, was reported to induce paraptosis in cancer cells. In this study, intrinsic EGFR‐TKI‐resistant NSCLC cell lines H23 (EGFR wild‐type and KRAS mutation) and H292 (EGFR wild‐type and overexpression) were used to test whether celastrol could overcome primary afatinib resistance through paraptosis induction. The synergistic effect of celastrol and afatinib on survival inhibition of the NSCLC cells was evaluated by CCK‐8 assay and isobologram analysis. The paraptosis and its modulation were assessed by light and electron microscopy, Western blot analysis, and immunofluorescence. Xenografts models were established to investigate the inhibitory effect of celastrol plus afatinib on the growth of the NSCLC tumors in vivo. Results showed that celastrol acted synergistically with afatinib to suppress the survival of H23 and H292 cells by inducing paraptosis characterized by extensive cytoplasmic vacuolation. This process was independent of apoptosis and not associated with autophagy induction. Afatinib plus celastrol‐induced cytoplasmic vacuolation was preceded by endoplasmic reticulum stress and unfolded protein response. Accumulation of intracellular reactive oxygen species and mitochondrial Ca2+ overload may be initiating factors of celastrol/afatinib‐induced paraptosis and subsequent cell death. Furthermore, Celastrol and afatinib synergistically suppressed the growth of H23 cell xenograft tumors in vivo. The data indicate that a combination of afatinib and celastrol may be a promising therapeutic strategy to surmount intrinsic afatinib resistance in NSCLC cells. [ABSTRACT FROM AUTHOR]

Growing evidence suggest that transcription factors (TFs) play vital roles in serous ovarian cancer (SOC). In the present study, TFs mRNA expression profiles of 564 SOC subjects in the TCGA database, and 70 SOC subjects in the GEO database were screened. A 17-TFs related prognostic signature was constructed using lasso cox regression and validated in the TCGA and GEO cohorts. Consensus clustering analysis was applied to establish a cluster model. The 17-TFs related prognostic signature, risk score and cluster models were effective at accurately distinguishing the overall survival of SOC. Analysis of genomic alterations were used to elaborate on the association between the 17-TFs related prognostic signature and genomic aberrations. The GSEA assay results suggested that there was a significant difference in the inflammatory and immune response pathways between the high-risk and low-risk score groups. The potential immune infiltration, immunotherapy, and chemotherapy responses were analyzed due to the significant difference in the regulation of lymphocyte migration and T cell-mediated cytotoxicity between the two groups. The results indicated that patients with low-risk score were more likely to respond anti-PD-1, etoposide, paclitaxel, and veliparib but not to gemcitabine, doxorubicin, docetaxel, and cisplatin. Also, the prognostic nomogram model revealed that the risk score was a good prognostic indicator for SOC patients. In conclusion, we explored the prognostic values of TFs in SOC and developed a 17-TFs related prognostic signature to predict the survival of SOC patients. [ABSTRACT FROM AUTHOR]

Due to the DNA repair defect, BRCA1/2 deficient tumor cells are more sensitive to PARP inhibitors (PARPi) through the mechanism of synthetic lethality. At present, several PAPRi targeting poly (ADP-ribose) polymerase (PARP) have been approved for ovarian cancer and breast cancer indications. However, PARPi resistance is ubiquitous in clinic. More than 40% BRCA1/2-deficient patients fail to respond to PARPi. In addition, lots of patients acquire PARPi resistance with prolonged oral administration of PARPi. Homologous recombination repair deficient (HRD), as an essential prerequisite of synthetic lethality, plays a vital role in killing tumor cells. Therefore, Homologous recombination repair restoration (HRR) becomes the predominant reason of PARPi resistance. Recently, it was reported that DNA replication fork protection also contributed to PARPi resistance in BRCA1/2-deficient cells and patients. Moreover, various factors, such as reversion mutations, epigenetic modification, restoration of ADP-ribosylation (PARylation) and pharmacological alteration lead to PARPi resistance as well. In this review, we reviewed the underlying mechanisms of PARP inhibitor resistance in detail and summarized the potential strategies to overcome PARPi resistance and increase PARPi sensitivity. [ABSTRACT FROM AUTHOR]

The Lower Cambrian shale cores in southeast Chongqing were systematically collected, observed and described. Using total organic carbon content, XRD analyses, methane isothermal adsorption and nitrogen adsorption method, the nanoscale pore structure types, characteristics and influenced factors were analyzed and its impact on gas content was discussed. The results show that the nanoscale pore structures in the shale are complex, and are divided into three structure types based on the nitrogen adsorption-desorption curves and pore diameter distribution. The nanoscale pores mainly consist of cylinder pores with two open ends, slit type pores with parallel plates, and wedge shape pores with all sides open, which are related to the organic matter. The pore diameters are generally less than 60 nm, and have 2-5, 8-12 and 24-34 nm peak distributions. Total volume percentage of macropore (>50 nm) is 8. 5%,the BET surface area percentage is 0. 3%. Total volume percentage of mesopore (2-50 nm) is 82.1%, the BET surface area percentage is 79.0%. Total volume percentage of micropore (<2 nm) is 9.4%, and the BET surface area percentage is 20.7%. TOC is the main controlling factor of nanoscale pore structure characteristics and the organic matter is the material basis of total pore volume and BET surface area. There is an obvious linear correlation between total pore volume, BET surface area and gas adsorption capacity. [ABSTRACT FROM AUTHOR]

Background: To explore the association between serum human epidermal growth factor receptor 2 (HER 2) extracellular domain (ECD) levels and tissue HER 2 status in metastatic gastric cancer. Patients and Methods: HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ) patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH) and immunohistochemistry (IHC) assay. Results: Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren’s classification), liver metastasis, multiple metastasis (>2) and increased LDH levels, but not with overall survival. Conclusions: The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Platinum-based chemotherapy is the recognized first-line treatment for metastatic nasopharyngeal carcinoma (NPC). However there is no standard second-line treatment. This study was designed to evaluate the efficacy and safety of a gemcitabine and vinorelbine combination (GV) in patients with metastatic NPC previously treated with platinum-based chemotherapy. Methods: A total of 61 patients with metastatic NPC after prior platinum-based chemotherapy were enrolled. Gemcitabine (1000mg/m2) and vinorelbine (25mg/m2) were administered intravenously on Day 1 and Day 8 every 3weeks. Results: In this study, the overall response rate was 37.7% (95% CI, 25.5–49.9%) one complete response (1.6%) and 22 partial responses (36.1%). The median progression-free survival was 5.2months (95% CI, 3.4–7.0months) and the median overall survival was 14.1months (95% CI, 11.1–17.1months). Grade 3/4 toxicity including leucopenia (19.7%), neutropenia (18%), anemia (4.9%) and thrombocytopenia (6.5%) were tolerable. Univariate and multivariate analyses indicated age and salvage treatment after failure of GV treatment were independently significant prognostic factors. Conclusion: Our preliminary result shows gemcitabine and vinorelbine combination is effective and safe for the patients with advanced NPC pretreated with platinum-based chemotherapy. Further clinical study is warranted. [ABSTRACT FROM AUTHOR]

Abstract: A rapid and selective high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method for simultaneous determination of isoniazid (INH), rifampicin (RFP) and levofloxacin (LVX) in mouse tissues and plasma has been developed and validated, using gatifloxacin as the internal standard (I.S.). The compounds and I.S. were extracted from tissue homogenate and plasma by a protein precipitation procedure with methanol. The HPLC separation of the analytes was performed on a Welch materials C4 column (250mm×4.6mm, 5.0μm, USA) at 25°C, using a gradient elution program with the initial mobile phase constituting of 0.05% formic acid and methanol (93:7, v/v) at a flow-rate of 1.0ml/min. For all the three analytes, the recoveries varied between 83.3% and 98.8% in tissues and between 75.5% and 90.8% in plasma, the accuracies ranged from 91.7% to 112.0% in tissues and from 94.6% to 108.8% in plasma, and the intra- and inter-day precisions were less than 13.3% in tissues and less than 8.2% in plsama. Calibration ranges for INH were 0.11–5.42μg/g in tissues and 0.18–9.04μg/ml in plasma, for RFP were 0.12–1200μg/g in tissues and 4.0–200μg/ml in plasma, and for LVX were 0.13–26.2μg/g in tissues and 0.09–4.53μg/ml in plasma. The lower limits of quantification (LLOQs) for INH, RFP and LVX in mouse tissues were 0.11, 0.12 and 0.13μg/g and for those in mouse plasma were 18.1, 20.0 and 21.8ng/ml, respectively. The limits of detection (LODs) for INH, RFP and LVX in mouse tissues were 0.04, 0.05 and 0.05μg/g and for those in mouse plasma were 5.5, 6.0 and 6.6ng/ml, respectively. The established method was successfully applied to simultaneous determination of isoniazid, rifampicin and levofloxacin in mouse plasma and different mouse tissues. [ABSTRACT FROM AUTHOR]

Thermochomic VO 2 thin films are fabricated by using high power impulse magnetron sputtering at room temperature. In order to increase the crystallinity and transparency of VO 2 thin films, first a buffer layer of TiO 2 is deposited on the glass substrate. Then TiO 2 /VO 2 stacks are post-annealed at a temperature of 500 °C for 3 min. The transmittance as functions of film thickness and O 2 /Ar ratio during film deposition is discussed. It is found that the O/V atomic ratio decreases with increasing O 2 /Ar ratio, which is due to serious inter-diffusion inside stacked layers. At high O 2 /Ar ratio, columnar-shaped crystals are suggested, which belongs to V 2 Ti 3 O 9 :Si quaternary oxide. The depth profiles of binding energies measured by X-ray photoelectron spectroscopy are compared with different O 2 /Ar ratios. Good endurance property for a thermal stress cycle of 25 °C/85 °C is obtained under the O 2 /Ar ratio of 6%. The laminated film shows satisfactory optical properties with an excellent solar regulation efficiency (Δ T sol = 10.4%) and an applicable luminous transmittance (T lum = 35.2%) in a low-temperature state. • VO 2 films are fabricated by HIPIMS and annealed with a low thermal budget. • Films show good solar regulation efficiency and applicable luminous transmittance. • Good endurance properties are obtained. [ABSTRACT FROM AUTHOR]