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To solve the problems of high error on both sides and high coefficient of variation during liquid manure distribution, this work designed a distribution mechanism integrating conveying, stirring and distribution functions, combined with the physical properties of selected liquid manure. Taking rotor speed, inlet flow and moving cutter structure as test factors, the Design-Expert 8.0.6 software was used to design "three-factor three-level quadratic regression" orthogonal test and establish response surface regression model. Through observing relative error and coefficient of variation, uniform distribution characteristics test and parameter optimization of liquid manure were performed. The results showed that the primary and secondary order of influencing factors on the relative error is rotor speed> inlet flow > moving cutter structure; the primary and secondary order of influencing factors on the coefficient of variation is inlet flow > moving cutter structure> rotor speed. Further, the optimization test indicated that 170 r/min rotor speed, 80 m3/h inlet flow, combined with arc-shaped moving cutter structure could output 10.50% relative error and 9.30% variation rate, which was less than 5% relative to the model predicted value.

A major challenge in human genetics is to identify the molecular mechanisms of trait-associated and disease-associated variants. To achieve this, quantitative trait locus (QTL) mapping of genetic variants with intermediate molecular phenotypes such as gene expression and splicing have been widely adopted(1,2). However, despite successes, the molecular basis for a considerable fraction of trait-associated and disease-associated variants remains unclear(3,4). Here we show that ADAR-mediated adenosine-to-inosine RNA editing, a post-transcriptional event vital for suppressing cellular double-stranded RNA (dsRNA)-mediated innate immune interferon responses(5–11), is an important potential mechanism underlying genetic variants associated with common inflammatory diseases. We identified and characterized 30,319 cis-RNA editing QTLs (edQTLs) across 49 human tissues. These edQTLs were significantly enriched in genome-wide association study signals for autoimmune and immune-mediated diseases. Colocalization analysis of edQTLs with disease risk loci further pinpointed key, putatively immunogenic dsRNAs formed by expected inverted repeat Alu elements as well as unexpected, highly over-represented cis-natural antisense transcripts. Furthermore, inflammatory disease risk variants, in aggregate, were associated with reduced editing of nearby dsRNAs and induced interferon responses in inflammatory diseases. This unique directional effect agrees with the established mechanism that lack of RNA editing by ADAR1 leads to the specific activation of the dsRNA sensor MDA5 and subsequent interferon responses and inflammation(7–9). Our findings implicate cellular dsRNA editing and sensing as a previously underappreciated mechanism of common inflammatory diseases.

Ultra-high-performance concrete (UHPC) has been regarded as promising alternative to provide reliable connections between difference segments (e.g., columns and pier footing/cap) during accelerated bridge construction (ABC) procedures. This paper proposes an innovative layered-UHPC connection for the pre-fabricated segmental (PFS) pier, whose seismic performance was validated through quasi-static experiment. The corresponding design procedure for PFS pier with this type of connections is presented based on the test results. The layered-UHPC connection ensures the emulative performance of pre-fabricated bridge as cast-in-place (CIP) ones, as well as provides greater economic efficiency than traditional UHPC connections. Based on experimental results, key issues concerning this connection, including the tensile behavior of UHPC, height of connection region, thickness of UHPC layer and steel bars in grouting bed, are presented and discussed. Then a seismic design procedure is proposed utilizing the capacity protection philosophy widely adopted in design specifications. The layered-UHPC connection is expected as capacity-protected component without damage, since it provides anchorage for steels extended from columns and pier cap/footing. While the pre-fabricated region is designed as ductile component undergoing nonlinearity during strong earthquakes. Following the detailed elaborations about the design philosophy, requirement and implementation steps, this procedure is further presented through illustration examples using PFS piers with various heights. The results show that PFS piers designed according to this procedure could meet the requirement under both frequent and rare earthquakes. Note that the PFS piers with this layered-UHPC connections could be designed similar to and emulative as CIP ones, which is believed friendly to designers in engineering practice.

Purpose This paper aims to explore the effect of automatic transmission fluid (ATF) temperature on the dynamic friction-wear properties of the friction component in a wet multi-disc clutch during the running-in process. Design/methodology/approach The running-in evolution was explored in terms of global friction performance and instantaneous friction characteristics. The variation of friction torque of the initial 300 engagement cycles was obtained by wet-clutch tests. Finally, an optical microscope was used to detect the wear mechanism of friction surfaces. Findings The ATF temperature showed a significant effect on the friction-wear performance in the clutch running-in process. The mean coefficient of friction decreased with the increase of the ATF temperature and decreased rapidly in the approximately initial 60 clutch engagements. The higher the ATF temperature was, the thinner the ATF film was, and more asperity summits were cut, thus leading to a smoother surface. Considering the slightly instantaneous friction fluctuation and the wear performance, a proper ATF temperature is necessary. Originality/value The results provide theoretical guidance for selecting the optimal ATF temperature during the running-in process.

Grain size is one of the essential determinants of rice yield. Our previous studies revealed that ethylene plays an important role in grain-size control; however, the precise mechanism remains to be determined. Here, we report that the ethylene response factor OsERF115 functions as a key downstream regulator for ethylene-mediated grain development. OsERF115 encodes an AP2/ERF-type transcriptional factor that is specifically expressed in young spikelets and developing caryopses. Overexpression of OsERF115 significantly increases grain length, width, thickness and weight by promoting longitudinal elongation and transverse division of spikelet hull cells, as well as enhancing grain-filling activity, whereas its knockout mutations lead to the opposite effects, suggesting that OsERF115 positively regulates grain size and weight. OsERF115 transcription is strongly induced by ethylene, and OsEIL1 directly binds to the promoter to activate its expression. OsERF115 acts as a transcriptional repressor to directly or indirectly modulate a set of grain-size genes during spikelet growth and endosperm development. Importantly, haplotype analysis reveals that the SNP variations in the EIN3-binding sites of OsERF115 promoter are significantly associated with the OsERF115 expression levels and grain weight, suggesting that natural variations in the OsERF115 promoter contribute to grain-size diversity. In addition, the OsERF115 orthologues are identified only in grass species, implying a conserved and unique role in the grain development of cereal crops. Our results provide insights into the molecular mechanism of ethylene-mediated grain-size control and a potential strategy based on the OsEIL1-OsERF115-target gene regulatory module for genetic improvement of rice yield.

Spiroindoles are key scaffolds in a large number of natural products, pharmaceuticals, and agrochemicals. Selective C–H activation has emerged as a powerful synthetic approach to streamline the synthesis of substituted spiroindoles. To date, various 2- and 3-indolyl-tethered aza-spiro-centers have been successfully achieved via C–H activation. However, introduction of spiro-containing systems onto the benzenoid core of indole still remains challenging. Herein, a method of Rh(III)-catalyzed selective C7-H activation/cyclization of indole with maleimide to afford novel spiroindole derivatives is reported, which incorporate both succinimide and spirocycle into indole unit. Gram-scale synthesis demonstrates the utility of this protocol, further modification via click chemistry offered a novel scaffold as a versatile spiro linker.

Indocyanine green fluorescence cholangiography is a new type of cholangiography that has emerged in recent years. It has many advantages, such as simplicity, safety, and efficiency, and is expected to become a routine procedure for intraoperative cholangiography in the future. However, there is no bibliometric analysis of horizontal generalization in this field. Therefore, this study aims to assess the current research status and developmental trends in this field from a global perspective and to help guide the focus of future research.This study was conducted by retrieving the literature related to ICG fluorescence cholangiography published in English from 2000 to 2021 from Web of Science. The Histcite. Pro tool was used to analyze the bibliometric indicators, and VOSviewer was used to visualize the research trends and hotspots in this field.192 related studies were finally included. For the past 20 years, the number of related publications in this field have increased yearly, with 2010 being a breakthrough point for research in this field. Research has developed rapidly since 2013 and may continue to expand in the next several years. The USA and Japan play leading roles in this field. "SURG ENDOSC", "SURG INNOV", and "J LAPAROENDOSC ADV S" are core journals that publish high-quality literature and the latest developments in this field. Some authors who have a large number of high-quality publications include Ishizawa T and Kokudo N. The current research hotspots in this field are focused on exploring the factors that affect ICG cholangiography and optimization measures.In general, the number of documents related to ICG fluorescence cholangiography is growing rapidly, with the USA and Japan being influential countries and China being one of the major producers of these documents. The optimization of this new technology will affect key developments in future research.

In order to slow down the cooling rate of mixture and reduce the low-temperature cracking of asphalt pavement in large temperature difference areas, polyurethane solid–solid low-temperature phase change materials (PSLPCMs) were prepared by prepolymer method in this study. The PSLPCMs were incorporated into hot mix asphalt mixture to prepare PSLPCMs particle asphalt mixture. The pavement performance and phase change temperature control behavior of this special type of mixture were analyzed from the perspectives of particle content and particle size. Studies have shown that PSLPCMs have good phase change thermal storage performance and thermal stability. Different PSLPCMs content and particle size have certain improvement effect on the high temperature stability and low temperature crack resistance of the mixture, and have no obvious adverse effect on the water stability of the mixture. At the same dosage, with the increase of particle size, the improvement effect of PSLPCMs particles on the road performance of the mixture is more obvious. With the increase of PSLPCMs particle content, the specific heat capacity of asphalt mixture increases, and the thermal conductivity decreases. The temperature regulation effect of asphalt mixture shows an increasing trend, and the cooling rate slows down. The PSLPCMs particles with particle size of 1.18–2.36 mm have better improvement effect on the temperature regulation performance of the mixture. When the content of PSLPCMs is 7 wt%, the maximum temperature regulation effect of the mixture reaches 3.4 °C.

Infrared and near-infrared spectroscopy were used to investigate the gelation process of thermosensitive block copolymers. Intermolecular hydrogen bond dissociation of hydrophobic blocks is the main driving force for gelation process.

We study a Monge-Ampère type equation that interpolates the classical {σ_2} -Yamabe equation in conformal geometry and the 2-Hessian equation in dimension 4., 37 pages

Permeable asphalt mixtures are widely used to achieve good permeability of the pavements used for urban road surfaces. Based on the law of water migration in permeable road structures, the water-holding performance of permeable asphalt mixtures was analyzed and the evaluation indexes were determined. Open-graded asphalt friction course (OGFC-13) permeable asphalt mixture was selected, and the changes in the saturation, water retention, and water-holding rate of OGFC-13 permeable asphalt mixtures with different porosities were compared using water-holding equipment. The water-holding characteristics of permeable pavement materials under different seepage conditions were analyzed. A model of the relationship governing the water-holding capacity of the permeable asphalt mixture, water action conditions, and material porosity was established by a linear fitting method, and the reliability of the model was verified by comparison with laboratory test results, providing a foundation for related research on the water-holding and cooling behavior of permeable pavements.

Gallium-based liquid metals (LMs) featuring both high conductivity and fluidity are ideal conductors for soft and stretchable electronics. However, their liquid nature is a double-edged sword in many key applications since LMs are inherently prone to mechanical damage. Although additional encapsulation is frequently used for the protection of delicate LM electrodes, it hinders the electrical interfacing with other objects for interconnection, sensing, and stimulation. Here, different from conventional patterning methods that deposit LM on or inside substrates, we for the first time report a simple strategy to create surface-embedded LM of eutectic gallium-indium (EGaIn) circuits with mechanical damage endurance. This was achieved by using direct magnetic printing to overcome the high surface tension of LM, allowing it to be passively filled into the laser-patterned microgrooves on soft substrates. We show that the surface-embedded LM circuits are resistant to mechanical erasure, washing, and peeling. We also show the applications of our surface-embedded LM electrodes in respiration monitoring and electrical stimulation of nerves. This work provides a simple and efficient way to create mechanically reliable LM microelectrodes, holding great promise for wearable and implantable bioelectronics.

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Soil water–salt variations at different spatiotemporal scales and their influencing factors are essential for regional vegetation restoration and management. However, the study of soil water–salt of the alpine area has not taken into account the effect of topography, especially in the long time series. This work investigated the spatiotemporal characteristics of water and salt in topsoil from 2000 to 2021, using regression analysis of on-site data and MODIS products. The heterogeneity and trends of soil water–salt in various topographic factors (elevation, slope, and aspect) were also explored by selecting the maximum area of each gradient factor as the constrained condition with the help of ArcGIS software. The results revealed that 1) the models applied to SWC (soil water content), EC (electrical conductivity), and pH utilizing vegetation indices were suitable for estimating the spatiotemporal variations of soil water–salt. 2) Soil water–salt exhibited local aggregation characteristics with an upward trend in SWC and a downward trend in EC and pH as a whole. 3) Mean annual SWC peaked at 3,400–3,800 m with increasing elevation and trended downward with increasing slope. The aspect of mean annual SWC was characterized by lower values in the southwest and south and higher values in the north, while the results for pH were reversed. The slope had a greater influence on EC than on SWC and pH. 4) The trend change of SWC, EC, and pH fluctuated at 2000–2,400 m and >4,600 m with a clear inflection point at 4°–8° and 20°–24°, respectively. In summary, the effects of topography responded to the distribution and trends of soil water–salt. The results have significant implications for implementing ecological improvements in regions with complicated topography and can serve as a reference for formulating future ecological policies.

The plant-specific

Recently, molecular generation models based on deep learning have attracted significant attention in drug discovery. However, most existing molecular generation models have serious limitations in the context of drug design wherein they do not sufficiently consider the effect of the three-dimensional (3D) structure of the target protein in the generation process. In this study, we developed a new deep learning-based molecular generator, SBMolGen, that integrates a recurrent neural network, a Monte Carlo tree search, and docking simulations. The results of an evaluation using four target proteins (two kinases and two G protein-coupled receptors) showed that the generated molecules had a better binding affinity score (docking score) than the known active compounds, and the generated molecules possessed a broader chemical space distribution. SBMolGen not only generates novel binding active molecules but also presents 3D docking poses with target proteins, which will be useful in subsequent drug design. The code is available at https://github.com/clinfo/SBMolGen.

As we all know, the complexity and diversity of complex sample are confronting with challenge of high-sensitive mass spectrometry analysis, especially direct mass spectrometry. The work proposed a two-dimensional carbon microfiber fractionation (2DμCFs) system for the reduction of ion suppression effects in electrospray ionization mass spectrometry (ESI-MS). The 2DμCFs system can on-line fractionated the complex sample into strong-polar, medium-polar and weak-polar fractions for sequential MS analysis. Direct analysis brings about the strong ion suppression effect up to 85%, but the fractionated analysis of 2DμCFs system can distinctly reduce the ion suppression effect to less than 43%, even close to none. And the fractionated analysis not only decrease the number of analytes of direct analysis, but also narrows down the polarity range of analytes within the droplets of ESI, contributing to the homogeneous distribution to reduce the ion suppression effect. As an example, the 2DμCFs system coupled with tandem mass spectrometry (MS/MS) was applied for fractionated analysis of Radix Puerariae extract in 4.5 min. Compared with direct MS/MS, the 2DμCFs-MS/MS shows the lower ion suppression and the more ionic species (m/z). In addition, and most of ionic species detected by the 2DμCFs-MS/MS, are the same as those by HPLC MS/MS. Furthermore, the 2DμCFs-MS/MS exhibit the good analysis repeatability of real sample with the RSDs less than 10.32% (intra-day), 7.12% (inter-day) and 14.28% (inter-batch of CFs and ACFs). The carbon fibers (CFs) and active carbon fibers (ACFs) columns, as the key parts, are conducive to achieve on-line fractionation of compounds based on the difference of polarity. The 2DμCFs system has the merits of on-line, speediness, low-pressure and recycle. More importantly, such fast and high-throughput method is advantageous for comprehensive screening of complex samples in drug, clinical, environment and plant.

B-box (BBX) proteins are one of the zinc-finger transcription factor that plays a critical role in plant development, growth, and multiple stress responses. Although BBX genes have been reported in many model organisms, no comprehensive study has yet been conducted on the BBX genes in Melilotus albus, and the biological functions of this family remain unknown. In this study, a total of 20 BBX (MaBBX) genes were identified in M. albus and were phylogenetically divided into five clades. BBX members within the same clade showed similar conserved domain, suggesting similarity of potential biological function. Analysis of MaBBX conserved motifs showed that every subfamily contained two common motifs. Distribution mapping shows that BBX proteins are nonrandomly localized in eight chromosomes. The synteny showed that most homologous gene pairs of the MaBBX gene family were amplified by segmental replication, which meant segmental replication was the main way for the MaBBX gene family to evolve. Additionally, the cis-element analysis predicted light-responsive, various hormone and stress-related elements in the promoter regions of MaBBXs. Furthermore, the expression levels of all 20 MaBBX genes were detected by qRT-PCR under salt, cold, and dark stresses in M. albus. Moreover, it was observed that 16 genes had higher expression levels after 3 h of salt treatment, 10 genes were significantly upregulated after 3 h of cold treatment, and all genes were up regulated after 3 h of dark treatment, and then appeared to decline. In addition, it was also noticed that MaBBX13 may be an important candidate for improving tolerance to abiotic stress. The prediction of protein tertiary structure showed that the tertiary structures of members of the same subfamily of MaBBX proteins were highly similar. The hypothesis exhibited that most of the MaBBX proteins were predicted to be localized to the nucleus and cytoplasm and was validated by transient expression assays of MaBBX15 in tobacco leaf epidermal cells. This study provides useful information for further investigating and researching the regulatory mechanisms of BBX family genes in response to abiotic stresses in M. albus.

Genome instability is a hallmark of cancer, and the function of lncRNAs in regulating genomic stability has been gradually characterized. However, the prognostic value of lncRNAs related to genetic instability has not been found in breast cancer. Here we constructed a genetic instability-related lncRNA model including U62317.4, SEMA3B-AS1, MAPT-AS1, AC115837.2, LINC01269, AL645608.7, and GACAT2. This model can evaluate the risk and predict the survival outcomes of patients. Further analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immunity and cornified envelope formation pathways. In addition, M2 macrophages infiltrated more obviously in the high-risk group. In summary, lncRNAs related to genetic instability may influence the development of breast cancer through immune infiltration and keratinization. This study provides a wider insight into breast cancer development and treatment.

The stress hormone ethylene plays a key role in plant adaptation to adverse environmental conditions. Nitrogen (N) is the most quantitatively required mineral nutrient for plants, and its availability is a major determinant for crop production. Changes in N availability or N forms can alter ethylene biosynthesis and/or signaling. Ethylene serves as an important cellular signal to mediate root system architecture (RSA) adaptation, N uptake and translocation, ammonium toxicity, anthocyanin accumulation, and premature senescence, thereby adapting plant growth and development to external N status. Here, we review the ethylene-mediated morphological and physiological responses and highlight how ethylene transduces the N signals to the adaptive responses. We specifically discuss the N-ethylene relations in rice, an important cereal crop in which ethylene is essential for its hypoxia survival. This article is protected by copyright. All rights reserved.

When considering the transition probability matrix of ordinal patterns, transition permutation entropy (TPE) can effectively extract fault features by quantifying the irregularity and complexity of signals. However, TPE can only characterize the complexity of the vibration signals at a single scale. Therefore, a multiscale transition permutation entropy (MTPE) technique has been proposed. However, the original multiscale method still has some inherent defects in the coarse-grained process, such as considerably shortening the length of time series at large scale, which leads to a low entropy evaluation accuracy. In order to solve these problems, a composite multiscale transition permutation entropy (CMTPE) method was proposed in order to improve the incomplete coarse-grained analysis of MTPE by avoiding the loss of some key information in the original fault signals, and to improve the performance of feature extraction, robustness to noise, and accuracy of entropy estimation. A fault diagnosis strategy based on CMTPE and an extreme learning machine (ELM) was proposed. Both simulation and experimental signals verified the advantages of the proposed CMTPE method. The results show that, compared with other comparison strategies, this strategy has better robustness, and can carry out feature recognition and bearing fault diagnosis more accurately and with improved stability.

DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence, and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted DBC1 to interact with SIAH2 but not OTUD5, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin–proteasome pathway. SIAH2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of SIAH2/CCAR2. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.

Bio-fertilizer practice considers not only economical but also environmentally friendly, sustainable agriculture. Endophytes can play important beneficiary roles in plant development, directly, indirectly, or synergistically. In this study, the majority of our endophytic actinobacteria were able to possess direct plant growth-promoting (PGP) traits, including auxin (88%), ammonia (96%), siderophore production (94%), and phosphate solubilization (24%), along with cell-wall degrading enzymes such as protease (75%), cellulase (81%), lipase (81%), and chitinase (18%). About 45% of tested strains have an inhibitory effect on the phytopathogen