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Objective: Solving the limitations of single chemotherapy in the treatment of non‐small cell lung cancer (NSCLC). Methods: About 100 patients with NSCLC treated in First Hospital of Jiaxing, Zhejiang from June 2016 to June 2018 were selected and randomly divided into MPC group and MGC group, with 50 cases in each group. The patients in MPC group were treated with microwave ablation (MWA) combined with PC while patients in MGC group were given MWA combined with gemcitabine plus cisplatin (GC). The therapeutic effects of the two groups as well as the complications and adverse reactions (ADRs) were observed and recorded. Results: There was no significant difference in disease response rate (MPC group 33.3% vs MGC group 32.0%), disease control rate (MPC group 86.4% vs MGC group 78.0%) and overall survival (1‐, 2‐ and 3‐year survival, MPC group 65%, 59%, 32.7% vs MGC group 58%, 46%, 30%) between the two groups. In addition, the ADR myelosuppression was slighter in MPC group. There were 12 cases (23%) developed myelosuppression in the MPC group and 20 cases (42%) in MGC group, with a significant difference between the two groups (P < 0.05). The treatment was interrupted for 0 case (0%) in MPC group because of myelosuppression while 4 cases (8.3%) in MGC group. Conclusion: The two therapeutic regimens have similar efficacy in treatment of advanced NSCLC, but MPC causes slighter myelosuppression and can be the first‐line therapy for advanced NSCLC. [ABSTRACT FROM AUTHOR]

Background. Prognosis is a main factor affecting the survival of patients with lung adenocarcinoma (LUAD), yet no robust prognostic model of high effectiveness has been developed. This study is aimed at constructing a stable and practicable gene signature-based model via bioinformatics methods for predicting the prognosis of LUAD sufferers. Methods. The mRNA expression data were accessed from the TCGA-LUAD dataset, and paired clinical information was collected from the GDC website. R package "edgeR" was employed to select the differentially expressed genes (DEGs), which were then used for the construction of a gene signature-based model via univariate COX, Lasso, and multivariate COX regression analyses. Kaplan-Meier and ROC survival analyses were conducted to comprehensively evaluate the performance of the model in predicting LUAD prognosis, and an independent dataset GSE26939 was accessed for further validation. Results. Totally, 1,655 DEGs were obtained, and a 7-gene signature-based risk score was developed and formulated as risk _ score = 0.000245 ∗ NTSR 1 + 7.13 E − 05 ∗ RHOV + 0.000505 ∗ KLK 8 + 7.01 E − 05 ∗ TNS 4 + 0.000288 ∗ C 1 QTNF 6 + 0.00044 ∗ IVL + 0.000161 ∗ B 4 GALNT 2. Kaplan-Meier survival curves revealed that the survival rate of patients in the high-risk group was lower in both the TCGA-LUAD dataset and GSE26939 relative to that of patients in the low-risk group. The relationship between the risk score and clinical characteristics was further investigated, finding that the model was effective in prognosis prediction in the patients with different age (age > 65 , age < 65) and TNM stage (N0&N1, T1&T2, and tumor stage I/II). In sum, our study provides a robust predictive model for LUAD prognosis, which boosts the clinical research on LUAD and helps to explore the mechanism underlying the occurrence and progression of LUAD. [ABSTRACT FROM AUTHOR]

• Igf2bp3 was strongly upregulated in the gsdf -deficient ovary in medaka. • Igf2bp3 plays an essential role in oocyte development across phyla. • gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development in medaka. Gonadal soma-derived factor (Gsdf) is a unique TGF-β factor essential for both ovarian and testicular development in Hd-rR medaka (Oryzias latipes). However, the downstream genes regulated by Gsdf signaling remain unknown. Using a high-throughput proteomic approach, we identified a significant increase in the expression of the RNA-binding protein Igf2bp3 in gsdf -deficient ovaries. We verified this difference in transcription and protein expression against normal gonads using real-time PCR quantification and Western blotting. The genomic structure of igf2bp3 and the syntenic flanking segments are highly conserved across fish and mammals. igf2bp3 expression was correlated with oocyte development, which is consistent with the expression of the igf2bp3 ortholog Vg1-RBP/Vera in Xenopus. In contrast to the normal ovary, cysts of H3K27me3- and Igf2bp3-positive germ cells were dramatically increased in the one-month-old gsdf -deficient ovary, indicating that the gsdf depletion led to a dysregulation of Igf2bp3-mediated oocyte development. Our results provide novel insights into the Gsdf-Igf2bp3 signaling mechanisms that underlie the fundamental process of gametogenesis; these mechanisms may be well conserved across phyla. [ABSTRACT FROM AUTHOR]

Heterogeneity has attracted mounting attention across multiple disciplines and is confirmed to be a greater promoter of cooperation. It is often the case that the heterogeneity always exists in investment and payoff allocation concurrently instead of separately. In addition, the factors that affect heterogeneous investment and payoff allocation are various. Inspired by this, this paper extends the previous models by incorporating heterogeneous investment and payoff allocation into the typical PGG model to further investigate the incentive mechanisms of cooperative behavior. In order to better understand the model, three different feedback mechanisms, namely the wealth-preference mechanism, the social-self-preference mechanism, and the mixed-preference mechanism, are addressed. The former two mechanisms correspond to the case of single factor and the latter corresponds to the case of double factors. The numerical simulations indicate that feedback mechanism by bridging the connections between the investment and the payoff allocation can reduce the free-rider problem. Furthermore, it is found that the cooperative frequency and average payoff perform better in the case of the mixed-preference mechanism where players will not only take previous payoff feedback as well as current investment but also their social status into their game decision-making process. In addition, full cooperation and profitability over all players can be promoted by means of increasing r or reducing α . At last, compared with another two classic networks, the extent of cooperation is promoted under the structures of the BA scale free networks. [ABSTRACT FROM AUTHOR]

The meiotic entry of undifferentiated germ cells is sexually specific and strictly regulated by the testicular or ovarian environment. Germline stem cells with a set of abnormal sex chromosomes and associated autosomes undergo defective meiotic processes and are eventually eliminated by yet to be defined post‐transcriptional modifications. Herein, we report the role of gsdf, a member of BMP/TGFβ family uniquely found in teleost, in the regulation of meiotic entry in medaka (Oryzias latipes) via analyses of gametogenesis in gsdf‐deficient XX and XY gonads in comparison with their wild‐type siblings. Several differentially expressed genes, including the FKB506‐binding protein 7 (fkbp7), were significantly upregulated in pubertal gsdf‐deficient gonads. The increase in alternative pre‐mRNA isoforms of meiotic synaptonemal complex gene sycp3 was visualized using Integrative Genomics Viewer and confirmed by real‐time qPCR. Nevertheless, immunofluorescence analysis showed that Sycp3 protein products reduced significantly in gsdf‐deficient XY oocytes. Transmission electron microscope observations showed that normal synchronous cysts were replaced by asynchronous cysts in gsdf‐deficient testis. Breeding experiments showed that the sex ratio deviation of gsdf−/− XY gametes in a non‐Mendelian manner might be due to the non‐segregation of XY chromosomes. Taken together, our results suggest that gsdf plays a role in the proper execution of cytoplasmic and nuclear events through receptor Smad phosphorylation and Sycp3 dephosphorylation to coordinate medaka gametogenesis, including sex‐specific mitotic divisions and meiotic recombination. [ABSTRACT FROM AUTHOR]

The acquired resistance of the first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a main factor leading to poor prognosis of non-small cell lung cancer (NSCLC), so we researched whether the high expression of hypoxia-inducible factor-1α (HIF-1α) in EGFR-TKIs sensitive NSCLC tissue tends to induce the acquired resistance. We detected the HIF-1α in normal lung tissue, EGFR-TKIs sensitive NSCLC tissue, the first generation EGFR-TKIs acquired resistant NSCLC tissue and acquired EGFR T790M mutation NSCLC tissue with the method of immunohistochemistry. Then, we compared the expression of HIF-1α in these tissues, and evaluate the effect of HIF-1α expression to the occurrence of acquired resistance. The expression of HIF-1α was much higher in the EGFR-TKIs sensitive NSCLC tissue than that in normal lung tissue. HIF-1α level became higher after the occurrence acquired resistance. There was negative correlation between HIF-1α level before receiving treatment and the time of acquired resistance occurring as well as the acquired EGFR T790M mutation occurring. As the treatment going on, EGFR-TKIs sensitivity rate of low HIF-1α level group was much higher than that of high level group. The high expression of HIF-1α related with the acquired resistance of the first generation EGFR-TKIs, and HIF-1α can be a biomarker to predict the early occurrence of acquired resistance. [ABSTRACT FROM AUTHOR]

Abstract The relationships in human society are heterogeneous and dynamically change with interactions, which have a strong effect on individual’s learning behaviors. In this light we present a new mechanism of preferential learning based on dynamic relationship into evolutionary spatial prisoner’s dilemma game to further investigate the incentive mechanisms of cooperative behaviors. In detail, we consider that the strength of relationship between pairwise individuals adaptively changes according to their mutual strategies and the adjusting rate is related to individuals’ sensitivity to interactions. Based on the heterogeneous and dynamic relationship, individuals prefer neighbors with stronger relationship to learn from instead of learning randomly The learning preference is measured by the preference intensity. By means of Monte Carlo simulations, we find that both the sensitivity factor and the preference intensity have multiple effects on the evolution of cooperation. Furthermore, to validate the multiple effects in a microcosmic view, strategy transitions during the evolution are also discussed. Interestingly, we find that there exists a trade-off between the influence of the sensitivity factor and the preference intensity on the evolution of cooperation. Presented results are robust to variations of the network structures and may provide a new understanding to the emergence of cooperative behaviors. Highlights • Introduce dynamic relationship-based preferential learning mechanism into evolutionary prisoner’s dilemma game model. • Construct a method to update the strength of relationship according to mutual strategies. • Both the sensitivity factor and the preference intensity has multiple effects on promotion of cooperation. • There exists a trade-off between the influences of the sensitivity factor and the preference intensity. [ABSTRACT FROM AUTHOR]

Context: Although there were reports on the protective functions of tanshinone IIA (TSA) on rat myocardial ischemia, the exerting mechanism has not been completely clarified. Objective: An attempt was made to further verify the protective effect of TSA on myocardial ischemia reperfusion injury and elucidate its underlying mechanism. Materials and methods: The rats were given TSA (10, 20, and 40 mg/kg bw per day) in intraperitoneal injection for 15 d. Rami anterior descending branch of coronary artery was ligated for 30 min and then re-perfused for 120 min to establish a reperfusion model. Effects of TSA on the infarct area, creatine kinase (CK), aspartate aminotransferase (AST), high mobility group box B1 protein (HMGB1), and inflammation and oxidation were investigated. Results: Compared with those in the IR group, infarct size percentages of rats’ myocardium in L-TSA, M-TSA, and H-TSA groups were reduced by 1.21, 4.26, and 12.50%, respectively, CK activities by 7.4, 11.2, and 12.5%, respectively, and AST activities also declined (p < 0.05). Furthermore, compared with those in the IR group, SOD and GSH-Px activities increased, and MDA, TNF-α, IL-6, and iNOS levels decreased in L-TSA, M-TSA, and H-TSA groups (p < 0.05). Meanwhile, compared with those in the IR group, HMGB1 expressions in L-TSA, M-TSA, and H-TSA groups were lowered by 21.9, 32.4, and 35.6%, respectively. Discussion and conclusion: The protective function of TSA on myocardial ischemia reperfusion injury may be possibly exerted by inhibiting the increase of ROS caused by the reperfusion to attenuate the expression of HMGB1 and inhibit inflammation. [ABSTRACT FROM AUTHOR]

Food waste can meet diverse demand if treated harmlessly while may bring severe environmental problems if managed improperly. China is currently trying to facilitate food waste harmless disposal and resource utilization by urban food waste management. However, conflicts of interest among government departments, restaurants and waste disposal companies often make it difficult to achieve effective urban food waste management. This paper conducts a theoretical modeling and simulation analysis of behavioral strategy interaction of the above three participants by a combination of evolutionary game and system dynamics approach. To avoid opportunistic behaviors and regulation inefficiency that occurred in fixed penalty scheme (F-scheme), we introduce random inspection penalty scheme (R-scheme) to the tripartite evolutionary game in urban food waste management. Then an in-depth scenario analysis under F-scheme and R-scheme is carried out to investigate the influences of key variables on strategy evolution of participants. The results indicate that, compared with F-scheme, R-scheme contributes to both system stability promotion and practicality enhancement. Food waste treatment fee and regulation cost are influencing factors that respectively affect the strategic choices of restaurants and government departments. To a certain extent, exposure probability that represents informal regulation of the public and NGO can improve urban food waste management. Therefore, it is critical for government departments to adopt R-scheme, take advantage of the informal regulation of the public and NGO, gradually reduce food waste treatment fee and maintain a reasonable regulation cost to improve urban food waste management, thereby promoting food waste harmless disposal and resource utilization. • Penalty under R-scheme can be enforced according to random inspection results. • We use a SD model of evolutionary game to study urban food waste management. • R-scheme contributes to both system stability promotion and practicality enhancement. • Exposure probability can to a certain extent improve urban food waste management. • Policy recommendations for urban food waste management are proposed. [ABSTRACT FROM AUTHOR]

• We investigate the transmission of AQI fluctuation by complex network theory. • AQI networks of various time periods display small-world effect. • It is observed that some extreme short-term AQI fluctuation can be controlled. • Complex network analysis contributes to the prediction of AQI fluctuation. • Policy recommendations for environment management are proposed. Although many works have focused on the issues related to Air Quality Index (AQI) from the perspective of statistics or economics, the dynamic and temporal characteristics of AQI time series remain unclear. The main reason is that AQI time series has both non-linearity and complexity, which cannot be characterized by conventional ways. The inherent transmission laws of AQI volatility are of great importance for environment monitoring and management system. Thus, this paper has endeavored to address the issue from the interdisciplinary perspective of complex network theory. First, we collect the annual and the total AQI data of three cities (Shanghai, Wuhan and Guangzhou) in China from January 1, 2015 to December 31, 2017. Then the coarse graining method is employed in combination with the theory of phase space reconstruction to convert AQI time series into complex network. The coarse graining method is used to transform yearly and total AQI time series into the corresponding symbol sequences. In accordance with the theory of phase space reconstruction, we adopt C C method and false nearest neighbor algorithm to estimate the optimal time delay and embedding dimension of AQI time series, respectively. The optimal time delay is integrated with the embedding dimension to map symbol sequences into AQI complex network. Based on complex network theory, we investigate the transmission of AQI fluctuation by the temporal characteristics and dynamics of yearly AQI networks (YAN) and total AQI networks (TAN), which include node strength, betweenness centrality and community structure. The empirical results show: (1) the AQI networks of various periods display small-world effect; (2) network evolution tends to be more complex and the modality in YAN has less alternative transformation paths than that in TAN; (3) the node strength and betweenness centrality in measuring the importance of nodes achieve a relative consistency; (4) the three cities have the same dominant fluctuation modalities both in YAN and in TAN; (5) the uneven distribution of transmission ability between clusters implies a preferential transmission whether in YAN or TAN. These findings not only help us to interpret the frequent volatility of AQI and control some extreme short-term AQI fluctuation, but also contribute to the reliability assessment of AQI and the prediction of AQI fluctuation. In summary, this paper not only reveals the temporal dynamic properties of AQI time series, but also provides some policy recommendations for environmental monitoring and management. [ABSTRACT FROM AUTHOR]