TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer.

Ovarian cancer is a major cause of death among cancer patients. Recent research has shown that the transmembrane emp24 domain (TMED) protein family plays a role in the progression of various types of cancer. In this study, we investigated the expression of TMED3 in ovarian cancer tumors compared to nontumor tissues using immunohistochemical staining. We found that TMED3 was overexpressed in ovarian cancer tumors, and its high expression was associated with poor disease-free and overall survival. To understand the functional implications of TMED3 overexpression in ovarian cancer, we conducted experiments to knockdown TMED3 using short hairpin RNA (shRNA). We observed that TMED3 knockdown resulted in reduced cell viability and migration, as well as increased cell apoptosis. Additionally, in subcutaneous xenograft models in BALB-c nude mice, TMED3 knockdown inhibited tumor growth. Further investigation revealed that SMAD family member 2 (SMAD2) was a downstream target of TMED3, driving ovarian cancer progression. TMED3 stabilized SMAD2 by inhibiting the E3 ligase NEDD4-mediated ubiquitination of SMAD2. To confirm the importance of SMAD2 in TMED3-mediated ovarian cancer, we performed functional rescue experiments and found that SMAD2 played a critical role in this process. Moreover, we discovered that the PI3K-AKT pathway was involved in the promoting effects of TMED3 overexpression on ovarian cancer cells. Overall, our study identifies TMED3 as a prognostic indicator and tumor promoter in ovarian cancer. Its function is likely mediated through the regulation of the SMAD2 and PI3K-AKT signaling pathway. These findings contribute to our understanding of the molecular mechanisms underlying ovarian cancer progression and provide potential targets for therapeutic intervention.

Near-noiseless and small-footprint phase sensitive optical parametric amplifier using AlGaAs-on-insulator waveguides.

Phase sensitive amplifiers (PSAs) based on optical parametric amplification feature near noiseless amplification, which is of considerable benefit for improving the performance of optical communication systems. Currently, the majority of research on PSAs is carried out on the basis of highly nonlinear fibers or periodically poled lithium niobite waveguides, with the impediments of being susceptible to environmental interference and requiring complex temperature control systems to maintain quasi-phase matching conditions, respectively. Here, a near-noiseless and small-footprint PSA based on dispersion-engineered AlGaAs-on-insulator (AlGaAsOI) waveguides is proposed and demonstrated theoretically. The phase-dependent gain and the phase-to-phase transfer function of the PSA are calculated to analyze its characteristics. Furthermore, we investigate in detail the effects of linear loss, nonlinear coefficient, and pump power on the PSA gain and noise figure (NF) in AlGaAsOI waveguides. The results show that a PSA based on an AlGaAsOI waveguide is feasible with a maximum phase sensitive gain of 33 dB, achieving an NF of less than 1 dB over a gain bandwidth of 245 nm with a gain of >15d B, which completely covers the S + C + L band. This investigation is worthwhile for noiseless PSAs on photonic integrated chips, which are promising for low-noise optical amplification, multifunctional photonic integrated chips, quantum communication, and spectroscopy, and as a reference for low-noise PSAs depending on the third-order nonlinearity, χ (3), of the waveguide material.

Evaluating blended learning effectiveness: an empirical study from undergraduates' perspectives using structural equation modeling.

Following the global COVID-19 outbreak, blended learning (BL) has received increasing attention from educators. The purpose of this study was: (a) to develop a measurement to evaluate the effectiveness of blended learning for undergraduates; and (b) to explore the potential association between effectiveness with blended learning and student learning outcomes. This research consisted of two stages. In Stage I, a measurement for evaluating undergraduates' blended learning perceptions was developed. In Stage II, a non-experimental, correlational design was utilized to examine whether or not there is an association between blended learning effectiveness and student learning outcomes. SPSS 26.0 and AMOS 23.0 were utilized to implement factor analysis and structured equation modeling. The results of the study demonstrated: (1) The hypothesized factors (course overview, course objectives, assessments, 1148 class activities, course resources, and technology support) were aligned as a unified system in blended learning. (2) There was a positive relationship between the effectiveness of blended learning and student learning outcomes. Additional findings, explanations, and suggestions for future research were also discussed in the study.

Is valve-sparing aortic root replacement better than total aortic root replacement? An overview of reviews.

Background: Total aortic root replacement (TRR) is certainly beneficial for aortic root disease, but does it still have an advantageous prognosis for patients compared to valve-sparing aortic root replacement (VSRR)? An overview of reviews was conducted to assess each of their clinical efficacy/effectiveness. Review methods: Systematic reviews (SRs)/Meta-analyses comparing the prognosis of TRR and VSRR in aortic root surgery were collected from 4 databases, all searched from the time of database creation to October 2022. Two evaluators independently screened the literature, extracted information and applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) tool, Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and Risk of Bias in Systematic Reviews (ROBIS) to evaluate the quality of reporting, methodological quality, risk of bias, and level of evidence of the included studies. Main results: A total of 9 SRs/Meta-analyses were ultimately included. In terms of the reporting quality of the included studies, PRISMA scores ranged from 14 to 22.5, with issues mainly in reporting bias assessment, risk of study bias, credibility of evidence, protocol and registration, and funding sources. The methodological quality of the included SRs/Meta-analyses was generally low, with key items 2, 7, and 13 having major flaws and non-key items 10, 12, and 16. In terms of risk of bias assessment, the overall assessment of the included 9 studies was high-risk. The quality of the evidence was rated as low to very low quality for the three outcome indicators selected for the GRADE quality of evidence rating: early (within 30 days postoperatively or during hospitalization) mortality, late mortality, and valve reintervention rate. Conclusions: VSRR has many benefits including reduced early and late mortality after aortic root surgery and reduced rates of valve-related adverse events, but the methodological quality of the relevant studies is low, and there is a lack of high-quality evidence to support this. Systematic Review Registration: https://www.PROSPERO, identifier: CRD42022381330.

Associations between the helpfulness of teacher induction programs, teacher self-efficacy, and anticipated first-year teacher retention.

First-year teachers need help because they are confronted with various challenges and are more likely to leave the profession within a few years. Studies have demonstrated the efficacy of evidence-based teacher induction programs (TIPs) in enhancing the performance of new teachers and promoting positive student outcomes. However, there has been opposition to this assertion, with some suggesting alternative explanations for the observed effects. This study applied Horn et al's high-quality TIP model as the theoretical framework and employed a non-experimental, correlational design to address the research questions by collecting data from 408 first-year primary school teachers in Shanghai. Correlations and multiple regressions were examined in the study. The results revealed the following: (1) the perceptions of the helpfulness of TIP were not found to correlate significantly with teacher self-efficacy; (2) there was a limited negative correlation (r = -0.142, p < 0.01) between self-efficacy and anticipated retention, suggesting that higher self-efficacy scores were associated with low anticipated retention, contrary to the study's hypothesis; (3) anticipated retention was found to be significantly affected by gender, major, and ratings of TIP. Anticipated retention was found to be significantly affected by gender, major, and ratings of TIP helpfulness. The results, implications, and recommendations are discussed further in the study.

Fourier Transform Infrared Spectrometry Detection of Phaeodactylum tricornutum Biomacromolecules in Response to Environmental Changes.

Environmental factors play an important role in the lipid, protein, and carbohydrate compositions of microalgae, wherein temperature and light are key influencing factors. Fourier transform infrared (FTIR) spectrometry was used in this study to detect biomacromolecules in Phaeodactylum tricornutum cells under different temperatures (10, 15, 20, and 25 °C) and different illumination conditions (1000, 2000, 3000, and 4000 lx) to study the corresponding changes in lipid, protein, and carbohydrate contents. Results indicate that the biomacromolecule content at different temperatures has different patterns. Specifically, the patterns at 15 and 25 °C are similar to each other and the contents accumulate with extended culture time. However, the pattern at 20 °C is different. The carbohydrate and protein contents peaked during the early stage of the exponential phase, whereas lipid accumulation lagged behind the former two, peaking during the middle of the culture stage and then decreasing. Lipid content was analyzed by transmission electron microscopy (TEM), which revealed that the highest lipid content was observed at 15 °C. Results also show that all of the lipid, protein, and carbohydrate contents in cells were the highest when the illumination was at 2000 lx and that the contents decreased with increasing illumination. By using FTIR, less samples were needed as compared to the traditional chemical quantitative detection methods. Moreover, the relative content changes of various biomacromolecules during the growth of P. tricornutum could be accurately determined by a single detection, thereby providing a new technique for the further study of metabolic mechanisms.

Hsa_circ_0001944 enhanced GSPT1 expression via sponging miR-498 to promote proliferation and invasion of gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. CircRNAs may provide new insights into the development of GC by acting as oncogenes or tumor suppressors. In this study, we aim to examine the biological role of hsa_circ_0001944 (circFIRRE) in tumor progression of GC. METHODS: The bioinformatic analysis, qPCR, Western blotting, and immunohistochemistry were fulfilled to detect the expression of hsa_circ_0001944, miR-498, and GSPT1 in gastric cancer. Gain or loss of function approaches were used to investigate the biological functions of hsa_circ_0001944. MTS, EDU, wound healing, and transwell assays were performed to study the proliferation, invasion, and migration of GC cells. These molecular mechanisms were detected by luciferase reporter assays and chromatin immunoprecipitation assays. RESULTS: We screened out hsa_circ_0001944, whose expression was significantly increased in gastric cancer tissues. Knockdown of hsa_circ_0001944 significantly suppressed the cell proliferation, invasion, and migration. Mechanistic investigations showed that hsa_circ_0001944 can bind to and sponge miR-498. Moreover, hsa_circ_0001944 sponged miR-498 to increase GSPT1 expression, thereby promoted excessive proliferation and maintained the malignant phenotype of GC cells. CONCLUSION: The present study demonstrates the hsa_circ_0001944/miR-498/GSPT1 axis contributes to GC development. This may provide a target for GC therapy and potential prognostic biomarker.

Energy metabolism response induced by microplastic for marine dinoflagellate Karenia mikimotoi.

Microplastic contaminations threaten the entire marine ecosystem and cause severe ecological stress. This study explored the energy metabolism change of Karenia mikimotoi under exposure to nanoplastics (NPs) and microplastics (MPs) (65 nm, 100 nm, and 1 µm polystyrene (PS), and 100 nm polymethyl methacrylate (PMMA)) at a concentration of 10 mg L-1. Membrane potential, esterase activity, polysaccharide content, and ATPase activity were detected to assess the energy metabolism of K. mikimotoi under MPs/NPs exposure. Transcriptome and metabolomic analyses were used to investigate the intrinsic mechanisms of energy metabolism changes. Smaller PS particles caused greater damage to the cell membrane potential, increased the polysaccharide content, and resulted in a heavier weakening of the ATPase enzymatic activity in K. mikimotoi cells, suggesting that smaller-sized PS had more influence on esterase activity and energy metabolism than the bigger-sized PS. The results evidenced that energy metabolism relates to the size and type of MPs/NPs, and nano-scale plastic particles could induce greater metabolic changes.

Microplastic-induced apoptosis and metabolism responses in marine Dinoflagellate, Karenia mikimotoi.

Microplastics (MPs) occur widely in marine environments, and disturb the balance of aquatic ecosystems. In this study, programmed cell apoptosis in marine dinoflagellate, Karenia mikimotoi exposed to 10 mg L-1 micro/nanoplastics (MPs/NPs; polystyrene and polymethyl methacrylate) for 72 h was assessed. Prior to the toxicity assay, MPs/NPs were dialyzed to remove possible additives. Cell viability, membrane integrity, cell apoptosis, and total DNA concentration were measured to assess programmed cell apoptosis in K. mikimotoi following exposure to MPs/NPs. A transcriptome analysis was used to explore the potential toxic mechanism of MPs to K. mikimotoi. Programmed cell apoptosis was related to the size of MPs/NPs, and NPs could more easily impair cell viability, and reduced cell membrane integrity and DNA concentration. NP particles caused continuous apoptosis of K. mikimotoi compared to MP particles. Size had the greatest effect on toxicity in K. mikimotoi. In conclusion, the results evidenced that both MPs and NPs have a negative impact on the marine dinoflagellate, K. mikimotoi. However, NPs were more harmful to K mikimotoi than MPs, highlighting the potential ecological problems associated with exposure to NPs.

Rapid and sensitive detection of Karenia mikimotoi by loop-mediated isothermal amplification combined with a lateral flow dipstick.

Harmful algal blooms frequently occur in various coastal regions worldwide, deteriorating marine ecology and causing huge economic losses. Therefore, developing a potential method for rapid detection of harmful algae species is highly necessitated. In this study, a loop-mediated isothermal amplification (LAMP) method coupled with a lateral flow dipstick (LFD) was developed for detecting the harmful algae Karenia mikimotoi. In this method, the internal transcribed spacer (ITS) sequence of K. mikimotoi was used as the template, and the corresponding specific primers were designed by the online software PrimerExplorer V5. Biotin was labeled on the 5' end of forward inner primer (FIP), and the LAMP reaction was performed under the determined optimal conditions of 63℃ and 60 min. The lowest concentration of K. mikimotoi DNA tested using LAMP was 3.3 × 10-1 pg/µL. Additionally, a 6-FAM-labeled probe was designed and displayed on the LFD after hybridization of the amplified product with the probe. The results demonstrated that LAMP-LFD could be a promising approach for detecting and monitoring harmful algae due to its high sensitivity and specificity.

Extraperitoneal laparoscopy for para-aortic lymphadenectomy in endometrial carcinoma staging: an approach with higher efficiency.

BACKGROUND: Removing more inframesenteric nodes is not only significantly increases the likelihood of finding metastasis for endometrial cancer, but also can add survival advantage. As most patients diagnosed with endometrial cancer are overweight or obesity, a high efficiency approach is important. Aim of this study was to compare the surgical outcomes of extraperitoneal laparoscopic, transperitoneal laparoscopic, and laparotomic para-aortic lymphadenectomy in endometrial carcinoma staging. METHODS: We retrospectively reviewed data of all patients diagnosed with primary endometrial carcinoma who were treated at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from 1 January 2017 to 31 December 2019. The numbers of para-aortic lymph nodes, surgical time, complications, blood loss and hospital stay were compared. The patients' medical records and pathological reports were carefully reviewed. Statistical significance was defined as p < 0.05. RESULTS: We retrospectively compared patients who underwent extraperitoneal laparoscopy (Group E, n = 20), transperitoneal laparoscopy (group T, n = 21), and laparotomy (group L, n = 135). The median number of para-aortic lymph nodes was significantly higher in group E than in groups T and L (9.5, 5, and 6, respectively; p = 0.004 and 0.0004, respectively). All patients in group E underwent successfully dissection to the renal vessel level. The median operation time was significantly shorter in group L than in groups T and E (94, 174, and 233 min, respectively; p < 0.0001). The median estimated blood loss volume was higher in group L than in groups T and E (200, 100, and 142.5 ml, respectively; all comparisons p < 0.001), and the length of hospital stay was significantly longer in group L than in Groups T and E (6, 5, and 6 days, respectively; all comparisons p < 0.001). CONCLUSION: The extraperitoneal laparoscopic approach for staging endometrial carcinoma harvested higher numbers of para-aortic lymph nodes which could be considered for endometrial carcinoma staging, especially for para-aortic lymph node harvest.

Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia.

BACKGROUND: Epithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC. METHODS: Bioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment. RESULTS: EOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment. NPTX2 knockdown abolished the hypoxia-induced malignant phenotypes in ECO. CONCLUSIONS: The above results suggest that NPTX2 may play a novel role in ovarian cancer's malignant phenotype and act as a promising treatment target for EOC molecular therapy.

Rapid nitrate determination with a portable lab-on-chip device based on double microstructured assisted reactors.

Determining the nitrate levels is critical for water quality monitoring, and traditional methods are limited by high toxicity and low detection efficiency. Here, rapid nitrate determination was realized using a portable device based on innovative three-dimensional double microstructured assisted reactors (DMARs). On-chip nitrate reduction and chromogenic reaction were conducted in the DMARs, and the reaction products then flowed into a PMMA optical detection chip for absorbance measurement. A significant enhancement of reaction rate and efficiency was observed in the DMARs due to their sizeable surface-area-to-volume ratios and hydrodynamics in the microchannels. The highest reduction ratio of 94.8% was realized by optimizing experimental parameters, which is greatly improved compared to conventional zinc-cadmium based approaches. Besides, modular optical detection improves the reliability of the portable device, and a smartphone was used to achieve a portable and convenient nitrate analysis. Different water samples were successfully analysed using the portable device based on DMARs. The results demonstrated that the device features fast detection (115 s per sample), low reagent consumptions (26.8 µL per sample), particularly low consumptions of toxic reagents (0.38 µL per sample), good reproducibility and low relative standard deviations (RSDs, 0.5-1.38%). Predictably, the portable lab-on-chip device based on microstructured assisted reactors will find more applications in the field of water quality monitoring in the near future.

Role of adjuvant therapy after radical hysterectomy in intermediate-risk, early-stage cervical cancer.

OBJECTIVE: Adjuvant treatment remains a controversial issue for intermediate-risk cervical cancer. The aim of this study was to compare the prognosis of patients who underwent no adjuvant treatment, pelvic radiotherapy alone, or concurrent chemoradiotherapy after radical hysterectomy for intermediate-risk, early-stage cervical cancer. METHODS: Patients with stage IB1-IIA2 (FIGO 2009) cervical squamous cell carcinoma treated with radical hysterectomy and pelvic lymph node dissection, with negative lymph nodes, surgical margins, or parametria, who had combined intermediate risk factors as defined in the Gynecologic Oncology Group trial (GOG-92; Sedlis criteria) were included in the study. Recurrence-free survival and disease-specific survival were compared. RESULTS: Of 861 patients included in the analysis, 85 patients received no adjuvant treatment, 283 patients were treated with radiotherapy, and 493 patients with concurrent chemoradiotherapy. After a median follow-up of 63 months (IQR 45 to 84), adjuvant radiotherapy or concurrent chemoradiotherapy was not associated with a survival benefit compared with no adjuvant treatment. The 5-year recurrence-free survival and corresponding disease-specific survival were 87.1%, 84.2%, 89.6% (p=0.27) and 92.3%, 87.7%, 91.4% (p=0.20) in the no adjuvant treatment, radiotherapy alone, and concurrent chemoradiotherapy groups, respectively. Lymphovascular space invasion was the only independent prognostic factor for both recurrence-free survival and disease-specific survival. Additionally, significant heterogeneity exists in Sedlis criteria: higher risk of relapse (HR=1.88; 95% CI 1.19 to 2.97; p=0.007) and death (HR=2.36; 95% CI 1.41 to 3.95; p=0.001) occurred in patients with lymphovascular space invasion and deep 1/3 stromal invasion compared with no lymphovascular space invasion, middle or deep 1/3 stromal invasion, and tumor diameter ≥4 cm. CONCLUSIONS: Radical hysterectomy alone without adjuvant treatment may achieve a favorable survival for patients with intermediate-risk cervical cancer as defined by Sedlis criteria. Criteria for adjuvant treatment in patients without high risk factors need to be further evaluated.

A Portable and Accurate Phosphate Sensor Using a Gradient Fabry-Pérot Array.

Here, a portable and accurate phosphate sensor using a gradient Fabry-Pérot array (FPA) is proposed. It can form a bidirectional gradient concentration (absorbance) distribution in the gradient FPA, simplifying the complex operations to get a standard curve and saving time. The gradient FPA can effectively filter out the interference (bubbles, light intensity, and salinity) while improving the absorbance, achieving a highly accurate and stable detection. Besides, the smartphone simplifies data processing and makes sensors more portable. In this work, the detection errors of standard solutions (100, 50, and 30 µM) are 0.39, 1.48, and 1.84%, respectively, and it has also been demonstrated with errors of 2.46 (sample 1, seawater), 2.08 (sample 2, lake water), and 1.83% (sample 3, sewage) for natural samples detection, which is more accurate than a traditional analyzer. The sensor has a good performance when affected by bubbles, light intensity, and salinity. In addition, the detection time is shortened to 80 s, which is more time saving compared with traditional devices, and the limit of detection (LOD) is 0.4 µM. It can be predicted that the novel optofluidic sensor is conducive to build a smart nutrient monitoring system and will be applied in the field of biochemistry and environmental chemistry.

Effect of Temperature on Biological Macromolecules of Three Microalgae and Application of FT-IR for Evaluating Microalgal Lipid Characterization.

This study had shown the growth of Phaeodactylum tricornutum, Chlorella vulgaris, and Nannochloropsis sp. under different temperatures and their structure and relative content of polysaccharide, protein, and lipid. Lipid was more suitable to accumulate under the condition of low temperature; however, polysaccharide and protein were not; they had a similar change trend but different amounts. The correlation between the relative content of the lipid and the total lipid and fatty acid in a single microalga cell was also analyzed. The results showed that the relative content of the lipid detected by Fourier transform infrared (FTIR) spectroscopy and the total lipid and the unsaturated fatty acids (UFAs) obtained by a gravimetric method in a single microalga cell had a good linear relationship (R 2 ≈ 0.8) while the correlation of saturated fatty acids is poor (R 2 < 0.5). These studies had demonstrated that temperature was a key factor for phytoplankton that can influence their growth and biological macromolecule content. Moreover, FTIR spectroscopy was proved to be a meaningful technology for selecting the microalgae rich in total lipid and UFAs.

Distinctive clinicopathologic characteristics and prognosis for different histologic subtypes of early cervical cancer.

OBJECTIVES: To compare clinicopathologic characteristics and prognosis for different histologic subtypes in early cervical cancer. METHODS: Patients who underwent radical surgery for stage IA2-IIA2 cervical cancer with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma between March 2006 and February 2014 at our institution were retrospectively evaluated. The two-sample t-test was used to compare the mean values of continuous variables. The Chi-square test was used to assess differences in the distribution of categorical variables. Survival curves were generated by the Kaplan-Meier method using log-rank test. Univariable and multivariable analyses were performed using Cox regression analysis. RESULTS: Of 5181 patients evaluated, 4510 had squamous cell carcinoma, 488 had adenocarcinoma, and 183 had adenosquamous carcinoma. Compared with squamous cell carcinoma, adenocarcinoma was associated with earlier stage, smaller tumor size, less lymphovascular space invasion (26.7% vs 37.9%), less deep (>2/3 depth) stromal invasion (30.4% vs 36.2%), and more ovarian metastasis (4.2% vs 0.7%) (all p<0.001). Compared with adenosquamous carcinoma, adenocarcinoma was associated with earlier stage (p=0.011), smaller tumor size (p<0.001), less lymphovascular space invasion (26.7% vs 41.5%, p<0.001), and less peripheral nerve infiltration (5.7% vs 15.4%, p<0.001). Except for more peripheral nerve infiltration in adenosquamous carcinoma (15.4% vs 8.4%, p=0.002), no significant differences in other clinicopathologic characteristics were noted between squamous cell carcinoma and adenosquamous carcinoma. Five-year recurrence-free survival was 85.1%, 78.2%, and 72.3% for squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, respectively (p<0.001). Corresponding 5-year overall survival was 89.7%, 83.1%, and 79.6%, respectively (p<0.001). In multivariable analysis, adenocarcinoma and adenosquamous carcinoma were independent prognostic factors for worse recurrence-free survival for adenocarcinoma versus squamous cell carcinoma (HR 2.594 (95% CI 2.030 to 3.316), p<0.001) and for adenosquamous carcinoma versus squamous cell carcinoma (HR 2.105 (95% CI 1.517 to 2.920), p<0.001), and overall survival for adenocarcinoma versus squamous cell carcinoma (HR 2.976 (95% CI 2.226 to 3.977), p<0.001) and for adenosquamous carcinoma versus squamous cell carcinoma (HR 2.295 (95% CI 1.579 to 3.338), p<0.001). CONCLUSION: Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma carried distinctive patterns of clinicopathologic characteristics. Adenocarcinoma and adenosquamous carcinoma had worse survival outcomes than squamous cell carcinoma.

Effects and improvements of different reagents preservation methods on the determination of phosphate in seawater by phosphomolybdenum blue spectrophotometric method.

This work attempted to prolong the validity of the molybdate mixed solution and ascorbic acid solution used in the phosphomolybdenum blue spectrophotometric method by improving their preservation according to the influence factors. The results showed that the molybdate mixed solution can be directly preserved in darkness with validity over half a year. The ascorbic acid solution is influenced by light, temperature, pH, metal ions, oxygen, and bacteria. The validity of ascorbic acid is shortened as the temperature rises. Through keeping in darkness, adding complexing agents, adjusting pH, removing oxygen and sterilization, the validity of ascorbic acid solution was prolonged to over 2.7 times under 4 °C and over 5 times under 25 °C. At the same time, the hybrid solution of ascorbic acid solution and molybdate mixed solution should be preserved separately, otherwise the using effect is poor.

Role of Solid Wall Properties in the Interface Slip of Liquid in Nanochannels.

A two-dimensional molecular dynamics model of the liquid flow inside rough nanochannels is developed to investigate the effect of a solid wall on the interface slip of liquid in nanochannels with a surface roughness constructed by rectangular protrusions. The liquid structure, velocity profile, and confined scale on the boundary slip in a rough nanochannel are investigated, and the comparison of those with a smooth nanochannel are presented. The influence of solid wall properties, including the solid wall density, wall-fluid coupling strength, roughness height and spacing, on the interfacial velocity slip are all analyzed and discussed. It is indicated that the rough surface induces a smaller magnitude of the density oscillations and extra energy losses compared with the smooth solid surface, which reduce the interfacial slip of liquid in a nanochannel. In addition, once the roughness spacing is very small, the near-surface liquid flow dominates the momentum transfer at the interface between liquid and solid wall, causing the role of both the corrugation of wall potential and wall-fluid coupling strength to be less obvious. In particular, the slip length increases with increasing confined scales and shows no dependence on the confined scale once the confined scale reaches a critical value. The critical confined scale for the rough channel is larger than that of the smooth scale.

Hepatocyte growth factor-induced mesenchymal-epithelial transition factor activation leads to insulin-like growth factor 1 receptor inhibitor unresponsiveness in gastric cancer cells.

Insulin-like growth factor 1 receptor (IGF-1R) inhibitors have been developed as potential therapeutics for cancer treatment; however, the phase III trials have not produced promising overall survival rates. Therefore, understanding the mechanism underlying intrinsic resistance to IGF-1R-targeted agents is urgently required. A number of studies have revealed that activation of alternative receptor tyrosine kinases can mediate resistance to IGF-1R-targeted therapy. The present study investigated whether activated mesenchymal-epithelial transition factor (MET; also known as c-Met and hepatocyte growth factor receptor) confers resistance to an IGF-1R inhibitor (NVP-AEW541) of gastric cancer (GC) cells. NCI-N87 and MGC-803 cells were treated with varying concentrations and combinations of NVP-AEW541, hepatocyte growth factor (HGF) and MET small interfering (si)-RNA or crizotinib (a MET inhibitor). The effects of these agents on cell proliferation and pro-apoptotic events were assessed by Cell Counting Kit-8 assays and flow cytometry. Receptor activation and the downstream signaling pathway were examined using western blot analysis. Expression and/or activation of MET and IGF-1R in 156 GC specimens were evaluated by immunohistochemistry. The results demonstrated that NVP-AEW541 inhibited cell growth, with dephosphorylation of IGF-1R and protein kinase B (AKT), in NCI-N87 and MGC-803 cells. Application of HGF activated MET and the downstream AKT signaling pathways, decreased apoptotic events and restored cell proliferation, which were reversed by MET inhibition via crizotinib or siRNA knockdown. Furthermore, combination therapy of NVP-AEW541 and crizotinib exhibited an enhanced effectiveness in vitro. In addition, >40% of IGF-1R overexpressed GC specimens showed MET expression and activation. In conclusion, HGF-induced MET activation may represent a novel mechanism conferring unresponsiveness to IGF-1R-targeted agents in GC, and inhibition of MET may improve the efficacy of IGF-1R inhibitors.