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A two-stage catalytic membrane reactor (CMR) that couples CO2 splitting with methane oxidation reactions was constructed based on an oxygen-permeable perovskite asymmetric membrane. The asymmetric membrane comprises a dense SrFe0.9Ta0.1O3-δ (SFT) separation layer and a porous Sr0.9(Fe0.9Ta0.1)0.9Cu0.1O3-δ (SFTC) catalytic layer. In the first stage reactor, a CO2 splitting reaction (CDS: 2CO2 → 2CO + O2) occurs at the SFTC catalytic layer. Subsequently, the O2 product is selectively extracted through the SFT separation layer to the permeated side for the methane combustion reaction (MCR), which provides an extremely low oxygen partial pressure to enhance the oxygen extraction. In the second stage, a Sr0.9(Fe0.9Ta0.1)0.9Ni0.1O3-δ (SFTN) catalyst is employed to reform the products derived from MCR. The two-stage CMR design results in a remarkable 35.4% CO2 conversion for CDS at 900 °C. The two-stage CMR was extended to a hollow fiber configuration combining with solar irradiation. The solar-assisted two-stage CMR can operate stably for over 50 h with a high hydrogen yield of 18.1 mL min−1 cm−2. These results provide a novel strategy for reducing CO2 emissions, suggesting potential avenues for the design of the high-performance CMRs and catalysts based on perovskite oxides in the future.

Abstract Community detection is a critical component of network analysis and a hot topic in social computing. Detecting community structure in dynamic networks has important theoretical and practical implications for understanding the intrinsic function of networks and predicting network behavior. However, the majority of existing dynamic community detection methods adopt shallow models, which have limited ability to excavate complex non-linear structures and tend to generate undesirable community structures. In order to obtain an accurate and robust community structure in dynamic networks, we are inspired by network representation learning and utilize the deep learning to detect evolving communities in dynamic networks. In this paper, we propose a novel dynamic community detection method by fusing Deep Learning and Evolutionary Clustering (DLEC). This work attempts to combine deep learning and evolutionary clustering into a unified framework. First, we propose a matrix construction strategy to fully reveal the inherent community structures via the underlying community memberships. Then, we develop a novel multi-layer deep autoencoder framework that consists of multiple non-linear functions to extract the latent deep representation of the dynamic network. Based on the evolutionary clustering framework, a graph regularization term is introduced to ensure the smoothness of the community evolution. Finally, we employ the K-means clustering algorithm on the low-dimensional network space to obtain the community structure. Extensive experimental results on synthetic and real-world networks show that the proposed DLEC algorithm can effectively detect high-quality communities in dynamic networks.

Abstract The genetic analysis of potato is hampered by the complexity of tetrasomic inheritance. An ongoing effort aims to transform the clonally propagated tetraploid potato into a seed-propagated diploid crop, which would make genetic analyses much easier owing to disomic inheritance. Here, we construct and report the large-scale genetic and heterotic characteristics of a diploid F2 potato population derived from the cross of two highly homozygous inbred lines. We investigate 20,382 traits generated from multi-omics dataset and identify 25,770 quantitative trait loci (QTLs). Coupled with gene expression data, we construct a systems-genetics network for gene discovery in potatoes. Importantly, we explore the genetic basis of heterosis in this population, especially for yield and male fertility heterosis. We find that positive heterotic effects of yield-related QTLs and negative heterotic effects of metabolite QTLs (mQTLs) contribute to yield heterosis. Additionally, we identify a PME gene with a dominance heterotic effect that plays an important role in male fertility heterosis. This study provides genetic resources for the potato community and will facilitate the application of heterosis in diploid potato breeding.

Abstract Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC–MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops.

Abstract Hair cell bundles consist of stereocilia arranged in rows of increasing heights, connected by tip links that transmit sound-induced forces to shorter stereocilia tips. Auditory mechanotransduction channel complexes, composed of proteins TMC1/2, TMIE, CIB2, and LHFPL5, are located at the tips of shorter stereocilia. While most components can interact with the tip link in vitro, their ability to maintain the channel complexes at the tip link in vivo is uncertain. Using mouse models, we show that an additional component, LOXHD1, is essential for keeping TMC1-pore forming subunits at the tip link but is dispensable for TMC2. Using SUB-immunogold-SEM, we showed that TMC1 localizes near the tip link but mislocalizes without LOXHD1. LOXHD1 selectively interacts with TMC1, CIB2, LHFPL5, and tip-link protein PCDH15. Our results demonstrate that TMC1-driven mature auditory channels require LOXHD1 to stay connected to the tip link and remain functional, while TMC2-driven developmental channels do not.

Abstract Electron microscopy paired with immunogold labeling is the most precise tool for protein localization. However, these methods are either cumbersome, resulting in small sample numbers and restricted quantification, or limited to identifying protein epitopes external to the membrane. Here, we introduce SUB-immunogold-SEM, a scanning electron microscopy technique that detects intracellular protein epitopes proximal to the membrane. We identify four critical sample preparation factors contributing to the method’s sensitivity. We validate its efficacy through precise localization and high-powered quantification of cytoskeletal and transmembrane protein distribution. We evaluate the capabilities of SUB-immunogold-SEM on cells with highly differentiated apical surfaces: (i) auditory hair cells, revealing the presence of nanoscale MYO15A-L rings at the tip of stereocilia; and (ii) respiratory multiciliate cells, mapping the distribution of the SARS-CoV-2 receptor ACE2 along the motile cilia. SUB-immunogold-SEM extends the application of SEM-based nanoscale protein localization to the detection of intracellular epitopes on the exposed surfaces of any cell.

Rapeseed meal is a promising food ingredient, but its utilization is limited by the presence of some potentially harmful ingredients, such as glucosinolates. Fermentation is a cost-effective method of detoxication but a food-grade starter culture with glucosinolates degradation capacity is required. In this study, 46 strains of lactic acid bacteria from traditional paocai brines were screened for their ability to glucosinolate degradation. The results showed that more than 50% of the strains significantly degraded glucosinolates. Two strains of Lactiplantibacillus (p7 and s7) with high capacity of glucosinolates degradation through producing enzymes were identified. Then, an optimized condition for rapeseed meal fermentation by p7 was established to degrade glucosinolates, which can achieve about 80% degradation. UPLC/Q-TOF-MS analysis showed that the degradation rate of individual glucosinolates was different and the degradation rate of gluconapin and progoitrin in rapeseed meal can reach more than 90%. Meanwhile, fermentation with p7 can improve safety of rapeseed meal by inhibiting the growth of Enterobacteriaceae and improve its nutritional properties by degrading phytic acid. The in vitro digestion experiments showed that the content of glucosinolates in rapeseed meal decreased significantly during gastric digestion. Meanwhile, fermentation with p7 can greatly improve the release of soluble protein and increase the contents of free essential amino acids, such as lysine (increased by 12 folds) and methionine (increased by 10 folds).

Wheat bran, a principal byproduct of flour milling, stands as an abundant source of dietary fiber, yet its economic potential remains under-exploited in current forage applications. Arabinoxylan (AX), constituting the core of dietary fiber, emerges as a versatile compound with multifaceted functionalities. Its nutritional significance, coupled with its role in cereal food processing, has prompted a surge of studies focusing on the valorization of wheat bran AX. Moreover, the hydrolyzed derivative, arabinoxylan oligosaccharides (AXOS), demonstrates prebiotic and antioxidant properties, offering potential avenues to mitigate the risk of chronic diseases. This review summarizes current knowledge on the valorization of wheat bran AX in terms of the processing and nutritional properties of AX. Moreover, multiple novel applications of AX in the materials area, including biodegradable food packaging films, delivery of bioactive substances as nanoparticles, and the manufacture of food emulsifiers, are also highlighted to extend the utilization of AX. This review underscores the immense potential of wheat bran AX, advocating for its exploitation not only as a nutritional asset but also as a primary ingredient in advanced materials. The synthesis of nutritional and materials perspectives accentuates the multifaceted utility of wheat bran AX, thereby paving the way for sustainable valorization pathways. By unraveling the latent potential within AX, this paper advocates for the holistic and sustainable utilization of wheat bran in diverse, value-added applications.

Abstract Background Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. Methods In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5’ end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. Results This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965–0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. Conclusion Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.

Abstract Introduction The EQ Health and Wellbeing (EQ-HWB) is a new questionnaire for measuring quality of life (QoL) from a broad perspective. The items of the EQ-HWB were derived based on a ‘qualitative review’ of literature, which reported primarily on Western studies. It can be argued that the QoL is a cultural-related concept and therefore people from China have a different understanding of the QoL. This study aimed to explore whether Chinese citizens could understand the EQ-HWB’s candidate items and what they thought of those items. In doing so, we wanted to examine the face validity of the candidate items and explore if further cultural adaptation is necessary. Methods This research was part of the E-QALY project, in which 36 candidate items were selected for the EQ-HWB from a 97-item pool. In China, three interviewers investigated the face validity of these EQ-HWB candidate items in semi-structured qualitative face-to-face interviews. Respondents were invited to report ‘problems’ with regard to the interpretation of the items and these problems were grouped into themes. We explored to what extent those themes related to specific cultural aspects in China. We also classified the rates of reported problems for each item into three groups: 1) less than 20%, 2) from 20–50%, and 3) over 50%. Results For 17 items the rate of reported problems was less than 20%, 15 items fell into the second group (with 20 − 50%) and for 4 items the rate of problems reported was more than 50%. The thematic analysis revealed eight themes: ambiguous problems in the interpretation of 16 items; difficult to understand (11); contained a complex negative expression (10); examples used seemed inappropriate (7); misleading connotation in Chinese (2); long and complex (2); complex response options (1); and use of non-colloquial language (1). Discussion Our research shows that EQ-HWB candidate items require careful examination to make them more comprehensible. Most of the reported problem themes were generic problems related to the items, and only a few face validity issues appeared to relate to specific cultural aspects in China, even though most of the items were based on Western studies. Our findings are reassuring for the instrument’s international application, especially in China.

Abstract Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Abstract On a global note, oral health plays a critical role in improving the overall human health. In this vein, dental-related issues with dentin exposure often facilitate the risk of developing various oral-related diseases in gums and teeth. Several oral-based ailments include gums-associated (gingivitis or periodontitis), tooth-based (dental caries, root infection, enamel erosion, and edentulous or total tooth loss), as well as miscellaneous diseases in the buccal or oral cavity (bad breath, mouth sores, and oral cancer). Although established conventional treatment modalities have been available to improve oral health, these therapeutic options suffer from several limitations, such as fail to eradicate bacterial biofilms, deprived regeneration of dental pulp cells, and poor remineralization of teeth, resulting in dental emergencies. To this end, the advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources. This review presents a comprehensive overview of different nanoarchitectured composites for improving overall oral health. Initially, we emphasize various oral-related diseases, providing detailed pathological circumstances and their effects on human health along with deficiencies of the conventional therapeutic modalities. Further, the importance of various nanostructured components is emphasized, highlighting their predominant actions in solving crucial dental issues, such as anti-bacterial, remineralization, and tissue regeneration abilities. In addition to an emphasis on the synthesis of different nanostructures, various nano-therapeutic solutions from diverse sources are discussed, including natural (plant, animal, and marine)-based components and other synthetic (organic- and inorganic-) architectures, as well as their composites for improving oral health. Finally, we summarize the article with an interesting outlook on overcoming the challenges of translating these innovative platforms to clinics. Graphical abstract

Abstract The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Abstract Background Virtual reality (VR) and augmented reality (AR) are emerging technologies that can be used for cardiopulmonary resuscitation (CPR) training. Compared to traditional face-to-face training, VR/AR-based training has the potential to reach a wider audience, but there is debate regarding its effectiveness in improving CPR quality. Therefore, we conducted a meta-analysis to assess the effectiveness of VR/AR training compared with face-to-face training. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, and Wanfang databases from the inception of these databases up until December 1, 2023, for randomized controlled trials (RCTs) comparing VR- and AR-based CPR training to traditional face-to-face training. Cochrane's tool for assessing bias in RCTs was used to assess the methodological quality of the included studies. We pooled the data using a random-effects model with Review Manager 5.4, and assessed publication bias with Stata 11.0. Results Nine RCTs (involving 855 participants) were included, of which three were of low risk of bias. Meta-analyses showed no significant differences between VR/AR-based CPR training and face-to-face CPR training in terms of chest compression depth (mean difference [MD], -0.66 mm; 95% confidence interval [CI], -6.34 to 5.02 mm; P = 0.82), chest compression rate (MD, 3.60 compressions per minute; 95% CI, -1.21 to 8.41 compressions per minute; P = 0.14), overall CPR performance score (standardized mean difference, -0.05; 95% CI, -0.93 to 0.83; P = 0.91), as well as the proportion of participants meeting CPR depth criteria (risk ratio [RR], 0.79; 95% CI, 0.53 to 1.18; P = 0.26) and rate criteria (RR, 0.99; 95% CI, 0.72 to 1.35; P = 0.93). The Egger regression test showed no evidence of publication bias. Conclusions Our study showed evidence that VR/AR-based training was as effective as traditional face-to-face CPR training. Nevertheless, there was substantial heterogeneity among the included studies, which reduced confidence in the findings. Future studies need to establish standardized VR/AR-based CPR training protocols, evaluate the cost-effectiveness of this approach, and assess its impact on actual CPR performance in real-life scenarios and patient outcomes. Trial registration CRD42023482286.

Abstract To assess the health utility value (HUV) of Rheumatoid Arthritis (RA) patients and its influencing factors in China. A cross-sectional survey was conducted in 8 tertiary hospitals across four capital-cities. The demographic characteristics, patient-reported outcomes including the HUV got by EQ-5D-5L, clinical characteristics, and clinician-reported outcomes of 171 RA patients were collected both from themselves and their physicians. Both the univariate and multivariate analyses were used to assess the potential factors of EQ-5D-5L HUV of the patients. The mean age of the patients was 50.7 years, with female being 64.9% (n = 111). The mean HUV and EQ visual analogue scale score of all patients were 0.586 and 47.3, respectively. The univariate analysis showed that the patients who were female, older, living in rural areas, with lower education level, advanced disease stage, higher the patient's assessment of arthritis pain visual analogue scale (PtAAP-VAS), the patient's global assessment of disease activity visual analogue scale (PtGADA-VAS), and the Physician’s global assessment of disease activity visual analogue scale (PhGADA-VAS) scores had significantly lower EQ-5D-5L HUVs. The multivariate analysis further suggested that older age, female, higher body mass index and higher PtGADA-VAS score were statistically significantly related to lower HUVs. The study provided the HUVs for RA patients with different characteristics and outcomes, which could be used in the economic evaluation of interventions for the RA patients. The identified factors could also assist the health care managing and improving the health-related quality of life on RA patients.

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. Methods 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1–2, and the moderate neuromuscular block group maintained TOF = 1–2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. Results MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg−1·h−1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), μg·kg−1·min−1, P

Abstract To assess the efficacy of stent grafts (SGs) in managing central venous obstruction disease (CVOD) in hemodialysis (HD) patients with arteriovenous (AV) access, and to identify predictive factors influencing the SG treatment outcomes. HD subjects with CVOD who underwent SGs placement at our center between August 2018 and June 2022 were enrolled. Survival curve analysis using the Kaplan–Meier method and log-rank test was performed. Cox proportional hazards regression analysis was employed to identify predictive factors associated with outcomes. A total of 59 SG implantation procedures for CVOD were analyzed, comprising 30 cases of stenosis and 29 cases of occlusion. The access circuit primary patency (ACPP) at 6, 12, and 24 months post-SG placement were 80.9%, 53.8%, and 31.4%, respectively, while, the target lesion primary patency (TLPP) were 91.3%, 67.6%, and 44.5%, respectively. Subgroup analysis revealed higher TLPP in the stenosis group compared to the occlusion group, although the difference was not statistically significant (P = 0.165). The TLPP was significantly improved by SG placement in those who had antecedent balloon dilations (P

ObjectiveThe aim of this case report is to assess the clinicopathological characteristics and differential diagnosis of orbital granular cell tumor (GCT).MethodsClinical and imaging data of a rare case of orbital GCT involving the superior rectus muscle were collected. Its clinical characteristics, imaging, and histopathological features were observed.ResultsA 36-year-old female patient presented with a 2-year history of left eye proptosis. Magnetic resonance imaging (MRI) enhancement suggested a space-occupying lesion in the left superior rectus muscle region. On T1-weighted and T2-weighted MRI, the tumor was isointense to gray matter and significantly enhanced on the enhanced scan. Microscopic examination revealed that most tumor cells exhibited diffuse growth with unclear boundaries, and some cells were arranged in small nests. The tumor cells were large, with abundant, coarse eosinophilic granules in the cytoplasm. Occasional cells contained larger round eosinophilic droplets in the cytoplasm. Focal areas showed foamy cells, small and central round or oval nuclei with occasional nuclear enlargement and mild atypia, inconspicuous nucleoli, rare mitoses, and low proliferative activity. Immunohistochemistry results were Vimentin (+), S-100 (+), CD68 (+), Ki67 (2%+), Inhibin-a (−), CK (−), SMA (−), and Desmin (−). The pathological examination of a specimen harvested from the mass corresponded to a GCT.ConclusionOrbital GCT is rare and should be considered in the differential diagnosis of orbital tumors. It is essential to distinguish it from thyroid-associated ophthalmopathy, inflammatory pseudotumor, and myohemangioma. Definitive diagnosis requires a comprehensive analysis of clinical, histopathological, and immunohistochemical findings. Surgical excision is the primary treatment for orbital GCTs. For patients with incomplete tumor resection, close follow-up is necessary. Proton beam radiation therapy can be considered to prevent recurrence or metastasis if needed.

We study radiative transfer in participating binary stochastic mixtures in two dimensions (2D) by developing an accurate and efficient simulation tool. For two different sets of physical parameters, 2D benchmark results are presented, and it is found that the influence of the stochastic mixture on radiative transfer is clearly parameter-dependent. Our results confirm that previous multidimensional results obtained in different studies are basically consistent, which is interpreted in terms of the relationship between the photon mean free path lp and the system size L. Nonlinear effects, including those due to scattering and radiation–material coupling, are also discussed. To further understand the particle size effect, we employ a dimensionless parameter lp/L, from which a critical particle size can be derived. On the basis of further 2D simulations, we find that an inhomogeneous mix is obtained for lp/L > 0.1. Furthermore, 2D material temperature distributions reveal that self-shielding and particle–particle shielding of radiation occur, and are enhanced when lp/L is increased. Our work is expected to provide benchmark results to verify proposed homogenized models and/or other codes for stochastic radiative transfer in realistic physical scenarios.

Introduction Stroke survivors often face motor dysfunction, increasing fall risk. Lower extremity muscle weakness is a key factor affecting walking ability. Tai chi (TC) has been shown to improve muscle strength and mobility in patients with stroke more effectively than traditional walking training. However, existing TC programmes for stroke rehabilitation are often too simplified and fail to fully use TC’s benefits. Additionally, subjective assessment scales are time-consuming and prone to bias. This study proposes integrating TC’s early movement features with neurodevelopmental therapy, using surface electromyography and inertial measurement unit (IMU) sensors to thoroughly analyse diverse TC movements. Tailored exercises, based on stroke-induced impairments, will be objectively assessed through biomechanical analysis.Methods and analysis The study unfolds in two phases. The initial phase employs the IMU sensor and electromyography to objectively analyse TC’s biomechanics, informing personalised rehabilitation plans aligned with distinct movement impairments. The second phase adopts a randomised, single-blind, parallel controlled trial design involving 60 patients with stroke randomly assigned to either the intervention or control group. The intervention group undergoes biomechanics-based TC training alongside routine rehabilitation for 12 weeks, practicing the 24-form TC three times weekly. The control group engages in routine rehabilitation thrice weekly for the same duration. Primary and secondary outcomes, including kinematic/dynamic data, surface electromyography, motion analysis, comprehensive the international classification of functioning, disability and health Core Set for Stroke, Modified Barthel Index and Fugl-Meyer Assessment, will be evaluated at baseline and post-intervention.Ethics and dissemination The study has received approval from the Ethics Committee of Zhongda Hospital Southeast University (2023ZDSYLL378-P01). All prospective participants will receive comprehensive information regarding the study protocol, and their informed consent will be obtained before their participation. Additionally, the trial will be registered with the Chinese Clinical Trial Registry to ensure transparency and compliance with research regulations. Results from this study will be disseminated through peer-reviewed journals, conference presentations and public databases to ensure wide accessibility and to contribute to the advancement of medical knowledge.Protocol version 2.0 (14 June 2024).Trial registration number www.chictr.org.cn, identifier ChiCTR2400080158.

IntroductionMyocardial ischemia/reperfusion (I/R) injury remains a major obstacle in cardiovascular therapies. Hydrogen sulfide (H2S) shows promise for mitigating I/R injury, but conventional delivery methods, such as NaHS injections or adenovirus-mediated CSE gene therapy, face low efficiency and systemic side effects. This study explores the use of angiotensin 1 (AT1) peptide-conjugated CdSe/ZnS quantum dots (QDs) for targeted delivery of cystathionine-γ-lyase (CSE) plasmids to the myocardium, aiming to boost local H2S production and minimize I/R injury.MethodsCdSe/ZnS QDs were conjugated with AT1 peptides to create a nanocarrier system capable of delivering the CSE plasmid specifically to the myocardium. In vivo fluorescence imaging confirmed heart-specific accumulation. Myocardial infarct size, cardiac function, cell death, and oxidative stress were evaluated. Endoplasmic reticulum stress and mitophagy markers, including CHOP/GRP78/eIF2α, were analyzed, and the CHOP gene's role was further assessed using an adenovirus vector.ResultsThe AT1-conjugated nanocarriers significantly increased CSE expression in the myocardium, as confirmed by fluorescence imaging, without affecting other organs. This localized delivery reduced myocardial infarct size, improved cardiac function, and decreased oxidative stress and cell death. Importantly, a reduction in endoplasmic reticulum stress and mitophagy markers was observed, suggesting that cardioprotection was mediated via the CHOP/GRP78/eIF2α signaling pathway. Reintroduction of CHOP using an adenovirus vector reversed these protective effects, confirming the pathway's involvement.DiscussionThis study demonstrates that AT1 peptide-conjugated QDs can effectively deliver CSE plasmids to the heart, providing significant protection against I/R injury through enhanced localized H2S production. This approach offers a promising, targeted, and side-effect-free therapy for myocardial I/R injury, with potential for clinical translation.

Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with dyslipidemia recognized as a significant risk factor. Dyslipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), is associated with an increased lifetime risk of CVD. Although alfalfa’s cholesterol-lowering effects have been demonstrated in animal models, clinical trial data supporting its efficacy in human dyslipidemia treatment are limited. Methods: A randomized controlled trial was conducted from September 20, 2021, to January 12, 2023, involving patients diagnosed with dyslipidemia. Approved by the China Ethics Committee of Registering Clinical Trials, the study included multiple sites in China. Eligible participants were adults aged 18 years or older, meeting criteria from the Chinese Guidelines for the Prevention and Treatment of Adult Blood Lipid Disorders. Participants were randomly assigned to either a health education-only group or a combined alfalfa powder supplementation and health education group for a three-month intervention period. Results: A total of 160 eligible patients were enrolled and randomized into two groups: the Alfalfa group (n = 80) and the Education group (n = 80). The intervention resulted in significant improvements in key lipid parameters in the Alfalfa group, including reductions in TC, LDL-C, and Apo A1 levels. Although changes in HDL-C levels were not significantly different between the groups, the Alfalfa group exhibited a larger increase. Serum lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the combined intervention did not significantly alter the overall blood lipid metabolome but identified fifteen regulated differential metabolites, with the glycerophospholipid metabolism pathway significantly affecting lipid metabolism levels. Conclusion: Supplementation with alfalfa powder combined with health education significantly reduced TC, LDL-C, and Apo A1 levels in patients with dyslipidemia. KEGG pathway analysis suggests an association between the glycerophospholipid metabolism pathway and dyslipidemia. Further research is warranted to validate these findings and explore the underlying mechanisms.

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

Cigarette smoke (CS) is a prevalent chemical indoor air contaminant known to be the primary cause of EMT during airway remodeling in COPD. While some evidence indicates the involvement of SMAD4 in EMT across certain diseases, its specific role in CS-induced EMT in airway remodeling associated with COPD is not established. In our research, we observed a substantial upregulation in SMAD4 expression, O-GlcNAcylation and EMT in patients with COPD, as well as in vitro and in vivo COPD models induced by CS, than those of the controls. Downregulation of SMAD4 resulted in a reduction in CS-induced EMT in vitro and in vivo. As a post-translational modification of proteins, O-GlcNAcylation is dynamically controlled by the duo of enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA). We further discovered the enhancement of O-GlcNAcylation levels induced by CS was due to an elevated OGT expression, as the expression of OGA remained unchanged. Using an OGT inhibitor (OSMI-1) counteracted the effects of SMAD4 on EMT. Whereas, overexpressing OGT increased SMAD4 expression and promoted EMT. OGT-mediated SMAD4 O-GlcNAcylation shielded SMAD4 from proteasomal degradation by reducing its ubiquitination, thereby aiding in SMAD4 stabilization in response to EMT induced by CS. Overall, this research uncovers a fresh pathway for CS-induced EMT in the airway remodeling of COPD and offers valuable insights.

ZCL-278 is a selective small molecule specifically inhibiting the Cdc42-intersectin interaction, yet its in-vivo pharmacokinetic and pharmacodynamic properties against renal diseases had not been determined. Thus, our study explored the absorption, distribution and excretion of ZCL-278 as well as its pharmacological efficacy against chronic kidney disease (CKD). With the optimized detection method, absolute oral bioavailability of ZCL-278 was determined as 10.99 % in male and 17.34 % in female rats. ZCL-278 was rapidly and abundantly distributed in various tissues, especially the kidney and heart, while few excreted through urine and feces. In the adenine-induced CKD mice, the increased plasma creatinine and urea, the decreased body weight as well as the renal pathological alterations, including vacuolization of renal tubular epithelial cells, granular degeneration, cell flattening, luminal dilation, and cylindruria, were significantly ameliorated after ZCL-278 administration. Moreover, ZCL-278 could also reverse the increased intensities of renal inflammation and fibrosis in the CKD mice. These results clarified the pharmacokinetics of ZCL-278 in rats and preliminarily indicated that ZCL-278 has favorable pharmacodynamic properties for CKD primed for lead development and optimization, warranting further drug development.

Globally, water scarcity threatens food security, especially in arid and semi-arid food-producing regions, such as the Hetao Irrigation District (HID), where the water consumption during the non-growth season (spring irrigation, autumn irrigation) accounts for more than 30 % of the total irrigation volume. Meanwhile, mapping the characteristics of spatial and temporal evolution of the area of cropland irrigated in the spring and autumn and the pattern of water consumption is crucial for strengthening the management of agricultural water use. Evaporation and infiltration of irrigation water are difficult to capture in time due to insufficient timeliness or accuracy of single remote sensing data. This study integrates seven remote sensing datasets (Landsat5, Landsat7, Landsat8, HJ-1A/B, GF-1, Sentinel-2 and MODIS) for the first time to build a high spatial-temporal resolution dataset, and combines the water index NDWI and MNDWI to extract the maximum water range formed after irrigation by manually adjusting the threshold method. In addition to the global land use/cover dataset (GLC FCS30–1985_2020), the cropland layer was superimposed to accurately identify the cropland spring irrigation and autumn irrigation range from 2000 to 2021 in the HID. In the past 20 years, spring-irrigated (SI) areas increased by 1012.60 km2 (+49.96 %), and the autumn-irrigated (AI) areas decreased by 512.63 km2 (-11.02 %). Combined with the quantity of water diversion and displacement, the characteristics of irrigation water consumption in the non-growth season were further analysed. The results showed that the water consumption of spring irrigation increased by 0.67×108 m3 (+22.26 %), and that of autumn irrigation increased by 4.34×108 m3 (+38.82 %). The decrease of autumn- irrigated area and the increase of water consumption were mainly related to the stability of autumn irrigation water, imperfect irrigation and drainage conditions and insufficient field water management. In 2020­2021, the area of non-growth “autumn irrigation - spring irrigation” repeated irrigation is about 1271.52 km2, which can be used as a key control area. This study provides a theoretical basis and direction for rational water use in non-growth seasons of irrigation districts.

IntroductionThis study investigates the correlation between neuroelectrop-hysiological assessments such as motor unit number estimation (MUNE) and F-waves with upper extremity motor function and one-year prognosis in stroke patients.MethodsNeuroelectrophysiological assessments of the abductor pollicis brevis muscle, including MUNE and F-waves, were conducted. Upper extremity motor function was evaluated using the Fugl-Meyer Assessment of Upper Extremity (FMA-UE) and the Modified Ashworth Scale (MAS). Pearson correlation and multiple linear regression analyses were performed to explore the relationship between upper extremity motor function and variables such as MUNE and F-waves. ROC curve analysis assessed the predictive ability of MUNE and F-waves for upper extremity motor function, and binary logistic regression analysis examined factors related to motor function improvement 1 year post-discharge.ResultsA total of 130 patients were ultimately included. Significant differences in MUNE and occupancy rate of non-repeater F-waves (non-ORF) were found between hemiplegic and unaffected sides (p

We present a novel method for investigating laser-driven dynamic fragmentation in tin using in situ X-ray diffraction. Our experimental results demonstrate the feasibility of the method for simultaneously identifying the phase and temperature of fragments through analysis of the diffraction pattern. Surprisingly, we observe a deviation from the widely accepted isentropic release assumption, with the temperature of the fragments being found to be more than 100 K higher than expected, owing to the release of plastic work during dynamic fragmentation. Our findings are further verified through extensive large-scale molecular dynamics simulations, in which strain energies are found to be transferred into thermal energies during the nucleation and growth of voids, leading to an increase in temperature. Our findings thus provide crucial insights into the impact-driven dynamic fragmentation phenomenon and reveal the significant influence of plastic work on material response during shock release.

Background: Stomach adenocarcinoma (STAD) is one of the most common malignancies. Infection of helicobacter pylori (H. pylori) is a major risk factor that leads to the development of STAD. This study constructed a risk model based on the H. pylori-related macrophages for predicting STAD prognosis. Methods: The single-cell RNA sequencing (scRNA-seq) dataset and the clinic information and RNA-seq datasets of STAD patients were collected for establishing a prognostic model and for validation. The “Seurat” and “harmony” packages were used to process the scRNA-seq data. Key gene modules were sectioned using the “limma” package and the “WGCNA” package. Kaplan-Meier (KM) and Receiver Operating Characteristic Curve (ROC) analyses were performed with “survminer” package. The “GSVA” package was employed for single sample gene set enrichment analysis (ssGSEA). Cell migration and invasion were measured by carrying out wound healing and trans-well assays. Results: A total of 17397 were screened and classified into 8 cell type clusters, among which the macrophage cluster was closely associated with the H. pylori infection. Macrophages were further categorized into four subtypes (including C1, C2, C3, and C4), and highly variable genes of macrophage subtype C4 could serve as an indicator of the prognosis of STAD. Subsequently, we developed a RiskScore model based on six H. pylori -associated genes (TNFRSF1B, CTLA4, ABCA1, IKBIP, AKAP5, and NPC2) and observed that the high-risk patients exhibited poor prognosis, higher suppressive immune infiltration, and were closely associated with cancer activation-related pathways. Furthermore, a nomogram combining the RiskScore was developed to accurately predict the survival of STAD patients. ABCA1 in the RiskScore model significantly affected the migration and invasion of tumor cells. Conclusion: The gene expression profile served as an indicator of the survival for patients with STAD and addressed the clinical significance of using H. pylori-associated genes to treat STAD. The current findings provided novel understandings for the clinical evaluation and management of STAD.

Colorectal cancer (CRC) is a malignant tumor with a high incidence, ranking first among gastrointestinal malignancies. We investigated the impact of polyphyllin I (PPI), a natural compound found in Paris polyphylla, on CRC. PPI has been documented to exhibit anticancer activity against various tumors. This study aimed to assess the effects of PPI on colorectal cancer and explore its potential mechanisms. Our research demonstrated that PPI inhibited proliferation, promoted apoptosis, and induced G2 cell-cycle arrest in a dose-dependent manner. Additionally, our results indicated that PPI suppressed Notch signaling by downregulating the Notch1 receptor, its ligand Jagged1, and the downstream target Hes1 expression. Furthermore, we confirmed the antitumor effect of PPI on patient-derived organoids. In conclusion, our study indicates that PPI impedes the growth of colon cancer by suppressing the Notch signaling pathway.

BackgroundBronchiolitis and pneumonia are both significant lower respiratory tract infections with a profound impact on children’s health. The purpose of this study is to explore the economic burden and related influence factors of pediatric patients with bronchiolitis and pneumonia in China.MethodsA face-to-face interview was employed for the investigation of hospitalized patients (≤5 years old) with bronchiolitis and pneumonia, along with their guardians from January to October 2019. Demographic and costs were collected from Shanghai, Zhengzhou, and Kunming, representing three regions with different levels of economic development in China. Multiple linear regression analysis was used to explore factors associated with the economic burden of the diseases.ResultsA total of 338 patients with bronchiolitis and 529 patients with pneumonia were included in the analysis. The average hospitalization and total cost for patients with bronchiolitis are 4,162 CNY and 5,748 CNY, respectively, while those with pneumonia are 6,096 CNY and 7,783 CNY. Patients from Shanghai, both bronchiolitis and pneumonia, exhibited the lowest cost expenditures, with average total costs of 3,531 CNY and 3,488 CNY, respectively. Multiple regression analysis indicated that, among bronchiolitis patients, factors such as region, medical insurance, relationship, loss of work time, and length of stay were found to be significantly associated with both hospitalization cost and total cost (p

ABSTRACT: Mycoplasma synoviae (MS) is an essential pathogenic mycoplasma in poultry worldwide, posing a serious threat to the poultry industry's health. Timely detection is imperative for early diagnosis, prevention, and control of MS infection. Current laboratory methods for MS detection are generally complicated, time-consuming, and require sophisticated equipment. Therefore, a simple and rapid method is urgently needed. This study developed a novel real-time fluorescence-based recombinase-aided amplification (RF-RAA) technique for detecting MS nucleic acids, enabling target gene amplification within 20 min at 39°C. The RF-RAA outcomes are interpretable in 2 modalities: real-time fluorescence monitoring employing a temperature-controlled fluorescence detector or direct visual inspection facilitated by a portable blue light transilluminator. This method exhibits robust specificity, demonstrating no cross-reactivity with various common poultry pathogens, and achieves high sensitivity, detecting as low as 10 copies/μL for the standard plasmid. Seventy-one clinical samples of chicken throat swabs were detected by RF-RAA and real-time fluorescence quantitative polymerase chain reaction (qPCR) methods. The diagnostic coincidence rates of qPCR with RF-RAA (fluorescence monitoring) and RF-RAA (visual observation) were determined to be 100% and 97.2% (69/71), respectively. In conclusion, the RF-RAA method developed in this study provides a rapid and visually observable approach for MS detection, offering a novel technique to diagnosing MS infection, especially in resource-limited settings.

Abstract Background Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. Case presentation The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. Conclusion Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Abstract Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.

The current trend of increasing the precision lifetime of high-performance bearings forces scientists and engineers to optimize the heat treatment and processing technology to endure higher fatigue frequencies from rolling/sliding motion. In this study, the influences of two crucial factors, hardness and spherical carbides, on the wear behavior of AISI 52100 bearing steel were investigated using elaborate heat treatments to control the variables. The results showed that avoiding excessive hardness and improving the content of spherical carbides could reduce the wear volume during sliding friction and enhance wear resistance. On the one hand, high hardness is correlated to high carbon concentration and high micro-plastic strain in the martensite matrix, inducing the propagation of microcracks and formation of large-size shallow micro-pitting, which accelerates wear loss. On the other hand, spherical carbides effectively inhibit severe plastic deformation of the martensite matrix, which inhibits the wear loss caused by micro-cutting and decreases the formation of wear debris. In this case, densely distributed carbides can improve the wear performance.

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

Abstract This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs.

Abstract Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients’ health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient’ health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants. Methods A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL. Results A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well. Conclusion Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.

Logistics is playing a significant role in supporting economic growth and material security during the epidemic period and it has been experiencing a rapid development in recent years. With the issues of personalisation and cost, the economy and society ask for higher requirements for logistics storage systems. The rational design of the functional area layout is an essential step to improve the operational efficiency of the logistics warehousing system. In reality, due to warehouse design and equipment application, there has been a gradual increase in irregular warehouses. By taking an irregular warehouse as an example, combining the operation status quo, this paper clarifies the functional area settings and constructs a 0–1 integer planning model based on the grid and systematic layout planning method with constraints, such as the unique functional attributes of the grid. We optimised the genetic algorithm based on the warehouse irregularity factor and the grids factor, and then solve it through MATLAB. Finally, by using the Flexsim software, simulation metrics were selected for evaluation, the method feasibility is verified.

Neighborhood relationships play a pivotal role in rough set theory, addressing the limitations of equivalence relations. This article focuses on defining upper and lower approximation operators using neighborhood relationships and exploring their properties in terms of serialization, inverse serialization, reflexivity, symmetry, transitivity, and Euclidean relations. Furthermore, a necessary and sufficient condition for the upper approximation operator to function as a topological closure operator is derived. Overall, this research sheds light on the significance of neighborhood relationships and their implications within rough set theory.

Abstract Background Prior research has reaffirmed lifestyle risk behaviors to cluster among adolescents. However, the lifestyle cluster effect on suicidal thoughts and behaviors (STBs) was unclear among adolescents in low- and middle-income countries (LMICs). No comparison of such associations was conducted across nations. Methods Data from 45 LMICs were obtained from the Global School-based Student Health Survey (GSHS) between 2009 and 2019. Lifestyle behavior factors were collected through a structured questionnaire. Suicidal ideation, plan, and attempt were ascertained by three single-item questions. Lifestyle risk scores were calculated via a sufficient dimension reduction technique, and lifestyle risk clusters were constructed using a latent class analysis. Generalized linear mixed models with odds ratio (OR) and 95% confidence interval (CI) were used to estimate the lifestyle-STB associations. Results A total of 229,041 adolescents were included in the final analysis. The weighted prevalence of suicidal ideation, plan, and attempt was 7.37%, 5.81%, and 4.59%, respectively. Compared with the favorable lifestyle group, the unfavorable group had 1.48-, 1.53-, and 3.11-fold greater odds of suicidal ideation (OR = 1.48, 95%CI: 1.30–1.69), plan (OR = 1.53, 95%CI 1.34–1.75), and attempt (OR = 3.11, 95%CI 2.64–3.65). Four clusters of lifestyle risk behaviors were identified, namely healthy lifestyles (H–L), insufficient intake of vegetables and fruit (V-F), frequent consumption of soft drinks and fast food (D-F), and tobacco smoking and alcohol drinking (S-A) clusters. Compared with H–L cluster, V-F cluster was associated with 43% and 42% higher odds of suicidal ideation and plan, followed by S-A cluster (26% for ideation and 20% for plan), but not significant in D-F cluster (P > 0.05). D-F cluster was associated with 2.85-fold increased odds of suicidal attempt, followed by V-F cluster (2.43-fold) and S-A cluster (1.18-fold). Conclusions Clustering of lifestyle risk behaviors is informative for risk stratification of STBs in resource-poor settings. Lifestyle-oriented suicide prevention efforts should be initiated among school-attending adolescents in LMICs.

Abstract The Chinese traditional educational primer San Zi Jing (三字经) was immensely appreciated by Western missionaries, who frequently leveraged it to spur Chinese-language learning or to decipher Chinese thought. Walter Henry Medhurst (1796–1857), affiliated with the London Missionary Society (LMS), translated and reconstructed biblical scriptures into the format and style of the Chinese-language San Zi Jing, henceforth referred to as the “disguised San Zi Jing” in this article. The disguised San Zi Jing was initially published in Batavia in 1823 and reprinted in several locations, occasionally with minor modifications to its content. First, this study examines the complex qualities of the original San Zi Jing, which made it an ideal translation target, and the unique natures of the disguised San Zi Jing, which served as the ultimate translation product. Second, referencing Edward Said’s traveling theory, a diachronic investigation finds that the disguised San Zi Jing traveled in four stages, from Nanyang to Lingnan to Jiangnan and finally across Pan-China (more regions of China). Last, the article examines the indigenization process of the disguised San Zi Jing in space and content over time and analyzes the power dynamics underlying indigenization. The study contributes to translation history studies as well as studies of Christianity in China.

Abstract Public concern regarding safety policies serious consequences is anticipated to persist over an extended duration. A study examining a case of rapid public health policy adaptation in China during the COVID-19 epidemic was conducted by gathering public opinion data from major social media platforms. A systematic approach to comprehend public opinion was developed. Five fundamental elements and four dimensions were delineated. An indicator system was established utilizing the K-means text clustering model. Public prediction, expectation, and their evolution underlying public concern were elucidated employing TF–IDF text mining models. The HMM elucidated the way public opinion influences policy adjustments. The findings underscore that public concern regarding enduring events undergoes temporal shifts, mirroring the evolution of public opinion towards policy. Public opinion aroused by both the original event and derived events collaboratively influence policy adjustments. In China, public opinion serves as a mechanism for policy feedback and oversight; notably, negative public sentiment plays a pivotal role in expediting policy transitions. These findings aid in refining policies to mitigate emergencies through a feedback loop, thereby averting the emergence of safety risks such as social unrest prompted by public opinion.

Background A series of cases have reported graft delamination as a rare complication of early-cannulation arteriovenous graft (ecAVG). The unique multilayer structure of ecAVGs contributes to the property of cannulation as early as hours after implantation, but on other hand it takes the risk of graft delamination. However, the underlying mechanism and management of graft delamination as well as its effects on the long-term patency of ecAVGs have not been systemically analyzed.Methodsz A retrospective study was conducted in a cohort of patients who required an ecAVG for hemodialysis (HD) access in our center between April 2017 and December 2021. The characteristics of graft delamination and the outcomes of its different treatments were analyzed.Results A total of 144 ecAVGs were established in 141 end-stage renal disease (ESRD) patients, including 124 (86.1%) Acuseal grafts and 20 (13.9%) Flixene grafts. During follow-up 24.5(11.5, 45.8) months, 11 (7.6%) subjects had graft infection with an incidence of 0.03 patient-year. Thirteen (9.0%) subjects had graft delamination at 9.3(5.0,12.4) months after ecAVG implantation, with an incidence of 0.04 per patient-year. ecAVG delamination was observed in both Acuseal grafts (0.037 per patient-year) and Flixene grafts (0.055 per patient-year). Thrombosis or venous hypertension was the most common complaints. Seven delamination was observed at 1.3 (0.1, 4.2) months after an endovascular procedure. The primary patency, primary assistant patency and secondary patency in delamination group were significantly lower than that in non-delamination group (p

Cellular structures (i.e., solidification cells) are a unique feature within alloys fabricated through rapid solidification, such as laser-powder bed fusion (L-PBF). Ever since the report of these structures’ beneficial effects on the material's mechanical properties, numerous studies have been devoted to the understanding of their formation mechanisms. Yet, the integrity and stability of the cellular structures are often less investigated, despite their significance on property interpretation and evolution. In this work, a stepwise in-situ heating transmission electron microscopy (TEM) experiment was performed on the exemplary LPBF-fabricated AlFeSiMoZr alloy. A critical threshold of 325 °C was identified, beyond which the cellular structures start to decompose in conjunction with precipitate coarsening. Preferred precipitate nucleation sites and their subsequent coarsening kinetics were determined and presented. Nanometer-sized crystalline embryos (3.81 ± 0.66 nm) were discovered within the cellular structure boundaries in their as-built condition, offering new insights on the precipitate formation and evolution at elevated temperatures.

Multi-material additive manufacturing holds immense potential for performance and functionality enhancement. Past research efforts primarily focused on the horizontal interface (perpendicular to the sample build direction) during the laser-powder bed fusion (LPBF) of multi-materials, whereas a few studies demonstrated that the vertical interface (parallel to the sample build direction) is in fact the main obstacle towards high-integrity multi-material fabrication in a three-dimensional space. In this work, facilitated by our own patented powder spreading device, we explored the mechanisms behind defect formation along both the horizontal and vertical interfaces during the LPBF production of 316L stainless steel and K220 copper multi-materials. High-fidelity fluid dynamics simulations were also conducted to rationalise the experimental observations. A practical process parameter optimisation approach is also proposed at the end, with the aim of mitigating those large defects currently occurring near the vertical interface.

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

Abstract Excellent castability, significantly refined microstructure, and good mechanical properties make eutectic high‐entropy alloys (EHEAs) a natural fit for rapid solidification processes, e.g., additive manufacturing. Previous investigations have focused on developing EHEAs through trial and error and mixing known binary eutectic materials. However, eutectic compositions obtained from near‐equilibrium conditions do not guarantee a fully eutectic microstructure under rapid solidifications. In this work, a thermodynamically guided high‐throughput framework is proposed to design EHEAs for rapid solidification. Empirical formulas derived from past experimental observations and thermodynamic computations are applied and considered phase growth kinetics under rapid solidification (skewed phase diagram). The designed alloy candidate, Co25.6Fe17.9Ni22.4Cr19.1Ta8.9Al6.1 (wt.%), contains nanostructured eutectic lamellar and shows a high Vickers hardness of 675 Hv. In addition to this specific composition, the alloy design toolbox enables the development of new EHEAs for rapid solidification without the limitation of previous knowledge.

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P < 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P < 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P < 0.05), while malondialdehyde increased significantly (P < 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P < 0.05), total bile acid secretion decreased significantly (P < 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P < 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P < 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.