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ERAP1 is an emerging target for a large subclass of severe autoimmune diseases known as “MHC-I-opathy”, together with tumor immunity. Nevertheless, effective inhibitors targeting ERAP1 remain a challenge. In this study, a novel food-derived natural product ERAP1-targeting inhibitor, carnosic acid, was identified, and to our knowledge, it is one of the best active compounds among the highly selective inhibitors targeting the orthosteric site of ERAP1. The results reveal that carnosic acid could bind strongly, like a key to the ERAP1 active site in the biased S1′ pocket, which is different from the binding mode of the existing orthosteric site inhibitors. HLA-B27-mediated cell modeling validated that carnosic acid has the activity to reverse the AS-associated cellular phenotype brought on by ERAP1 through inhibition. Our findings provide insights into the design of potent inhibitors against the ERAP1 orthosteric site and the discovery of a key direct target of carnosic acid.

In recent years, micronano-structure-functionalized perovskite optoelectronics, which can improve their photoluminescence and photoelectric properties, have been booming. The traditional fabrication processes of micronano-patterned perovskites, such as nanoimprint and optical lithography have complex processes and high environmental requirements. In this article, a method based on a laser-induced periodic surface structure and controlled deposition of metal nanoparticles is first proposed to enhance the light absorption of optoelectronic devices. This method specifically includes wet etching-assisted femtosecond laser writing and deposition of Au nanoparticles by a galvanic displacement reaction. The finite-difference time-domain simulation results show that compared with the silicon substrate without Au nanoparticles, the light absorption rate of the silicon substrate with Au nanoparticles at 300 and 600 nm increased by about 6 and 5.5%, respectively, which is also proved by ultrafast transient absorption spectroscopy. The results of scanning electron microscopy images and energy-dispersive spectrometry mappings show that the deposition density and uniformity of Au nanoparticles are the best when the deposition time is 2.5 min. The photocurrent of the perovskite photodetector prepared in this way shows an enhanced photocurrent, which is about three times that of the device without any treatment. This method has potential applications in photodetectors, solar cells, and so on.

Although reducing students' aggressive behaviors and improving their creativity are both important commitments of educators, they are usually treated independently as unrelated tasks. However, cumulative evidence suggests potential links between aggression and creativity, not only from the perspectives of personality traits and psychological development, but also from their shared cognitive mechanisms. This implies that there may be an approach to achieving these two goals through a single intervention. Moreover, this new approach may overcome the limitation of the usually adopted aggression intervention, which is limited in its regulatory effectiveness and might bring about some disadvantageous impacts on creativity that are closely associated with aggression. To test this possibility, the present study implemented a four‐session, 2‐week creative thinking training (CTT) intervention for students with high aggression scores to examine whether it could simultaneously downregulate aggression and increase creativity. Our results demonstrate that, compared to the control group, the intervention group experienced significant improvements in creativity and a reduction in aggression following the CTT intervention. Furthermore, our findings suggest that this regulatory effect can persist for up to 6 months. The CTT‐induced creativity change (increase) could significantly correlate with and predict the CTT‐induced aggression decrease, thus suggesting that the CTT could transform aggression into creativity.

Zirconia toughened alumina (ZTA) ceramic particles reinforced high chromium cast iron (HCCI) architectural composites (ZTA/HCCI composites) are widely used in many fields. In this study, the ZTA/HCCI composites wear performance and interfacial characterization after the actual working condition were all studied. The wear resistance of the ZTA/HCCI composites in this actual working condition were promoted for fourfold compared to the HCCI. The mainly composition of the worn surface were α-Al2O3, t-ZrO2and less carbide. In the service process, ZTA ceramic particles had performed a major supportive function according to the composites' worn surface structure. The wear characteristics show complexity, including the wear of metal matrix supported by ZTA ceramics and the intense wear surface of ZTA ceramics. The interfacial layer was formed at high temperature and was polycrystalline type after the wear process in the actual working condition. After actual working condition, the wear mechanism of ZTA/HCCI composites shows mixed characteristics of various stages. In this study, these series characterizations could enrich the wear mechanism of these kinds of composites.

Purpose: Heart failure (HF) is a serious and complex syndrome with a high mortality rate. In clinical diagnosis, the correct classification of HF is helpful. In our previous work, we proposed a self-supervised learning framework of HF classification (SSLHF) on cine cardiac magnetic resonance images (Cine-CMR). However, this method lacks the integration of three dimensions of spatial information and temporal information. Thus, this study aims at proposing an automatic 4D HF classification algorithm. Methods: To construct a 4D classification model, we proposed an extensional framework called 4D-SSLHF. It mainly consists of self-supervised image restoration and HF classification. The image restoration proxy task utilizes three image transformation methods to enhance the exploration of spatial and temporal information in the Cine-CMR. In the classification task, we proposed a Siamese Conv-LSTM network by combining the Siamese network and bi-directional Conv-LSTM to integrate the features of the four dimensions simultaneously. Results: Experimental results on 184 patients from Shanghai Chest Hospital achieved an AUC of 0.8794 and an ACC of 0.8402 in the five-fold cross-validation. Compared with our previous work, the improvements in AUC and ACC were 2.89 % and 1.94 %, respectively. Conclusions: In this study, we proposed a novel self-supervised learning framework named 4D-SSLHF for HF classification based on Cine-CMR. The proposed 4D-SSLHF can mine 3D spatial information and temporal information in Cine-CMR images well and accurately classify different categories of HF. The good classification results show our method’s potential to assist physicians in choosing personalized treatment.

Highly crystalline carbon nitride (CCN), benefiting from the reduced structural imperfections, enables improved electron–hole separation. Yet, the crystalline phase with insufficient inherent defects suffers from a poor performance toward the reaction intermediate adsorption with respect to the amorphous phase. Herein, a crystalline–amorphous carbon nitride (CACN) with an isotype structure was constructed via a two-step adjacent calcination strategy. Through specific oxygen etching and crystallization, the formation of a built-in electric field at the interface could drive charge transfer and separation, thus promoting photoredox reaction. As expected, the optimized CACN exhibited a H2O2generation efficiency as high as 2.15 mM gcat–1h–1, paired with a promoted pollutant degradation efficiency, which outperform its crystalline (CCN) and amorphous [amorphous carbon nitride (ACN)] counterparts. The detailed electron/hole transportation via a built-in electronic field and free radical formation based on the enhanced adsorption of oxygen were considered, and the synchronous reaction pathway was carried out. This work paves a novel pathway for the synthesis of carbon nitride with an isotype structure from the perspective of interfacial engineering.

The rise of Internet of Things technologies has promoted the rapid advancement of wearable health monitoring devices. While medical ultrasound technology holds promise for long-term monitoring to detect critical chronic diseases, current commercial ultrasound probes often lack the flexibility, miniaturization, and comfort necessary for medical wearable devices. To address this gap, we propose a weavable and wearable polymer ultrasonic transducer comprising a matching layer, a backing layer, and a piezoelectric layer. This transducer exhibits a bandwidth of 93%, which is six times that of transducers made from piezoelectric ceramics, and could withstand over 10,000 cycles of bending and twisting deformations. The transducer successfully monitors blood flow velocity and measures vessel thickness in the carotid artery and cardiac vessel, achieving a signal-to-noise ratio comparable to that of commercial probes. Its wideband property, with a bandwidth of 3.68–10.08 MHz, allows for the monitoring of various tissues through frequency adjustment. Furthermore, the weavable ultrasonic transducer in fiber form is seamlessly integrated into breathable textiles for real-time cardiovascular monitoring without compromising comfort.

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The kinematic approach [i.e., kinematic precise point positioning (PPP)] has been extensively employed in real-time precise orbit determination (RTPOD) of low Earth orbit (LEO) satellites. Nonetheless, this approach typically suffers from a degraded accuracy and robustness due to its sensitivity to global navigation satellite system (GNSS) ephemeris errors and observation quality/geometry. To address this issue, we propose a novel method that incorporates the backpropagation neural network (BPNN) model into LEO kinematic RTPOD (KRTPOD) to improve its accuracy and robustness. The historical KRTPOD results are compared with external orbit products to compute orbit errors. Meanwhile, multiple features are generated from the historical KRTPOD processing. We train the BPNN model to discover the nonlinear relationship between these features and orbit errors. Based on the trained model, orbit errors of LEO KRTPOD can be forecast according to the input features and then serve as the orbit compensation to improve LEO orbits in real time. Data throughout 2022 from six LEO satellites are processed to examine the performance of this method. Our findings reveal that the proposed method can significantly improve the accuracy of LEO KRTPOD by up to 39.0%. Benefiting from this method, a promising accuracy of 3.2 cm can be achieved in LEO KRTPOD. We also demonstrate the superior generalization ability of the new method under different scenarios. Moreover, this method can enhance the robustness of LEO KRTPOD by mitigating the contamination caused by large GNSS ephemeris errors and accelerating convergence.

Smart electronic textiles with electronic functions like displaying can provide transformative opportunities for wearable devices that traditional rigid devices are hard to realize. A general strategy of enabling textiles to display is weaving light-emitting fibers into textiles and designing control circuits. However, it remains challenging for the current electronic textiles to display full-color images and videos. Here, we demonstrate a large-area integrated electronic textile system (with a size of 72 cm × 50 cm) by weaving light-emitting diode (LED) fibers, touch-sensing fibers and polyester fibers, which could display full-color images (with a gamut of 117.6% NTSC) and continuous videos (with a refresh rate of 11.7 Hz) by designing low-voltage supply mode and parallelly transmitting circuits. After integration of touch-sensing fibers, such textile system could achieve various touch display and interactive functions like smart phones or computers, including hand input of text, hand painting, computing and playing games. The stability and durability of textile system withstanding 5000 bending cycles was also demonstrated for wearable applications. The integrated electronic textile system shows similar flexibility and breathability with regular textiles, which is promising to serve as new human-machine interface to change the way in which people interact with electronics.

77-GHz automotive multiple input multiple output (MIMO) radar is traditionally implemented in the bulky PCB board in a cascaded format to achieve a high resolution. This article reports mold-on-mold fan-out wafer-level packaging (FOWLP) antenna-in-packages (AiP) technology to directly mold the radar dies into the package while with the mold-on-mold advantage of integrating the antenna seamlessly on the top of the package. This process combined with the patented MIMO layout makes a high-resolution MIMO radar achievable in a very compact format: within a space of $64\times 32\times 0.7$ mm, two $32\times 16$ mm AiPs and two $16\times 16$ mm AiPs, with each AiP carrying one transceiver die, are configured to achieve both long range radar (LRR) and medium range radar (MRR) functions with 1° angular resolution in both vertical and horizontal sensing operations. We disclose the FOWLP AiP structure and key design details to implement such a MIMO radar, including AiP element and RF passive circuits modeling and test; the MIMO AiP performance is shown in terms of impedance bandwidth, patterns, feed line consistency, and isolations; the LRR and MRR MIMO detection range and resolution performance are finally evaluated.

Light source and photodetector are necessary elements for liquid concentration sensing system. Normally, two different devices are needed to realize these functions. The coexistence of emission and detection properties in multi-quantum well light emitting diodes (MQWs LEDs) brings convenience to the design of new concentration sensors. In this letter, we present a transmission-type sensing module using two identical AlGaInP red LEDs. With a designed collimation system, any two LEDs can form a sensing channel. Concentration-induced optical signal changes will be transformed into various photocurrents on the receiving side and realize a sensing. Choosing methylene blue solution as the tracer agent, the sensing performance of the system is evaluated. The sensor can detect methylene blue solution concentrations in the range of 0 to $24.23~\mu $ mol/L, providing a novel measurement approach for monitoring substances in wastewater.

Recycling is the current development direction for the treatment of sulfuric acid wastewater, where the concentration of chloride (Cl(−i)) impurity below 50 mg L−1is a prerequisite. In this study, a clean, cheap and effective advanced oxidation approach was proposed for the removal of Cl(−i) using photoactivated peroxymonosulfate (PMS) or persulfate (PS). The removal efficiency of Cl(−i) viaPMS or PS under ultraviolet (UV) light or sunlight was successively determined, and the mechanism for the removal of Cl(−i) was explored. For PMS, the contribution ratios of direct oxidation viaPMS, indirect oxidation viahydroxyl (·OH) radicals and indirect oxidation viasulfate (·SO4−) radicals were 13.3%, 14.9% and 71.8%, respectively, under UV light. For PS, the contribution ratios of ·OH and ·SO4−radicals under UV irradiation were 28.3% and 71.7%, respectively. Under suitable conditions, both PMS and PS showed excellent performance for the removal of Cl(−i) with a residual concentration of Cl(−i) below 50 mg L−1. Owing to its higher stability in air, lower dosage under sunlight, shorter reaction time and lower power consumption, PMS exhibited more advantages in the aspects of storage convenience, electricity and reagent cost, and application possibilities under sunlight compared to PS.

Intelligent monitoring technology plays an important role in promoting the development of coal mine safety management. Low illumination in the coal mine underground leads to difficult recognition of monitoring images and poor personnel detection accuracy. To alleviate this problem, a low illuminance image enhancement method proposed for personnel safety monitoring in underground coal mines. Specifically, the local enhancement module maps low illumination to normal illumination at pixel level preserving image details as much as possible. The transformer-based global adjustment module is applied to the locally enhanced images to avoid over-enhancement of bright areas and under-illumination of dark areas, and to prevent possible color deviations in the enhancement process. In addition, a feature similarity loss is proposed to constrain the similarity of target features to avoid the possible detrimental effect of enhancement on detection. Experimental results show that the proposed method improves the detection accuracy by 7.1% on the coal mine underground personal dataset, obtaining the highest accuracy compared to several other methods. The proposed method effectively improves the visualization and detection performance of low-light images, which contributes to the personnel safety monitoring in underground coal mines.

Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a ‘possible’ cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.

Chiral covalent organic frameworks (CCOFs) benefit from superior stability, abundant chiral environment, and homogeneous pore configuration. In its constructive tactics, only the post-modification method allows for the integration of supramolecular chiral selectors into achiral COFs. Here, the finding utilizes 6-deoxy-6-mercapto-β-cyclodextrin (SH-β-CD) as chiral subunits and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde (DVA) as the platform molecule to synthesize chiral functional monomers through thiol-ene click reactions and directly establish ternary “pendant-type” SH-β-CD COFs. The chiral site density on SH-β-CD COFs was regulated by changing the proportion of chiral monomers to obtain an optimal construction strategy and remarkably improve the ability of chiral separation. SH-β-CD COFs were coated on the inner wall of the capillary in a covalently bound manner. The prepared open tubular capillary was achieved for the separation of six chiral drugs. By combining the outcomes of selective adsorption and chromatographic separation, we observed the higher density of chiral sites in the CCOFs, and poorer results were achieved. From the perspective of spatial conformational distribution, we interpret the variation in the performance of these chirality-controlled CCOFs for selective adsorption and chiral separation.

Advanced knowledge engineering (KE), represented by knowledge graph (KG), drives the development of various fields and engineering technologies and provides various knowledge fusion and knowledge empowerment interfaces. At the same time, advanced system engineering (SE) takes model-based system engineering (MBSE) as the core to realize formal modeling and process analysis of the whole system. The two complement each other and are the key technologies for the transition from 2.0 to 3.0 in the era of artificial intelligence and the transition from perceptual intelligence to cognitive intelligence. This survey summarizes an advanced information fusion system, from model-driven to knowledge-enabled. Firstly, the concept, representative methods, key technologies and application fields of model-driven system engineering are introduced. Then, it introduces the concept of knowledge-driven knowledge engineering, summarizes the architecture and construction methods of advanced knowledge engineering and summarizes the application fields. Finally, the combination of advanced information fusion systems, development opportunities and challenges are discussed.

Zirconia toughened alumina (ZTA) ceramic particles can significantly enhance the wear resistance of high chromium cast iron (HCCI). In this study, the effect on the wear resistance of quenched and quenched-tempered heat treatment for ZTA/HCCI architecture composites has been investigated. After three-body abrasive wear, the quality loss ratio of quenched and quenched-tempered composites was 0.31 % and 0.29 %, respectively; while the quality loss ratio of quenched-tempered HCCI was 0.58 %, which means the wear resistance of ZTA/HCCI composites enhanced. The matrix microstructure of HCCI transferred to martensite or tempered martensite, which made the metal uniformly distribute and ensure the relatively high hardness of ZTA/HCCI architecture composites. Then, the worn surface structure of the ZTA/HCCI architecture composites revealed that ZTA ceramic particles have a shadow effect to enhance the wear resistance of HCCI. The wear process of the composite can be summarized into four stages: First, martensite or tempered martensite peels off and accompanies by a work-hardening process at the surface. Second, carbide starts to crack and break. Third, the size of the composite diffusion layer boundary starts to decrease. Finally, ZTA ceramic particle surface breaks and the composite enters a state of instability. The ZTA/HCCI composites heat treatment process can give an idea for machinability and excellent wear resistance.

Silver-indium solid solution is the key material in advancing low-temperature/pressure solid-state technology for electronics packaging, due to its rare solid solution softening (SSS) phenomenon. In this work, the critical resolved shear stress (CRSS) for slip, ideal shear strength and critical twinning stress of silver-indium disordered solid solutions were systematically evaluated by the generalized planar fault energy (GPFE) analysis, using first-principles modelling. Compared with others, Ag-based metals have much lower ideal shear strength and critical twinning stress, whereas the CRSS for slip of silver-indium solid solutions decreases with the increases of indium content, therefore exhibiting a general trend of softening behaviors. For the first time, the electronic origin of silver-indium SSS mechanism has been unveiled, where the modification of its GPFE structure was the fundamental cause for the reduction of CRSS for slip, critical twinning stress and the corresponding SSS phenomenon. As confirmed by transmission electron microscopy, this work presents a new design criterion for the next-generation solid-state bonding materials development.

The widespread use of distributed energy sources (DERs) raises significant challenges for power system design, planning, and operation, leading to wide adaptation of tools on hosting capacity analysis (HCA). Traditional HCA methods conduct extensive power flow analysis. Due to the computation burden, these time-consuming methods fail to provide online hosting capacity (HC) in large distribution systems. To solve the problem, we first propose a deep learning-based problem formulation for HCA, which conducts offline training and determines HC in real time. The used learning model, long short-term memory (LSTM), implements historical time-series data to capture periodical patterns in distribution systems. However, directly applying LSTMs suffers from low accuracy due to the lack of consideration on spatial information, where location information like feeder topology is critical in nodal HCA. Therefore, we modify the forget gate function to dual forget gates, to capture the spatial correlation within the grid. Such a design turns the LSTM into the Spatial-Temporal LSTM (ST-LSTM). Moreover, as voltage violations are the most vital constraints in HCA, we design a voltage sensitivity gate to increase accuracy further. The results of LSTMs and ST-LSTMs on feeders, such as IEEE 34-, 123-bus feeders, and utility feeders, validate our designs.

Ionic liquids (ILs) have attracted increasing attention since last few decades due to their high molecular design abilities and wide applications in different fields. In this study, four novel fluorescent isoquinolino [2,1-a]quinoxalin-5-ium ILs were designed and synthesized viaa two-step process including a simple dual Schiff's base formation and a subsequent [RhCp∗Cl2]2-catalyzed oxidative C–H activation/annulation reaction. The as-synthesized ILs were extensively characterized using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, HSQC-NMR, HMBC-NMR and HR-MS. Their photophysical properties were determined by steady-state fluorescence spectroscopy. The results demonstrate that all these ILs showed dual or triple emissions, large stokes shift (90 nm) and mechanochromic behaviors. Basing on solvatochromism and titration experiments, it is thought that the emission bands of the ILs are raised from their local excited states, charge transfer states or excited state proton transfer of cations, while the substitute effect of these quinoxaline derived ILs on their stokes shifts is negligible.

To enhance the high-temperature adaptability of copper-based composite materials and C–C/SiC discs, this article innovatively introduces a method of replacing graphite with sepiolite, resulting in the successful fabrication of samples with exceptional mechanical and friction properties. The results reveal that moderate incorporation (less 6%) of sepiolite provides a particle reinforcement effect, resulting in an improvement of mechanical properties. Interestingly, the addition of sepiolite causes a change in the traditional saddle-shaped friction curve due to high temperature lubrication. Meanwhile, the primary advantage of sepiolite lies in its superior abrasion resistance, evident in the increased friction coefficient and altered wear mechanisms with higher sepiolite content. The wear resistance is optimal at 200 ​Km/h (400 ​°C). Particularly, the unique composition of the friction layer (outermost layer: a composite film consisting of B2O3, sepiolite, graphite, and metal oxide films; intermediate layer: metal oxide films) plays a pivotal role in improving friction stability. Finally, there are significant optimizations in the GA algorithm, especially GA-GB model has the best prediction effect on the maximum friction temperature.

The microgrid is increasingly important because of the rapid development of renewable energy. Meanwhile, power converter is an important interface, where the stable operation of microgrid need effective inverter control strategy. The virtual synchronous generator technology emulates the synchronous generator’s electromechanical transient characteristics, which has been used in the inverter of microgrid in both the grid-connected and islanded mode. While switching from islanded mode to grid-connected mode, the virtual synchronous generator based microgrid need a pre-synchronization method to avoid voltage distortion and current surge. The previous pre-synchronization methods usually focus on the synchronization of single inverter, which may lead to the dynamic power distribution problem in mode switch. This paper presents an improved pre-synchronization method for virtual synchronous generator based multi-inverter microgrids, which can realize the seamless switching and rational power distribution. In addition, to optimize the performance in mode switch, the influence of pre-synchronization parameters on the pre-synchronization microgrid is analyzed, which provides useful advice to the parameter design. Finally, the experimental platform of microgrid based on dSPACE is built to verify the effectiveness of the proposed control strategy.

The grid-connected inverter needs to know the phase information of the grid voltage. The traditional method is to use the phase-locked loop (PLL) to capture the phase of the grid. However, the PLL takes some time to capture the phase and affects the stability of the grid-connected inverter. Based on this, this paper proposes a vector control strategy without PLL. Firstly, the virtual vector axis is constructed, and the grid voltage is transformed as the reference phase angle. Then the instantaneous power formula in this case is derived. The corresponding control block diagram is constructed. The method reduces the coordinate transformation operation and simplifies the control structure while ensuring the stability of the control system. The simulation results under MATLAB/Simulink show that the control effect of this method is better than that of the PLL vector control strategy, and the method has smaller computational complexity, less resources and more cost savings.

β-Cyclodextrin covalent organic frameworks (β-CD COFs) show great potential in enantioseparation due to their uniformly distributed chiral recognition sites and good chemical stability. The hydroxyl and amino groups of β-CD COFs enable facile post-modification to introduce the desired functionality into the frameworks. In this study, we perform post-modification of β-CD COFBPDAwith 1,4-butane sultone and [(3R,4R)-4-acetyloxy-2,5-dioxooxolan-3-yl] acetate to construct two kinds of novel functional β-CD COFs. The capillary columns prepared with these two functional β-CD COFs separated chiral dihydropyridines and fluoroquinolones with excellent selectivity and repeatability in capillary electrochromatography, while β-CD COFBPDA-modified capillary columns did not present the chiral recognition ability for these drugs. The mechanism of chiral recognition and the enhanced enantioselectivity of functional β-CD COFs were further demonstrated by molecular docking simulation. The divergent chiral separation performances of β-CD COFs suggest that the introduction of functional groups enables the modification of β-CD COF properties and tuning of its chiral recognition abilities for the diversity of enantioseparation.

Ulcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta , in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor- α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota. [ABSTRACT FROM AUTHOR]

The new Global Navigation Satellite System (GNSS) satellites, including GLONASS, Galileo, and BeiDou system, are equipped with Laser Retroreflector Arrays (LRA) to support Satellite Laser Ranging (SLR) tracking, which contributes to the estimation of global geodetic parameters. In this study, we estimate the global geodetic parameters using the SLR observations to GNSS satellites and also investigate the effects of different data processing strategies on the estimated Earth Rotation Parameters (ERP), geocenter motion, and terrestrial scale. The results indicate that setting range bias parameters for each satellite-station pair can effectively account for the satellite-specific biases induced by LRAs, leading to smaller Root Mean Square Errors (RMSE) of the post-fit SLR residuals. Furthermore, estimating the range biases for each satellite-station pair improves the accuracy of the estimated station coordinates and ERP. We also examine the impact of different arc lengths on the estimates of ERP, geocenter motion, and terrestrial scale. The results show that extending arc length can significantly reduce the formal error of ERP. The 7-day strategy produces the smallest RMSEs of 473 microarcseconds and 495 microarcseconds for the estimated X- and Y-component of pole coordinates, and 52 microseconds for length-of-day, respectively. However, the estimated geocenter motion is less affected by the arc length, even the shortest 1-day arc strategy can capture the seasonal variations of geocenter motion in Zcomponent. For scale estimation, extending the arc length notably improves the accuracy of the estimated station coordinates and scale, but this advantage becomes less noticeable in longer arcs. The 7-day solution also obtains the closet scale results compared to ITRF2014, with the RMSE of 2.10 × 10–9.

Integer Ambiguity Resolution (IAR) can significantly improve the accuracy of GNSS Precise Orbit Determination (POD). Traditionally, the IAR in POD is achieved at the Double Differenced (DD) level. In this contribution, we develop an Un-Differenced (UD) IAR method for Global Positioning System (GPS)+ BeiDou Navigation Satellite System (BDS) + Galileo navigation satellite system (Galileo)+ Global'naya Navigatsionnaya Sputnikovaya Sistema (GLONASS) quad-system POD by calibrating UD ambiguities in the raw carrier phase and generating the so-called carrier range. Based on this method, we generate the UD ambiguity-fixed orbit and clock products for the Wuhan Innovation Application Center (IAC) of the International GNSS Monitoring and Assessment System (iGMAS). One-year observations in 2020 from 150 stations are employed to investigate performance of orbit and clock products. Notably, the UD Ambiguity Resolution (AR) yields more resolved integer ambiguities than the traditional DD AR, scaling up to 9%, attributable to its avoidance of station baseline formation. Benefiting from the removal of ambiguity parameters, the computational efficiency of parameter estimation undergoes a substantial 70% improvement. Compared with the float solution, the orbit consistencies of UD AR solution achieve the accuracy of 1.9, 5.2, 2.8, 2.1, and 2.7 cm for GPS, BeiDou-2 Navigation Satellite System (BDS-2), BeiDou-3 Navigation Satellite System (BDS-3), Galileo, and GLONASS satellites respectively, reflecting enhancements of 40%, 24%, 54%, 34%, and 42%. Moreover, the standard deviations of Satellite Laser Ranging (SLR) residuals are spanning 2.5–3.5 cm, underscoring a comparable accuracy to the DD AR solution, with discrepancies below 5%. A notable advantage of UD AR lies in its capability to produce the Integer Recovered Clock (IRC), facilitating Precise Point Positioning (PPP) AR without requiring additional Uncalibrated Phase Delay (UPD) products. To assess the performance of quad-system kinematic PPP based on IRC, a network comprising 120 stations is utilized. In comparison to the float solution, the IRC-based PPP AR accelerates convergence time by 31% and enhance positioning accuracy in the east component by 54%.

Subgroup identification is crucial in dealing with the heterogeneous population and has wide applications in various areas, such as clinical trials and market segmentation. With the prevalence of multi-source data, there is a practical need to identify subgroups based on multi-source data. This paper proposes a working-independence pseudo-loglikelihood and integrates the parameters of each source into a pairwise fusion penalty for simultaneous parameter estimation and subgroup identification. To implement the proposed method, an alternating direction method of multipliers (ADMM) algorithm is derived. Furthermore, the weak oracle properties of parameter estimation are established, illustrating the latent subgroups can be consistently identified. Finally, numerical simulations and an analysis of a randomized trial on reduced nicotine standards for cigarettes are conducted to evaluate the performance of the proposed method. [ABSTRACT FROM AUTHOR]

During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society1. The recently emerged B.1.617.2/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the spring of 2021 (ref. 2). However, the virological properties of B.1.617.2/Delta remain unclear. Here we show that the B.1.617.2/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2/Delta variant and is associated with enhanced pathogenicity.

A diastereoselective copper and NHC-ligand-catalyzed three-component difunctionalization of allenes with bis(pinacolato)diboron and 2H-azirines to afford borylated allylaziridines is described. The reaction exhibits complete diastereoselectivity and good yields, and the further chlorination of the corresponding borylated products was also performed. It is believed that the high ring-strain force of 2H-azirines facilitates the reaction. More chemical transformations of borylated allylaziridines are also reported.

A multiphase mathematic model based on realizable k-εturbulence model for subsonic flow was presented to investigate the mixing flow behaviors between gas and water in the gas-liquid ejector. The simulation was carried out to predict the pumping performance of the ejector by a commercial computational code ANSYS-FLUENT 15.0. General agreements between the predicted results and experimental data validated the present theoretical model. Using the present approach, the pressure, velocity, and turbulence intensity distribution along center-line and contours of gas and liquid volume fraction profiles were predicted. It is found that the mixing process between gas and water in ejector can be divided into three periods, co-axial flow, mixing shock flow, and bubble flow. The prediction results show that the mixing shock is a dominant position in affecting the mixing flow behavior in gas-liquid ejector and the ejector’s performances.

This article sheds light on an unexpected phenomenon of partial-cycling-induced feigned death in graphite electrodes (coin half cells). The partial cycling within specific voltage windows can trigger rapid but recoverable capacity fading of graphite electrodes. During partial cycling, the extremely rapid capacity fading (up to 80 %) appears in the initial dozens of cycles, and the voltage profile gradually becomes abnormal. Nevertheless, the capacity fading phenomenon can be erased by one full cycling cycle. By combining multiple characterizations (including scanning electron microscope, energy dispersive spectrometer, electrochemical impedance spectroscopy, and X-ray diffraction) with evaluating the influence of the fluoroethylene carbonate additive, it is further confirmed that the partial-cycling-induced feigned death in graphite electrodes is directly related to the composition evolution of solid electrolyte interphase. Meanwhile, a necessary condition for triggering the feigned death is that the lower cut-off voltage is close to the voltage plateaus for LiC18/LiC12transition and LiC12/LiC6transition. Based on these findings, this work provides an in-depth understanding of the cycling performance of graphite electrodes and also presents a challenge for the electrolyte design.

The efficient exploration and extraction of shale gas is essential for China's energy structure as a replacement for natural gas. In this research, shale samples from the Longmaxi Formation in Changning, Sichuan Province were investigated for their pore structure. To achieve this, X-ray diffraction (XRD) and nuclear magnetic resonance (NMR) experiments were performed on the samples. Fractal theory was employed to characterize the pore structure and fractal features of the shale reservoirs. The fractal characteristics of reservoir rocks were correlated with physical parameters and mineral components to identify the controlling factors for the multifractal dimension. The results indicate the following: ① Quartz predominates in the mineral composition of shale in the study area, while clay minerals are the least abundant. ② The primary pore types observed in the samples are bound fluid pores, primarily controlled by mesopores (2nm≤r≤50nm). ③ The calculated multifractal parameters show that the heterogeneous pore structure exhibits multifractal characteristics. ④ The low probability multifractal parameters Dmin-D0and αmax-α0were found to be negatively correlated with reservoir porosity, permeability, and clay mineral content, while the high probability multifractal parameters D0-Dmaxand α0-αminwere found to be positively correlated with them. The comprehensive fractal characterization of reservoir rocks demonstrates the applicability of multifractal dimensions in characterizing the heterogeneity of shale reservoir pore structures, which holds potential promise for coal methane exploration.

Constructing self-supporting electrodes with the combination of excellent flexibility and superior electrochemical properties is essential to the development of high-performance supercapacitors for flexible electronics and wearable devices. Herein, a highly flexible polypyrrole/reduced graphene oxide/modified-polyimide composite fibrous membranes (PPy/RGO/M-PI CFMs) are prepared via electrostatic self-assembly of reduced graphene oxide (RGO) and in-situ deposition of polypyrrole onto SnCl2-modified polyimide electrospun fibrous membranes (M-PI FMs). M-PI FMs ensure rich pore structure and remarkable flexible properties, the electronic conductivity of the sample is greatly promoted by RGO, and polypyrrole (PPy) provide the capability of high redox pseudo capacitive charge storage for the electrode. Benefiting from the compact assembly of RGO and the uniform deposition of polypyrrole on the fiber surface of the M-PI FMs, the synthesized PPy/RGO/M-PI CFMs have a remarkable area capacitance of 1437.1 mF cm−2, a long cycle life of 84.9 % retention over 5000 cycles, and outstanding mechanical stability. And the assembled symmetric supercapacitor with PPy/RGO/M-PI CFMs deliver an exceptional area capacitance of 363.1 mF cm−2, superior energy density of 32.3 μWh cm−2and 77.6 % capacitance retention after 5000 cycles. Therefore, this flexible and free-standing PPy/RGO/M-PI CFMs can be regarded as a promising candidate for flexible supercapacitor electrodes.

An efficient and practical method for the straightforward construction of unsymmetrical selenoureas and cycloselenoureas via the combination of selenium powder, chloroform, and two different amines was comprehensively achieved in one-pot with only the assistance of a base under mild conditions. Thirty-three new structures of unsymmetrical selenoureas including three chiral examples and eight cycloselenoureas were achieved. 1,1-Dimethyl-3-phenylselenourea II,which shows good fungicidal activity, was practically synthesized through this protocol in gram-scale. Isoselenocyanate was further confirmed as a key intermediate by control experiment.

ObjectiveTumour heterogeneity represents a major obstacle to accurate diagnosis and treatment in gastric adenocarcinoma (GA). Here, we report a systematic transcriptional atlas to delineate molecular and cellular heterogeneity in GA using single-cell RNA sequencing (scRNA-seq).DesignWe performed unbiased transcriptome-wide scRNA-seq analysis on 27 677 cells from 9 tumour and 3 non-tumour samples. Analysis results were validated using large-scale histological assays and bulk transcriptomic datasets.ResultsOur integrative analysis of tumour cells identified five cell subgroups with distinct expression profiles. A panel of differentiation-related genes reveals a high diversity of differentiation degrees within and between tumours. Low differentiation degrees can predict poor prognosis in GA. Among them, three subgroups exhibited different differentiation grade which corresponded well to histopathological features of Lauren’s subtypes. Interestingly, the other two subgroups displayed unique transcriptome features. One subgroup expressing chief-cell markers (eg, LIPFand PGC) and RNF43with Wnt/β-catenin signalling pathway activated is consistent with the previously described entity fundic gland-type GA (chief cell-predominant, GA-FG-CCP). We further confirmed the presence of GA-FG-CCP in two public bulk datasets using transcriptomic profiles and histological images. The other subgroup specifically expressed immune-related signature genes (eg, LY6Kand major histocompatibility complex class II) with the infection of Epstein-Barr virus. In addition, we also analysed non-malignant epithelium and provided molecular evidences for potential transition from gastric chief cells into MUC6+TFF2+spasmolytic polypeptide expressing metaplasia.ConclusionAltogether, our study offers valuable resource for deciphering gastric tumour heterogeneity, which will provide assistance for precision diagnosis and prognosis.

When non-cooperative body attachment occurs in space, the inertia of the new combination and the change of the system’s momentum are unknown. This uncertainty may lead to the instability of the spacecraft’s attitude control. In order to solve this problem, we propose an adaptive control scheme based on the inertia estimation of the new, combined system of non-cooperative body and satellite. This method can allow the new combination of different situations to reach a stable state with a high level of precision and speed. In this paper, the stability of the adaptive control scheme is proven by constructing a Lyapunov function. A simulation environment in which a non-cooperative body attaches to a satellite attaches to is constructed. The simulation shows that the attitude error converges to a small field when using the control scheme, regardless of unfavorable cases, including unknown inertia parameters, added momentum. In addition, the simulation results show the strong robustness of the control scheme for the new combination.

Carbohydrate-deficient transferrin (CDT) is a reliable biomarker for chronic alcohol abuse. We developed a method for CDT analysis by capillary isoelectric focusing, followed by immunodetection directly in the capillary, in an automated fashion and on a single platform (Peggy Sue™; ProteinSimple, CA, USA). Transferrin glycoforms in serum samples, including disialo-transferrin, were separated and their apparent isoelectric points and relative percentages were determined. The relative CDT values (percent of total transferrin) matched expected values for both healthy and alcoholic samples. Because the method leveraged the sensitivity of an immunoassay, CDT was measured when serum samples were diluted up to 1200-fold, reducing the volume of serum required. Finally, the process is fully automated, with up to 96 samples analyzed per batch.

Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms “avascular necrosis of the femoral head,” “necrosis of the femoral head,” “steroid-induced necrosis of the femoral head,” “osteonecrosis,” and “avascular necrosis of the bone” were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The “THSWD-drug-active compound-intersection gene-hub gene-AVNFH” network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

The objective of this paper is to investigate the feasibility of one side 3-D scanning (OSS) method for the shape characterization of aggregate particles in 3-D. Seventy two typical crushed stone particles and 77 typical gravel particles were selected for the investigation. Each selected particle was tested 3 times by the OSS method using a handheld 3-D laser scanner with randomly resting it on a flat plane. The size and shape indicators were calculated for each OSS test and the optimized results were also obtained by a proposed optimizing procedure in accordance with the results of th e 3 times of OSS tests. The whole digital particle (WDP) data of each selected particle was acquired at the same time and the WDP based size and shape indicators were calculated as the references of the feasibility investigation. The statistical tests of all sizes and shape indicators between each OSS based result set and WDP based result set were performed. The OSS based length (L) and thickness (T) show good reliability for each test. Not every OSS test can obtain reliable results of width (W). However, the optimized results of all the 3 OSS based size indicators have enough reliability. All the shape indicators derived from the optimized OSS based size indicators also have enough reliability. The OSS method with employing the optimized results based on multiple (3 or more) tests is statistically feasible. And it is a time-saving way which is suitable for extensive testing in engineering application.

Accurately evaluating tumor responses to immunotherapy is clinically relevant. However, non‐invasive, real‐time visualization techniques to evaluate tumor immunotherapy are still lacking. Herein, a smart responsive fluorescence‐MR dual‐modal nanoprobe, QM(GP)‐MZF(CP), is reported that can be targeted for cleavage by the cytotoxic T cell activation marker granzyme B and the apoptosis‐related marker cysteine‐aspartic acid‐specific protease 3 (Caspase‐3). The probe uses quinoline‐malononitrile (QM), an aggregation‐induced emission luminogen, and Mn‐Zn ferrite magnetic nanoparticles (MZF‐MNPs), a T2‐weighted imaging (T2WI) contrast agent, as imaging molecules that are linked with the substrate peptides specific to granzyme B and Caspase‐3. Therefore, both granzyme B and Caspase‐3 can target and cleave the substrate peptides in QM(GP)‐MZF(CP). Via aggregation‐induced fluorescence imaging of QM and the aggregation‐induced T2WI‐enhanced imaging effect of MZF‐MNPs, the status of T cells after tumor immunotherapy and the subsequent triggering of tumor cell apoptosis can be determined to identify tumor responsiveness to immunotherapy and thereby evaluate the effectiveness of this therapy in the early stages of treatment. A smart responsive fluorescence‐MR nanoprobe is developed to monitor the tumor responses to immunotherapy by targeting the two key nodes of cytotoxic T cell activation and triggering tumor cell apoptosis after treatment. The probe can reflect the changes in granzyme B and Caspase‐3 in the tumor after immunotherapy via targeting and cleaving the substrate peptide and enhancing QM and MZF‐MNP aggregation imaging to evaluate the effectiveness of immunotherapy.

Tumor suppressor p53 is inactivated by thousands of heterogeneous mutations in cancer, but their individual druggability remains largely elusive. Here, we evaluated 800 common p53 mutants for their rescue potencies by the representative generic rescue compound arsenic trioxide (ATO) in terms of transactivation activity, cell growth inhibition, and mouse tumor–suppressive activities. The rescue potencies were mainly determined by the solvent accessibility of the mutated residue, a key factor determining whether a mutation is a structural one, and the temperature sensitivity, the ability to reassemble the wild-type DNA binding surface at a low temperature, of the mutant protein. A total of 390 p53 mutants were rescued to varying degrees and thus were termed as type 1, type 2a, and type 2b mutations, depending on the degree to which they were rescued. The 33 type 1 mutations were rescued to amounts comparable to the wild type. In PDX mouse trials, ATO preferentially inhibited growth of tumors harboring type 1 and type 2a mutants. In an ATO clinical trial, we report the first-in-human mutant p53 reactivation in a patient harboring the type 1 V272M mutant. In 47 cell lines derived from 10 cancer types, ATO preferentially and effectively rescued type 1 and type 2a mutants, supporting the broad applicability of ATO in rescuing mutant p53. Our study provides the scientific and clinical communities with a resource of the druggabilities of numerous p53 mutations (www.rescuep53.net) and proposes a conceptual p53-targeting strategy based on individual mutant alleles rather than mutation type.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein mediates membrane fusion between the virus and the target cells, triggering viral entry into the latter. Here, we describe a SARS-CoV-2 spike-protein-mediated membrane fusion assay using a dual functional split reporter protein to quantitatively monitor the fusion kinetics of the viral and target cell membranes in living cells. This approach can be applied in various cell types, potentially predicting the pathogenicity of newly emerging variants.

Over the past years the International Global Navigation Satellite System (GNSS) Monitoring and Assessment System (iGMAS) Wuhan Innovation Application Center (IAC) dedicated to exploring the potential of multi-GNSS signals and providing a set of products and services. This contribution summarizes the strategies, achievements, and innovations of multi-GNSS orbit/clock/bias determination in iGMAS Wuhan IAC. Both the precise products and Real-Time Services (RTS) are evaluated and discussed. The precise orbit and clock products have comparable accuracy with the precise products of the International GNSS Service (IGS) and iGMAS. The multi-frequency code and phase bias products for Global Positioning System (GPS), BeiDou Navigation Satellite System (BDS), Galileo navigation satellite system (Galileo), and GLObal NAvigation Satellite System (GLONASS) are provided to support multi-GNSS and multi-frequency Precise Point Positioning (PPP) Ambiguity Resolution (AR). Compared with dual-frequency PPP AR, the time to first fix of triple-frequency solution is improved by 30%. For RTS, the proposed orbit prediction strategy improves the three dimensional accuracy of predicted orbit by 1 cm. The multi-thread strategy and high-performance matrix library are employed to accelerate the real-time orbit and clock determination. The results with respect to the IGS precise products show the high accuracy of RTS orbits and clocks, 4–9 cm and 0.1–0.2 ns, respectively. Using real-time satellite corrections, real-time PPP solutions achieve satisfactory performance with horizontal and vertical positioning errors within 2 and 4 cm, respectively, and convergence time of 16.97 min.