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Abstract Metabolic reprogramming is a pivotal biological process in which cellular metabolic patterns change to meet the energy demands of increased cell growth and proliferation. In this review, we explore metabolic reprogramming and its impact on fibrotic diseases, providing a detailed overview of the key processes involved in the metabolic reprogramming of renal fibrosis, including fatty acid decomposition and synthesis, glycolysis, and amino acid catabolism. In addition, we report that Chinese medicine ameliorates renal inflammation, oxidative stress, and apoptosis in chronic kidney disease by regulating metabolic processes, thereby inhibiting renal fibrosis. Furthermore, we reveal that multiple targets and signaling pathways contribute to the metabolic regulatory effects of Chinese medicine. In summary, this review aims to elucidate the mechanisms by which Chinese medicine inhibits renal fibrosis through the remodeling of renal cell metabolic processes, with the goal of discovering new therapeutic drugs for treating renal fibrosis.

Abstract Necroptosis is intimately associated with the initiation and progression of colon adenocarcinoma (COAD). However, studies on necroptosis-related genes (NRGs) and the regulating long non-coding RNAs (NRGlncRNAs) in the context of COAD are limited. We retrieved the cancer genome atlas (TCGA) to collect datasets of NRGs and NRGlncRNAs on COAD patients. The risk model constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression was then employed to identify NRGs and NRGlncRNAs with prognostic significance. Subsequently, we validated the results using gene expression omnibus (GEO) datasets from different populations, conducted Mendelian randomization (MR) analysis to explore the potential causal relationships between prognostic NRGs and COAD, and conducted cell experiments to verify the expression of prognostic NRGlncRNAs in COAD. Furthermore, we explored potential pathways and regulatory mechanisms of these prognostic NRGlncRNAs and NRGs in COAD through enrichment analysis, immune cell correlation analysis, tumor microenvironment analysis, immune checkpoint analysis, tumor sample clustering, and so on. We identified eight NRGlncRNAs (AC245100.5, AP001619.1, LINC01614, AC010463.3, AL162595.1, ITGB1-DT, LINC01857, and LINC00513) used for constructing the prognostic model and nine prognostic NRGs (AXL, BACH2, CFLAR, CYLD, IPMK, MAP3K7, ATRX, BRAF, and OTULIN) with regulatory relationships with them, and their validation was performed using GEO and GWAS datasets, as well as cell experiments, which showed largely consistent results. These prognostic NRGlncRNAs and NRGs modulate various biological functions, including immune inflammatory response, oxidative stress, immune escape, telomere regulation, and cytokine response, influencing the development of COAD. Additionally, stratified analysis of the high-risk and low-risk groups based on the prognostic model revealed elevated expression of immune cells, increased expression of tumor microenvironment cells, and upregulation of immune checkpoint gene expression in the high-risk group. Finally, through cluster analysis, we identified tumor subtypes, and the results of cluster analysis were essentially consistent with the analysis between risk groups. The prognostic NGRlncRNAs and NRGs identified in our study serve as prognostic indicators and potential therapeutic targets for COAD, providing a theoretical basis for the clinical diagnosis and treatment of COAD and offering guidance for further research.

Abstract There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p

Wheat, being a crucial global food crop, holds immense significance for food safety and agricultural economic stability, as the quality and condition of its grains are critical factors. Traditional methods of wheat grain detection are inefficient, and the advancements in deep learning offer a novel solution for fast and accurate grain recognition. This study proposes an improved deep learning model based on YOLOv8n, referred to as YOLO-SDL, aiming to achieve efficient wheat grain detection. A high-quality wheat grain dataset was first constructed, including images of perfect, germinated, diseased, and damaged grains. Multiple data augmentation techniques were employed to enhance the dataset’s complexity and diversity. The YOLO-SDL model incorporates the ShuffleNetV2 architecture in its backbone and combines depthwise separable convolutions (DWConv) with the large separable kernel attention (LSKA) mechanism in its neck structure, significantly improving detection speed and accuracy while ensuring the model remains lightweight. The results indicate that YOLO-SDL achieves superior performance in wheat grain detection, balancing lightweight design and performance optimization. The model achieved a P of 0.942, R of 0.903, mAP50 of 0.965, and mAP50-95 of 0.859, with low computational complexity, making it suitable for resource-constrained environments. These findings demonstrate the efficiency of the ShuffleNetV2, DWConv, and LSKA structures. The proposed YOLO-SDL model provides a new technical solution for agricultural automation and serves as a reliable reference for detecting other crops.

Abstract Existential state of solutes substantially affects the efficiency and direction of various chemical and biological processes, about which current consensus is still limited at macro and micro levels. At the trace level, solutes assume a pivotal role across a spectrum of critical fields. However, their existential states, especially at interfaces, remain largely elusive. Herein, an exceptional evolution of solute molecules is unveiled from micro to trace, solution to interface, with the aid of surface‐enhanced Raman spectroscopy, extinction, DLS and theoretical simulations. Given predominant existence of monomers within the solution, these aggregates dominate the interfacial behavior of solute molecules. Moreover, a universal, aggregate‐controlled mechanism is demonstrated that aggregates triggered by cosolvent, which can dramatically promote efficiency of catalytic reactions. The results provide novel insights into the interaction mechanisms between reactants and catalysts, potentially offering fresh perspectives for the manipulation of multiphase catalysis and related biological processes.

Copper and copper alloy are commonly used to fabricate ship propellers and sealing valves that encounter harsh corrosion and wear. To improve their service life, Cu coating and Cu–AlN composite coatings with different volume content of AlN (10%, 20%, 30%) were prepared by cold spraying. The investigation focused on analyzing the coatings’ microstructure, microhardness, resistance to wear, and corrosion. Results show that the composite coatings with AlN have fewer pores and denser microstructure than the Cu coating. The coating demonstrates a relatively low deposition efficiency, resulting in the attainment of only 3.8 vol% of AlN when the feedstock AlN powder content was 30 vol%. The microhardness of Cu-3.8AlN coating is 159.7 HV, about 53.1% higher than that of Cu coating. The specific wear rate of Cu-3.8AlN coating is reduced by about 73.5% compared to that of Cu coating, measuring at 1.69 × 10−3 mm3/(N·m). Compared with other coatings, Cu-3.8AlN has the highest corrosion resistance (Ecorr = −0.199 V, Icorr = 1.2 μA/cm2, Rct = 3200 Ω·cm2). The Cu-3.8AlN coating exhibits superior wear and corrosion resistance among the four coatings, attributed to its highest level of densification and the presence of AlN particles.

A novel (Co40Cr25(FeNi)31Mo4)99·5C0.5 HEA (high entropy alloy) was prepared by vacuum arc melting furnace and hot rolled with a reduction of 20 % at 1100 °C, cold rolled with a reduction of ∼50 %, and then annealed at 800, 850, 900, 950, 1000, and 1100 °C for 6 min, respectively. The effect of annealed on the microstructure evolution and mechanical properties of HEAs were systematically analyzed. The results showed that the HEAs still maintains single FCC(Face-centered cubic) crystal structure after different annealing temperatures. With increasing annealed temperature, the area of abnormal grain gradually decreases and forming equiaxed grain finally. Annealing at lower temperature (800 °C) gives rise to the formation of nanoscale and submicron M23C6 carbide, which hindered the recrystallization of grains and resulting to the higher tensile strength of ∼1352 MPa and lower elongation of ∼37 % when comparing with other annealed HEAs. However, the amount of M23C6 precipitates decreases when the annealing temperature was increased to 1100 °C. At this time, the alloy structure was consisting of recrystallized grains and a large number of annealing twins, and the tensile strength decreased to ∼1062 MPa and the elongation increased to ∼85 %. Due to annealing twins effect and grain refinement, the 1100 °C annealed HEA achieved superior strength-ductility balance (TS × EL) of ∼90.3 GPa%, while the strength-ductility balance (TS × EL) of 800 °C annealed HEA was only ∼50 GPa%. The 1100 °C annealed HEA possesses excellent comprehensive mechanical properties, which is superior to a majority of reported HEAs and conventional metal alloys.

The number of wheat spikes has an important influence on wheat yield, and the rapid and accurate detection of wheat spike numbers is of great significance for wheat yield estimation and food security. Computer vision and machine learning have been widely studied as potential alternatives to human detection. However, models with high accuracy are computationally intensive and time consuming, and lightweight models tend to have lower precision. To address these concerns, YOLO-FastestV2 was selected as the base model for the comprehensive study and analysis of wheat sheaf detection. In this study, we constructed a wheat target detection dataset comprising 11,451 images and 496,974 bounding boxes. The dataset for this study was constructed based on the Global Wheat Detection Dataset and the Wheat Sheaf Detection Dataset, which was published by PP Flying Paddle. We selected three attention mechanisms, Large Separable Kernel Attention (LSKA), Efficient Channel Attention (ECA), and Efficient Multi-Scale Attention (EMA), to enhance the feature extraction capability of the backbone network and improve the accuracy of the underlying model. First, the attention mechanism was added after the base and output phases of the backbone network. Second, the attention mechanism that further improved the model accuracy after the base and output phases was selected to construct the model with a two-phase added attention mechanism. On the other hand, we constructed SimLightFPN to improve the model accuracy by introducing SimConv to improve the LightFPN module. The results of the study showed that the YOLO-FastestV2-SimLightFPN-ECA-EMA hybrid model, which incorporates the ECA attention mechanism in the base stage and introduces the EMA attention mechanism and the combination of SimLightFPN modules in the output stage, has the best overall performance. The accuracy of the model was P=83.91%, R=78.35%, AP= 81.52%, and F1 = 81.03%, and it ranked first in the GPI (0.84) in the overall evaluation. The research examines the deployment of wheat ear detection and counting models on devices with constrained resources, delivering novel solutions for the evolution of agricultural automation and precision agriculture.

Objectives: Fungal bloodstream infection (fBSI) following pediatric liver transplantation presents a significant challenge; however, there remains a paucity of guidance regarding antifungal prophylaxis in this population. This study aimed to evaluate the effectiveness of universal antifungal prophylaxis and propose a desirable strategy. Methods: We enrolled 604 pediatric patients who underwent liver transplantation between 2020 and 2023, including 242 patients with empirical prophylaxis and 362 patients with universal prophylaxis. Univariate and multivariate logistic regression analyses were performed to identify independent factors for fBSI. Results: Eight (2.2%) pediatric recipients in the universal prophylaxis group and 13 (5.4%) in the empirical group developed fBSI (P = 0.038). Universal prophylaxis was a protective factor (P = 0.044), while high-volume intraoperative plasma transfusion and deceased donor liver transplantation were independent risk factors for fBSI (P = 0.035 and 0.008, respectively). Universal antifungal strategy showed an increased overall survival trend after liver transplantation although without significant statistical difference (P = 0.217). Patients with fBSI had poorer survival than those without fBSI (P

Fabricating SiC ceramics via the digital light processing (DLP) technology is of great challenge due to strong light absorption and high refractive index of deep-colored SiC powders, which highly differ from those of resin, and thus significantly affect the curing performance of the photosensitive SiC slurry. In this paper, a thin silicon oxide (SiO2) layer was in-situ formed on the surface of SiC powders by pre-oxidation treatment. This method was proven to effectively improve the curing ability of SiC slurry. The SiC photosensitive slurry was fabricated with solid content of 55 vol% and viscosity of 7.77 Pa·s (shear rate of 30 s−1). The curing thickness was 50 μm with exposure time of only 5 s. Then, a well-designed sintering additive was added to completely convert low-strength SiO2 into mullite reinforcement during sintering. Complex-shaped mullite-bond SiC ceramics were successfully fabricated. The flexural strength of SiC ceramics sintered at 1550 ℃ in air reached 97.6 MPa with porosity of 39.2 vol%, as high as those prepared by spark plasma sintering (SPS) techniques.

Anomaly detection for the Internet of Things (IoT) is a major intelligent service required by many fields, including intrusion detection, state monitoring, device-activity analysis, and security supervision. However, the heterogeneous distribution of data and resource-constrained end nodes in ubiquitous IoT systems present challenges for existing anomaly detection models. Due to the advantages of flexible deployment and multi-dimensional resources, high altitude platform stations (HAPSs) and unmanned aerial vehicles (UAVs), which are important components of vertical heterogeneous networks (VHetNets), have significant potential for sensing, computing, storage, and communication applications in ubiquitous IoT systems. In this paper, we propose a novel VHetNet-enabled asynchronous federated learning (AFL) framework by adopting the compound-action actor-critic (CA2C) algorithm for UAV selection, which enables decentralized UAVs to collaboratively train a global anomaly detection model based on their local sensory data from IoT devices. In the VHetNet-enabled AFL framework, the UAV selection process aims to prevent UAVs with low local model quality and large energy consumption from affecting the learning efficiency and model accuracy. Due to the wide coverage as well as strong storage and computation capabilities, a HAPS operates as a central aerial server for aggregating local models of UAVs asynchronously and making decisions intelligently. Moreover, we propose a CA2C-based joint device association, UAV selection, and UAV placement algorithm to further enhance the overall federated execution efficiency and detection model accuracy under UAV energy constraints. Extensive experimental evaluation on real-world datasets demonstrates that the proposed algorithm can achieve high detection accuracy with short federated execution time and low energy consumption.

Doping divalent metal cations into Ga2O3 films plays a key role in adjusting the conductive behavior of the film. N-type high-resistivity β-Ga2O3:Mg films were prepared using electron beam evaporation and subsequent postannealing processing. Various characterization methods (X-ray diffraction, X-ray photoelectron spectroscopy, photoluminescence, etc.) revealed that the Mg content plays an important role in affecting the film quality. Specifically, when the Mg content in the film is 3.6%, the S2 film’s resistivity, carrier content, and carrier mobility are 59655.5 Ω·cm, 1.95 × 1014 cm3/C, and 0.53682 cm2/Vs. Also, the film exhibits a smoother surface, more refined grains, and higher self-trapped exciton emission efficiency. The Mg cation mainly substitutes the Ga+ cation at a tetrahedral site, acting as a trap for self-trapped holes.

In this study, a novel algorithm to retrieve the current speed along the range direction under extreme sea states is developed from C-band synthetic aperture radar imagery. To this aim, a Sentinel-1 (S-1) dual-polarized synthetic aperture radar (SAR) dataset consisting of 2300 images is collected during 200 tropical cyclones (TCs). The dataset is complemented with collocated wave simulations from the Wavewatch-III (WW3) model and reanalysis currents from the HYbrid Coordinate Ocean Model (HYCOM). The corresponding TC winds are officially released by IFRMER, while the Stokes drift following the wave propagation direction is estimated from the waves simulated by WW3. In this study, first the dependence of wind, Stokes drift, and range current on the Doppler centroid anomaly is investigated, and then the extreme gradient boosting (XGBoost) machine learning model is trained on 87% of the S-1 dataset for range current retrieval purposes. The rest of the dataset is used for testing the retrieval algorithm, showing a root mean square error (RMSE) and a correlation coefficient (r) of 0.11 m/s and 0.97, respectively, with the HYCOM outputs. A validation against measurements collected from two high-frequency (HF) phased-array radars is also performed, resulting in an RMSE and r of 0.12 m/s and 0.75, respectively. Those validation results are better than the 0.22 m/s RMSE and 0.28 r achieved by the empirical CDOP model. Hence, the experimental results confirm the soundness of the XGBoost, exhibiting a certain improvement over the empirical model.

Mycoplasma pneumoniae (M. pneumoniae, Mp) is a cell wall-deficient microorganism known to cause chronic respiratory infections in both children and adults. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor primarily responsible for identifying muramyl dipeptide (MDP) found in bacterial cell walls. Previous experiments have demonstrated that Mycoplasma ovipneumoniae induces macrophage autophagy through NOD2. In this study, we conducted RNA-seq analysis on macrophages infected with M. pneumoniae and observed an up-regulation in the expression of genes associated with the NOD2 signaling pathway. Mechanistic investigations further revealed the involvement of the NOD2 signaling pathway in the inflammatory response of macrophages activated by M. pneumoniae. We utilized GST pull-down technology in conjunction with liquid chromatography–tandem mass spectrometry (LC–MS/MS) to pinpoint the M. pneumoniae proteins that interact with NOD2. Additionally, co-immunoprecipitation (Co-IP) and immunofluorescence co-localization techniques were used to confirm the interaction between DUF16 protein and NOD2. We found that DUF16 protein can enter macrophages and induce macrophage inflammatory response through the NOD2/RIP2/NF-κB pathway. Notably, the region spanning amino acids 13–90 was identified as a critical region necessary for DUF16-induced inflammation. This research not only broadens our comprehension of the recognition process of the intracellular receptor NOD2, but also deepens our understanding of the development of M. pneumoniae infection.

Prescottella, a distinct genus separate from Rhodococcus, has garnered attention for its adaptability and ecological versatility. In this study, a Gram-stain positive and ovoid-rod shaped the actinobacterium strain R16 was isolated from deep-sea sediment (with a depth of 6,310 m) in the Western Pacific. On the basis of 16S rRNA gene sequence analysis, average nucleotide identity and phylogenomic analysis, strain R16 clearly represents a novel species within the genus Prescottella. Genomic analyses indicate Prescottella sp. R16 contains a circular chromosome of 4,531,251 bp with an average GC content of 68.9%, 4,208 protein-coding genes, 51 tRNA genes, and 12 rRNA operons. Additionally, four CRISPRs and 24 genomic islands are also identified. The presence of rich categories related to catalytic activity, membrane part and metabolic process highlights their involvement in cellular component, biological process, and molecular function. The genome sequence of strain R16 also revealed the presence of 13 putative biosynthetic gene clusters for secondary metabolites, including those for ε-Poly-L-lysine, ectoine, heterobactin, isorenieratene and corynecin, suggesting its potential for antibiotic production and warranting further exploration.

Effect of cold rolling on microstructural evolution and mechanical properties of a novel (Fe50Mn30Co10Cr10)97C2Mo1 high entropy alloy has been investigated via electron microscopy and tensile testing. The results show that the alloy is mainly deformed via dislocation and twinning due to its low stacking fault energy. With increasing thickness reduction, the dislocation density first increases, up to a maximum of ∼29.3 × 1014 m−2 at CR 60 %, then reduces, to 21.1 × 1014 m−2 at CR 90 %. The width and spacing of the deformation twins gradually decrease with an increase of thickness reduction. TEM examination also reveals that shear bands produce in CR 40 % sample, and that its volume fraction gradually increases with increasing thickness reduction. Such microstructural evolution with cold rolling, gives rise to a quick enhancement of yield strength of the alloy (1926 MPa for CR 90 % vs. 239 MPa for the as-homogenized sample) whereas a clear loss in ductility. However, the cold-rolled samples at low to medium strains show a good combination of strength and ductility, e.g., CR 20 % sample has a yield strength of 800 MPa (, which is 3.3 times higher than that of as-homogenized HEA) and an elongation of 30 %, while 1300 MPa yield strength and 15 % elongation for CR 40 % sample.

The CoCrFeNiMn high-entropy alloy and TiB2p/CoCrFeNiMn high-entropy composite (HEC) were manufactured by Selective laser melting. For the CoCrFeNiMn, a coarse epitaxial columnar microstructure with strong crystallographic textures was generated. While in the TiB2p/CoCrFeNiMn, TiB2 particles are distributed in the significantly refined dendrites and nearly equiaxial grains, and phase transformation occurs to form σ phase. TiB2 and σ phase construct a strong interface relationship with the matrix. TiB2p/CoCrFeNiMn HEC has extremely high microhardness (329 ± 2 HV) and excellent wear resistance (coefficients of friction 0.31 ± 0.02). The wear mechanism of the HEC was studied refer to the microstructure, composition and hardness.IMPACT STATEMENTTiB2-reinforced CoCrFeNiMn-based high-entropy composite is successfully fabricated by Selective laser melting, which exhibits exceptional hardness and the best wear resistance.

Abstract Purpose Endothelial cell dysfunction is a major cause of early atherosclerosis. Although the role of extracellular vesicles in stabilizing atherosclerotic plaques is well established, the effect of circulating exosomes on plaque formation is still unknown. Here, we explored the effect of exosomes on atherosclerosis based on the function that exosomes can act on intercellular communication. Patients and methods We extracted serum exosomes from the blood of CHD patients (CHD-Exo) and healthy individuals (Con-Exo). The obtained exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) in vitro. In addition, we determined that circ_0001785 functions as a competing endogenous RNA (ceRNAs) in coronary artery disease by dual luciferase reporter gene analysis. The protective effect of circ_0001785 against endothelial cell injury was also verified using over-expression lentiviral transfection functional assays. In vivo experiments, we injected over-expressed circ_0001785 lentivirus into the tail vein of mice to observe its therapeutic effect on a mouse model of atherosclerosis. Results The vitro co-cultured results showed that the amount of plasma-derived exosomes have an increase in patients with coronary artery disease, and the inflammation and apoptosis of endothelial cells were exacerbated. Over-expression of circ_0001785 reduced endothelial cell injury through the ceRNA network pathway of miR-513a-5p/TGFBR3. Quantitative reverse transcription-polymerase chain reaction identified that the expressed amount of circ_0001785 was reduced in the circulating peripheral blood of CHD patients and increased within human and mouse atherosclerotic plaque tissue. The results of in vivo experiments showed that circ_0001785 reduced aortic endothelial cell injury and the formation of intraplaque neo-vascularization, and enhanced left ventricular diastolic function, thereby delaying the development of atherosclerosis in mice. Conclusion Our results demonstrated a new biomarker, exosome-derived circ_0001785, for atherogenesis, which can reduce endothelial cell injury and thus delay atherogenesis through the miR-513a-5p/TGFBR3 ceRNA network mechanism, providing an exosome-based intervention strategy for atherosclerosis.

TiB2 nano-particle reinforced CoCrFeMnNi composite has been additively manufactured by using laser powder bed fusion (LPBF) technique. In comparison with the matrix CoCrFeMnNi sample, the average grain size of the TiB2 doped CoCrFeMnNi (CoCrFeMnNi + TiB2) sample reduces from 26.27 μm to 7.51 μm, appearing a morphological transformation from columnar grains to fine equiaxed grains and fine dendritic grains. Correspondingly, the compressive yield strength (σy) sharply increases from 484.41 ± 57.81 MPa of CoCrFeMnNi HEA to 952.62 ± 38.15 MPa of CoCrFeMnNi + TiB2, and the tensile yield strength increases from 480.27 ± 1.25 MPa to 834.21 ± 15.93 MPa, revealing a substantial enhancement of mechanical properties. The structural analysis unveils that the CoCrFeMnNi + TiB2 sample formed a tetragonal σ phase beside the FCC matrix and TiB2 phases compared with the single FCC phase of CoCrFeMnNi HEA. Especially, atomic resolution scanning transmission electron microscopy discloses that the TiB2 nanoparticles epitaxially grow onto the FCC matrix phase with [01–10]TiB2//[011]FCC orientation relationship. Theoretical calculations indicate that the enhancement mechanism of the CoCrFeMnNi + TiB2 sample should originate from a synergistic strengthening effect which is induced by grain refinement, TiB2 particles, σ phases and dislocations. Our work should provide a new view to utilize the rapid solidification process of LPBF and ceramic nano-particle reinforcement for the enhanced mechanical properties of HEAs with great potential.

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography–mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material–solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1β in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.

For the air-to-air missile warhead, there is a cabin with a certain thickness at a distance around the fragments. At present, the influence of missile cabin has not yet been taken into account in the study of fragment velocity. In this paper, based on the law of conservation of energy, the theoretical equation of fragment velocity considering the kinetic energy of cabin debris was deduced. Then, the rationality of the theoretical formula is validated through the static explosion experiments of two prototype warheads, one with a titanium alloy cabin and the other without any cabin. It was found that after the warhead is equipped with the cabin, part of the energy is consumed to drive the cabin debris, resulting in a decrease in fragment velocity, but the velocity of cabin debris was greater than that of fragment of warheads without any cabin. Besides, through numerical simulation, the driving process of fragments and cabin debris during explosive detonation loading of the warhead with the cabin was studied, which can be divided into six stages, and the error between numerical result and experimental value is not more than 4.8%. Finally, the variety regulation of fragment velocity and cabin debris velocity at different interval distances was further studied by numerical simulation. The results indicate that fragment velocity of warheads with cabin at different interval distances is basically the same, but cabin debris velocity decreases with the increase of interval distance. This conclusion can provide a reference for the structural design and fragment velocity evaluation of warheads with cabin.

BackgroundDiabetic nephropathy (DN) is a prevalent and debilitating disease that represents the leading cause of chronic kidney disease which imposes public health challenges Tongmai Jiangtang capsule (TMJT) is commonly used for the treatment of DN, albeit its underlying mechanisms of action are still elusive.MethodsThis study retrieved databases to identify the components and collect the targets of TMJT and DN. Target networks were constructed to screen the core components and targets. Samples from the GEO database were utilized to perform analyses of targets and immune cells and obtain significantly differentially expressed core genes (SDECGs). We also selected a machine learning model to screen the feature genes and construct a nomogram. Furthermore, molecular docking, another GEO dataset, and Mendelian randomization (MR) were utilized for preliminary validation. We subsequently clustered the samples based on SDECG expression and consensus clustering and performed analyses between the clusters. Finally, we scored the SDECG score and analyzed the differences between clusters.ResultsThis study identified 13 SDECGs between DN and normal groups which positively regulated immune cells. We also identified five feature genes (CD40LG, EP300, IL1B, GAPDH, and EGF) which were used to construct a nomogram. MR analysis indicated a causal link between elevated IL1B levels and an increased risk of DN. Clustering analysis divided DN samples into four groups, among which, C1 and CI were mainly highly expressed and most immune cells were up-regulated. C2 and CII were the opposite. Finally, we found significant differences in SDECG scores between C1 and C2, CI and CII, respectively.ConclusionTMJT may alleviate DN via core components (e.g. Denudatin B, hancinol, hirudinoidine A) targeting SDECGs (e.g. SRC, EGF, GAPDH), with the involvement of feature genes and modulation of immune and inflammation-related pathways. These findings have potential implications for clinical practice and future investigations.

Bone marrow mesenchymal stem cells (BMSCs) are capable of multidirectional differentiation, and engrafted BMSCs can be used to replace damaged chondrocytes for treatment of intervertebral disc disease. However, chondroblast differentiation of implanted BMSCs is inhibited by the anoxic environment of the articular cavity. Here, we found that leptin enhanced the transformation of BMSCs into chondrocytes under hypoxic conditions. BMSCs isolated from mice were cultured in medium supplemented with leptin under hypoxia. The expression of MFN1/2 and OPA1 were increased only in BMSCs cultured in an anoxic environment. In addition, in hypoxic environments cell energy metabolism relies on glycolysis regulated by leptin, rather than by mitochondrial oxidation. The expression of the de‐SUMOylation protease SENP1 was elevated, leading to SIRT3‐mediated activation of PGC‐1α; these processes were regulated by CREB phosphorylation, and promoted mitochondrial fusion and cell differentiation. The chondrogenic activity of BMSCs isolated from SIRT3‐knockout mice was lower than that of BMSCs isolated from wildtype mice. Implantation of SIRT3‐knockout murine‐derived BMSCs did not significantly improve the articular cartilage layer of the disc. In conclusion, the hypoxic microenvironment promoted BMSC differentiation into chondrocytes, whereas osteoblast differentiation was inhibited. SENP1 activated SIRT3 through the deSUMOylation of mitochondria and eliminated the antagonistic effect of SIRT3 acetylation on phosphorylation. When phosphorylation activity of CREB was increased, phosphorylated CREB is then transferred to the nucleus, affecting PGC‐1α. This promotes mitochondrial fusion and differentiation of BMSCs. Leptin not only maintains chondrogenic differentiation homeostasis of BMSCs, but also provides energy for differentiation of BMSCs under hypoxic conditions through glycolysis.

Objectives: This study investigated the antimicrobial effect and anti-inflammatory activities of PGLa-loaded TiO2 nanotube arrays (TiO2 NTs) in osteoblast-like MG-63 cells.Methods: The surface morphology and roughness of three titanium (Ti) substrates (Ti, TiO2 NTs, PGLa-loaded TiO2 NTs) were evaluated by scanning electron microscopy (SEM) and atomic force microscope (AFM). The wettability of three titanium substrates was evaluated by contact angle. Biocompatibility of PGLa-loaded TiO2 NTs were evaluated in MG-63 cells (cell adhesion, proliferation, cytoskeletal evaluation and alkaline phosphatase activity). Spread plate counting method was used to evaluate antibacterial abilities of the titanium substrates. The calcein AM/PI staining evaluated cell viability of MG-63 cells on the substrates with or without proinflammatory factors (TNF-α).Results: The average surface roughness of untreated Ti, TiO2 NTs, PGLa-loaded TiO2 NTs were found to be 135.8 ± 6.4 nm, 300.5 ± 10.5 nm, 348.9 ± 16.9 nm, respectively. The contact angle of the untreated Ti was 77.4° ± 6.6°. TiO2 NTs displayed excellent wettability which of contact angle was 12.1° ± 2.9°. The contact angle of the PGLa-loaded TiO2 NTs was 34.6° ± 4.9°. MG-63 cells on surface of PGLa-loaded TiO2 NTs showed better cell adhesion, proliferation and osteogenic activity. The antibacterial rate of PGLa-loaded TiO2 NTs group significantly increased (84.6% ± 5.5%, p < 0.05). The rate of dead cells on the surfaces of the PGLa-loaded TiO2 NTs with TNF-α decreased significantly (4.49% ± 0.02, p < 0.01).Conclusion: PGLa-loaded TiO2 NTs have multi-biofunctions including biocompatibility, antibacterial and anti-inflammatory properties.

Based on the transient-performance calculation model of a dual-spool mixed-flow turbofan engine, this article improves the dynamic algorithm of geometric adjustment mechanisms and establishes a transient-performance calculation model suitable for a three-stream adaptive cycle engine (three-stream ACE). Using this model, the transient characteristics of a three-stream ACE were analyzed. The results indicate that the delay in the area of the fan nozzle significantly reduces the surge margin of the front fan during deceleration, while the delay in the angle of the front-fan and aft-fan guide vanes significantly reduces the surge margin of the front fan during acceleration, therefore becoming a limitation of the transient performance of the engine. At the same time, to meet the demand for equal-thrust mode switching, this article also proposes a mode-switching control scheme that solves the problem of engine state oscillation during the mode-conversion process and achieves a smooth conversion with thrust fluctuations within 1%. The research results of this article can guide the optimization design of three-stream ACE transition-state control laws and the design of control system architecture, which has important engineering significance.

A sulfated polysaccharide (AG) was extracted and isolated from the sea cucumber H. fuscopunctata, consisting of GlcNAc, GalNAc, Gal, Fuc and lacking any uronic acid residues. Importantly, several chemical depolymerization methods were used to elucidate the structure of the AG through a bottom-up strategy. A highly sulfated galactose (oAG-1) and two disaccharides labeled with 2,5-anhydro-D-mannose (oAG-2, oAG-3) were obtained from the deaminative depolymerized product along with the structures of the disaccharide derivatives (oAG-4~oAG-6) identified from the free radical depolymerized product, suggesting that the repeating building blocks in a natural AG should comprise the disaccharide β-D-GalS-1,4-D-GlcNAc6S. The possible disaccharide side chains (bAG-1) were obtained with mild acid hydrolysis. Thus, a natural AG may consist of a keratan sulfate-like (KS-like) glycosaminoglycan with diverse modifications, including the sulfation types of the Gal residue and the possible disaccharide branches α-D-GalNAc4S6S-1,2-α/β-L-Fuc3S linked to the KS-like chain. Additionally, the anticoagulant activities of the AG and its depolymerized products (dAG1-9) were evaluated in vitro using normal human plasma. The AG could prolong activated partial thromboplastin time (APTT) in a dose-dependent manner, and the activity potency was positively related to the chain length. The AG and dAG1-dAG3 could prolong thrombin time (TT), while they had little effect on prothrombin time (PT). The results indicate that the AG could inhibit the intrinsic and common coagulation pathways.

Tumour hypoxia is an important factor in tumorigenesis and cancer therapy. Here, the authors present a micro oxygenation factory, capable of providing an oxygen supply through photosynthesis, and demonstrate its utility in cancer therapy.

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels and has become the third leading threat to human health after cancer and cardiovascular disease. Recent studies have shown that autophagy is closely associated with diabetes. Under normal physiological conditions, autophagy promotes cellular homeostasis, reduces damage to healthy tissues and has bidirectional effects on regulating diabetes. However, under pathological conditions, unregulated autophagy activation leads to cell death and may contribute to the progression of diabetes. Therefore, restoring normal autophagy may be a key strategy to treat diabetes. High-mobility group box 1 protein (HMGB1) is a chromatin protein that is mainly present in the nucleus and can be actively secreted or passively released from necrotic, apoptotic, and inflammatory cells. HMGB1 can induce autophagy by activating various pathways. Studies have shown that HMGB1 plays an important role in insulin resistance and diabetes. In this review, we will introduce the biological and structural characteristics of HMGB1 and summarize the existing knowledge on the relationship between HMGB1, autophagy, diabetes, and diabetic complications. We will also summarize potential therapeutic strategies that may be useful for the prevention and treatment of diabetes and its complications.

Salix babylonica L. is a species of willow tree that is widely cultivated worldwide as an ornamental plant, but its medicinal resources have not yet been reasonably developed or utilized. Herein, we extracted and purified the total flavonoids from willow buds (PTFW) for component analysis in order to evaluate their in vitro anti-tumor and hypoglycemic activities. Through Q-Orbitrap LC-MS/MS analysis, a total of 10 flavonoid compounds were identified (including flavones, flavan-3-ols, and flavonols). The inhibitory effects of PTFW on the proliferation of cervical cancer HeLa cells, colon cancer HT-29 cells, and breast cancer MCF7 cells were evaluated using an MTT assay. Moreover, the hypoglycemic activity of PTFW was determined by investigating the inhibitory effects of PTFW on α-amylase and α-glucosidase. The results indicated that PTFW significantly suppressed the proliferation of HeLa cells, HT-29 cells, and MCF7 cells, with IC50 values of 1.432, 0.3476, and 2.297 mg/mL, respectively. PTFW, at different concentrations, had certain inhibitory effects on α-amylase and α-glucosidase, with IC50 values of 2.94 mg/mL and 1.87 mg/mL, respectively. In conclusion, PTFW at different doses exhibits anti-proliferation effects on all three types of cancer cells, particularly on HT-29 cells, and also shows significant hypoglycemic effects. Willow buds have the potential to be used in functional food and pharmaceutical industries.

Marine crustaceans are severely threatened by environmental factors such as ocean acidification, but, despite the latter’s negative impact on growth, molting, and immunity, its effects on intestinal microflora remain poorly understood. This work studied the gut morphology and intestinal microflora of Exopalaemon carinicauda, grown in seawater of different pH levels: 8.1 (control group), 7.4 (AC74 group), and 7.0 (AC70 group). Ocean acidification was found to cause intestinal damage, while significantly altering the microflora’s composition. However, the α-diversity did not differ significantly between the groups. At the phylum level, the relative abundance of Proteobacteria decreased in the acidification groups, while at the genus level, the relative abundance of Sphingomonas decreased. Babeliales was a prominent discriminative biomarker in the AC74 group, with Actinobacteriota, Micrococcales, Beijerinckiaceae, Methylobacterium, and Flavobacteriales being the main ones in the AC70 group. The function prediction results also indicated an enrichment of pathways related to metabolism for the acidification groups. At the same time, those related to xenobiotics’ biodegradation and metabolism were inhibited in AC74 but enhanced in AC70. This is the first study examining the impact of ocean acidification on the intestinal microflora of crustaceans. The results are expected to provide a better understanding of the interactions between shrimp and their microflora in response to environmental stressors.

The phases of high-entropy alloys (HEAs) are closely related to their properties. However, phase prediction bears a significant challenge due to the extensive search space and complex formation mechanisms of HEAs. This study demonstrates a precise and timely methodology for predicting alloy phases. It first developed a machine learning classifier using 145 features and a dataset with 1009 samples to differentiate the four types of alloy phases. Feature selection was performed on the feature set using an Embedded algorithm and a genetic algorithm, resulting in the selection of nine features. The Light GBM algorithm was chosen to train the machine learning model. Finally, the implementation of oversampling and cost-sensitive methods enables LightGBM to tackle the problem of insufficient accuracy in BCC+FCC phase classification. The resulting accuracy of the alloy phase prediction model, evaluated through ten-fold cross-validation, stands at 0.9544.

There is a growing concern about human health of residents living in areas where mining and smelting occur. In order to understand the exposure to the potentially toxic elements (PTEs), we here identify and examine the cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn) in scalp hair of residents living in the mining area (Bayan Obo, n = 76), smelting area (Baotou, n = 57) and a reference area (Hohhot, n = 61). In total, 194 hair samples were collected from the volunteers (men = 87, women = 107) aged 5–77 years old in the three areas. Comparing median PTEs levels between the young and adults, Ni levels were significantly higher in adults living in the smelting area while Cr was highest in adults from the mining area, no significant difference was found for any of the elements in the reference area. From the linear regression model, no significant relationship between PTEs concentration, log10(PTEs), and age was found. The concentrations of Ni, Cd, and Pb in hair were significantly lower in the reference area when compared to both mining and smelting areas. In addition, Cu was significantly higher in the mining area when compared to the smelting area. Factor analysis (FA) indicated that men and women from the smelting area (Baotou) and mining area (Bayan Obo), respectively, had different underlying communality of log10(PTEs), suggesting different sources of these PTEs. Multiple factor analysis quantilized the importance of gender and location when combined with PTEs levels in human hair. The results of this study indicate that people living in mining and/or smelting areas have significantly higher PTEs (Cu, Ni, Cd, and Pb) hair levels compared to reference areas, which may cause adverse health effects. Remediation should therefore be implemented to improve the health of local residents in the mining and smelting areas.

Winterberry (Ilex verticillata (L.) A. Gray) is a recently introduced ornamental tree species in China that has not been closely investigated for its drought resistance. In this study, we used two-year-old cuttings from I. verticillata (L.) A. Gray and two representative varieties derived from it, I. verticillata ‘Oosterwijk’ and I. verticillata ‘Jim Dandy’, as materials to investigate how this plant responds to drought stress and whether exogenous spermidine (SPD) can alleviate the negative effects caused by drought stress. The results showed that as the degree of drought stress increased, the leaves of winterberry seedlings became chlorotic, and their edges became dry. Similarly, the relative water content, specific leaf weight, chlorophyll content, leaf nitrogen content, net photosynthetic rate, stomatal conductance and transpiration rate were significantly reduced, whereas the content of malondialdehyde continuously increased with the degree of drought stress. The activities of superoxide dismutase, peroxidase, and catalase increased under moderate drought stress and then decreased under severe drought stress. The levels of soluble sugar and abscisic acid continued to increase, while those of auxin and gibberellic acid decreased. When compared with individual drought stress, an increase in the amount of external SPD clearly alleviated the effect of drought stress on winterberry seedlings. The combined phenotypes and physiological indices of the winterberry leaves under drought stress conditions revealed that the drought resistance of the native species was significantly higher than its two varieties. This finding serves as an important theoretical foundation for the popularization and application of I. verticillata (L.) A. Gray and the two varieties.

A synthetic aperture radar (SAR) has the capability to observe ocean surface winds with a high spatial resolution, even under extreme conditions. The purpose of this work was to develop a new method for wind speed retrieval with the combination of SAR dual-polarized signals. In this study, we collected 28 tropical cyclone imageries observed using the Sentinel-1 dual-polarization mode. These imageries were collocated with radiometer wind speed measurements and reanalysis of wind vector products. In the new method, the wind speed was set as the output. VV-polarized (vertical transmitting–vertical receiving polarized) normalized radar cross section (NRCS), incident angle, VH-polarized (vertical transmitting–horizontal receiving polarized) NRCS, and wind direction were set as the inputs. Based on different output combinations, wind retrieval models were developed with multiple linear regression (MLR). According to the validation and comparison, the proposed models performed better than the traditional piecewise VH-polarization geophysical model functions (GMFs). The impact of thermal noise on the retrieval of low wind speeds (

Abstract Background The novel coronavirus disease 2019 (COVID-19) spreads rapidly among people and causes a pandemic. It is of great clinical significance to identify COVID-19 patients with high risk of death. Methods A total of 2169 adult COVID-19 patients were enrolled from Wuhan, China, from February 10th to April 15th, 2020. Difference analyses of medical records were performed between severe and non-severe groups, as well as between survivors and non-survivors. In addition, we developed a decision tree model to predict death outcome in severe patients. Results Of the 2169 COVID-19 patients, the median age was 61 years and male patients accounted for 48%. A total of 646 patients were diagnosed as severe illness, and 75 patients died. An older median age and a higher proportion of male patients were found in severe group or non-survivors compared to their counterparts. Significant differences in clinical characteristics and laboratory examinations were found between severe and non-severe groups, as well as between survivors and non-survivors. A decision tree, including three biomarkers, neutrophil-to-lymphocyte ratio, C-reactive protein and lactic dehydrogenase, was developed to predict death outcome in severe patients. This model performed well both in training and test datasets. The accuracy of this model were 0.98 in both datasets. Conclusion We performed a comprehensive analysis of COVID-19 patients from the outbreak in Wuhan, China, and proposed a simple and clinically operable decision tree to help clinicians rapidly identify COVID-19 patients at high risk of death, to whom priority treatment and intensive care should be given.

In order to achieve specific enrichment of target glycoproteins, double molecular recognition ligands functionalized surface solid-phase adsorption materials that can play a role under physiological pH conditions, have obvious advantages. In this work, a novel strategy was proposed for the synthesis of double molecular recognition functionalized magnetic graphene nanocomposites. Horseradish peroxidase was selected as the template proteins for evaluating the selectivity and binding capacity of the adsorption material. The bimolecular recognition was realized by introducing 4-carboxyphenylboronic acid (CPBA) and Suberic acid bis(3-sulfo-N-hydroxysuccinimide ester) sodium salt (Sulfo-DSS) as functional ligands. The abundant oxygen-containing groups in the complex (abbreviated as CPDS/CMCS/Fe3O4-rGO) were beneficial to reduce the pKa value of CPBA. Finally, CPDS/CMCS/Fe3O4-rGO realized the selective adsorption of glycoproteins in the neutral environment (pH 7.0). The resultant CPDS/CMCS/Fe3O4-rGO exhibited a high adsorption capacity of 1280.6 mg g−1 and excellent specificity toward glycoproteins compared to nonglycoproteins. Moreover, CPDS/CMCS/Fe3O4-rGO with strong magnetic responses (59.29 emu·g−1), could achieve rapid aggregation and separation under the external magnetic field. The results demonstrated the great potential of CPDS/CMCS/Fe3O4-rGO composites to separate and enrich glycoproteins from the complex biological sample for the glycoproteins analysis.

Purpose: This study aimed to examine the effect of radiation esophagitis (RE) and the dynamics of RE on subsequent survival in non-small cell lung cancer (NSCLC) patients who underwent radiotherapy. Experimental Design: Patients with NSCLC treated with fractionated thoracic radiotherapy enrolled in prospective trials were eligible. RE was graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 per protocol requirement weekly during-RT and 1 month after RT. This study applied conditional survival assessment which has advantage over traditional survival analysis as it assesses the survival from the event instead of from the baseline. P-value less than 0.05 was considered to be significant. The primary endpoint is overall survival. Results: A total of 177 patients were eligible, with a median follow-up of 5 years. The presence of RE, the maximum RE grade, the evolution of RE and the onset timing of RE events were all correlated with subsequent survival. At all conditional time points, patients first presented with RE grade1 (initial RE1) had significant inferior subsequent survival (multivariable HRs median: 1.63, all P-values

We demonstrate the construction of the optical system in the atomic clock-beyond atomic fountain based on 87Rb atom. The optical system includes a high-stability laser system and an optical lattice. The high-stability laser system with the new scheme of frequency locking and shift is introduced in detail, which is an important laser source for laser cooling. The optimized frequency and intensity stability are achieved to 4 × 10–14τ−1/2 (τ is the averaging time) and 4 × 10–5τ−1/2, respectively, which are highly stable. On the basis of the conventional atomic fountain clock, the optical lattice is specially investigated along the direction of gravity and its characteristics are studied systematically. For the optimized and novel exploration, we predict the achievable stability of 3.6×10−14τ−1/2 and it has the potential to be improved to 3.6×10−15τ−1/2. The realizability of the construction due to the stabilized laser and optical lattice makes the beyond fountain promising candidate for the next-generation high performance microwave atomic clock.

Abstract Despite the clinical potential, photodynamic therapy (PDT) relying on singlet oxygen (1O2) generation is severely limited by tumor hypoxia and endosomal entrapment. Herein, a proton‐driven transformable 1O2‐nanotrap (ANBDP NPs) with endosomal escape capability is presented to improve hypoxic tumor PDT. In the acidic endosomal environment, the protonated 1O2‐nanotrap ruptures endosomal membranes via a “proton‐sponge” like effect and undergoes a drastic morphology‐and‐size change from nanocubes (≈94.1 nm in length) to nanospheres (≈12.3 nm in diameter). Simultaneously, anthracenyl boron dipyrromethene‐derived photosensitizer (ANBDP) in nanospheres transforms to its protonated form (ANBDPH) and switches off its charge‐transfer state to achieve amplified 1O2 photogeneration capability. Upon 730 nm photoirradiation, ANBDPH prominently produces 1O2 and traps generated‐1O2 in the anthracene group to form endoperoxide (ANOBDPH). Benefitting from the hypoxia‐tolerant 1O2‐release property of ANOBDPH in the dark, the 1O2‐nanotrap brings about sustained therapeutic effect without further continuous irradiation, thereby achieving remarkable antitumor performance.

Abstract Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.

The high undercooling of binary Co-4.54%Sn alloy has a significant influence on its microstructural characteristics and physical properties. Here, we report that the dendritic growth and physical properties of broad-temperature-range Co-4.54%Sn alloy remarkably depends on the undercooling during the rapid solidification. The maximum undercooling attains 208 K at molten state, and the dendritic growth velocity is quite sluggish in highly undercooled liquid Co-4.54%Sn alloy because it has a broad solidification range of 375 K (0.21 TL); the maximum value is only 0.95 m/s at the undercooling of 175 K, which then decreases with undercooling. The microstructure refines visibly and the volume fraction of the interdendritic βCo3Sn2 phase obviously decreases with undercooling. The microhardness and electrical resistivity increase with undercooling owing to the enhancement of solute content of the primary αCo phase and refinement of the microstructure where the increased crystal boundary hinders the electronic transmission. Meanwhile, the saturation magnetization also reduces with undercooling due to the crystal particle and boundary increasing significantly, and the dendritic growth velocity and solute content increase in the primary αCo phase under rapid solidification.

Sea surface current is a research hotspot in oceanography. Space-borne along-track interferometric synthetic aperture radar (along-track InSAR, ATI) is a promising sensor for measuring high-resolution sea surface current field, and there is no operational system in orbit yet. To support future space-borne ATI systems, based on the ATI experimental mode of the Gaofen-3 (GF-3) satellite, the first sea surface current observing experiment was conducted in the Jiaozhou Gulf in China, in 2019. Meanwhile, SAR observations and in situ instrument measurements of the current are obtained in the experiments. The data is first preprocessed by a processor specially developed for the GF-3 ATI data. Then, the current is extracted based on the M4S mode. The retrieved current of the Jiaozhou Gulf is compared with ground-based high frequency surface wave radar data. The results show that the root mean square error of the surface current observed by the GF-3 satellite is less than 0.2 m/s.

In this study, an automatic test platform suitable for steering gears was established, which can test four sets of rudder systems separately. In addition, we propose an anomaly detection method based on deep learning technology to complete the automated multi-fault classification of the steering gear test. This paper combines the particle swarm optimization algorithm and the grey wolf optimization algorithm to optimize the convolutional neural networks (HPSOGWO-CNN). The proposed HPSOGWO-CNN model is constructed in two stages to realize the efficient and high-accuracy anomaly detection of the rudder system. In the first stage, through 10-fold cross validation, the optimal number of search agents of the HPSOGWO algorithm is obtained, and the performance is compared with GWO and PSO algorithms respectively. The results demonstrate that HPSOGWO algorithm is an excellent technique for automatic selection of hyper-parameters. In the second stage, the designed HPSOGWO algorithm is used to fine-tune the hyper-parameters of CNN, and a highly matched model for anomaly detection of rudder system test parameters was finally obtained. The experimental results show that the accuracy of this method is 99.846%, the precision is 99.748%, the recall is 99.498%, the F-score is 99.618%, and Kappa reaches 0.99565. CNN-based hybrid optimization for anomaly detection of rudder system, is advanced in comparison to KNN, SVM, BP, CNN, PSO-CNN, GWO-CNN, MGWO-CNN, WdGWO-CNN, RW-GWO-CNN models, in terms of accuracy, precision, recall, F-score, and kappa, respectively. Moreover, it is not affected by the imbalance samples, and can achieve accurate classification for small training samples.

Introduction When COVID-19 patients develop hypoxaemic respiratory failure, they often undergo early intubation. Such a potentially aerosol-generating approach places caregivers at increased risk of contracting COVID-19. This protocol aims to evaluate the clinical efficacy and safety of a high-flow nasal cannula (HFNC) for the treatment of COVID-19 patients with acute hypoxaemic respiratory failure.Methods and analysis We intend to search MEDLINE, Embase, Web of Science and Cochrane Library to identify all randomised controlled trials (RCTs) on the use of HFNC in COVID-19 patients with acute respiratory failure. We will screen the RCTs against eligibility criteria for inclusion in our review. Two reviewers will independently undertake RCT selection, data extraction and risk of bias assessment. Primary outcome will be the rate of intubation, and secondary outcomes will be intensive care unit (ICU)/hospital mortality, ICU/hospital length of stay and risks of infection transmission. We will conduct meta-analyses to determine the risk ratio for dichotomous data and the mean difference (MD) or standardised MD for continuous data. Subgroup analyses will be performed based on the different quality of studies, different levels of disease severity, and the age and sex of participants.Ethics and dissemination Ethical approval is not required for this study considering this is a systematic review protocol that uses only published data. The findings of this study will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration number CRD42021236519.

BackgroundLymphopenia is a known significant factor for treatment outcome in cancer patients, with underlying risk factor poorly understood in breast cancer. We hypothesize that the effective dose to the circulating immune cells (EDIC) which was related with lymphopenia in lung cancer will also have significant effect for radiation induced lymphopenia (RIL) in patients with breast cancer.Material and MethodsPatients treated with adjuvant radiotherapy (RT) and with complete blood tests within one week from RT end/start (post/preRT) were eligible in this study. Radiation dosimetric factors were collected retrospectively, and EDIC for each patient was calculated based on the doses to lung, heart and total body according to the model description, as previously reported. RIL was defined by the CTCAE5.0 based on postRT peripheral lymphocyte count (PLC). Linear regression was first used to test the correlation between EDIC with post/preRT PLC ratio and postRT PLC, using all these as continuous variables. Normal tissue complication probability (NTCP) was used to develop models that predict the CTCAE graded RIL from EDIC.ResultsA total of 735 patients were eligible. The mean post/preRT PLC ratio was 0.66 (95% CI: 0.64-0.68) and mean EDIC of breast cancer was 1.70Gy (95% CI: 1.64-1.75). Both post/preRT PLC ratio and postRT PLC were significantly correlated with EDIC (P

Abstract Background A successful osseointegration of total hip arthroplasty (THA) relies on the interplay of implant surface and bone marrow microenvironment. This study was undertaken to investigate the impact of perioperative biochemical molecules (Ca2+, Mg2+, Zn2+, VD, PTH) on the bone marrow osteogenetic factors (BMP2, BMP7, Stro-1+ cells) in the metaphyseal region of the femoral head, and further on the bone mineral density (BMD) of Gruen R3. Methods Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 51 patients with THA. Flow cytometry was used to measure the Stro-1+ expressing cells. ELISA was used to measure the concentrations of bone morphologic proteins (BMP2 and BMP7) and the content of TRACP5b in serum. TRAP staining was used to detect the osteoclast activity in the hip joint. The perioperative concentrations of the biochemical molecules above were measured by radioimmunoassay. The BMD of Gruen zone R3 was examined at 6 months after THA, using dual-energy X-ray absorptiometry (DEXA). Results Our data demonstrated that the concentration of Ca2+ was positively correlated with BMP7 expression, and with the postoperative BMD of Gruen zone R3. However, the concentration of Mg2+ had little impact on the R3 BMD, although it was negatively correlated with the expression of BMP7. Osteoclast activity in hip joint tissue of patients with femoral neck fractures was increased. Compared with the patients before THA, the levels of TRACP5b in serum of patients after THA were decreased. The data also suggested that the other biochemical molecules, such as Zn2+, VD, and PTH, were not significantly correlated with any bone marrow osteogenetic factors (BMP2, BMP7, Stro-1+ cells). The postoperative R3 BMD of patients of different gender and age had no significant difference. Conclusions These results indicate the local concentration of Ca2+ may be an indicator for the prognosis of THA patients.

It is unclear whether 2D metal dichalcogenides (TMD) alone can cause ferroptotic cell death. Here, the authors show TMD nanosheets induced ferroptosis in mammalian cell lines and in a mouse model after aspiration of TMD materials into lungs, causing ferroptotic cell death.

Abstract Background Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice. Methods Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA. Results The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice. Conclusions SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.