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Abstract Studying the regulatory mechanisms in different tissues of pepper is crucial for understanding organ formation, growth, and development. However, relevant studies are far from sufficient. In the current study, the stipe, calyx, pericarp, placenta, and seed of ripe pepper were sampled, and metabolites were determined by the untargeted metabolomics method. Transcriptome sequencing was performed by Illumina NovaSeq 6000, and then a high-throughput data set was built. The results showed that a total of 4879 annotated metabolites were detected in 15 samples of the five tissues under positive and negative ion mode. A total of 110.66 Gb of clean data was obtained by transcriptome sequencing, the clean data of each sample reached 6.21 Gb, and a total of 35 336 annotated expression genes were obtained. Furthermore, validate the accuracy of the data by combining principal component analysis and other methods. In summary, this study provides valuable information for the genetic improvement and breeding of peppers, and it holds potential application value, particularly in enhancing the quality and nutritional value of pepper fruits.

We construct a theoretical model based on the task-based approach to study how industrial intelligence affects the residents’ income gap through employment substitution and creation effect on different skilled labor, compensation effect on industries and industrial structure upgrading effect on industrial sectors. Subsequently, we present the benchmark regression analysis elucidating the impact of industrial intelligence on income inequality among urban residents in China. We employ a comprehensive set of control variables including economic development indicators, financial metrics, trade openness measures, government intervention variables, and other relevant factors to ensure the robustness of our findings. Furthermore, we explore heterogeneous effects to uncover how industrial intelligence affects income inequality differently across various demographic groups and regions. Based on our empirical analysis, we discover several key findings. Firstly, the advancement of industrial intelligence has notably exacerbated the income disparity among urban residents in China. This conclusion remains true even after conducting robustness test and endogenous treatment. Secondly, the impact of industrial intelligence on income inequality operates through distinct mechanisms. While it widens the income gap through employment substitution and creation effect as well as industrial upgrading effects, it also narrows the gap via the compensation effect. Lastly, industrial intelligence disproportionately affects certain demographic groups and regions. Specifically, it exacerbates income inequality among middle-aged and elderly individuals and in areas with weaker employment protection measures in China. The insights derived from our research can inform policymakers about striking a balance between economic growth and the well-being of the population, ultimately guiding the formulation of effective and inclusive policies in response to technological advancements.

To date, the exploration of multi-principal element alloys (MPEAs) has rarely ventured into the realm of hexagonal close-packed (HCP) structures. In this research, we embarked on a pioneering systematic comparison between a single-phase Ti-Zr-Hf HCP-MPEA and Ti regarding their dislocation activities and mesoscale deformation homogeneity. Through large-area high-resolution quasi-in-situ slip trace analysis and crystal plasticity finite element modeling, we identified HCP-MPEA’s significantly enhanced pyramidal slip activities—resulted from minimized disparities among different deformation modes—notably improve the material’s intragranular deformation homogeneity. Alongside MPEA’s intrinsically high slip resistance, it renders HCP-MPEA an outstanding strength-toughness combination relative to its conventional HCP counterparts.

Abstract Additive manufacturing provides an efficient way of producing metallic components with complex geometries. Their microstructure is substantially different to those from conventional processing, creating opportunities for manipulating the final microstructure and properties via heat treatment. Here, we demonstrate that as-built heterostructures in an Al-Zn-Mg-Cu-Nb alloy produced during the solidification of molten pools provide a driving force and additional Zener pinning sources for recrystallization. This creates a bimodal grain structure after solution treatment, causing additional hetero-deformation-induced strengthening and hardening. Coarse grains are found to promote work hardening and blunt the propagate of cracks during deformation, increasing ductility. Together with precipitation strengthening from a high number density nanoprecipitates, the simultaneous improvement of strength and ductility in a highly alloyed Al-Zn-Mg-Cu-Nb alloy is achieved. These results provide a simple strategy for the development of additively manufactured age-hardening alloys with improved strength and ductility for high performance structural applications.

Abstract Background Mitochondria play essential roles in tumorigenesis; however, little is known about the contribution of mitochondrial DNA (mtDNA) to esophageal squamous cell carcinoma (ESCC). Whole-genome sequencing (WGS) is by far the most efficient technology to fully characterize the molecular features of mtDNA; however, due to the high redundancy and heterogeneity of mtDNA in regular WGS data, methods for mtDNA analysis are far from satisfactory. Methods Here, we developed a likelihood-based method dMTLV to identify low-heteroplasmic mtDNA variants. In addition, we described fNUMT, which can simultaneously detect non-reference nuclear sequences of mitochondrial origin (non-ref NUMTs) and their derived artifacts. Using these new methods, we explored the contribution of mtDNA to ESCC utilizing the multi-omics data of 663 paired tumor-normal samples. Results dMTLV outperformed the existing methods in sensitivity without sacrificing specificity. The verification using Nanopore long-read sequencing data showed that fNUMT has superior specificity and more accurate breakpoint identification than the current methods. Leveraging the new method, we identified a significant association between the ESCC overall survival and the ratio of mtDNA copy number of paired tumor-normal samples, which could be potentially explained by the differential expression of genes enriched in pathways related to metabolism, DNA damage repair, and cell cycle checkpoint. Additionally, we observed that the expression of CBWD1 was downregulated by the non-ref NUMTs inserted into its intron region, which might provide precursor conditions for the tumor cells to adapt to a hypoxic environment. Moreover, we identified a strong positive relationship between the number of mtDNA truncating mutations and the contribution of signatures linked to tumorigenesis and treatment response. Conclusions Our new frameworks promote the characterization of mtDNA features, which enables the elucidation of the landscapes and roles of mtDNA in ESCC essential for extending the current understanding of ESCC etiology. dMTLV and fNUMT are freely available from https://github.com/sunnyzxh/dMTLV and https://github.com/sunnyzxh/fNUMT , respectively.

Background: Lung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosis-related genes within lung CSCs. Methods: We systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein‒protein interaction networks to identify hub genes. LC‒MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene–thioredoxin-interacting protein (TXNIP).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between TXNIP and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of TXNIP, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. Results: A total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and TXNIP were singled out as hub genes, with TXNIP showing particularly noteworthy expression. The expression of the ferroptosis-related gene TXNIP exhibited correlations with the presence of an immunosuppressive microenvironment, TNM stages, and the degree of histological differentiation.Also, the ferroptosis-markers GPX4 and NCOA4 displayed correlations with LUAD. This comprehensive analysis underscores the significance of TXNIP in the context of ferroptosis-related processes and their potential implications in cancer development and progression. Conclusion: The investigation conducted in this study systematically delved into the role of the ferroptosis-related gene TXNIP in Lung CSCs. The identification of TXNIP as a potentially valuable biomarker in this context could have significant implications for refining prognostic assessments and optimizing therapeutic strategies for advanced lung cancer.

Abstract Gastrointestinal (GI) cancers (gastric cancer, oesophageal cancer, liver cancer, colorectal cancer, etc.) are the most common cancers with the highest morbidity and mortality in the world. The therapy for most GI cancers is difficult and is associated with a poor prognosis. In China, upper GI cancers, mainly gastric cancer (GC) and oesophageal cancer (EC), are very common due to Chinese people’s characteristics, and more than half of patients are diagnosed with distant metastatic or locally advanced disease. Compared to other solid cancers, such as lung cancer and breast cancer, personalized therapies, especially targeted therapy and immunotherapy, in GC and EC are relatively lacking, leading to poor prognosis. For a long time, most studies were carried out by using in vitro cancer cell lines or in vivo cell line-derived xenograft models, which are unable to reproduce the characteristics of tumours derived from patients, leading to the possible misguidance of subsequent clinical validation. The patient-derived models represented by patient-derived organoid (PDO) and xenograft (PDX) models, known for their high preservation of patient tumour features, have emerged as a very popular platform that has been widely used in numerous studies, especially in the research and development of antitumour drugs and personalized medicine. Herein, based on some of the available published literature, we review the research and application status of PDO and PDX models in GC and EC, as well as detail their future challenges and prospects, to promote their use in basic and translational studies or personalized therapy.

Abstract This study examined the effect of local officials' political capital on poverty alleviation by using a manually compiled database of county party secretaries (CPSs) in impoverished counties in China. The empirical results reveal that CPSs with political capital positively affect poverty alleviation. Mechanism tests indicated that CPSs with political capital contribute to greater agricultural and financial development, attract more enterprise investment, and increase fiscal expenditure. The promotional effect of local officials' political capital on poverty alleviation was influenced by CPSs' characteristics (e.g., tenure, education level, and age) and was less pronounced during central government inspection and when the provincial government was less concerned about local officials' poverty alleviation. Our results suggest that local officials' political capital can alleviate poverty in emerging economies.

In this work, the effect of Zn content on the formability and aging precipitation of Al–Zn–Mg–Cu–Nb alloys prepared by laser powder bed fusion (LPBF) were investigated via experiments and in-depth characterization. Results show that the increase in Zn content narrows the LPBF processing window, owing to the significant evaporation of Zn element during LPBF. The increase of Zn content not only accelerates the aging kinetics of Al–Zn–Mg–Cu–Nb alloys, but also increases the number density of nanoprecipitates and reduces the PFZ width, resulting in an enhancement in the peak microhardness. The microstructure evolution and aging behavior of alloys during direct aging (DA) and traditional solution treatment and aging (STA) were compared. DA can maintain fine equiaxed grains, while a bimodal grain structure with coarse and fine grains can be obtained after STA. The peak microhardness and the number density of nanoprecipitates in alloys treated with STA is higher than that of alloys treated with DA, which indicates that the traditional STA heat treatment is still applicable to Al–Zn–Mg–Cu–Nb alloys fabricated by LPBF.

SOX8 plays an important role in several physiological processes. Its expression is negatively associated with overall survival in patients with colorectal carcinoma (CRC), suggesting SOX8 is a potential prognostic factor for this disease. However, the role of SOX8 in CRC remains largely unknown. In this study, our data showed that SOX8 expression was upregulated in CRC cell lines and tumor tissues. Stable knockdown of SOX8 in CRC cell lines dramatically reduced cell proliferation, migration, and invasion. Furthermore, the knockdown of SOX8 decreased the phospho-GSK3β level and suppressed Frizzled-6 (FZD6) transcription; restoration of FZD6 expression partially abolished the effect of SOX8 on Wnt/β-catenin signaling and promote CRC cell proliferation. In conclusion, our findings suggested that SOX8 served as an oncogene in CRC through the activation of FZD6-dependent Wnt/β-catenin signaling.

Abstract Background Increasing evidence indicates that radiotherapy (RT) has synergistic inhibitory efficiency with immunotherapy agents in multiple cancers and enhances abscopal effects by regulating the innate immune response, which was further investigated in this study. Neutrophils are recruited in radiated tumors. Therefore, neutrophil membrane-coated nanoparticles potentially deliver R837 (Toll-like receptor 7 agonist) to radiated tumors. Methods A novel nanoparticle R837@PLGA@Neu was prepared by initially assembling PLGA (poly (lactic-co-glycolic acid)) with R837 (TLR7 agonist) into R837@PLGA followed by coating with neutrophil membrane. Characterizations of R837@PLGA@Neu were performed. Tumor targeting efficiency was evaluated by in vivo fluorescent imaging of CT26-bearing mice. Treatments of R837@PLGA@Neu combined with RT were carried out in unilateral and bilateral CRC tumor-bearing mice, followed by validations of immune cells in tumors by flow cytometry. Results The characteristics of R837@PLGA@Neu were well identified, and it was confirmed to have high uptake ability and low cytotoxicity in colorectal cancer (CRC) cells in vitro, as well as its strong tumor-targeting efficiency in vivo in CRC tumor-bearing mice. The exciting findings were that R837@PLGA@Neu combined with RT exerted prominent tumor inhibition not only in radiated tumors, but also in distant tumors without RT, suggesting its enhancement of the efficacy and abscopal effect of RT. The possible underlying mechanisms were remodeling of the tumor microenvironment by triggering mature dendritic cells and CD8+ T cells. Conclusion In summary, our findings suggested that neutrophil membrane-derived nanoparticle R837@PLGA@Neu with high uptake ability and low cytotoxicity showed strong tumor-targeting efficiency, and combination with RT had a promising effect in CT26-bearing mice via immune cell regulation. Our results provide a probable combination strategy for CRC treatment.

Abstract In the digital economy, the relationship between digital transformation and a company's total factor productivity has profound implications for high-quality business development. Heavy polluters are given more environmental responsibility because of their high pollution and emission characteristics. This paper analyses the theoretical framework for the impact of digital transformation on the total factor productivity of heavily polluting firms. Using a sample of Shanghai and Shenzhen A-share heavy polluters from 2010 to 2020, we explore how the digital transformation of heavy polluters affects the total factor productivity of firms. The study found that the digital transformation of heavily polluting companies can effectively improve total factor productivity, internally by increasing their level of green technology innovation and externally by increasing their willingness and capacity for corporate social responsibility. At the same time, digital transformation can improve total factor productivity by reducing cost stickiness, revealing the "black box" in which digital transformation affects the total factor productivity of an enterprise. It was further found that the digital transformation of companies with high levels of environmental investment, large enterprises, those in non-manufacturing industries, and heavy polluters of a state-owned nature had a more significant impact on total factor productivity. The findings of the study provide empirical evidence for the digital transformation of heavily polluting companies to improve productivity and the green transformation of the economy for companies under the low carbon goal.

Abstract Based on 22 qualitative traits, 13 quantitative traits, and 27 molecular markers (26 SSR and 1 InDel), in the current study we compared the diversity and population structure of 94 local landraces and 85 current breeding lines of pepper in China. The results showed that the Shannon Diversity indices of 9 qualitative traits and 8 quantitative traits in current breeding lines were greater than those of landraces, of which 11 were fruit organ-related traits. Compared with current breeding lines, the mean values of Gene Diversity index and Polymorphism Information content of local landraces were higher by 0.08 and 0.09, respectively. Population structure and phylogenetic tree analysis showed that the 179 germplasm resources could be divided into two taxa, dominated by local landraces and current breeding lines, respectively. The above results indicated that the diversity of quantitative traits of current breeding lines were higher than that of local landraces, especially traits related to fruit organs, but the genetic diversity based on molecular markers was lower than that of local landraces. Therefore, in the future breeding process, we should not only focus on the selection of target traits, but also strengthen the background selection based on molecular markers. Moreover, the genetic information of other domesticated species and wild species will be transferred to the breeding lines through interspecific crosses to expand the genetic background of the breeding material.

Drought stress limits wheat production around the world. Here, the authors report allelic variation of a WD40 encoding gene TaWD40-4B.1 contributes to wheat drought tolerance by interacting with canonical catalases as a chaperone to promote their activities to avoid ROS over accumulation.

The structure and function of retinal vessels play a crucial role in diagnosing and treating various ocular and systemic diseases. Therefore, the accurate segmentation of retinal vessels is of paramount importance to assist a clinical diagnosis. U-Net has been highly praised for its outstanding performance in the field of medical image segmentation. However, with the increase in network depth, multiple pooling operations may lead to the problem of crucial information loss. Additionally, handling the insufficient processing of local context features caused by skip connections can affect the accurate segmentation of retinal vessels. To address these problems, we proposed a novel model for retinal vessel segmentation. The proposed model is implemented based on the U-Net architecture, with the addition of two blocks, namely, an MsFE block and MsAF block, between the encoder and decoder at each layer of the U-Net backbone. The MsFE block extracts low-level features from different scales, while the MsAF block performs feature fusion across various scales. Finally, the output of the MsAF block replaces the skip connection in the U-Net backbone. Experimental evaluations on the DRIVE dataset, CHASE_DB1 dataset, and STARE dataset demonstrated that MsAF-UNet exhibited excellent segmentation performance compared with the state-of-the-art methods.

Background Gastric cancer (GC) is an extremely heterogeneous malignancy with a complex tumor microenvironment (TME) that contributes to unsatisfactory prognosis. Methods The overall activity score for assessing the immune activity of GC patients was developed based on cancer immune cycle activity index in the Tracking Tumor Immunophenotype (TIP). Genes potentially affected by the overall activity score were screened using weighted gene co-expression network analysis (WGCNA). Based on the expression profile data of GC in The Cancer Genome Atlas (TCGA) database, COX analysis was applied to create an immune activity score (IAS). Differences in TME activity in the IAS groups were analyzed. We also evaluated the value of IAS in estimating immunotherapy and chemotherapy response based on immunotherapy cohort. Gene expression in IAS model and cell viability were determined by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and Cell Counting Kit-8 (CCK-8) assay, respectively. Results WGCAN analysis screened 629 overall activity score-related genes, which were mainly associated with T cell response and B cell response. COX analysis identified AKAP5, CTLA4, LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 as critical genes affecting the prognosis of GC, based on which the IAS was developed. Further RT-qPCR analysis data showed that the expression of AKAP5 and CTLA4 was downregulated, while that of LRRC8C, AOAH-IT1, NPC2, RGS1 and SLC2A3 was significantly elevated in GC cell lines. Inhibition of AKAP5 increased cell viability but siAOAH-IT1 promoted viability of GC cells. IAS demonstrated excellent robustness in predicting immunotherapy outcome and GC prognosis, with low-IAS patients having better prognosis and immunotherapy. In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. Conclusion IAS was a reliable prognostic indicator. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC.

Introduction: Epithelial ovarian cancer (EOC) is a highly aggressive disease whose unique metastatic site is the omentum. Coiled-coil domain containing 3 (CCDC3) is an adipocyte-derived secreted protein that is specifically elevated in omental adipose tissue. However, its function is still unknown. Material and methods: Initially, a Kaplan–Meier plot was applied to evaluate the prognostic value of CCDC3 expression in patients with EOC. A bioinformatics analysis was next used to explore the biological function of CCDC3 in EOC. Western blot, quantitative real-time polymerase chain reaction, and in vitro invasion and migration assays were performed using SKOV3 cells and CCDC3 secreted by rat adipocytes to analyzes the impact of CCDC3 on EOC and the underlying mechanism. Results: Overexpression of CCDC3 was associated with poor prognosis of EOC. CCDC3 interacted with multiple key signalling pathways, including the Wnt/β-catenin pathway. EOC cellular proliferation, migration, and invasion were promoted in vitro when co-cultured with CCDC3 enriched conditioned medium, and this tumour-promoting effect was induced by activating the Wnt/β-catenin pathway. Furthermore, the epithelial-mesenchymal transition of EOC cells was reversed after CCDC3 silencing. Conclusions: Our results support that CCDC3 promotes EOC tumorigenesis through the Wnt/β-catenin pathway and that CCDC3 may serve as a novel prognostic biomarker and therapeutic target for metastatic EOC.

The biological and clinical implications of high genome instability in esophageal squamous cell carcinoma (ESCC) remain to be explored. Here, the authors analyse 528 whole genomes and investigate the landscape and molecular mechanisms underlying structural variations in ESCC patients.

Diabetic retinopathy is a prevalent eye disease that poses a potential risk of blindness. Nevertheless, due to the small size of diabetic retinopathy lesions and the high interclass similarity in terms of location, color, and shape among different lesions, the segmentation task is highly challenging. To address these issues, we proposed a novel framework named nmODE-Unet, which is based on the nmODE (neural memory Ordinary Differential Equation) block and U-net backbone. In nmODE-Unet, the shallow features serve as input to the nmODE block, and the output of the nmODE block is fused with the corresponding deep features. Extensive experiments were conducted on the IDRiD dataset, e_ophtha dataset, and the LGG segmentation dataset, and the results demonstrate that, in comparison to other competing models, nmODE-Unet showcases a superior performance.

Lithium-ion batteries (LIBs) account for the majority of energy storage devices due to their long service life, high energy density, environmentally friendly, and other characteristics. Although the cathode materials of LIB led by LiFePO4 (LFP), LiCoO2 (LCO), and LiNixCoyMn1-x-yO2 (NCM) occupy the majority of the market share at present, the demand of LiMn2O4 (LMO) cathode battery is also increasing year by year in recent years. With the rising price of various raw materials of LIBs and the need of environmental protection, the efficient recycling of spent LIBs has become a hot research topic. At present, the recycling of spent LIBs mainly focuses on LFP, LCO, and NCM batteries. However, with the continuous improvement of people’s safety of LIBs, LiMnxFe1-xPO4 (LMFP) batteries show better potential, which also improves the recycling value of LMO batteries. Therefore, this paper reviews current methods of spent LMO recovery, focusing on the characteristics of the recovery and separation process, which can serve as a reference for subsequent research on LMO recovery, increasing environmentally friendly recovery routes. Finally, the future development direction of LIBs recycling is prospected. Overall, this review is helpful to understand the current progress of LMO battery recycling.

Crop rotation has widely contributed to increasing farmland biodiversity as well as to improving soil carbon pools and microbial diversity. However, there is a weak understanding of the suitability of winter crop rotation intensification in double rice fields, especially rotation with various winter crops. For this task, a long-term field experiment based on one from 2012 was conducted with five winter crop systems for double rice: winter fallow (T0), winter milk vetch (T1), winter rape (T2), winter garlic (T3), winter rotation intensification with potato, milk vetch, and rape (T4). Parameters such as crop yield, soil carbon, nitrogen, and soil microorganism were measured. It was found that compared to winter fallow, winter milk vetch, rape, garlic, and crop rotation intensification practices increased the late rice yield by 2.5%, 2.3%, 4.5%, and 3.7%, respectively; winter garlic and crop rotation intensification also increased the early rice yield by 4.6% and 3.5%, respectively. This is associated with the promotion of rice tillering. At the same time, for winter crop rotation, compared to winter fallow, the soil organic carbon increased by 21%. With the input of diversified crop residues, winter crops were effective in soil carbon sequestration, improving soil microbial structure, and increasing soil microbial diversity. The Shannon diversity index of winter crops ranged from 9.75 to 9.91, while winter fallow was 9.38. The Simpson’s diversity index of winter crops ranged from 0.997 to 0.998, while winter fallow was 0.996. In conclusion, winter crop practices, especially winter crop rotation intensification, can enhance soil health and sustainability in double rice fields through its positive feedback on crop yield, soil carbon sequestration, and microorganisms.

BackgroundOxycodone hydrochloride is a semisynthetic narcotic analgesic agent. This study aimed to explore optimal titration strategy of controlled-release (CR) oxycodone hydrochloride in patients with cancer pain.Methods258 patients, who used regular strong opioids (morphine and CR oxycodone hydrochloride) for cancer pain across 25 three grade class hospitals in China during January 15th 2017 to April 30th 2017, were retrospectively studied. The patients were divided into 4 groups according to treatment regimens titrated. The pain remission rate and numeric rating scale (NRS) of cancer pain was recorded at 0, 12, 24, 36, 48, 60, 72 h after opioid titration. The incidence of adverse events (AEs) with therapy were also observed.Results12 h after treatment, pain remission rate of Group B, C and D was significantly higher (P < 0.001) than Group A. For the complete remission rate, there were also significant differences among the four groups (P < 0.001). No significant difference was found among four groups for pain remission rate at 24, 72 h after treatment. Multiple comparison of NRS scores showed that the both Group B and C varied significantly with Group D (P = 0.028, P = 0.05, respectively), showing superior analgesic effect over Group D. AEs were significantly different among groups (P < 0.01), with the most frequent AEs in Group A, lowest in Group B.ConclusionThe rapid titration strategy of background CR oxycodone hydrochloride was effectiveness and safety in patients with moderate-to-severe cancer pain.

The advent of green energies contributes to their high penetration in the energy sector. It could be guessed from the beginning that societies would so excited about the advantages of these energy sources to deploy in the infrastructure of energy systems even before deep investigation about their possible disadvantages. Unfortunately, the management of these sources has become challenging due to the uncertainty associated with environmental factors which can make social, economic, and technical issues. On the other hand, new emerging technologies such as electric vehicles (EVs) have helped much to reduce air pollution and thus make positive effects on human life. Still, we all accept that new technology can make the problem structure much more complicated. This article proposes an innovative management approach for risk-based optimal bidding strategies of energy aggregators in the energy market considering green sources. Moreover, it proposes a new strategy for the bidding offer strategy for green energy aggregators in the spot electricity market. An innovative bi-level optimization approach is developed for the maximization of the profit of the non-participatory companies considering all the technical and social limitations. The equilibrium market spots in this method are calculated as per the Nash equilibrium rule. In such a system, all producers and consumers are considered market players to propose the EV's behavior and as a result, provide a more competitive environment. The results clearly show the high performance of the proposed model for energy management in a green social and economic framework.

Intercropping system plays a crucial role in improving crop yield, nitrogen utilisation efficiency (NUE) and economic benefit. The difference in crop yield and interspecific relationship under different bandwidth and row ratio allocation patterns are still unclear. A field experiment was carried out to explore change regularities between crop yield and interspecific relationships under maize soybean intercropping with different bandwidths and row ratios. The results showed that the yield of intercropped crops was lower than that of the sole crop. The nitrogen accumulation (NA), NUE and nitrogen competition ratio was the highest under the intercropping mode with a bandwidth of 2.0 m, which indicated that this mode was more conducive to the N uptake and utilisation in crops. In all intercropping systems, nitrogen equivalent ratio (NER) and land equivalent ratio (LER) were all greater than one, indicating that intercropping systems were conducive to improving land utilisation efficiency and NUE. Under the same bandwidth pattern, expanding the maize soybean row ratio from 2:4 to 3:4 was beneficial to the improvement of LER, NER, NUE, crop group yield. In conclusion, it was preferable in the NA, NUE, crop group yield under the system of bandwidth 2.0 m and row ratio 2:2, which could be a reference for maize soybean intercropping system.

Heavy metals (HMs) toxicity is serious abiotic stress that is significantly reducing crop productivity and posing a serious threat to human health, soil and environmental quality. Therefore, it is urgently needed to find appropriate measures to mitigate the adverse impacts of HMs on soil, plants, humans and the environment. Biochar (BC) has emerged as an excellent soil amendment to minimize the adverse impacts of HMs and to improve soil fertility and environmental quality. Biochar application decreases HMs uptake and their translocation to plant parts by forming complexes and precipitation. Biochar also has improved soil pH, soil fertility and soil cation exchange capacity (CEC) and it also increases adsorption of HMs thus reduces their mobility and subsequent availability to plants. BC application also maintains membrane stability and improves uptake of nutrients, osmolytes accumulation, antioxidant activities, and gene expression, therefore, improves the plant performance under HMs stress. Biochar application also improves the photosynthetic performance by increasing the synthesis of photosynthetic pigments, stomata conductance and increasing the water uptake by plants. Besides this, BC also scavenges ROS by increasing the antioxidant activities, gene expression, and accumulation of proline in HMs contaminated soils. This review highlights the role of BC to mitigate the HMs toxicity in plants. We have discussed the role of BC in the modification of soil properties to induce tolerance against HMs toxicity. Moreover, we have discussed various mechanisms mediated by BC at the plant level to induce tolerance against HMs. Additionally, we also identified research gaps that must be fulfilled in future research studies.

Colorectal cancer (CRC) is associated with numerous genetic disorders and cellular abnormalities, and liver metastasis is a common health concern in patients with CRC. Exploring newer and more efficient therapies to block liver metastasis is pivotal for prolonging patient survival. Therefore, small interfering RNAs (siRNAs) are expected to be remarkable tools capable of regulating gene expression by participating in a process called RNA interference (RNAi). RNAi is a biological process among eukaryotes wherein specific messenger RNA (mRNA) molecules are destroyed and gene expression is inhibited. This technology is a promising therapeutic agent in the treatment of CRC liver metastasis (CRLM). Nevertheless, crucial problems in siRNA therapeutics, including inherent poor serum stability and nonspecific uptake into biological systems, must be recognized. For this reason, delivery systems are being developed in an attempt to solve these problems. Here, we discuss the utility of siRNA therapy for the treatment of CRCLM by targeting the major metastasis-related signaling pathways. siRNA therapy has the potential to be one of the most effective methods for CRLM treatment in the future.

ObjectiveThis study aimed to investigate the relationship between prognostic and tumor parameters of cervical cancer patients, such as tumor size (TS), tumor volume (TV), and tumor volume reduction rate (TVRR) after external beam radiotherapy.MethodsA total of 217 patients with advanced cervical cancer, classified as Federation of Gynecology and Obstetrics (FIGO) IIa–IVa, were enrolled in the study. Pre- and mid-RT pelvic magnetic resonance imaging (MRI) were performed twice, during RT and just before brachytherapy.ResultsThe median follow-up time was 51 months (range, 7–111 months). The 5-year overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS) rates were 81.3, 85.1, and 92.9%, respectively. Multivariate analysis revealed that tumor parameters including FIGO stage >II (Hazard Ratio, 2.377 and 95% confidence interval [CI], 1.091–5.182; P = 0.029), pre-RT TV >61.6 cm3 (HR, 0.417 and 95% CI, 0.188–0.926; P = 0.032), and mid-RT TV >11.38 cm3 (HR, 3.192 and 95% CI, 1.094–9.316; P = 0.034) were observably associated with OS. Univariate analysis showed that the tumor volume reduction rate (TVRR) was dramatically associated with overall survival (HR, 0.204 and 95% CI 0.033–1.282; P

Abstract Background The main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs. Methods A real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation. Results Two subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification. Conclusion This study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy.

Abstract Background Malignant tumors of the musculoskeletal system, especially osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, pose a major threat to the lives and health of adolescents and children. Current treatments for musculoskeletal tumors mainly include surgery, chemotherapy, and radiotherapy. The problems of chemotherapy resistance, poor long-term outcome of radiotherapy, and the inherent toxicity and side effects of chemical drugs make it extremely urgent to seek new treatment strategies. Main text As a potent gene editing tool, the rapid development of CRISPR/Cas9 technology in recent years has prompted scientists to apply it to the study of musculoskeletal tumors. This review summarizes the application of CRISPR/Cas9 technology for the treatment of malignant musculoskeletal tumors, focusing on its essential role in the field of basic research. Conclusion CRISPR, has demonstrated strong efficacy in targeting tumor-related genes, and its future application in the clinical treatment of musculoskeletal tumors is promising.

Patient-derived organoids (PDO), based on the advanced three-dimensional (3D) culture technology, can provide more relevant physiological and pathological cancer models, which is especially beneficial for developing and optimizing cancer therapeutic strategies. Radiotherapy (RT) is a cornerstone of curative and palliative cancer treatment, which can be performed alone or integrated with surgery, chemotherapy, immunotherapy, or targeted therapy in clinical care. Among all cancer therapies, RT has great local control, safety and effectiveness, and is also cost-effective per life-year gained for patients. It has been reported that combing RT with chemotherapy or immunotherapy or radiosensitizer drugs may enhance treatment efficacy at faster rates and lower cost. However, very few FDA-approved combinations of RT with drugs or radiosensitizers exist due to the lack of accurate and relevant preclinical models. Meanwhile, radiation dose escalation may increase treatment efficacy and induce more toxicity of normal tissue as well, which has been studied by conducting various clinical trials, very expensive and time-consuming, often burdensome on patients and sometimes with controversial results. The surged PDO technology may help with the preclinical test of RT combination and radiation dose escalation to promote precision radiation oncology, where PDO can recapitulate individual patient’ tumor heterogeneity, retain characteristics of the original tumor, and predict treatment response. This review aims to introduce recent advances in the PDO technology and personalized radiotherapy, highlight the strengths and weaknesses of the PDO cancer models, and finally examine the existing RT-related PDO trials or applications to harness personalized and precision radiotherapy.

Abstract APTEEN is a typical routing protocol for wireless sensor networks, but when clustering, cluster heads are randomly selected, which makes it easy to select nodes with low residual energy as cluster heads, thus forming network holes. At the same time, in multi hop transmission, the cluster head near the sink node is overloaded due to forwarding a large amount of data. Aiming at these problems, this paper introduces PSO algorithm and proposes ADCH-EPE-APTEEN routing protocol. In order to make the particle swarm optimization algorithm more suitable for routing protocol, this paper first proposes DCA-PSO based on particle swarm optimization algorithm. DCA-PSO uses the classification adaptive change inertia weight for different states of particles in the optimization process. At the same time, dynamic learning factor is used to improve the influence of particle experience and other particle experience on convergence speed and to improve the optimization accuracy and speed of the algorithm. Secondly, when APTEEN routing protocol is networked, the cluster head is selected by DCA-PSO, in which the residual energy of nodes, the location of nodes, and the energy distribution around nodes are fully taken into consideration. Thirdly, considering the distance between nodes and the sink node, the residual energy and the energy distribution around nodes, a front area is set up in the cluster located in the upper half and the assistant cluster head is selected in the front area through the DCA-PSO algorithm. The simulation results show that the DCA-PSO algorithm can significantly improve the search speed and precision compared with the PSO algorithm. Compared with APTEEN routing protocol, the ADCH-EPE-APTEEN routing protocol can reduce the network energy consumption rate and extend network lifetime by 173%.

The maturity and commercialization of emerging digital technologies represented by artificial intelligence, cloud computing, block chain and virtual reality are giving birth to a new and higher economic form, that is, digital economy. Digital economy is different from the traditional industrial economy. It is clean, efficient, green and recyclable. It represents and promotes the future direction of global economic development, especially in the context of the sudden COVID-19 pandemic as a continuing disaster. Therefore, it is essential to establish the comprehensive evaluation model of digital economy development scientifically and reasonably. In this paper, first on the basis of literature analysis, the relevant indicators of digital economy development are collected manually and then screened by the grey dynamic clustering and rough set reduction theory. The evaluation index system of digital economy development is constructed from four dimensions: digital innovation impetus support, digital infrastructure construction support, national economic environment and digital policy guarantee, digital integration and application. Next the subjective weight and objective weight are calculated by the group FAHP method, entropy method and improved CRITIC method, and the combined weight is integrated with the thought of maximum variance. The grey correlation analysis and improved VIKOR model are combined to systematically evaluate the digital economy development level of 31 provinces and cities in China from 2013 to 2019. The results of empirical analysis show that the overall development of China’s digital economy shows a trend of superposition and rise, and the development of digital economy in the four major economic zones is unbalanced. Finally, we put forward targeted opinions on the construction of China’s provincial digital economy.

Background: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study. Methods: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986). Findings: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA). Interpretation: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC. Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

The clevis-grip tensile test is usually employed to evaluate the mechanical properties of textile reinforced concrete (TRC) composites, which is actually a bond test and is unsuitable for determining reliable design parameters. Thus, the clevis-grip tensile test needs further improvement to obtain foreseeable results concerning TRC tensile behavior. This paper presents the experimental results of twenty-one tension tests performed on basalt TRC (BTRC) thin plates with different test setups, i.e., clevis-grip and improved clevis-grip, and with different textile ratios. The influences of test setups and textile ratios on crack patterns, failure mode, and tensile stress-strain curves with characteristic parameters were analyzed in depth to judge the feasibility of the new test setup. The results indicated that with the new test setup, BTRC composites exhibited textile rupture at failure; in addition, multi-cracks occurred to the BTRC composites as the textile ratio exceeded 1.44%. In this case, the obtained results relied on textile properties, which can be considered reliable for design purposes. The modified ACK model with a textile utilization rate of 50% provided accurate predictions for the tensile stress-strain behavior of the BTRC composite derived from the improved test setup. The proposed test setup enables the adequate utilization of BTRC composite and the reliability of obtained results related to the occurrence of textile rupture; nevertheless, further work is required to better understand the key parameters affecting the textile utilization rate, such as the strength of the concrete matrix.

Intercropping plays an indispensable role in sustainable agriculture. The response of bandwidth row ratio configuration to crop interspecific relationships and land productivity in the maize–soybean intercropping system (MSI) is still unclear. A 2-year field experiment was conducted with sole maize (SM) and sole soybean (SS), two different bandwidths (2.4 m (B1), 2.8 m (B2)), two different maize and soybean row ratios (2:3 (R1), and 2:4 (R2)) for MSI. The results showed that intercropping had advantages for land productivity compared with sole planting. Intercropping cropping had significant differences on crop yield under different intercropping treatments. The 2-yr average land equivalent ratio (LER, 1.59) and group yield under the intercropping patterns of B1R2 were significantly higher than other intercropping treatments (p < 0.05). With a bandwidth of 2.4 m and planting four rows of intercropped soybean, the total LER and group yield increased by 7.57% and 10.42%, respectively, compared to planting three rows of soybean. Intercropped maize was the dominant species and also had a higher nutrient aggressivity than intercropped soybean. The complementarity effect was higher than the select effect in the MSI system, and intercropping advantage was mainly derived from the complementarity effect, which was significantly correlated with intercropped maize yield. Nitrogen and phosphorus nutrient aggressivity in intercropped maize showed significant correlations with group yield and intercropped maize yield. In conclusion, bandwidth 2.4 m, row ratio 2:4 was a reasonable planting pattern because of its superior land productivity, crop nutrients uptake advantage, and harmonious interspecific relationship, which could provide a reference for MSI promotion and application research.

Abstract Background Immunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity. Methods The expression of MACC1, c‐Met, and PDL1 in human GC tissues was first assessed using quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c‐Met, and PDL1 using RT‐PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo. Results We found that expression of MACC1, c‐Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c‐Met and PDL1 expression levels, and c‐Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo. Conclusions From these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

In this paper, APTEEN is applied to cognitive wireless sensor networks, and an ant colony-based uneven clustering APTEEN algorithm (ACUCAPTEEN) is proposed. The algorithm combines routing and spectrum allocation with cross-layer design method, improves energy efficient uneven clustering protocol and introduces it to APTEEN, and uses ant colony algorithm to complete inter-cluster path search, which reduces the task of cluster head. In the candidate cluster head selection process, the residual energy is not considered and the competition radius is fixed, so that the nodes with many idle channels but low residual energy become cluster heads, and the cluster heads far away from the base station still have more intra-cluster tasks with less residual energy. For these problems, an optimized ACUCAPTEEN algorithm(OACUCAPTEEN) is proposed to optimize the candidate cluster heads, the residual energy is taken as a factor of the candidate cluster head probability, and the competition radius is optimized. The simulation results show that the ACUCAPTEEN algorithm and optimization algorithm can reduce the node death rate and extend the network life cycle.

The aim of this study is to evaluate different renewable energy investments alternatives. Within this framework, six different criteria are chosen to represent financial and non-financial dimensions. Additionally, five renewable energy investment alternatives (biomass, hydropower, geothermal, wind and solar) are selected. Fuzzy AHP and fuzzy DEMATEL methods are considered to weight these criteria whereas alternatives are ranked by using fuzzy TOPSIS and fuzzy VIKOR approaches. The findings show that fuzzy AHP and fuzzy DEMATEL methods also give coherent results. It is concluded that environmental effects and earnings are the most significant criteria. Moreover, wind and solar are the most attractive renewable energy investment alternatives. Therefore, it is recommended that governmental incentives should be widely used for effective location selection of both energy alternatives. This situation could be also attractive for foreign investors in renewable energy market. In addition, large-scale investments should be handled by merger and acquisition to increase overall performance. Hence, it can be possible to raise earnings, improve capital adequacy and enhance organizational capacity with the extensive investments. Furthermore, easy access to the sources and good contract conditions should also be provided for this purpose so that it can be much easier to attract the attention of these investors. Also, customer expectations should be understood effectively with a detailed analysis. With the help of this issue, appropriate products can be presented according to customer needs and it significantly contributes to the success in renewable energy investment.

HIF means hypoxia-inducible factor gene family, and it could regulate various biological processes, including tumor development. In 2021, the FDA approved the new drug Welireg for targeting HIF-2a, and it is mainly used to treat von Hippel-Lindau syndrome, which demonstrated its good prospects in tumor therapy. As the fourth deadliest cancer worldwide, gastric cancer endangers the health of people all across the world. Currently, there are various treatment methods for patients with gastric cancer, but the five-year survival rate of patients with advanced gastric cancer is still not high. Therefore, here we reviewed the regulatory role and target role of HIF in gastric cancer, and provided some references for the treatment of gastric cancer.

Family planning is a basic national policy in China. An intrauterine device (IUD) is an important method of achieving family planning owing to its high safety, low cost, and convenient use. The indwelling birth control ring has no obvious adverse effects on the sexual life of women after the operation, and the process is reversible. This ring can be removed for women who want to have children again. There are approximately 100 million women with IUDs worldwide, with approximately 80 million in China. This finding accounts for approximately 40% of women of childbearing age in China. Although an IUD is safe, the invasive operation inevitably leads to complications, such as pelvic infection, abnormal menstruation, and damage to adjacent organs. Among them, ectopic bladder stone formation is a rare complication, but several related cases have been reported. We report four cases of heterotopia of an IUD and cystolithiasis, with diagnosis based on the medical history, clinical manifestations, imaging, and cystoscopic findings. The four patients with ectopic IUDs were treated with cystoscopy combined with laparoscopy (or hysteroscopy). We describe the process of diagnosis and treatment of our patients, and the related literature on an ectopic IUD is reviewed.

Immunotherapy has revolutionized lung cancer treatment in the past decade. By reactivating the host’s immune system, immunotherapy significantly prolongs survival in some advanced lung cancer patients. However, resistance to immunotherapy is frequent, which manifests as a lack of initial response or clinical benefit to therapy (primary resistance) or tumor progression after the initial period of response (acquired resistance). Overcoming immunotherapy resistance is challenging owing to the complex and dynamic interplay among malignant cells and the defense system. This review aims to discuss the mechanisms that drive immunotherapy resistance and the innovative strategies implemented to overcome it in lung cancer.

This study aims to identify the factors affecting economic inequality in emerging seven (E7) countries. Within this framework, first, a wide literature review has been made and 12 different criteria which are thought to affect economic inequality have been determined. These criteria were weighted according to their importance with the help of interval type-2 (IT2) fuzzy Decision-Making Trial and Evaluation Laboratory (DEMATEL) method. Then, by using these weighted criteria, the E7 countries were ranked according to economic equality performance with IT2 fuzzy Multi-Objective Optimization by Ratio Analysis (MOORA) and IT2 fuzzy Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) methods. The findings show that fair taxation, the equality of education provided by the state, and the uncontrolled growth of financial markets have a significant effect on the economic inequality. On the other side, Russia and China are the most successful countries in terms of economic equality, whereas India and Brazil have the worst performances. While considering these results, it can be said that the taxation system must be fair to eliminate the economic inequality. For this purpose, E7 countries should implement direct taxes, such as wealth tax to transfer funds from the rich to middle- and low-income groups. In addition, these countries should offer equal education opportunities to all citizens which affects their future income level. Finally, legal authorities should make the necessary arrangements and prevent excessive risk of financial system in the country so that the financial system in the country can be maintained in a healthy manner.

This study aims to evaluate the innovation performance of the Turkish banking industry. For this purpose, eight different financial and nonfinancial criteria are identified as a result of literature review. Moreover, five biggest Turkish deposit banks are selected as alternatives. Interval type 2 fuzzy decision-making trial and evaluation laboratory (IT2 FDEMATEL) is taken into account to weight the dimensions. On the other side, to rank the alternatives, interval type 2 fuzzy Vise Kriterijumska Optimizacija I Kompromisno Resenje (IT2 FVIKOR) approach is considered. The findings show that market share and return on investment are the most important factors in the innovation performance of retail banking services. This situation gives information that the when banks are more successful in the market, they can make investment to the innovation more effectively. The main reason is that these banks have enough capacity to make this kind of investments. Thus, it is recommended that Turkish banks should first make an efficiency analysis to increase their profit margin so that their capacities can be improved. For this purpose, many different factors should be taken into account by Turkish banks, such as personnel competency and technological development. Within this scope, these banks should make financial analysis of the innovation effectively by generating a qualified team. However, necessary research and development activities should be conducted to reach this objective. Hence, it can be possible to minimize ineffective innovation for the banks.

Abstract Background No approved targeted agents are available for esophageal squamous cell carcinoma (ESCC). Informative genomic analysis and mouse patient-derived xenografts (PDX) also called mouse avatar can greatly expedite drug discovery. Methods Six ESCC cell lines and 7 out of 25 PDX models derived from 188 biopsies with clear molecular features were employed to evaluate the sensitivity of several EGFR blockers in vitro and in vivo, as well as the underlying antitumor mechanisms of the most promising EGFR-TKI afatinib. Mechanisms involved in acquired resistance of afatinib were explored based on established resistant cell lines and PDX models followed by an attempt to reverse resistance. Results Compared with other EGFR blockers, the second-generation EGFR-TKI afatinib exerted superior antitumor effects in ESCC, and EGFR copy number gain (CNG) or overexpression was proposed to be predictive biomarkers. Afatinib played its antitumor effects by inhibiting EGFR downstream pathways, as well as inducing apoptosis and cell cycle arrest at G1. It was increased phosphorylation of Src family kinases (SFKs), rather than MET upregulation, that conferred to acquired resistance of afatinib. Dual blockade of EGFR and SFKs could overcome afatinib resistance and warrants validation in clinical practice. Conclusion Both ESCC cell lines and PDXs with EGFR CNG or overexpression are potential candidates for afatinib, and concomitant EGFR/SFKs inhibition could reverse afatinib-acquired resistance caused by SFKs activation in ESCC.

Abstract Due to the limited energy of the sensor nodes, the unreasonable clustering routing algorithm will cause node premature death and low utilization of energy efficiency in wireless sensor network (WSN). In Adaptive Threshold-sensitive Energy Efficient Network (APTEEN), the assignments of the cluster head (CH) are much heavier than other nodes. The CH unbalanced energy dissipation between nodes that make them die prematurely. Ant colony algorithm can avoid this problem, so this paper presents a double cluster heads Adaptive Threshold-sensitive Energy Efficient Network based on ant colony (ADCAPTEEN). ADCAPTEEN optimizes the cluster head election method compared with APTEEN. It suggests that one master cluster head (MCH) and one vice cluster head (VCH) will be selected in each cluster. The double cluster heads (DCH) can co-work on data collection, fusion, transition, etc. To make routes more stable and energy efficient, this paper proposes a Multiple Adaptive Threshold-sensitive Energy Efficient Network based on Ant-colony (AMAPTEEN). It is the optimization of ADCAPTEEN. And CH selects intermediate node (IM_node) multiple times with ant colony algorithm per round in each cluster, and this way forms multiple route transmission data. Simulation in OPNET proves that compared with APTEEN, ADCAPTEEN reduces energy dissipation, improves node survival rate, and extends network life cycle. AMAPTEEN delays the time of node death, balances energy consumption, and extends network lifetime further operating in the same settings compared with ADCAPTEEN. The proposed two algorithms have good scalability, and they are suitable for large-scale network.

Abstract Background Melanoma is notoriously resistant to all current modalities of cancer therapies including chemotherapy. In recent years, microRNAs (miRNAs) have emerged as molecular regulators in the development and progression of melanoma. However, the relationship between microRNA and chemo-resistance of melanoma is little known. In present study, we aimed to investigate the miRNAs related to cisplatin-resistance in melanoma cells. Methods After cisplatin (DDP) resistant melanoma cells (M8/DDP and SK-Mel-19/DDP) were established in-vitro, high-throughput screening of differentially expressed miRNAs between resistant cells and parental cells were performed. Results It was found that a cancer-related miRNA, miR-30a-5p, was highly over-expressed in resistant cells. Transfection of miR-30a-5p mimic or inhibitor could alter the sensitivity of melanoma cells to cisplatin. Next, we showed that Insulin Like Growth Factor 1 Receptor (IGF1R) gene turned out to be a direct target of miR-30a-5p. Knockdown of IGF1R in melanoma cells could not only reduce the sensitivity to cisplatin but also lead to cell cycle arrest by regulating phosphorylation of Serine-Threonine Protein Kinase (P-AKT (Ser473)) and Tumor Protein P53 (P53). Conclusion Taken together, our study demonstrated that miR-30a-5p could influence chemo-resistance by targeting IGF1R gene in melanoma cells, which might provide a potential target for the therapy of chemo-resistant melanoma cells.

Abstract In order to improve the energy efficiency of cognitive wireless sensor network, this paper introduces threshold-sensitive energy efficient sensor network (TEEN) routing protocol into cognitive wireless sensor network. To make routing and spectrum more stable, this paper presents advanced threshold-sensitive energy efficient sensor network (A-TEEN), which is the optimization of TEEN. A-TEEN optimized the cluster head election method compared with TEEN. Simulation result shows that compared with low-energy adaptive clustering hierarchy, TEEN increases the energy efficiency and extends life cycle of cognitive wireless sensor network. A-TEEN improves the energy efficiency and lifetime further operating in the same settings compared with the regular TEEN.

Aiming at the problem of distance measurement by using key sensors and sensor networks in battlefield, border patrol, search and rescue, critical structure monitoring, and surveillance, a plane-space algorithm is proposed in this paper, and its range and boundary are estimated. In the view of how to use two image sensors with different positions to measure the target points' coordinates, the plane-space algorithm is proposed. By comparing the target point coordinates obtained from two different image sensors, the actual coordinates of the target points are calculated. The definition domain of the acquisition value of the image sensor is defined as the domain of the plane-space algorithm. By calculating the range of the plane-space algorithm under its defined domain, this paper presents a range scanning algorithm and uses it to calculate the range of the plane-space algorithm and gets a range point set. In order to solve the problem of large amount of work in the range scanning algorithm, the extreme value elimination method is proposed. Considering the boundary points and poles of the target, the maximum value of each variable is eliminated at its extreme value and the final target is obtained. Finally, the Matplotlib library-based on Python 2.7 is used to simulate the algorithm. The simulation data shows that the theoretical value of the plane-space algorithm is consistent with the actual value, and the measurement boundary of the plane-space algorithm is calculated when resolution of the image sensor is 480 × 640 pixel with the distance of two sensors being 1000 pixel.