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Surface waves have a considerable effect on vertical mixing in the upper ocean. In the past two decades, the vertical mixing induced through nonbreaking surface waves has been used in ocean and climate models to improve the simulation of the upper ocean. Thus far, several nonbreaking wave-induced mixing parameterization schemes have been proposed; however, no quantitative comparison has been performed among them. In this paper, a one-dimensional ocean model was used to compare the performances of five schemes, including those of Qiao et al. (Q), Hu and Wang (HW), Huang and Qiao (HQ), Pleskachevsky et al. (P), and Ghantous and Babanin (GB). Similar to previous studies, all of these schemes can decrease the simulated sea surface temperature (SST), increase the subsurface temperature, and deepen the mixed layer, thereby alleviating the common thermal deviation problem of the ocean model for upper ocean simulation. Among these schemes, the HQ scheme exhibited the weakest wave-induced mixing effect, and the HW scheme exhibited the strongest effect; the other three schemes exhibited roughly the same effect. In particular, the Q and P schemes exhibited nearly the same effect. In the simulation based on observations from the Ocean Weather Station Papa, the HQ scheme exhibited the best performance, followed by the Q scheme. In the experiment with the HQ scheme, the root-mean-square deviation of the simulated SST from the observations was 0.43°C, and the mixed layer depth (MLD) was 2.0 m. As a contrast, the deviations of the SST and MLD reached 1.25°C and 8.4 m, respectively, in the experiment without wave-induced mixing. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia in aged population. Oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Investigation of hub genes for the development of potential therapeutic targets and candidate biomarkers is warranted. The differentially expressed genes (DEGs) in AD were screened in GSE48350 dataset. The differentially expressed oxidative stress genes (DEOSGs) were analyzed by intersection of DEGs and oxidative stress-related genes. The immune-related DEOSGs and hub genes were identified by weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) analysis, respectively. Enrichment analysis was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The diagnostic value of hub genes was assessed by receiver operating characteristic analysis and validated in GSE1297. The mRNA expression of diagnostic genes was determined by qRT-PCR analysis. Finally, we constructed the drug, transcription factors (TFs), and microRNA network of the diagnostic genes. A total of 1160 DEGs (259 up-regulated and 901 down-regulated) were screened in GSE48350. Among them 111 DEOSGs were identified in AD. Thereafter, we identified significant difference of infiltrated immune cells (effector memory CD8 T cell, activated B cell, memory B cell, natural killer cell, CD56 bright natural killer cell, natural killer T cell, plasmacytoid dendritic cell, and neutrophil) between AD and control samples. 27 gene modules were obtained through WGCNA and turquoise module was the most relevant module. We obtained 66 immune-related DEOSGs by intersecting turquoise module with the DEOSGs and identified 15 hub genes through PPI analysis. Among them, 9 hub genes (CCK, CNR1, GAD1, GAP43, NEFL, NPY, PENK, SST, and TAC1) were identified with good diagnostic values and verified in GSE1297. qRT-PCR analysis revealed the downregulation of SST, NPY, GAP43, CCK, and PENK and upregulation of NEFL in AD. Finally, we identified 76 therapeutic agents, 152 miRNAs targets, and 91 TFs regulatory networks. Our study identified 9 key genes associated with oxidative stress and immune reaction in AD pathogenesis. The findings may help to provide promising candidate biomarkers and therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

The aim of the study is to explore the efficacy and safety of dendritic cell-cytokine-induced killer cell (DC-CIK) immunotherapy combined with chemotherapy in the treatment of locally advanced gastric cancer (LAGC). Among 106 patients with LAGC, 53 received the treatment of oxaliplatin-5-fluorouracil chemotherapy (control group), while the remaining 53 received DC-CIK immunotherapy combined with chemotherapy (DC-CIK group). The short-term efficacy and the changes in immune function indexes (cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+, and natural killer (NK) cells) were analyzed. The overall response rate (ORR) was 47.2% (25/53) and 41.5% (22/53), and the disease control rate (DCR) was 69.8% (37/53) and 50.9% (27/53), respectively, in the DC-CIK group and the control group. It could be seen that the ORR had no statistically significant difference between the two groups, while the DCR in the DC-CIK group was significantly better than that in the control group. After treatment, the proportions of CD3+ T lymphocytes, CD4+ T lymphocytes, CD4+/CD8+ cells, and NK cells obviously rose, while the proportion of CD8+ T lymphocytes obviously declined in the DC-CIK group compared with those in the control group. After treatment, the scores in the function module of the QLQ-C30 scale were greatly higher in the DC-CIK group than those in the control group, while the scores of loss of appetite, constipation, dyspnea, fatigue, pain, and sleep disorders in the symptom module were significantly lower in the DC-CIK group than those in the control group. The median survival time was 23.4 months and 18.6 months, respectively, in the DC-CIK group and the control group. The results of the log-rank test showed that the OS in the DC-CIK group was remarkably superior to that in the control group. DC-CIK immunotherapy combined with chemotherapy can improve the immune cell function, ameliorate the quality of life, and prolong the survival time of LAGC patients, with fewer adverse reactions. [ABSTRACT FROM AUTHOR]

Oceanic turbulence measurements made by an acoustic Doppler velocimeter (ADV) suffer from noise that potentially affects the estimates of turbulence statistics. This study examines the abilities of Kalman filtering and autoregressive moving average models to eliminate noise in ADV velocity datasets of laboratory experiments and offshore observations. Results show that the two methods have similar performance in ADV de-noising, and both effectively reduce noise in ADV velocities, even in cases of high noise. They eliminate the noise floor at high frequencies of the velocity spectra, leading to a longer range that effectively fits the Kolmogorov −5/3 slope at mid-range frequencies. After de-noising adopting the two methods, the values of the mean velocity are almost unchanged, while the root-mean-square horizontal velocities and thus turbulent kinetic energy decrease appreciably in these experiments. The Reynolds stress is also affected by high noise levels, and de-noising thus reduces uncertainties in estimating the Reynolds stress. [ABSTRACT FROM AUTHOR]

Insufficient vertical mixing in the upper ocean during summer is a common problem of oceanic circulation and climate models. The turbulence associated with non-breaking waves is widely believed to effectively solve this problem. In many studies, non-breaking surface wave processes are attributed to the effects of Langmuir circulations (LCs). In the present work, the influences of LCs on the upper-ocean thermal structure are examined by using one-and three-dimensional ocean circulation, as well as climate, models. The results indicated that the effect of vertical mixing enhanced by LCs is limited to the upper ocean. The models evaluated, including those considering LC effects alone and the combined effects of LCs and wave breaking, failed to produce a reasonable summertime thermocline, resulting in a large cold bias in the subsurface layer. Therefore, while they can slightly reduce the biases of mixed layer depths and sea surface temperatures in models, LCs are insufficient to solve the problem of insufficient vertical mixing. Moreover, restriction of non-breaking surface wave-induced processes in LCs may be questionable. [ABSTRACT FROM AUTHOR]

Compared with observations, the simulated upper ocean heat content (OHC) determined from climate models shows an underestimation bias. The simulation bias of the average annual water temperature in the upper 300 m is 0.2°C lower than the observational results. The results from our two numerical experiments, using a CMIP5 model, show that the non-breaking surface wave-induced vertical mixing can reduce this bias. The enhanced vertical mixing increases the OHC in the global upper ocean (65°S–65°N). Using non-breaking surface wave-induced vertical mixing reduced the disparity by 30% to 0.14°C. The heat content increase is not directly induced by air-sea heat fluxes during the simulation period, but is the legacy of temperature increases in the first 150 years. During this period, additional vertical mixing was initially included in the climate model. The non-breaking surface wave-induced vertical mixing improves the OHC by increasing the air-sea heat fluxes in the first 150 years. This increase in air-sea heat fluxes warms the upper ocean by 0.05–0.06°C. The results show that the incorporation of vertical mixing induced by nonbreaking surface waves in our experiments can improve the simulation of OHC in the global upper ocean. [ABSTRACT FROM AUTHOR]

Malignant glioma is the most common primary brain carcinoma in the world and has a poor survival rate. Previous studies have demonstrated that p53 dysfunction contributes to the development and severity of malignant glioma. It has also been demonstrated that Newcastle disease virus (NDV) may be a viable candidate for the treatment of various types of cancer. In the present study, a p53 oncolytic agent delivered using recombinant NDV (rNDV-p53) was constructed and its anti-tumor effects in vitro and in vivo were assessed. Glioma cell lines and a xenograft mouse model were utilized to assess the ability of p53 and rNDV to promote apoptosis and induce immunotherapy, respectively. The mechanism of rNDV-p53 in glioma therapy was investigated using quantitative polymerase chain reaction and immunohistochemistry. Tumor-specific cytotoxic T-lymphocyte (CTL) responses and lymphocyte infiltration were also analyzed in glioma-bearing models. The results of the present study demonstrate that rNDV-p53 may be a potential therapeutic agent that improves the prognosis of mice with glioma. It was revealed that rNDV-p53 inhibits glioma cell growth and aggressiveness in vitro and in vivo compared with rNDV and p53 alone. The results also demonstrated that rNDV-p53 induced glioma cell apoptosis by upregulating apoptosis-related genes. In addition, the present study demonstrated that rNDV-p53 significantly stimulated CTL responses and lymphocyte infiltration whilst increasing the number of apoptotic bodies in vivo. Furthermore, rNDV-p53 therapy inhibited tumor regression and prolonged the survival of glioma-bearing mice. In conclusion, rNDV-p53 invoked an immune response against glioma cells, which may serve as a comprehensive immunotherapeutic schedule for glioma. [ABSTRACT FROM AUTHOR]

Abstract: Compared to observations, the simulated multi‐model mean surface oceanic mixed layer depth (MLD) during winter in the subtropical regions of both hemispheres shows deep bias from 45 CMIP5 climate models. Our results from two numerical experiments using one of CMIP5 models show that the non‐breaking surface wave‐induced vertical mixing can serve as a remedy. The enhanced vertical mixing increases the heat content of the upper ocean and reduces the oceanic potential density in winter which then stabilize the upper ocean and shallow the simulated winter MLD in subtropical regions. This heat content increase is not directly induced by air‐sea heat fluxes during winter, but is the legacy of temperature increase during summer, when the additional vertical mixing induces an enhanced surface heating. The simulation biases of the annually averaged water temperatures in the upper 400 m reduced by 43% and 28% in south and north latitude bands between 20°and 40°, respectively. The non‐breaking surface wave‐induced vertical mixing shallows both boreal and austral winter MLDs by 2–11 m (a change of 5–20%) in both northern and southern subtropical regions. These results indicate that the incorporation of vertical mixing induced by the non‐breaking surface waves in our experiments can improve the simulation of boreal and austral winter MLDs in northern and southern subtropical regions. [ABSTRACT FROM AUTHOR]

Future potential sea level change in the South China Sea (SCS) is estimated by using 24 CMIP5 models under different representative concentration pathway (RCP) scenarios. By the end of the 21st century (2081-2100 relative to 1986-2005), the multimodel ensemble mean dynamic sea level (DSL) is projected to rise 0.9, 1.6, and 1.1 cm under RCP2.6, RCP4.5, and RCP8.5 scenarios, respectively, resulting in a total sea level rise (SLR) of 40.9, 48.6, and 64.1 cm in the SCS. It indicates that the SCS will experience a substantial SLR over the 21st century, and the rise is only marginal larger than the global mean SLR. During the same period, the steric sea level (SSL) rise is estimated to be 6.7, 10.0, and 15.3 cm under the three scenarios, respectively, which accounts only for 16%, 21% and 24% of the total SLR in this region. The changes of the SSL in the SCS are almost out of phase with those of the DSL for the three scenarios. The central deep basin has a slightly weak DSL rise, but a strong SSL rise during the 21st century, compared with the north and southwest shelves. [ABSTRACT FROM AUTHOR]

Background and Purpose: Shikonin was reported to induce necroptosis in leukemia cells, but apoptosis in glioma cell lines. Thus, it is needed to clarify whether shikonin could cause necroptosis in glioma cells and investigate its underlying mechanisms. Methods: Shikonin and rat C6 glioma cell line and Human U87 glioma cell line were used in this study. The cellular viability was assayed by MTT. Flow cytometry with annexin V-FITC and PI double staining was used to analyze cellular death modes. Morphological alterations in C6 glioma cells treated with shikoinin were evaluated by electronic transmission microscopy and fluorescence microscopy with Hoechst 33342 and PI double staining. The level of reactive oxygen species was assessed by using redox-sensitive dye DCFH-DA. The expressional level of necroptosis associated protein RIP-1 was analyzed by western blotting. Results: Shikonin induced cell death in C6 and U87 glioma cells in a dose and time dependent manner. The cell death in C6 and U87 glioma cells could be inhibited by necroptosis inhibitor necrotatin-1, not by pan-caspase inhibitor z-VAD-fmk. Shikonin treated C6 glioma cells presented electron-lucent cytoplasm, loss of plasma membrane integrity and intact nuclear membrane in morphology. The increased ROS level caused by shikonin was attenuated by necrostatin-1 and blocking ROS by anti-oxidant NAC rescued shikonin-induced cell death in both C6 and U87 glioma cells. Moreover, the expressional level of RIP-1 was up-regulated by shikonin in a dose and time dependent manner as well, but NAC suppressed RIP-1 expression. Conclusions: We demonstrated that the cell death caused by shikonin in C6 and U87 glioma cells was mainly via necroptosis. Moreover, not only RIP-1 pathway, but also oxidative stress participated in the activation of shikonin induced necroptosis. [ABSTRACT FROM AUTHOR]

The influence of the nonbreaking surface wave-induced mixing under the mixed layer on the oceanic circulation was investigated using an isopycnal-coordinate oceanic circulation model. The effect of the wave-induced mixing within the mixed layer was eliminated via a bulk mixed layer model. The results show that the wave-induced mixing can penetrate through the mixed layer and into the oceanic interior. The wave-induced mixing under the mixed layer has an important effect on the distribution of temperature of the upper ocean at middle and high latitudes in summer, especially the structure of the seasonal thermocline. Moreover, the wave-induced mixing can affect the oceanic circulation, such as western boundary currents and the North Equatorial Currents through changes of sea surface height associated with the variation of the thermal structure of the upper ocean. [ABSTRACT FROM AUTHOR]

The influence of horizontal mixing on the thermal structure of the equatorial Pacific Ocean is examined based on a sigma coordinate model. In general, the distributions of the temperature and currents simulated by the sigma coordinate model are very close to the climatology. However, the simulated thermocline along the equator is slightly diffusive so that there is a cold bias above the main thermocline, while there is a warm bias under the main thermocline. Both horizontal diffusivity and viscosity have important effects on the upper thermal structure in the equatorial Pacific Ocean, while their detailed dynamics are different. Horizontal diffusivity affects the thermal structure in the upper ocean mainly through regulating the vertical diffusivity, while the horizontal viscosity does mainly through regulating directly the circulate system. A large horizontal diffusivity or a small horizontal viscosity can be in favor of simulating a more realistically thermal structure in the equatorial Pacific Ocean. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC. [ABSTRACT FROM AUTHOR]