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Building use identification is crucial in urban planning and management. Current identification methods often rely on a single data source and neglect spatial proximity. In this paper, we propose a stepwise urban building use identification framework that integrates remote sensing and social sensing data with spatial constraints based on the association of buildings with Point of Interest (POI), Area of Interest (AOI) and remote sensing data. First, the study data are preprocessed using geometric correction and POI and AOI reclassification. Then, we identify buildings with the quantitative-density index of the POIs as well as the spatial relationships between the AOIs and the buildings. Next, we generate Traffic Analysis Zones (TAZs) from road network data and utilize the similarity in physical features of buildings from remote sensing data to identify building use within spatial constraints. Finally, POI kernel density estimation is used to determine the semantic features of the buildings, and the similarity of the features between the buildings is utilized to identify the remaining buildings. The specificity of our proposed framework lies not only in the combination of multiple source data at the building-level but also in the introduction of the spatial relationships of AOIs and spatial constraints. Shenyang is selected as an example. The proposed framework identifies buildings as commercial, residential, industrial, public service and scenic spots. The accuracy assessment indicates that the proposed framework performs well, with an Overall Accuracy (OA) of 87.1% and a kappa coefficient (kappa) of 73.4%. The results of the comparison experiments show that the consideration of spatial constraints and the integration of multiple data sources help to improve the accuracy of building use identification. The proposed framework provides a new tool for better identification of urban building use, and the generated data are suitable for in-depth analyses such as building-level urban heat islands.

Abstract The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.

Abstract Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.

Abstract Purpose To provide a method for the differential diagnosis of Robert’s uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment. Methods A patient who had Robert’s uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case . Results Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital’s examination identified Robert’s uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient’s CA125 level to 14 U/mL and normalized her condition. Conclusion We pioneered a new therapeutic approach for the treatment of Robert’s uterus with adenomyosis. Some valuable references are provided for clinical practice.

Abstract Background Management of inferior ramus of the pubis-ischium ramus remains controversial, and related research is sparse. The main intention of this study is to describe the biomechanical and clinical outcomes of pubis-ischium ramus fractures in Tile B pelvic injuries and to identify the feasibility and necessity of fixation of the inferior ramus of the pubis-ischium ramus. Methods This study comprised two parts: a biomechanical test and a retrospective clinical study. For the biomechanical tests, Tile B-type pelvic injuries were modeled in six cadaver specimens by performing pubis-ischium osteotomies and disruption of the anterior and interosseous sacroiliac ligaments. The superior and/or inferior rami of the pubis-ischium ramus were repaired with reconstruction plates and separated into three groups (A, B, and C). Specimens were placed in the standing position and were loaded axially with two-leg support for three cycles at 500 N. The displacements of sacroiliac joints at osteotomy were measured with Vernier calipers and compared using statistical software. To investigate the clinical outcomes of this technique, 26 patients were retrospectively analyzed and divided into a superior ramus fixation group (Group D) and a combined superior and inferior ramus of the pubis-ischium ramus fixation group (Group E). The main outcome measures were time of operation, blood loss, postoperative radiographic reduction grading, and functional outcomes. Results In the vertical loading test, Group E showed better pelvic ring stability than Group D (P

Abstract C–H bond activation enables the facile synthesis of new chemicals. While C–H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C–H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C–C coupling mediated by 2D TMDCs to promote C–H activation and carbon dots synthesis. Our results shed light on 2D materials for C–H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

Abstract This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.

Abstract Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell Gs signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell Gs signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α−cell Gs-coupled A2A adenosine receptors. Studies with α-cell-specific Gαs knockout mice showed that α-cell Gs also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched Gs-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.

Abstract The brain–bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain–bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain–bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain–bone axis and its implications for human health and disease.

Abstract Rapid tool wear conditions during the manufacturing process are crucial for the enhancement of product quality. As an extension of our recent works, in this research, a generic in-situ tool wear condition monitoring during the end milling process based on dynamic mode and abnormal evaluation is proposed. With the engagement of dynamic mode decomposition, the real-time response of the sensing physical quantity during the end milling process can be predicted. Besides, by constructing the graph structure of the time series and calculating the difference between the predicted signal and the real-time signal, the anomaly can be acquired. Meanwhile, the tool wear state during the end milling process can be successfully evaluated. The proposed method is validated in milling tool wear experiments and received positive results (the mean relative error is recorded as 0.0507). The research, therefore, paves a new way to realize the in-situ tool wear condition monitoring.

Abstract Background Compared with the time-consuming and labor-intensive for biological validation in vitro or in vivo, the computational models can provide high-quality and purposeful candidates in an instant. Existing computational models face limitations in effectively utilizing sparse local structural information for accurate predictions in circRNA-disease associations. This study addresses this challenge with a proposed method, CDA-DGRL (Prediction of CircRNA-Disease Association based on Double-line Graph Representation Learning), which employs a deep learning framework leveraging graph networks and a dual-line representation model integrating graph node features. Method CDA-DGRL comprises several key steps: initially, the integration of diverse biological information to compute integrated similarities among circRNAs and diseases, leading to the construction of a heterogeneous network specific to circRNA-disease associations. Subsequently, circRNA and disease node features are derived using sparse autoencoders. Thirdly, a graph convolutional neural network is employed to capture the local graph network structure by inputting the circRNA-disease heterogeneous network alongside node features. Fourthly, the utilization of node2vec facilitates depth-first sampling of the circRNA-disease heterogeneous network to grasp the global graph network structure, addressing issues associated with sparse raw data. Finally, the fusion of local and global graph network structures is inputted into an extra trees classifier to identify potential circRNA-disease associations. Results The results, obtained through a rigorous five-fold cross-validation on the circR2Disease dataset, demonstrate the superiority of CDA-DGRL with an AUC value of 0.9866 and an AUPR value of 0.9897 compared to existing state-of-the-art models. Notably, the hyper-random tree classifier employed in this model outperforms other machine learning classifiers. Conclusion Thus, CDA-DGRL stands as a promising methodology for reliably identifying circRNA-disease associations, offering potential avenues to alleviate the necessity for extensive traditional biological experiments. The source code and data for this study are available at https://github.com/zywait/CDA-DGRL .

Abstract To construct a prediction model of olfactory dysfunction after transnasal sellar pituitary tumor resection based on machine learning algorithms. A cross-sectional study was conducted. From January to December 2022, 158 patients underwent transnasal sellar pituitary tumor resection in three tertiary hospitals in Sichuan Province were selected as the research objects. The olfactory status was evaluated one week after surgery. They were randomly divided into a training set and a test set according to the ratio of 8:2. The training set was used to construct the prediction model, and the test set was used to evaluate the effect of the model. Based on different machine learning algorithms, BP neural network, logistic regression, decision tree, support vector machine, random forest, LightGBM, XGBoost, and AdaBoost were established to construct olfactory dysfunction risk prediction models. The accuracy, precision, recall, F1 score, and area under the ROC curve (AUC) were used to evaluate the model's prediction performance, the optimal prediction model algorithm was selected, and the model was verified in the test set of patients. Of the 158 patients, 116 (73.42%) had postoperative olfactory dysfunction. After missing value processing and feature screening, an essential order of influencing factors of olfactory dysfunction was obtained. Among them, the duration of operation, gender, type of pituitary tumor, pituitary tumor apoplexy, nasal adhesion, age, cerebrospinal fluid leakage, blood scar formation, and smoking history became the risk factors of olfactory dysfunction, which were the key indicators of the construction of the model. Among them, the random forest model had the highest AUC of 0.846, and the accuracy, precision, recall, and F1 score were 0.750, 0.870, 0.947, and 0.833, respectively. Compared with the BP neural network, logistic regression, decision tree, support vector machine, LightGBM, XGBoost, and AdaBoost, the random forest model has more advantages in predicting olfactory dysfunction in patients after transnasal sellar pituitary tumor resection, which is helpful for early identification and intervention of high-risk clinical population, and has good clinical application prospects.

Abstract Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most common genetic cause is the recurrent IKBKG △4–10 deletion resulting from recombination between two MER67B repeats. Detection of variants in IKBKG is challenging due to the presence of a highly homologous non-pathogenic pseudogene IKBKGP1. In this study, we successfully identified four pathogenic variants in four IP patients using a strategy based on single-tube long fragment read (stLFR) sequencing with a specialized analysis pipeline. Three frameshift variants (c.519-3_519dupCAGG, c.1167dupC, and c.700dupT) were identified and subsequently validated by Sanger sequencing. Notably, c.519-3_519dupCAGG was found in both IKBKG and IKBKGP1, whereas the other two variants were only detected in the functional gene. The IKBKG △4–10 deletion was identified and confirmed in one patient. These results demonstrate that the proposed strategy can identify potential pathogenic variants and distinguish whether they are derived from IKBKG or its pseudogene. Thus, this strategy can be an efficient genetic testing method for IKBKG. By providing a comprehensive understanding of the whole genome, it may also enable the exploration of other genes potentially associated with IP. Furthermore, the strategy may also provide insights into other diseases with detection challenges due to pseudogenes.

Abstract Objective It has been reported that in western countries malignancy risk was higher in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with that in the general population. In the current study, we investigated the incidence, spectrum and risk factors of malignancy in Chinese AAV patients. Methods AAV patients diagnosed from 1995 to 2021 in Peking University First Hospital with a follow-up more than 12 months were recruited. Standardized incidence ratios (SIR) were calculated to describe the risk of malignancy, adjusted for sex, age and follow-up time. Results A total of 552 AAV patients were recruited, among which 23 patients had malignancies either preceding or concurrent with AAV diagnosis, and 43 of the remaining 529 patients developed malignancies within 4.3 ± 4.2 years post AAV diagnosis (SIR: 2.24; 95% CI: 1.68–2.99; p

Abstract With the acceleration of urbanization in China, the urban population continues to grow, leading to frequent occurrences of crowded public spaces, which in turn trigger traffic congestion and even safety accidents. In order to more effectively control pedestrian flow, enhance the efficiency and safety of public spaces, this experiment conducts in-depth research and improvement on the traditional Dynamic Window Approach (DWA), and applies it to the fine control of pedestrian flow. Specifically, this study comprehensively reviews and analyzes the characteristics of pedestrian traffic flow and the working principles of traditional DWA. Based on this, the shortcomings of traditional DWA in dealing with complex pedestrian flow scenarios are identified, and targeted improvement solutions are proposed. The core of this improvement scheme lies in the introduction of a new evaluation function, enabling DWA to more accurately balance various factors in the decision-making process, including pedestrian movement speed, direction, and spatial distribution. Subsequently, the improved DWA is validated through simulation experiments. The experimental scenario is set in an area of 18 m*18 m, and compared with traditional DWA, the improved DWA shows significant advantages in trajectory length and travel time. Specifically, the trajectory length of the traditional DWA robot is 19.4 m, with a required time of 34.8 s, while the trajectory length of the improved DWA robot is shortened to 18.7 m, and the time is reduced to 18.6 s. This result fully demonstrates the effectiveness of the improved DWA in optimizing pedestrian flow control. The improved DWA proposed in this study not only has strong scientific validity but also demonstrates high efficiency in practical applications. This study has important reference value for improving the safety of urban public spaces and improving pedestrian traffic flow conditions, and provides new ideas for the further development of pedestrian flow control technology in the future.

Abstract Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers.

Abstract Variations in functional traits serve as measures of plants’ ability to adapt to environment. Exploring the patterns of functional traits of desert plants along elevational gradients is helpful to understand the responses and adaptation strategies of species to changing environments. However, it is unknown whether the relationship between functional traits and elevation is affected by differences in the species’ elevational distributions (elevation preference and species’ range). Importantly, most researches have concerned with differences in mean trait values and ignored intraspecific trait variation. Here, we measured functional traits of desert plants along a wide elevational gradient in the Tibetan Plateau and adjacent areas and explored functional trait patterns over elevation in species with different elevational distributions. We decomposed trait variation and further investigated characterizations of intraspecific variation. Ultimately, the main drivers of trait variation were identified using redundancy analysis. We found that species’ elevational distributions significantly influenced the relationship of functional traits such as plant height, leaf dry matter content, leaf thickness, leaf nitrogen and carbon content with elevation. Species with a lower elevational preference showed greater trait variation than species with a higher elevational preference, suggesting that species that prefer high elevation are more conservative facing environmental changes. We provide evidence that interspecific trait variation in leaf thickness and leaf carbon content decreased with increasing species’ range, indicating that increased variations in resistance traits within species make greater responsiveness to environmental changes, enabling species a wider range. Elevation, temperature and precipitation were the main drivers of trait variation in species with a low elevational preference, while the effect of precipitation on trait variation in species with a high elevational preference was not significant. This study sheds new insights on how plants with different elevational distributions regulate their ecological strategies to cope with changing environments.

Abstract Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.

Abstract Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3β-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3β-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3β-tigloyloxytropane synthase (TS), catalyzes 3β-tropanol and tigloyl-CoA to form 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3β-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3β-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3β-tigloyloxytropane from tiglic acid and 3β-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3β-tigloyloxytropane.

Abstract In order to realize the intelligent monitoring of the high-precision positioning of the hole position and the real-time control of the verticality of the pile, an intelligent monitoring system was developed based on the combination positioning technology of BDS and UWB and the biaxial tilt sensor, and the numerical simulation and comparative analysis of the verticality of the pile were carried out by abaqus. The deviation of pile foundation in different directions and the deviation of pile body are controlled by the monitoring system, and abnormal warning is made when the deviation exceeds the permissible range.Through the application of intelligent monitoring system in the pile foundation engineering area of Changshui Airport, it is found that the plane offset and perpendicularity of all piles meet the standard requirements and the construction error is controlled at a small value. The results show that the application of intelligent inspection system can not only ensure the construction quality of pile foundation, but also meet and improve the level of digitization and information technology of smart construction site.

Abstract Background Maxillary sinus squamous cell carcinoma (MS-SCC) is an infrequent malignancy, and determining the optimal neck management for patients with cT3/4N0 MS-SCC remains a topic of ongoing debate. The purpose of this study was to compare the prognoses and quality of life outcomes of patients who underwent either elective neck dissection (END) or elective neck irradiation (ENI) for cT3/4N0 MS-SCC. Methods In this retrospective study, we enrolled patients with surgically treated cT3/4N0 MS-SCC, and the impact of different neck management strategies on regional control and disease-specific survival was compared using propensity score matching. The effect of surgical intervention on quality of life was evaluated using the Mann-Whitney U test. Results Of the 120 patients included, 36 underwent END. After propensity score matching, our analysis indicated that END did not lead to superior outcomes than ENI, as demonstrated by comparable rates of regional control (p = 0.990) and disease-specific survival (p = 0.999). However, in the 70 returned questionnaires, patients who underwent END reported higher scores in the domains of appearance, chewing, and speech than did patients who underwent ENI. Conclusions Our findings suggest that while END and ENI contribute to similar prognoses, END yields superior functional outcomes.

Abstract Background Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. Results In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson’s disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. Conclusion These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

Abstract Immunosenescence increases the risk and severity of diseases in elderly individuals and leads to impaired vaccine-induced immunity. With aging of the global population and the emerging risk of epidemics, developing adjuvants and vaccines for elderly individuals to improve their immune protection is pivotal for healthy aging worldwide. Deepening our understanding of the role of immunosenescence in vaccine efficacy could accelerate research focused on optimizing vaccine delivery for elderly individuals. In this review, we analyzed the characteristics of immunosenescence at the cellular and molecular levels. Strategies to improve vaccination potency in elderly individuals are summarized, including increasing the antigen dose, preparing multivalent antigen vaccines, adding appropriate adjuvants, inhibiting chronic inflammation, and inhibiting immunosenescence. We hope that this review can provide a review of new findings with regards to the impacts of immunosenescence on vaccine-mediated protection and inspire the development of individualized vaccines for elderly individuals.

Abstract This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of

Abstract Antigen-specific T cell receptor-engineered T cell (TCR-T) based immunotherapy has proven to be an effective method to combat cancer. In recent years, cross-talk between the innate and adaptive immune systems may be requisite to optimize sustained antigen-specific immunity, and the stimulator of interferon genes (STING) is a promising therapeutic target for cancer immunotherapy. The level of expression or presentation of antigen in tumor cells affects the recognition and killing of tumor cells by TCR-T. This study aimed at investigating the potential of innate immune stimulation of T cells and engineered T cells to enhance immunotherapy for low-expression antigen cancer cells. We systematically investigated the function and mechanism of cross-talk between STING agonist diABZI and adaptive immune systems. We established NY-ESO-1 full knockout Mel526 cells for this research and found that diABZI activated STING media and TCR signaling pathways. In addition, the results of flow cytometry showed that antigens presentation from cancer cells induced by STING agonist diABZI also improved the affinity of TCR-T cells function against tumor cells in vitro and in vivo. Our findings revealed that diABZI enhanced the immunotherapy efficacy of TCR-T by activating STING media and TCR signaling pathways, improving interferon-γ expression, and increasing antigens presentation of tumor cells. This indicates that STING agonist could be used as a strategy to promote TCR-T cancer immunotherapy.

Abstract The main objective was to establish a prognostic model utilising long non‐coding RNAs associated with disulfidptosis and cuproptosis. The data for RNA‐Sequence and clinicopathological information of Colon adenocarcinoma (COAD) were acquired from The Cancer Genome Atlas. A prognostic model was constructed using Cox regression and the Least Absolute Shrinkage and Selection Operator method. The model's predictive ability was assessed through principal component analysis, Kaplan–Meier analysis, nomogram etc. The ability of identifying the rates of overall survival, infiltration of immune cells, and chemosensitivity was also explored. In vitro experiments were conducted for the validation of differential expression and function of lncRNAs. A disulfidptosis and cuproptosis‐related lncRNA prognostic model was constructed. The prognostic model exhibits excellent independent predictive capability for patient outcomes. Based on the authors’ model, the high‐risk group exhibited higher tumour mutation burdened worse survival. Besides, differences in immune cell infiltration and responsiveness to chemotherapeutic medications exist among patients with different risk scores. Furthermore, aberrant expressions in certain lncRNAs have been validated in HCT116 cells. In particular, FENDRR and SNHG7 could affect the proliferation and migration of colorectal cancer cells. Our study developed a novel prognostic signature, providing valuable insights into prognosis, immune infiltration, and chemosensitivity in COAD patients.

For advanced aero-engine design and research, modeling and simulation in a digital environment is indispensable, especially for engines of complicated configurations, such as variable cycle engines (VCE) and adaptive cycle engines (ACE). Also, in the research of future smart engines, reliable real-time digital twins are paramount. However, the 2 dominant methods that used in solving the simulation models, Newton-Raphson (N-R) method and volume-based method, are not fully qualified for the study requirements, because neither of them reaches the satisfactory balance of convergence rate and calculating efficiency. In this study, by deeply analyzing the mathematical principle of these 2 methods, a novel modeling and solving method for aero-engine simulation, which integrates the advantages of both N-R and volume-based methods, is established. It has distributed architecture and local quadratic convergence rate. And a novel modeling method for variable area bypass injectors (VABI) is put forward. These facilitate simulation of various configurations of aero-engines. The modeling cases, including a high bypass-ratio (BPR) turbofan and an ACE, illustrate that the novel technique decreases the iterations by about two-thirds comparing with volume-based method, while the success rate of convergence remains over 99%. This proves its superiority in both convergence and calculating efficiency over the conventional ones. This technique can be used in advanced gas turbine engine design and control strategy optimization, and study of digital twins.

Abstract Background The treatment for colon adenocarcinoma (COAD) faces challenges in terms of immunotherapy effectiveness due to multiple factors. Because of the high tumor specificity and immunogenicity, neoantigen has been considered a pivotal target for cancer immunotherapy. Therefore, this study aims to identify and predict the potential tumor antigens of MUC somatic mutations (MUCmut) in COAD. Methods Three databases of TCGA, TIMER2.0, and cBioPortal were used for a detailed evaluation of the association between MUCmut and multi-factors like tumor mutation burden (TMB), microsatellite instability (MSI), prognosis, and the tumor microenvironment within the context of total 2242 COAD patients. Next, TSNAdb and the differential agretopicity index (DAI) were utilized to predict high-confidence neopeptides for MUCmut based on 531 COAD patients’ genomic information. DAI was calculated by subtraction of its predicted HLA binding affinity of the MUCmut peptide from the corresponding wild-type peptide. Results The top six mutation frequencies (14 to 2.9%) were from MUC16, MUC17, MUC5B, MUC2, MUC4 and MUC6. COAD patients with MUC16 and MUC4 mutations had longer DFS and PFS. However, patients with MUC13 and MUC20 mutations had shorter OS. Patients with the mutation of MUC16, MUC5B, MUC2, MUC4, and MUC6 exhibited higher TMB and MSI. Moreover, these mutations from the MUC family were associated with the infiltration of diverse lymphocyte cells and the expression of immune checkpoint genes. Through TSNAdb 1.0/NetMHCpan v2.8, 452 single nucleotide variants (SNVs) of MUCmut peptides were identified. Moreover, through TSNAdb2.0/NetMHCpan v4.0, 57 SNVs, 1 Q-frame shift (TS), and 157 short insertions/deletions (INDELs) of MUCmut were identified. Finally, 10 high-confidence neopeptides of MUCmut were predicted by DAI. Conclusions Together, our findings establish the immunogenicity and therapeutic potential of mutant MUC family-derived neoantigens. Through combining the tools of TSNAdb and DAI, a group of novel MUCmut neoantigens were identified as potential targets for immunotherapy.

Abstract Objective Alzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia. Methods We used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features. Results There were lower levels of tau pathology (β = 1.86–2.96, p

Abstract Owing to the specific electronic-redistribution and spatial proximity, diatomic catalysts (DACs) have been identified as principal interest for efficient photoconversion of CO2 into C2H4. However, the predominant bottom-up strategy for DACs synthesis has critically constrained the development of highly ordered DACs due to the random distribution of heteronuclear atoms, which hinders the optimization of catalytic performance and the exploration of actual reaction mechanism. Here, an up-bottom ion-cutting architecture is proposed to fabricate the well-defined DACs, and the superior spatial proximity of CuAu diatomics (DAs) decorated TiO2 (CuAu-DAs-TiO2) is successfully constructed due to the compact heteroatomic spacing (2-3 Å). Owing to the profoundly low C-C coupling energy barrier of CuAu-DAs-TiO2, a considerable C2H4 production with superior sustainability is achieved. Our discovery inspires a novel up-bottom strategy for the fabrication of well-defined DACs to motivate optimization of catalytic performance and distinct deduction of heteroatom synergistically catalytic mechanism.

Abstract Study question The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. Summary answer A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy. What is known already Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF. Study design, size, duration A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022. Participants/materials, setting, methods This study included 462 patients in the RIF group and 4750 patients in the control group. The patients’ basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200). Main results and the role of chance (1) An increased duration of infertility (1.978; 95% CI, 1.264–3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185–4.336), low AMH levels (0.504; 95% CI, 0.275–0.922), insulin resistance (3.548; 95% CI, 1.931–6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-β2-glycoprotein I antibody (A-β2-GPI Ab)-positive status (5.515; 95% CI, 1.481–20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870–0.929) for the training cohort and 0.895 (95% CI, 0.865–0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015–1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181–0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597–0.748). Limitations, reasons for caution This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation. Wider implications of the findings Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes. Study funding/competing interest(s) This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82,201,792, 82,301,871, 81,971,446, and 82,374,212) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare. Trial registration number This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).

Abstract The flower thrips Frankliniella intonsa (Thysanoptera: Thripidae) is a common insect found in flowers of many plants. Sometimes, F. intonsa causes damage to crops through direct feeding and transmission of plant viruses. Here, we assembled a chromosomal level genome of F. intonsa using the Illumina, Oxford Nanopore (ONT), and Hi-C technologies. The assembled genome had a size of 209.09 Mb, with a contig N50 of 997 bp, scaffold N50 of 13.415 Mb, and BUSCO completeness of 92.5%. The assembled contigs were anchored on 15 chromosomes. A set of 14,109 protein-coding genes were annotated in the genome with a BUSCO completeness of 95.0%. The genome contained 491 non-coding RNA and 0.57% of interspersed repeats. This high-quality genome provides a valuable resource for understanding the ecology, genetics, and evolution of F. intonsa, as well as for controlling thrips pests.

Abstract Background Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. Methods We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. Results All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. Conclusion Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

Abstract Background The spread of the coronavirus has led to significant anxiety among university students, resulting in various mental health problems that could potentially impact their academic performance. Method To examine the mediating role of emotional regulation and online social support in the relationships between COVID-19 psychological pressures, depression, and the fear of missing out (FoMO) among young adult university students, a cross-sectional research design was employed using an online survey. The sample consisted of 521 full-time university students from China, currently enrolled in undergraduate and postgraduate programs. Results Findings revealed that more than half (55.09%, n=287) of the university students experienced COVID-19 psychological pressures. These pressures directly contributed to increased levels of depression (β = 0.339, p < .001) and fear of missing out (β = 0.236, p < .001). Moreover, online social support and emotional regulation exhibited partial mediating effects on the association between COVID-19 psychological pressures, depression, and the fear of missing out. The results indicated that COVID-19 psychological pressures were linked to higher levels of depressive symptoms and a greater fear of missing out among university students. Conclusions However, the provision of timely and adequate online social support, as well as the implementation of emotional regulation strategies, mitigated the negative effects of the pandemic on students' social and emotional well-being. Consequently, this led to reduced levels of depression and fear of missing out.

Sex control techniques are in great demand for aquaculture because of the huge benefits of mono-sex production. In a previous study on yellow catfish (Tachysurus fulvidraco), intersex individuals were produced by administrating 17α-methyltestosterone (MT) or aromatase inhibitor letrozole (LZ). The ovarian and testicular portions of intersexual gonads developed well and were completely separated, arousing our interest in producing self-fertilizable fish and clone-like fish populations. In this study, yellow catfish fry were treated with a combination of MT and LZ at a low dose (5 mg kg−1 MT, 300 mg kg−1 LZ) at a low water temperature (27.0 °C, mixed sex-producing temperature, LL group) and a high temperature (33.5 °C, male-producing temperature, HL group), and with a high dose (10 mg kg−1 MT, 600 mg kg−1 LZ) at a low water temperature (LH group), during 12–65 days post-hatching, the critical period of sex differentiation. Both XX and XY intersex were produced with different percentages at the same time through co-treatment with MT and LZ, with or without the help of male-producing temperature. The highest percentage of XY intersex (53% in XY, 36% in XX and XY) and XX intersex (47% in XX, 25% in XX and XY) was produced in LH and HL groups, respectively. Results of gonadal morphology, histology, and sperm dynamic analysis indicate that some XX and XY intersex individuals were capable of self-fertilization through artificial insemination. The reproductive performance of these intersex individuals was then investigated by injecting spawning agents, dissecting gonads, and artificially fertilizing eggs with their own sperm. The XX, XY, and YY genotypic individuals were produced by the self-fertilization of XY intersex individuals. The present study successfully produced high percentages of XX and XY intersex and conducted self-fertilization by mating the eggs and sperm of a single intersex individual. Self-fertilization in fish will show great potential in aquaculture genetics and breeding, for example, generating highly homozygous (or ‘‘clonal’’) genetic material, producing mono-sex populations, and identifying unknown sex determination modes. In particular, the cloning method of producing genetic materials will be greatly beneficial for maintaining advantageous traits through self-fertilization generation after generation.

Neuregulin 4 (Nrg4), an epidermal growth factor (EGF) family member, can bind to and activate the ErbB4 receptor tyrosine kinase. Nrg4 has five different isoforms by alternative splicing and performs a wide variety of functions. Nrg4 is involved in a spectrum of physiological processes including neurobiogenesis, lipid metabolism, glucose metabolism, thermogenesis, and angiogenesis. In pathological processes, Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory diseases. In addition, Nrg4 could ameliorate obesity, insulin resistance, and cardiovascular diseases. Furthermore, Nrg4 improves non-alcoholic fatty liver disease (NAFLD) by promoting autophagy, improving lipid metabolism, and inhibiting cell death of hepatocytes. Besides, Nrg4 is closely related to the development of cancer, hyperthyroidism, and some other diseases. Therefore, elucidation of the functional role and mechanisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.

Hemophilia B (HB) is an inherited bleeding disorder caused by defects in the FⅨ gene, leading to severe coagulation dysfunction. This study designed eight pairs of primers covering eight exons of the FⅨ gene and used PCR and DNA sequencing to detect FⅨ gene mutations in 31 HB patients. Sequencing results were compared with normal sequences using Chromas software on Blast to identify mutation sites. Findings revealed the CpG dinucleotide region as a mutation hotspot and the 192nd nucleotide (FⅨ192) as a dinucleotide polymorphism site in the Chinese population. Pathogenic mutations included point mutations, deletions, insertions, and mutations affecting amino acids or splicing sites. For cases with only polymorphic sites, further exon sequencing is needed. This study adds new mutation data to the global HB database, supports research on racial differences in FⅨ gene mutations, and contributes to domestic HB statistics. The results aid in understanding the FⅨ gene's role in coagulation, elucidating HB pathogenesis, and providing a basis for future gene therapy.

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a serious pulmonary vascular disease characterized by residual thrombi in the pulmonary arteries and distal pulmonary microvascular remodeling. The pathogenesis of CTEPH remains unclear, but many factors such as inflammation, immunity, coagulation and angiogenesis may be involved. Monocytes are important immune cells that can differentiate into macrophages and dendritic cells and play an important role in thrombus formation. However, the distribution, gene expression profile and differentiation trajectory of monocyte subsets in CTEPH patients have not been systematically studied. This study aims to reveal the characteristics and functions of monocytes in CTEPH patients using single-cell sequencing technology, and to provide new insights for the diagnosis and treatment of CTEPH.MethodsSingle-cell RNA sequencing (scRNA-seq) were performed to analyze the transcriptomic features of peripheral blood mononuclear cells (PBMCs) from healthy controls, CTEPH patients and the tissues from CTEPH patients after the pulmonary endarterectomy (PEA). We established a CTEPH rat model with chronic pulmonary embolism caused by repeated injection of autologous thrombi through a central venous catheter, and used flow cytometry to detect the proportion changes of monocyte subsets in CTEPH patients and CTEPH rat model. We also observed the infiltration degree of macrophage subsets in thrombus tissue and their differentiation relationship with peripheral blood monocyte subsets by immunofluorescence staining.ResultsThe results showed that the monocyte subsets in peripheral blood of CTEPH patients changed significantly, especially the proportion of CD16+ monocyte subset increased. This monocyte subset had unique functional features at the transcriptomic level, involving processes such as cell adhesion, T cell activation, coagulation response and platelet activation, which may play an important role in pulmonary artery thrombus formation and pulmonary artery intimal remodeling. In addition, we also found that the macrophage subsets in pulmonary endarterectomy tissue of CTEPH patients showed pro-inflammatory and lipid metabolism reprogramming features, which may be related to the persistence and insolubility of pulmonary artery thrombi and the development of pulmonary hypertension. Finally, we also observed that CD16+ monocyte subset in peripheral blood of CTEPH patients may be recruited to pulmonary artery intimal tissue and differentiate into macrophage subset with high expression of IL-1β, participating in disease progression.ConclusionCD16+ monocytes subset had significant gene expression changes in CTEPH patients, related to platelet activation, coagulation response and inflammatory response. And we also found that these cells could migrate to the thrombus and differentiate into macrophages with high expression of IL-1β involved in CTEPH disease progression. We believe that CD16+ monocytes are important participants in CTEPH and potential therapeutic targets.

BackgroundAcetaminophen is a commonly used medication, yet its recommendation for patients with comorbid conditions of gout and hypertension is contradictory, and the impact of its usage on clinical outcomes in real-world practical settings remains uncertain. The aim of this study was to investigate the association between acetaminophen administration and clinical outcomes in critically ill patients with gout and hypertension, utilizing real-world data.MethodsA retrospective cohort study was conducted based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with gout and hypertension were included in the analysis. The exposure was acetaminophen use during ICU stay. The primary outcome was in-hospital mortality. The secondary endpoints were frequent hospitalization, 30-day, and 60-day all-cause mortality, and incidence of hypertensive emergencies. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders.ResultsThe pre-matched and propensity score-matched cohorts included 2448 and 1012 patients, respectively. In the PSM analysis, in-hospital mortality was 9.7% (49/506) in the acetaminophen use group and 12.1% (61/506) in the no use group. Acetaminophen use was associated with a decrease in-hospital mortality (hazard ratio [HR], 0.62; 95% CI, 0.41–0.92; P = 0.018). In terms of secondary endpoints, after PSM, there was no statistically significant difference for both 30-day and 60-day all-cause mortality reductions in the acetaminophen use group, and HRs were 0.78 (95% CI 0.55–1.11; P = 0.175), and 0.75 (95% CI 0.55–1.02; P = 0.069), respectively. According to the analysis of dosage and treatment group, the use of APAP within the dosage range of 2–4 g and within 3–5 days of treatment significantly reduced the mortality rate of the entire cohort and PSM cohort, with statistical differences. Subgroup analysis demonstrated that lower in-hospital mortality was consistent across different baselines (age, gender, BMI, liver disease, and renal disease), with no interactions in all subgroups (interaction p-values >0.05), thereby affirming the robustness and reliability of the findings.ConclusionAcetaminophen use was associated with lower in-hospital mortality in critically ill patients with gout and hypertension. Prospective studies are needed to verify this finding.

Abstract Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of “immune cold” tumors into “immune hot” tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor‐exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium‐based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium‐based down‐conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near‐infrared imaging system and improves radiation efficacy via lutetium‐based radio‐sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging‐guided tumor delineation, radio‐sensitization, and immune activation post‐radiation, thus presenting an efficient radio‐immunotherapeutic approach for TNBC.

BackgroundPolycyclic aromatic hydrocarbons (PAHs), as organic pollutants widely present in daily environments, have been shown by existing epidemiological studies to be significantly associated with deficits in learning and memory functions in children and adults. However, the association between exposure to PAHs and cognitive function in older adults remains unclear. Additionally, existing related studies have only assessed the association between individual PAH exposures and cognitive assessments, overlooking the risks posed by mixed exposures. This study aims to use three statistical models to investigate the individual and overall effects of mixed PAH exposures on the cognition of older adults in the United States.MethodsThe study cohort was obtained from the NHANES database, which included individuals aged 60 and older from 2011 to 2014. Weighted generalized linear models (GLM), weighted quantile sum (WQS) models, and Bayesian kernel machine regression (BKMR) models were utilized to evaluate the connections between urinary PAH metabolites and the standardized Z-scores of four cognitive tests: Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST).ResultsOur analysis involved 899 individuals aged 60 and above. In the fully adjusted GLM, 2-hydroxynaphthalene (2-OHNa), 3-hydroxyfluorene (3-OHFlu), and 2-hydroxyfluorene (2-OHFlu) demonstrated negative associations with DSST Z-scores. In the WQS model, six urinary PAH metabolites were negatively linked to AFT Z-scores (β (95% confidence intervals [CI]): −0.120 (−0.208, −0.033), p = 0.007) and DSST Z-scores (β (95% CI): −0.182 (−0.262, −0.103), p

Background：Increasing evidence indicates that clinicopathologic phenotypes and ANCA serotypes may differ ethnically and geographically. This review highlights the progress in the prevalence, pathogenesis, management, and outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in China. Summary: AAV is not rare in China. Cumulative evidence has demonstrated a significant preponderance of microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA AAV in China. Even in patients with granulomatosis with polyangiitis (GPA), there is a predominance of MPO-ANCA over proteinase 3 (PR3)-ANCA, presenting a unique subset. The pathogenesis of AAV is multifactorial, with the role of complement activation being highlighted during recent years. Treatment strategies for AAV in China have also been refined recently. A rapid tapering of glucocorticoids to minimize exposure has been recommended by the Chinese guidelines. Along with a better understanding of the disease, B cell-targeted therapy and complement-targeted therapy are developing. A considerable number of patients in China received rituximab treatment and achieved remission. However, infection risk and associated mortality still remain concerns. Therefore, less rituximab exposure should be considered and evaluated in Chinese AAV patients. Prognostic factors have been reviewed. Of note, along with improved outcomes, there is an increase of cardiovascular and malignant related death, warranting specific care. Recently, a modified renal risk score model has been validated for early risk prediction in Chinese AAV patients. Moreover, emerging biomarkers for AAV, including complement components, have been identified in Chinese patients. Key Messages: There is a preponderance of MPA and MPO-ANCA in China. Treatment strategies for Chinese AAV patients generally align with those in western countries, and to some extent, less aggressive. Prognostic factors and emerging biomarkers for AAV in China have been identified. Further challenges include optimizing interventions, minimizing treatment-related comorbidities, improving disease monitoring, and enhancing life qualities of AAV patients.

Peptide-functionalized hydrogel is one of commonly used biomaterials to introduce hydrogel-induced vessel regeneration. Despite many reports about the discoveries of high-active peptides (or ligands) for regeneration, the study on the conjugating methods for the hydrogel functionalization with peptides is limited. Here, we compared the vasculogenic efficacy of the peptide-functionalized hydrogels prepared by two commonly used conjugating methods, 1-ethyl-3-(3-dimethylamino propyl) carbodiimide (EDC) and Click methods, through cell models, organ-on-chips models, animal models, and RNA sequencing analysis. Two vascular-related cell types, the human umbilical vein endothelial cells (HUVECs) and the adipose-derived stem cells (ADSCs), have been cultured on the hydrogel surfaces prepared by EDC/Click methods. It showed that the hydrogels prepared by Click method supported the higher vasculogenic activities while the ones made by EDC method compromised the peptide activities on hydrogels. The vasculogenesis assays further revealed that hydrogels prepared by Click method promoted a better vascular network formation. In a critical ischemic hindlimb model, only the peptide-functionalized hydrogels prepared by Click method successfully salvaged the ischemic limb, significantly improved blood perfusion, and enhanced the functional recoveries (through gait analysis and animal behavior studies). RNA sequencing studies revealed that the hydrogels prepared by Click method significantly promoted the PI3K-AKT pathway activation compared to the hydrogels prepared by EDC method. All the results suggested that EDC method compromised the functions of the peptides, while Click method preserved the vascular regenerating capacities of the peptides on the hydrogels, illustrating the importance of the conjugating method during the preparation of the peptide-functionalized hydrogels.

Abstract BackgroundThe core Healthy Days measures were used to track the population-level health status in the China Chronic Disease and Risk Factor Surveillance; however, they were not easily combined to create a summary of the overall health-related quality of life (HRQOL), limiting this indicator’s use. ObjectiveThis study aims to develop a summary score based on the Chinese version of the core Healthy Days measures (HRQOL-5) and apply it to estimate HRQOL and its determinants in a Chinese population. MethodsFrom November 2018 to May 2019, a multistage stratified cluster survey was conducted to examine population health status and behavioral risk factors among the resident population older than 15 years in Weifang City, Shandong Province, China. Both exploratory factor analyses and confirmatory factor analyses were performed to reveal the underlying latent construct of HRQOL-5 and then to quantify the overall HRQOL by calculating its summary score. Tobit regression models were finally carried out to identify the influencing factors of the summary score. ResultsA total of 26,269 participants (male: n=13,571, 51.7%; mean age 55.9, SD 14.9 years) were included in this study. A total of 71% (n=18,663) of respondents reported that they had excellent or very good general health. One summary factor was extracted to capture overall HRQOL using exploratory factor analysis. The confirmatory factor analysis further confirmed this one-factor model (Tucker-Lewis index, comparative fit index, and goodness-of-fit index >0.90; root mean square error of approximation 0.02). Multivariate Tobit regression analysis showed that age (β=–0.06), educational attainments (primary school: β=0.72; junior middle school: β=1.46; senior middle school or more: β=2.58), average income (≥¥30,000 [US $4200]: β=0.69), physical activity (β=0.75), alcohol use (β=0.46), self-reported disease (β=−6.36), and self-reported injury (β=–5.00) were the major influencing factors on the summary score of the HRQOL-5. ConclusionsThis study constructs a summary score from the HRQOL-5, providing a comprehensive representation of population-level HRQOL. Differences in summary scores of different subpopulations may help set priorities for health planning in China to improve population HRQOL.

Abstract Background Synonymous variants are non‐pathogenic due to non‐substitution of amino acids. However, synonymous exonic terminal nucleotide substitutions may affect splicing. Splicing variants are easily analyzed at RNA level for genes expressed in blood cells. Minigene analysis provides another method for splicing variant analysis of genes that are poorly or not expressed in peripheral blood. Methods Whole exome sequencing was performed to screen for potential pathogenic mutations in the proband, which were validated within the family by Sanger sequencing. The pathogenicity of the synonymous mutation was analyzed using the minigene technology. Results The proband harbored the compound heterogeneous variants c. [291G >A; 572‐50C >T] and c.681 + 1G >T in F7, of which the synonymous variant c.291G >A was located at the terminal position of exon 3. Minigene analysis revealed exon3 skipping due to this mutation, which may have subsequently affected protein sequence, structure, and function. Conclusion Our finding confirmed the pathogenicity of c.291G >A, thus extending the pathogenic mutation spectrum of F7, and providing insights for effective reproductive counseling.

Abstract Electrochemical synthesis of ammonia (NH3) in aqueous electrolyte has long been suffered from poor nitrogen (N2) supply owing to its low solubility and sluggish diffusion kinetics. Therefore, creating a N2 rich microenvironment around catalyst surface may potentially improve the efficiency of nitrogen reduction reaction (NRR). Herein, a delicately designed N2 filtering membrane consisted of polydimethylsiloxane is covered on catalyst surface via superspreading. Because this membrane let the dissolved N2 molecules be accessible to the catalyst but block excess water, the designed N2 rich microenvironment over catalyst leads to an optimized Faradaic efficiency of 39.4% and an NH3 yield rate of 109.2 µg h−1 mg−1, which is superior to those of the most report metal‐based catalysts for electrochemical NRR. This study offers alternative strategy for enhancing NRR performance.

Background Machine learning classifiers are increasingly used to create predictive models for pathological complete response (pCR) in breast cancer after neoadjuvant therapy (NAT). Few studies have compared the effectiveness of different ML classifiers. This study evaluated radiomics models based on pre- and post-contrast first-phase T1 weighted images (T1WI) in predicting breast cancer pCR after NAT and compared the performance of ML classifiers. Methods This retrospective study enrolled 281 patients undergoing NAT from the Duke-Breast-Cancer-MRI dataset. Radiomic features were extracted from pre- and post-contrast first-phase T1WI images. The Synthetic Minority Oversampling Technique (SMOTE) was applied, then the dataset was randomly divided into training and validation groups (7:3). The radiomics model was built using selected optimal features. Support vector machine (SVM), random forest (RF), decision tree (DT), k-nearest neighbor (KNN), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM) were classifiers. Receiver operating characteristic curves were used to assess predictive performance. Results LightGBM performed best in predicting pCR [area under the curve (AUC): 0.823, 95% confidence interval (CI) [0.743–0.902], accuracy 74.0%, sensitivity 85.0%, specificity 67.2%]. During subgroup analysis, RF was most effective in pCR prediction in luminal breast cancers (AUC: 0.914, 95% CI [0.847–0.981], accuracy 87.0%, sensitivity 85.2%, specificity 88.1%). In triple-negative breast cancers, LightGBM performed best (AUC: 0.836, 95% CI [0.708–0.965], accuracy 78.6%, sensitivity 68.2%, specificity 90.0%). Conclusion The LightGBM-based radiomics model performed best in predicting pCR in patients with breast cancer. RF and LightGBM showed promising results for luminal and triple-negative breast cancers, respectively.

Vitamins are dietary components necessary for cellular metabolic balance, especially redox homeostasis; deficient or excessive supply may give rise to symptoms of psychiatric disorders. Exploring the nutritional and metabolic pathways of vitamins could contribute to uncovering the underlying pathogenesis of ferroptosis-associated diseases. This mini-review aims to provide insights into vitamins closely linked to the regulation of ferroptosis from the perspective of cellular reactive oxygen species biology. The mainstream reprogramming mechanisms of ferroptosis are overviewed, focusing on unique biological processes of iron metabolism, lipid metabolism, and amino acid metabolism. Moreover, recent breakthroughs in therapeutic interventions targeting ferroptosis via fully utilizing vitamin-based pharmacological tools were overviewed, covering vitamins (B, C, E, and K). Finally, mechanism insight related to vitamin-associated nutrient signaling was provided, highlighting the pharmacological benefits of metabolically reprogramming ferroptosis-associated diseases.

ObjectiveTo investigate the current situation of olfactory dysfunction in patients after endoscopic transsphenoidal resection of pituitary tumors, and analyze its influencing factors, to provide references for clinical nursing and rehabilitation.MethodsA cross-sectional study design and convenience sampling method were used to investigate 158 patients with pituitary tumors treated by endoscopic transsphenoidal pituitary tumor resection in the Department of Neurosurgery of three Grade-A general hospitals in Sichuan Province from January 2022 and June 2023. The olfactory function of patients was evaluated 1 week after surgery, and the general clinical data and olfactory related data of patients were collected, and the influencing factors of olfactory disorder were analyzed by logistic regression.ResultsThe incidence of olfactory dysfunction was 73.42%. analysis revealed that the formation of blood scabs, nasal cavity adhesion, cerebrospinal fluid leakage and operation time were independent risk factors for olfactory dysfunction in patients after transsphenoidal pituitary tumor resection (p