METTL3-m6A methylation inhibits the proliferation and viability of type II alveolar epithelial cells in acute lung injury by enhancing the stability and translation efficiency of Pten mRNA.

BACKGROUND: The pathogenesis of acute lung injury (ALI) involves a severe inflammatory response, leading to significant morbidity and mortality. N6-methylation of adenosine (m6A), an abundant mRNA nucleotide modification, plays a crucial role in regulating mRNA metabolism and function. However, the precise impact of m6A modifications on the progression of ALI remains elusive. METHODS: ALI models were induced by either intraperitoneal injection of lipopolysaccharide (LPS) into C57BL/6 mice or the LPS-treated alveolar type II epithelial cells (AECII) in vitro. The viability and proliferation of AECII were assessed using CCK-8 and EdU assays. The whole-body plethysmography was used to record the general respiratory functions. M6A RNA methylation level of AECII after LPS insults was detected, and then the "writer" of m6A modifications was screened. Afterwards, we successfully identified the targets that underwent m6A methylation mediated by METTL3, a methyltransferase-like enzyme. Last, we evaluated the regulatory role of METTL3-medited m6A methylation at phosphatase and tensin homolog (Pten) in ALI, by assessing the proliferation, viability and inflammation of AECII. RESULTS: LPS induced marked damages in respiratory functions and cellular injuries of AECII. The m6A modification level in mRNA and the expression of METTL3, an m6A methyltransferase, exhibited a notable rise in both lung tissues of ALI mice and cultured AECII cells subjected to LPS treatment. METTL3 knockdown or inhibition improved the viability and proliferation of LPS-treated AECII, and also reduced the m6A modification level. In addition, the stability and translation of Pten mRNA were enhanced by METTL3-mediated m6A modification, and over-expression of PTEN reversed the protective effect of METTL3 knockdown in the LPS-treated AECII. CONCLUSIONS: The progression of ALI can be attributed to the elevated levels of METTL3 in AECII, as it promotes the stability and translation of Pten mRNA through m6A modification. This suggests that targeting METTL3 could offer a novel approach for treating ALI.

Unraveling Lattice-Distortion Hardening Mechanisms in High-Entropy Carbides.

Uncovering the hardening mechanisms is of great importance to accelerate the design of superhard high-entropy carbides (HECs). Herein, the hardening mechanisms of HECs by a combination of experiments and first-principles calculations are systematically explored. The equiatomic single-phase 4- to 8-cation HECs (4-8HECs) are successfully fabricated by the two-step approach involving ultrafast high-temperature synthesis and hot-press sintering techniques. The as-fabricated 4-8HEC samples possess fully dense microstructures (relative densities of up to ≈99%), similar grain sizes, clean grain boundaries, and uniform compositions. With the elimination of these morphological properties, the monotonic enhancement of Vickers hardness and nanohardness of the as-fabricated 4-8HEC samples is found to be driven by the aggravation of lattice distortion. Further studies show no evident association between the enhanced hardness of the as-fabricated 4-8HEC samples and other potential indicators, including bond strength, valence electron concentration, electronegativity mismatch, and metallic states. The work unveils the underlying hardening mechanisms of HECs and offers an effective strategy for designing superhard HECs.

Methylprednisolone alleviates lung injury in sepsis by regulating miR-151-5p/USP38 pathway.

BACKGROUND: Acute lung injury (ALI) is manifested by increased blood vessel permeability within the lungs and subsequent impairment of alveolar gas exchange. Methylprednisolone (MP) is commonly used as a treatment for ALI to reduce inflammation, yet its molecular mechanism remains unclear. This study aims to explore the underlying mechanisms of MP on ALI in a model induced by lipopolysaccharide (LPS). MATERIAL AND METHODS: The proliferation, viability, apoptosis, and miR-151-5p expression of alveolar type II epithelial cells (AECII) were detected using the cell EdU assay, Annexin V/PI Apoptosis Kit, counting kit-8 (CCK-8) assay, and RT-qPCR. Western blot analysis was used to detect the Usp38 protein level. IL-6 and TNF-α were measured by ELISA. The combination of miR-151-5p and USP38 was determined by chromatin immunoprecipitation (ChIP)-PCR and dual-luciferase reporter assay. RESULTS: MP greatly improved pulmonary function in vivo, reduced inflammation, and promoted the proliferation of the alveolar type II epithelial cells (AECII) in vitro. By comparing the alterations of microRNAs in lung tissues between MP treatment and control groups, we found that miR-151-5p exhibited a significant increase after LPS-treated AECII, but decreased after MP treatment. Confirmed by a luciferase reporter assay, USP38, identified as a downstream target of miR-151-5p, was found to increase after MP administration. Inhibition of miR-151-5p or overexpression of USP38 in AECII significantly improved the anti-inflammatory, anti-apoptotic, and proliferation-promotive effects of MP. CONCLUSION: In summary, our data demonstrated that MP alleviates the inflammation and apoptosis of AECII induced by LPS, and promotes the proliferation of AECII partially via miR-151-5p suppression and subsequent USP38 activation.

Why do dipole moments of HCl-water clusters fail to determine acid dissociation?

This paper quantitatively examines why dipole moments of HCl(H2O)n=1-8 cannot serve as the dissociation criterion for acid molecules using the Hirshfeld-I approach. Also, we propose the possible experimental parameter 〈P(HCl)〉, whose statistical average enables the assessment of acid dissociation in mixed clusters. Furthermore, our calculations reveal that a minimum of four water molecules are necessary to dissociate an HCl molecule.

Tailoring Mechanical Properties of a Ceramic Nanowire Aerogel with Pyrolytic Carbon for In Situ Resilience at 1400 °C.

Resilient ceramic aerogels with a unique combination of lightweight, good high-temperature stability, high specific area, and thermal insulation properties are known for their promising applications in various fields. However, the mechanical properties of traditional ceramic aerogels are often constrained by insufficient interlocking of the building blocks. Here, we report a strategy to largely increase the interlocking degree of the building blocks by depositing a pyrolytic carbon (PyC) coating onto Si3N4 nanowires. The results show that the mechanical performances of the Si3N4 nanowire aerogels are intricately linked to the microstructure of the PyC nodes. The compression resilience of the Si3N4@PyC nanowire aerogels increases with an increase of the interlayer cross-linking in PyC. Additionally, benefiting from the excellent high-temperature stability of PyC, the Si3N4@PyC nanowire aerogels demonstrate significantly superior in situ resilience up to 1400 °C. The integrated mechanical and high-temperature properties of the Si3N4@PyC nanowire aerogels make them highly appealing for applications in harsh conditions. The facile method of manipulating the microstructure of the nodes may offer a perspective for tailoring the mechanical properties of ceramic aerogels.

Ultrastrong and High Thermal Insulating Porous High-Entropy Ceramics up to 2000 °C.

High mechanical load-carrying capability and thermal insulating performance are crucial to thermal-insulation materials under extreme conditions. However, these features are often difficult to achieve simultaneously in conventional porous ceramics. Here, for the first time, it is reported a multiscale structure design and fast fabrication of 9-cation porous high-entropy diboride ceramics via an ultrafast high-temperature synthesis technique that can lead to exceptional mechanical load-bearing capability and high thermal insulation performance. With the construction of multiscale structures involving ultrafine pores at the microscale, high-quality interfaces between building blocks at the nanoscale, and severe lattice distortion at the atomic scale, the materials with an ≈50% porosity exhibit an ultrahigh compressive strength of up to ≈337 MPa at room temperature and a thermal conductivity as low as ≈0.76 W m-1 K-1. More importantly, they demonstrate exceptional thermal stability, with merely ≈2.4% volume shrinkage after 2000 °C annealing. They also show an ultrahigh compressive strength of ≈690 MPa up to 2000 °C, displaying a ductile compressive behavior. The excellent mechanical and thermal insulating properties offer an attractive material for reliable thermal insulation under extreme conditions.

Electric-Field-Induced Selective Directed Transport of Diverse Droplets.

Droplet directional transport is one of the central topics in microfluidics and lab-on-a-chip applications. Selective transport of diverse droplets, particularly in another liquid phase environment with controlled directions, is still challenging. In this work, we propose an electric-field gradient-driven droplet directional transport platform facilitated by a robust lubricant surface. On the platform, we clearly demonstrated a liquid-inherent critical frequency-dominated selective transport of diverse droplets and a driving mechanism transition from electrowetting to liquid dielectrophoresis. Enlightened by the Kelvin-Helmholtz theory, we first realize the directional droplet transport in another liquid phase whenever a permittivity difference exists. Co-transport of multiple droplets and various combinations of droplet types, as well as multifunctional droplet transport modes, are realized based on the presented powerful electric-field gradient-driven platform, overcoming the limitations of the surrounding environment, liquid conductivity, and intrinsic solid-liquid wetting property existing in traditional droplet transport strategies. This work may inspire new applications in liquid separation, multiphase microfluidic manipulation, chemical reagent selection, and so on.

Deformation of confined liquid interfaces by inhomogeneous electric fields and localized particle forces.

HYPOTHESIS: Oil-water interfaces that are created by confining a certain amount of oil in a square shaped pixel (∼200 x 200 µm2 with a height of ∼10 µm) topped by a layer of water, have a curvature that depends on the amount of oil that happens to be present in the confining area. Under the application of an electric field normal to the interface, the interface will deform due to inhomogeneities in the electric field. These inhomogeneities are expected to arise from the initial curvature of the meniscus, from fringe fields that emerge at the confining pixel walls and, if applicable, from interfacially adsorbed particles. MODELING AND EXPERIMENTS: We model the shape of the confined oil-water interface invoking capillarity and electrostatics. Furthermore, we measure the initial curvature by tracking the position of interfacially adsorbed particles depending on sample tilt. FINDINGS: We found that the pixels exhibited meniscus curvature radii ranging from 0.6-7 mm. The corresponding model based minimum oil film thicknesses range between 0.7 and 9 µm. Furthermore, the model shows that the initial meniscus curvature can increase up to 76 percent relative to the initial curvature by the electric field before the oil film becomes unstable. The pixel wall and particles are shown to have minimal impact on the interface deformation.

Strong yet flexible ceramic aerogel.

Ceramic aerogels are highly efficient, lightweight, and chemically stable thermal insulation materials but their application is hindered by their brittleness and low strength. Flexible nanostructure-assembled compressible aerogels have been developed to overcome the brittleness but they still show low strength, leading to insufficient load-bearing capacity. Here we designed and fabricated a laminated SiC-SiOx nanowire aerogel that exhibits reversible compressibility, recoverable buckling deformation, ductile tensile deformation, and simultaneous high strength of up to an order of magnitude larger than other ceramic aerogels. The aerogel also shows good thermal stability ranging from -196 °C in liquid nitrogen to above 1200 °C in butane blow torch, and good thermal insulation performance with a thermal conductivity of 39.3 ± 0.4 mW m-1 K-1. These integrated properties make the aerogel a promising candidate for mechanically robust and highly efficient flexible thermal insulation materials.

Analysis of the risk factors of radiation pneumonitis and the predictive ability of dosiomics in non-small-cell lung cancer.

Purpose: This prospective study investigated the incidence of radiation pneumonitis (RP) after immunotherapy followed by radiotherapy in non-small-cell lung cancer, analyzed the risk factors for RP, and explored the predictive performance of dosimetry and dosiomics. Methods & materials: Risk factors for grade ≥2 RP were calculated by using a logistic regression model. Predictive performance was compared on the basis of area under the curve values. Results: Grade ≥2 RP occurred in 16 cases (26.7%). The AUC values of V5 Gy, gray-level dependence matrix-small dependence high gray-level emphasis (GLDM-SDHGLE) and combined features were 0.685, 0.724 and 0.734, respectively. Conclusion: Smoking history, bilateral lung V5 Gy and GLDM-SDHGLE were independent risk factors for RP. Dosiomics can effectively predict RP.

Radiation pneumonia predictive model for radiotherapy in esophageal carcinoma patients.

BACKGROUND: The machine learning models with dose factors and the deep learning models with dose distribution matrix have been used to building lung toxics models for radiotherapy and achieve promising results. However, few studies have integrated clinical features into deep learning models. This study aimed to explore the role of three-dimension dose distribution and clinical features in predicting radiation pneumonitis (RP) in esophageal cancer patients after radiotherapy and designed a new hybrid deep learning network to predict the incidence of RP. METHODS: A total of 105 esophageal cancer patients previously treated with radiotherapy were enrolled in this study. The three-dimension (3D) dose distributions within the lung were extracted from the treatment planning system, converted into 3D matrixes and used as inputs to predict RP with ResNet. In total, 15 clinical factors were normalized and converted into one-dimension (1D) matrixes. A new prediction model (HybridNet) was then built based on a hybrid deep learning network, which combined 3D ResNet18 and 1D convolution layers. Machine learning-based prediction models, which use the traditional dosiomic factors with and without the clinical factors as inputs, were also constructed and their predictive performance compared with that of HybridNet using tenfold cross validation. Accuracy and area under the receiver operator characteristic curve (AUC) were used to evaluate the model effect. DeLong test was used to compare the prediction results of the models. RESULTS: The deep learning-based model achieved superior prediction results compared with machine learning-based models. ResNet performed best in the group that only considered dose factors (accuracy, 0.78 ± 0.05; AUC, 0.82 ± 0.25), whereas HybridNet performed best in the group that considered both dose factors and clinical factors (accuracy, 0.85 ± 0.13; AUC, 0.91 ± 0.09). HybridNet had higher accuracy than that of Resnet (p = 0.009). CONCLUSION: Based on prediction results, the proposed HybridNet model could predict RP in esophageal cancer patients after radiotherapy with significantly higher accuracy, suggesting its potential as a useful tool for clinical decision-making. This study demonstrated that the information in dose distribution is worth further exploration, and combining multiple types of features contributes to predict radiotherapy response.

The Impact of Shared Information Presentation Time on Users' Privacy-Regulation Behavior in the Context of Vertical Privacy: A Moderated Mediation Model.

Combining data-sharing models and algorithm technologies has led to new data flow structures and usage patterns. In this context, the presentation time of shared low-sensitivity information across platforms has become a crucial factor that affects user perception and privacy-regulation behavior. However, previous studies have not conducted an in-depth exploration of this issue. Based on privacy process theory, this study discusses the impact and potential mechanism of the presentation time (immediate or delayed) of shared low-sensitivity information across platforms on privacy-regulation behavior. Through a pre-study and two online survey experimental studies, which included 379 participants in total, we verified that the immediate information presentation time has a significantly higher impact on online vigilance and privacy-regulation behavior than the delayed condition, ßdirect = 0.5960, 95% CI 0.2402 to 0.9518; ßindirect = 0.1765, 95% CI 0.0326 to 0.3397, and users' perceived control as the moderating role influences online vigilance and privacy-regulation behaviors (preventive or corrective), ßpreventive = -0.0562, 95% CI -0.1435 to -0.0063; ßcorrective = -0.0581, 95% CI -0.1402 to -0.0065. Based on these results, we suggest that the presentation time of using shared low-sensitivity information across platforms should be concerned by companies' recommendation algorithms to reduce users' negative perceptions and privacy behaviors and improve user experience.

Accurate and Wide-Voltage-Range Modeling of Electrowetting with a Lattice Boltzmann Approach.

The lattice Boltzmann method (LBM) has been widely used in multi-phase fluid mechanics and is known to be more computationally efficient than the traditional method of numerically solving Navier-Stokes and Cahn-Hilliard equations. Electrowetting is an important component of interfacial sciences, in which the liquid-liquid and solid-liquid interfaces are tuned by electrostatics. Modeling electrowetting using the LBM can be categorized into surface and bulk methods. By modifying the surface tension scalar, the surface method easily reproduces the fundamental Young-Lippmann (YL) equation at low voltages but fails to capture contact angle saturation at high voltages. With fully coupled hydrodynamics and electrostatics in the form of spatially dependent matrices, the bulk method can successfully show contact angle saturation, but it is often unable to reproduce the YL equation due to its intrinsic inaccuracies. The inaccuracies are mainly due to the fact that while the hydrodynamics are all described by continuous physical quantities in the framework of diffusive interfaces, the interfacial electrostatics are governed by discontinuous electric fields caused by sheet charge density. In this paper, we show that accurately modeling electrowetting using the LBM is non-trivial. Additional modeling work, especially the treatment of interfacial electric fields, is needed to recover the fundamental YL equation at low voltages and predict contact angle saturation at high voltages, with a systematic model validation over key parameters and applications.

An edge-based approach for virtual network embedding based on the graph edit distance.

Virtualization and resource isolation techniques have enabled the efficient sharing of networked resources. How to control network resource allocation accurately and flexibly has gradually become a research hotspot due to the growth in user demands. Therefore, this paper presents a new edge-based virtual network embedding approach to studying this problem that employs a graph edit distance method to accurately control resource usage. In particular, to manage network resources efficiently, we restrict the use conditions of network resources and restrict the structure based on common substructure isomorphism and an improved spider monkey optimization algorithm is employed to prune redundant information from the substrate network. Experimental results showed that the proposed method achieves better performance than existing algorithms in terms of resource management capacity, including energy savings and the revenue-cost ratio.

Highly cross-linked carbon tube aerogels with enhanced elasticity and fatigue resistance.

Carbon aerogels are elastic, mechanically robust and fatigue resistant and are known for their promising applications in the fields of soft robotics, pressure sensors etc. However, these aerogels are generally fragile and/or easily deformable, which limits their applications. Here, we report a synthesis strategy for fabricating highly compressible and fatigue-resistant aerogels by assembling interconnected carbon tubes. The carbon tube aerogels demonstrate near-zero Poisson's ratio, exhibit a maximum strength over 20 MPa and a completely recoverable strain up to 99%. They show high fatigue resistance (less than 1.5% permanent degradation after 1000 cycles at 99% strain) and are thermally stable up to 2500 °C in an Ar atmosphere. Additionally, they possess tunable conductivity and electromagnetic shielding. The combined mechanical and multi-functional properties offer an attractive material for the use in harsh environments.

GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma.

Background: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma. Methods: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers. Results: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid. Conclusions: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.

An evolutionary game analysis of digital currency innovation and regulatory coordination.

The innovation and regulatory coordination of digital currency is an important proposition in the new era of Fintech. There is increasing competition between traditional currencies and new digital currencies, so a spontaneous game model of currencies is analyzed. By introducing the role of financial coordination, this paper revises the evolutionary game model of digital currency innovation, and analyzes their competition strategies through case and simulation. The results show that: first, the dominant result of digital currency spontaneous game is that both parties tend to digital cooperation strategy. Second, with the introduction of financial regulation, the dominant result of digital currency tripartite evolutionary game is that financial institutions tend to participate in coordination and both currency parties tend to cooperate. Third, the choice strategy of currency is more sensitive to the changes of willingness to participate in cooperation, cooperation costs and cooperation benefits of financial coordination. The selection strategy of financial coordination institutions for digital currency is more influenced by changes in cooperation costs and incentive return in the process of participating in cooperation.

Hierarchical SiC-Graphene Composite Aerogel-Supported Ni-Mo-S Nanosheets for Efficient pH-Universal Electrocatalytic Hydrogen Evolution.

MoS2 exhibits good prospects in electrocatalytic hydrogen evolution. Whereas, the electrocatalytic property of MoS2 is restrained by its insufficient active sites, low electrical conductivity, and slow water dissociation processes. Herein, an aerogel composed of silicon carbide (SiC) and graphene (SiCnw-RGO) was constructed by growing SiC nanowires (SiCnw) in the graphene aerogel (RGO) via the CVD method, and then Ni-Mo-S nanosheets were hydrothermally synthesized on the SiCnw-RGO composite aerogel to develop an efficient pH-universal electrocatalyst. Ni-Mo-S nanosheets supported on SiCnw-RGO (Ni-Mo-S@SiCnw-RGO) exhibit an interesting hierarchical three-dimensional interconnected structure of composite aerogel. The optimal Ni-Mo-S@SiCnw-RGO electrocatalyst exhibits excellent catalytic performance with low Tafel slopes of 60 mV/dec under acidic conditions and 90 mV/dec under alkaline conditions. Density functional theory calculations demonstrate a composite catalyst exhibits advantageous hydrogen adsorption free energy and water dissociation energy barrier. This study provides a reference to design an efficient hierarchical aerogel electrocatalyst.

Conservatively transmitted alleles of key agronomic genes provide insights into the genetic basis of founder parents in bread wheat (Triticum aestivum L.).

BACKGROUND: Founder parents play extremely important roles in wheat breeding. Studies into the genetic basis of founder parents and the transmission rules of favorable alleles are of great significance in improving agronomically important traits in wheat. RESULTS: Here, a total of 366 founder parents, widely grown cultivars, and derivatives of four representative founder parents were genotyped based on efficient kompetitive allele-specific PCR (KASP) markers in 87 agronomically important genes controlling yield, quality, adaptability, and stress resistance. Genetic composition analysis of founder parents and widely grown cultivars showed a consistently high frequency of favorable alleles for yield-related genes. This analysis further showed that other alleles favorable for resistance, strong gluten, dwarf size, and early heading date were also subject to selective pressure over time. By comparing the transmission of alleles from four representative founder parents to their derivatives during different breeding periods, it was found that the genetic composition of the representative founder parents was optimized as breeding progressed over time, with the number and types of favorable alleles carried gradually increasing and becoming enriched. There are still a large number of favorable alleles in wheat founder parents that have not been fully utilized in breeding selection. Eighty-seven agronomically important genes were used to construct an enrichment map that shows favorable alleles of four founder parents, providing an important theoretical foundation for future identification of candidate wheat founder parents. CONCLUSIONS: These results reveal the genetic basis of founder parents and allele transmission for 87 agronomically important genes and shed light on breeding strategies for the next generation of elite founder parents in wheat.

TaTPP-7A positively feedback regulates grain filling and wheat grain yield through T6P-SnRK1 signalling pathway and sugar-ABA interaction.

Grain size and filling are two key determinants of grain thousand-kernel weight (TKW) and crop yield, therefore they have undergone strong selection since cereal was domesticated. Genetic dissection of the two traits will improve yield potential in crops. A quantitative trait locus significantly associated with wheat grain TKW was detected on chromosome 7AS flanked by a simple sequence repeat marker of Wmc17 in Chinese wheat 262 mini-core collection by genome-wide association study. Combined with the bulked segregant RNA-sequencing (BSR-seq) analysis of an F2 genetic segregation population with extremely different TKW traits, a candidate trehalose-6-phosphate phosphatase gene located at 135.0 Mb (CS V1.0), designated as TaTPP-7A, was identified. This gene was specifically expressed in developing grains and strongly influenced grain filling and size. Overexpression (OE) of TaTPP-7A in wheat enhanced grain TKW and wheat yield greatly. Detailed analysis revealed that OE of TaTPP-7A significantly increased the expression levels of starch synthesis- and senescence-related genes involved in abscisic acid (ABA) and ethylene pathways. Moreover, most of the sucrose metabolism and starch regulation-related genes were potentially regulated by SnRK1. In addition, TaTPP-7A is a crucial domestication- and breeding-targeted gene and it feedback regulates sucrose lysis, flux, and utilization in the grain endosperm mainly through the T6P-SnRK1 pathway and sugar-ABA interaction. Thus, we confirmed the T6P signalling pathway as the central regulatory system for sucrose allocation and source-sink interactions in wheat grains and propose that the trehalose pathway components have great potential to increase yields in cereal crops.