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Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor outcomes, especially in older AML patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer drug because it selectively induces the extrinsic apoptosis of tumor cells without affecting normal cells. However, clinical trials have shown that the responses of patients to TRAIL are significantly heterogeneous. It is necessary to explore predictable biomarkers for the preselection of AML patients with better responsiveness to TRAIL. Here, we investigated the critical role of tumor protein p53 inducible nuclear protein 2 (TP53INP2) in the AML cell response to TRAIL treatment. Methods: First, the relationship between TP53INP2 and the sensitivity of AML cells to TRAIL was determined by bioinformatics analysis of Cancer Cell Line Encyclopedia datasets, Cell Counting Kit-8 assays, flow cytometry (FCM) and cell line-derived xenograft (CDX) mouse models. Second, the mechanisms by which TP53INP2 participates in the response to TRAIL were analyzed by Western blot, ubiquitination, coimmunoprecipitation and immunofluorescence assays. Finally, the effect of TRAIL alone or in combination with the BCL-2 inhibitor venetoclax (VEN) on cell survival was explored using colony formation and FCM assays, and the effect on leukemogenesis was further investigated in a patient-derived xenograft (PDX) mouse model. Results: AML cells with high TP53INP2 expression were more sensitive to TRAIL in vitro and in vivo. Gain- and loss-of-function studies demonstrated that TP53INP2 significantly enhanced TRAIL-induced apoptosis, especially in AML cells with nucleophosmin 1 (NPM1) mutations. Mechanistically, cytoplasmic TP53INP2 maintained by mutant NPM1 functions as a scaffold bridging the ubiquitin ligase TRAF6 to caspase-8 (CASP 8), thereby promoting the ubiquitination and activation of the CASP 8 pathway. More importantly, simultaneously stimulating extrinsic and intrinsic apoptosis signaling pathways with TRAIL and VEN showed strong synergistic antileukemic activity in AML cells with high levels of TP53INP2. Conclusion: Our findings revealed that TP53INP2 is a predictor of responsiveness to TRAIL treatment and supported a potentially individualized therapeutic strategy for TP53INP2-positive AML patients. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) play vital roles in the plant life cycle and synthetic BRs are widely used to increase crop yield and plant stress tolerance. Among them are 24R-methyl-epibrassinolide (24-EBL) and 24S-ethyl-28-homobrassinolide (28-HBL), which differ from brassinolide (BL, the most active BR) at the C-24 position. Although it is well known that 24-EBL is 10% active as BL, there is no consensus on the bioactivity of 28-HBL. A recent outpouring of research interest in 28-HBL on major crops accompanied with a surge of industrial-scale synthesis that produces mixtures of active (22R,23R)-28-HBL and inactive (22S,23S)-28HBL, demands a standardized assay system capable of analyzing different synthetic "28-HBL" products. In this study, the relative bioactivity of 28-HBL to BL and 24-EBL, including its capacity to induce the well-established BR responses at molecular, biochemical, and physiological levels, was systematically analyzed using the whole seedlings of the wild-type and BR-deficient mutant of Arabidopsis thaliana. These multi-level bioassays consistently showed that 28-HBL exhibits a much stronger bioactivity than 24-EBL and is almost as active as BL in rescuing the short hypocotyl phenotype of the dark-grown det2 mutant. These results are consistent with the previously established structure–activity relationship of BRs, proving that this multi-level whole seedling bioassay system could be used to analyze different batches of industrially produced 28-HBL or other BL analogs to ensure the full potential of BRs in modern agriculture. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with a nucleophosmin 1 (NPM1) mutation is a unique subtype of adult leukemia. Recent studies show that NPM1-mutated AML has high autophagy activity. However, the mechanism for upholding the high autophagic level is still not fully elucidated. In this study, we first identified that tumor protein p53 inducible nuclear protein 2 (TP53INP2) was highly expressed and cytoplasmically localized in NPM1-mutated AML cells. Subsequent data showed that the expression of TP53INP2 was upregulated by fat mass and obesity-associated protein (FTO)-mediated m6A modification. Meanwhile, TP53INP2 was delocalized to the cytoplasm by interacting with NPM1 mutants. Functionally, cytoplasmic TP53INP2 enhanced autophagy activity by promoting the interaction of microtubule-associated protein 1 light chain 3 (LC3) - autophagy-related 7 (ATG7) and further facilitated the survival of leukemia cells. Taken together, our study indicates that TP53INP2 plays an oncogenic role in maintaining the high autophagy activity of NPM1-mutated AML and provides further insight into autophagy-targeted therapy of this leukemia subtype. [ABSTRACT FROM AUTHOR]

This work focuses on integrated stability assessment of rocky tunnel slopes along a planned railway, namely, the Dujiangyan City to Siguniang Mountain Railway (DS Railway), which is an important transportation corridor in Southwest China. Investigating the stability of slopes at the entrances and exits of tunnels represents the first step of railway construction. Based on detailed geological engineering studies, the stability of 32 tunnel slopes was measured and evaluated by means of the slope mass rating (SMR), Chinese slope mass rating (CSMR) and Chinese continuous slope mass rating (CCSMR) systems. Moreover, a kinematic analysis technique was also employed to identify the potential failure modes of the jointed rock masses in tunnel slopes. The results reveal that the CSMR, by considering the slope height and discontinuity condition coefficient, can more robustly assess the slope stability than the SMR. Similarly, the CCSMR, which is based on continuous functions and can identify potentially dangerous slopes that should be reinforced, can reduce subjectivity. Many slopes deemed unstable and completely unstable by the CSMR and CCSMR are located on the banks of the river from Longchi to Longtan and from Xindianzi to Siguniang Mountain. The potential failure modes of the 32 slopes determined by kinematic analysis are basically consistent with the results obtained by the slope mass classification systems. These research results pave the way for stability assessment and intervention decision-making during the construction of the DS Railway. [ABSTRACT FROM AUTHOR]

• Experiences from SWH systems mandatory installation in China were summarized. • The interaction of seven stakeholders in SWH building application was analyzed. • Three key factors for the successful mandatory installation of SWH were summarized. • Recommendations were given for using the mandatory installation policy effectively. • The government should regularly evaluate the effectiveness of policy implementation. The paper summarizes the implementation experiences and lessons learned from the solar water heating (SWH) system mandatory installation policy in China. In-depth interviews, questionnaire surveys and field investigation were conducted to understand the prevailing attitudes of the stakeholders associated with the application of SWH in buildings. Scenario analysis was used to analyze the effect of expanding the coverage of mandatory installation policies. The results show that due to the strong market externalities of SWH building applications, the government must provide inducements to stakeholders through mandatory policies or fiscal incentives to create an impetus for them to use SWH extensively. For China, it is necessary to strengthen and support the utilization of renewable energy policies and extend the mandatory installation policy of SWH systems to taller buildings to fulfill the national renewable energy application goals. The most reasonable technical route, full process control, and attention to system operation and maintenance are the three key factors for the successful implementation of a mandatory installation policy for SWH systems. The policy recommendations presented in this paper can not only be applied to China but also other developing countries as well. [ABSTRACT FROM AUTHOR]

• Experience and lessons summarized on the first solar district heating system in rural Beijing. • A solar-assisted GSHP system is a reliable solution for district heating. • Solar collectors contribute to heat balance of the soil heat storage. • An optimized scenario with a reduction of overall operating cost by 10.9% proposed. • The combination of domestic hot water and space heating is worth promoting in China. Experimental and theoretical investigations have been carried out on the first large scale solar assisted ground source heat pump (SAGSHP) for heating and cooling of a village in the outskirts of Beijing. Long term performances of the system without and with solar heating were monitored. A TRNSYS model of the SAGSHP system was developed and validated against the measured data. Based on a parametrical investigation using the model, an optimized solution was proposed. It is shown that adding a domestic hot water system to the original SAGSHP system will not only help to secure thermal balance of the ground but also reduces primary energy consumption for hot water by 70%. The system COP increases by 9.4% from 2.42 to 2.65 and the annual overall operating cost decreases from 892,000 CNY to 794,000 CNY with only a small increase in equipment cost. Under the premise of ensuring thermal balance of the ground, there is an optimal match between the size of the ground heat storage, the collector area and the tank volume. Experience and lessons learned from the project are conducive to successful implementation of similar projects in the future. [ABSTRACT FROM AUTHOR]

Study on the weathering characteristics of Niche of Sakyamuni Entering Nirvana at Dazu Rock Carvings is the first step of scientific conservation. Based on the in-depth investigation on the weathering characteristics of Niche of Sakyamuni Entering Nirvana, the weathering degree was measured and evaluated by means of the in-situ non-destructive surface hardness test and ultrasonic test. The results reveal that the weathering types of Niche of Sakyamuni Entering Nirvana consist of granular disintegration, salt efflorescence, scaling, blistering, cracking, missing parts, biological colonization, and water seepage. The weathering degree of the head and foot of the statues are higher than that of the chest and abdomen in the horizontal direction, and the weathering degree of the upper parts of the statues and the ground area are higher than that between them in the vertical direction. The results of surface hardness and ultrasonic velocity are in close accordance with the weathering degree of the statues. Sedimentary and structural characteristics of sandstone lay a material foundation for various weathering characteristics and degree. The research results pave the way for condition assessment, intervention decision-making, and preventative conservation of the studied statues. [ABSTRACT FROM AUTHOR]

Abstract Solar thermal has contributed little for space heating in China. In 2014, although China shared 75.8% of the total solar collector installations in the world, only less than 0.3% of the solar collectors were used for space heating. To promote solar district heating (SDH) in China, based on Danish experiences and Chinese clean heating transformation practices, a PEST (policy, economics, social, and technology) analysis and a SWOT (strengths, weaknesses, opportunities, and threats) analysis on SDH development in China were conducted. An extensive survey and on-site investigation were carried out to identify the applicability of SDH in rural areas. SDH development strategies, roadmap, and decision-making process for a SDH project are summarized. SDH has a broad application prospect in China with abundant solar resources and favorable policies. The solar heated floor area can achieve 756 million m2 with an assumption of 3% coverage of the total heat demand of buildings. Particular areas with low population density, scarce resources, and strict environmental requirements, e.g., Tibet, should be given a high priority for SDH. Rural villages and small towns with better infrastructure, e.g., district heating networks, are the best target market for SDH in the next five years. With the development of seasonal heat storage technologies and the accumulation of practical experience, SDH can be expanded to industrial parks, large residential communities in sparsely populated northwest China. Integration of solar heat with existing heating networks in big cities with central heating will be challenging in the long run. Highlights • The solar heated area can achieve 756 million m2 with an assumption of 3% coverage of the total heated area in China. • High-performance flat plate collectors will significantly increase the reliability of solar district heating systems. • A solar assisted ground source heat pump system is a reliable solution as a form of solar district heating. • Particular areas with low population density should be given high priority for solar district heating. • Land availability is a significant obstacle to the development of large-scale solar district heating. [ABSTRACT FROM AUTHOR]

China is the second-largest economy country, and the largest country worldwide in total solar energy system capacity installed. More than 70% of total solar collector capacity worldwide is installed in China. The production of solar collector in China had decreased significantly from 64 million m2 in 2012 to 37 million m2 in 2017, corresponding to a reduction of around 40% of the market in 2012. There are very limited comprehensive studies in existing literature, which have investigated the reasons on the decline of Chinese solar thermal market. This study aims to identify the reasons from both the demand and the supply sides in details. Furthermore, with the rise of emerging markets, such as the rapid development of the "Clean Heating Initiative" for space heating in North China, solar heat industrial process, and the mandatory installation of solar domestic hot water system for residential buildings below 100 m in urban area, the Chinese solar thermal market is expected to recover soon, called "U-shaped curve" in this study. The market share of flat plate collector and evacuated tube collector is predicted to change in the near future. The research and development of flat plate solar collectors will increase continually in the market other than evacuated tube solar collectors like the past 10 years. The main driver for the solar thermal market development in China in the near future will be the demand from the urban area. • The largest solar thermal market worldwide has been presented. • The market share of flat plate collector will continue to grow gradually. • Market factors from both supply and demand sides are analyzed in detail. • Scenarios is predicted in short, middle and long terms. [ABSTRACT FROM AUTHOR]

Slow light devices have important applications in many fields such as optical communication, optical storage, optical signal shaping and synchronization. Although a variety of high-performance slow light devices can be purchased in the market, it is still a worthwhile research topic to design slow light devices according to specific wavelengths and requirements. Here we employ machine learning method to inverse design electromagnetically induced transparency (EIT) based slow light devices in communication band using metal–dielectric hybrid metamaterials. Three characteristic points of transmittance as well as the group refractive index and bandwidth are chosen as input parameters. By replacing the complex fully connected layer with a one-dimensional convolutional neural network (1DCNN) layer to optimize the fully connected network, the proposed model can break the limitation of passive modulation and find the best slow light structure parameters. The slow light parameters could reach a bandwidth of 38.71 nm and average group refractive index of 10.51. In addition, the model can predict hybrid metamaterial structure parameters of slow light devices in the communication band from 1400 nm to 1600 nm. By combining active and passive modulation technologies, our proposed method improves the adjustment range of design parameters of slow light devices. The procedure can be potentially applied in the design of other nano optical devices. • The proposed model can find the optimal slow light structure parameters by utilizing a 1D convolutional neural network (1DCNN) layer to optimize the fully connected network. • By the prediction of the model, the slow light parameters could reach a bandwidth of 38.71 nm and average group refractive index of 10.51 in our metamaterial. • The model can predict hybrid metamaterial structure parameters of slow light devices in the communication band from 1400 nm to 1600 nm. [ABSTRACT FROM AUTHOR]

In the past decades, solar heat for industrial processes (SHIP) have been rapidly developed and applied, and also getting more and more attention all over the world. China is the largest energy consumer with industry accounting for almost 70% of its total energy consumption. Low- and medium-temperature heat takes up 45% of process heat, covering 50–70% of industrial energy consumption, which provides a favorable condition for solar application in industrial processes. China has built developed some demonstration projects to make industrial processes well integrated with solar heating systems. This paper briefly summarizes the status of China's energy consumption, integration of SHIP, as well as available matching solar technologies. Ten typical industrial sectors are selected to specifically describe their potential of SHIP. Moreover, 26 SHIP cases covering the selected 10 sectors are presented by field researches, with capacity of energy saving and emission reduction previously investigated according to their own proportion of SHIP. The potential of SHIP in the 10 sectors are further predicted by optimistically and conservatively making their proportion in SHIP 5.5% and 2% respectively during the period of 2016–2020. The results show that at least 39.40 million tons of coal equivalent and 98.22 million tons of CO 2 emission is expected to be reduced in 2020 in China's all industrial sectors although solar can meet different proportions of heat demand in different industrial sectors. [ABSTRACT FROM AUTHOR]

We aim to identify the potential genes and signaling pathways associated with the nasopharyngeal carcinoma (NPC) prognosis using Weighted Gene Co-Expression Network Analysis (WGCNA). Gene Expression Omnibus (GEO) query was utilized to download two NPC mRNA microarray data. WGCNA was conducted on differentially expressed genes (DEGs) to obtain tumor-associated gene modules. Genes in core modules were intersected with DEGs for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis and the results were confirmed by quantitative polymerase chain reaction (qPCR). Co-expression networks were built, and we detected 12 gene modules. The Brown module and Magenta module were extremely associated with NPC samples. GO functional analysis and KEGG pathway analysis was carried out to the genes in the Brown and Magenta modules. Our data indicated that DEGs in Brown module and Magenta module were correlated with the biological regulation, metabolic process, reproduction, and cellular proliferation. Twenty-six hub genes were obtained and were considered to be closely related to NPC. GSE102349 dataset was devoted to identifying prognostic hub genes by survival analysis. The expression of IL33, MPP3 and SLC16A7 in GSE102349 dataset was significantly correlated with the progression-free survival (PFS). The results of qPCR indicated a strong correlation between SLC16A7 expression and the overall survival (OS). WGCNA contributed to the detection of gene modules and identification of hub genes and crucial genes. These crucial genes might be potential targets for pharmaceutic therapies with potential clinical significance. [ABSTRACT FROM AUTHOR]

Background. Biomarker research in head and neck squamous cell carcinoma (HNSCC) is constantly revealing promising findings. An enhancer of polycomb homolog 1 (EPC1) was found to play a procancer role in nasopharyngeal carcinoma (NPC), but its role in HNSCC with strong heterogeneity is still unclear. Herein, we investigated the prognostic significance and related mechanisms of EPC1 in HNSCC. Methods. The Kaplan-Meier plotter was used to evaluate the prognostic significance of EPC1. Based on a range of published public databases, the multiomics expression of EPC1 in HNSCC was explored to investigate the mechanisms affecting prognosis. Results. According to the clinical data, high EPC1 expression in HNSCC was a predictor of patient prognosis (hazard ratio HR = 0.64 ; 95% confidence interval (CI) 0.49-0.83; P < 0.01). EPC1 expression varied among clinical subtypes and was related to key factors, such as TP53 and human papillomavirus (HPV) (P < 0.05). At the genetic level, EPC1 expression level may be associated with protein phosphorylation, cell adhesion, cancer-related pathways, etc. For the noncoding region, a competing endogenous RNA network was constructed, and 6 microRNAs and 12 long noncoding RNAs were identified. At the protein level, a protein-protein interaction (PPI) network related to EPC1 expression was constructed and found to be involved in HPV infection, endocrine resistance, and multiple cancer pathways. At the immune level, EPC1 expression was correlated with a variety of immune cells and immune molecules, which together constituted the immune microenvironments of tumors. Conclusion. High EPC1 expression may predict a better prognosis in HNSCC, as it is more frequently found in HNSCC with HPV infection. EPC1 may participate in the genomics, transcriptomics, proteomics, and immunomics of HNSCC, and the results can provide a reference for the development of targeted drugs and evaluation of patient prognosis. [ABSTRACT FROM AUTHOR]

To find an optimal economic solution for solar district heating (SDH) in China, an evaluation model based on the levelized cost of heat (LCoH) is developed. A Python program is developed to calculate the LCoH of SDH systems using the quasi-dynamic test method. Based on these calculations, the trend of LCoH with solar collector area under different heating load intensities, heating terminal units, heated areas and land rents is discussed. The optimal solar collector area and the solar fraction are determined for combinations of solar thermal with four types of auxiliary heat sources, including air source heat pumps, ground source heat pumps, gas boilers and gas boilers with seasonal heat storage. The calculations show an economic optimal solar fraction of 11%–33% for a SDH system with heat pumps. High dependency of LCoH on network temperature is found for a SDH system with gas boilers. Seasonal heat storage minimizes LCoH of a SDH system with gas boilers at 100% solar fraction. The findings can be used as a reference for local authorities, consultants and engineers in the early energy planning to determine the optimal proportion of solar energy in a district heating system with the lowest operating cost. • An optimal solar fraction of 11%–33% for a SDH system with heat pumps. • High dependency of LCoH on network temperature for a SDH system with gas boilers. • Heat storage minimizes LCoH of a SDH system with gas boilers at 100% solar fraction. • The higher the heat demand, the greater the solar contributed economic benefits are. • With biomass >1100 CNY/ton, the biomass heating system reduces LCoH by adding solar. [ABSTRACT FROM AUTHOR]

High-rise buildings have a significant impact on the surrounding environment. Building-integrated solar water heating (SWH) systems are effective ways to use renewable energy in buildings. Impediments, such as security concerns, aesthetics and functionality, make it difficult to apply SWH systems in high-rise buildings. At present, only China uses SWH systems on a large scale in such buildings. What are China's experiences and lessons learned in applying SWH systems in high-rises? Are these experiences scalable to other countries? This study used a combination of field investigation, literature review and case study to summarize 36 systems that had been in operation for 1–14 years. System types, collector types, installation methods, types of auxiliary heat sources, economic performance and various basic principles were summarized. The economic performance of SWH systems in high-rise buildings was analyzed and verified by a case study in Shanghai. The results show that the installation of SWH systems in high-rise buildings is feasible and reliable. Individual household systems (61%) were more popular than centralized systems (25%) and hybrid systems account (14%). The average area of solar collectors per household was 2.17 m2/household, the average design solar fraction was 52%. Flat plate solar collectors (53%) was the most commonly used collector, while electric heating elements (89%) were the most common auxiliary heat sources for SWH systems, followed by gas water heaters and air source heat pumps. The cost of SWH systems per m2 of a building area was between 22 CNY/m2 to 75 CNY/m2. China's unique practical experience gives a reference for other countries in their efforts to make high-rise buildings more sustainable. [ABSTRACT FROM AUTHOR]

Objective. We aim to investigate the correlation between FCGR2A mRNA level and prognosis of head and neck squamous cancer (HNSC) in public databases. In addition, we investigated the correlation between FCGR2A expression and clinicopathological characteristics and tumor-infiltrating immune cells in HNSC patients. Methods. FCGR2A mRNA expression in multiple cancers was analyzed based on Gene Expression Profiling Interactive Analysis. A protein-protein interaction network was obtained based on the STRING database. The 10 proteins most closely related to FCGR2A (i.e., CD3G, PLCG2, LAT, LYN, SYK, FCGR3A, PIK3R1, HCK, ITGAM, and ITGB2) were screened, followed by establishing the protein-protein interaction network. The correlation between FCGR2A expression and immunocytes was investigated, together with the effects of FCGR2A on the metastasis, recurrence, and survival of HNSC. Results. FCGR2A expression in several carcinoma tissues was significantly higher than that of adjacent tissues. Significant differences were noticed in the HNSC samples and the adjacent tissue samples except the seven samples of grade 4. There were statistical differences between the FCGR2A expression in tissues of grade 1, grade 2, and grade 3 (P < 0.05). In the tissues of grade 4, the expression of FCGR2A was the lowest. The FCGR2A protein was a type of II-a receptor in γFc of the low-affinity immunoglobulin, which could bind with the Fc region of the immunoglobulin γ. There was a correlation between the FCGR2A gene and the distal HNSC metastasis. FCGR2A gene expression was correlated with the survival and prognosis. The GSE65858 dataset was selected for the validation. The FCGR2A expression was significantly correlated with total survival (P = 0.0107) and progression-free survival (P = 0.0362). Conclusions. Our findings shed light on the importance of FCGR2A in HNSC and illustrated a potential relationship between FCGR2A and tumor-immune interactions. [ABSTRACT FROM AUTHOR]

The trajectory-planning method for a novel 4-degree-of-freedom high-speed parallel robot is studied herein. The robot's motion mechanism adopts RR(SS)2 as branch chains and has a single moving platform structure. Compared with a double moving platform structure, the proposed parallel robot has better acceleration and deceleration performance since the mass of its moving platform is lighter. An inverse kinematics model of the mechanism is established, and the corresponding relationship between the motion parameters of the end-moving platform and the active arm with three end-motion laws is obtained, followed by the optimization of the motion laws by considering the motion laws' duration and stability. A Lamé curve is used to transition the right-angled part of the traditional gate trajectory, and the parameters of the Lamé curve are optimized to achieve the shortest movement time and minimum acceleration peak. A method for solving Lamé curve trajectory interpolation points based on deduplication optimization is proposed, and a grasping frequency experiment is conducted on a robot prototype. Results show that the grasping frequency of the optimized Lamé curve prototype can be increased to 147 times/min, and its work efficiency is 54.7% higher than that obtained using the traditional Adept gate-shaped trajectory. [ABSTRACT FROM AUTHOR]

Oxidative stress is the downstream of various adverse stresses which impairs meat quality of broiler chickens. Yet, the specific molecular mechanisms of oxidative stress in meat quality of broiler thigh muscle remains unclear. This study investigated the effects and mechanisms of H 2 O 2 -induced oxidative stress on meat quality of broiler thigh muscle, with particular emphasis on apoptosis and autophagy and the ROS/NF-κB signaling pathway. The results showed that 10%H 2 O 2 -treated broilers exhibited significantly higher drip loss and shear force and lower pH 24h and muscle weight. Moreover, the ROS formation, the contents of oxidation products, the expressions of caspases (3, 6, 8, 9), Beclin1, and LC3-II/LC3-I were significantly increased, whereas the levels of antioxidation products and the expression of phosphorylation of NF-κBp65 were significantly decreased. These findings from the present study indicating that H 2 O 2 -induced oxidative stress significantly impaired the meat quality by inducing apoptosis and abnormal autophagy via ROS/NF-κB signaling pathway in the broiler thigh muscle. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) carrying nucleophosmin (NPM1) mutations has been defined as a distinct entity of acute leukaemia. Despite remarkable improvements in diagnosis and treatment, the long‐term outcomes for this entity remain unsatisfactory. Emerging evidence suggests that leukaemia, similar to other malignant diseases, employs various mechanisms to evade killing by immune cells. However, the mechanism of immune escape in NPM1‐mutated AML remains unknown. In this study, both serum and leukemic cells from patients with NPM1‐mutated AML impaired the immune function of CD8+ T cells in a co‐culture system. Mechanistically, leukemic cells secreted miR‐19a‐3p into the tumour microenvironment (TME) via small extracellular vesicles (sEVs), which was controlled by the NPM1‐mutated protein/CCCTC‐binding factor (CTCF)/poly (A)‐binding protein cytoplasmic 1 (PABPC1) signalling axis. sEV‐related miR‐19a‐3p was internalized by CD8+ T cells and directly repressed the expression of solute‐carrier family 6 member 8 (SLC6A8; a creatine‐specific transporter) to inhibit creatine import. Decreased creatine levels can reduce ATP production and impair CD8+ T cell immune function, leading to immune escape by leukemic cells. In summary, leukemic cell‐derived sEV‐related miR‐19a‐3p confers immunosuppression to CD8+ T cells by targeting SLC6A8‐mediated creatine import, indicating that sEV‐related miR‐19a‐3p might be a promising therapeutic target for NPM1‐mutated AML. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1), which displays a distinct long noncoding RNA (lncRNA) expression profile, has been defined as a unique subgroup in the new classification of myeloid neoplasms. However, the biological roles of key lncRNAs in the development of NPM1-mutated AML are currently unclear. Here, we aimed to investigate the functional and mechanistic roles of the lncRNA HOTAIRM1 in NPM1-mutated AML. Methods: The expression of HOTAIRM1 was analyzed with a public database and further determined by qRT-PCR in NPM1-mutated AML samples and cell lines. The cause of upregulated HOTAIRM1 expression was investigated by luciferase reporter, chromatin immunoprecipitation and ubiquitination assays. The functional role of HOTAIRM1 in autophagy and proliferation was evaluated using western blot analysis, immunofluorescence staining, a Cell Counting Kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, flow cytometric analyses and animal studies. The action mechanism of HOTAIRM1 was explored through RNA fluorescence in situ hybridization, RNA pulldown and RNA immunoprecipitation assays. Results: HOTAIRM1 was highly expressed in NPM1-mutated AML. High HOTAIRM1 expression was induced in part by mutant NPM1 via KLF5-dependent transcriptional regulation. Importantly, HOTAIRM1 promoted autophagy and proliferation both in vitro and in vivo. Mechanistic investigations demonstrated that nuclear HOTAIRM1 promoted EGR1 degradation by serving as a scaffold to facilitate MDM2-EGR1 complex formation, while cytoplasmic HOTAIRM1 acted as a sponge for miR-152-3p to increase ULK3 expression. Conclusions: Taken together, our findings identify two oncogenic regulatory axes in NPM1-mutated AML centered on HOTAIRM1: one involving EGR1 and MDM2 in the nucleus and the other involving the miR-152-3p/ULK3 axis in the cytoplasm. Our study indicates that HOTAIRM1 may be a promising therapeutic target for this distinct leukemia subtype. [ABSTRACT FROM AUTHOR]

Highlights • The largest solar district heating market worldwide has been presented. • Characters of solar district heating plants in Denmark were summarized. • Possibility of solar district heating in smart renewable energy system was shown. • Potential trend of solar district heating plants in Denmark was discussed. Abstract Large solar collector fields are very popular in district heating system in Denmark, even though the solar radiation source is not favorable at high latitudes compared to many other regions. Business models for large solar heating plants in Denmark has attracted much attention worldwide. Denmark is not only the biggest country in both total installed capacities and numbers of large solar district heating plants, but also is the first and only country with commercial market-driven solar district heating plants. By the end of 2017, more than 1.3 million m2 solar district heating plants are in operation in Denmark. Furthermore, more than 70% of the large solar district heating plants worldwide are constructed in Denmark. Based on the case of Denmark, this study reviews the development of large solar district heating plants in Denmark since 2006. Success factors for Danish experiences was summarized and discussed. Novel design concepts of large solar district heating plants are also addressed to clarify the future development trend. Potential integration of large solar district heating plants with other renewable energy technologies are discussed. This paper can provide references to potential countries that want to exploit the market for solar district heating plants. Policy-makers can evaluate the advantages and disadvantages of solar district heating systems in the national energy planning level based on the know-how and experiences from Denmark. [ABSTRACT FROM AUTHOR]

Multiple studies have demonstrated that excessive glucose utilization is a common feature of cancer cells to support malignant phenotype. Acute myeloid leukemia (AML) is recognized as a heterogeneous disorder of hematopoietic stem cells characterized by altered glucose metabolism. However, the role of glucose metabolic dysfunction in AML development remains obscure. In this study, glucose and 2-Deoxy- D -glucose (2-DG) treatment were applied to analyze the relationship between glucose metabolism and cell survival. Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM) assays were used to examine the cell viability and apoptosis rate. Glucose consumption and lactate production were measured to assess the glucose metabolism pathway. The results demonstrated that abnormally increased glucose effectively promoted proliferation of leukemic cells and inhibited cell apoptosis, while 2-DG ameliorated leukemic phenotypes. Importantly, glucose exposure induced active glycolysis by increasing glucose consumption and lactate production. Furthermore, the levels of key glycolysis-related genes glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1) were upregulated. Mechanistic investigations revealed that AKT/mTOR signaling pathway was activated in glucose condition. In conclusion, our findings indicate that glucose induced-AKT/mTOR activation plays a growth-promoting role in AML, highlighting that inhibition of glycolysis would be a vital adjuvant therapy strategy for AML. [Display omitted] • Glucose treatment promotes leukemic cell growth and inhibits cell apoptosis. • Glucose treatment induces glycolysis in leukemic cells. • AKT/mTOR signaling pathway is involved in glycolysis and leukemic cell survival. [ABSTRACT FROM AUTHOR]

A novel adhesion-enhancing polyhydrosiloxane containing acrylate groups (MPMS-PHMS) was prepared via the hydrolysis of 3-methacryloyloxypropylmethyldimethoxysilane and the ring-opening polymerization of octamethylcyclotetrasiloxane and tetramethylcyclotetrasiloxane, and was used as cross-linker for addition-cure silicone encapsulant (ASE) with a large amount of alumina as thermally conductive fillers. The chemical structure of MPMS-PHMS was characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, silicon nuclear magnetic resonance spectroscopy, and gel permeation chromatography. The effect of MPMS-PHMS on the properties of ASE was investigated. The results indicated that when using MPMS-PHMS as cross-linker, the cross-linking density of ASE was much higher than that of ASE using commercial poly(hydromethylsiloxane) cross-linker. It was also found that MPMS-PHMS not only markedly improved the adhesion strength of ASE to aluminum substrate but also significantly enhanced the mechanical properties of ASE. Appropriately increasing cure temperature and prolonging cure time were favorable to improve the adhesion strength of ASE. The optimal content of MPMS-PHMS was 10 phr, and the suitable cure temperature and time were approximately between 130 and 150°C and 2 h, respectively. [ABSTRACT FROM AUTHOR]