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Abstract The vacancy effect in quantum spin liquid (QSL) has been extensively studied. A finite density of random vacancies in the Kitaev model can lead to a pileup of low-energy density of states (DOS), which is generally experimentally determined by a scaling behavior of thermodynamic or magnetization quantities. Here, we report detailed muon spin relaxation (μSR) results of H3LiIr2O6, a Kitaev QSL candidate with vacancies. The absence of magnetic order is confirmed down to 80 mK, and the spin fluctuations are found to be persistent at low temperatures. Intriguingly, the time-field scaling law of longitudinal-field (LF)-μSR polarization is observed down to 0.1 K. This indicates a dynamical scaling, whose critical exponent of 0.46 is excellently consistent with the scaling behavior of specific heat and magnetization data. All the observations point to the finite DOS with the form $$N(E)\sim {E}^{-\nu }$$ N ( E ) ∼ E − ν , which is expected for the Kitaev QSL in the presence of vacancies. Our μSR study provides a dynamical fingerprint of the power-law low-energy DOS and introduces a crucial new insight into the vacancy effect in QSL.

Abstract A comprehensive digital transformation has been undergone by the oil and gas industry, wherein digital twins are leveraged to enable real-time data analysis, providing predictive and diagnostic engineering insights. The potential for developing intelligent oil and gas fields is substantial with the implementation of digital twins. A digital twin framework for gear rack drilling rigs is proposed, built upon an understanding of the digital twin composition and characteristics of the gear rack drilling rig lifting system. The framework encompasses descriptions of digital twin characteristics specific to drilling rigs, the application environment, and behavioral rules. The modeling approach integrates mechanism modeling, real-time performance response, instantaneous data transmission, and data visualization. To illustrate this framework, exemplary case studies involving the transmission unit and support unit of the lifting system are presented. Mechanism models are constructed to analyze dynamic gear performance and support unit response. Real-time data transmission is facilitated through sensor-based monitoring, enhancing the prediction speed and accuracy of dynamic performance through a synergy of mechanism modeling, machine learning, and real-time data analysis. The digital twin of the lifting system is visualized utilizing the Unity3D platform. Furthermore, functionalities on data acquisition, processing, and visualization across diverse application scenarios are encapsulated into modular components, streamlining the creation of high-fidelity digital twins. The frameworks and modeling methodologies presented herein can serve as a foundational and methodological guide for the exploration and implementation of digital twin technology within the oil and gas industry, ultimately fostering its advancement in this sector.

With the continuous advancement in socioeconomic development and transportation infrastructure, the daily traffic volume on highways has been steadily increasing, resulting in the growing frequency of traffic congestion incidents. Thus, the accurate prediction of highway traffic flow is of great significance for implementing traffic congestion warnings, guiding traffic diversion, and developing the concept of intelligent highways. Traffic flow exhibits intricate spatial and temporal dependencies: in the spatial dimension, the relationships between various traffic nodes are not fixed, changing dynamically over time; in the temporal dimension, multiple temporal patterns of traffic flow sequences are entangled with each other. In addition, an efficient method for fusing spatiotemporal relationships is lacking, making the accurate prediction of traffic flow a challenging endeavor. In this regard, a methodology for forecasting highway traffic flow is proposed based on dynamic graph convolutional networks and spatiotemporal feature extraction modules. Given the challenge posed by the static nature of predefined graph structures in capturing dynamic spatial relationships among traffic nodes, a dynamic graph adjustment module is introduced. Initially, the spatial features of each traffic node are extracted. Subsequently, utilizing these extracted spatial features, spatial similarity scores between traffic nodes are computed. Based on these scores, a traffic network graph structure is adapted: connections between nodes with high similarity scores, previously unlinked, are established with a certain probability, while connections between nodes with low similarity scores, previously linked, are severed with a certain probability. Furthermore, by employing the spatiotemporal feature extraction module and leveraging the updated graph structure, spatial relationships are extracted through graph convolution. This is complemented by integrating a patch concept from temporal processing methodologies. Herein, a one-dimensional traffic flow sequence is decomposed and transformed into two-dimensional data. Through convolutional operations, temporal features within and between periods are simultaneously extracted before reverting the data back to its original dimensionality. This comprehensive approach enables the modeling of spatiotemporal dependencies within the traffic flow data. To validate the effectiveness of the proposed model, experiments were conducted on four highway traffic datasets, contrasting its performance with baseline models. The proposed model achieved the mean absolute error (MAE) values of 15.6, 19.7, 16.8, and 5.21 on the PeMS03, PeMS04, PeMS08, and Fuzhou Jingtai highway datasets, respectively. These results show that the proposed method reaches an advanced level in traffic flow forecasting. Lastly, to assess the efficacy of individual model components, ablative experiments were conducted, and their results were compared. These experiments validate the effectiveness of each component, thereby affirming the efficacy of the proposed model in highway traffic flow forecasting.

Highlights Developed more efficient boron activation strategies, while establishing various low-melting growth systems. The preparation temperature of boron nitride nanotubes has been reduced to 850 °C.

Abstract Converting solar energy into fuels is pursued as an attractive route to reduce dependence on fossil fuel. In this context, photothermal catalysis is a very promising approach through converting photons into heat to drive catalytic reactions. There are mainly three key factors that govern the photothermal catalysis performance: maximized solar absorption, minimized thermal emission and excellent catalytic property of catalyst. However, the previous research has focused on improving solar absorption and catalytic performance of catalyst, largely neglected the optimization of thermal emission. Here, we demonstrate an optically selective catalyst based Ti3C2Tx Janus design, that enables minimized thermal emission, maximized solar absorption and good catalytic activity simultaneously, thereby achieving excellent photothermal catalytic performance. When applied to Sabatier reaction and reverse water-gas shift (RWGS) as demonstrations, we obtain an approximately 300% increase in catalytic yield through reducing the thermal emission of catalyst by ~70% under the same irradiation intensity. It is worth noting that the CO2 methanation yield reaches 3317.2 mmol gRu −1 h−1 at light power of 2 W cm−2, setting a performance record among catalysts without active supports. We expect that this design opens up a new pathway for the development of high-performance photothermal catalysts.

Objectives: Silicon carbide ceramics, as a typical hard and brittle material, are difficult to process, with challenges such as low efficiency, significant tool wear, and poor surface quality during processing. Ultrafast laser processing can effectively inhibit the processing damage, which is an important method for the precision processing of silicon carbide ceramics. However, existing research on femtosecond laser processing of silicon carbide primarily focuses on the laser ablation characteristics of the material. The specific removal process of the material, in relation to the composition distribution and laser ablation mechanism, is still lacking in the relevant research. This paper analyzes the microstructure of the surface of silicon carbide ceramics processed by femtosecond laser pulses and its evolution law. It reveals the material removal process by examining the changes in chemical components in the ablation area, further improving the femtosecond laser processing mechanism of silicon carbide ceramics from the perspective of changes in material's physicochemical properties. Methods: Under the premise of a fixed laser repetition frequency, the silicon carbide ceramics were processed by varying the laser energy density and the number of pulses. The changes in the physical and chemical properties of silicon carbide were observed and analyzed. A field emission scanning electron microscope was used to observe the microscopic morphology of the processed surface, while a matching energy spectrum analyzer was used to analyze the composition of the processed area. Additionally, X-ray photoelectron spectroscopy was employed to detect the chemical components of the surface before and after processing. A field emission transmission electron microscope was used to detect the cross-sectional morphology of the microstructure. An OLS4100 confocal laser microscope was used to scan the three-dimensional morphology of the micropores formed by the pulsed processing, measuring the diameter and depth of the micropores. The diameter and depth of the micropores were measured. Results: It was found that when femtosecond laser processing silicon carbide ceramics with a single pulse at low energy density, the surface of the processed ceramic was slightly ablated, forming a melting characteristic zone. At high energy density, localized high temperatures were generated in the central processed area, reaching the boiling point of the material, leading to the boiling of the material and the formation of a boiling characteristic zone. Simultaneously, due to the relatively lower energy in the edge area, the material melted, forming a melting characteristic zone. The surface morphology of the boiling region mainly consisted of gasification pits and micro-projectile structures formed by gasification, while the morphology of the melting region was not obvious, with the local appearance of unclear contours of a periodic stripe structure. Using the radius of the feature area and the Gaussian laser intensity function, the evaporation and melting thresholds for the formation of the boiling and melting zones were calculated to be 3.779 J/cm2 and 0.860 J/cm2, respectively. Under the influence of multi-pulse laser processing, the morphology of the processed area was primarily striped when the laser energy was between the melting and evaporation thresholds, with coarse stripe structures in the central area and fine stripe structures in the edge area. The center region produced coarse streaks, and fine streaks were produced in the edge region. When the laser energy exceeded the evaporation threshold, the central region's structural appeared as a hole structure formed by vaporization, followed by the formation of concentric coarse and fine stripe structures extending to the edge region. As the laser energy density and the number of pulses increased, the micropore diameter and ablation depth exhibited an increasing trend, with the micropore diameter leveling off after an energy density of 9.46 J/cm2 and 50 pulses. Phase explosion performed a shielding effect on oxygen and material oxidation reactions; due to the decreasing distribution of laser energy and temperature from the center to the edge of the laser beam, the extent of the phase explosion decreased. In the central region, oxygen in the air did not center the material, while in the middle to the edge regions, exposure to oxygen increased, resulting in an increasing trend in oxygen content from the center to the edge. Meanwhile, through transmission and compositional analysis, it was found that the material subjected to laser action produced a metamorphic layer in the depth direction, showing a distribution pattern of an oxide layer-C-rich layer-silicon carbide matrix. Conclusions: This article investigates the ablation mechanism of silicon carbide ceramics processed by femtosecond laser. In terms of the removal process, laser removal of silicon carbide ceramics is a process in which photothermal and photochemical effects act sequentially. The laser beam irradiates the surface of the material, and the absorbed energy causes an internal temperature rise, accelerating atomic movement. As the energy continues to increase, it leads to a plasma phase explosion of the material, which jets outward, allowing oxygen from the air to react chemically within the material, completing the removal process. In terms of pulse processing, two characteristic regions, boiling and melting, are formed in the ablation region under the action of a Gaussian beam when processing with a single pulse. The evaporation threshold and the melting threshold of the characteristic region are 3.779 J /cm2 and 0.860 J/cm2, respectively. During multi-pulse processing, when the laser energy is between the melting and the boiling thresholds, the generation of structural defects in the hole structure can be avoided. The temperature of the ablation region decreases from the center of the laser beam to the edge region. In the high-temperature area, the material removal mechanism is primarily direct evaporation of the matrix, while in the low-temperature region, it is the thermal decomposition of the material and the oxidation reaction. This results in the formation of microstructures in the ablation region that are consistent from the center to the edge during multi-pulse processing.

Abstract Epitaxial growth of two-dimensional (2D) materials with uniform orientation has been previously realized by introducing a small binding energy difference between the two locally most stable orientations. However, this small energy difference can be easily disturbed by uncontrollable dynamics during the growth process, limiting its practical applications. Herein, we propose a quasi-equilibrium growth (QEG) strategy to synthesize inch-scale monolayer α-In2Se3 single crystals, a semiconductor with ferroelectric properties, on fluor-phlogopite substrates. The QEG facilitates the discrimination of small differences in binding energy between the two locally most stable orientations, realizing robust single-orientation epitaxy within a broad growth window. Thus, single-crystal α-In2Se3 film can be epitaxially grown on fluor-phlogopite, the cleavage surface atomic layer of which has the same 3-fold rotational symmetry with α-In2Se3. The resulting crystalline quality enables high electron mobility up to 117.2 cm2 V−1 s−1 in α-In2Se3 ferroelectric field-effect transistors, exhibiting reliable nonvolatile memory performance with long retention time and robust cycling endurance. In brief, the developed QEG method provides a route for preparing larger-area single-crystal 2D materials and a promising opportunity for applications of 2D ferroelectric devices and nanoelectronics.

Abstract Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Abstract Phosphorus pentamers (cyclo-P5) are unstable in nature but can be synthesized at the Ag(111) surface. Unlike monolayer black phosphorous, little is known about their electronic properties when in contact with metal electrodes, although this is crucial for future applications. Here, we characterize the atomic structure of cyclo-P5 assembled on Ag(111) using atomic force microscopy with functionalized tips and density functional theory. Combining force and tunneling spectroscopy, we find that a strong charge transfer induces an inward dipole moment at the cyclo-P5/Ag interface as well as the formation of an interface state. We probe the image potential states by field-effect resonant tunneling and quantify the increase of the local change of work function of 0.46 eV at the cyclo-P5 assembly. Our experimental approach suggest that the cyclo-P5/Ag interface has the characteristic ingredients of a p-type semiconductor-metal Schottky junction with potential applications in field-effect transistors, diodes, or solar cells.

Abstract Atomic sawtooth surfaces have emerged as a versatile platform for growth of single-crystal van der Waals layered materials. However, the mechanism governing the formation of single-crystal atomic sawtooth metal (copper or gold) films on hard substrates (tungsten or molybdenum) remains a puzzle. In this study, we aim to elucidate the formation mechanism of atomic sawtooth metal films during melting–solidification process. Utilizing molecular dynamics, we unveil that the solidification of the liquid copper initiates at a high-index tungsten facet with higher interfacial energy. Subsequent tungsten facets follow energetically favourable pathways of forming single-crystal atomic sawtooth copper film during the solidification process near melting temperature. Formation of atomic sawtooth copper film is guaranteed with a film thickness exceeding the grain size of polycrystalline tungsten substrate. We further demonstrate the successful growth of centimeter-scale single-crystal monolayer hexagonal boron nitride films on atomic sawtooth copper films and explore their potential as efficient oxygen barrier.

Abstract Background Triple-negative breast cancer (TNBC) is a recurrent, heterogeneous, and invasive form of breast cancer. The treatment of TNBC patients with paclitaxel and fluorouracil in a sequential manner has shown promising outcomes. However, it is challenging to deliver these chemotherapeutic agents sequentially to TNBC tumors. We aim to explore a precision therapy strategy for TNBC through the sequential delivery of paclitaxel and fluorouracil. Methods We developed a dual chemo-loaded aptamer with redox-sensitive caged paclitaxel for rapid release and non-cleavable caged fluorouracil for slow release. The binding affinity to the target protein was validated using Enzyme-linked oligonucleotide assays and Surface plasmon resonance assays. The targeting and internalization abilities into tumors were confirmed using Flow cytometry assays and Confocal microscopy assays. The inhibitory effects on TNBC progression were evaluated by pharmacological studies in vitro and in vivo. Results Various redox-responsive aptamer-paclitaxel conjugates were synthesized. Among them, AS1411-paclitaxel conjugate with a thioether linker (ASP) exhibited high anti-proliferation ability against TNBC cells, and its targeting ability was further improved through fluorouracil modification. The fluorouracil modified AS1411-paclitaxel conjugate with a thioether linker (FASP) exhibited effective targeting of TNBC cells and significantly improved the inhibitory effects on TNBC progression in vitro and in vivo. Conclusions This study successfully developed fluorouracil-modified AS1411-paclitaxel conjugates with a thioether linker for targeted combination chemotherapy in TNBC. These conjugates demonstrated efficient recognition of TNBC cells, enabling targeted delivery and controlled release of paclitaxel and fluorouracil. This approach resulted in synergistic antitumor effects and reduced toxicity in vivo. However, challenges related to stability, immunogenicity, and scalability need to be further investigated for future translational applications.

Abstract Background Zinc finger SWIM-type containing 4 (ZSWIM4) is a zinc finger protein with its function largely uncharacterized. In this study, we aimed to investigate the role of ZSWIM4 in gastrointestinal stromal tumors (GISTs). Results We found that ZSWIM4 expression is inhibited by the predominantly mutated protein KIT in GISTs, while conversely, ZSWIM4 inhibits KIT expression and downstream signaling. Consistent with the observation, ZSWIM4 inhibited GIST cell survival and proliferation in vitro. RNA sequencing of GISTs from KITV558A/WT mice and KITV558A/WT/ZSWIM4−/− mice showed that loss of ZSWIM4 expression increases the expression of circadian clock pathway member BMAL1 which contributes to GIST cell survival and proliferation. In addition, we found that KIT signaling increases the distribution of ZSWIM4 in the nucleus of GIST cells, and which is important for its inhibition of KIT and BMAL1. In agreement with the results in vitro, the in vivo studies showed that ZSWIM4 deficiency increases the tumorigenesis of GISTs in KITV558A/WT mice. Conclusions Taken together, our results revealed that the entry of ZSWIM4 to the nucleus is important for its inhibition of KIT and BMAL1, ultimately attenuating GIST tumorigenesis. The results provide a novel insight in the understanding of signal transduction in GISTs and lay strong theoretical basis for the advancement of GIST treatment.

Abstract Through applying a 4‐MHz linear frequency modulation waveform, which has high range resolution and signal intensity, we successfully detected for the first time the ionospheric 150‐km echo enhancement at 430–450 MHz of the Ultra‐High‐Frequency (UHF) band using the newly built Sanya Incoherent Scatter Radar (SYISR). The obtained low signal enhancement (less than 0.5 dB) explains why previous UHF experiments did not detect them. We also found that our measured fine structure shows a much wider forbidden region than previous results and covers a much larger altitudinal and local time region. In comparison with recent upper‐hybrid instability theory and simulation, our results confirmed the predicted higher altitude occurrence, wider gaps between enhancements, the turn corner feature around sunrise, and perhaps the weak enhancement, which provide an independent evaluation of the newly proposed mechanism in UHF band. Future UHF experiments could further improve the physical understanding of 150‐km echo phenomenon.

ObjectiveTo explore the association between representative insulin resistance (IR) indices and the risk of kidney stone disease in an American adult population. The representative IR indices referred to metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride glucose-body mass index (TyG-BMI), visceral adiposity index (VAI), and homeostatic model assessment of IR (HOMA-IR).MethodsWe investigated adult participants who joined the 2015–2018 National Health and Nutrition Examination Survey (NHANES) and reported kidney stone histories. Weighted proportions, multivariable regression analysis, and restricted cubic splines were used to evaluate the associations between IR indices and kidney stones after their adjustment for gender, age, race, education, smoking status, alcohol drinking frequency, hypertension and diabetes status, physical activity level, water intake, and levels of calcium, cholesterol, and uric acid.ResultsA total of 19,225 participants were included. The weighted prevalence of kidney stone was 11.1%. A multivariable logistic regression model showed a dose–response relationship between the METS-IR and kidney stone [odds ratio (OR) = 1.02, 95% confidence interval (CI) (1.01, 1.04), p

An in-depth understanding of material cutting deformation forms the foundation for manufacturing Zirconium-based bulk metallic glass (Zr-based BMG) parts. This study explores the transition in chip segmentation mode from shear slip to shear fracture in Zr-based BMG during mechanical machining. The investigation covers chip micromorphology, cyclic cutting force, machined surface quality, and the themo-mechanical properties under various chip segmentation modes linked to cutting conditions. A size-dependent transition in chip segmentation has been observed in the cutting of Zr-based BMG. At a specific cutting speed, a smaller uncut chip thickness favors chip formation via shear slip, resulting in a smooth primary shear zone (PSZ). Conversely, a larger uncut chip thickness leads to chip shear fracture, with the PSZ displaying fishbone-like and dimple patterns. The integration of the modified cutting kinematic model with the free volume-dependent shear transformation zone (STZ) model suggests that the transition from shear slip to fracture is due to an increase in uncut chip thickness, which causes a greater STZ volume in the PSZ. When the STZ volume surpasses a threshold, the intrinsic structural recovery of material from shearing cannot fully compensate for the free volume softening, leading to excessive free volume that ultimately triggers shear fracture. During the chip shear fracture process, the evolution from fishbone-like patterns to dimples in the PSZ is attributed to faster crack propagation at greater uncut chip thickness or higher cutting speeds. In practical applications, it is advisable to avoid chip shear fracture during machining to maintain high-quality machined surface quality.

Abstract Carbon nanotubes (CNTs), hollow cylinders of carbon, hold great promise for advanced technologies, provided their structure remains uniform throughout their length. Their growth takes place at high temperatures across a tube-catalyst interface. Structural defects formed during growth alter CNT properties. These defects are believed to form and heal at the tube-catalyst interface but an understanding of these mechanisms at the atomic-level is lacking. Here we present DeepCNT-22, a machine learning force field (MLFF) to drive molecular dynamics simulations through which we unveil the mechanisms of CNT formation, from nucleation to growth including defect formation and healing. We find the tube-catalyst interface to be highly dynamic, with large fluctuations in the chiral structure of the CNT-edge. This does not support continuous spiral growth as a general mechanism, instead, at these growth conditions, the growing tube edge exhibits significant configurational entropy. We demonstrate that defects form stochastically at the tube-catalyst interface, but under low growth rates and high temperatures, these heal before becoming incorporated in the tube wall, allowing CNTs to grow defect-free to seemingly unlimited lengths. These insights, not readily available through experiments, demonstrate the remarkable power of MLFF-driven simulations and fill long-standing gaps in our understanding of CNT growth mechanisms.

Abstract Compared to transition metal dichalcogenide (TMD) monolayers, rhombohedral-stacked (R-stacked) TMD bilayers exhibit remarkable electrical performance, enhanced nonlinear optical response, giant piezo-photovoltaic effect and intrinsic interfacial ferroelectricity. However, from a thermodynamics perspective, the formation energies of R-stacked and hexagonal-stacked (H-stacked) TMD bilayers are nearly identical, leading to mixed stacking of both H- and R-stacked bilayers in epitaxial films. Here, we report the remote epitaxy of centimetre-scale single-crystal R-stacked WS2 bilayer films on sapphire substrates. The bilayer growth is realized by a high flux feeding of the tungsten source at high temperature on substrates. The R-stacked configuration is achieved by the symmetry breaking in a-plane sapphire, where the influence of atomic steps passes through the lower TMD layer and controls the R-stacking of the upper layer. The as-grown R-stacked bilayers show up-to-30-fold enhancements in carrier mobility (34 cm2V−1s−1), nearly doubled circular helicity (61%) and interfacial ferroelectricity, in contrast to monolayer films. Our work reveals a growth mechanism to obtain stacking-controlled bilayer TMD single crystals, and promotes large-scale applications of R-stacked TMD.

Abstract Modifications of complexes by attachment of anchor groups are widely used to control molecule-surface interactions. This is of importance for the fabrication of (catalytically active) hybrid systems, viz. of surface immobilized molecular catalysts. In this study, the complex fac-Re(S-Sbpy)(CO)3Cl (S-Sbpy = 3,3′-disulfide-2,2′-bipyridine), a sulfurated derivative of the prominent Re(bpy)(CO)3Cl class of CO2 reduction catalysts, was deposited onto the clean Ag(001) surface at room temperature. The complex is thermostable upon sublimation as supported by infrared absorption and nuclear magnetic resonance spectroscopy. Its anchoring process has been analyzed using scanning tunneling microscopy (STM) and density functional theory (DFT) calculations. The growth behavior was directly contrasted to the one of the parent complex fac-Re(bpy)(CO)3Cl (bpy = 2,2′-bipyridine). The sulfurated complex nucleates as single molecule at different surface sites and at molecule clusters. In contrast, for the parent complex nucleation only occurs in clusters of several molecules at specifically oriented surface steps. While this shows that surface immobilization of the sulfurated complex is more efficient as compared to the parent, symmetry analysis of the STM topographic data supported by DFT calculations indicates that more than 90% of the complexes adsorb in a geometric configuration very similar to the one of the parent complex.

Abstract Cholesteryl ester transfer protein (CETP) is a promising therapeutic target for cardiovascular diseases. It effectively lowers the low-density lipoprotein cholesterol levels and increases the high-density lipoprotein cholesterol levels in the human plasma. This study identified novel and highly potent CETP inhibitors using virtual screening techniques. Molecular docking and molecular dynamics (MD) simulations revealed the binding patterns of these inhibitors, with the top 50 compounds selected according to their predicted binding affinity. Protein–ligand interaction analyses were performed, leading to the selection of 26 compounds for further evaluation. A CETP inhibition assay confirmed the inhibitory activities of the selected compounds. The results of the MD simulations revealed the structural stability of the protein–ligand complexes, with the binding site remaining significantly unchanged, indicating that the five compounds (AK-968/40709303, AG-690/11820117, AO-081/41378586, AK-968/12713193, and AN-465/14952302) identified have the potential as active CETP inhibitors and are promising leads for drug development. Graphical Abstract

Abstract Vertical semiconducting fins integrated with high-κ oxide dielectrics have been at the centre of the key device architecture that has promoted advanced transistor scaling during the last decades. Single-fin channels based on two-dimensional (2D) semiconductors are expected to offer unique advantages in achieving sub-1 nm fin-width and atomically flat interfaces, resulting in superior performance and potentially high-density integration. However, multi-fin structures integrated with high-κ dielectrics are commonly required to achieve higher electrical performance and integration density. Here we report a ledge-guided epitaxy strategy for growing high-density, mono-oriented 2D Bi2O2Se fin arrays that can be used to fabricate integrated 2D multi-fin field-effect transistors. Aligned substrate steps enabled precise control of both nucleation sites and orientation of 2D fin arrays. Multi-channel 2D fin field-effect transistors based on epitaxially integrated 2D Bi2O2Se/Bi2SeO5 fin-oxide heterostructures were fabricated, exhibiting an on/off current ratio greater than 106, high on-state current, low off-state current, and high durability. 2D multi-fin channel arrays integrated with high-κ oxide dielectrics offer a strategy to improve the device performance and integration density in ultrascaled 2D electronics.

Abstract Interactions between monatomic ions and water molecules are fundamental to understanding the hydration of complex polyatomic ions and ionic process. Among the simplest and well-established ion-related reactions is dissolution of salt in water, which is an endothermic process requiring an increase in entropy. Extensive efforts have been made to date; however, most studies at single-ion level have been limited to theoretical approaches. Here, we demonstrate the salt dissolution process by manipulating a single water molecule at an under-coordinated site of a sodium chloride film. Manipulation of molecule in a controlled manner enables us to understand ion–water interaction as well as dynamics of water molecules at NaCl interfaces, which are responsible for the selective dissolution of anions. The water dipole polarizes the anion in the NaCl ionic crystal, resulting in strong anion–water interaction and weakening of the ionic bonds. Our results provide insights into a simple but important elementary step of the single-ion chemistry, which may be useful in ion-related sciences and technologies.

Acyl-CoA: cholesterol acyltransferase (ACAT), a pivotal enzyme in the absorption and metabolism of cholesterol, is primarily responsible for intracellular esterification. ACAT inhibition is expected to diminish plasma lipid levels by impeding intestinal cholesterol absorption, thereby preventing the progression of atherosclerotic lesions. A previous study shows that selective inhibition of ACAT2 significantly mitigated hypercholesterolaemia and atherosclerosis in mouse models. Therefore, the need for ACAT2 selective inhibitors becomes particularly urgent. In this study, we established a multilayer virtual screening workflow and subjected biologically evaluated representative compounds to enzyme inhibitory assays. The experimental results indicated that the two compounds, STL565001 (inhibition rate at 25 μM: 75.7 ± 27.8%, selectivity = 6) and STL528213 (inhibition rate at 25 μM: 87.8 ± 12.4%, selectivity = 13), demonstrated robust activity against ACAT2, displaying greater selectivity for ACAT2 than for ACAT1. The molecular mechanisms governing the inhibitory activities of the selected compounds were systematically elucidated using computational approaches. In addition, hotspot residues in ACAT2 that are crucial for ligand binding were successfully identified. In summary, we devised a multilayer screening scheme to expeditiously and efficiently identify compounds with enzyme inhibitory activity, offering novel scaffolds for subsequent drug design centred on ACAT2 targets.

In an attempt to drive tourist interest, Taiwan implemented a series of changes in 2016 seeking to attract new and repeat visitors. Using a sample of 2339 international tourists visiting Taiwan from 2017 to 2020, we aimed to analyze the attractiveness factors of Southeast Asian tourists to Taiwan and their impact on tourism consumption demand. Employing the Almost Ideal Demand System model by Deaton and Muellbauer (1980), our findings indicate that specialty food, natural scenery, and shopping are the main attractive factors for Southeast Asian tourists to Taiwan. This study’s theoretical contribution is significant, as it demonstrates the direct or indirect influence of tourist attractiveness factors on the pattern of tourism consumption expenditure. Moreover, the findings have practical implications, suggesting considerable variation in Southeast Asian tourists’ tourism consumption demands and price elasticity across different countries.

Introduction Regional citrate anticoagulation is a preferred option for renal replacement therapy in critically ill patients. However, current implementations ignore individual differences that may exist in the fluctuation of patients’ ionized calcium levels. To address this problem, individualized citrate and calcium supplementation models were established based on the pharmacokinetic and clearance characteristics of citrate, and an automated regional citrate anticoagulation system was built with these models as its core to facilitate the treatment of clinical patients. This study was designed to preliminarily evaluate the safety and efficacy of this system, the SuperbMed® RCA-SP100 automated regional citrate anticoagulation system, in prolonged intermittent renal replacement therapy.Methods Seven patients undergoing prolonged intermittent renal replacement therapy completed treatment with the SuperbMed® RCA-SP100 system. In vivo and in vitro ionized calcium levels were measured every hour before and after the start of dialysis. The accuracy and alarm sensitivity of the pumps were also monitored.Results During seven treatments, the average extracorporeal ionized calcium level was 0.34 ± 0.02 mmol/L, and the mean ionized calcium level in vivo was 1.09 ± 0.07 mmol/L. No patient required intervention, and there was no filter coagulation. The pumps all had an absolute accuracy less than 5%, and alarms could be triggered precisely.Conclusions We reported on an automated system that allows for individualized citrate and calcium supplementation in prolonged intermittent renal replacement therapy and enables the precise and secure implementation of regional citrate anticoagulation.

Abstract Tissue‐engineered extraction products, such as apoptotic extracellular vesicles (ApoEVs), significantly promote tissue regeneration, endowing them with the potential to improve osseointegration. However, there is an urgent need to determine how to effectively load these materials onto a material surface to maximize their function. Considering that all such products have a phospholipid bilayer, a phospholipid‐modified implant coating is designed that can effectively load tissue‐engineered products with a phospholipid bilayer structure. ApoEVs are effectively loaded onto the surface and the osteogenic effect improved, achieving good osseointegration. In vitro experiments show that this material improves angiogenesis by promoting macrophage M1 polarization and NO secretion in the early stages. In vivo experiments show that after implantation, it effectively improve the peri‐implant vascularization of the implant, thereby improving the new bone formation ability and osseointegration. This study provides a universal solution for loading vesicular tissue‐engineered products onto an implant surface and validates its ability to improve bone fusion using ApoEVs as an example while exploring its mechanism.

Abstract Radiation enteritis is the most common complication of pelvic radiotherapy, but there is no effective prevention or treatment drug. Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell‐derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2′3′ cyclic GMP‐AMP (cGAMP) and activates cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS‐STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.

Abstract Background Human immunodeficiency virus (HIV) infection is an important risk factor for Coronavirus Disease 2019 (COVID‐19), but data on the prevalence of COVID‐19 among people living with HIV (PLWH) is limited in low‐income countries. Our aim was to assess the seroprevalence of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) specific antibodies and associated factors among PLWH in Sierra Leone. Methods We conducted a cross‐sectional survey of PLWH aged 18 years or older in Sierra Leone between August 2022 and January 2023. Participants were tested for SARS‐CoV‐2 antibodies using a rapid SARS‐CoV‐2 antibody (immunoglobulin M/immunoglobulin G [IgG]) kits. Stepwise logistic regression was used to explore factors associated with SARS‐CoV‐2 antibody seroprevalence with a significance level of p

Abstract Understanding the environmental health and safety of nanomaterials (NanoEHS) is essential for the sustained development of nanotechnology. Although extensive research over the past two decades has elucidated the phenomena, mechanisms, and implications of nanomaterials in cellular and organismal models, the active remediation of the adverse biological and environmental effects of nanomaterials remains largely unexplored. Inspired by recent developments in functional amyloids for biomedical and environmental engineering, this work shows their new utility as metallothionein mimics in the strategically important area of NanoEHS. Specifically, metal ions released from CuO and ZnO nanoparticles are sequestered through cysteine coordination and electrostatic interactions with beta‐lactoglobulin (bLg) amyloid, as revealed by inductively coupled plasma mass spectrometry and molecular dynamics simulations. The toxicity of the metal oxide nanoparticles is subsequently mitigated by functional amyloids, as validated by cell viability and apoptosis assays in vitro and murine survival and biomarker assays in vivo. As bLg amyloid fibrils can be readily produced from whey in large quantities at a low cost, the study offers a crucial strategy for remediating the biological and environmental footprints of transition metal oxide nanomaterials.

As a new seawater standard, the International Thermodynamic Equation of Seawater-2010 (TEOS-10) has made it possible to accurately calculate salinity changes caused by small changes in the relative proportions of inorganic dissolved constituents in the open ocean and thus to accurately calculate the thermodynamic properties of seawater. However, offshore and semi-enclosed seas are subject to the dual influence of geo-biochemical processes and terrestrial inputs, and the spatial and temporal variations in the relative composition of their seawater are more complex, resulting in very few studies of salinity change due to changes in the relative composition in these regions, and the applicability of the TEOS-10 in these seas needs to be further evaluated. The Bohai Sea is a typical semi-enclosed sea that has accumulated a large amount of physical oceanography and marine chemistry measurements, making it an ideal area to study the effects of changes in the relative composition of seawater on salinity. Based on repeated measurements of Section B in the Bohai Sea from 1985 to 2020, complemented by quasi-synchronous large-scale measurements of the Bohai Sea from 2006 to 2007, this study found that [HCO3−] and [Ca2+] ions anomalies dominate the relative composition anomalies of dissolved substances in this sea relative to the Standard Sea Water (SSW). These additional components could increase the absolute salinity SA by up to 0.1 g·kg-1 and the practical salinity SP by 0~0.04 according to the TEOS-10 algorithm and the mathematical model Pa08. Based on the specific environmental characteristics of the Bohai Sea, the sources, spatial and temporal variations, and influencing factors of the relative compositional anomalies are analyzed, and the empirical formulas of the absolute salinity anomaly δSA and practical salinity anomaly δSP for the Bohai Sea are further fitted, with the uncertainty of 0.007~0.021 g·kg-1 for δSA and 0.003~0.008 for δSP. The above results can not only improve the accuracy of the thermodynamic properties of the Bohai Seawater, but also provide the compatibility level of the long-term salinity changes in the Bohai Sea and its adjacent waters.

The proof in zk-SNARK has a fixed length and can be verified quickly, promoting the application of zero-knowledge proof in areas such as digital signature, blockchain, distributed storage, and outsourced computing. However, the generation of proofs is time-consuming and frequently used. As a result, NTT (number theoretic transform), one of the most time-consuming parts in proof-generation, needs to be accelerated significantly. However, the existing general NTT hardware acceleration methods cannot meet the requirements of large-bitwidth and large-scale in zk-SNARK. To address this issue, this paper proposes a highly pipelined architecture for NTT. First of all, large-bitwidth modular arithmetic is optimized and low-latency Montgomery modular multiplication hardware unit is designed. And then, the large-scale NTT tasks are divided into smaller sub-tasks through two-dimensional partitioning, which improves the parallelism of NTT computation and eliminates the data dependence among sub-tasks, thus reali-zing the pipeline among sub-tasks. Finally, the “data reordering” technique is introduced among multiple rounds of butterfly operations in a sub-task, which effectively alleviates the memory access requirements, thus realizing the bottom-level pipeline in each sub-task, among butterfly operations with different step sizes. This architecture can be flexibly scaled to different scales of FPGAs. The accelerator is prototyped on the AMD-Xilinx Alveo U50 card (UltraScale+XCU50 FPGA). To balance computing efficiency and flexibility, the OpenCL equipped with high-level synthesis (HLS) is used to implement the system. The evaluation results show that the NTT module performs 1.95 times faster than the one in PipeZK and the accelerator achieves 27.98 and 1.74 times speedup, 6.9 and 6 times energy efficiency improvement than AMD Ryzen 9 5900X respectively, when it is integrated into the well-known ZKP open-source project, bellman.

The accurate and rapid identification of safflower filaments is a prerequisite for automating harvesting. This paper proposes a lightweight, high-precision detection model for safflower filaments based on YOLOv5s, named YOLOv5s-MCD, to address the issues of large existing network model sizes and low detection accuracy in complex natural environments. The Backbone of the YOLOv5s-MCD model was optimized into a lightweight improved network MobileNetv2 with DSC and CA modules, and the neck part incorporated the CA attention mechanism. The loss function is improved from DIoU’s non-maximum suppression method to CIoU to reduce the model size and improve the detection accuracy and speed. The experimental results show that the size of the YOLOv5s-MCD model is its size by 7.69 MB compared to the original YOLOv5s model, with a mean Average Precision (mAP) of 95.6% and an average detection time of only 3.2ms per image. When tested under unobstructed, obstructed, backlighting, shaking, and wide-angle natural environments, the improved YOLOv5s-MCD model increased the mAP value by 4.4, 0.7, 3.3, 3.4, and 1.0 percentage, respectively, compared with the YOLOv5s model, with improved F1 scores and confidence levels. This indicates that the improved lightweight model can achieve fast, real-time, and accurate detection of the safflower filaments in complex environments. The research results can provide a technical reference for the development of field safflower filament-harvesting robots.

Abstract Alzheimer’s disease (AD) is a major cause of dementia debilitating the global ageing population. Current understanding of the AD pathophysiology implicates the aggregation of amyloid beta (Aβ) as causative to neurodegeneration, with tauopathies, apolipoprotein E and neuroinflammation considered as other major culprits. Curiously, vascular endothelial barrier dysfunction is strongly associated with Aβ deposition and 80-90% AD subjects also experience cerebral amyloid angiopathy. Here we show amyloid protein-induced endothelial leakiness (APEL) in human microvascular endothelial monolayers as well as in mouse cerebral vasculature. Using signaling pathway assays and discrete molecular dynamics, we revealed that the angiopathy first arose from a disruption to vascular endothelial (VE)-cadherin junctions exposed to the nanoparticulates of Aβ oligomers and seeds, preceding the earlier implicated proinflammatory and pro-oxidative stressors to endothelial leakiness. These findings were analogous to nanomaterials-induced endothelial leakiness (NanoEL), a major phenomenon in nanomedicine depicting the paracellular transport of anionic inorganic nanoparticles in the vasculature. As APEL also occurred in vitro with the oligomers and seeds of alpha synuclein, this study proposes a paradigm for elucidating the vascular permeation, systemic spread, and cross-seeding of amyloid proteins that underlie the pathogeneses of AD and Parkinson’s disease.

Abstract Background Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. Results Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. Conclusions In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

The traditional soil-based rice seedling production methods for mechanical transplanting are resource-intensive, time consuming and laborious. The improvement and optimization of nutrient management in soil-less nursery raising methods like tandem long-mat seedlings (TLMS) are necessary for the resource-efficient cultivation of rice. In the present study, a controlled-release fertilizer (CRF)-polymer-coated compound fertilizer with 3 months release period (PCCF-3M) was applied as seedling fertilizer (SF), and five different dosages of SF (SF-0, SF-10, SF-20, SF-30, and SF-40) were compared with an organic substrate as the control (CK). Among all SF treatments, the best results were obtained with the application of 20 g/tray of SF (SF-20), as the seedling quality and machine transplanting quality were comparable to those of CK. In contrast, the lower dosages (SF-0 and SF-10) resulted in low nitrogen content and reduced shoot growth, while the higher dosages (SF-30 and SF-40) resulted in toxicity (increased malondialdehyde accumulation) and inhibited the root growth. Similarly, SF-20 increased panicle number (5.6–7.0%) and yield (4.3–5.3%) compared with CK, which might be related to the remaining SF entangled in the roots supporting the tiller growth of rice seedlings in the field. Moreover, SF-20 reduced the seedling block weight (53.1%) and cost of seedling production (23.5%) but increased the gross margin, indicating that it was easy to handle and economical. Taken together, our results indicate that SF-20 is a cost-effective way to promote the growth and transplanting efficiency of rice seedlings. To our knowledge, this study is the first to determine the optimum dosage of CRF for the soil-less production of rice seedlings.