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Acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations exhibits distinct biological and clinical features, accounting for approximately one-third of AML. Recently, the N6-methyladenosine (m6A) RNA modification has emerged as a new epigenetic modification to contribute to tumorigenesis and development. However, there is limited knowledge on the role of m6A modifications in NPM1-mutated AML. In this study, the decreased m6A level was first detected and high expression of fat mass and obesity-associated protein (FTO) was responsible for the m6A suppression in NPM1-mutated AML. FTO upregulation was partially induced by NPM1 mutation type A (NPM1-mA) through impeding the proteasome pathway. Importantly, FTO promoted leukemic cell survival by facilitating cell cycle and inhibiting cell apoptosis. Mechanistic investigations demonstrated that FTO depended on its m6A RNA demethylase activity to activate PDGFRB/ERK signaling axis. Our findings indicate that FTO-mediated m6A demethylation plays an oncogenic role in NPM1-mutated AML and provide a new layer of epigenetic insight for future treatments of this distinctly leukemic entity.

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.

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.

Additional file 12 : Figure S7. HOTAIRM1 expression in the different transfected cells. a-b HOTAIRM1 expression in HOTAIRM1-silenced (a) and HOTAIRM1-enforced OCI-AML3 cells (b). c-d HOTAIRM1 expression in HOTAIRM1-silenced (c) as well as HOTAIRM1-enforced OCI-AML2 + NPM1-mA cells (d). e HOTAIRM1 expression in HOTAIRM1-enforced OCI-AML2 cells.

Additional file 10 : Figure S5. Enrichment of KLF5 on the E2 fragment of the HOTAIRM1 promoter was measured by ChIP assays in leukemia cells.

Additional file 17 : Figure S12. Screening for the ubiquitin ligase of EGR1. a Network view of the predicted E3 ubiquitin ligase for EGR1. b Recognition motif for the potential E3 ubiquitin ligase MDM2 in the EGR1 sequence.

Additional file 4 : Table S4. The top 10 predicted factors bound to HOTAIRM1 promoter by JASPAR database analysis.

Additional file 16 : Figure S11. EGR1 does not affect the expression of HOTAIRM1. a The efficiency of EGR1 overexpression in OCI-AML3 cells was validated by western blotting. b qRT-PCR was used to detect the expression of HOTAIRM1 in EGR1-enforced OCI-AML3 cells. The data are presented as the mean ± SD of three independent experiments. n.s. indicates no significant difference.

Additional file 3 : Table S3. Primers used for ChIP-qPCR.

Additional file 11 : Figure S6. Co-IP assays were used to evaluate the binding of NPM1 and KLF5, NPM1-wt and WWP1 in OCI-AML3 cells. a-b The interaction between NPM1-mA (a) or NPM1-wt (b) and KLF5 in OCI-AML3 cells were determined by IP assays. c IP assays were used to determine the binding of WWP1 to NPM1-wt in OCI-AML3 cells.

Additional file 19 : Figure S14. Cytoplasmic HOTAIRM1 promotes leukemia cell autophagy and proliferation through ULK3. a, c Western blot analysis of LC3-II, p62 and ULK3 levels in HOTAIRM1-silenced OCI-AML3 cells following ULK3 overexpression (a) and HOTAIRM1-overexpressed OCI-AML2 cells following ULK3 knockdown (c). b, d CCK-8 assays were used to analyze cell proliferation in transfected OCI-AML3 (b) and OCI-AML2 cells (d). The data are presented as the mean ± SD of three independent experiments. *P

Additional file 1 : Table S1. Clinical characteristics of newly diagnosed AML patients.

Additional file 6 : Figure S1. Stable NPM1-mA-GFP expressing OCI-AML2 cells (OCI-AML2 + NPM1-mA) were generated. a Cytoplasmic localization of NPM1-mA in the OCI-AML2 stably expressing Flag-GFP tagged NPM1-mA. Cytospun cells were fixed and stained with DAPI. b The level of NPM1-mA in leukemia cells were measured by western blot analysis.

Additional file 13 : Figure S8. HOTAIRM1 promotes autophagy and proliferation in transfected OCI-AML2 + NPM1-mA leukemia cells. a, i Western blot analysis of LC3-II and p62 levels in OCI-AML2 + NPM1-mA cells after transfection of shHOTAIRM1 (a) and HOTAIRM1 expression vector (i). b, j Representative microscopy images of LC3 puncta in HOTAIRM1-silenced OCI-AML2 + NPM1-mA (b) and HOTAIRM1-enforced OCI-AML2 + NPM1-mA (j). The bar graphs showed the quantification of the fluorescent puncta data. Scale bar: 25 μm. c, k Evaluation of cell viability in OCI-AML2 + NPM1-mA cells transfected with shHOTAIRM1 (c) or HOTAIRM1 plasmid (k) for indicated by CCK-8 assays. d, l Evaluation of cell proliferation in HOTAIRM1-silenced (d) and HOTAIRM1-enforced OCI-AML + NPM1-mA cells (l) for indicated by EdU assays. The bar graphs showed the percentage of EdU positive cells. Scale bar: 100 μm. e, m Flow cytometry was performed to assess cell cycle of HOTAIRM1-silenced (e) and HOTAIRM1-enforced OCI-AML2 + NPM1-mA cells (m). The bar graph shows the percentages of G0/G1-, S-, and G2/M-phase cells. f, n Flow cytometry was used to detect apoptosis of HOTAIRM1-silenced (f) and HOTAIRM1-enforced OCI-AML2 + NPM1-mA cells (n). LL, dead cells; UL, viable cells; LR, early apoptotic cells; UR, late apoptotic cells. g, o Flow cytometric analysis was performed to analyze apoptosis of OCI-AML2 + NPM1-mA cells after transfection with shHOTAIRM1 (g) or HOTAIRM1 plasmid (o), followed by treatment with 200 nM Ara-C for 48 h. h, p The protein levels of Cyclin D1, CDK4, Bax and Bcl-2 in HOweTAIRM1-silenced (h) and HOTAIRM1-enforced OCI-AML2 + NPM1-mA cells (p). The data are presented as the mean ± SD of three independent experiments. **P

Additional file 5 : Table S5. The top 10 proteins with specific binding to HOTAIRM1 identified by mass spectrometry analysis.

Additional file 18 : Figure S13. Nuclear HOTAIRM1 promotes cell cycle progression and inhibits apoptosis in leukemia cells through EGR1. a, c Flow cytometry was used to determine and compare the differences in cell cycle progression in differently transfected groups of OCI-AML3 (a) and OCI-AML2 cells (c). b, d Flow cytometry was used to determine and compare differences in apoptosis in differently transfected groups of OCI-AML3 (b) and OCI-AML2 cells (d). The data are presented as the mean ± SD of three independent experiments. *P

Additional file 7 : Figure S2. The expression levels of HOTAIRM1 in the nucleus and cytoplasm of leukemia cells were measured by qRT-PCR.

Additional file 20 : Figure S15. Cytoplasmic HOTAIRM1 promotes cell cycle progression and inhibits apoptosis in leukemia cells through ULK3. a-b Flow cytometry was used to analyze the changes in cell the cycle (a) and apoptosis (b) in HOTAIRM1-silenced OCI-AML3 cells following ULK3 upregulation. c-d Flow cytometry was used to analyze the change in the cell cycle (c) and apoptosis (d) in HOTAIRM1-overexpressed OCI-AML2 cells following ULK3 downregulation. The data are presented as the mean ± SD of three independent experiments. *P

Additional file 8 : Figure S3. NPM1-mA expression in leukemia cells in the different treatment groups. a The efficiency of RNA interference-mediated knockdown of NPM1-mA expression was determined by qRT-PCR. b The efficiency of RNA interference-mediated knockdown of NPM1-mA expression was determined by western blotting. c NPM1-mA protein levels in NPM1-mA enforced OCI-AML2 cells. d Western blot analysis of NPM1-mA in OCI-AML3 cells treated with KPT-330. β-tubulin as the cytoplasmic control and PCNA as the nuclear control. The data are presented as the mean ± SD of three independent experiments.

Additional file 14 : Figure S9. HOTAIRM1 promotes autophagy and proliferation in transfected OCI-AML2 leukemia cells. a Western blot analysis of LC3-II and p62 levels in OCI-AML2 cells after transfection of HOTAIRM1 expression vector. b Representative microscopy images of LC3 puncta in HOTAIRM1-enforced OCI-AML2 cells. The bar graphs showed the quantification of the fluorescent puncta data. Scale bar: 25 μm. c Evaluation of cell viability in OCI-AML2 cells transfected with HOTAIRM1 plasmid for indicated by CCK-8 assays. d Evaluation of cell proliferation in HOTAIRM1-enforced OCI-AML2 cells for indicated by EdU assays. The bar graphs showed the percentage of EdU positive cells. Scale bar: 100 μm. e Flow cytometry was performed to assess cell cycle of HOTAIRM1-enforced OCI-AML2 cells. The bar graph shows the percentages of G0/G1-, S-, and G2/M-phase cells. f Flow cytometry was used to detect apoptosis of HOTAIRM1-enforced OCI-AML2 cells. LL, dead cells; UL, viable cells; LR, early apoptotic cells; UR, late apoptotic cells. g The protein levels of Cyclin D1, CDK4, Bax and Bcl-2 in HOTAIRM1-enforced OCI-AML2 cells. The data are presented as the mean ± SD of three independent experiments. **P

Additional file 2 : Table S2. Primers used for qRT-PCR.

Additional file 15 : Figure S10. HOTAIRM1 expression in HOTAIRM1-silenced OCI-AML3 cells transfected with different vectors.

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.

Solar thermal contributes little to 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. The Chinese solar thermal market status was reviewed and a market transition trend based on a prediction model and extensive market survey was proposed. The status and prospect of solar heat for industrial processes in China was discussed. Lessons from experiences on the mandatory installation of solar water heating systems in China in terms of technology application and policy implementation were summarized.To promote solar district heating (SDH) in China, based on Danish experiences and Chinese clean heating transformation practices, an extensive survey and on-site investigation were carried out to identify the applicability of SDH in China. The potentiality and feasibility of SDH in China were explored.To find optimal economic solutions for SDH and compare the economics of SDH with household solar heating in China, two evaluation models based on the levelized cost of heat (LCoH) were proposed. A Python program was developed based on the two evaluation models to calculate the LCoH of SDH systems and household solar heating systems using the quasi-dynamic test (QDT) method. The calculation results were discussed.To explore the economic rationality and regional adaptability of solar heating technologies in different cities in China, the methods in the research on economics were used to calculate the LCoH values for nine cities in China. The LCoH curves for the target cities show that the calculation models can not only be used to judge economics of different technology combinations in a city but also can be used to judge economics of one technology combination in different cities.To fully understand the operating performance and potential optimizations of a demonstration SDH system built on the outskirts of Beijing, a TRNSYS model of the solar assisted ground source heat pump system (SAGSHP) was established and validated by the measured operating data. The climatic conditions of the site, the inlet and outlet temperatures of the borehole heat exchangers, the inlet and outlet temperatures of the solar collector field and the electricity consumption of various components were measured. Through the simulation analysis of the model, an optimized solution was proposed. The process of modelling and analysing in details were described.Through extensive investigations and research on demonstration projects, the study considers that SDH has a broad application prospect in China with abundant solar resources and favourable policies. Rural villages and small towns with better infrastructure are the best target market for SDH in the next five years. Particular areas with low population density, scarce resources, and strict environmental requirements, e.g., Tibet, should be given high priority for SDH. The solar-heated area can achieve 756 million m2 with an assumption of 3% coverage of the total heat demand of buildings. The solar thermal plus heat pump heating system shows strong climate adaptability and gives the lowest LCoH in most cities. Seasonal heat storage can maximize the advantages of solar thermal when gas boilers are used as an auxiliary heat source. The solar thermal system can achieve higher cost reductions in larger SDH systems. A solar-assisted GSHP system is a reliable solution as a form of SDH. An auxiliary solar collector field can be added to those GSHP systems that do not recharge enough heat in the soil to improve the system efficiency and to reduce operating costs. Maintain the heat balance of the soil is the key to the sustainable operation of a solar assisted GSHP system. The research findings of the thesis are helpful for policymakers to fully understand the development trend of China's solar thermal market, and on this basis, profoundly understand the prospects, technical routes, economics and regional adaptability of SDH in China. The dynamic calculation method on LCoH proposed in this study can be used not only as a useful planning tool but also to optimize technical combinations for engineering companies and to improve production efficiency for manufacturing companies.

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.

Currently there are many different cooling methodologies used for outdoor cabinets; among them, the most used ones are the Heat Exchanger system (HXS) and the Air Direct Cooling System (ADCS). ADCS has the higher cooling efficiency, but on the other side it needs frequent maintenance given that sand, dust and dirt reduces the air flow passing through the filter. This study is focused on how to automatically clean up the filter, therefore strongly reducing the maintenance cost as well as the total OPEX.

Geological environment condition is the basic factor for city existence and stability and the foundation for city construction. In city construction belts with comparably stable earth crust and good geological environment is preferable. Hence, engineering geological condition must be taken into consideration during urban construction. And city is a place where the geological environment is much influenced by human activities whose forming type, function, land used and development have a close relationship with geological environment. To survive and get maximum benefit, human make the best of environment to construct in many ways. Nowadays city planning and construction is developed from simplex plane style to the dimensional style. Increase of high-rising, unceasing construction of substructure work, development of higher, deeper, longer, larger, heavier, clustered urban construction arouse engineering geological problems brought by city construction. Characteristic of city construction is that it comes along with city and its harmfulness increases with city development. Yet an effective management way is to keep to the conception that human and geological environment should be in harmony among planning, construction and geological environment.