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Abstract Background This study aims to construct a clinical prediction model and create a visual line chart depicting the risk of acute kidney injury (AKI) following resuscitation in cardiac arrest (CA) patients. Additionally, the study aims to validate the clinical predictive accuracy of the developed model. Methods Data were retrieved from the Dryad database, and publicly shared data were downloaded. This retrospective cohort study included 347 successfully resuscitated patients post-cardiac arrest from the Dryad database. Demographic and clinical data of patients in the database, along with their renal function during hospitalization, were included. Through data analysis, the study aimed to explore the relevant influencing factors of acute kidney injury (AKI) in patients after cardiopulmonary resuscitation. The study constructed a line chart prediction model using multivariate logistic regression analysis with post-resuscitation shock status (Post-resuscitation shock refers to the condition where, following successful cardiopulmonary resuscitation after cardiac arrest, some patients develop cardiogenic shock.), C reactive protein (CRP), Lactate dehydrogenase (LDH), and Alkaline phosphatase (ALP) identified as predictive factors. The predictive efficiency of the fitted model was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results Multivariate logistic regression analysis showed that post-resuscitation shock status, CRP, LDH, and PAL were the influencing factors of AKI after resuscitation in CA patients. The calibration curve test indicated that the prediction model was well-calibrated, and the results of the Decision Curve Analysis (DCA) demonstrated the clinical utility of the model constructed in this study. Conclusion Post-resuscitation shock status, CRP, LDH, and ALPare the influencing factors for AKI after resuscitation in CA patients. The clinical prediction model constructed based on the above indicators has good clinical discriminability and practicality.

Abstract This study aimed to understand the health status of low-income individuals living alone and to identify influencing factors. Using systematic random sampling methods, low-income individuals living alone were randomly selected. Via telephone interviews, we gathered information about their general health status. A logistic regression model was used to analyze relevant factors about the physical health of this population. The study included 1583 low-income individuals living alone. The prevalence rate of all kinds of diseases in low-income living alone in this survey was 88.63%. The multifactorial logistic regression analysis revealed that the risk factors for illness in this population were age ≥ 60 (OR 1.842, 95% CI 1.135–2.926, P = 0.006), self-rated poor mental health (OR 2.538, 95% CI 1.128–3.828, P = 0.005), and self-rated poor hearing status (OR 2.781, 95% CI 1.586–3.647, P = 0.001). Being female (OR 0.469, 95% CI 0.178–0.821, P = 0.033) was identified as a protective factor. Low-income individuals living alone are a unique group who lack familial care and economic and social support, and are thus in a disadvantaged social position. Therefore, this population requires increased attention, especially regarding their physical health. Implementing targeted assistance policies to improve their health status and enhance their quality of life is essential.

Abstract Background Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq). Methods Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization. Results Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI. Conclusion The macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

Abstract Background Sjögren’s Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. Methods The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. Findings CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM’s diagnostic accuracy is closer to skilled pathologists compared to beginners. Interpretation Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Abstract The impact of efferocytosis-related genes (ERGs) on the diagnosis of colorectal cancer (CRC) remains unclear. In this study, efferocytosis-associated biomarkers for the diagnosis of CRC were identified by integrating data from transcriptome sequencing and public databases. Finally, the expression of biomarkers was validated by real-time quantitative polymerase chain reaction (RT-qPCR). Our study may provide a reference for CRC diagnosis. Background It has been shown that some efferocytosis related genes (ERGs) are associated with the development of cancer. However, it is still uncertain how ERGs may influence the diagnosis of colorectal cancer (CRC). Methods In our study, the CRC cohorts were gained from transcriptome sequencing and the gene expression omnibus (GEO) database (GSE71187). Efferocytosis related biomarkers with diagnostic utility for CRC were identified through combining differentially expressed analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Then, infiltration abundance of immune cells between CRC and control was evaluated. The regulatory networks (including mRNA-miRNA-lncRNA and miRNA/transcription factors (TF)-mRNA networks) were created. Finally, the expression of biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). Results There were 3 biomarkers (ELMO3, P2RY12, and PDK4) related diagnosis for CRC patients gained. ELMO3 was highly expressed in CRC group, while P2RY12 and PDK4 was lowly expressed. Besides, the infiltrating abundance of 3 immune cells between CRC and control groups was significantly differential, namely activated CD4 memory T cells, macrophages M0, and resting mast cells. We then constructed a mRNA-miRNA-lncRNA network containing 3 mRNAs, 33 miRNAs, and 22 lncRNAs, and a miRNA/TF-mRNA network including 3 mRNAs, 33 miRNAs, and 7 TFs. Additionally, RT-qPCR results revealed that the expression trends of all biomarkers were consistent with the transcriptome sequencing data and GSE71187. Conclusion Taken together, this study provides three efferocytosis related biomarkers (ELMO3, P2RY12, and PDK4) for diagnosis of CRC, providing a scientific reference for further studies of CRC.

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE) intervention timing and liver injury periodization in patients with exertional heat stroke(EHS). Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected, then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT, AST, TBIL and DBIL. According to propensity score matching analysis, 11 patients in the survival group and 12 patients in the death group were included in the statistical analysis, and 20 of them were treated with TPE. The changes in indicators and clinical outcomes before and after TPE were observed, in order to evaluate the impact of intervention timing on prognosis. Results Among the 23 patients, 14 had no liver injury or could progress to the repair phase, resulting in 3 deaths(with the mortality rate of 21.43%), while 9 patients failed to progress to the repair phase, resulting in 9 deaths(with the mortality rate of 100%), with significant differences(P

Objective To review the occurrence of allergic reactions during therapeutic plasma exchange (TPE) and to explore the risk factors of TPE allergic reactions. Methods The clinical data of 929 patients treated with TPE using plasma components by the Department of Transfusion Medicine in our medical center from 2018 to 2023 were collected. The influencing factors of allergic reactions were analyzed by univariate analysis, and the independent risk factors of allergic reactions were analyzed by logistic multivariate regression analysis. Results A total of 4 071 TPEs were performed in 929 patients.Among them, 198 patients (21.31%) experienced 349 times (8.57%) of allergic reactions, with the incidence of grade Ⅰ, Ⅱ and Ⅲ allergic reactions of 16.33%, 81.38% and 2.29%, respectively, and no deaths. The univariate analysis showed that the patient′s age, allergy history, diagnosis of immune-related diseases, ICU admission, plasma consumption, total blood volume, maximum blood flow rate and combined use of albumin were related to the occurrence of allergic reactions (P

Rock breaking has always been a challenging problem that must be solved in projects such as excavating mountains, drilling wells, and constructing railways. Among the rock-breaking cutter steels, AISI H13 steel and wear-resistant high manganese steel have become the best choices. From the characteristics and failure modes of the two, rock-breaking cutter steels should simultaneously have high strength, high toughness and high wear resistance to avoid short-term fracture/damage and cost increase. Analyzing the problems existing in the molding process of rock-breaking cutter steels such as die casting, forging, and hot stamping, traditional strengthening technologies such as alloying optimization, heat treatment, and surface treatment can achieve certain performance enhancement. After reaching the limits of traditional strengthening technologies, a series of nanoparticle strengthening technologies came into being. The selection, addition amount, and addition method of nanoparticles all affect the microstructure, mechanical properties and wear. To this end, this article summarizes the research progress and challenges of rock-breaking cutter steels, and discusses traditional strengthening technologies and mainstream nanoparticle strengthening technologies. It provides a reference for the future development of high-quality and high-performance rock-breaking cutter steels, with aim to simultaneously expand their application potentials to other fields.

Abstract This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database. The study employed a combination of signal quantification techniques, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), to enhance the accuracy of signal detection and reduce the risk of false positives or negatives. Between the first quarter of 2017 and the third quarter of 2023, the FAERS database collected a total of 11,485,105 drug AE reports, of which 5772 were related to Nusinersen. Through signal mining analysis, 218 preferred term (PT) signals involving 27 system organ classes (SOCs) were identified. The study discovered AEs related to metabolism and nutrition disorders, psychiatric disorders, and cardiac disorders SOCs, which were not mentioned in the product information. Additionally, complications directly related to the intrathecal administration of Nusinersen, such as increased CSF pressure, positive CSF red blood cell count, and AEs related to the method of drug use, such as neuromuscular scoliosis and cerebrospinal fluid reservoir placement, were highlighted. Notably, AEs related to renal function abnormalities, such as abnormal Urine protein/creatinine ratio and protein urine presence, showed higher frequency and signal strength. The findings of this study emphasize the importance of comprehensive safety monitoring in the clinical application of Nusinersen. These results are significant for guiding future clinical practices, improving disease management strategies, and developing safer treatment protocols.

Abstract To explore the diagnostic efficacy of tomosynthesis spot compression (TSC) compared with conventional spot compression (CSC) for ambiguous findings on full-field digital mammography (FFDM). In this retrospective study, 122 patients (including 108 patients with dense breasts) with ambiguous FFDM findings were imaged with both CSC and TSC. Two radiologists independently reviewed the images and evaluated lesions using the Breast Imaging Reporting and Data System. Pathology or at least a 1-year follow-up imaging was used as the reference standard. Diagnostic efficacies of CSC and TSC were compared, including area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The mean glandular dose was recorded and compared for TSC and CSC. Of the 122 patients, 63 had benign lesions and 59 had malignant lesions. For Reader 1, the following diagnostic efficacies of TSC were significantly higher than those of CSC: AUC (0.988 vs. 0.906, P = 0.001), accuracy (93.4% vs. 77.8%, P = 0.001), specificity (87.3% vs. 63.5%, P = 0.002), PPV (88.1% vs. 70.5%, P = 0.010), and NPV (100% vs. 90.9%, P = 0.029). For Reader 2, TSC showed higher AUC (0.949 vs. 0.909, P = 0.011) and accuracy (83.6% vs. 71.3%, P = 0.022) than CSC. The mean glandular dose of TSC was higher than that of CSC (1.85 ± 0.53 vs. 1.47 ± 0.58 mGy, P

Abstract Trace NO2 detection is essential for the production and life, where the sensing strategy is appropriate for rapid detection but lacks molecular specificity. This investigation proposes a sensing mechanism dominated by surface-scattering to achieve the molecularly-specific detection. Two-dimensional Bi2O2Se is firstly fabricated into a Schottky-junction-based gas-sensor. Applied with an alternating excitation, the sensor simultaneously outputs multiple response signals (i.e., resistance, reactance, and the impedance angle). Their response times are shorter than 200 s at room temperature. In NO2 sensing, these responses present the detection limit in ppt range and the sensitivity is up to 16.8 %·ppb−1. This NO2 sensitivity presents orders of magnitude higher than those of the common gases within the exhaled breath. The impedance angle is involved in the principle component analysis together with the other two sensing signals. Twelve kinds of typical gases containing NO2 are acquired with molecular characteristics. The change in dipole moment of the target molecule adsorbed is demonstrated to correlate with the impedance angle via surface scattering. The proposed mechanism is confirmed to output ultra-sensitive sensing responses with the molecular characteristic.

Abstract Background Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. Methods We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. Results We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p

Abstract Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 μs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.

Vehicle model recognition (VMR) benefits the parking, surveillance, and tolling system by automatically identifying the exact make and model of the passing vehicles. Edge computing technology enables the roadside facilities and mobile cameras to achcieve VMR in real-time. Current work generally relies on a specific view of the vehicle or requires huge calculation capability to deploy the end-to-end deep learning network. This paper proposes a lightweight two-stage identification method based on object detection and image retrieval techniques, which empowers us the ability of recognizing the vehicle model from an arbitrary view. The first-stage model estimates the vehicle posture using object detection and similarity matching, which is cost-efficient and suitable to be programmed in the edge computing devices; the second-stage model retrieves the vehicle’s label from the dataset based on gradient boosting decision tree (GBDT) algorithm and VGGNet, which is flexible to the changing dataset. More than 8 000 vehicle images are labeled with their components’ information, such as headlights, windows, wheels, and logos. The YOLO network is employed to detect and localize the typical components of a vehicle. The vehicle postures are estimated by the spatial relationship between different segmented components. Due to the variety of the perspectives, a 7-dimensional vector is defined to represent the relative posture of the vehicle and screen out the images with a similar photographic perspective. Two algorithms are used to extract the features from each image patch: (1) the scale invariant feature transform (SIFT) combined with the bag-of-features (BoF) and (2) pre-trained deep neural network. The GBDT is applied to evaluate the weight of each component regarding its impact on VMR. The descriptors of each component are then aggregated to retrieve the best matching image from the database. The results showed its advantages in terms of accuracy (89.2%) and efficiency, demonstrating the vast potential of applying this method to large-scale vehicle model recognition.

Background: Liquid biopsy-based biomarkers, including circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB), are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors (ICIs), despite insufficient sensitivity of single biomarker detection. This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects. Methods: This prospective two-center cohort trial, consisting of discovery and validation datasets, enrolled unresectable locally advanced non-small-cell lung cancer (LA-NSCLC) patients and assigned them to chemoradiotherapy (CRT) or CRT + consolidation ICI cohorts from 2018 to 2022. Blood specimens were collected pretreatment, 4 weeks post-CRT, and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing. Dynamic ∆bTMB was calculated as post-CRT bTMB minus baseline bTMB levels. Decision curve analyses were performed to calculate Concordance index (C-index). Results: One hundred twenty-eight patients were enrolled. In the discovery dataset (n = 73), patients treated with CRT and consolidation ICI had significantly longer overall survival (OS; median not reached [NR] vs 20.2 months; P < 0.001) and progression-free survival (PFS; median 25.2 vs 11.4 months; P = 0.011) than those without ICI. Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT (P < 0.001) but a relative increase with disease progression. Post-CRT detectable residual ctDNA correlated with significantly shorter OS (median 18.3 months vs NR; P = 0.001) and PFS (median 7.3 vs 25.2 months; P < 0.001). For patients with residual ctDNA, consolidation ICI brought significantly greater OS (median NR vs 14.8 months; P = 0.005) and PFS (median 13.8 vs 6.2 months; P = 0.028) benefit, but no significant difference for patients with ctDNA clearance. Dynamic ∆bTMB was predictive of prognosis. Patients with residual ctDNA and increased ∆bTMB (∆bTMB > 0) had significantly worse OS (median 9.0 vs 23.0 months vs NR; P < 0.001) and PFS (median 3.4 vs 7.3 vs 25.2 months; P < 0.001). The combinatorial model integrating post-CRT ctDNA with ∆bTMB had optimal predictive effects on OS (C-index = 0.723) and PFS (C-index = 0.693), outperforming individual features. In the independent validation set, we confirmed residual ctDNA predicted poorer PFS (median 50.8 vs 14.3 months; P = 0.026) but identified more consolidation ICI benefit (median NR vs 8.3 months; P = 0.039). The combined model exhibited a stable predictive advantage (C-index = 0.742 for PFS). Conclusions: The multiparameter assay integrating qualitative residual ctDNA testing with quantitative ∆bTMB dynamics improves patient prognostic risk stratification and efficacy predictions, allowing for personalized consolidation therapy for LA-NSCLC.

Abstract The members of the classic B7 family regulate the immune microenvironment of several malignant tumors. However, the potential relationship between the B7 family and the breast cancer (BrCa) tumor immune microenvironment has remained elusive. In the present study, we provide a comprehensive explanation of the expression, clinical significance, mutation, and immune cell infiltration of B7 family molecules in BrCa. First, we recruited 10 patients with BrCa surgery from the Wuxi Maternal and Child Health Hospital and performed single-cell RNA sequencing (scRNA-seq) analysis to investigate the distribution of B7 family members in multiple immune cell subsets. We focused on B7-2, B7-H3, and B7-H5 molecules of the B7 family and constructed tumor microarrays by self-recruiting patients to perform multiple immunohistochemical (mIHC) analyses and study tumor expression of B7-2, B7-H3, B7-H5 and CD8+ immune cell infiltration. B7-H5 displayed a strong correlation with CD8+ immune cell infiltration. In summary, B7-H5 provides a new perspective for the identification of immunothermal subtypes of BrCa and could function as a switch to reverse BrCa from an “immunologically cold” state to an “immunologically hot” state. Graphical abstract

Abstract Background Horsfieldia hainanensis Merr., an indicator species of China’s humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. Results and discussion The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30–35℃.

Abstract Background The development of pulmonary fibrosis involves a cascade of events, in which inflammation mediated by immune cells plays a pivotal role. Chemotherapeutic drugs have been shown to have dual effects on fibrosis, with bleomycin exacerbating pulmonary fibrosis and bortezomib alleviating tissue fibrotic processes. Understanding the intricate interplay between chemotherapeutic drugs, immune responses, and pulmonary fibrosis is likely to serve as the foundation for crafting tailored therapeutic strategies. Methods A model of bleomycin-induced pulmonary fibrosis was established, followed by treatment with bortezomib. Tissue samples were collected for analysis of immune cell subsets and functional assessment by flow cytometry and in vitro cell experiments. Additionally, multi-omics analysis was conducted to further elucidate the expression of chemokines and chemokine receptors, as well as the characteristics of cell populations. Results Here, we observed that the expression of CXCL16 and CXCR6 was elevated in the lung tissue of a pulmonary fibrosis model. In the context of pulmonary fibrosis or TGF-β1 stimulation in vitro, macrophages exhibited an M2-polarized phenotype and secreted more CXCL16 than those of the control group. Moreover, flow cytometry revealed increased expression levels of CD69 and CXCR6 in pulmonary CD4 T cells during fibrosis progression. The administration of bortezomib alleviated bleomycin-induced pulmonary fibrosis, accompanied by reduced ratio of M2-polarized macrophages and decreased accumulation of CD4 T cells expressing CXCR6. Conclusions Our findings provide insights into the key immune players involved in bleomycin-induced pulmonary fibrosis and offer preclinical evidence supporting the repurposing strategy and combination approaches to reduce lung fibrosis.

Abstract Background Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy. Methods We analyzed transcriptomic collagen activity and immune signatures in 649 patients with cancer undergoing ICB therapy. This analysis led to the identification of three distinct immuno‐collagenic subtypes predictive of ICB responses. We validated these subtypes using the transcriptome data from 9,363 cancer patients from The Cancer Genome Atlas (TCGA) dataset and 1,084 in‐house samples. Additionally, novel therapeutic targets were identified based on these established immuno‐collagenic subtypes. Results Our categorization divided tumors into three subtypes: “soft & hot” (low collagen activity and high immune infiltration), “armored & cold” (high collagen activity and low immune infiltration), and “quiescent” (low collagen activity and immune infiltration). Notably, “soft & hot” tumors exhibited the most robust response to ICB therapy across various cancer types. Mechanistically, inhibiting collagen augmented the response to ICB in preclinical models. Furthermore, these subtypes demonstrated associations with immune activity and prognostic predictive potential across multiple cancer types. Additionally, an unbiased approach identified B7 homolog 3 (B7‐H3), an available drug target, as strongly expressed in “armored & cold” tumors, relating with poor prognosis. Conclusion This study introduces histopathology‐based universal immuno‐collagenic subtypes capable of predicting ICB responses across diverse cancer types. These findings offer insights that could contribute to tailoring personalized immunotherapeutic strategies for patients with cancer.

Abstract Objective This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. Methods This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. Results The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). Conclusion Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

This is an article in the field of process mineralogy. The occurrence of zinc, associated dispersed elements Ga and Ge and the distribution characteristics of the main carrier minerals of a zinc ore in China are studied in detail by means of chemical analysis, microscope analysis and MLA mineral automatic quantitative technology.The results indicate that the zinc ore contains Zn 4.87%, Ga 4.10 g/t and Ge 59.00 g/t, no independent minerals of dispersed elements Ga and Geare found, Ga and Ge mainly occur in sphalerite. The theoretical recovery of Zn, Ga and Ge from sphalerite (including hemimorphite) are about 95%, 56% and 93% respectively. A small part of colloidal and fine grained sphalerite is difficult to obtain dissociation and easy to be lost in tailings, which has a certain effect on the recovery of zinc.

IntroductionResearch characterizing substance use disparities between gender minority youth (GMY) and non-GMY (i.e. girls and boys) is limited. The aim of this study was to examine the differences in substance use behaviours among gender identity (GI) groups and identify associated risk and protective factors. MethodsCross-sectional data from Canadian secondary school students (n = 42 107) that participated in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study were used. Hierarchal logistic regression models estimated current substance use (cigarettes, e-cigarettes, binge drinking, cannabis and nonmedical prescription opioids [NMPOs]). Predictor variables included sociodemographics, other substances, mental health outcomes, school connectedness, bullying and happy home life. Interaction terms were used to test mental health measures as moderators in the association between GI and substance use. ResultsCompared to non-GMY, GMY reported a higher prevalence for all substance use outcomes. In the adjusted analyses, GMY had higher odds of cigarette, cannabis and NMPO use and lower odds for e-cigarette use relative to non-GMY. The likelihood of using any given substance was higher among individuals who were involved with other substances. School connectedness and happy home life had a protective effect for all substances except binge drinking. Bullying victimization was associated with greater odds of cigarette, e-cigarette use and NMPOs. Significant interactions between GI and all mental health measures were detected. ConclusionFindings highlight the importance of collecting a GI measure in youth population surveys and prioritizing GMY in substance use–related prevention, treatment and harm reduction programs. Future studies should investigate the effects of GI status on substance use onset and progression among Canadian adolescents over time.

IntroductionLes travaux de recherche caractérisant les disparités en matière de consommation de substances entre les jeunes faisant partie de minorités de genre et les jeunes ne faisant pas partie de minorités de genre, c’est-à-dire les filles et les garçons, sont limités. L’objectif de cette étude était d’explorer les différences dans les comportements liés à la consommation de substances entre groupes d’identité de genre et de déterminer les facteurs de risque et les facteurs de protection correspondants. MéthodologieNous avons utilisé les données transversales associées aux élèves canadiens du secondaire (n = 42 107) qui avaient participé à l’année 8 (2019-2020) ou à l’année 9 (2020-2021) de l’étude COMPASS. Des modèles de régression logistique hiérarchiques nous ont permis d’estimer la consommation de substances (cigarettes, cigarettes électroniques, consommation excessive d’alcool, cannabis et opioïdes à des fins non médicales). Les variables prédictives comprenaient les caractéristiques sociodémographiques, la consommation d’autres substances, les résultats en matière de santé mentale, les liens avec l’école, l’intimidation et une vie familiale heureuse. Nous avons utilisé des termes d’interaction pour tester les mesures de la santé mentale en tant que modérateurs de l’association entre l’identité de genre et la consommation de substances. RésultatsComparativement aux jeunes ne faisant pas partie de minorités de genre, les jeunes faisant partie de minorités de genre avaient une prévalence plus élevée pour tous les résultats liés à la consommation de substances. Dans les analyses ajustées, les jeunes faisant partie de minorités de genre avaient une probabilité plus élevée de fumer des cigarettes, de consommer du cannabis et d’utiliser des opioïdes à des fins non médicales et une probabilité plus faible d’utiliser des cigarettes électroniques par rapport aux autres jeunes. La probabilité de consommer une substance donnée était plus élevée chez ceux qui consommaient d’autres substances. La connexion à l’école et une vie familiale heureuse avaient un effet protecteur contre toutes les substances, sauf la consommation excessive d’alcool. La victimisation par intimidation était associée à une plus grande probabilité d’usage de cigarettes, de cigarettes électroniques et d’opioïdes à des fins non médicales. Nous avons observé des interactions statistiquement significatives entre l’identité de genre et l’ensemble des mesures de la santé mentale. ConclusionNos constatations soulignent l’importance de recueillir une mesure de l’identité de genre dans les enquêtes sur les jeunes et de prioriser les jeunes faisant partie de minorités de genre dans les programmes de prévention, de traitement et de réduction des méfaits liés à la consommation de substances. Les études ultérieures devraient porter sur les effets de l’identité de genre sur le début et l’évolution de la consommation de substances chez les adolescents canadiens au fil du temps.

Abstract Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

Abstract Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein–protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.

Abstract Diffuse myocardial fibrosis is associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Dual-energy CT (DECT) can noninvasively assess myocardial fibrosis by quantification of extracellular volume (ECV) fraction. This study evaluated the association between ECV measured by DECT and clinical outcomes in patients with HFpEF. 125 hospitalized HFpEF patients were enrolled in this retrospective cohort study. ECV was measured using DECT with late iodine enhancement. The composite endpoint was defined as HFpEF hospitalization and all-cause mortality during the follow-up. During the median follow-up of 10.4 months, 34 patients (27.20%) experienced the composite outcomes, including 5 deaths; and 29 HFpEF hospitalizations. The higher DECT-ECV group had higher rates of composite outcomes than the low ECV group (log-rank X 2 = 6.818, P = 0.033). In multivariate Cox regression analysis, the ECV (HR 1.17, 95% CI 1.06–1.30, P = 0.001) and NT-pro BNP (HR 2.83, 95% CI 1.16–6.88, P = 0.022) were independent risk factors for the adverse outcomes. Myocardial ECV measured using DECT was an independent risk factor for adverse outcomes in patients with HFpEF.

Objectives: The relationship between antifungal susceptibility and mortality of cryptococcal meningitis (CM) in HIV-negative patients is poorly understood. Methods: We conducted a retrospective analysis of 1-year follow-up of 200 HIV-negative CM patients with an initial cerebrospinal fluid (CSF) culture for Cryptococcus neoformans. According to the cut-off values of minimum inhibitory concentration (MIC), two groups of five antifungal agents were classified: amphotericin B (AmB), ≤0.5 µg/mL, >0.5 µg/mL; 5-flucytosine (5-FC), ≤4 µg/mL, >4 µg/mL; fluconazole (FLU), ≤4 µg/mL, >4 µg/mL; itraconazole (ITR), ≤0.125 µg/mL, >0.125 µg/mL; and voriconazole (VOR),

The combination of straw return and nitrogen (N) fertilization is an effective strategy for increasing farmland productivity and improving soil structure while mitigating climate change. However, although straw return practices are widely recommended in agroecosystems targeting sustainable agriculture, few studies have explored changes in grain yield, resource use efficiency, water productivity, and potential interactions between these variables. A field experiment was conducted during 2022–2023 in Northeast China to study the effects of straw return modes and N fertilizer input on maize grain yield and the efficient use of radiation, water, and N. We investigated two straw return tillage methods (rotary tillage with straw returning, RTS; plow tillage with straw returning, PTS) and five N fertilizer levels (0, 112, 187, 262, and 337 kg N ha−1) based on a field location experiment that started in 2015. Compared with RTS treatment, the PTS treatment resulted in a higher photosynthetic capacity by regulating the leaf area index and photosynthetic metabolism, resulting in increased dry matter accumulation and transportation. Such physiological improvements are conducive to increasing the nutrient use efficiency, water productivity, and grain yield. Specifically, PTS combined with the N3 treatment was an efficient tillage mode that increased radiation use efficiency of grain by 123.48 % and 207.41 % and by 153.44 % and 167.37 % in 2022 and 2023, respectively, compared with the PTS and N0 treatment. Together with partial least squares path modeling, regression analysis, and random forest, the variations in the above parameters led to high productivity in terms of N uptake, water productivity, leaf area index, radiation use efficiency, N use efficiency, and dry matter accumulation. Our results highlight the key roles of straw return methods in affecting grain yield, and further suggest that PTS combined with optimized N fertilizer input can enhance resource utilization, leading to a productive, efficient, and sustainable maize population.

ABSTRACT Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using Brassica chinensis L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that Myroides xuanwuensis strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of Myroides xuanwuensis strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.

Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic β cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future.

Abstract Li−I2 batteries have attracted much interest due to their high capacity, exceptional rate performance, and low cost. Even so, the problems of unstable Li anode/electrolyte interface and severe polyiodide shuttle in Li−I2 batteries need to be tackled. Herein, the interfacial reactions on the Li anode and I2 cathode have been effectively optimized by employing a well‐designed gel polymer electrolyte strengthened by cross‐linked Ti–O/Si–O (GPETS). The interpenetrating network‐reinforced GPETS with high ionic conductivity (1.88 × 10−3 S cm−1 at 25°C) and high mechanical strength endows uniform Li deposition/stripping over 1800 h (at 1.0 mA cm−2, with a plating capacity of 3.0 mAh cm−2). Moreover, the GPETS abundant in surface hydroxyls is capable of capturing soluble polyiodides at the interface and accelerating their conversion kinetics, thus synergistically mitigating the shuttle effect. Benefiting from these properties, the use of GPETS results in a high capacity of 207 mAh g−1 (1 C) and an ultra‐low fading rate of 0.013% per cycle over 2000 cycles (5 C). The current study provides new insights into advanced electrolytes for Li−I2 batteries.

ObjectivesThis study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age.MethodsThis observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60–104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years.ResultsThe median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women’s eGFR decreased by 1.06 mL/min/1.73 m2 and men’s by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR.ConclusionThe eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

IntroductionCorpus callosum injury is a rare type of injury that occurs after a stroke and can cause lower limb dysfunction and a decrease in activities of daily living ability. Furthermore, there are no studies that focus on the progress in rehabilitation of the lower limb dysfunction caused by infarction in the corpus callosum and the effective treatment plans for this condition. We aimed to present a report of two patients with lower limb dysfunction caused by corpus callosum infarction after a stroke and a walking training method.MethodsWe implemented a walking training method that prioritizes bilateral symmetry and increases lateral swaying before the patients established sitting/standing balance. The plan is a rapid and effective method for improving walking dysfunction caused by corpus callosum infarction.Case characteristicsFollowing sudden corpus callosum infarction, both patients experienced a significant reduction in lower limb motor function scores and exhibited evident gait disorders. Scale evaluations confirmed that walking training based on symmetrical and increased lateral sway for patients with lower limb motor dysfunction after corpus callosum infarction led to significant symptom improvement.ConclusionWe report two cases of sudden motor dysfunction in patients with corpus callosum infarction. Symmetrical and increased lateral sway-based walking training resulted in substantial symptom improvement, as confirmed by scale assessments.

ABSTRACT: Avian pathogenic Escherichia coli (APEC) is one of the common extraintestinal infectious disease pathogens in chickens, geese, and other birds, inducing serious impediments to the development of the poultry industry. Hence, investigating how bacteria regulate themselves amidst different challenging conditions is immense essential in prevention and treatment for bacterial pathogen infections. The ArcA regulatory factor has been reported to regulate oxygen availability in strains, but its role in regulation of antibiotics resistance in APEC is unclear. This study delved into understanding how ArcA regulates antibiotic resistance in APEC. An E. coli APEC40 arcA knockout strain was constructed, and the regulatory mechanism of arcA on APEC antibiotic susceptibility was identified by drug sensitivity test, colony counting assay, real-time quantitative PCR, β-galactosidase assays and electrophoretic mobility shift assay (EMSA). The results showed that ArcA directly binds to the promoter region of the outer membrane protein OmpC/OmpW and regulates bacterial susceptibility to kanamycin and penicillin G. At the same time, the double knockout of ompW and ompW/arcA resulted in an increase in resistance to kanamycin compared to the deletion of the arcA gene. This outcome provided experimental proof suggesting that the outer membrane protein OmpW could serve as a crucial pathway for the ingress of kanamycin into cells. These results confirmed the important regulatory role of ArcA transcription factors under APEC antibiotic stress.

Abstract Breast cancer (BC) is the second-leading factor of mortality for women globally and is brought on by a variety of genetic and environmental causes. The conventional treatments for this disease have limitations, making it difficult to improve the lifespan of breast cancer patients. As a result, extensive research has been conducted over the past decade to find innovative solutions to these challenges. Targeting of the antitumor immune response through the immunomodulatory checkpoint protein B7 family has revolutionized cancer treatment and led to intermittent patient responses. B7-H3 has recently received attention because of its significant demodulation and its immunomodulatory effects in many cancers. Uncontrolled B7-H3 expression and a bad outlook are strongly associated, according to a substantial body of cancer research. Numerous studies have shown that BC has significant B7-H3 expression, and B7-H3 induces an immune evasion phenotype, consequently enhancing the survival, proliferation, metastasis, and drug resistance of BC cells. Thus, an innovative target for immunotherapy against BC may be the B7-H3 checkpoint. In this review, we discuss the structure and regulation of B7-H3 and its double costimulatory/coinhibitory function within the framework of cancer and normal physiology. Then we expound the malignant behavior of B7-H3 in BC and its role in the tumor microenvironment (TME) and finally focus on targeted drugs against B7-H3 that have opened new therapeutic opportunities in BC.

Abstract The reconstruction of rutile TiO2 (110) holds significant importance as it profoundly influences the surface chemistry and catalytic properties of this widely used material in various applications, from photocatalysis to solar energy conversion. Here, we directly observe the asymmetric surface reconstruction of rutile TiO2 (110)-(1×2) with atomic-resolution using in situ spherical aberration-corrected scanning transmission electron microscopy. Density functional theory calculations were employed to complement the experimental observations. Our findings highlight the pivotal role played by repulsive electrostatic interaction among the small polarons −formed by excess electrons following the removal of neutral oxygen atoms− and the subsequent surface relaxations induced by these polarons. The emergence and disappearance of these asymmetric structures can be controlled by adjusting the oxygen partial pressure. This research provides a deeper understanding, prediction, and manipulation of the surface reconstructions of rutile TiO2 (110), holding implications for a diverse range of applications and technological advancements involving rutile-based materials.

Abstract Background A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. Methods In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. Results The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. Conclusions CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.

Sitobion avenae F. is a highly prevalent and devastating pest in wheat crops, leading to significant yield losses. Silicon (Si) has been widely recognized as an effective inducer of plant resistance against aphids. Nevertheless, the underlying mechanisms governing the physiological and biochemical responses of plants induced by Si defense against S. avenae F. remain incompletely understood. In this study, we conducted experiments by treating wheat leaves with varying concentrations of Tetraethyl orthosilicate (TEOS) spray under aphid infestation. We meticulously observed and recorded the life cycle of S. avenae F. and measured the content of plant hormones, secondary metabolites, and the activity of defense enzymes in wheat leaves. Furthermore, we utilized structural equation modeling to discern the causal correlation between aphid performance and the physiological-biochemical responses of wheat under TEOS sprays. Our findings revealed that a concentration of 3 mmol/L TEOS significantly shortened the net reproductive rate, intrinsic rate and finite rate of increase, and mean generation time of S. avenae F., while simultaneously prolonging the population doubling time. Additionally, the content of lignin, total phenolics, flavonoids, alkaloids, tannin, jasmonic acid (JA), and salicylic acid in wheat leaves exhibited a substantial increase. Furthermore, the activity of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), catalase, and lipoxygenase in wheat leaves was significantly enhanced. Our results suggest that TEOS spray reduced the survival and population growth of S. avenae F. while enhancing the defense response of wheat against aphids by activating the activity of PAL and PPO in wheat, and increasing the content of total phenolic and JA. This work provides valuable insights for the development of appropriate Si fertilizers for effective pest management and offers robust theoretical support for wheat aphid control through agricultural fertilization strategies.

Abstract At present, the separation technology of fluorite and calcite is still immature, and the research in this paper can promote the improvement of the separation technology of fluorite and calcite. The selective inhibition mechanism of tannin and humate sodium on calcite was studied by means of actual ore flotation test, single mineral flotation test, Zeta potential measurement and FT-IR spectroscopy. The results show that the mixture of tannin and sodium humate inhibitor has a good inhibitory effect on carbonate under weak alkaline condition. The reaction products of sodium humate, tannin and calcium ions in solution interact with organic compounds adsorbed on the surface of calcite, forming multilayer adsorption on the surface of calcite, making calcite more hydrophilic. Based on density functional theory, Materials Studio (MS) was used to calculate the relevant adsorption energy, and the result was as follows: (a) compared with fluorite, tannin and humate sodium molecules are more easily adsorbed on the surface of calcite. (b) Compared with calcite alone adsorption of tannin molecules or sodium humate molecules, the adsorption state will be more stable, and the effect of tannin and sodium humate synergistic inhibition of calcite is better than the effect of inhibition alone. Therefore, using tannin and sodium humate as a combination inhibitor can effectively separate fluorite and calcite, which will promote the development and utilization of fluorite ore in industry.

Abstract Hypoxia, which activates a variety of signaling pathways to enhance tumor cell growth and metabolism, is among the primary features of tumor cells. Hypoxia-inducible factors (HIFs) have a substantial impact on a variety of facets of tumor biology, such as epithelial-mesenchymal transition, metabolic reprogramming, angiogenesis, and improved radiation resistance. HIFs induce hypoxia-adaptive responses in tumor cells. Many academics have presented preclinical and clinical research targeting HIFs in tumor therapy, highlighting the potential applicability of targeted HIFs. In recent years, the discovery of numerous pharmacological drugs targeting the regulatory mechanisms of HIFs has garnered substantial attention. Additionally, HIF inhibitors have attained positive results when used in conjunction with traditional oncology radiation and/or chemotherapy, as well as with the very promising addition of tumor immunotherapy. Immune checkpoint inhibitors (CPIs), which are employed in a range of cancer treatments over the past decades, are essential in tumor immunotherapy. Nevertheless, the use of immunotherapy has been severely hampered by tumor resistance and treatment-related toxicity. According to research, HIF inhibitors paired with CPIs may be game changers for multiple malignancies, decreasing malignant cell plasticity and cancer therapy resistance, among other things, and opening up substantial new pathways for immunotherapy drug development. The structure, activation mechanisms, and pharmacological sites of action of the HIF family are briefly reviewed in this work. This review further explores the interactions between HIF inhibitors and other tumor immunotherapy components and covers the potential clinical use of HIF inhibitors in combination with CPIs.

Highlights The engineering design principles for enhancing interfacial contact between the electrodes (Li anodes and S cathode) and solid-state electrolytes in solid-state Li–S batteries are classified and discussed. Research progresses of experimental strategies for reducing interfacial impedance in solid-state Li–S batteries are summarized. Challenges and future perspectives of rational interfacial strategies in solid-state Li–S batteries are highlighted.

Abstract Triple-negative breast cancer (TNBC) is generally regarded as the most aggressive subtype among breast cancers, but exhibits higher chemotherapeutic and immunotherapeutic responses due to its unique immunogenicity. Thus, appropriate discrimination of subtypes is critical for guiding therapeutic options in clinical practice. In this research, using multiple in-house and public cohorts, we investigated the expression features and immuno-correlations of B7-H3 in breast cancer and checked the anti-tumor effect of the B7-H3 monoclonal antibody in a mouse model. We also developed a novel classifier combining B7-H3 and PD-L1 expression in TNBC. B7-H3 was revealed to be related to immuno-cold features and accumulated collagen in TNBC. In addition, targeting B7-H3 using the monoclonal antibody significantly suppressed mouse TNBC growth, reversed the armored-cold phenotype, and also boosted anti-PD-1 immunotherapy. In addition, patients with B7-H3 high and PD-L1 low expression showed the lowest anti-tumor immune infiltration, the highest collagen level, and the lowest therapeutic responses to multiple therapies, which mostly belong to armored-cold tumors. Overall, this research provides a novel subtyping strategy based on the combination of B7-H3/PD-L1 expression, which leads to a novel approach for the management of TNBC.

Abstract Background With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID‐19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID‐19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll‐out and to identify risk factors associated with hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality. Methods We performed a retrospective cohort study of cancer patients with COVID‐19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID‐19, and 30‐day COVID‐19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. Results Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID‐19, severe COVID‐19, and 30‐day COVID‐19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID‐19 but with no impact on hospitalization or mortality due to COVID‐19. Conclusion Our study highlights a significant benefit of COVID‐19 vaccination for cancer patients—specifically its protection against severe COVID‐19.

Abstract Background Very little research has examined how perceptions of cannabis access among underage youth in Canada have changed since cannabis was legalized and since the onset of the COVID-19 pandemic. As such, this paper examines the effect of the early and ongoing stages of the COVID-19 pandemic period on youth perceptions of cannabis access over time since the onset of the Cannabis Act in 2018 in a large sample of Canadian youth. Methods Using data from the COMPASS study (T1:2018/19, T2:2019/20, T3:2020/21), we used both repeat cross-sectional data [T1 (n = 38,890), T2 (n = 24,109), and T3 (n = 22,795)] to examine overall trends in perceptions of cannabis access, and sequential cohort longitudinal data [n = 4,677 students linked from T1 to T3] to examine the differential changes in perceptions of cannabis access among students over time. Results In the cross-sectional sample, the frequency of students reporting that cannabis was easy to access decreased by 26.7% from T1 (51.0%) to T3 (37.4%), although respondents who have used cannabis were more likely to report access was easy. In the longitudinal sample, perceptions of cannabis access being easy increased over time, especially among cannabis users. Perceived ease of access appears to have been slightly impeded during the initial pandemic period but rebounded during the ongoing pandemic period. Conclusions While the prevalence of youth reporting that cannabis is easy to access has declined since legalization and throughout the early and ongoing pandemic periods, a substantial number of underage youth continue to report that cannabis is easy to access. This suggest that there is an ongoing need for continued cannabis control efforts to address this issue.

Abstract Background Kupffer cells (KCs) originate from yolk-sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at a steady state and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adults remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. Methods We first traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate-mapping mouse models, respectively. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC-depletion in mice. Finally, we traced the fate of hematopoietic stem cells (HSCs) in an HSC-specific fate-mapping mouse model, in the context of chronic liver inflammation induced by repeated carbon tetrachloride treatment. Results By using fate-mapping mouse models, we found no evidence that repopulating KCs originate from preexisting KCs or MOs and found that in response to KC-depletion, HSCs proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Then, in the chronic liver inflammation context, we confirmed that repopulating KCs originated directly from HSCs. Conclusion Taken together, these findings provided in vivo fate-mapping evidence that repopulating KCs originate directly from HSCs, which presents a completely novel understanding of the cellular origin of repopulating KCs and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

Abstract Cyclic GMP–AMP synthase (cGAS), initially identified as a cytosolic DNA sensor, detects DNA fragments to trigger an innate immune response. Recently, accumulating evidence reveals the presence of cGAS within the nucleus. However, the biological functions of nuclear cGAS are not fully understood. Here, we demonstrate that nuclear cGAS represses LINE-1 (L1) retrotransposition to preserve genome integrity in human cells. Mechanistically, the E3 ligase TRIM41 interacts with and ubiquitinates ORF2p to influence its stability, and cGAS enhances the association of ORF2p with TRIM41, thereby promoting TRIM41-mediated ORF2p degradation and the suppression of L1 retrotransposition. In response to DNA damage, cGAS is phosphorylated at serine residues 120 and 305 by CHK2, which promotes cGAS-TRIM41 association, facilitating TRIM41-mediated ORF2p degradation. Moreover, we show that nuclear cGAS mediates the repression of L1 retrotransposition in senescent cells induced by DNA damage agents. We also identify several cancer-associated cGAS mutations that abolish the suppressive effect on L1 retrotransposition by disrupting the CHK2-cGAS-TRIM41-ORF2p regulatory axis. Together, these findings indicate that nuclear cGAS exhibits an inhibitory function in L1 retrotransposition which could provide avenues for future interventions in both aging and tumorigenesis.

Abstract. Background. Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis. Thus, personalized treatment strategies for bladder cancer are essential for improving patient outcomes. Materials and methods. We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids (BCOs), which maintains the homology with the original patient tumors and the heterogeneity between different individuals. In addition, we constructed chimeric antigen receptor (CAR)-T cells targeting B7H3 and evaluated the antitumor function of CAR-T cells by coculturing them with BCOs. Results. The BCOs closely resembled the characteristics of human tumors and were used to test individual sensitivity to platinum-based drugs and olaparib therapy. Coculture with CAR-T cells demonstrated specific antigen recognition and immune activation, indicating their potential in immunotherapy. Conclusions. Our study highlights the potential of BCOs to facilitate the development of personalized medicine for bladder cancer and improve the efficiency of drug discovery for bladder cancer therapy.

Digital information on sea ice extent, thickness, volume, and distribution is crucial for understanding Earth's climate system. The Snow and Ice Mass Balance Apparatus (SIMBA) is used to determine snow and ice temperatures in Arctic, Antarctic, ice-covered seas, and boreal lakes. Snow depth and ice thickness are derived from SIMBA temperature regimes (SIMBA_ET and SIMBA_HT). In warm conditions, SIMBA_ET temperature-based ice thickness may have errors due to the isothermal vertical profile. SIMBA_HT provides a visible ice-bottom interface for manual quantification. We propose an unmanned approach, combining neural networks, wavelet analysis, and Kalman filtering (NWK), to mathematically establish NWK and retrieve ice bottoms from various SIMBA_HT datasets. In the Arctic, NWK-derived total thickness showed a bias range of −5.64 cm to 4.01 cm and a correlation coefficient of 95%−99%. For Baltic Sea ice, values ranged from 1.31 cm to 2.41 cm (88%−98% correlation), and for boreal lake ice, −0.7 cm to 2.6 cm (75%−83% correlation). During ice growth, thermal equilibrium, and melting, the bias varied from −3.93 cm to 2.37 cm, −1.92 cm to 0.04 cm, and −4.90 cm to 3.96 cm, with correlation coefficients of 76%−99%. These results demonstrate NWK's robustness in retrieving ice bottom evolution in different water environments.