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Abstract Ultraflat metal foils are essential for semiconductor nanoelectronics applications and nanomaterial epitaxial growth. Numerous efforts have been devoted to metal surface engineering studies in the past decades. However, various challenges persist, including size limitations, polishing non-uniformities, and undesired contaminants. Thus, further exploration of advanced metal surface treatment techniques is essential. Here, we report a physical strategy that utilizes surface acoustic wave assisted annealing to flatten metal foils by eliminating the surface steps, eventually transforming commercial rough metal foils into ultraflat substrates. Large-area, high-quality, smooth 2D materials, including graphene and hexagonal boron nitride (hBN), were successfully grown on the resulting flat metal substrates. Further investigation into the oxidation of 2D-material-coated metal foils, both rough and flat, revealed that the hBN-coated flat metal foil exhibits enhanced anti-corrosion properties. Molecular dynamics simulations and density functional theory validate our experimental observations.

Abstract Objective The objective of the case report is to analyze the clinical manifestations and imaging features of gouty long head of biceps tendinitis, and to summarize the methods and effects of shoulder arthroscopic surgery. Clinical presentation and intervention The clinical data of a 39-year-old Han Chinese female with gouty long head of the biceps tendinitis was retrospectively analyzed, and the clinical manifestations, imaging features, and diagnosis and treatment were analyzed. The patient presented with pain and limited movement of right shoulder joint. Computed tomography showed irregular high-density shadows above the glenoid and adjacent to the coracoid process of the right shoulder. Magnetic resonance imaging revealed superior labrum anterior and posterior injury with edema in the upper recess and axillary sac. After arthroscopic surgery, the “tofu residue” tissue of the long head of the biceps was removed, and the postoperative pathological examination proved that it was gout stone. Conclusion Gouty long head of the biceps tendinitis is a rare disease. Arthroscopic surgery can probe the structural lesions of shoulder cavity in all aspects, improve the surgical accuracy, and reduce the trauma.

Abstract Hexagonal boron nitride (hBN), as one of the few two-dimensional insulators, holds strategic importance for advancing post-silicon electronic devices and circuits. Achieving wafer-scale, high-quality monolayer hBN is essential for its integration into the semiconductor industry. However, the physical mechanisms behind the chemical vapor deposition (CVD) synthesis of hBN are not yet well understood. Investigating morphology engineering is critical for developing scalable synthetic techniques for the large-scale production of high-quality hBN. In this study, we explored the underlying mechanisms of the CVD growth process of hBN and found that the involvement of a small amount of oxygen effectively modulates the shape of the single-crystal hBN islands. By tuning the oxygen content in the CVD system, we synthesized well-aligned hexagonal hBN islands and achieved a continuous, high-quality single-crystal monolayer hBN film through the merging of these hexagonal islands on conventional single-crystal metal-foil substrates. Density functional theory was used to study the edges of hBN monolayers grown in an oxygen-assisted environment, providing insights into the formation mechanism. This study opens new pathways for controlling the island shape of 2D materials and establishes a foundation for the industrial-scale production of high-quality, large-area, single-crystal hBN.

Abstract. Background:. Early detection of esophageal squamous cell carcinoma (ESCC) can considerably improve the prognosis of patients. Aberrant cell-free DNA (cfDNA) methylation signatures are a promising tool for detecting ESCC. However, available markers based on cell-free DNA methylation are still inadequate. This study aimed to identify ESCC-specific cfDNA methylation markers and evaluate the diagnostic performance in the early detection of ESCC. Methods:. We performed whole-genome bisulfite sequencing (WGBS) for 24 ESCC tissues and their normal adjacent tissues. Based on the WGBS data, we identified 21,469,837 eligible CpG sites (CpGs). By integrating several methylation datasets, we identified several promising ESCC-specific cell-free DNA methylation markers. Finally, we developed a dual-marker panel based on methylated KCNA3 and OTOP2, and then, we evaluated its performance in our training and validation cohorts. Results:. The ESCC diagnostic model constructed based on KCNA3 and OTOP2 had an AUC of 0.91 [95% CI: 0.85–0.95], and an optimal sensitivity and specificity of 84.91% and 94.32%, respectively, in the training cohort. In the independent validation cohort, the AUC was 0.88 [95% CI: 0.83–0.92], along with an optimal sensitivity of 81.5% and specificity of 92.9%. The model sensitivity for stage I–II ESCC was 78.4%, which was slightly lower than the sensitivity of the model (85.7%) for stage III–IV ESCC. Conclusion:. The dual-target panel based on cfDNA showed excellent performance for detecting ESCC and might be an alternative strategy for screening ESCC.

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is an important interferon-stimulated and apoptotic gene. However, how XAF1 regulates bone formation and remodeling is unknown. Methods: We generate global and chimeric Xaf1 knockout mouse models and utilize these models to explore the function and mechanism of XAF1 in regulating bone formation and remodeling in vivo and in vitro. Results: We show that XAF1 depletion enhances osteoclast generation in vitro. XAF1 knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, XAF1 deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7. Conclusions: Our data illustrates an essential role of XAF1 in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Offshore wind power is a crucial clean energy source for coastal countries and advances blue economies. Accurate spatial mapping of offshore wind turbines supports energy assessment and the sustainable development of marine resources. Offshore wind power has developed rapidly in China, but the spatiotemporal distribution characteristics of offshore wind turbines and farms remain poorly understood. Extracting nearshore small targets from Sentinel-1 synthetic aperture radar images remain challenging due to noise from the rough sea surface background and the diverse substrate types in offshore wind turbine (OWT) distributions. Here, to address these issues, we first created a dataset of China’s offshore wind turbines (COWTs) that contained typical substrate types (e.g. seawater and tidal flats). Then, a deep learning model integrating an attention mechanism and receptive fields was used to accurately detect COWTs. The well-trained model was used to detect the changes in COWTs from 2015 to 2022. Our model detected an increase in the number of offshore wind farms in China from 7 to 114 (clusters counted as an offshore wind farm), while COWTs increased from 305 to 6451 from 2015 to 2022. The Taiwan Strait exhibited the highest wind speeds, yet the Jiangsu and Guangdong regions had the most installed turbines. Over 90% of COWTs were located in areas with offshore wind energy resources less than 500 W/m3, indicating a mismatch between COWT installation and wind resource distribution. This study demonstrated temporal and geographical generalizability, which is promising for global wind power detection. Our analysis of spatiotemporal variation in COWTs facilitates informed decision-making for future field establishment and sustainable marine planning.

Abstract The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don’t match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.

Purpose: To evaluate synthetic magnetic resonance imaging (SyMRI) and iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) imaging for a comprehensive evaluation of rotator cuff injuries (RCI). Methods: Ninety-seven patients with RCI were classified into four groups based on the arthroscopic results: (grade II), partial tear (grade III), complete tear (grade IV), and controls (grade I). T1 (Transverse Relaxation Time 1), T2 (Transverse Relaxation Time 2), proton density (PD), and fat fraction (FF) were evaluated using SyMRI and IDEAL-IQ. Measurement reliability was assessed using intraclass correlation coefficients (ICC). The diagnostic potential for grading RCI was evaluated using ordinal regression and ROC analyses. Results: A high measurement reliability (ICC > 0.7) was observed across subregions. T1 and T2 significantly varied across grades, particularly T2 in the lateral subregion between grades III and IV (P < 0.001) and the central subregion between grades II and III (P < 0.001). ROC analyses yielded valuable diagnostic accuracy, including T2 in the lateral subregion with an AUC of 0.891, distinguishing grade I from grade IV. Positive correlations were found between T2 values in specific shoulder subregions and injury grade (r = 0.615 for lateral, r = 0.542 for medial, both P < 0.001). In grade IV, FF was notably increased in the supraspinatus, infraspinatus, and subscapularis muscles compared with grades I-III. There were no significant FF variations in the teres minor muscle among grades. Conclusions: Quantitative MRI parameters from SyMRI and IDEAL-IQ, especially T2 and FF, may classify and assess RCI severity. The results could help improve the accuracy of diagnosing different grades of RCI, offering clinicians additional tools for improving patient outcomes through personalized medicine.

Salt marshes are pivotal in the global carbon cycle, serving as significant contributors to the blue carbon sink. Accurately estimating carbon stock in salt marshes relies on precise vegetation classification. Here, we developed the Salt Marsh Vegetation Classification Network (SVCN), a deep learning algorithm designed to classify three primary vegetation canopies (S. alterniflora, P. australis, and S. mariqueter) spanning from 2016 to 2023 over the Yangtze River estuary, China. The SVCN was initially trained using 412 vegetation samples and Sentinel-1 Synthetic Aperture Radar (SAR) data in 2018. Additionally, we trained three traditional machine learning models – Classification and Regression Trees, Random Forests, and K-Nearest Neighbors – to facilitate a comparative analysis of model performance. Leveraging the classified vegetation outcomes, we conducted salt marsh carbon stock estimations using the InVEST model. The results showed that the SVCN model outperformed the other three models, achieving an overall accuracy of 0.97. Salt marsh carbon stocks in the Yangtze River estuary exhibited an overall increasing trend from 2016 to 2023, with an average annual increase of 3.13 ×103Mg⋅year−1. However, there was a notable decrease of 10.36% in 2017, primarily attributed to reductions in the area covered by S. alterniflora and P. australis, which decreased by 11.18% and 10.11%, respectively. These findings highlight the potential of deep learning models and the incorporation of salt marshes in carbon stock estimates to enhance accuracy.

Summary: Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.

The anomaly detection in data links aims to identify the state of the link during data transmission, which is a critical task for ensuring information transmission security. Most anomaly detection methods focus solely on individual link characteristics, disregarding the inter-link structural information, thus hindering effective generalization to graph-structured data. In this study, we introduce a Graph Learning-based Data Link Anomaly Detection model (GLDAE) that considers both the link features and the communication network structure. Specifically, GLDAE comprises a graph enhancement module, a link feature autoencoder, a structure autoencoder, and a discriminator, enabling simultaneous learning of edge features and the latent representation of the graph structure. Moreover, to enhance the model’s generalization capability, we employ contrastive learning between the original graph and its enhanced version. Additionally, to achieve joint learning of edge features and graph structure, we integrate edge feature embeddings and structure embeddings as inputs to the decoder. Finally, utilizing the well-trained encoder to encode link features and derive a new feature representation, we feed it into an MLP classifier to determine the link’s status. Experimental evaluations were conducted on four authentic datasets (NF-UNSW-NB15, NF-UNSW-NB15-v2, NF-ToN-IoT, NF-ToN-IoT-v2), comparing our model against state-of-the-art baseline models, showcasing the substantial potential of our approach.

Abstract Roundabout guidance receptor 2 (Robo2) is closely related to malignant tumors such as pancreatic cancer and liver fibrosis, but there is no relevant research on the role of Robo2 in HCC. The study will further explore the function and mechanism of Robo2 and its downstream target genes in HCC. Firstly, Robo2 protein levels in human HCC tissues and paired adjacent normal liver tissues were detected. Then we established HepG2 and Huh7 hepatoma cell lines with knock-down Robo2 by transfection with lentiviral vectors, and examined the occurrence of EMT, proliferation and apoptosis abilities in HCC cells by western blot, flow cytometry, wound healing assay and TUNEL staining. Then we verified the interaction between Robo2 and its target gene by Co-IP and immunofluorescence co-staining, and further explored the mechanism of Robo2 and YB-1 by rescue study. The protein expression level of Robo2 in HCC was considerably higher than that in the normal liver tissues. After successfully constructing hepatoma cells with knock-down Robo2, it was confirmed that down-regulated Robo2 suppressed EMT and proliferation of hepatoma cells, and accelerated the cell apoptosis. High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC.

Co-firing NH3 with conventional hydrocarbon fuels is an important approach for reducing CO2 emissions in existing combustion systems. Besides CO2, the blending of NH3 would also notably affect soot formation and its oxidation behaviors. In the present study, we focus on the effects of NH3 on the nanostructure and oxidation characteristics of soot produced in diffusion flames of n-heptane/toluene mixtures. Two configurations of laminar co-flow diffusion flame, including both normal and inverse diffusion flames (NDF and IDFs), were used for investigation. High-resolution transmission electron microscopy (HRTEM), Raman spectroscopy (Raman), and Thermogravimetric analysis (TGA) were employed for soot characterization. The HRTEM and Raman spectra showed that with the increase of NH3 blending ratio, the fringe length (La) and the degree of graphitization decreased while the microcrystal tortuosity (Tf) increased. The results are in consistent with TGA analysis which suggests the promoting effects of NH3 on the soot oxidation reactivity. Difference between NDF and IDF with respect to the soot nanostructure and oxidation activity were discussed. It is our hope that the present results could deepen our understanding on the effects of NH3 on soot nanostructure and oxidation behavior and benefit the design of particulate filters for combustion devices fueled with hydrocarbon/NH3 mixtures.

Fabric defect detection is a pivotal step in quality control in the textile manufacturing industry. Due to the diversity and complexity of defects, manual visual inspection and traditional fabric defect detection methods suffer from low efficiency and accuracy. To address the issues, a saliency model capable of mining local and global information from CNN and vision Transformer is proposed for fabric defect detection in this paper, named ACCTNet. Specifically, to enhance the feature interaction of different scales, an adjacent context coordination module composed of one local branch and two adjacent branches is proposed. Meanwhile, a contrast-aggregation module is proposed to highlight the defects from low contrast background using pooling and subtraction operations. In addition, vision Transformer is adopted to capture global contextual information with long-range dependencies, which can guide local information to further refines the defect detection results. Experimental results demonstrate that the proposed method can accurately inspect the defects from plain and patterned fabric surfaces, achieving E m values of 78.49% and 97.19% respectively, which significantly surpasses the existing state-of-the-art fabric defect detection methods.

Synthetic single-stranded oligonucleotides play crucial roles in DNA amplification reactions for various applications, such as serving as primers, enabling magnetic separation, and generating dsDNA for subsequent digestion. Typically, these oligos are added in excess to ensure rapid binding to their intended targets. However, while performing rolling circle amplification (RCA) using phi29 DNA polymerase, we observed a decrease in amplification efficiency when oligos were present in the reaction. This phenomenon was consistently observed in two separate laboratories, prompting this study to delve into the root causes responsible for the decline in RCA efficiency. The lowered efficiency was consistent regardless of the manufacturer or any mutations in the phi29 polymerase. We identified several variables that influenced RCA efficiency, mainly the length of the oligos used and the presence of modifications, particularly those obstructing 3’ end digestion. This strongly suggests that the exonuclease domain of phi29 DNA polymerase is responsible for the competition-based inhibition. Our investigation shows that even picomole quantities of oligos can significantly reduce total DNA production during the phi29 DNA polymerase-mediated amplification process. Conversely, the addition of oligos to the reaction did not impede the efficiency of Bst 3.0 polymerase, likely due to the lack of an exonuclease domain of said polymerase. While increasing the quantity of phi29 DNA polymerase in the reaction partially alleviated the adverse effects of excess oligos, we believe it is crucial to carefully optimize the oligo quantities to achieve maximum amplification of the desired targets.

ObjectivesDomain adaptive technology is widely used in the bearing fault diagnosis of variable operating conditions. However, most domain adaptive technology only focuses on the global domain distribution and ignores the subdomain distribution, and the domain-invariant feature quality is easily affected by noise, leading to a significant decrease in diagnostic accuracy under varying operation conditions. Therefore, a fault diagnosis method based on a self-attention subdomain adaptive adversarial network (SASAAN) is proposed.MethodsFirst, a convolutional block attention module (CBAM) is utilized to extract the fault-related domain-invariant features in the vibration signals of the source and target domains. The adversarial network and subdomain adaptive module are then combined to reduce differences in the global and local domain edge distributions of different operating condition data, thereby improving the transferability of the data. The loss function is optimized by back propagation using the Adam optimizer to improve the diagnostic performance of the model, and the hyperparameter tuning of the model is also performed. Finally，the diagnostic results on the target domain test set are output by the failure classifier, and the Ottawa bearing data set is used to validate the effectiveness of the proposed method. ,ResultsThe results show that the fault diagnosis accuracy of the proposed method is higher than 96% under the condition of strong noise and varying operation conditions, which is obviously better than other methods.ConclusionThe results of this study can provide valuable references for the fault diagnosis of rolling bearings under varying operation conditions.

Abstract Improving diabetes self-management (DSM) is facing real-world challenges among people with type 2 diabetes mellitus (T2DM) who have a low education level in resource-limited areas. This study aimed to investigate whether diabetes knowledge could predict glycemic levels in people with T2DM in rural China. This analytical cross-sectional study recruited 321 people with T2DM from eight villages by purposive sampling at baseline. After 10 months, 206 patients completed the follow-up survey and HbA1c tests, with a response rate of 64.17% (206/321). Multiple regression analysis was employed to explore the correlation between diabetes knowledge and HbA1c levels. The patient's diabetes knowledge was significantly negatively correlated with HbA1c levels before and after controlling for covariates in both hierarchical multiple regression and multiple logistic regression (p

As the application of renewable energy becomes increasingly extensive, heat pump technology with renewable energy as the heat source is achieving good results. Air-source heat pumps and water-source heat pumps can be widely used in cold areas. In this work, an integrated combined storage and supply system of an air-source heat pump and a water-source heat pump was studied, and the heating characteristics of the system at the beginning, middle, and end of the heating period were examined. It was found that, when the outdoor temperature of the system was very low, the efficiency of the combined storage and supply system reached the highest value of 2.57 when the source-side water tank was kept at 30 °C, and the performance of the combined storage and supply system was better than that of the air-source heat pump and the water-source heat pump in cold regions. Meanwhile, the independent storage of the air-source heat pump and the combined storage and supply system can be used for heating at the beginning and end of the heating period.

The micropore structure of porous media (such as natural rocks and man-made materials) is very complex and has strong micro heterogeneity, and pore structure is a critical parameter to estimate the rock quality. However, the pore structure characterization of rocks under load is not studied well. In this paper, sandstone specimens were preloaded to six different stress levels, and then the pore structure of rock was characterized by SEM and NMR, respectively. The results show the following: (1) The damage in sandstone increases with predefined stress, and the rate significantly increases over 0.8 uniaxial compressive strength (UCS). (2) There is a critical value in the process of rock damage (0.8 UCS), and when it is less than this critical value, the microstructure in the rock is mainly composed of pores and micro-cracks, and the length is generally less than 5 μm; when it exceeds the critical value, there are obvious cracks or even groups of cracks inside the rock. (3) The changes in porosity can be divided into three stages, showing a “√” shape tendency. (4) The pore structure can be visually presented using NMR and SEM, and the distribution mode of the pores changes from separated points to concentrated patches to finally interconnected networks of pores with an increase in the predefined stress. Overall, NMR provides a new method for characterizing rock damage and studying rock microstructure.

Abstract Background In recent years, neoadjuvant immunotherapy with chemotherapy has shown increasing promise for locally advanced non-small cell lung cancer (NSCLC). However, to establish its clinical efficacy and safety, it is imperative to amass more real-world clinical data. This retrospective study aims to assess the safety and effectiveness of combing sintilimab, a PD-1 inhibitor, with chemotherapy as a neoadjuvant treatment modality in patients diagnosed with potentially resectable NSCLC. Methods We retrospectively reviewed patients with stage II-III NSCLC receiving neoadjuvant chemoimmunotherapy in Sichuan Cancer Hospital between February 2021 and February 2023. Sintilimab injection (intravenously,200 mg, iv, d1, q3w) and platinum-based chemotherapy were administered intravenously every 3 weeks, with radical lung cancer resection planned approximately 4–11 weeks after the last dose. The primary endpoint of the study was pathologic complete response (pCR). The secondary endpoints were objective response rate (ORR), and safety. Result Thirteen patients were enrolled, they were mostly diagnosed with stage III NSCLC (IIB 15.4% IIIA 38.5%; IIIB 46.2%). Most of them had pathologically confirmed squamous cell carcinoma (69.2%). All patients received sintilimab combined with platinum-based chemotherapy for 2 to 4 cycles. Notably, none of the patients necessitated a reduction in initial dosages or treatment postponement due to intolerable adverse events. Then, all of them underwent surgical operation. Impressively, nine patients (69.2%) achieved a pathologic complete response. The objective response rate (ORR) stood at 46.15%. Nine patients experienced neoadjuvant treatment-related adverse events (TRAEs), with only one patient (7.6%) encountering a grade 4 neoadjuvant TRAE. Conclusion Therefore, the current study suggested that neoadjuvant sintilimab plus platinum-based chemotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

ABSTRACT Bone homeostasis, the equilibrium between bone resorption and formation, is essential for maintaining healthy bone tissue in adult humans. Disruptions of this process can lead to pathological conditions such as osteoporosis. Dual‐targeted agents, capable of inhibiting excessive bone resorption and stimulating bone formation, are being explored as a promising strategy for developing new treatments to address osteoporosis. In this study, we investigated the effects of P7C3 on bone remodeling and its potential therapeutic role in osteoporosis treatment in mice. Specifically, P7C3 can remarkably suppress receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclast differentiation in bone marrow macrophages via the Akt‐NF‐κB‐NFATc1 signaling pathway. Additionally, RNA sequencing (RNAseq) analysis revealed that P7C3 promoted osteoblast differentiation and function through the Wnt/β‐catenin signaling pathway, thereby enhancing bone formation. Furthermore, μCT analysis and histological examination of bone tissues from P7C3‐treated mice showed attenuation of both Ti‐induced bone erosion and ovariectomy (OVX)‐induced bone loss. These findings suggest that P7C3 may have a novel function in bone remodeling and may be a promising therapeutic agent for the treatment of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Intertidal vegetation plays an essential role in habitat provision for waterbirds but suffers great losses due to human activities. However, it is challenging in tracking the human-driven loss and degradation of intertidal vegetation due to rapid urbanization in a high temporal resolution. In this study, a methodological framework based on full Landsat time-series (FLTS) is proposed to detect the year of change (YOC) of intertidal vegetation converted to impervious surfaces (ISs) and artificial ponds (APs), and the condition of the remaining intertidal vegetation was also assessed by FLTS, in the Fujian province, a subtropical coastal area lying in southeast China. The accuracies of the YOC detection of intertidal vegetation converted to IS and AP were 91.84% and 72.73%, with mean absolute errors of 0.26 and 1.06, respectively. The total areas of intertidal vegetation encroached by IS and AP were 31.68 km2 and 23.85 km2, respectively. Most ISs were developed later than 2010, and most APs were developed earlier than 2005, which are highly related to the implementation of local policies for economic development. The remaining intertidal vegetation in growing, stable, and degraded conditions were 43.05%, 56.38%, and 0.57%, respectively. The results indicated that areas of intertidal vegetation were reclaimed for anthropogenic uses at a considerable rate, although the intertidal vegetation still increased owing to natural development after the establishment of natural reserves. The study demonstrates that the FLTS has capacities in monitoring the dynamics in coastal zones solely for its dense earth observations.

Microphytobenthos (MPB) are central to benthic tidal flat ecological networks. Large-scale information on total MPB biomass is difficult to obtain from traditional in-situ measurements. Here, we assessed the effectiveness of using surface sediment properties as proxies for predicting the total (depth-integrated) MPB biomass with Sentinel satellite data. First, the best subset regression was applied to the in-situ data to determine the properties that best predict the biomass decay rate with depth (sampling every cm up to 10 cm depth). Then, data from a controlled laboratory experiment were used to analyse the spectral response to different sediment properties (i.e., variations in sediment grain size, organic matter and water content). Subsequently, an algorithm was developed to obtain the spatial distribution of the sediment properties and the depth-integrated total MPB biomass from remote sensing data. Finally, we presented a case study in which the seasonal dynamics of total (depth-integrated) MPB biomass were obtained from Sentinel-2 Multispectral Instrument (MSI) satellite data using the Google Earth Engine (GEE) platform. The results showed that (1) the vertical distribution of MPB biomass on a tidal flat could be predicted by the surface MPB biomass, median grain-size (D50) and water content (W0) of the sediment (top 1 cm); (2) the near infrared (NIR) band absorption depth was a key feature in estimating D50 and W0; and (3) the seasonal variation in the total (depth-integrated) MPB biomass was prominent in Chongming Dongtan, Changjiang Estuary. We concluded that the depth-integrated exponential decay algorithm was useful for estimating total MPB biomass and, combined with mappable sediment-surface data, could help map the total MPB biomass in estuarine tidal flats at a large scale.

Abstract Background This study aimed to explore the relationship between communication skills, health service quality, and patient trust in primary health services. Method This study was conducted in village clinics in rural China. A simple random sampling method was used to select volunteer village clinics and patients. In total, 574 participants from 25 village clinics were selected with the help of local health officers and village doctors. The response rate was 90%. Statistical analyses (hierarchical linear regression analysis and a structural equation model) were performed to analyze the data. Results Patient trust in doctors in rural primary health was influenced by patient perceptions of doctors’ communication skills and health service quality. However, health service quality fully mediated the relationship between doctors’ communication skills and patient trust in village clinics. In other words, doctors’ communication skills indirectly influence patients’ trust in doctors. Conclusions This study found a link between doctors’ communication skills and patient trust. The findings suggest that health managers and doctors should attach great value to communication skills and health service quality in promoting the rural doctor-patient relationship. Moreover, the relationship between doctors and patients should be considered when reforming the primary health system.

Fabric defect detection plays a critical role for measuring quality control in the textile manufacturing industry. Deep learning-based saliency models can quickly spot the most interesting regions that attract human attention from the complex background, which have been successfully applied in fabric defect detection. However, most of the previous methods mainly adopted multi-level feature aggregation yet ignored the complementary relationship among different features, and thus resulted in poor representation capability for the tiny and slender defects. To remedy these issues, we propose a novel saliency-based fabric defect detection network, which can exploit the complementary information between different layers to enhance the representation features ability and discrimination of defects. Specifically, a multi-scale feature aggregation unit (MFAU) is proposed to effectively characterize the multi-scale contextual features. Besides, a feature fusion refinement module (FFR) composed of an attention fusion unit (AFU) and an auxiliary refinement unit (ARU) is designed to exploit complementary important information and further refine the input features for enhancing the discriminative ability of defect features. Finally, a multi-level deep supervision (MDS) is adopted to guide the model to generate more accurate saliency maps. Under different evaluation metrics, our proposed method outperforms most state-of-the-art methods on our developed fabric datasets.

Wetlands are globally critical for human survival and Earth's sustainable development. However, wetlands are experiencing rapid degradation and loss due to pollution, reclamation, climate change, invasions, etc. Ramsar sites are globally recognized as wetland hotspots that have been designated Wetlands of International Importance under the Ramsar Convention. However, the long-term trends of change that affect these sites remain unclear. This study explored the ecological changes and characteristics of Ramsar sites using 7 ecological indicators from three aspects: vegetation status, hydrological dynamics and anthropogenic disturbance, with the support of 36-year dense Landsat imagery and the trend and mutation analysis algorithms of Theil-Sen and BreakoutDetection. The results showed that (1) for the long-term trend, the ecological status of 55% of China's Ramsar sites experienced a trend of degradation, and the remaining Ramsar sites showed a trend of restoration in the past 36 years. (2) After the mutation was analysed, 47% of the Ramsar sites showed an environmental and ecological improvement trend in the recent period. (3) More than 50% of Ramsar sites were found to have ecological reversals in vegetation status and hydrological dynamics in the past 36 years.

Photovoltaic (PV) solar energy generation attracts considerable attention to archive carbon neutrality goals worldwide. Geospatial data describing the PV system based on satellite images are critical for PV deployment. However, it remains challenging to obtain relative data in coastal zones due to frequent cloud cover. There have also been relatively few studies on spatial analysis of PV development in terms of solar resources and the energy demands. Therefore, this study took Chinese coastal provinces as example, and proposed a random forest classification method with information on morphology, optics, and SAR to address cloud pollution. The results obtained were analyzed with geographical and socioeconomic factors to determine its development status. The results have shown that (1) by October 2022, the total PV area in Chinese coastal provinces reached 837.3 km2, with an overall accuracy of 96.9 % and a Kappa coefficient of 0.91. Water-based PV represents 33.7 % which tended to be distributed near the shoreline. (2) Bounded by the Huai River, the PV density in the north was 9.0 km2 per 104 km2, which is more than twice that in the south. The development of water-based PV is a key reason for the high PV construction density in coastal areas. (3) PV distribution was slightly mismatched with solar resource and power demand, especially in Liaoning and Guangdong. Liaoning has relatively high potential for PV development. The study findings can play a key role in evaluation of PV power generation, development potential, and ecological environmental impacts.

Abstract The frequency diverse array (FDA) can provide degrees of freedom in both the range and angle domains by controlling the frequency offset across adjacent elements. Nevertheless, the time‐variant problem affects the analysis and application of FDA, and there is a notable lack of research on the receivers of multicarrier FDA. In this paper, a novel perspective to understand the factor of time parameter is proposed. Furthermore, combined with the multiple input and multiple output scheme, two multicarrier FDA radar receivers are proposed to obtain the time‐invariant and dot‐shaped beampattern. Numerical simulations demonstrate the validity of theoretical results.

Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid with pharmaceutical and nutraceutical functions that plays an important role in treating several neurological disorders. One major source of NA is plant seed oil. Here we report fatty acid profiles of seeds and germplasm diversity of six plant species, including three woody plants with high amounts of NA-enriched seed oil, Malania oleifera, Macaranga adenantha, and M. indica. M. oleifera had the largest seed (average 7.40 g single seed), highest oil content (58.71%), and highest NA level (42.22%). The germplasm diversity of M. oleifera is associated with its habitat but not elevation. Seeds of M. adenantha contained higher NA levels (28.41%) than M. indica (21.77%), but M. indica contained a significantly higher oil content (29.22%) and seed yield. M. adenantha germplasm varied among populations, with one population having seeds with high oil content (22.63%) and NA level (37.78%).Although M. indica grow naturally at a range of elevations, no significant differences were detected between M. indica populations. These results suggest that M. indica and M. oleifera have greater potential as a source of NA, which will contribute to constructing a germplasm resource nursery and establishing a selection and breeding program to improve the development of NA-enriched plants.

Abstract NAD-dependent protein deacetylase Sirtuin 2 (SIRT2), which regulates several cellular pathways by deacetylating multiple substrates, has been extensively studied in the context of Parkinson’s disease (PD). Although several studies based on the MPTP model of PD show that SIRT2 deletion can protect against dopaminergic neuron loss, the precise mechanisms of SIRT2-mediated neuronal death have largely remained unknown. Here, we show that SIRT2 knockout can effectively ameliorate anomalous behavioral phenotypes in transgenic mouse models of PD. Importantly, in both cellular and animal models of PD, it was observed that SIRT2 translocates from the cytoplasm to the nucleus. Further, the nuclear translocation of SIRT2 promotes neuronal death. Moreover, the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of SIRT2 at the Ser331 and Ser335 sites appears to be necessary for such nuclear translocation. Taken together, the results provide insights into the mechanisms involved in the regulation of neuronal death during PD progression via the Cdk5-dependent nuclear–cytoplasmic shuttling of SIRT2.

Prefabricated pavement is increasingly applied worldwide due to the rapid construction on-site. This paper presents a state-of-the-art review of the precast systems and assembly connection of concrete slabs, as well as the precast pavement features. The previous research indicates that: (1) both super-slab and Michigan systems are recommended with the satisfied road performance close to the cast-in-place; (2) flexible base material is suggested for the fabricated pavement for the satisfied leveling and stress distribution; (3) to prevent the voiding phenomenon of the fabricated pavement, the sand cushion course, dry mixed mortar or self-leveling mortar, and other flowable materials could be used for the secondary leveling of the base after the pavement splicing; (4) two-direction dowel bars are recommended for slab connections of the fabricated pavement, which helps to improve the load transfer capacity of the joints and enhance the durability of the fabricated pavement structure; (5) the sealing treatment of precast slab joints needs strengthening to reduce the impact of surface runoff on the base course; (6) the further research focuses are designing with functional, composite, mechanized, intelligent, lightweight, and flexible pavement slabs. Besides, pavement mechanical properties induced by temperature overlapping traffic loads need to be revealed.

Using a three-chamber vicarious social defeat stress model in mice, Qi et al. show that chronic emotional stress (CES) induced anxiety-like behavior and transient social interaction changes. Bidirectional modulation of NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior.

Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, L. acidophilus KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of L. acidophilus KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether L. acidophilus KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut–liver axis. The results showed that Lactobacillus KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. L. acidophilus KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after L. acidophilus KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that L. acidophilus KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that L. acidophilus KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, L. acidophilus KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that L. acidophilus KLDS1.0901 can be used as a candidate to ameliorate NAFLD.

Purpose: To select individuals and families with a low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with maculopathies. Design: Genetic association study based on targeted and whole-exome sequencing. Participants: A total of 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families. Methods: We focused on 150 genes involved in the complement, coagulation, and inflammatory pathways. Single-variant tests were performed on 7755 variants shared among ≥ 5 subjects using logistic regression. Gene-based tests were used to evaluate aggregate effects from rare and low-frequency variants (at minor allele frequency [MAF] ≤ 5% or ≤ 1%) in a gene using burden tests. For families whose affected members had a low burden of genetic risk based on known common and rare variants related to AMD, we searched for rare variants (MAF < 0.001) whose risk alleles occurred in ≥ 80% of affected individuals but not in controls. Immunohistochemistry was performed to determine the protein expression of a novel gene (coagulation factor II thrombin receptor-like 2 [F2RL2]) in retinal tissues. Main Outcome Measures: Genotypes and phenotypes of macular degeneration. Results: We confirmed the association of a synonymous variant in complement factor H (Ala473, rs2274700, proxy to intronic rs1410996, r2 = 1) with maculopathy (odds ratio, 0.64; P = 4.5 × 10–4). Higher AMD polygenic risk scores (PRSs) were associated with intermediate and advanced AMD. Among families with low PRSs and no known rare variants for maculopathy, we identified 2 novel, highly penetrant missense rare variants in ADAM15, A disintegrin and metalloprotease, metallopeptidase domain 15 (p.Arg288Cys) and F2RL2 (p.Leu289Pro). Immunohistochemistry analyses revealed F2RL2 protein expression in cone photoreceptor outer segments and Müller glia cells of human and pig retinas. Coagulation factor II thrombin receptor-like 2 expression appeared increased in fibrotic areas in advanced AMD samples with neovascularization, suggesting that F2RL2 may play a role in the progression to advanced macular disease. Conclusions: New missense rare variants in the genes ADAM15 and F2RL2 were associated with maculopathies. Results suggest that novel genes related to the coagulation and immune pathways may be involved in the pathogenesis of macular diseases.

Abstract Increasing population size and economic dependence on the coastal zone, coupled with the growing need for residential, agricultural, industrial, commercial and green space infrastructure, are key drivers of land reclamation. Until now, there has been no comprehensive assessment of the global distribution of land use on reclaimed space at the coast. Here, we analyze Landsat satellite imagery from 2000 to 2020 to quantify the spatial extent, scale, and land use of urban coastal reclamation for 135 cities with populations in excess of 1 million. Findings indicate that 78% (106/135) of these major coastal cities have resorted to reclamation as a source of new ground, contributing a total 253,000 ha of additional land to the Earth's surface in the 21st century, equivalent to an area the size of Luxembourg. Reclamation is especially prominent in East Asia, the Middle East, and Southeast Asia, followed by Western Europe and West Africa. The most common land uses on reclaimed spaces are port extension (>70 cities), followed by residential/commercial (30 cities) and industrial (19 cities). While increased global trade and the rapid urbanization have driven these uses, we argue that a city's prestigious place‐making effort to gain global reputation is emerging as another major driver underlying recent reclamation projects to create tourist and green spaces Meanwhile, the study suggests that 70% of recent reclamation has occurred in areas identified as potentially exposed to extreme sea level rise (SLR) by 2100 and this presents a significant challenge to sustainable development at the coast.

ObjectiveTo explore the corrective effect of 6 degree of freedom couch on rotation errors in intensity modulated radiotherapy (IMRT) for postoperative rectal cancer patients, further to probe into the clinical application value of 6 degree of freedom couch in radiotherapy.MethodsFrom January 1, 2020 to December 1, 2020, 30 patients with rectal cancer receiving postoperative intensity modulated radiotherapy in The First Hospital of Hebei Medical University were included in this retrospective study. The setup error values in all direction of patients before and after 6 degree of freedom correction were collected during each radiotherapy session.ResultsIn this study, a total of 382 data before and after the correction of 6 degree of freedom couch were collected. It was found that the setup errors in the Y direction gradually increased, was maximal in the third week, and then became smaller, and the setup errors in the other directions increased with the extension of radiotherapy time and reached the maximum at the 5th week. In the translation direction, the setup errors value in Z direction occurred more frequently than that in X and Y directions between the range of 0.21-0.80 cm. In the rotation direction, the setup errors value in rotation X direction occurred more frequently than that in rotation Y and Z directions between the range of 0.21°-2.99°. In addition, after the correction of the 6 degree of freedom couch in real time, the setup errors in patients were significantly reduced in all directions (P < 0.05).ConclusionIn summary, it was recommended to clinically use 6 degree of freedom couch combined with IMRT for real-time correction of placement errors in patients with rectal cancer undergoing radiotherapy. At the same time, it was necessary to observe the tumor size and body weight changes of patients on the 5th week. If necessary, radiotherapy positioning and planning should be performed in time.

To address the problem of chloride ion transport in cement concrete in marine environment, this study investigates the effect of metakaolin dosage on the chloride ion diffusion resistance of mortar and its mechanism by testing the chloride ion binding capacity and microstructure of mortar under the coupling effect of chlorine salt-sulfate-carbonation multiple factors. The results show that the coupling of sulfate or carbonation reduces chloride ion transport to some extent compared with single chlorine salt attack, while the three-factor coupled environment promotes free chloride ion diffusion. This is because the products of calcium alumina, gypsum, and calcium carbonate grow together and compete with each other to form more large capillaries; thus, accelerating the diffusion of chloride ions in cement mortar. Metakaolin, due to its higher pozzolanic activity, increases the monocarbon aluminate content in the erosion products, promotes F-salt generation, and increases the Al/Si ratio, which strengthens the binding ability of C-S-H gel to chloride ions, so the free chloride ion concentration inside the specimens doped with metakaolin is lower. In particular, the three-factor coupled environment has less 0.05–10 μm capillary pore content and higher F-salt stability in the specimens, which has the strongest effect on chloride ion curing, and the free chloride ion concentration integral in M-SCCl is reduced by nearly 30% compared with MF-SCCl and F-SCCl.

Introduction Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes—such as symptoms, daily functioning and quality of life—between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery.Methods and analysis Overall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery—a validated lung cancer surgery-specific scale—will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients’ quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student’s t-test, non-parametric test or Χ2 test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups.Ethics and dissemination The Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals.Trial registration number ChiCTR2200060753.

There are great differences in oil and gas enrichment at different locations in petroliferous basins, and faults are an important factor affecting the differential enrichment of oil and gas. In this paper, taking the No. 2 structure in the Nanpu Sag, Bohai Bay Basin, East China, as an example, based on the analysis of fault geometry and kinematics characteristics, the determination of oil source faults, the analysis of fault trap origin and effectiveness, and the analysis of fault caprock combinations are carried out to study the differences and mechanisms of oil and gas enrichment east and west of the Nanpu No. 2 structure. The results show that the fault-source contact relationship affects the direction of oil and gas migration. The No. 2 structure in the Nanpu Sag has a dual-source hydrocarbon supply. The western structure supplies hydrocarbons from the north and east, with oil and gas migrating along the direction parallel and perpendicular to the fault strike. The east structure supplies hydrocarbons from the south and north, with oil and gas migrating along the direction perpendicular to the fault strike. The effectiveness of fault traps affects the scale of oil and gas accumulation. Most of the traps of the Nanpu No. 2 structure formed before hydrocarbon expulsion, which are all effective traps and are conducive to oil and gas accumulation. The relationship between fault and caprock determines the vertical accumulation layers of oil and gas: The faulted thickness of the east structure is large, the fault is vertically closed, and oil and gas are enriched mainly in the deep layer. The faulted thickness of the west structure is small, and oil and gas are enriched in both deep and shallow layers.

Abstract Background Carbon dots (CDs) are widely used in cell imaging due to their excellent optical properties, biocompatibility and low toxicity. At present, most of the research on CDs focuses on biomedical application, while there are few studies on the application of microbial imaging. Results In this study, B- and N-doped carbon dots (BN-CDs) were prepared from citric acid, ethylenediamine, and boric acid by microwave hydrothermal method. Based on BN-CDs labeling yeast, the dead or living of yeast cell could be quickly identified, and their growth status could also be clearly observed. In order to further observe the morphology of yeast cell under different lethal methods, six methods were used to kill the cells and then used BN-CDs to label the cells for imaging. More remarkably, imaging of yeast cell with ultrasound and antibiotics was significantly different from other imaging due to the overflow of cell contents. In addition, the endocytosis mechanism of BN-CDs was investigated. The cellular uptake of BN-CDs is dose, time and partially energy-dependent along with the involvement of passive diffusion. The main mechanism of endocytosis is caveolae-mediated. Conclusion BN-CDs can be used for long-term stable imaging of yeast, and the study provides basic research for applying CDs to microbiol imaging. Graphical Abstract

We evaluated the effects of hydration heat inhibitors on the early hydration heat release process of cement and its main mineral components. We used a microcalorimetric method to determine the effects of various proportions and properties of hydration heat inhibitors on the hydration of portland cement, tricalcium silicate, and tricalcium aluminate: concentration (C) = 40% m/m hydroxydiphosphonic acid (HEDP) (1-hydroxyethylidene-1,1-diphosphonic acid) and C = 40% m/m diethylene triamine pentonyphosphonic acid (DTPMPA) (diethylenetriaminepentamethylene phosphonic acid). We also analyzed and tested the heat release rate and cumulative heat release during the hydration of cement and its main mineral components. The hydration heat inhibitors decreased the heat release rate of cementitious materials by means of adsorption, chelation, precipitation, complex formation, and control of calcium hydroxide crystals. Among these materials, the hydration heat inhibitor had the most substantial effect on the composition of tricalcium silicate clinker, reducing the peak temperature at the initial stage of hydration and delaying its occurrence time. These results are pertinent to controlling and selecting the early hydrothermal release process of cement systems.

BackgroundAs a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study.MethodsThe Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer.ResultsFrom 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer).ConclusionResearch on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial–mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.

Abstract Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)‐expressing hematopoietic stem cells (HSCs) are genetically engineered for bone‐targeted delivery of the transforming growth factor beta (TGF‐β) small‐molecule inhibitor SB‐505124 (SB@HSCs‐PD‐1). Intriguingly, compared to anti‐PD‐L1 monoclonal antibodies, as “living drugs”, HSCs‐PD‐1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD‐1 molecules. The SB released from HSCs‐PD‐1 competitively bound to TGF‐β receptors on CD4+ T cells and facilitate CD4+ T cell differentiation to helper T (TH)1 and TH2 cells, thereby reprogramming the local immunosuppressive milieu of the bone marrow. Additionally, HSCs‐PD‐1 can block programmed death‐ligand 1 on tumor and myeloid cells, resulting in reinvigorated anti‐tumor immunity of T cells. In conclusion, in the present study, an alternative cell engineering strategy is delineated for immune checkpoint blockade therapy, to target bone metastasis using HSCs as a platform, which shows great promise in the treatment of bone metastases.

To address the challenges posed by the large scale and dense distribution of small targets in remote sensing images, as well as the issues of missed detection and false detection, this paper proposes a one-stage target detection algorithm, DCN-YOLO, based on refined feature extraction techniques. First, we introduce DCNv2 and a residual structure to reconstruct a new backbone network, which enhances the extraction of shallow feature information and improves the network’s accuracy. Then, a novel feature fusion module is employed in the neck network to adaptively adjust the fusion weight for integrating texture information from shallow features with deep semantic information. This targeted approach effectively suppresses noise caused by extracting shallow features and enhances the representation of key features. Moreover, the normalized Gaussian Wasserstein distance loss, replacing Intersection over Union (IoU), is used as the regression loss function in the model, to enhance the detection capability of multi-scale targets. Finally, comparing our evaluations against recent advanced methods such as YOLOv7 and YOLOv6 demonstrates the effectiveness of the proposed approach, which achieves an average accuracy of 20.1% for small targets on the DOTAv1.0 dataset and 29.0% on the DIOR dataset.

As a volatile air pollutant, formaldehyde can enter people’s living environment through interior decoration, furniture and paint, causing serious harm to human health. Therefore, it is necessary to develop a sensor for the real-time detection of formaldehyde in low concentrations. According to the chemical interaction between amino groups and formaldehyde, a MIL-101(Cr) aminated-material-based formaldehyde cantilever sensor was prepared, of which ethylenediamine- functionalized MIL-101(Cr) named ED-MIL-101(Cr)) showed the best gas sensing performance. Using quasi-in situ infrared spectroscopy, ED-MIL-101(Cr) was found bound to formaldehyde through a Schiff base. The adsorption enthalpy of formaldehyde-bound ED-MIL-101(Cr) was −52.6 kJ/mol, which corresponds to weak chemical adsorption, so the material showed good selectivity. In addition, ED-MIL-101(Cr) has the most active sites, so its response value to formaldehyde is larger and it takes longer to reach saturation adsorption than bare MIL-101(Cr). Through the research on the gas sensing performance of functionalized MIL-101(Cr) material, we found that it has a strong application potential in the field of formaldehyde monitoring, and the material performance can be quantitatively and accurately evaluated through combining calculation and experimentation for understanding the gas sensing mechanism.

Corneal neovascularization (CoNV) leads to visual impairment, affecting over 1.4 million people in the United States per year. It is caused by a variety of pathologies, such as inflammation, hypoxia, and limbal barrier dysfunction. Injection of the anti-vascular endothelial growth factor (VEGF) drug KH902 (conbercept) can inhibit CoNV but requires repeated dosing that produces associated side effects, such as cornea scar. To explore more efficacious and long-lasting treatment of CoNV, we employed recombinant adeno-associated virus (rAAV)2 and rAAV8 vectors to mediate KH902 expression via a single intrastromal injection and investigated its anti-angiogenic effects and safety in both alkali-burn- and suture-induced CoNV mouse models. Our results showed that rAAV-mediated KH902 mRNA expression in the cornea was sustained for at least 3 months after a single intrastromal injection. Moreover, the expression level of rAAV8-KH902 far exceeded that of rAAV2-KH902. A single-dose rAAV8-KH902 treatment at 8 × 108 genome copies (GCs) per cornea dramatically inhibited CoNV for an extended period of time in mouse CoNV models without adverse events, whereas the inhibition of CoNV by a single intrastromal administration of the conbercept drug lasted for only 10−14 days. Overall, our study demonstrated that the treatment of CoNV with a single dose of rAAV8-KH902 via intrastromal administration was safe, effective, and long lasting, representing a novel therapeutic strategy for CoNV.

Abstract Background Continuous care is essential for people living with HIV. This study aimed to measure continuous care uptake and investigate the association between higher uptake of continuous care and behavioral and social factors, including HIV-acquisition risk and socioeconomic characteristics. Methods A hospital-based cross-sectional study was conducted from April to November 2019 in an HIV treatment center of a specialized hospital in Kunming city, China. Fourteen service indicators were used to calculate composite care scores, which were classified into three levels (low, middle, and high), using principal component analysis. The Behavioral Model for Vulnerable Populations was employed to examine predisposing, enabling, and need factors associated with composite care scores among people living with HIV. Results A total of 702 participants living with HIV aged ≥ 18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1–5 years were recruited. Based on ordinal logistic regression modeling, predisposing factors: being employed (adjusted odds ratio (AOR): 1.54, 95% confidence interval (CI): 1.13–2.11), heterosexuals (AOR: 1.58, 95% CI: 1.11–2.25) and men who have sex with men (AOR: 2.05, 95% CI: 1.39–3.02) and enabling factors: Urban Employee Basic Medical Insurance (AOR: 1.90, 95% CI: 1.03–3.54), middle socioeconomic status (SES) (AOR: 1.42, 95% CI: 1.01–2.01), were positively associated with the higher level of continuous care uptake, compared to the unemployed, people who inject drugs, those with no medical insurance and low SES, respectively. Conclusion There were large differences in continuous care uptake among people living with HIV. HIV-acquisition risk categories and socioeconomic factors were significant determinants of uptake of continuous care. Our findings could inform the development of evidence-based strategies that promote equitable healthcare for all people living with HIV.

Abstract The clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.