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Aberrant activation of B cell receptor (BCR) signal transduction cascade contributes to the propagation and maintenance of B cell malignancies. The discovery of mall molecules with high potency and selectivity against Bruton’s tyrosine kinase (BTK), a key signaling molecule in this cascade, is particularly urgent in modern treatment regimens. Herein, a series of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives were reported as potent BTK inhibitors. Compounds 17 and 18 displayed strong BTK inhibitory activities in the enzymatic inhibition assay, with the IC50 values of 1.2 and 0.8 nM, respectively, which were comparable to that of ibrutinib (IC50 = 0.6 nM). Additionally, compound 17 had a more selective profile over EGFR than ibrutinib. According to the putative binding poses, the molecular basis of this series of compounds with respect to potency against BTK and selectivity over EGFR was elucidated. In further experiments at cellular level, compounds 17 and 18 significantly inhibited the proliferation of Ramos and TMD8 cells. And they arrested 75.4% and 75.2% of TMD8 cells in G1 phase, respectively, at the concentration of 1 µM.

Molecular self-assemblies based on a solution system and solid-state reaction have been largely developed and achieved great success during last few decades; however, the knowledge on the molecular recognition and potential formation of orderly molecular hybrids in the vapor phase is quite limited and examples are still rare. Herein, we confirmed that the molecular recognition organized by intermolecular π–π interaction can be achieved based on a facile vapor deposition process. Through a continuous heating–cooling process of the self-assembled units (such as dibenzothiophene and tetracyanobenzene), the obtained co-crystalline hybrids present an orderly one-dimensional (1D) hollow tubular structure, which also features a high fluorescence quantum yield (47%), optical waveguide, and two-photon emission properties. A combination of crystal morphology prediction and experimental observation deduced that the 1D micro-sized tubular co-crystals were formed based on a growth mechanism of random aggregation. Moreover, this strategy based on vapor-phase molecular recognition can be further extended to the construction of other 1D co-crystal systems. Therefore, this study supplies a facile and environmentally friendly way to prepare high-quality 1D co-crystals towards potential photonic and photofunctional applications.

Electrocatalytical nitrogen reduction reaction (NRR) under ambient conditions provides a promising substitute to the typical Haber−Bosch process that involves high energy and greenhouse gases emission. Herein, we develop non-noble metal based hollow hierarchical nanotubes (HHNTs) of CoVP@NiFeV-layered double hydroxides (LDHs) heterostructures as a high-performance electrocatalyst for NRR, in which the novel 3D hollow hierarchical structure provides highly rich surface active sites for the adsorption and reduction of nitrogen to NH3. Electrochemical measurements for NRR reveal high activity (NH3 rate: 1.6 × 10−6 mol h−1 cm−2), high Faradaic efficiency (13.8%) and excellent selectivity at −0.3 V versus reversible hydrogen electrode (RHE), outperforming other noble metals catalysts for N2 fixation and most of state-of-the-art metal-free NRR electrocatalysts. Furthermore, CoVP@NiFeV-LDHs HHNTs could maintain high selectivity and durability over repeated reaction cycles. Therefore, this work highlights the first example of CoVP@NiFeV-LDHs hierarchical micro/nanostructures, which serve as electrocatalysts towards high-efficiency, pH-universal NRR to ammonia synthesis.

Bioturbation (i.e. particle reworking and bio-irrigation) is a key process in benthic coastal and estuarine ecosystems, and act as crucial control on important ecosystem functions, such as nutrient cycling. Particle reworking and bio-irrigation are affected by a wide array of environmental and biological factors and are therefore expected to be highly variable in heterogeneous ecosystems, such as estuaries. To assess the spatial and temporal variability of these benthic ecosystem processes in the Scheldt estuary (Belgium and the Netherlands), we carried out seasonal surveys during four seasons in 2015 and 2016, at three habitats with different hydrodynamic regimes (low-dynamic intertidal, high-dynamic intertidal, subtidal) in the three main salinity zones (polyhaline, mesohaline, oligohaline). Sediment communities were sampled and incubated in the laboratory; macrobenthos was identified and weighed. Luminophore tracers were applied to the incubation cores to measure sediment particle mixing and changes over time in the concentration of the inert tracer sodium bromide in the water column were used to estimate pore water exchange rate as a proxy for bio-irrigation. Particle reworking was quantified both by the rate of mixing, and the maximal penetration depth of luminophores. Luminophore profiles showed that biodiffusion was the dominant particle reworking mode. Both particle reworking and bio-irrigation were highly variable among seasons and habitats, and different species were found to contribute unevenly to both processes, and between habitats and seasons. Habitat structuring effects on populations, density-dependent interactions with the habitat, and temperature-driven variability in macrobenthos activity and living position are suggested to explain the observed spatial and temporal differences.

Middle cerebral artery (MCA) aneurysm is a serious medical condition mainly occurring in the proximal and bifurcation tracts. Evidence has indicated that endovascular treatment is an effective surgical method for patients with MCA aneurysm. In the present study, the efficacy of endovascular treatment with low-profile visualized intraluminal support (LVIS) stent for MCA aneurysms was evaluated in comparison with that using a non-LVIS stent device. A total of 92 patients who underwent endovascular treatment of MCA aneurysms with LVIS stent or non-LVIS stent were included in the present study. The clinical presentation, aneurysmal characteristics, technical feasibility, procedural complications, as well as angiographic and clinical follow-up results were analyzed. The computed tomography scan demonstrated that endovascular treatment with LVIS stent markedly reduced pre-operative and intra-operative ruptures. It was indicated that endovascular treatment with LVIS stent resulted in less post-operative symptoms and cases of disability according to the modified Rankin scale score. In conclusion, the present outcomes provide evidence that endovascular treatment with an LVIS stent is an efficient method for the treatment of MCA aneurysm.

The vibration signals generated during the operation of the blast furnace opener contain various noises, which are disturbing and superimposed, and it is difficult to identify the operating status of the open machine, put forward a kind of based on Empirical Mode Decomposition (EMD) filter method. From the physical structure of the opening machine, the complexity of the vibration signal is qualitatively analyzed. The EMD technology is used to adaptively decompose the vibration signal into a single intrinsic mode function (IMF) with different frequency components. the high frequency noise components is filtered in the IMF component, the remaining IMF components are reconstructed to form a new vibration signal and compared with the results of the wavelet threshold denoising way. The consequences show that the EMD filtering method can overcome the disadvantages of glitches and signal superposition after wavelet denoising, and can fully preserve the nonlinear characteristics of the vibration signal. It is an effective method for filtering and denoising detection of mechanical vibration signals of blast furnace opening machines.

This paper focuses on the problem that mobile vehicles easily collide with regular pedestrians in dangerous area, and the gray prediction algorithm is applied to establish the markov model of regular pedestrian data. Predict their walking trajectory according to the regular pedestrian movement trend, and provide active and safe predictive control for vehicle braking in the region. Taking the coke oven coal transportation area as an example, a set of regular pedestrian trajectory data is selected to verify the model and prediction method. The experimental results show that this method can predict this type of pedestrian trajectory. When it is compared with the results of the traditional gray model prediction, the error is smaller and the accuracy is higher.

With the periodic rotation of gear, the characteristic of intermittent fault in gear system is periodic with fixed amplitude. The aim at this study is to identify the three states of the gear system, i.e., normal state (NS), intermittent fault state (IFS) and permanent fault state (PFS). Based on Wavelet Packet Transform (WPT) and Gaussian Mixture Hidden Markov Model (GHMM), an algorithm used in the gear intermittent fault detection and classification is put forward in this paper. The WPT method is adopted to decompose the vibration signal of gear into different individual frequency bands and extract the energy feature vector. Then input the observation sequence composed of the energy feature vectors into GHMM for training and identification. According to the experimental results, this method can be effectively applied to gear intermittent fault diagnosis.

The author analyzes different micro areas of the chip carrier board with scanning electron microscope (SEM) and X-ray energy dispersive spectrometer(EDS) to find out the reasons why a type of chip is detached from the carrier board and the device does not work properly. The results show that the phenomenon of chip shedding due to the presence of contaminants between the chip and the carrier board.

Self-lubricating wear-resistant NiCr–Cr3C2–MoS2–CeO2 layers were fabricated on 38CrMoAl extruder screws by laser processing. The effect of scanning speeds on microstructure, phases, microhardness, and wear behavior was investigated. The obtained results indicate that the laser-processed layers had fine and nonuniform microstructures with undissolved MoS2 particles distributed on the matrix. With an increase of the laser-scanning speeds, the microstructures changed from hypoeutectic to hypereutectic, volume fraction of martensite increased, microhardness increased, and thickness and friction coefficients of the layers decreased. Wear resistance of the optimized layer was increased by 29.76 times compared with that of the substrate. The undissolved MoS2 was separated from the matrix on loading. In addition to the grain-refining and solution-strengthening effects, oxide films formed on the surface of the layers shielded them and enhanced their wear resistance. The crack or fracture behavior of the laser-processed layers on loading was determined by its toughness, which also had an important effect on the wear behavior of the processed layers.

The development of durable, low-cost, and efficient photo-/electrolysis for the oxygen and hydrogen evolution reactions (OER and HER) is important to fulfill increasing energy requirements. Herein, highly efficient and active photo-/electrochemical catalysts, that is, CoMn-LDH@g-C

Methanosarcina barkeri (DSM 800) is a metabolically versatile methanogen and shows distinct metabolic status under different substrate regimes. However, the mechanisms underlying distinct transcriptional profiles under different substrate regimes remain elusive. In this study, based on transcriptional analysis, the growth performances and gene expressions of M. barkeri fed on acetate, H2 + CO2, and methanol, respectively, were investigated. M. barkeri showed higher growth performances under methanol, followed by H2 + CO2 and acetate, which corresponded well with the variations of gene expressions. The α diversity (evenness) of gene expressions was highest under the acetate regime, followed by H2 + CO2 and methanol, and significantly and negatively correlated with growth performances. The gene co-expression analysis showed that “Energy production and conversion,” “Coenzyme transport and metabolism,” and “Translation, ribosomal structure, and biogenesis” showed deterministic cooperation patterns of intra- and inter-functional classes. However, “Posttranslational modification, protein turnover, chaperones” showed exclusion with other functional classes. The gene expressions and especially the relationships among them potentially drove the shifts of metabolic status under different substrate regimes. Consequently, this study revealed the diversity-related ecological strategies that a high α diversity probably provided more fitness and tolerance under natural environments and oppositely a low α diversity strengthened some specific physiological functions, as well as the co-responses of gene expressions to different substrate regimes.

This paper mainly deals with the adaptive anti-synchronization problem of memristor-based complex-valued neural networks with time delays. By using the concept of adaptive control technology, a specific feedback controller is designed to achieve anti-synchronization. Compared to the anti-synchronization of complex-valued memristor-based delays neural networks, we use adaptive controller in the article. The adaptive controller can adjust system itself according to different updating laws. The obtained result is more reliable and improve some of the existing achievements. Finally, a numerical example is given to illustrate the effectiveness of the theoretical result.

Polarized and up-conversion luminescent films have great potential for use in the design of various optical devices. In this work, we report transparent and flexible thin films based on alternate layer-by-layer assembly of sulfonated Eu- and Tb-based lanthanide complexes (LCs) and Mg–Al-layered double hydroxide (LDH) nanosheets. UV-visible absorption and fluorescence spectroscopy showed an orderly growth of the two types of thin films (TFs) upon increasing the number of deposition cycles. XRD, AFM and SEM measurements indicated that the films feature periodic layered structures as well as uniform surface morphology. Moreover, by combining the assembly of both the Eu- and/or Tb-based LC systems, these TFs can exhibit well-defined one- and two-color polarized fluorescence with high polarization anisotropy. In addition, it was observed that the two TFs exhibited obvious red and green up-conversion emission upon excitation by near-IR laser light. Therefore, this work provides a facile way to develop new types of LC TFs with both up-conversion and color-tunable luminescence, which have great potential applications for the design of various LC-based optical films and flexible devices.

Hala Lake is located in the Qilian Mountains, Qinghai Province, China, at 4,078 m a.s.l. Its sediments contain an archive of climate and hydrologic changes during the Late Quaternary, as it is located close to the area influenced by the East-Asian summer monsoon and westerly-driven air masses. Sedimentation patterns and depositional conditions within the lake were investigated using eight sediment cores from different water depths, and this information was used to evaluate the feasibility of using a single core to reconstruct past climate and hydrological conditions. Long core H7, from the center of the lake (65 m water depth) and core H8 from a western, near-shore location (20 m water depth), were compared in detail using sediment composition and geochemical data (X-ray fluorescence, loss-on-ignition and CNS analysis). Age models were constructed using 17 AMS radiocarbon dates and indicate negligible reservoir error for sediments from the lake center and ~1,000 year errors for the near-shore sediment core. Cores H1–H5 and HHLS21-1 revealed a sediment succession from sand and silty clay to laminated clay on the southern side of the lake. Undisturbed, finely laminated sediments were found at water depths ≥15 m. Core H5 (2.5 m long), from 31 m water depth, yielded abundant green algal mats mixed with clayey lake deposits and was difficult to interpret. Algae occurred between 25 and 32 m water depth and influenced the dissolved oxygen content of the stratified lake. Comparison of cores H7 and H8 yielded prominent mismatches for different time periods, which may, in part, be attributed to internal lacustrine processes, independent of climate influence. We thus conclude that data from a single sediment core may lead to different climate inferences. Common shifts among proxy data, however, showed that major climate shifts, of regional to global significance, can be tracked and allow reconstruction of lake level changes over the last 24,000 years. Results indicate advance of glaciers into the lake basin during the LGM, at which time the lake experienced lowest levels, 25–50 m below present stage. Stepwise refilling began at ca. 16 kyr BP and reached the −25 m level during the Bolling/Allerod warm phase, ca. 13.5 kyr BP. A desiccation episode falls within the Younger Dryas, followed by a substantial lake level rise during the first millennium of the Holocene, a result of climate warming, which promoted glacier melt. By ca. 7.6 kyr BP, the lake reached a stable high stand similar to the present level, which persisted until ca. 6 kyr BP. Disturbed sediments in core H7 indicate a single mass flow that was most likely triggered by a major seismic event ~8.5 kyr BP. Subsequent lake development remains unclear as a consequence of data mismatches, but may indicate a general trend to deteriorating conditions and lake level lowstands at ca. 5.0–4.2, 2.0 and 0.5 kyr BP.

Mechanochromic luminescent materials have attracted much attention and present a variety of applications in information security, data recording, and storage devices. However, most of these smart luminescent systems are based on typical fluorescence and/or phosphorescence mechanisms; the mechanochromic delayed fluorescence (MCDF) materials involving switching singlet and triplet states are rarely studied to date. Herein, new 2D layered metal–organic micro/nanosheets, [Cd(9‐AC)2(BIM)2] (named as MCDF‐1; 9‐AC = anthracene‐9‐carboxylate and BIM = benzimidazole) and its solvate form containing interlayer CH3CN (named as MCDF‐2), which exhibit reversible mechanochromic delayed fluorescence characteristics, are presented. With applying the mechanical force, the luminescent center of MCDF‐1 can be converted from 9‐AC/BIM exciplex to 9‐AC/9‐AC excimer, resulting in alternations of delayed fluorescence. Such luminescent change can be further recovered by CH3CN fumigation, accompanied by the structural transformation from MCDF‐1 to MCDF‐2. Furthermore, the force‐responsive process also refers to the energy redistribution between singlet and triplet states as inferred by both temperature‐dependent photophysics and theoretical calculations. Therefore, this work not only develops new 2D micro/nanosheets as MCDF materials, but also supplies a singlet–triplet energy switching mechanism on their reversible mechanochromic process.

Environmental friendly water retention agent has been widely used in agriculture, since its ability to absorb water, hold in water, resist salt. In this study, the water rentention agent was polymerized with using wood cellulose as raw material, acrylamide as monomer, N, N - methylene double acrylamide as crosslinking agent, ammonium persulfate as the initiator. The optimized technological conditions was obtained by the orthogonal experiments: the quality ratio of cellulose and acrylamide was in 1:6, ammonium persulfate was 1.5 wt%(of the total amount of cellulose and monomer), N, N - methylene double acrylamide 0.25 wt%(of the total amount of cellulose and monomer). The maximum water absorbency of water retention agent was 330.07g/g in distilled water and 117.48g/g in 0.9 wt% KCl solution. On the basis of this, using water retention agent as the coating for coal gangue ceramsite, and the maximum water absorbency of water retention agent was 332.15g/g in distilled water and 118.91g/g in 0.9wt% KCl solution. The results show that adopting above process not only can obtain good water retention agent, but also can enhance the water retention and salt resistance by using with ceramsite.

Background Temperature is an important factor determining the performance and stability of the anaerobic digestion process. However, the microorganism-regulated mechanisms of temperature effects on the performance of anaerobic digestion systems remain further elusive. To address this issue, we investigated the changes in composition, diversity and activities of microbial communities under temperature gradient from 25 to 55 °C using 16S rRNA gene amplicon sequencing approach based on genomic DNA (refer to as “16S rDNA”) and total RNA (refer to as “16S rRNA”). Results Microbial community structure and activities changed dramatically along the temperature gradient, which corresponded to the variations in digestion performance (e.g., daily CH4 production, total biogas production and volatile fatty acids concentration). The ratios of 16S rRNA to 16S rDNA of microbial taxa, as an indicator of the potentially relative activities in situ, and whole activities of microbial community assessed by the similarity between microbial community based on 16S rDNA and rRNA, varied strongly along the temperature gradient, reflecting different metabolic activities. The daily CH4 production increased with temperature from 25 to 50 °C and declined at 55 °C. Among all the examined microbial properties, the whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities showed highest correlations to the performance. Conclusions The whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities were sensitive indicators for the performance of anaerobic digestion systems under temperature gradient, while beta-diversity could predict functional differences. Microorganism-regulated mechanisms of temperature effects on anaerobic digestion performance were likely realized through increasing alpha-diversity of both microbial communities and potentially relative activities to supply more functional pathways and activities for metabolic network, and increasing the whole activities of microbial community, especially methanogenesis, to improve the strength and efficiency in anaerobic digestion process. Electronic supplementary material The online version of this article (doi:10.1186/s12934-016-0491-x) contains supplementary material, which is available to authorized users.

Additional file 1. Additional figures.

Background:Several epidemiological studies have focused on the association between polymorphisms in toll-like receptors (TLRs) and asthma. However, the results remained inconclusive.Methods:We systematically reviewed the database of PubMed, EMBASE, Web of Science, CNKI, and Google scholar fo

Rationale: Inflammatory myofibroblastic tumor (IMT) is an uncommon neoplastic entity with a tendency of local recurrence and a low risk of distant metastasis. Involvement of trachea is extremely rare. Patient concerns: A 34-week pregnant woman previously diagnosed with asthma for 2 months was admitted with persistent wheezing and hemoptysis. A computed tomography scan and bronchoscopy revealed a gigantic polyp in the trachea. Diagnoses: Tracheal inflammatory myofibroblastic tumor. Interventions: The mass was removed with an electrocautery snare and identified histologically as an IMT. Further immunochemical staining showed strong positive staining for smooth muscle actin and platelet-derived growth factor receptor α (PDGFRA), weak positive staining for caldesmon, and negative staining for anaplastic lymphoma kinase (ALK)1, desmin, S-100, and CD34. The tracheal IMT strongly expressed estrogen receptor-α (ER-α), which indicated that the development of this rare IMT might have been associated with hormone fluctuations that occurred during the pregnancy. Outcomes: Follow-up and histological analyses revealed no evidence of recurrence and metastasis. Lessons: This report describes an extremely rare case of a tracheal IMT that presented a diagnostic dilemma for the clinician and the pathologist. Tracheal IMT is a challenge for the clinician in diagnosis due to the nonspecific clinical presentation. Histology and immunohistochemistry are required to reach an accurate diagnosis of IMT.

In this paper, an integrated methodology of wavelet transform and ACO-SVM is applied to predicting share price. On the one hand, the instability of the time series could lead to decrease of prediction accuracy, so wavelet transform (WT) is employed as a preprocessor of SVM to eliminate the fluctuant component of original data. On the other hand, two parameters of SVM must be carefully predetermined in establishing an efficient LS-SVM model, in order to solve this problem, the ant colony optimization algorithm (ACO) is used to optimize the parameters of SVM. A practical prediction of Huaneng Guoji show that the integrated methodology of wavelet transform and ACO-SVM can serve as a promising alternative for share price prediction.