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Abstract Understanding building morphology is crucial for accurately simulating interactions between urban structures and hydroclimate dynamics. Despite significant efforts to generate detailed global building morphology datasets, there is a lack of practical solutions using publicly accessible resources. In this work, we present GLAMOUR, a dataset derived from open-source Sentinel imagery that captures the average building height and footprint at a resolution of 0.0009° across urbanized areas worldwide. Validated in 18 cities, GLAMOUR exhibits superior accuracy with median root mean square errors of 7.5 m and 0.14 for building height and footprint estimations, indicating better overall performance against existing published datasets. The GLAMOUR dataset provides essential morphological information of 3D building structures and can be integrated with other datasets and tools for a wide range of applications including 3D building model generation and urban morphometric parameter derivation. These extended applications enable refined hydroclimate simulation and hazard assessment on a broader scale and offer valuable insights for researchers and policymakers in building sustainable and resilient urban environments prepared for future climate adaptation.

Arthroscopic surgery is a primary technique for treating joint-related diseases, widely embraced in clinical practice for its minimally invasive and precise nature. However, intraoperative bleeding often generates blood mist, significantly impairing the surgeon’s field of view and necessitating prompt high-flow drainage for clearance. Therefore, accurate bleeding detection and localization is a prerequisite for blood mist removal. This paper introduces a pixel-based feature extraction scheme aimed at detecting bleeding frames in arthroscopic videos. In contrast to previous bleeding detection methods, this approach utilizes statistical features based on composite color to analyze arthroscopic images and extract features. Then, a feature selection strategy is proposed to select the best features from the extracted features.Subsequently, the selected features are fused and then classified using an improved KNN classifier to differentiate between bleeding and non-bleeding images. In addition to this, a post-processing scheme is introduced to enhance bleed frame detection performance by exploiting temporal variations across consecutive frames in arthroscopic videos. Lastly, a region-based detection algorithm is proposed for identifying bleeding zones within images depicting bleeding. By conducting extensive experimental analysis on the arthroscopic image and video dataset. The proposed method achieves accuracies of 95.8%, 97.3%, and 95.3% for bleed frame detection in terms of accuracy, sensitivity, and specificity respectively. The results demonstrate that the proposed algorithm effectively detects bleeding frames and bleeding zones in arthroscopic videos.

Abstract Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC‐LT) has not been explored. In this study, it is found that intra‐tumoral TLS abundance is significantly correlated with recurrence‐free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single‐cell RNA‐seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S‐phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non‐invasive manner. The classifier demonstrates remarkable performance in predicting intra‐tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra‐tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC‐LT.

Abstract Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism of immune cells can effectively modulate the host immune response. Itaconate, an intermediate metabolite derived from the tricarboxylic acid (TCA) cycle of immune cells, is produced through the decarboxylation of cis-aconitate by cis-aconitate decarboxylase in the mitochondria. The gene encoding cis-aconitate decarboxylase is known as immune response gene 1 (IRG1). In response to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing the metabolic status of macrophages. Therefore, itaconate serves as a link between macrophage metabolism, oxidative stress, and immune response, ultimately regulating macrophage function. Studies have demonstrated that itaconate acts on various signaling pathways, including Keap1-nuclear factor E2-related factor 2-ARE pathways, ATF3–IκBζ axis, and the stimulator of interferon genes (STING) pathway to exert antiinflammatory and antioxidant effects. Furthermore, several studies have reported that itaconate affects cancer occurrence and development through diverse signaling pathways. In this paper, we provide a comprehensive review of the role IRG1/itaconate and its derivatives in the regulation of macrophage metabolism and functions. By furthering our understanding of itaconate, we intend to shed light on its potential for treating inflammatory diseases and offer new insights in this field.

The North Mountain landslide in Lijie Town has been in a long-term creeping deformation state and has experienced multiple landslide and debris flow disasters. Monitoring the surface deformation of landslide to grasp the surface deformation pattern of disaster body is a reliable basis for realizing early warning prediction of geological disaster. In this paper, a machine learning model is introduced to predict the relevant data, and a long and short-term memory network is used to predict the landslide deformation by monitoring the displacement data of North Mountain in Lijie, and the prediction results are compared with the actual data and analyzed. In this paper, root mean square error , mean absolute error , coefficient of determination and explainable variance are used to evaluate the prediction results, among which the coefficient of determination and explainable variance reach 0.99. It shows that the long short-term memory network used in this paper achieves good prediction performance in the prediction of landslide deformation in the North Mountain of Lijie.

Over the past six decades, the computing systems field has experienced significant transformations, profoundly impacting society with transformational developments, such as the Internet and the commodification of computing. Underpinned by technological advancements, computer systems, far from being static, have been continuously evolving and adapting to cover multifaceted societal niches. This has led to new paradigms such as cloud, fog, edge computing, and the Internet of Things (IoT), which offer fresh economic and creative opportunities. Nevertheless, this rapid change poses complex research challenges, especially in maximizing potential and enhancing functionality. As such, to maintain an economical level of performance that meets ever-tighter requirements, one must understand the drivers of new model emergence and expansion, and how contemporary challenges differ from past ones. To that end, this article investigates and assesses the factors influencing the evolution of computing systems, covering established systems and architectures as well as newer developments, such as serverless computing, quantum computing, and on-device AI on edge devices. Trends emerge when one traces technological trajectory, which includes the rapid obsolescence of frameworks due to business and technical constraints, a move towards specialized systems and models, and varying approaches to centralized and decentralized control. This comprehensive review of modern computing systems looks ahead to the future of research in the field, highlighting key challenges and emerging trends, and underscoring their importance in cost-effectively driving technological progress.

Abstract Oxaliplatin is widely used in chemotherapy for colorectal cancer (CRC), but its sensitivity has become a major obstacle to limiting efficacy. Many literatures reported that Nrf2 activation promoted tumor chemoresistance. In this study, we explored the role and mechanism of Nrf2 inhibition in oxaliplatin-based chemosensitivity of CRC. In vitro experiments, we applied 4-octyl itaconate (4-OI) to activate Nrf2, and used lentivirus to knock down Nrf2 in CRC cell lines. By measuring cell viability, colony formation, apoptosis, reactive oxygen species production, and western blot, we found that oxaliplatin and lobaplatin suppressed the growth of HCT-116 and LOVO cells in a dose-dependent manner, and promoted the expression of Nrf2. 4-OI, an Nrf2 activator, reduced the sensibility of CRC cells to oxaliplatin and lobaplatin, while the knockdown of Nrf2 promoted the sensibility of CRC cells to oxaliplatin and lobaplatin. Through the public databases, we found that the expression of GPX4 in normal tissues was lower compared with cancer tissues in CRC, and the high GPX4 expression predicted a poor prognosis. Meanwhile, we found that oxaliplatin reduced the expression of GPX4 in vitro. The knockdown of Nrf2 enhanced the effects of oxaliplatin to reduce the expression of GPX4 and GSH content, and increase the MDA content, which enhanced oxaliplatin-induced ferroptosis. Subsequently, we found that oxaliplatin promoted the expression of GSDME-N, and induced LDH, IL-1β, and TNF-a release, and the knockdown of Nrf2 aggravated the occurrence of GSMDE-mediated pyroptosis. Finally, we found that the knockdown of Nrf2 enhanced the inhibition of oxaliplatin on HCT116 xenograft tumor growth in vivo. Thus, our study showed that Nrf2 inhibition improved sensitivity to oxaliplatin of CRC cells by promoting ferroptosis and pyroptosis, which provided a new target for overcoming chemoresistance in CRC.

Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder, while the treatment effect is not satisfactory. Immune responsive gene 1 (IRG1) is a highly expressed gene in macrophage in response to inflammatory response and catalyzes the production of itaconate. Studies have reported that IRG1/itaconate has a significant antioxidant effect. This study aimed to investigate the effect and mechanism of IRG1/itaconate on dextran sulfate sodium (DSS)-induced colitis in vivo and in vitro. In vivo experiments, we found IRG1/itaconate exerted protective effects against acute colitis by increasing mice weight, the length of colon, reducing disease activity index and colonic inflammation. Meanwhile, IRG1 deletion aggravated the macrophages/CD4+/CD8+ T-cell accumulation, and increased the release of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, the activation of nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, and gasdermin D (GSDMD) mediated pyroptosis. Four-octyl itaconate (4-OI), a derivative of itaconate, attenuated these changes, therefore relieved DSS-induced colitis. In vitro experiment, we found 4-OI inhibited the reactive oxygen species production, thereby inhibiting the activation of MAPK/NF-κB signaling pathway in RAW264.7 and murine bone-marrow-derived macrophages. Simultaneously, we found 4-OI inhibited caspase1/GSDMD-mediated pyroptosis to reduce the release of cytokines. Finally, we found anti-TNF-α agent reduced the severity of DSS-induced colitis and inhibited gasdermin E (GSDME)-mediated pyroptosis in vivo. Meanwhile, our study revealed that 4-OI inhibited caspase3/GSDME-mediated pyroptosis induced by TNF-α in vitro. Taken together, IRG1/itaconate exerted a protective role in DSS-induced colitis by inhibiting inflammatory response and GSDMD/GSDME-mediated pyroptosis, which could be a promising candidate for IBD therapy.

IntroductionProprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role in cancer pathophysiology remains incompletely defined. Recently, a pivotal role for PCSK9 in cancer immunotherapy was proposed based on the finding that PCSK9 inhibition was associated with enhancing the antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results of a comprehensive pan-cancer analysis of PCSK9 that assessed its prognostic and immunological functions in cancer.MethodsUsing a variety of available online cancer-related databases including TIMER, cBioPortal, and GEPIA, we identified the abnormal expression of PCSK9 and its potential clinical associations in diverse cancer types including liver, brain and lung. We also validated its role in progression-free survival (PFS) and immune infiltration in neuroblastoma.ResultsOverall, the pan-cancer survival analysis revealed an association between dysregulated PCSK9 and poor clinical outcomes in various cancer types. Specifically, PCSK9 was extensively genetically altered across most cancer types and was consistently found in different tumor types and substages when compared with adjacent normal tissues. Thus, aberrant DNA methylation may be responsible for PCSK9 expression in many cancer types. Focusing on liver hepatocellular carcinoma (LIHC), we found that PCSK9 expression correlated with clinicopathological characteristics following stratified prognostic analyses. PCSK9 expression was significantly associated with immune infiltrate since specific markers of CD8+ T cells, macrophage polarization, and exhausted T cells exhibited different PCSK9-related immune infiltration patterns in LIHC and lung squamous cell carcinoma. In addition, PCSK9 was connected with resistance of drugs such as erlotinib and docetaxel. Finally, we validated PCSK9 expression in clinical neuroblastoma samples and concluded that PCSK9 appeared to correlate with a poor PFS and natural killer cell infiltration in neuroblastoma patients.ConclusionPCSK9 could serve as a robust prognostic pan-cancer biomarker given its correlation with immune infiltrates in different cancer types, thus potentially highlighting a new direction for targeted clinical therapy of cancers.

On one hand, anti-slide shaft technology can overcome the problems of blocking the seepage and drainage path in the slope by traditional anti-slide piles. On the other hand, it can reduce the excavation quantities when the vertical drainage and anti slide structures are separately constructed. Besides, it can fully provide the hydration-heat dissipation surface to ensure the overall structure quality. It has been an important technology in modern landslide prevention engineering, and the novel one of geological disaster, hydrogeology and underground engineering in recent years. The anti-slide shaft technology involves hydrodynamic mechanics and solid mechanics, as well as hydrodynamic model, structural model, engineering geological model, etc. Besides, its promoted application is restricted by some problems, such as the lack of mature theoretical system, the relatively complex of this spatial structural combination, and the difficulty of the construction technology. Thus, it is necessary to carry out targeted current status summary research. Based on a large number of relevant documents, patents and practical engineering applications at home and abroad, we summarize the characteristics and classification of anti-slide shaft structure (anti-liquefaction pile, hollow anti-slide shaft, box anti-slide shaft, etc), and find that the anti-slide shaft structure are mostly pile-type or tie-type, forming a 3-D structure system with the combination characteristics of seepage, collection, drainage and anti-slide. This kind of seepage-collection-drainage structures usually include water permeable holes, radiant seepage holes and drainage pipes. The demonstration of typical application examples show that although the anti-slide shafts have the advantage of significant improvement on the stability, there is still a large optimization space from its extensive use and diversification. Thus, the current complex construction process, unclear mechanical properties and drainage characteristics, imperfect stability calculation theory, plane layout optimization method to be improved in anti-slide shaft technology are important scientific issues and research trend, which need to be paid attention in the future. The solutions of these scientific problems are not only beneficial to improving the mechanical and drainage theory, but also beneficial to improving the overall application level of anti-slide shaft technology.

Wannanhua (WH) is a pig breed indigenous to Anhui Province, China. This breed has a high intramuscular fat (IMF) content, making it an ideal model for investigating lipid deposition mechanisms in pigs. IMF content is one of the main indicators of meat quality in pigs and is regulated by multiple genes and metabolic pathways. Building upon our prior transcriptomic investigation, the present study focused on the longissimus dorsi muscle tissue of Wannanhua (WH) pigs in the rapid fat-deposition stages (120 and 240 days of age). Employing 4D label-free quantitative proteomic analysis, we identified 106 differentially expressed proteins (DEPs). Parallel reaction monitoring (PRM) technology was used to verify the DEPs, and the results showed that the 4D label-free results were reliable and valid. Functional enrichment and protein–protein interaction analyses showed that the DEPs were mainly involved in the skeletal-muscle-associated structural proteins, mitochondria, energy metabolism, and fatty acid metabolism. By integrating transcriptomic data, we identified seven candidate genes including ACADL, ACADM, ANKRD2, MYOZ2, TNNI1, UCHL1, and ART3 that play a regulatory role in fat deposition and muscle development. These findings establish a theoretical foundation for future analyses of lipid deposition traits, contributing to potential enhancements in pig meat quality during breeding and advancing the selection process for Chinese indigenous breeds.

Whether natural variations of plant virus resistance are enriched in genes of RNA interference pathway is unknown. Here, via genome-wide association studies, the authors identify regulators of the RDR6 and DCL2 antiviral pathways are involved in quantitative resistance to cucumber mosaic virus in Arabidopsis.

Cuproptosis, a novel copper-induced cell death pathway, is linked to mitochondrial respiration and mediated by protein lipoylation. The discovery of cuproptosis unfolds new areas of investigation, particularly in cancers. The present study aimed to explore the role of cuproptosis in colorectal cancer progression. The genetic alterations of cuproptosis in colon cancer were evaluated using a database. MTT assays, colony formation, and flow cytometry were used to examine the effect of elesclomol-Cu and 4-Octyl itaconate (4-OI) on colorectal cancer cell and oxaliplatin-resistant cell viability. The anti-tumor effect of elesclomol with 4-OI was verified in vivo assay. The results showed that FDX1, SDHB, DLAT, and DLST genes were more highly expressed in normal tissues than those in primary tumor tissues. Patients with high expressions of these genes in tumor tissues had a better prognosis. Using MTT assay and colony formation analysis, elesclomol-Cu pulse treatment showed significant inhibition of cell viability in HCT116, LoVo, and HCT116-R cells. In addition, flow cytometry revealed elesclomol-Cu significantly promoted apoptosis. Tetrathiomolybdate, a copper chelator, markedly inhibited cuproptosis. Subsequently, we found 2-deoxy-D-glucose, a glucose metabolism inhibitor, sensitized cuproptosis. Furthermore, galactose further promoted cuproptosis. Interestingly, 4-OI significantly enhanced cuproptosis which was irrelevant to ROS production, apoptosis, necroptosis, or pyroptosis pathways. Aerobic glycolysis was inhibited by 4-OI through GAPDH, one of the key enzymes of glycolysis, sensitizing cuproptosis. Meanwhile, FDX1 knockdown weakened the ability of 4-OI to promote cuproptosis. In vivo experiments, 4-OI with elesclomol-Cu showed better anti-tumor effects. These results indicated that elesclomol-Cu rapidly halted cell growth in colorectal cancer cells and oxaliplatin-resistant cell line. Importantly, we revealed that 4-OI inhibited aerobic glycolysis by targeting GAPDH to promote cuproptosis.

In previous research on treadmills, the main focus has been on comparing the physiological differences induced by running on treadmill decks and other exercise surfaces, with relatively little research on the mechanical properties of treadmill decks. Reducing sports injuries is a common desire of runners, which may be closely related to muscle activity. Obviously, the mechanical properties of the treadmill play an important role in this process. Muscle activity was evaluated based on a mass-spring-damper (MSD) model that provides a simulated signal of the ground reaction forces (GRF) and vibration of the lower-limb soft tissues (LLST) during the landing of the human body during running. We improved the original human motion model by considering the stiffness and damping effect of the treadmill deck. In addition, based on the theory of muscle activity regulation, the dimensionless objective function is established, and the particle swarm optimization algorithm is used to find the best range of treadmill deck parameters under pre- and post-fatigue conditions. The results show that the hardness of the treadmill deck can affect the regulation of muscle activity. Based on this, the parameters of the specific safe area of the treadmill deck are obtained, and the size of the safe area after fatigue is significantly reduced compared to that before fatigue. By studying the physiological effects of the mechanical properties of the treadmill deck on runners, the research results are expected to provide references for the design of treadmill deck parameters and reduce the risk of runners’ sports injuries, which has practical application value for treadmill design and runners’ health.

The Huai pig is a well-known indigenous pig breed in China. The main advantages of Huai pigs over Western commercial pig breeds include a high intramuscular fat (IMF) content and good meat quality. There are significant differences in the meat quality traits of the same muscle part or different muscle parts of the same variety. To investigate the potential genetic mechanism underlying the meat quality differences in different pig breeds or muscle groups, longissimus dorsi (LD), psoas major (PM), and biceps femoris (BF) muscle tissues were collected from two pig breeds (Huai and Duroc). There were significant differences in meat quality traits and amino acid content. We assessed the muscle transcriptomic profiles using high-throughput RNA sequencing. The IMF content in the LD, PM, and BF muscles of Huai pigs was significantly higher than that in Duroc pigs (p < 0.05). Similarly, the content of flavor amino acids in the three muscle groups was significantly higher in Huai pigs than that in Duroc pigs (p < 0.05). We identified 175, 110, and 86 differentially expressed genes (DEGs) between the LD, PM, and BF muscles of the Huai and Duroc pigs, respectively. The DEGs of the different pig breeds and muscle regions were significantly enriched in the biological processes and signaling pathways related to muscle fiber type, IMF deposition, lipid metabolism, PPAR signaling, cAMP signaling, amino acid metabolism, and ECM–receptor interaction. Our findings might help improve pork yield by using the obtained DEGs for marker-assisted selection and providing a theoretical reference for evaluating and improving pork quality.

The deployment of a manufacturing execution system (MES) holds promising potential in facilitating the accumulation of a substantial amount of inspection data. Low quality levels in discrete manufacturing environments are the result of multi-factor coupling and the failure to detect quality issues promptly in accordance with manufacturing settings, which may trigger the propagation of downstream defects. Currently, most inspection quality methods consist of direct measurements followed by manual judgment. The integration of deep learning methods provides a feasible way in which to identify defects on time, thus improving the acceptance rate of factories. This paper focuses on the design of a data-driven quality prediction and control model, built around discrete manufacturing characteristics, and uses fuzzy theory to evaluate the quality levels of production stages. Furthermore, a multivariate long- and short-term memory sequence model is proposed in order to explore the qualitative information from time domain features. The data regarding the produced water dispensers are validated using three evaluation indices, namely, RMSE, MAE, and MAPE. The results indicate that the multivariate long- and short-term memory model exhibits stronger prediction performance.

Abstract Background Identification of genomic biomarkers to predict the anticancer effects of indicated drugs is considered a promising strategy for the development of precision medicine. DNA endonuclease MUS81 plays a pivotal role in various biological processes during malignant diseases, mainly in DNA damage repair and replication fork stability. Our previous study reported that MUS81 was highly expressed and linked to tumor metastasis in gastric cancer; however, its therapeutic value has not been fully elucidated. Methods Bioinformatics analysis was used to define MUS81-related differential genes, which were further validated in clinical tissue samples. Gain or loss of function MUS81 cell models were constructed to elucidate the effect and mechanism of MUS81 on WEE1 expression. Moreover, the antitumor effect of targeting MUS81 combined with WEE1 inhibitors was verified using in vivo and in vitro assays. Thereafter, the cGAS/STING pathway was evaluated, and the therapeutic value of MUS81 for immunotherapy of gastric cancer was determined. Results In this study, MUS81 negatively correlated with the expression of cell cycle checkpoint kinase WEE1. Furthermore, we identified that MUS81 regulated the ubiquitination of WEE1 via E-3 ligase β-TRCP in an enzymatic manner. In addition, MUS81 inhibition could sensitize the anticancer effect of the WEE1 inhibitor MK1775 in gastric cancer in vitro and in vivo. Interestingly, when MUS81 was targeted, it increased the accumulation of cytosolic DNA induced by MK1775 treatment and activated the DNA sensor STING-mediated innate immunity in the gastric cancer cells. Thus, the WEE1 inhibitor MK1775 specifically enhanced the anticancer effect of immune checkpoint blockade therapy in MUS81 deficient gastric cancer cells. Conclusions Our data provide rational evidence that targeting MUS81 could elevate the expression of WEE1 by regulating its ubiquitination and could activate the innate immune response, thereby enhancing the anticancer efficacy of WEE1 inhibitor and immune checkpoint blockade combination therapy in gastric cancer cells.

Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study, we demonstrated the mechanism of tumor-derived DNA on the CXCL12-CXCR4 and CCL21-CCR7 axes of hepatocellular carcinoma (HCC) cells and the regulatory effect of sinomenine hydrochloride. Tumor-derived DNA was separated from HCCLM cell lines. Tumor-derived DNA was transfected into SK-Hep1 cells by Lipofectamine 2000. We found that sinomenine hydrochloride reduced the expression of CXCR4, CXCR12, CCR7, and CCL21 in HCC cells, suppressed the growth and invasion of HCC cells, and increased apoptosis. In contrast to the controls, the protein expressions of CXCR4, CXCL12, CCR7, CCL21, P-ERK1/2, MMP-9, and MMP-2 in SK-Hep1 cells were significantly increased after transfection of tumor-derived DNA, while the increase was reversed by sinobine hydrochloride. Acid sinomenine interferes with tumor-derived DNA and affects ERK/MMP signaling via the CXCL12/CXCR4 axis in HCC cells. CXCR4 siRNA and CCR7 siRNA attenuated tumor-derived DNA activation of ERK1/2/MMP2/9 signaling pathways in HCC cells. CXCR4-oe and CCR7-OE enhance the stimulation of erK1/2/MMP2/9 signaling pathway by tumor-derived DNA in HCC cells. Tumor-derived DNA reduced apoptosis and increased invasion of SK-Hep1 cells by CXCL12-CXCR4 axis and CCL21-CCR7 axis, and sinobine hydrochloride reversed this regulation. These results strongly suggest that tumor-derived DNA can increase the growth and invasion of oncocytes via the upregulation of the expression of CXCL12-CXCR4 and CCL21-CCR7 axis and through ERK1/2/MMP2/9 signaling pathway in HCC cells, and sinobine hydrochloride can inhibit this signaling pathway, thus inhibiting HCC cells. These results provide new potential therapeutic targets for blocking the progression of HCC induced by CXCL12-CXCR4 axis and CCL21-CCR7.

Weather radar plays an important role in accurate weather monitoring and modern weather forecasting, as it can provide timely and refined weather forecasts for the public and for decision makers. Deep learning has been applied in radar nowcasting tasks and has exhibited a better performance than traditional radar echo extrapolation methods. However, current deep learning-based radar nowcasting models are found to suffer from a spatial “blurry” effect that can be attributed to a deficiency in spatial variability representation. This study proposes a Spatial Variability Representation Enhancement (SVRE) loss function and an effective nowcasting model, named the Attentional Generative Adversarial Network (AGAN), to alleviate this blurry effect by enhancing the spatial variability representation of radar nowcasting. An ablation experiment and a comparison experiment were implemented to assess the effect of the generative adversarial (GA) training strategy and the SVRE loss, as well as to compare the performance of the AGAN and SVRE loss function with the current advanced radar nowcasting models. The performances of the models were validated on the whole test set and inspected in two storm cases. The results showed that both the GA strategy and SVRE loss function could alleviate the blurry effect by enhancing the spatial variability representation, which helps the AGAN to achieve better nowcasting performance than the other competitor models. Our study provides a feasible solution for high-precision radar nowcasting applications.

Sever fever with thrombocytopenia syndrome (SFTS) is a new infectious disease that has emerged in recent years and is widely distributed, highly contagious, and lethal, with a mortality rate of up to 30%, especially in people with immune system deficiencies and elderly patients. SFTS is an insidious, negative-stranded RNA virus that has a major public health impact worldwide. The development of a vaccine and the hunt for potent therapeutic drugs are crucial to the prevention and treatment of Bunyavirus infection because there is no particular treatment for SFTS. In this respect, investigating the mechanics of SFTS–host cell interactions is crucial for creating antiviral medications. In the present paper, we summarized the mechanism of interaction between SFTS and pattern recognition receptors, endogenous antiviral factors, inflammatory factors, and immune cells. Furthermore, we summarized the current therapeutic drugs used for SFTS treatment, aiming to provide a theoretical basis for the development of targets and drugs against SFTS.

MUS81 is a critical endonuclease involved in heterodimer formation with Eme1/Mms4 and an important DNA damage repair regulatory molecule. Our previous study suggested that MUS81 was overexpressed and its high expression was positively correlated with gastric cancer metastasis. However, the therapeutic potential of targeting MUS81 in gastric cancer requires further exploration. Therefore, in this study, the Cancer Genome Atlas (TCGA) data were analyzed and showed that MUS81 is a key regulator of cell cycle distribution and DNA damage repair in gastric cancer. In vitro and in vivo, MUS81 knockdown significantly enhanced the anticancer effect of the PARP inhibitor talazoparib. Mechanistically, MUS81 inhibition impaired the activation of the ATR/CHK1 cell cycle signaling pathway and promoted gastric cancer cells with talazoparib-induced DNA damage to continue mitosis. Moreover, addition of the bromodomain-containing protein 4 inhibitor AZD5153 increased the anticancer effect of talazoparib via MUS81 inhibition in gastric cancer cells, and this combination effect was largely impaired when MUS81 was knocked down. In conclusion, these data suggested that MUS81 regulated ATR/CHK1 activation, a key signaling pathway in the G2M checkpoint, and targeting MUS81 enhanced the antitumor efficacy of talazoparib. Therefore, AZD5153 combined with talazoparib may represent a promising therapeutic strategy for patients with MUS81 proficient gastric cancer.

Drugs, viruses, and chemical poisons stimulating live in a short period of time can cause acute liver injury (ALI). ALI can further develop into serious liver diseases such as cirrhosis and liver cancer. Therefore, how to effectively prevent and treat ALI has become the focus of research. Numerous studies have reported Maresin1 (MaR1) has anti-inflammatory effect and protective functions on organs. In the present study, we used d-galactosamine/lipopolysaccharide (D-GalN/LPS) to establish an ALI model, explored the mechanism of liver cells death caused by D-GalN/LPS, and determined the effect of MaR1 on D-GalN/LPS-induced ALI. In vivo experiments, we found that MaR1 and ferrostatin-1 significantly alleviated D-GalN/LPS-induced ALI, reduced serum alanine transaminase and aspartate transaminase levels, and improved the survival rate of mice. Meanwhile, MaR1 inhibited hepatocyte death, inhibited tissue reactive oxygen species (ROS) expression, reduced malondialdehyde (MDA), reduced glutathione (GSH), GSH/oxidized glutathione (GSSG), and iron content induced by D-GalN/LPS in mice. In addition, MaR1 inhibited ferroptosis-induced liver injury through inhibiting the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6. Subsequently, western blot showed that MaR1 improved the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4). In vitro experiments, we found that MaR1 inhibited LPS-induced and erastin-induced cell viability reduction. Meanwhile, we found that MaR1 increased the MDA and GSH levels in cells. Western blot showed that MaR1 increased the expression level of Nrf2/HO-1/GPX4. Next, the Nrf2 was knocked down in HepG2 cells, and the results showed that the protective effect of MaR1 significantly decreased. Finally, flow cytometry revealed that MaR1 inhibited ROS production and apoptosis. Overall, our study showed MaR1 inhibited ferroptosis-induced liver injury by inhibiting ROS production and Nrf2/HO-1/GPX4 activation.

BackgroundTo evaluate the difference and efficacy of two donor liver procurement methods for treatment of pediatric acute liver failure (PALF) by living donor liver transplantation (LDLT).MethodsA total of 17 patients (12 men, 5 women) with PALF who underwent LDLT in our hospital between October 2016 and October 2020, and prognostic efficacy of donors and recipients using two donor liver procurement methods were analyzed.ResultsThe donors and recipients were both divided into laparoscopic (7 cases) and open (10 cases) donor liver procurement groups. In the recipients, two deaths occurred in the laparoscopic group and one in the open group, and there were three postoperative complications in the laparoscopic group and six in the open group. The cumulative 1-year and 3-year survival rates in the laparoscopic group and the open group were 80.0% and 85.7% separately. There was no difference in the postoperative survival and complications rates between the two groups. In the donors, the operation time, postoperative hospital stay, and blood loss of the laparoscopic group was significantly reduced compared with the open group (P ≤ 0.01). No death or serious complication occurred in either donor group.ConclusionLaparoscopic donor liver procurement is worth recommending than open donor liver procurement for treatment of PALF combined with LDLT in qualified transplant centers.

Rockfill materials, conducted by impermeable stone, are frequently used in subgrade construction projects. The irregularity and variability of particle shape are demonstrated to affect the mechanical properties of rockfill subgrade, such as void ratio and coordination number. This study first identifies the subgrade rockfill particle contour by machine learning algorithms, including AdaBoost, Cascade, and sliding windows. Then, the shape evaluation indexes of length flatness, edge angle, and roughness are quantified, and the statistical analysis of each index is presented. In addition, the discrete element method (DEM) simulation is implemented on the compaction of rockfill subgrade to explore the impact of roundness on characteristics of particles. Finally, the macroanalysis on the void ratio and cumulative settlement and the microanalysis on particle coordination number, rotation momentum, and displacement are studied. The results illustrate that roundness has a significant effect on the mechanical characteristics of subgrade rockfill materials. With the increase of rolling passes, the porosity of packing decreases, whereas the settlement increases gradually. The change rate starts fast and ends slowly.

4-Octyl itaconate (OI) is a novel anti-inflammatory metabolite that exerts protective effects in many various disease models. However, its function in autoimmune hepatitis- (AIH-) associated hepatic injury has not been investigated. In this study, we successfully used concanavalin A (Con A) to establish an AIH-associated liver injury model. Furthermore, we investigated the effect of OI in Con A-induced liver injury and found that OI mitigated Con A-induced histopathological damage. OI administration reduced serum levels of alanine transaminase and aspartate transaminase in Con A-treated mice and attenuated the infiltration of macrophages induced by Con A. Moreover, OI effectively inhibited the expression of proinflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and IL-1β induced by Con A. Furthermore, OI decreased hepatocyte apoptosis and malondialdehyde levels and increased the reduced glutathione/oxidized glutathione ratio in the Con A-induced liver injury model. In addition, we found that OI inhibited Con A-induced hepatocyte apoptosis in vitro, while Nrf2 deletion eliminated this effect. Furthermore, we administrated the Nrf2 inhibitor ML385 in OI+Con A-treated mice and found that ML385 eliminated the protective effect of OI in vivo. In addition, OI inhibited Con A-induced activation of nuclear factor-kappa B (NF-𝜅B) and the expression of proinflammatory cytokines in macrophages. Therefore, OI protected mice from Con A-induced liver damage and may be associated with Nrf2 activation and NF-𝜅B inhibition. Finally, our study revealed that OI inhibited TNF-α, or supernatants from Con A-treated RAW264.7 cells induced hepatocyte apoptosis. In conclusion, our study indicated that OI alleviated Con A-induced hepatic damage by reducing inflammatory response, oxidative stress, and apoptosis.

Abstract Background The links between the p53/MDM2 pathway and the expression of pro-oncogenic immune inhibitory receptors in tumor cells are undefined. In this report, we evaluate whether there is p53 and/or MDM2 dependence in the expression of two key immune receptors, CD276 and PD-L1. Methods Proximity ligation assays were used to quantify protein-protein interactions in situ in response to Nutlin-3. A panel of p53-null melanoma cells was created using CRISPR-Cas9 guide RNA mediated genetic ablation. Flow cytometric analyses were used to assess the impact of TP53 or ATG5 gene ablation, as well as the effects of Nutlin-3 and an ATM inhibitor on cell surface PD-L1 and CD276. Targeted siRNA was used to deplete CD276 to assess changes in cell cycle parameters by flow cytometry. A T-cell proliferation assay was used to assess activity of CD4+ T-cells as a function of ATG5 genotype. Results CD276 forms protein-protein interactions with MDM2 in response to Nutlin-3, similar to the known MDM2 interactors p53 and HSP70. Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. PD-L1 was also unexpectedly induced by Nutlin-3, but PD-L1 does not bind MDM2. The ATM inhibitor KU55993 reduced the levels of PD-L1 under conditions where Nutlin-3 induces PD-L1, indicating that MDM2 and ATM have opposing effects on PD-L1 steady-state levels. PD-L1 is also up-regulated in response to genetic ablation of TP53 in A375 melanoma cell clones under conditions in which CD276 remains unaffected. A549 cells with a deletion in the ATG5 gene up-regulated only PD-L1, further indicating that PD-L1 and CD276 are under distinct genetic control. Conclusion Genetic inactivation of TP53, or the use of the MDM2 ligand Nutlin-3, alters the expression of the immune blockade receptors PD-L1 and CD276. The biological function of elevated CD276 is to promote altered cell cycle progression in response to Nutlin-3, whilst the major effect of elevated PD-L1 is T-cell suppression. These data indicate that TP53 gene status, ATM and MDM2 influence PD-L1 and CD276 paralogs on the cell surface. These data have implications for the use of drugs that target the p53 pathway as modifiers of immune checkpoint receptor expression.

Abstract Background Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported. Methods We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models. Results Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e−06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis. Conclusions In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma. Impact The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility.

The liver is an important metabolic organ, and acute liver injury (ALI) is potentially lethal. Itaconate, a metabolic intermediate from the tricarboxylic acid cycle, showed emerging anti-oxidative and anti-inflammation properties, and an accumulating protective effect in multiple diseases, but its role in ALI still needs to be further explored. Here we established an ALI model induced by carbon tetrachloride in mice. Our results showed that 4-Octyl itaconate (OI), a derivate of itaconate, mitigated hepatic damage by improving liver function, reducing histopathological damage, and decreasing the death of hepatocytes. Additionally, OI decreased myeloperoxidase and thiobarbituric acid reactive substances (TBARS) levels in the ALI model. OI also inhibited the inflammatory response by reducing pro-inflammatory cytokine secretion (IL-6, TNF-α, IL-1β, and MCP-1) and infiltration of macrophages and neutrophils in the ALI model. However, administration of ML385, a specified Nrf2 inhibitor, eliminated the protective properties of OI in the CCl4-induced liver injury model by increasing hepatic damage and oxidative stress. Furthermore, OI increased the expression and nuclear translocation of Nrf2 and elevated the expression of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1, while knockdown of Nrf2 eliminated these effects in murine hepatocyte NCTC 1469 under CCl4 treatment. Moreover, we found that OI reduced serum High-mobility group box 1 (HMGB1) levels in CCl4-treated mice. Finally, OI inhibited nuclear translocation of factor-kappa B (NF-𝜅B) and inflammatory cytokine production in murine macrophages. In conclusion, these results indicated that OI ameliorated CCl4-induced ALI by mitigating oxidative stress and the inflammatory response. The possible mechanism was associated with the elevation of Nrf2 nuclear translocation and inhibition of HMGB1 mediated the nuclear translocation of NF-𝜅B.

Graded crushed stone (GCS), as a cheap and essential component, is of great importance in road construction. The irregularity and variability of particle shape is known to affect the packing characteristics of GCS, such as compactness and void ratio. In this study, the realistic particle outline is first automatically extracted based on digital image processing and deep learning algorithms. Then, the elongation (EI), roundness (Rd), and roughness (Rg) of GCS are quantified by shape evaluation algorithms. Moreover, based on the establishment of the GCS shape library, the gravity deposition with various elongations is simulated using the discrete element method to study the packing features of GCS. The elongation effects on the macroscopic and microscopic quantities are explored. Finally, the shear behavior of GCS is studied. The results illustrate that elongation has a significant effect on the packing of GCS.

Purpose: Postoperative anemia has been a threat to total hip arthroplasty patients. We introduced a novel medullary cavity hemostasis (MCH) technique and combined it with tranexamic acid (TXA) to prevent postoperative anemia in elder patients. This trial was conducted to evaluate the effectiveness and safety of this technique. Methods: In this retrospective consecutive study, each group has 88 patients who were all over 70 years old. In the control group, patients were given TXA. In the experimental group, the MCH technique and same TXA application were used. Results: The average of total blood loss, drainage volume, and hidden blood loss were significantly less in the experimental group. The postoperative hemoglobin (Hb) level was significantly higher in the experimental group (100.6 g/dL) than it is in the control group (81.4 g/dL). None of the patient has shown signs of prosthesis subsidence, periprosthetical osteolysis, or stem loosening during follow-ups in the average follow-up time of 3 years. Conclusion: We discovered that application of TXA alone is not sufficient to prevent postoperative moderate anemia in patients over 70 years old. Combination of TXA and MCH is an effective and safe way to alleviate the severity of postoperative anemia.

BackgroundCoronary artery disease (CAD) is a type of cardiovascular disease that greatly hurts the health of human beings. Diabetic status is one of the largest clinical factors affecting CAD-associated gene expression changes. Most of the studies focus on diabetic patients, whereas few have been done for non-diabetic patients. Since the pathophysiological processes may vary among these patients, we cannot simply follow the standard based on the data from diabetic patients. Therefore, the prognostic and predictive diagnostic biomarkers for CAD in non-diabetic patient need to be fully recognized.Materials and MethodsTo screen out candidate genes associated with CAD in non-diabetic patients, weighted gene co-expression network analysis (WGCNA) was constructed to conduct an analysis of microarray expression profiling in patients with CAD. First, the microarray data GSE20680 and GSE20681 were downloaded from NCBI. We constructed co-expression modules via WGCNA after excluding the diabetic patients. As a result, 18 co-expression modules were screened out, including 1,225 differentially expressed genes (DEGs) that were obtained from 152 patients (luminal stenosis ≥50% in at least one major vessel) and 170 patients (stenosis of

Big data has a strong demand for a network infrastructure with the capability to support data sharing and retrieval efficiently. Information-centric networking (ICN) is an emerging approach to satisfy this demand, where big data is cached ubiquitously in the network and retrieved using data names. However, existing authentication and authorization schemes rely mostly on centralized servers to provide certification and mediation services for data retrieval. This causes considerable traffic overhead for the secure distributed sharing of data. To solve this problem, we employ identity-based cryptography (IBC) to propose a Distributed Authentication and Authorization Scheme (DAAS), where an identity-based signature (IBS) is used to achieve distributed verifications of the identities of publishers and users. Moreover, Ciphertext-Policy Attribute-based encryption (CP-ABE) is used to enable the distributed and fine-grained authorization. DAAS consists of three phases: initialization, secure data publication, and secure data retrieval, which seamlessly integrate authentication and authorization with the interest/data communication paradigm in ICN. In particular, we propose trustworthy registration and Network Operator and Authority Manifest (NOAM) dissemination to provide initial secure registration and enable efficient authentication for global data retrieval. Meanwhile, Attribute Manifest (AM) distribution coupled with automatic attribute update is proposed to reduce the cost of attribute retrieval. We examine the performance of the proposed DAAS, which shows that it can achieve a lower bandwidth cost than existing schemes.

Optimizing the spatial distribution of plants under normal conditions of water and fertilizer is widely used by farmers to improve soybean yield. However, the relationship between soybean yield and spatial plant distribution in the field has not been well studied. This study examined the effect of planting density and plant distribution pattern on soybean plant growth, yield components, canopy light interception, and dry matter accumulation. We also analyzed the relationship between photosynthetic rate, dry matter accumulation, and yield under different planting densities and plant distribution. A two year field experiment was conducted during the 2018 and 2019 soybean planting seasons. Two planting densities (1.8 × 105 and 2.7 × 105 plants ha−1) and two plant distribution patterns (uniform and non-uniform plant spacing) were tested. Higher planting density significantly increased the canopy light interception and dry matter accumulation during soybean growth, leading to increased soybean productivity. The seed yield of soybean under higher planting density was 22.8% higher than under normal planting density. Soybean planted under uniform spacing significantly reduced the differences plant-to-plant. Uniform plant spacing significantly increased the canopy light interception and dry matter accumulation of the soybean population. In addition, the coefficient of variation of seed weight per plant between individual plants under uniform plant distribution decreased by 71.5% compared with non-uniform plant distribution. Furthermore, uniform plant distribution increased soybean seed yield by 9.5% over non-uniform plant distribution. This study demonstrates that increasing planting density under uniform plant distribution can be useful to obtain higher seed yield without increasing other farm inputs.

Multiple cropping systems boost grain yields and have an immense potential to increase land productivity. In such cropping systems in China, soybean is directly seeded after the wheat harvest in early June. After the wheat harvest, the farmland has low amounts of soil moisture and contains large amounts of wheat straw, which negatively affect soybean growth and yields. To address these challenges, an integrated management practice (IMP) than can achieve precise direct seeding and straw mulching return, was developed. In this study, differences in the soil temperature and moisture, seedling quality, dry matter accumulation, soybean yield, and greenhouse gas emissions were investigated between IMP and the farmers’ practices (FP). Compared with the FP treatment, IMP significantly increased the soil moisture and decreased the soil temperature in the topsoil layer. In addition, under the IMP treatment, the rate of emergence and developmental uniformity of soybean plants significantly increased by 21.7% and 99.5%, respectively, thus increasing the leaf area index by 30.0% and dry matter accumulation by 12.0% and, in turn, increasing soybean yields by 24.7%. A principal component analysis showed that the dry matter weight, relative water content, leaf area index, and developmental uniformity were strong sensitivity indices for the IMP treatment. In addition, the intensity of emission of N2O and greenhouse gases under IMP both decreased significantly by 25.1% and 28.9% compared with the FP, respectively. Thus, it was concluded that IMP is a suitable farming practice for sustainable agricultural production, and it has broad prospects for application in wheat–soybean double cropping systems in China and other similar areas globally.

Diagnosis of the presence of tumors and subsequent prognosis based on tumor microenvironment becomes more clinically practical because tumor-adjacent tissues are easy to collect and they are more genetically homogeneous. The purpose of this study was to identify new prognostic markers in prostate stroma that are near the tumor. We have demonstrated the prognostic features of FGFR1, FRS2, S6K1, LDHB, MYPT1, and P-LDHA in prostate tumors using tissue microarrays (TMAs) which consist of 241 patient samples from Massachusetts General Hospital (MGH). In this study, we investigated these six markers in the tumor microenvironment using an Aperio Imagescope system in the same TMAs. The joint prognostic power of markers was further evaluated and classified using a new algorithm named Weighted Dichotomizing. The classifier was verified via rigorous 10-fold cross validation. Statistical analysis of the protein expression indicated that in tumor-adjacent stroma FGFR1 and MYPT1 were significantly correlated with patient outcomes and LDHB showed the outcome-association tendency. More interestingly, these correlations were completely opposite regarding tumor tissue as previously reported. The results suggest that prognostic testing should utilize either tumor-enriched tissue or stroma with distinct signature profiles rather than using mixture of both tissue types. The new classifier based on stroma tissue has potential value in the clinical management of prostate cancer patients.

Increasing planting density is one of the key management practices to enhance soybean yield. A 2-yr field experiment was conducted in 2018 and 2019 including six planting densities and two soybean cultivars to determine the effects of planting density on branch number and yield, and analyze the contribution of branches to yield. The yield of ZZXA12938 was 4389 kg ha−1, which was significantly higher than that of ZH13 (+22.4%). In combination with planting year and cultivar, the soybean yield increased significantly by 16.2%, 31.4%, 41.4%, and 46.7% for every increase in density of 45,000 plants ha−1. Yield will not increase when planting density exceeds 315,000 plants ha−1. A correlation analysis showed that pod number per plant increased with the increased branch number, while pod number per unit area decreased; thus, soybean yield decreased. With the increase of branch number, the branch contribution to yield increased first, and then plateaued. ZH13 could produce a high yield under a lower planting density due to more branches, while ZZXA12938 had a higher yield potential under a higher planting density due to the smaller branch number and higher tolerance to close planting. Therefore, seed yield can be increased by selecting cultivars with a little branching capacity under moderately close planting.

Big data strongly demands a network infrastructure having the capability to efficiently collect, process, cache, share, and deliver the data, instead of simple transmissions. Such network designs show the requirements of energy efficiency, availability, high performance, and data-aware intelligence. To meet these requirements, we adopt the information-centric networking (ICN) approach, where data are retrieved through names and in-network caching is utilized. However, as the typical existing ICN architectures, content centric network (CCN) cannot efficiently utilize the caches for data sharing because of the on-path caching strategy, and network of information (NetInf) demonstrates the resolution latency for data retrievals. To design an efficient and effective ICN architecture for big data sharing, we combine the strong points of CCN and NetInf, where information islands (IOIs) and management plane are utilized for direct data retrieval and global data discovery, respectively. We provide a reference architecture and propose an aggregatable name-based routing (ANBR), which can naturally enable consumers to retrieve the closest copy of information. In this network, each piece of data can be cached at one IOI at most once, which greatly improves the efficiency of cache usages. The consumers first try to retrieve the data in the local IOI, and then try to globally retrieve it from the closest IOI, holding the copy of the data if necessary. We investigate the impact from the key factor, IOI size, to the energy consumption of ANBR. It shows that energy consumption first decreases and then increases as the IOI size increases, and the optimized IOI size can be found for deployment. Furthermore, we study the relation between the optimized IOI size and the average retrieval times for the data. The result shows that the optimized IOI size increases as the average retrieval times increase.

The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

Sepsis, frequently caused by infection of bacteria, is considered as an uncontrollable systematic inflammation response syndrome (SIRS). Maresin 1 (Mar1) is a new proresolving mediator with potent anti-inflammatory effect in several animal models. However, its effect in sepsis is still not investigated. To address this question, we developed sepsis model in BALB/c mice by cecal ligation and puncture (CLP) with or without Mar1 treatment. Our data showed that Mar1 markedly improved survival rate and decreased the levels of proinflammatory cytokines in CLP mice such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Furthermore, Mar1 reduced serum level of lipopolysaccharide (LPS) and enhanced the bacteria clearance in mice sepsis model. Moreover, Mar1 attenuated lung injury and decreased level of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cre), and blood urea nitrogen (BUN) in serum in mice after CLP surgery. Treatment with Mar1 inhibited activation of nuclear factor kappa B (NF-κb) pathway. In conclusion, Mar1 exhibited protective effect in sepsis by reducing LPS, bacteria burden in serum, inhibiting inflammation response, and improving vital organ function. The possible mechanism is partly involved in inhibition of NF-κb activation.

In the present study the capacity of Radix Paeoniae Rubra aqueous extract (RPRAE) as an antioxidant to protect against carbon tetrachloride (CCl4)-induced oxidative stress and hepatotoxicity in Wistar rats was investigated. Six groups of rats were used. Radix Paeoniae Rubra aqueous extract (100 or 200 or 300 mg/kg of bw) or bifendate (100 mg/kg of bw) were given daily by gavage to the animals on 28 consecutive days to elucidate the protective effects against CCl4-induced hepatotoxicity. The 20% CCl4/olive oil was gavage of gastric tube twice a week (on the third and seventh days of each week). The animals of normal control group were given only vehicle. The animals of CCl4-treated group were administered with CCl4 twice a week (on the third and seventh days of each week) and with vehicle on rest of the days. The test materials were found effective as hepatoprotective agents, as evidenced by plasma and liver biochemical parameters. Therefore, the results of this study show that Radix Paeoniae Rubra aqueous extract can protect the liver against CCl4-induced oxidative damage in rats, and the hepatoprotective effects might be correlated with its antioxidant and free radical scavenger effects.