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Abstract Nanocrystalline metallic materials have the merit of high strength but usually suffer from poor ductility and rapid grain coarsening, limiting their practical application. Here, we introduce a core-shell nanostructure in a multicomponent alloy to address these challenges simultaneously, achieving a high tensile strength of 2.65 GPa, a large uniform elongation of 17%, and a high thermal stability of 1173 K. Our strategy relies on an ordered superlattice structure that excels in dislocation accumulation, encased by a ≈3 nm disordered face-centered-cubic nanolayer acting as dislocation sources. The ordered superlattice with high anti-phase boundary energy retards dislocation motions, promoting their interaction and storage within the nanograins. The disordered interfacial nanolayer promotes dislocation emission and effectively accommodates the plastic strain at grain boundaries, preventing intergranular cracking. Consequently, the order-disorder core-shell nanostructure exhibits enhanced work-hardening capability and large ductility. Moreover, such core-shell nanostructure exhibits high coarsening resistance at elevated temperatures, enabling it high thermal stability. Such a design strategy holds promise for developing high-performance materials.

The novel Ni–Cr–W–Gd alloy have the gadolinium neutron absorption unit and the tungsten gamma ray shielding unit, which can be used for thermal neutron and gamma ray co-shielding. This Ni–Cr–W–Gd alloy have good strength and fracture elongation, however, its corrosion performance has not been reported yet. In this work, the corrosion behavior for Ni–Cr–W–Gd alloys was studied in the boric acid solution at 40 °C. Electrochemical measurement techniques, long-term immersion tests, corrosion morphology and composition analysis, and first principles calculation have been used. After 4000 h immersing, the maximum steady state corrosion rate among all alloys is only 0.3221 μm/yr. The increasing Gd promotes the increase in corrosion current density and make the weight loss of alloys more serve. Both the results of relative potential test and first principles calculation demonstrate the NiCrW matrix is the anode and Ni5Gd is the cathode in micro galvanic corrosion. The matrix around the interface of matrix/Ni5Gd suffer preferential anodic dissolution, resulting in the detachment of the Ni5Gd phase and formation of pores on the surfaces. The passive films are composed of Cr2O3 and WO3, moreover, the intensity of Gd2O3 increases with Gd content. This work contributes to the promotion of the novel alloys in spent fuel storage environments.

Abstract The membrane-delimited receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), which is expressed in the intestine, collaborates with broad neutral amino acid transporter 1 (B0AT1). Tryptophan (Trp) is transported into intestinal epithelial cells by ACE2 and B0AT1. However, whether ACE2 and its binding protein B0AT1 are involved in Trp-mediated alleviation of intestinal injury is largely unknown. Here, we used weaned piglets and IPEC-J2 cells as models and found that ACE2/B0AT1 alleviated lipopolysaccharide (LPS)-induced diarrhea and promoted intestinal barrier recovery via transport of Trp. The levels of the aryl hydrocarbon receptor (AhR) and mechanistic target of rapamycin (mTOR) pathways were altered by ACE2. Dietary Trp supplementation in LPS-treated weaned piglets revealed that Trp alleviated diarrhea by promoting ACE2/B0AT1 expression, and examination of intestinal morphology revealed that the damage to the intestinal barrier was repaired. Our study demonstrated that ACE2 accompanied by B0AT1 mediated the alleviation of diarrhea by Trp through intestinal barrier repair via the mTOR pathway.

Fine terrain classification is one of the main applications of Synthetic Aperture Radar (SAR). In the multiband fully polarized SAR operating mode, obtaining information on different frequency bands of the target and polarization response characteristics of a target is possible, which can improve target classification accuracy. However, the existing datasets at home and abroad only have low-resolution fully polarized classification data for individual bands, limited regions, and small samples. Thus, a multidimensional SAR dataset from Hainan is used to construct a multiband fully polarized fine classification dataset with ample sample size, diverse land cover categories, and high classification reliability. This dataset will promote the development of multiband fully polarized SAR classification applications, supported by the high-resolution aerial observation system application calibration and verification project. This paper provides an overview of the composition of the dataset, and describes the information and dataset production methods for the first batch of published data (MPOLSAR-1.0). Furthermore, this study presents the preliminary classification experimental results based on the polarization feature classification and classical machine learning classification methods, providing support for the sharing and application of the dataset.

Abstract Background The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy. Methods 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method. Results 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians’ potential cognition: ‘Iv is always better than oral’; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders. Conclusion Physicians’ in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists’ medication guidance were worth studying to help physicians develop antibiotic IVOS treatment.

Abstract Purpose This study aimed to assess the health-related quality of life (HRQoL) of the Chinese population by using the Chinese medicine quality of life-11 dimensions (CQ-11D) questionnaire and to identify factors associated with HRQoL. Methods The data was derived from a survey conducted by the Institute of Pharmacoeconomics Evaluation at Beijing University of Chinese Medicine on the quality of life of the Chinese population. The sex and age of respondents were considered through quota sampling. Demographic, socioeconomic, and health indicators were collected using the structured questionnaire. We performed bivariate analyses first to examine the associations between the above factors and the HRQoL of respondents measured by the CQ-11D. Multivariate linear regression and ordinal logistic regression models were established to analyze the factors (demographic, socioeconomic, and health indicators) differences in HRQoL, as well as the risk of each group reporting problems across the 11 dimensions of CQ-11D. Results From February 2021 to November 2022, a total of 7,604 respondents were involved and 7,498 respondents were included. The sample approximated the general adult Chinese population in terms of age, sex, and district of residence, and each geographic distribution ranged from 9.71 to 25.54%. Of the respondents, 45.84% were male, and 89.82% were Han ethnicity. The mean utility score ranged from 0.796 to 0.921 as age increased. According to the respondents, most health problems were identified in the PL (fatigue) (70.16%) and SM (quality of sleep) (63.63%) dimensions. The CQ-11D index scores varied with the demographic and socioeconomic characteristics of respondents, except for ethnicity (p > 0.05) and income (p > 0.05). The multivariate analysis revealed significant negative associations between health utility scores and various factors. These factors include sex (female), age over 65, belonging to ethnic minorities, rural household registration, being widowed or divorced, having a primary school education or below, being a student or unemployed, having a low income of 0–1,300, engaging in smoking or drinking, limited participation in physical activities, experiencing changes in self-perceived health status compared to the previous year, and having chronic diseases. The odds of respondents reporting problems in 11 dimensions varied among different socio-demographic groups. Conclusions This study reports the first Chinese population norms for the CQ-11D derived using a representative sample of the Chinese general population. Self-reported health status measured by the CQ-11D varies among different socio-economic groups. In addition to participation a physical activity and the presence of chronic disease, smoking and drinking also significantly influence HRQoL.

Abstract Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Abstract Background Programmed cell death (PCD) functions critically in cancers and PCD-related genes are associated with tumor microenvironment (TME), prognosis and therapeutic responses of cancer patients. This study stratified hepatocellular carcinoma (HCC) patients and develop a prognostic model for predicting prognosis and therapeutic responses. Methods Consensus clustering analysis was performed to subtype HCC patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) among the subtypes were filtered and subjected to the least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis to filter prognostic genes. A PCD-related prognostic gene signature in TCGA was constructed and validated in ICGC-LIRI-JP and GSE14520 datasets. TME was analyzed using CIBERSORT, MCP-counter, TIMER and EPIC algorithms. Drug sensitivity was predicted by oncoPredict package. Spearman analysis was used to detect correlation. Results Four molecular subtypes were categorized based on PCD-related genes. Subtype C1 showed the poorest prognosis, the most infiltration of Fibroblasts, dentritic cell (DC) and cancer-associated fibroblasts (CAFs), and the highest TIDE score. C4 had a better prognosis survival outcome, and lowest immune cell infiltration. The survival outcomes of C2 and C3 were intermediate. Next, a total of 69 co-DEGs were screened among the four subtypes and subsequently we identified five prognostic genes (MCM2, SPP1, S100A9, MSC and EPO) for developing the prognostic model. High-risk patients not only had unfavorable prognosis, higher clinical stage and grade, and more inflammatory pathway enrichment, but also possessed higher possibility of immune escape and were more sensitive to Cisplatin and 5. Fluorouracil. The robustness of the prognostic model was validated in external datasets. Conclusion This study provides new insights into clinical subtyping and the PCD-related prognostic signature may serve as a useful tool to predict prognosis and guide treatments for patients with HCC.

The effect of yttrium on the 475 °C brittleness and microstructure stability of Fe–13Cr–6Al–2Mo-0.5Nb-0.15Zr alloy after long-term aging at 475 °C has been investigated. At the early stage of aging, the nanoscale metastable transition phase precipitates in large quantities. After aging for 10,000 h, the nanophase in the Y-free alloy has completely disappeared, and only a great deal of granular Laves phases are left, while a large number of nanoscale phases still exist in the grain of Y-containing alloys. This is because the addition of yttrium combines with vacancies, hinders the diffusion of Laves phase-forming elements, and has the result that the transformation of nanoscale phases Fe2(Mo0.3Nb0.7)Al to Laves phase is inhibited during the aging process of the Y-containing alloys. During aging, precipitation-free zones (PFZ) are formed in the surrounding area where the Laves phase and grain boundaries exist. The elongation of Y-containing alloys decreases with yttrium content, but it is still higher than that of Y-free alloy. The addition of yttrium improves the aging plasticity and weakens the degree of 475 °C brittleness of the alloy, and the effectiveness is diminished with the yttrium. This plays a key role in the further study of Fe–Cr–Al alloys for fuel cladding materials.

Abstract This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P

This study takes a nearby foundation pit project of a high-speed railway in Yancheng City, Jiangsu Province as an example to investigate the impact of deep foundation pit projects on groundwater and the surrounding environment. Through on-site monitoring, in-situ testing, and numerical simulation, we conducted a comprehensive study of the impact of foundation pit projects on groundwater and the surrounding environment. The evolution of groundwater levels and surface displacement during the excavation of foundation pits was analyzed, and a method for measuring the permeability of target soil layers in situ was studied. The simulation of recharge under various soil conditions was performed, and the outcomes demonstrated the effective isolation of hydraulic connections between the interior and exterior of the foundation pit by the water-resistant curtain. Precipitation head and constant head recharging tests were employed to ascertain the actual permeability. The characteristic time method calculation exhibited remarkable efficiency and accuracy in determining the permeability coefficient of the recharging soil layer. Recharging phreatic and confined water layers has differing degrees of influence on surface deformation, with the impact of confined water layers requiring more time to stabilize. These findings contribute significantly to a more comprehensive understanding of the environmental repercussions associated with deep excavation projects, thereby enhancing safety and environmental protection measures in excavation construction practices.

IntroductionImmune cells are involved in the onset and progression of Sjögren’s syndrome (SS). This study explored the causal relationship between immune signature cells and SS, which has not been fully elucidated.MethodsWe conducted univariate, multivariate, and bidirectional Mendelian randomization to investigate the causal relationship between 731 immunological feature characteristic cells and SS pairs and explore the interaction of immune cells in SS.ResultsAfter false discovery rate correction, six immune cells were significantly associated with SS risk. Among them, four contributed to SS (CD24 on memory B cell, CD27 on IgD + CD24 + B cell, CD28 on CD39+ secreting CD4 Treg cell, and CD80 on CD62L + mDC); two appeared to reduce SS risk (CD3 on CD39 + CD8 + T cell and CD38 on IgD + CD38 + B cell). Pleiotropy and heterogeneity were not observed. Three immune cells exerted independent effects for SS (CD27 on IgD + CD24 + B cell, CD80 on CD62L + mDC, and CD38 on IgD + CD38 + B cell); two were risk factors (CD27 on IgD + CD24 + B cell and CD80 on CD62L + mDC); and one was a protective factor (CD38 on IgD + CD38 + B cell). Twenty-three immune cells showed a reverse causal relationship with SS.ConclusionThese findings demonstrate the influence of immune cells on SS risk and the effects of SS on immune cells, providing new clues for further research on the mechanisms underlying SS.

Abstract Background Particulate β‐glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. Methods C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). Results The 150 mg/kg OAW treatment mitigated OVA‐induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)‐α and IL‐6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. Conclusion These results highlight OAW's robust anti‐inflammatory properties, suggesting potential benefits in treating MC‐dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.

Background: Traditional working procedures requires a lot of clinical processes and processing time. Methods: The orthodontic metal appliances were made by applying oral scanners, digital images, computer-aided design and computer-aided manufacturing (CAD-CAM) printers. Results: The computer digital technology simplified the manufacturing process for dental appliances and shorten the duration for clinical operation and technical processing. Conclusions: The technique described in this paper can guarantee the accuracy of orthodontic appliances and bring revolution the field. Clinical significance: The CAD-CAM technology provides a fully digital workflow for manufacturing metal orthodontic appliances, which saves a considerable amount of labor and material costs, and significantly reduces heavy metal pollution in the working environment of dental technicians.

High-entropy alloys (HEAs) demonstrate superior mechanical properties at room temperature, highlighting potential for engineering applications. With the increasing demand for advanced materials, especially in modern applications facing rigorous conditions, it becomes imperative to gain profound insights into the dynamic behavior of HEAs. In this study, the (FeCoNi)86Al7Ti7 HEA, renowned for exceptional printability and room-temperature mechanical properties, has been fabricated by selective laser melting (SLM), and its tensile and impact behaviors at ambient and cryogenic temperatures are systematically investigated. Experimental results reveal enhanced tensile properties as temperature decreases, achieving a high ultimate strength of 1313.6 MPa and impressive ductility of 24.8 % at 77 K. This improvement is attributed to the synergistic deformation mechanisms, including dislocation slip, stacking faults, Lomer and Lomer-Cottrell locks, which maintain a high strain-hardening rate and thus suppress strain localization. In contrast, impact properties deteriorate due to constrained dislocation mobility at high strain rates and low temperatures, with Charpy impact energy decreasing from 8.1 J at 293 K to 5.1 J at 77 K. Consequently, cracks readily initiate at cellular boundaries or defects, propagating in an intergranular manner and inducing localized deformation. This study provides valuable insights for the future applications of 3D-printed HEAs in extreme operational environments.

Abstract Background The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. Methods Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin–eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. Results The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40–3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53–4.61 mm. Conclusions CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

The 3D human pose estimation is a technique used to determine the position of the human body in a three-dimensional space. This involves identifying body rotations, joint angles, and other pose-related information from image or video data. In this paper, we propose an end-to-end 3D human pose estimation network that is based on multi-level feature fusion.The network is composed of two main components. The first component utilizes the deepest features extracted by the backbone network. These features undergo initial data encoding and are then processed by the Semantic Information Extraction Module, which primarily consists of a multi-head self-attention mechanism. This module extracts deeper features, resulting in primary human body feature data. The second component focuses on the shallowest features and inputs them into the Global Information Processing Module, which performs global feature extraction.The features extracted from both components, along with the Bbox info (bounding box information), are collectively fed into the Iterative Regression Module. This module generates human pose data, which is then utilized to reconstruct and generate the human body using a human pose model. To evaluate the performance of our method, we train and test it on well-known benchmark datasets such as 3DPW, AGORA and MPII. Our method demonstrates exceptional performance, as it achieves a reduction of approximately 5.3% on the PA-MPJPE metric and approximately 5.1% on the MPJPE metric compared to the best model we referenced.

Abstract Background Type 1 diabetes is believed to be an autoimmune condition, characterized by destruction of insulin-producing cells, due to the detrimental inflammation in pancreas. Growing evidences have indicated the important role of type I interferon in the development of type 1 diabetes. Methods Trex1-deficient rats were generated by using CRISPR-Cas9. The fasting blood glucose level of rat was measured by a Roche Accuchek blood glucose monitor. The levels of insulin, islet autoantibodies, and interferon-β were measured using enzyme-linked immunosorbent assay. The inflammatory genes were detected by quantitative PCR and RNA-seq. Hematein-eosin staining was used to detect the pathological changes in pancreas, eye and kidney. The pathological features of kidney were also detected by Masson trichrome and periodic acid-Schiff staining. The distribution of islet cells, immune cells or ssDNA in pancreas was analyzed by immunofluorescent staining. Results In this study, we established a Trex1-deletion Sprague Dawley rat model, and unexpectedly, we found that the Trex1 −/− rats spontaneously develop type 1 diabetes. Similar to human diabetes, the hyperglycemia in rats is accompanied by diabetic complications such as diabetic nephropathy and cataract. Mechanistical investigation revealed the accumulation of ssDNA and the excessive production of proinflammatory cytokines, including IFN-β, in Trex1 null pancreas. These are likely contributing to the inflammation in pancreas and eventually leading to the decline of pancreatic β cells. Conclusions Our study links the DNA-induced chronic inflammation to the pathogenesis of type 1 diabetes, and also provides an animal model for type 1 diabetes studies.

Abstract Background Precise prediction of esophageal squamous cell carcinoma (ESCC) invasion depth is crucial not only for optimizing treatment plans but also for reducing the need for invasive procedures, consequently lowering complications and costs. Despite this, current techniques, which can be invasive and costly, struggle with achieving the necessary precision, highlighting a pressing need for more effective, non-invasive alternatives. Method We developed ResoLSTM-Depth, a deep learning model to distinguish ESCC stages T1-T2 from T3-T4. It integrates ResNet-18 and Long Short-Term Memory (LSTM) networks, leveraging their strengths in spatial and sequential data processing. This method uses arterial phase CT scans from ESCC patients. The dataset was meticulously segmented by an experienced radiologist for effective training and validation. Results Upon performing five-fold cross-validation, the ResoLSTM-Depth model exhibited commendable performance with an accuracy of 0.857, an AUC of 0.901, a sensitivity of 0.884, and a specificity of 0.828. These results were superior to the ResNet-18 model alone, where the average accuracy is 0.824 and the AUC is 0.879. Attention maps further highlighted influential features for depth prediction, enhancing model interpretability. Conclusion ResoLSTM-Depth is a promising tool for ESCC invasion depth prediction. It offers potential for improvement in the staging and therapeutic planning of ESCC.

Abstract Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P

The wear resistance of the part surface has become an important factor affecting its own service life. Laser cladding (LC), as a surface modification technology, can prepare a coating with good metallurgical bonding with the substrate, which can significantly improve the wear resistance of the material surface. High entropy alloys (HEAs) are an emerging coating material with excellent wear resistance. Therefore, this paper reviews the latest development status in wear resistance of laser cladding-high-entropy alloy coatings (LC-HEACs) in terms of the HEAs material system, LC process parameters, strengthening phase, amorphous phase strengthening, assisted cladding, and post-treatment. At the same time, this paper also expounds on the mechanism of LC-HEACs enhancing the surface wear resistance of materials, and the current research status of LC-HEACs in different engineering materials and application environments. Finally, the current research deficiencies, challenges, and future development trends of LC-HEACs in the field of wear resistance are also elaborated, and it is expected to provide some references for their future development and applications.

Abstract The archaeal ancestor of eukaryotes apparently belonged to the phylum Asgardarchaeota, but the ecology and evolution of Asgard archaea are poorly understood. The optimal GDP-binding temperature of a translation elongation factor (EF-1A or EF-Tu) has been previously shown to correlate with the optimal growth temperature of diverse prokaryotes. Here, we reconstruct ancestral EF-1A sequences and experimentally measure the optimal GDP-binding temperature of EF-1A from ancient and extant Asgard archaea, to infer the evolution of optimal growth temperatures in Asgardarchaeota. Our results suggest that the Asgard ancestor of eukaryotes was a moderate thermophile, with an optimal growth temperature around 53 °C. The origin of eukaryotes appears to coincide with a transition from thermophilic to mesophilic lifestyle during the evolution of Asgard archaea.

Chitosan (CTS) as an environment-friendly biological macromolecule was applied to investigate its effect in improving the property of zirconium-based Cr(III) conversion coating on Zn-55Al-1.6Si coated steel sheet (Zn55Al). High-resolution transmission electron microscope gave the key evidence that CTS can effectively wrap the main film-forming substances and participate in the construction of Zr@CTS-TCC. A comparative analysis of electrochemical measurements showed that the addition of 0.2 g·L–1 CTS can improve the corrosion resistance of Zr@CTS-TCC and decrease the surface density of micro defects. Surface spectroscopy characterization provided a theoretical explanation for the role of CTS as an electron supplier in reduction of Cr(VI). Results demonstrate the potential of CTS as an environmentally friendly and effective cross-linking additive, which provides an alternative approach in developing next generation of trivalent chromium or chromium-free passivator for nonferrous alloy and their coatings.

Background & aims: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) has long been recognized as an adipokine. However, the exact role of eNAMPT in alcoholic liver disease (ALD) and its relevance to brown adipose tissue (BAT) remain largely unknown. This study aimed to evaluate the impact of eNAMPT on liver function and the underlying mechanisms involved in BAT-Liver communication. Methods: Serum eNAMPT levels were detected in the serum of both ALD patients and mice. Chronic and binge ethanol feeding was used to induce alcoholic liver injury in mice. An eNAMPT antibody, a coculture model of brown adipocytes and hepatocytes, and BAT-specific Nampt knockdown mice were used to investigate the role of eNAMPT in ALD. Results: Serum eNAMPT levels are elevated in ALD patients and are significantly positively correlated with the liver injury index. In ALD mice, neutralizing eNAMPT reduced the elevated levels of circulating eNAMPT induced by ethanol and attenuated liver injury. In vitro experiments revealed that eNAMPT induced hepatocyte ferroptosis through the TLR4-dependent mitochondrial ROS-induced ferritinophagy pathway. Furthermore, ethanol stimulated eNAMPT secretion from brown adipocytes but not from other adipocytes. In the coculture model, ethanol-induced release of eNAMPT from brown adipocytes promoted hepatocyte ferroptosis. In BAT-specific Nampt-knockdown mice, ethanol-induced eNAMPT secretion was significantly reduced, and alcoholic liver injury were attenuated. These effects can be reversed by intraperitoneal injection of eNAMPT. Conclusion: Inhibition of ethanol-induced eNAMPT secretion from BAT attenuates liver injury and ferroptosis. Our study reveals a previously uncharacterized critical role of eNAMPT-mediated BAT-Liver communication in ALD and highlights its potential as a therapeutic target.

Rheumatoid arthritis (RA) is a persistent autoimmune condition with no identified cure currently. Recently, scientists have applied metabolomics to investigate altered metabolic profiles and unique diseases-associated metabolic signatures. Herein, we applied metabolomics approach to analyze serum samples of 41 RA patients and 42 healthy controls (HC) with the aim to characterize RA patients' metabolic profile, investigate related underlying pathological processes, and identify target metabolites. By utilizing ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we found 168 proposed metabolites and 45 vital metabolic pathways. Our analysis revealed that deoxyinosine (DI), a metabolite of the purine metabolic pathway, was the most significant reduced metabolite in RA patients. Furthermore, through targeted detection, we confirmed lower concentration of DI in RA patients' peripheral blood. Moreover, DI inhibited lipopolysaccharide-induced inflammation both in vitro and in vivo. We further assessed DI's therapeutic potential in a collagen-induced arthritis (CIA) murine model. The results revealed that DI attenuated CIA, as evidenced by significantly lowered clinical scores of arthritis, alleviated joint swelling, and mitigated bone destruction. Moreover, we elucidated the underlying mechanism by which DI increased the population of myeloid-derived suppressor cells (MDSCs) and suppressed the proliferation of induced T cells. Collectively, these findings suggested that DI potentially ameliorated RA by inducing immunosuppressive MDSCs. The study provides key observations on RA pathogenesis and may contribute to developing novel therapeutic strategies for this debilitating condition.

ABSTRACT: Ammonia (NH3) is a toxic gas that in intensive poultry houses, damages the poultry health and induces various diseases. This study investigated the effects of NH3 exposure (0, 15, 30, and 45 ppm) on growth performance, serum biochemical indexes, antioxidative indicators, tracheal and lung impairments in Pekin ducks. A total of 288 one-day-old Pekin male ducks were randomly allocated to 4 groups with 6 replicates and slaughtered after the 21-d test period. Our results showed that 45 ppm NH3 significantly reduced the average daily feed intake (ADFI) of Pekin ducks. Ammonia exposure significantly reduced liver, lung, kidney, and heart indexes, and lowered the relative weight of the ileum. With the increasing of in-house NH3, serum NH3 and uric acid (UA) concentrations of ducks were significantly increased, as well as liver malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX-Px) contents. High NH3 also induced trachea and lung injury, thereby increasing levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in the lung, and decreasing the mRNA expressions of zonula occludens 1 (ZO-1) and claudin 3 (CLDN3) in the lung. In conclusion, in-house NH3 decrease the growth performance in ducks, induce trachea and lung injuries and meanwhile increase the compensatory antioxidant activity for host protection.

IntroductionNovelty detection (ND, also known as one-class classification) is a machine learning technique used to identify patterns that are typical of the majority class and can discriminate deviations as novelties. In the context of Alzheimer's disease (AD), ND could be employed to detect abnormal or atypical behavior that may indicate early signs of cognitive decline or the presence of the disease. To date, few research studies have used ND to discriminate the risk of developing AD and mild cognitive impairment (MCI) from healthy controls (HC).MethodsIn this work, two distinct cohorts with highly heterogeneous data, derived from the Australian Imaging Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing project and the Fujian Medical University Union Hospital (FMUUH) China, were employed. An innovative framework with built-in easily interpretable ND models constructed solely on HC data was introduced along with proposing a strategy of distance to boundary (DtB) to detect MCI and AD. Subsequently, a web-based graphical user interface (GUI) that incorporates the proposed framework was developed for non-technical stakeholders.ResultsOur experimental results indicate that the best overall performance of detecting AD individuals in AIBL and FMUUH datasets was obtained by using the Mixture of Gaussian-based ND algorithm applied to single modality, with an AUC of 0.8757 and 0.9443, a sensitivity of 96.79% and 89.09%, and a specificity of 89.63% and 90.92%, respectively.DiscussionThe GUI offers an interactive platform to aid stakeholders in making diagnoses of MCI and AD, enabling streamlined decision-making processes. More importantly, the proposed DtB strategy could visually and quantitatively identify individuals at risk of developing AD.

Abstract Immunotherapy targeting PD‐L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine‐threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD‐L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN‐γ‐mediated PD‐L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti‐PD‐1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD‐L1/PD‐1 signaling and is a promising target for combined immunotherapy.

The passive behaviour of non-equiatomic multi-principal element alloys, Ni(58-x)Co20Cr22Tax (x = 0, 0.64, 1.64, 3.39 at.%), was investigated in 0.1 M H2SO4 at 25 °C by electrochemical methods and surface analysis. After 24 h immersion, the alloys were all found to be in a spontaneously passivated state, and the value of the open circuit potential shifted to the positive direction with the increase of Ta content. The grain size of the alloys reduced with increasing the Ta content. The relationship between the passive current density and the grain size was in agreement with a linear model. The capacitance measurements indicated that the passive film formed on the alloys was of n-type semiconductor characteristic and the donor density was decreased with the increase of Ta. The thickness of the passive film improved primarily due to the obstacle to the dissolution of the outer layer as the accumulation of Ta2O5 in the outer layer. The improved corrosion resistance of the alloys with increasing Ta content can be ascribed to the formation of a complex film containing more Ta2O5, which enhanced the stability, thickness, and compactness of the passive film. The developed alloys show good passivity in dilute sulfuric acid.

Anisotropic microstructure and mechanical properties are vital considerations in the practical applications of 3D-printed metallic materials; however, limited attention has been given to the anisotropy in 3D-printed high entropy alloys (HEAs). This study systematically explores the structural and mechanical anisotropy of (FeCoNi)86Al7Ti7 HEA with low porosity, fabricated via selective laser melting (SLM). The SLM process, characterized by directional and repeated thermal dissipation, creates an anisotropic structure consisting of epitaxial columnar grains aligned parallel to the building direction, subsequently influencing mechanical anisotropy. Tensile testing unveils slight anisotropy in strength but significant differences in ductility for the SLMed HEA. The 0° sample demonstrates the optimal combination of strength and plasticity, boasting a tensile elongation of 31.5 %, approximately 2.6 times higher than that of the 45° and 90° samples. The post-mortem microscopic analysis indicates that this ductility anisotropy primarily originates from the crack propagation behavior. In the 0° sample, crack propagation occurs through both intergranular and transgranular modes, with the robust interactions between the two modes providing an obstruction to crack propagation. On the contrary, crack widening occurs essentially along the continuous melting pool boundaries (MPBs) in 45° and 90° samples, leading to the straight crack propagation path along the MPBs and therefore reduced ductility.

In electromagnetic launching systems, arc erosion of rail material, such as Al2O3 dispersion-strengthened copper (ODS-Cu), remains a critical unresolved issue. Here, we report a cold-sprayed CuCrZr–W coating on ODS-Cu exhibiting enhanced arc erosion resistance. The coating was fabricated using a bimodal powder mixture comprising coarse CuCrZr and fine W particles, resulting in a dense structure with an embedded networks of fine W particles along intersplat boundaries. Compared to the ODS-Cu substrate, the CuCrZr–W coating displays superior arc erosion resistance, as evidenced by the reduced arc erosion area and depth, shorter arc duration, lower wielding force, and limited molten Al adhesion during arcing tests. The enhanced performance is attributed to a high density of W/CuCrZr interfaces that effectively disperse arcs, the W particle network that alters the flow path of molten Cu, lowering splashing and evaporation. This work provides valuable insights into developing high-performance, arc erosion-resistant coatings for applications where safeguarding against arc erosion is paramount.

Abstract Objective This study aimed to evaluate the association between the initial dose of MMI and the clinical course, as well as adverse effects on young people with GD. Methods One hundred and sixty-one children and adolescents with newly diagnosed GD were enrolled for this study and categorized into four groups based on initial serum-free T3 and T4 levels and daily MMI doses: Group A (mild, 0.3–0.5 mg/kg/day, n = 78), Group B (moderate, 0.6–0.8 mg/kg/day, n = 37), Group C (severe, 0.6–0.8 mg/kg/day, n = 24), and Group D (severe, 0.8-1.0 mg/kg/day, n = 22). The thyroid function, blood cell analysis and liver function were examined before treatment and at 4, 8 and 12 weeks after treatment. Outcome of long-term follow-up were also observed. Results After 12 weeks of treatment, 91.0% of the patients in group A and 90.9% of the patients in group D recovered to normalization of FT3, which was slightly higher than the other two groups; 70.8% of the patients in group C recovered to normalization of FT4, which was slightly lower than that in the other three groups. The incidence of minor adverse effects was 12.8% in group A, 13.5% in group B, 16.7% in group C and 40.9% in group D (P

Abstract Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.

Introduction: Chronic thyrotoxic myopathy (CTM) is a common, easily neglected complication of hyperthyroidism. There are currently no standard diagnostic criteria for CTM, and the ultrasonic characteristics of CTM-affected skeletal muscle remain unclear. Herein, we aimed to evaluate hyperthyroid patients for CTM by ultrasound and identify ultrasonic muscle parameter cutoffs for CTM diagnosis. Materials and methods: Each participant underwent ultrasonography. The original (muscle thickness (MT), pennation angle (PA), and cross-sectional area (CSA)) and corrected (MT/height (HT), MT/body mass index (BMI), CSA/HT, and CSA/BMI) parameters of the vastus lateralis and vastus medialis (VM) were evaluated. The diagnostic effectiveness of ultrasound for predicting CTM was determined using receiver operating characteristic (ROC) curve analysis. Our study included 203 participants: 67 CTM patients (18 males, 49 females), 67 non-CTM patients (28 males, 39 females) and 69 healthy controls (20 males, 49 females). Results: The CTM group had lower muscular ultrasonic and anthropometric parameters, higher thyroid hormone and thyroid-stimulating hormone receptor antibody (TRAb) levels, and a longer duration of hyperthyroidism than the non-CTM group (P < 0.05). The VM-PA, VM-CSA, VM-CSA/HT, and VM-CSA/BMI were lower in females than in males (P < 0.05). Free thyroxine (FT4) and TRAb both showed significant negative correlations with VM-MT, VM-MT/HT, VM-CSA, and VM-CSA/HT (P < 0.05). VM-MT/BMI and VM-CSA/HT, respectively, best predicted male and female CTM (AUC = 0.84, 0.85; cutoff ≤ 0.07, < 4.01). Conclusion: Ultrasound measurement of muscular parameters, especially in the VM, is a valid and feasible way of diagnosing and characterizing possible CTM in hyperthyroidism.

Abstract Background Abstracting cerebrovascular disease (CeVD) from inpatient electronic medical records (EMRs) through natural language processing (NLP) is pivotal for automated disease surveillance and improving patient outcomes. Existing methods rely on coders’ abstraction, which has time delays and under-coding issues. This study sought to develop an NLP-based method to detect CeVD using EMR clinical notes. Methods CeVD status was confirmed through a chart review on randomly selected hospitalized patients who were 18 years or older and discharged from 3 hospitals in Calgary, Alberta, Canada, between January 1 and June 30, 2015. These patients’ chart data were linked to administrative discharge abstract database (DAD) and Sunrise™ Clinical Manager (SCM) EMR database records by Personal Health Number (a unique lifetime identifier) and admission date. We trained multiple natural language processing (NLP) predictive models by combining two clinical concept extraction methods and two supervised machine learning (ML) methods: random forest and XGBoost. Using chart review as the reference standard, we compared the model performances with those of the commonly applied International Classification of Diseases (ICD-10-CA) codes, on the metrics of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Result Of the study sample (n = 3036), the prevalence of CeVD was 11.8% (n = 360); the median patient age was 63; and females accounted for 50.3% (n = 1528) based on chart data. Among 49 extracted clinical documents from the EMR, four document types were identified as the most influential text sources for identifying CeVD disease (“nursing transfer report,” “discharge summary,” “nursing notes,” and “inpatient consultation.”). The best performing NLP model was XGBoost, combining the Unified Medical Language System concepts extracted by cTAKES (e.g., top-ranked concepts, “Cerebrovascular accident” and “Transient ischemic attack”), and the term frequency-inverse document frequency vectorizer. Compared with ICD codes, the model achieved higher validity overall, such as sensitivity (25.0% vs 70.0%), specificity (99.3% vs 99.1%), PPV (82.6 vs. 87.8%), and NPV (90.8% vs 97.1%). Conclusion The NLP algorithm developed in this study performed better than the ICD code algorithm in detecting CeVD. The NLP models could result in an automated EMR tool for identifying CeVD cases and be applied for future studies such as surveillance, and longitudinal studies.

The creation of amorphous/crystalline (A/C) laminated structures offers a promising approach towards the production of damage-tolerant A/C metallic materials. However, constraints in fabrication techniques have resulted in limited explorations into the toughening behavior of bulk A/C laminates. This study scrutinizes the impact toughness of macroscale A/C Ni–P/Ni laminates through instrumented Charpy impact testing. The findings reveal that the thickness of the amorphous Ni–P layer significantly influences the impact toughness of A/C Ni–P/Ni laminates. A/C Ni–P/Ni laminates possessing thin Ni–P layers (1 or 4 μm) demonstrated high impact energy, which was comparable to the monolithic coarse-grained (CG) structure; however, the impact energy decreased with the increasing Ni–P layers thickness. Microstructural characterization of the crack-path profile disclosed that the desired impact toughness in the A/C Ni–P/Ni laminate with a thin Ni–P layer is primarily due to intrinsic toughening induced by plastic deformation ahead of the crack tip, and extrinsic toughening afforded by interface delamination. As the Ni–P layer thickens, brittle interface delamination emerges as the dominant extrinsic toughening source to resist fracture, thereby rendering the A/C Ni–P/Ni laminate vulnerable to impact loading. This work not only elucidates the dependence of toughening mechanism on the Ni–P layer thickness in A/C Ni–P/Ni laminates but also proposes an effective strategy for designing damage-tolerant metallic materials subject to impact loading by incorporating thin, brittle amorphous and thick, ductile crystalline materials to create laminated structures.

The combination of no-till farming and green manure is key to nourishing the soil and increasing crop yields. However, it remains unclear how to enhance the efficiency of green manure under no-till conditions. We conducted a two-factor field trial of silage maize rotated with hairy vetch to test the effects of tillage methods and returning. Factor 1 is the type of tillage, which is divided into conventional ploughing and no-tillage; factor 2 is the different ways of returning hairy vetch as green manure, which were also compared: no return (NM), stubble return (H), mulching (HM), turnover (HR, for CT only), and live coverage (LM, for NT only). Our findings indicate that different methods of returning hairy vetch to the field will improve maize yield and quality. The best results were obtained in CT and NT in HM and LM, respectively. Specifically, HM resulted in the highest dry matter quality and yield, with improvements of 35.4% and 31.9% over NM under CT, respectively. It also demonstrated the best economic and net energy performance. However, other treatments had no significant effect on the beneficial utilization and return of nutrients. The LM improved yields under NT by boosting soil enzyme activity, promoting nitrogen transformation and accumulation, and increasing nitrogen use efficiency for better kernel development. Overall, NTLM is best at utilizing and distributing soil nutrients and increasing silage maize yield. This finding supports the eco-efficient cultivation approach in silage maize production in the region.

Phosphorus is one of the major constraints to karst grassland productivity. Understanding the effects of different fertilization practices on soil phosphorus dynamics is essential for enhancing phosphorus bioavailability and rational management of soil phosphorus in karst grasslands. Here, we investigated the effects of fertilizers and manures on soil bioavailability of phosphorus fractions and explored the relationship between soil properties and soil phosphorus fractions. The four fertilizer application designs were as follows: control (CK; no fertilizer or manure); fertilization (F); manure application (M); fertilization and manure application (FM). The results showed that total phosphorus (TP) concentration was elevated by 23%, 1%, and 42% in F, M, and FM treatments, respectively, compared with CK. F and FM treatments enhanced the total inorganic phosphorus (Pi) concentration by 65% and 66%, respectively, while M and FM treatments enhanced the total organo-phosphorus (Po) concentration by 21% and 35%, respectively. FM treatment elevated bioavailable P, active Po, secondary mineral P, primary mineral P, and occluded P by 69%, 39%, 50%, 31%, and 41%, respectively. Fertilizers inhibited soil acid phosphatase activity, whereas alkaline phosphatase did not respond significantly to fertilizer management in low-latitude karst regions. SOM, TN, AP, and MBP are the key factors affecting the bioavailability of phosphorus fractions. The combined application of fertilizer and manure is the most beneficial measure for enhancing soil phosphorus bioavailability. This research helps deepen our understanding of soil phosphorus dynamics in the karst areas and provides a basis for further enhancement of nutrient availability and vegetation productivity of grassland ecosystems.

Cancer represents a significant threat to human health. The cells and tissues within the microenvironment of solid tumors exhibit complex and abnormal properties in comparison to healthy tissues. The efficacy of nanomedicines is inhibited by the presence of substantial and complex physical barriers in the tumor tissue. The latest generation of intelligent drug delivery systems, particularly nanomedicines capable of charge reversal, have shown promise in addressing this issue. These systems can transform their charge from negative to positive upon reaching the tumor site, thereby enhancing tumor penetration via transcytosis and promoting cell internalization by interacting with the negatively charged cell membranes. The modification of nanocarriers with 2,3-dimethylmaleic anhydride (DMMA) and its derivatives, which are responsive to weak acid stimulation, represents a significant advance in the field of charge-reversal nanomedicines. This review provides a comprehensive examination of the recent insights into DMMA-modified nanocarriers in drug delivery systems, with a particular focus on their potential in targeted therapeutics. It also discusses the synthesis of DMMA derivatives and their role in charge reversal, shell detachment, size shift, and ligand reactivation mechanisms, offering the prospect of a tailored, next-generation therapeutic approach to overcome the diverse challenges associated with cancer therapy.

This paper experimentally investigates the performance of piezoelectric force actuators. Using the same encapsulated piezoelectric stack, an inertial-type actuator and a frame-type actuator are constructed for performance comparison. The experimental results are also used to validate the recently established actuator models, whilst the mechanical and piezoelectrical parameters of the models are experimentally identified. The performance of the actuators is described by the transmitted force(s) and input power flow from the actuators to the base structure with reference to the same electrical input voltage to the stack. The validation is deemed successful due to the strong agreement observed between the measured and predicted actuator performances. Additionally, it is discovered that the frame-type actuator has the capacity to produce significantly higher transmitted forces and input power flow to the base structure compared to the inertial-type actuator. The mechanism underlying the performance disparity between these two types of actuators is also examined. This paper clarifies the mechanism, shedding light on the design and optimization of piezoelectric actuators.

BackgroundRecent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown.ObjectiveThe objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD.MethodThe effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved.ResultsAfter 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses.ConclusionsThis is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.

Background: Acral melanoma (AM), an aggressive subtype of melanoma with poor prognosis, has been increasingly studied. The present study aims to discuss the current status, hotspots and future directions of AM studies through visualized analysis with bibliometrics and knowledge graph. Method: Publications related to acral melanoma from January 1999 to May 2023 were searched and retrieved from the Web of Science. Data extraction and visualization of the top 10 publications by year of publication, journal, country and core author were performed using R Studio (Version 4.3.0) and Scimago Graphica (Version 1.0.34). Co-reference graphs regarding country/region, organization, author, and keywords, as well as reference collaborative network, co-occurrence network, and references were plotted using VOSviewer (Version 1.6.19) and CiteSpace (Version 6.2.R3). Results: A total of 1387 articles related to AM published in English from 1999 to 2023 were included in the present study. A total of 7499 authors were from 2092 organizations in 50 countries. The articles were published in 356 journals, involving 4131 keywords and 28,200 references. The 1387 articles related to AM had been cited a total of 10,014 times by the time of this study. The result showed that Journal of the American Academy of Dermatology had the largest number of citations and citation rate, with a total of 60 publications having been cited 2191 times. Having the top three productivity institutions in the world, the US is the most productive country in this field, with a total of 361 publications. The authors with the highest number of publications were Guo Jun (n = 43) and Si Lu (n = 38) from Peking University. The keyword burstiness test found that “ipilimumab”, “open label”, “efficacy” and “nivolumab” appeared most frequently in recent years. The co-cited reference timeline graph showed that the clustering of “advanced melanoma” and “melanocytic lesion” has been a hotspot since 2016. Conclusions: The number of AM-related studies has been increasing. The clinical characteristics and immunotherapy of AM are still key research directions, with the US playing a leading role in this field. This bibliometric analysis found up to 1387 publications, which not only comprehensively and quantitatively reflected the research trends and hotspots, but also provided a theoretical basis for future studies of AM. Researchers can benefit from choosing the right journals and finding potential collaborators or partner institutions.

ABSTRACTPharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4–5 months. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6 months using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of “fast-to-FIH” approaches in combination with BeiGene’s de-risk strategy achieved successful delivery of a complete CMC package within 10 months. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics.

This study presented a comprehensive investigation into the microstructures, strengthening mechanisms and deformation behaviours of a novel N-doped Co-28Cr-6Mo (CCMN) alloy fabricated by laser powder bed fusion (LPBF). In addition to the well-known cellular structures, lattice defects including dislocations and stacking faults (SFs), the near-spherical shaped Cr2N precipitates with two typical size distributions were detected. Tensile test results revealed that the LPBF fabricated CCMN alloy demonstrated superior yield strength of 845 ± 49 MPa and elongation to fracture of 12.7 ± 1.9%. The grain boundaries (∼277 MPa), high density of dislocations (∼176–193 MPa), Cr2N precipitates (∼243 MPa) and SFs (∼131 MPa) are regarded as the dominate strengthening contributors. On the other hand, HCP phase triggered by strain induced martensite transformation (SIMT) and the Lomer-Cottrell locks (L-C locks) associated with the numerous SFs significantly enhanced the alloy strain hardening rate. More importantly, the formed Cr2N nanoprecipitates effectively suppressed the strain localisation and the premature failure along the HCP/FCC interfaces by deflecting the continuous growth of SFs, further contributing to the high ductility of the LPBF processed CCMN alloy. The present study is expected to shed light on the future development of N-doped high-performance cobalt-based alloy for the LPBF process.

Bistatic interferometric Synthetic Aperture Radar (SAR) overcomes the baseline length limit of the configuration of single-station interferometric SAR with two antennas and has become the primary method of terrain mapping using spaceborne interferometric SAR. To reduce the cost of surveying and mapping while promoting the development and application of Unmanned Aerial Vehicle (UAV)-borne bistatic interferometric SAR, the Aerospace Information Research Institute, Chinese Academy of Sciences took the lead in designing and developing a UAV-borne bistatic interferometric SAR processing system and performed flight experiments at Bailing Airport in Inner Mongolia. Herein, the system design, composition, and performance are introduced, and the scheme and implementation of the first flight experiment, along with the preliminary data processing results, are presented. In addition, the key performance metrics of the system, such as 0.5 m-elevation measurement accuracy, are verified in this study. The system serves as a foundation for future research topics, such as distributed InSAR using a multiaviation platform and tomography data acquisition and processing.

Abstract Background Mangrove wetlands are coastal ecosystems with important ecological features and provide habitats for diverse microorganisms with key roles in nutrient and biogeochemical cycling. However, the overall metabolic potentials and ecological roles of microbial community in mangrove sediment are remained unanswered. In current study, the microbial and metabolic profiles of prokaryotic and fungal communities in mangrove sediments were investigated using metagenomic analysis based on PacBio single-molecule real time (SMRT) and Illumina sequencing techniques. Results Comparing to Illumina short reads, the incorporation of PacBio long reads significantly contributed to more contiguous assemblies, yielded more than doubled high-quality metagenome-assembled genomes (MAGs), and improved the novelty of the MAGs. Further metabolic reconstruction for recovered MAGs showed that prokaryotes potentially played an essential role in carbon cycling in mangrove sediment, displaying versatile metabolic potential for degrading organic carbons, fermentation, autotrophy, and carbon fixation. Mangrove fungi also functioned as a player in carbon cycling, potentially involved in the degradation of various carbohydrate and peptide substrates. Notably, a new candidate bacterial phylum named as Candidatus Cosmopoliota with a ubiquitous distribution is proposed. Genomic analysis revealed that this new phylum is capable of utilizing various types of organic substrates, anaerobic fermentation, and carbon fixation with the Wood-Ljungdahl (WL) pathway and the reverse tricarboxylic acid (rTCA) cycle. Conclusions The study not only highlights the advantages of HiSeq-PacBio Hybrid assembly for a more complete profiling of environmental microbiomes but also expands our understanding of the microbial diversity and potential roles of distinct microbial groups in biogeochemical cycling in mangrove sediment. Video Abstract

Abstract Urbanization is inevitable in both developing and developed countries. However, this growth and transformation of the urban area can pose a significant threat to urban cultural heritage, which is a sensitive component of the urban environment. As cities modernize and change, a risk of irreparable loss of cultural heritage exists. Therefore, taking steps to protect and preserve these sites for posterity is crucial. To better protect urban cultural heritage, decision-makers must rapidly assess the impact of urbanization on cultural heritage while maintaining a balance between cultural heritage preservation and urban growth. This study developed a risk-based cumulative impact assessment (CIA) method that integrates a set of quantifiable indicators to address these issues. This method generates standardized assessment results based on game theory and set pair analysis theory. In contrast to other CIA methods, this risk-based approach effectively manages scientific complexity and uncertainties, thus enhancing the quality of the assessment results. This method was applied to 21 classical gardens in Suzhou, China. The results show that Suzhou classical gardens are impacted by urbanization. This study confirmed that adopting a risk-based CIA method that considers the impact of adverse urbanization on cultural heritage sites is an efficient approach. Successful implementation of the proposed method can provide decision-making support for different types of cultural heritage in other areas.

Abstract Objective To explore generating a health utility value set for the Chinese medicine Quality of life-11 Dimensions (CQ-11D), a utility instrument designed to assess patients’ health status while receiving TCM treatment, among the Chinese population. Methods The study was designed to recruit at least 2400 respondents across mainland China to complete one-to-one, face-to-face interviews. Respondents completed ten discrete choice experiment with survival duration (DCETTO) tasks during interviews. The conditional logit models were used to generate the health utility value set for the CQ-11D using the DCETTO data. Results A total of 2,586 respondents were invited to participate in the survey and 2498 valid interviews were completed (a completion rate of 96.60%). The modified conditional logit model with combing logically inconsistent levels was ultimately selected to construct the health utility value set for the CQ-11D instrument. The range of the measurable health utility value was -0.868 ~ 1. Conclusion The study provides the first utility value set for the CQ-11D among the Chinese population. The CQ-11D and corresponding utility value set can be used to measure the health utility values of patients undergoing traditional Chinese medicine interventions, and further facilitate relevant cost-utility analyses. The application of the CQ-11D can support TCM resource allocation in China.

Wetland resources play an important role in maintaining the balance of surface ecosystem. Based on multi-source remote sensing images, this paper studies the spatial and temporal distribution characteristics and driving factors of wetland resources in Nanliu River Delta by using human disturbance index and "3S" technology. The results show that: (1) The total wetland area has shown an overall growth trend from 2005 to 2019, with the total wetland area increasing from 77.33 km2 in 2005 to 87.55 km2 in 2019. (2) Coastal wetland types have the fastest change rate, annual rate of 36.31%, followed by fish ponds and rice fields, the annual rate of 3.40% and 3.31% respectively. (3) The area of wetland is greatly affected by the change of river water and sediment and the change of management policy. (4) The degree of human disturbance to the coastal wetlands in the delta area increases year by year, and gradually develops to the coastal areas.

Chemotherapy remains the mainstay of cancer treatment, benefiting millions of patients each year, but the side effects of chemotherapy drugs severely limit their clinical use. Doxorubicin (DOX) can cause various side effects such as heart damage and treatment-related tumors. The effective use of active and passive targeting will improve the clinical application of DOX. Here, TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system (missiles) for DOX delivery (DOX missiles). By taking advantage of the EPR effect, DOX missiles are efficiently enriched at the tumor site. After being cleaved by matrix metalloproteinase2 (MMP2), the peptide (VRGD) targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated endocytosis. The intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor killing. This study provides an efficient approach for DOX delivery and toxicity reduction.