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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.

The wellbore of a sucker-rod pumping well experiences a multi-phase flow consisting of oil, gas, and water. The flow pattern and pump discharge pressure are greatly impacted by oil well production, which in turn significantly affects the simulation results of longitudinal vibration in the sucker-rod string. When calculating the discharge pressure in a hydrostatic column containing both oil and water (HC), the pressure is not affected by the oil well’s production. This thereby avoids interference between vibrations in the sucker-rod string’s longitudinal direction and the flow from the wellbore. Considering the coupling characteristics between the longitudinal vibration of the sucker-rod string and the wellbore flow, a mathematical model of the sucker-rod pumping system (CMSRS) and a mathematical model of the downhole energy efficiency parameters were established. In detail, the CMSRS comprises two parts: the discharge pressure mathematical models of multi-phase flow dynamics (MD) and the wave equation of the longitudinal vibration of the sucker-rod string. A numerical simulation model of the sucker-rod pumping system was constructed based on a mathematical model. We compared the experimental results, the simulation results of the CMSRS and the simulation results of the sucker-rod string based on the oil-water two–phase hydrostatic column (SMSRS) and found good agreement, indicating the feasibility of the CMSRS. The simulation details show the following: (1) The HC model’s discharge pressure exceeds that of the MD model by more than 33.52%. The polished rod load for the CMSRS is 18.01% lower than that of the SMSRS, and the pump input power for the CMSRS is 36.23% lower than that of the SMSRS. (2) The effective power simulation model based on the energy balance relationship is essentially the same as the effective power calculated by the model based on multi-phase flow effective power. This validates the accuracy of the multi-phase flow effective power model. (3) The limitations of the industry standard effective power model are that (i) the effective head is the net lift height of the fluid in the wellbore reduced to the oil and water phases rather than the effective lift height based on the energy balance relationship and (ii) the power of the gas phase delivered by the pumping pump is disregarded, and only the effective power of the pump delivering the oil-water mixture is considered. (4) The influence of the wellbore parameters on the wellbore efficiency and sub–efficiency is systematically analyzed. The analysis results have an important significance in the guidance of energy saving in pumping wells.

The five recognized zoonotic foodborne pathogens, namely, Listeria monocytogenes, Staphylococcus aureus, Streptococcus suis, Salmonella enterica and Escherichia coli O157:H7, pose a major threat to global health and social–economic development. These pathogenic bacteria can cause human and animal diseases through foodborne transmission and environmental contamination. Rapid and sensitive detection for pathogens is particularly important for the effective prevention of zoonotic infections. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) combined with recombinase polymerase amplification (RPA) were developed for the simultaneous quantitative detection of five foodborne pathogenic bacteria. Multiple T lines were designed in a single test strip for increasing the detection throughput. After optimizing the key parameters, the single-tube amplified reaction was completed within 15 min at 37 °C. The fluorescent strip reader recorded the intensity signals from the lateral flow strip and converted the data into a T/C value for quantification measurement. The sensitivity of the quintuple RPA-EuNP-LFSBs reached a level of 101 CFU/mL. It also exhibited good specificity and there was no cross-reaction with 20 non-target pathogens. In artificial contamination experiments, the recovery rate of the quintuple RPA-EuNP-LFSBs was 90.6–101.6%, and the results were consistent with those of the culture method. In summary, the ultrasensitive bacterial LFSBs described in this study have the potential for widespread application in resource-poor areas. The study also provides insights in respect to multiple detection in the field.

Porcine epidemic diarrhea virus (PEDV), porcine bocavirus (PBoV), and porcine rotavirus (PoRV) are associated with porcine viral diarrhea. In this study, triplex loop-mediated isothermal amplification (LAMP) combined with a lateral flow dipstick (LFD) was established for the simultaneous detection of PEDV, PoRV, and PBoV. The PEDV-gp6, PoRV-vp6, and PBoV-vp1 genes were selected to design LAMP primers. The amplification could be carried out at 64 °C using a miniature metal bath within 30 min. The triplex LAMP–LFD assay exhibited no cross-reactions with other porcine pathogens. The limits of detection (LODs) of PEDV, PoRV, and PBoV were 2.40 × 101 copies/μL, 2.89 × 101 copies/μL, and 2.52 × 101 copies/μL, respectively. The consistency between rt-qPCR and the triplex LAMP–LFD was over 99% in field samples testing. In general, the triplex LAMP–LFD assay was suitable for the rapid and simultaneous detection of the three viruses in the field.

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.

We aimed to confirm whether transmembrane serine protease 2 (TMPRSS2) regulates nidogen 1 (NID1) expression in extracellular vesicles (EVs) and metastatic hepatocellular carcinoma (HCC) cells. HCC cells, HUVEC cells, MRC-5 cells, HLE cells, MHCCLM3 cells, MHCC97L cells, H2P cells, H2M cells, as well as LO2 cells were cultured according to providers’ instruction and EV models were established by using BALB/cAnN-nu mice to facilitate the verifications. We found that TMPRSS2 expression was inversely correlated with the metastatic potential of HCC cell lines. The expression of TMPRSS2 decreased in a time-dependent manner in tumor-bearing model mice implanted with MHCCLM3 cells compared with uninoculated mice. TMPRSS2 overexpression in MHCCLM3 and MHCC97L cells led to the significant downregulation of NID1 expression in total cell lysates and isolated EVs. In contrast, TMPRSS2 silencing resulted in the elevation of NID1 expression in cells and EVs. Administration of EVs from MHCCLM3 and MHCC97L cells with overexpressed or silenced TMPRSS2 inhibited or strengthened, respectively, the invasion, proliferation, and migration of LO2 tumor cells. EVs derived from MHCCLM3 and MHCC97L cells with overexpressed or depleted TMPRSS2 also deactivated or activated fibroblasts, respectively. These EVs secrete inflammatory cytokines and phosphorylated p65, facilitate the colonization of fibroblasts, and augment fibroblast growth and motility. These findings provide evidence for a new candidate drug targeting tumorigenic EV-NID1 to treat HCC.