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Abstract In 2018, African swine fever virus (ASFV) emerged in China, causing extremely serious economic losses to the domestic pig industry. Infection with ASFV can cause disseminated coagulation, leading to the consumption of platelets and coagulation factors and severe bleeding. However, the mechanism of virus-induced coagulation has yet to be established. In our study, ASFV downregulated the coagulation process, as detected by D-dimer (D2D) and Factor X (F10) expression in pigs challenged with ASFV HLJ/18. In vitro, ASFV infection increased Factor IX (F9) and Factor XII (F12) expression while downregulating F10 expression in porcine alveolar macrophages (PAMs). African swine fever virus induced both intrinsic and extrinsic coagulation cascades. In addition, several encoded proteins affect the expression of the crucial coagulation protein F10, and among the encoded proteins, p72 inhibits the activity and expression of F10. Proteomic analysis also revealed that p72 is involved in the coagulation cascade. p72 can interact with F10, and its inhibitory functional domains include amino acids 423–432 and amino acids 443–452. Finally, we found that F10 and p72 interact with tripartite motif-containing protein 28 (TRIM28). TRIM28 knockdown resulted in a decrease in F10 expression. Importantly, TRIM28 contributes to the reduction in F10 protein expression regulated by p72. Our findings revealed an inhibitory effect of the viral protein p72 on the ASFV infection-induced coagulation cascade and revealed a role of TRIM28 in reducing F10 expression, revealing a molecular mechanism of ASFV-associated coagulation.

Abstract Ubiquitination is a prevalent post-translational modification that plays a crucial role in a wide range of pathophysiological processes, including cell proliferation, apoptosis, autophagy, immune response, and DNA damage repair. Among the enzymes involved in ubiquitination, E3 ubiquitin ligases are particularly significant, serving as key regulators of numerous diseases, including tumours. This review focuses on HECW2 (HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2, also known as NEDL2), providing a comprehensive overview of its interactors and its pathological roles in tumorous cancer and other diseases. The insights gained from this review may contribute to the development of novel treatment strategies for various diseases, particularly tumours.

Abstract Background The global population’s aging has led to an increasing demand for long-term care (LTC), especially in developing countries like China. Comprehensive assessment of LTC service demands by including the time and cost analysis is crucial to inform the planning and financing of LTC resources, yet such research is lacking in China. Our research team has developed a quantitative index system of the medical and nursing services needs of older adults (QISMNSNE) based on the framework of Time-Driven Activity-Based Costing (TDABC), providing a valuable tool for measuring LTC service needs. This study aimed to assess the LTC service needs of older adults in China and the factors associated with such needs. Methods A cross-sectional study was conducted in Changsha City, Hunan Province, China, from June 2021 to December 2022. A stratified multistage cluster sampling method was used to recruit 1,270 older adults from five nursing homes and three communities/streets in three regions of Changsha City. The LTC service needs were assessed by calculating the service time required from caregivers, nurses, and doctors and the total service time (min/d) using the QISMNSNE. Participants’ disability, activities of daily living (ADLs), mental status and social involvement (MSSI), and sensory and communication (SC) were assessed using standard scales. Generalized linear regression models were used to analyze factors associated with LTC service needs. Results The participants had an average age of 76.41 ± 8.38 years, with 43.7% being female. The median service time required from caregivers, nurses, and doctors was 53.34 min/d, 3.66 min/d, and 0.33 min/d, respectively, and the total service time was 83.31 min/d. The generalized linear regression model identified the following factors that were associated with higher total service time: aged 75–84 years, living in nursing homes, income over 5000 per month, ADLs, MSSI (9 ~ 40), SC, and having 3 ~ 4 kinds of geriatric comorbidity (P

Abstract The prevalence of food allergies is increasing worldwide, affecting approximately 8% of children. Food allergies that develop early in life can persist throughout an individual's life. Dietary patterns, particularly those involving fatty acids (FAs), play an important role in the regulation of immune cells, thereby affecting the development of food allergies. Aimed to investigate the effects of different FA patterns on food allergies, this study established a sensitised infant rat model and fed it with feeds containing different types of FAs. We then assessed the clinical allergy symptoms, immune balance, and gut microbiota. Our animal allergy model revealed that diets rich in specific FAs exerted different regulatory effects on food allergies. Notably, n‐3 long‐chain polyunsaturated FAs exhibited the strongest inhibitory effect on food allergies, accompanied by a reduction in allergy symptoms, lower serum antibody levels, and modulation of T cell differentiation. By contrast, high levels of medium‐chain FAs promoted the occurrence and progression of food allergies. In addition, various dietary FA patterns have varying impacts on the gut microbiota, influencing overall diversity, microbial composition, and function. N‐3 long‐chain polyunsaturated FAs may be associated with a significant increase in the copy number of 15‐cis‐phytoene synthase in the intestinal flora. These findings suggest that dietary intake of different FAs during early life can affect an individual's susceptibility to food allergies by shaping the gut microbiota, which may offer a novel therapeutic approach for the treatment of food allergies.

Abstract The increasing complexity and high-dimensional nature of real-world optimization problems necessitate the development of advanced optimization algorithms. Traditional Particle Swarm Optimization (PSO) often faces challenges such as local optima entrapment and slow convergence, limiting its effectiveness in complex tasks. This paper introduces a novel Hybrid Strategy Particle Swarm Optimization (HSPSO) algorithm, which integrates adaptive weight adjustment, reverse learning, Cauchy mutation, and the Hook-Jeeves strategy to enhance both global and local search capabilities. HSPSO is evaluated using CEC-2005 and CEC-2014 benchmark functions, demonstrating superior performance over standard PSO, Dynamic Adaptive Inertia Weight PSO (DAIW-PSO), Hummingbird Flight patterns PSO (HBF-PSO), Butterfly Optimization Algorithm (BOA), Ant Colony Optimization (ACO), and Firefly Algorithm (FA). Experimental results show that HSPSO achieves optimal results in terms of best fitness, average fitness, and stability. Additionally, HSPSO is applied to feature selection for the UCI Arrhythmia dataset, resulting in a high-accuracy classification model that outperforms traditional methods. These findings establish HSPSO as an effective solution for complex optimization and feature selection tasks.

Objectives: The research sought to examine the antibacterial properties of the conditioned media derived from dental pulp mesenchymal stem cells (DPSC) that were treated with curcumin. Methods: An investigation of the physicochemical characteristics of curcumin nanoparticles was conducted utilizing scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and mapping techniques. The optimal dose of curcumin for treating DPSC cells was determined using the MTT test. The study investigated the antioxidant properties of curcumin on DPSC cells by measuring ROS. Two groups were isolated, one without treatment (control) and the other treated with curcumin. The antibacterial and antifungal properties of the supernatant culture medium of DPSC cells were then investigated. Results: The present study results indicate that curcumin possesses suitable physicochemical properties, including morphology and purity. Additionally, it exhibits no toxicity at doses ranging from 0 to 1.25 (μg/ml) and displays antioxidant properties at the IC50 concentration. Furthermore, it increases DPSCs. The antimicrobial results demonstrate that CM-CUR, at various concentrations, reduces the viability of Streptococcus mutans (S. mutans) and inhibits the growth of Candida albicans (C. albicans) by 85%. Conclusion: The research results indicate that the combination of CM-CUR is suitable for antibacterial and antifungal applications in dentistry to enhance human health.

Three new species of Conostigmus Dahlbom, 1858 (Hymenoptera: Megaspilidae), Conostigmus quadripetalus Wang & Chen, sp. nov., Conostigmus electrinus Wang & Chen, sp. nov., Conostigmus acutus Wang & Chen, sp. nov. are characterized and illustrated from China. Conostigmus ampullaceus Dessart, 1997 is redescribed on the basis of 17 specimens and genitalia pictures are provided for the first time.

Abstract The electronic medical record management system plays a crucial role in clinical practice, optimizing the recording and management of healthcare data. To enhance the functionality of the medical record management system, this paper develops a customized schema designed for ophthalmic diseases. A multi-modal knowledge graph is constructed, which is built upon expert-reviewed and de-identified real-world ophthalmology medical data. Based on this data, we propose an auxiliary diagnostic model based on a contrastive graph attention network (CGAT-ADM), which uses the patient’s diagnostic results as anchor points and achieves auxiliary medical record diagnosis services through graph clustering. By implementing contrastive methods and feature fusion of node types, text, and numerical information in medical records, the CGAT-ADM model achieved an average precision of 0.8563 for the top 20 similar case retrievals, indicating high performance in identifying analogous diagnoses. Our research findings suggest that medical record management systems underpinned by multimodal knowledge graphs significantly enhance the development of AI services. These systems offer a range of benefits, from facilitating assisted diagnosis and addressing similar patient inquiries to delving into potential case connections and disease patterns. This comprehensive approach empowers healthcare professionals to garner deeper insights and make well-informed decisions.

Abstract Camellia oleifera is an important woody oil tree in China, in which the flowers and fruits appear during the same period. The endogenous hormone changes and transcription expression levels in different parts of the flower tissue (sepals, petals, stamens, and pistils), flower buds, leaves, and seeds of Changlin 23 high-yield (H), Changlin low-yield (L), and control (CK) C. oleifera groups were studied. The abscisic acid (ABA) content in the petals and stamens in the L group was significantly higher than that in the H and CK groups, which may be related to flower and fruit drops. The high N6-isopentenyladenine (iP) and indole acetic acid (IAA) contents in the flower buds may be associated with a high yield. Comparative transcriptome analysis showed that the protein phosphatase 2C (PP2C), jasmonate-zim-domain protein (JAZ), and WRKY-related differentially expressed genes (DEGs) may play an important role in determining leaf color. Gene set enrichment analysis (GSEA) comparison showed that jasmonic acid (JA) and cytokinin play an important role in determining the pistil of the H group. In this study, endogenous hormone and transcriptome analyses were carried out to identify the factors influencing the large yield difference in C. oleifera in the same year, which provides a theoretical basis for C. oleifera in the future.

Abstract Background Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. Methods BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested. Results Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. Conclusion The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Abstract Objectives To examine the putative functions and mechanisms of lysine crotonylation (Kcr) during the development and progression of papillary thyroid cancer (PTC). Methods Samples of thyroid cancer tissues were collected and subjected to liquid chromatography–tandem mass spectrometry. Crotonylated differentially expressed proteins (DEPs) and differentially expressed Kcr sites (DEKSs) were analyzed by Motif, dynamic expression model analysis (Mfuzz), subcellular localization, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, Go Ontology (GO) annotation, and protein–protein interaction analysis (PPI). Validation was performed by immunohistochemistry (IHC). Results A total of 262 crotonylated DEPs and 702 DEKSs were quantitated. First, for the tumor/normal comparison, a dynamic expression model analysis (Mfuzz) of the DEKSs revealed that clusters 1, 3, and 4 increased with the progression of thyroid cancer; however, cluster 6 showed a dramatic increase during the transition from N0-tumor to N1-tumor. Furthermore, based on GO annotation, KEGG, and PPI, the crotonylated DEPs were primarily enriched in the PI3K-Akt signaling pathway, Cell cycle, and Hippo signaling pathway. Of note, crosstalk between the proteome and Kcr proteome suggested a differential changing trend, which was enriched in Thyroid hormone synthesis, Pyruvate metabolism, TCA cycle, Cell cycle, and Apoptosis pathways. Similarly, for the LNM comparison group, the DEKSs and related DEPs were primarily enriched in Hydrogen peroxide catabolic process and Tight junction pathway. Finally, according to The Cancer Genome Atlas Program (TCGA) database, the differential expression of Kcr DEPs were associated with the prognosis of thyroid cancer, indicating the prognostic significance of these proteins. Moreover, based on the clinical validation of 47 additional samples, Kcr was highly expressed in thyroid tumor tissues compared with normal tissue (t = 9.792, P

Abstract Background Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Abstract Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n–π*/π–π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission.

Abstract Background Breast cancer (BC) is the most common malignant tumor in women worldwide, and further elucidation of the molecular mechanisms involved in BC pathogenesis is essential to improve the prognosis of BC patients. RNA Binding Motif Protein 8 A (RBM8A), with high affinity to a myriad of RNA transcripts, has been shown to play a crucial role in genesis and progression of multiple cancers. We attempted to explore its functional significance and molecular mechanisms in BC. Methods Bioinformatics analysis was performed on publicly available BC datasets. qRT-PCR was used to determine the expression of RBM8A in BC tissues. MTT assay, clone formation assay and flow cytometry were employed to examine BC cell proliferation and apoptosis in vitro. RNA immunoprecipitation (RIP) and RIP-seq were used to investigate the binding of RBM8A/EIF4A3 to the mRNA of IGF1R/IRS-2. RBM8A and EIF4A3 interactions were determined by co-immunoprecipitation (Co-IP) and immunofluorescence. Chromatin immunoprecipitation (Ch-IP) and dual-luciferase reporter assay were carried out to investigate the transcriptional regulation of RBM8A by TEAD4. Xenograft model was used to explore the effects of RBM8A and TEAD4 on BC cell growth in vivo. Results In this study, we showed that RBM8A is abnormally highly expressed in BC and knockdown of RBM8A inhibits BC cell proliferation and induces apoptosis in vitro. EIF4A3, which phenocopy RBM8A in BC, forms a complex with RBM8A in BC. Moreover, EIF4A3 and RBM8A complex regulate the expression of IGF1R and IRS-2 to activate the PI3K/AKT signaling pathway, thereby promoting BC progression. In addition, we identified TEAD4 as a transcriptional activator of RBM8A by Ch-IP, dual luciferase reporter gene and a series of functional rescue assays. Furthermore, we demonstrated the in vivo pro-carcinogenic effects of TEAD4 and RBM8A by xenograft tumor experiments in nude mice. Conclusion Collectively, these findings suggest that TEAD4 novel transcriptional target RBM8A interacts with EIF4A3 to increase IGF1R and IRS-2 expression and activate PI3K/AKT signaling pathway, thereby further promoting the malignant phenotype of BC cells.

Abstract Background Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. Methods A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. Results WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261–1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032–4.371, P for trend

Objective: This study aimed to investigate the impact of different imaging parameters on stent imaging and stenosis assessment in a fast heart rate model. The goal was to reduce the radiation dose while ensuring image quality, and to provide a theoretical basis for optimizing computed tomography (CT) imaging parameters for stent imaging in patients with fast heart rates in future clinical practice. Methods: Different imaging parameters were set to obtain multiple sets of CT images of stents in a fast heart rate model. Four coronary artery stents with different internal diameters were used. Each stent was set to four levels of stenosis. Two different concentrations of iodine contrast agents were injected in batches. The Canon 320 CT scanner was used to perform scans at 100 kV and 120 kV tube voltages, and image reconstruction was performed using the stent reconstruction mode. Two radiologists, with more than three years of experience in coronary CT diagnosis, used a 5-point scoring method to subjectively evaluate image quality based on stent visualization, image quality, and stenosis assessment. Multiple regression analysis was conducted to assess the influence of stent diameter, stenosis level, tube voltage, and iodine contrast agent concentration on the subjective image quality scores. Results: The structures of the four stents could be visualized in all parameter combinations, but there were significant differences in the intraluminal display. The stent diameter, stenosis level, and iodine contrast agent concentration had a significant impact on the subjective image quality scores. The scores increased as the stent diameter increased and the stenosis level and iodine contrast agent concentration decreased. Moreover, the stent diameter had the strongest impact on the scores. Tube voltage did not significantly affect the subjective image quality scores. Conclusion: In fast heart rate conditions, the stent diameter, stenosis level, and iodine contrast agent concentration directly affect the image quality of stent CT imaging. Conversely, tube voltage had no impact on image quality. Our findings provided a theoretical basis for optimizing stent imaging protocols in patients with fast heart rates.

Purpose: To investigate the efficacy and safety of a modified dual-incision ophthalmic viscosurgical device-free (OVD-free) method for implantable collamer lens (ICL) implantation in high myopic eyes. Methods: A total of 68 participants were enrolled in this prospective randomized clinical trial, including 33 in the OVD-free group and 35 in the standard group. Operation time and intraocular pressure (IOP) at 2 hours postoperatively were recorded. Visual acuity, refractive power, IOP, corneal endothelium parameters, and anterior segment parameters were assessed at 1 day, 1 week, 1 month, 3 months, and 6 months postoperatively. Postoperative subjective visual quality at 3 months was recorded through a Quality of Vision (QoV) questionnaire. Results: No significant differences in visual acuity, refractive outcomes, and corneal endothelial parameters were found, while the operation time was significantly shorter in the OVD-free group. Both groups showed a significant increase in IOP at 2 hours after surgery, but the increase in the OVD-free group was significantly smaller than that in the standard group. In addition, the frequency of ring-shaped dysphotopsia in the OVD-free group (15.15%) was significantly lower than that in the standard group (40%), and the severity and annoyance of this symptom were also significantly lower in the OVD-free group. Conclusion: The modified OVD-free ICL implantation is a safe, effective, and predictable method for myopia correction, which could be a better choice for short surgery time, better subjective visual perception, and low occurrence of IOP elevation.

Abstract Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity and is characterized by alveolar simplification and lung angiogenesis failure. The aim of this study was to explore the immune signatures of BPD. Differentially expressed gene analysis and immune infiltration analysis were conducted to identify key immune cell types and related genes by using the mRNA-seq dataset GSE25286. The expression patterns of key genes were validated in the scRNA-seq dataset GSE209664 and in experiments. The cell–cell crosstalk of key immune cells was explored with CellChat. We found that differentially expressed genes between BPD mice and controls were mostly enriched in leukocyte migration and M1 macrophages were highly enriched in BPD lungs. Hub genes (Cybb, Papss2, F7 and Fpr2) were validated at the single-cell level, among which the downregulation of Cybb was most closely related to macrophage infiltration. The reduced mRNA and protein levels of Cybb were further validated in animal experiments. Colocalization analysis of Cybb and macrophage markers demonstrated a significant decrease of Cybb in M1 macrophages. Cell–cell crosstalk found that alveolar epithelial cells interacted actively with macrophages through MIF-(CD74 + CD44) signalling. In conclusion, M1 macrophages played important roles in promoting BPD-like lung injury, which was correlated with a specific reduction of Cybb in macrophages and the potential activation of MIF signalling.

Abstract Background Primary thymic adenocarcinoma (PTAC) is an extremely rare disease with a poor prognosis. In the present study, we sought to analyze the clinical characteristics and prognostic factors of patients with PTAC. Methods A total of 14 patients with PTAC treated at our center from January 2000 to January 2019 were included in this study. We retrospectively collected information on sex, age, history of smoking, family history of cancer, comorbidities, symptoms, imaging tests, serum tumor marker levels, tumor, node, metastasis (TNM) staging, and treatment records. Follow‐up information was obtained by telephone interviews or outpatient clinic visit. Univariate and multivariate Cox regression analyses were performed to investigate the clinicopathological factors associated with survival. Results Among 14 patients with PTAC, there were five males and nine females, with an average age of 48.7 ± 9.3 years. A total of 23.1% of the patients had a history of smoking. The clinical symptoms of the patients were nonspecific and seven patients had elevated levels of serum tumor markers. Surgery was performed for nine patients, among which only four received R0 resection. The median survival time of the 14 patients was 16.0 months, and the 1‐, 3‐ and 5‐year survival rates were 57.1%, 35.7% and 21.4%, respectively. TNM stage was identified as an independent prognostic factor for PTAC patients (the median survival time of stage I–IIIA vs. stage IV was 44.0 months vs. 9.0 months, p = 0.002). Conclusions PTAC is highly aggressive malignancy with poor prognosis. Surgical treatment is feasible, but R0 resection is challenging. TNM staging is significantly associated with patient survival.

Abstract Background The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central‐type non‐small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). Methods Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan–Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. Results The disease‐free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan–Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs.

Abstract Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88–53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136–138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130–135.9 mmol/L), L3 (139–140.9 mmol/L), L4 (141–142.9 mmol/L), and L5 (143–147.0 mmol/L) groups were 0.31 (0.14–0.70, P = 0.005), 0.48 (030–0.78, P = 0.003), 0.56 (0.34–0.92, P = 0.022), and 0.37 (0.22–0.64, P

Abstract Background Disruptions in intracellular pH (pHi) homeostasis, causing deviations from the physiological range, can damage renal epithelial cells. However, the existence of an adaptive mechanism to restore pHi to normalcy remains unclear. Early research identified H+ as a critical mediator of ischemic preconditioning (IPC), leading to the concept of acidic preconditioning (AP). This concept proposes that short-term, repetitive acidic stimulation can enhance a cell’s capacity to withstand subsequent adverse stress. While AP has demonstrated protective effects in various ischemia-reperfusion (I/R) injury models, its application in kidney injury remains largely unexplored. Methods An AP model was established in human kidney (HK2) cells by treating them with an acidic medium for 12 h, followed by a recovery period with a normal medium for 6 h. To induce hypoxia/reoxygenation (H/R) injury, HK2 cells were subjected to hypoxia for 24 h and reoxygenation for 1 h. In vivo, a mouse model of IPC was established by clamping the bilateral renal pedicles for 15 min, followed by reperfusion for 4 days. Conversely, the I/R model involved clamping the bilateral renal pedicles for 35 min and reperfusion for 24 h. Western blotting was employed to evaluate the expression levels of cleaved caspase 3, cleaved caspase 9, NHE1, KIM1, FAK, and NOX4. A pH-sensitive fluorescent probe was used to measure pHi, while a Hemin/CNF microelectrode monitored kidney tissue pH. Immunofluorescence staining was performed to visualize the localization of NHE1, NOX4, and FAK, along with the actin cytoskeleton structure in HK2 cells. Cell adhesion and scratch assays were conducted to assess cell motility. Results Our findings demonstrated that AP could effectively mitigate H/R injury in HK2 cells. This protective effect and the maintenance of pHi homeostasis by AP involved the upregulation of Na+/H+ exchanger 1 (NHE1) expression and activity. The activity of NHE1 was regulated by dynamic changes in pHi-dependent phosphorylation of Focal Adhesion Kinase (FAK) at Y397. This process was associated with NOX4-mediated reactive oxygen species (ROS) production. Furthermore, AP induced the co-localization of FAK, NOX4, and NHE1 in focal adhesions, promoting cytoskeletal remodeling and enhancing cell adhesion and migration capabilities. Conclusions This study provides compelling evidence that AP maintains pHi homeostasis and promotes cytoskeletal remodeling through FAK/NOX4/NHE1 signaling. This signaling pathway ultimately contributes to alleviated H/R injury in HK2 cells.

Abstract Background Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance. Results In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate’s accuracy and 90.0% on top 10 candidate’s accuracy. Conclusion This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.

Abstract Although Omicron RBD of SARS-CoV-2 accumulates many mutations, the backbone region (truncated RBD) of spike protein is highly conserved. Here, we designed several subunit vaccines by keeping the conserved spike backbone region of SARS-CoV-2 Omicron BA.1 subvariant (S-6P-no-RBD), or inserting the RBD of Delta variant (S-6P-Delta-RBD), Omicron (BA.5) variant (S-6P-BA5-RBD), or ancestral SARS-CoV-2 (S-6P-WT-RBD) to the above backbone construct, and evaluated their ability to induce immune responses and cross-protective efficacy against various SARS-CoV-2 variants and SARS-CoV. Among the four subunit vaccines, S-6P-Delta-RBD protein elicited broad and potent neutralizing antibodies against all SARS-CoV-2 variants tested, including Alpha, Beta, Gamma, and Delta variants, the BA.1, BA.2, BA.2.75, BA.4.6, and BA.5 Omicron subvariants, and the ancestral strain of SARS-CoV-2. This vaccine prevented infection and replication of SARS-CoV-2 Omicron, and completely protected immunized mice against lethal challenge with the SARS-CoV-2 Delta variant and SARS-CoV. Sera from S-6P-Delta-RBD-immunized mice protected naive mice against challenge with the Delta variant, with significantly reduced viral titers and without pathological effects. Protection correlated positively with the serum neutralizing antibody titer. Overall, the designed vaccine has potential for development as a universal COVID-19 vaccine and/or a pan-sarbecovirus subunit vaccine that will prevent current and future outbreaks caused by SARS-CoV-2 variants and SARS-related CoVs.

Abstract Malicious online trolling is prevalent among Chinese college students and has recently garnered extensive attention from researchers due to the substantial harm it causes to the victims and the damage it inflicts on the online environment. Most previous studies have focused on examining how personal traits related to malicious online trolling. Further comprehensive research is needed to explore the mechanisms linking external environmental factors (antisocial media exposure) and malicious online trolling. A total of 1259 Chinese college students completed questionnaires regarding malicious online trolling, antisocial media exposure, hostile attribution bias, and empathy. The results indicated a positive association between antisocial media exposure and malicious online trolling among Chinese college students, with hostile attribution bias serving as a mediating factor. Furthermore, the direct and mediated paths between antisocial media exposure and malicious online trolling were moderated by empathy. Specifically, as the level of empathy increased among college students, the relations between the variables all weakened. Excessive exposure to antisocial media content among college students may trigger hostile attribution bias and lead to more malicious online trolling behavior. However, the relation between antisocial media exposure and malicious online trolling, hostile attribution bias and malicious online trolling, was attenuated when college students’ empathy levels were high.

Abstract Recent studies indicate that Glypican 1 (GPC-1) is aberrantly expressed and plays a key role in certain cancers, but little is known in the hepatocellular carcinoma. Raw data from TCGA, GTEx and TIMER databases were utilized to comprehensively analyze GPC-1 expression landscape in pan-cancer, and the biological function of GPC-1 was investigated in liver cancer cells. The results revealed that GPC-1 is highly expressed in HCC, negatively correlated with survival, and also positively correlated with immune infiltration and clinical stage. Furthermore, GPC-1 promoted cell proliferation and inhibited apoptosis in the HCC cell lines. WGCNA analysis and HCCDB database revealed that Akt acted as a key molecule related to GPC-1, influencing biological functions and regulating cell malignant behaviors via the AKT signaling pathway. In conclusion, our findings provide a relatively comprehensive understanding of the oncogenic role of GPC-1 in HCC, implying that GPC-1 could serve as an innovative therapeutic target.

Numerous evidences showed that human umbilical cord blood (UCB) mononuclear cells were a promising approach for the therapy of ischemic stroke(IS). The effect of stage-specific embryonic antigen 3 (SSEA3）positive subpopulation in UCB was not investigated in IS. In this study, we isolated SSEA3 positive cells from healthy UCB mononuclear cells, which comprised about 7.01% of the total UCB-mononuclear cells. Flow cytometry analysis revealed that SSEA3(+)UCB cells were almost positive for CD44 and CD45, and negative for CD73, CD90 and CD105. The expression of Oct3/4 in SSEA3(+)UCB cells were higher than that in UCB. SSEA3(+)UCB cells sorted by magnetic cell sorting were intravenously injected into the middle cerebral arterial occlusion(MCAO) rat model. Neurological score showed that SSEA3(+)UCB transplantation group exhibited significant improvements in the functional outcome of MCAO rats than UCB transplantation group. Nissl staining and microtubule association protein-2(MAP2) immunofluorescence staining showed that the SSEA3(+)UCB transplantation group decreased neuronal loss. SSEA3(+)UCB transplantation group reduced neuronal apoptosis, inhibited caspase3 expression, and decreased tumor necrosis factor α(TNF-α). These results indicate that SSEA3 positive cells are a novel subpopulation of UCB cells, which exhibit great potential for the treatment of ischemic stroke.

Abstract As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients.Design: Clinical study protocol, SPIRIT compliant.Setting: Prospective, single-center, randomized, and sham-controlled trial.Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients.Exposures: Intraoral or sham acupuncture.Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the “Drooling Severity and Frequency Scale” and “Functional Oral Intake Scale.” Results : : The results from this study will be published in peer-reviewed journals.Conclusion : : Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

Objective: To validate deep learning models’ ability to predict post-transplantation major adverse cardiovascular events (MACE) in patients undergoing liver transplantation (LT). Patients and Methods: We used data from Optum’s de-identified Clinformatics Data Mart Database to identify liver transplant recipients between January 2007 and March 2020. To predict post-transplantation MACE risk, we considered patients’ demographics characteristics, diagnoses, medications, and procedural data recorded back to 3 years before the LT procedure date (index date). MACE is predicted using the bidirectional gated recurrent units (BiGRU) deep learning model in different prediction interval lengths up to 5 years after the index date. In total, 18,304 liver transplant recipients (mean age, 57.4 years [SD, 12.76]; 7158 [39.1%] women) were used to develop and test the deep learning model’s performance against other baseline machine learning models. Models were optimized using 5-fold cross-validation on 80% of the cohort, and model performance was evaluated on the remaining 20% using the area under the receiver operating characteristic curve (AUC-ROC) and the area under the precision-recall curve (AUC-PR). Results: Using different prediction intervals after the index date, the top-performing model was the deep learning model, BiGRU, and achieved an AUC-ROC of 0.841 (95% CI, 0.822-0.862) and AUC-PR of 0.578 (95% CI, 0.537-0.621) for a 30-day prediction interval after LT. Conclusion: Using longitudinal claims data, deep learning models can efficiently predict MACE after LT, assisting clinicians in identifying high-risk candidates for further risk stratification or other management strategies to improve transplant outcomes based on important features identified by the model.

Cardiomyopathy is a severe cardiac condition characterized by complex immune regulatory mechanisms. While the role of immune genes is recognized, the specifics of their regulation in cardiomyopathy are not fully understood. Recent studies highlight the significance of transposable elements (TEs) in various diseases, particularly their potential to modulate immune responses. This paper utilizes publicly available databases to explore the role of TEs in myocarditis: RNA Seq data and single-cell sequencing data were analyzed, with a focus on the mouse model of experimental autoimmune myocarditis (EAM). The RNA-Seq analysis revealed substantial upregulation of a range of immune genes in cardiac tissue. Further investigation using single-cell sequencing of cardiac immune cells identified specific expression of certain transposable elements (TEs) across different types of immune cells in the heart. Additionally, there was an overall increase in the expression of the ERVB7-1. LTR-MM transposon across various cells in the EAM model, suggesting a widespread impact of this transposon on the immune response in this disease context. The findings of this study highlight the intricate interplay between transposable elements and the immune system in cardiomyopathy, providing new insights into the molecular mechanisms underlying this condition. The discovery of specific TEs expression in cardiac immune cells and the overall increase in ERVB7-1. LTR-MM expression across the EAM model underscore the potential of these elements in modulating immune responses and contribute to our understanding of cardiomyopathy's pathogenesis. These observations open avenues for further research into the role of TEs in cardiac disases and may lead to novel therapeutic strategies.

Lycium ruthenicum (LRM), endemic to Northwest China, is known as hei goji or black goji and is renowned for its rich bioactive compounds. This review analyzes LRM's geographic distribution and traceability and highlights challenges and future developments in geographical traceability. The work also focuses on LRM's bioactive constituents, especially on anthocyanins and polysaccharides, demonstrating a clear clue for understanding their updated extraction methods, identification, and diverse bioactive activities, including antioxidation, anti-inflammation, and immunomodulation, which is beneficial to developing novel functional foods and new medical materials. Moreover, the paper elucidates advances in the potential application of LRM in food preservation, packaging, and other domains. Notably, we figure out gaps in LRM research, such as traceability technology and the proven efficacy of biological activities. This study provides a foundation for future perspectives on developing nutraceuticals and functional foods, disease treatment supplements, and green food packaging materials by bridging these gaps.

As a dual-function protein, prosaposin (PSAP) is a lysosome-associated protein that participates in a variety of cellular processes. In the lysosome, PSAP is processed to activate enzymes that degrade lipids. In addition, PSAP proteins located extracellularly are involved in cancer progression, such as proliferation and tumor death suppression signaling. Moreover, under different situations, PSAP exhibits distinct metastasis potentials in tumors. However, comprehensive insight into PSAP in cancer progression has been lacking. Here, we provide a framework of the role of PSAP in cancer and its clinical application in cancer patients, providing a novel perspective on the clinical translation of PSAP.

ABSTRACT Background High‐intensity focused ultrasound (HIFU) is a promising minimally invasive treatment for liver cancer; however, its efficacy is often limited by the attenuation of ultrasonic energy. This study investigates the effectiveness of B7‐H3‐targeted microbubbles (T‐MBs) in enhancing HIFU ablation of liver cancer and explores their potential for clinical translation. Methods T‐MBs and isotype control microbubbles (I‐MBs) were synthesized through the conjugation of biotinylated anti‐B7‐H3 antibody and isotype control antibody to the microbubble surface, respectively. Contrast‐enhanced ultrasound imaging was performed to compare the accumulation of T‐MBs and I‐MBs in liver cancer at various time points. The efficacy of T‐MBs in enhancing HIFU treatment was evaluated by measuring the immediate tumor ablation rate and long‐term tumor growth suppression. Additionally, the induced antitumor immune response was assessed through cytokine quantification in serum and tumor tissue, along with immunofluorescence staining conducted on days 1, 3, and 7 post‐treatment. Results T‐MBs demonstrated superior liver cancer‐specific accumulation, characterized by higher concentrations and prolonged retention compared to I‐MBs. The combination of T‐MBs with HIFU resulted in significantly enhanced tumor ablation rates and superior tumor growth suppression. Post‐treatment analysis revealed a gradual uptick in cytokine levels within the tumor microenvironment, along with progressive infiltration of antitumor immune cells. Conclusion T‐MBs effectively enhance the therapeutic efficacy of HIFU for liver cancer treatment while simultaneously promoting an antitumor immune response. These findings provide a strong experimental foundation for the clinical translation of ultrasound molecular imaging combined with HIFU as a novel approach for tumor therapy.

ABSTRACT Objective This meta‐analysis aimed to evaluate the comparative diagnostic performance of amyloid‐β positron emission tomography (Aβ PET) and magnetic resonance imaging (MRI) in diagnosing Alzheimer's disease (AD). Methods An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Head‐to‐head comparative studies were included if they evaluated the diagnostic performance of Aβ PET and MRI in diagnosing Alzheimer's disease. Sensitivity and specificity were assessed using the DerSimonian and Laird method, followed by transformation via the Freeman–Tukey double inverse sine transformation. Results Six articles involving 560 patients were included in the meta‐analysis. When distinguishing AD from mild cognitive impairment (MCI), both methods showed comparable sensitivity (Aβ PET: 0.71, MRI: 0.62) and specificity (Aβ PET: 0.68, MRI: 0.69), with no statistically significant differences observed (p = 0.34 and 0.99). When identifying AD from normal cognitive control (NC), both Aβ PET and MRI showed similar results, with comparable sensitivity (Aβ PET: 0.93, MRI: 0.85) and specificity (Aβ PET: 0.95, MRI: 0.82), without significant differences (p = 0.38 and 0.19). Similarly, in detecting MCI from NC, both Aβ PET and MRI demonstrated similar sensitivity (Aβ PET: 0.69, MRI: 0.64) and specificity (Aβ PET: 0.75, MRI: 0.76) without significant differences (p = 0.40 and 0.94). However, 18F‐FMM seems to have a higher specificity compared to MRI when distinguishing AD from MCI (P = 0.03) and AD from NC (p = 0.04). Conclusions Our meta‐analysis indicates that Aβ PET demonstrates similar sensitivity and specificity to MRI in diagnosing Alzheimer's disease. However, the limited number of studies may impact the evidence of the current study; further larger sample prospective research is required to confirm these findings.

BackgroundResearch on how the physical activity home environment affects fundamental movement skills (FMS) in preschool children in China is limited. However, the role of moderate-to-vigorous physical activity (MVPA) in this relationship is still unclear. This study aims to analyze gender differences in FMS, explore associations between the physical activity home environment, MVPA, and FMS, and investigate MVPA's mediating role in these relationships.MethodsWe recruited 169 preschool children (95 boys, 74 girls; mean age 4.9 years) from four kindergartens in Hengyang, China. The Family Environment Scale on Motor Development for Preschool Urban Children (FESMPD) assessed physical activity home environment. Objective measurement of MVPA used ActiGraph wGT3-BT accelerometers. The Test of Gross Motor Development-3 (TGMD-3) evaluated FMS. Statistical analyses were conducted using the PROCESS macro in SPSS, with sociodemographic variables as controls.ResultsBoys exhibited significantly higher levels of MVPA, parenting style, locomotor skills, and object control skills compared to girls (P

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

Background: To enhance the accuracy of hepatocellular carcinoma (HCC) diagnosis using contrast-enhanced (CE) US, the American College of Radiology developed the CEUS Liver Imaging Reporting and Data System (LI-RADS). However, the system still exhibits limitations in distinguishing between HCC and non-HCC lesions. Purpose: To investigate the viability of employing machine learning methods based on quantitative parameters of contrast-enhanced ultrasound for distinguishing HCC within LR-M nodules. Materials and methods: This retrospective analysis was conducted on pre-treatment CEUS data from liver nodule patients across multiple centers between January 2013 and June 2022. Quantitative analysis was performed using CEUS images, and the machine learning diagnostic models based on quantitative parameters were utilized for the classification diagnosis of LR-M nodules. The performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and compared with the performance of four radiologists. Results: The training and internal testing datasets comprised 168 patients (median age, 53 years [IQR, 18 years]), while the external testing datasets from two other centers included 110 patients (median age, 54 years [IQR, 16 years]). In the internal independent test set, the top-performing Random Forest model achieved an AUC of 0.796 (95%CI: 0.729–0.853) for diagnosing HCC. This model exhibited a sensitivity of 0.752 (95%CI: 0.750–0.755) and a specificity of 0.761 (95%CI: 0.758–0.764), outperforming junior radiologists who achieved an AUC of 0.619 (95%CI: 0.543–0.691, p

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammatory tissue damage to the intestinal mucosa and forming intestinal epithelial ulcers. It is one of the most intractable diseases in the world. To date, the mechanism is unclear. Causonis japonica (Thunb.) Raf. (Wu Lianmei in Chinese; WLM), a traditional Chinese medicine, which has a long history as an anti-inflammatory, but its effect on UC was unconfirmed yet. Therefore, we established a dextran sodium sulfate (DSS)-induced UC mice model and evaluated the therapeutic effect of WLM extract. The results indicated that WLM inhibits DSS-induced inflammatory response in colitis in vivo, decrease DSS-induced clinical manifestations, reverses colon length shortening, and reduces tissue damage. The results of ELISA kits suggested that WLM could reverse the levels of DSS-induced inflammatory factors. To explore the mechanism of WLM in treating DSS-induced UC, 1H NMR and UHPLC-Q/Orbitrap MS were used to perform non-targeted metabolomics analysis; 21 differential metabolites in colon tissues were closely related to UC. Meanwhile, the pseudo-targeted lipidomics based on UHPLC-Q/Trap MS was used to analyze lipid metabolism disorders, and 60 differential lipid compounds were screened. These differential compounds were mainly involved in glycerophospholipid, arachidonic acid, glycerolipid, citric acid, tyrosine, and ether lipid metabolisms. The analysis of gut microbial showed that WLM may improve the symptoms of UC mice by reducing the abundance of Helicobacter and Streptococcus and increasing the abundance of Limosilactobacillus and Akkermansia. Moreover, the real-time qPCR results showed that WLM extract could decrease the mRNA levels of inflammatory factors and may be associated with protecting the integrity of intestinal mucosal barrier by destroying in vivo metabolic pathways, especially by regulating energy and lipid metabolisms and reducing inflammatory reactions. It provides a beneficial reference for studying WLM to elucidate the therapeutic mechanism of UC.

Background: Closed-loop electronic medication management systems are effective measures for preventing medication errors (MEs). However, there is limited evidence supporting this, and few studies have evaluated the long-term effects of these systems on safe medication. Objective: To evaluate the long-term effects of implementing a closed-loop medication order executive system on the safe clinical use of medications. Design: A quasi-experimental design. Method: Data from 2017 to 2023 were extracted and retrospectively analyzed. The primary outcome indicator was the ME rate. Secondary outcome indicators were the accuracy of order verification and patient identification and the implementation rate of fresh medicine dispensing. The autoregressive integrated moving average (ARIMA) model in time-series analysis was used to evaluate the level and trend changes in ME rates using SPSS 25.0 before and after system implementation. Root cause analysis and descriptive statistics were used to assess changes in types, stages, and causes of ME rates. The independent samples t -test was used to analyze secondary outcomes. Results: Overall, 295 MEs were reported with a mean of 0.26 ± 0.26 ME rates per month during 2017–2023. The ARIMA model showed a decrease in the average level of ME rates after system implementation, with no statistically significant decrease in the long term, and a significant drop in the ME rate in the short and medium term ( p

Various studies have demonstrated that directed evolution is a powerful tool in enhancing protein properties. In this study, directed evolution was used to enhance the efficacy of synthesised Anabas testudineus AtMP1 antimicrobial peptides (AMPs) in inhibiting the proliferation of cancer cells. The modification of antimicrobial peptides (AMPs) and prediction of peptide properties using bioinformatic tools were carried out using four databases, including ADP3, CAMP-R3, AMPfun, and ANTICP. One modified antimicrobial peptide (AMP), ATMP6 (THPPTTTTTTTTTTTTTAAPARTT), was chosen based on its projected potent anticancer effect, taking into account factors such as amino acid length, net charge, anticancer activity score, and hydrophobicity. The selected AMPs were subjected to study in deep-learning databases, namely ToxIBTL and ToxinPred2, to predict their toxicity. Furthermore, the allergic properties of these antimicrobial peptides (AMPs) were verified by utilising AllerTOP and AllergenFP. Based on the results obtained from the database study, it was projected that antimicrobial peptides (AMPs) demonstrate a lack of toxicity towards human cells that is indicative of the broader population. After 48 hours of incubation, the IC50 values of ATMP6 against the HS27 and MDA-MB-231 cell lines were found to be 48.03 ± 0.013 µg/ml and 7.52 ± 0.027 µg/ml, respectively. The IC50 values of the original peptide ATMP1 against the MDA-MB-231 and HS27 cell lines were determined to be 59.6 ± 0.14 µg/ml and 8.25 ± 0.14 µg/ml, respectively, when compared. Furthermore, the results indicated that the injection of ATMP6 induced apoptosis in the MDA-MB-231 cell lines. The present investigation has revealed new opportunities for advancing novel targeted peptide therapeutics to tackle cancer.

Objective: To explore the cause-effect relationship between uterine diseases (UDs) and breast cancer (BC) and underlying mechanism of the cause-effect relationship, enhance understanding of the association between BC and UDs. Methods: A two-sample bidirectional Mendelian randomization (MR) analysis was conducted. We obtained summary statistics data from GWAS for BC, endometriosis, endometrial cancer (EC), uterine leiomyoma (UL), uterine polyps (UP), and cervical cancer (CC). Independent SNPs were selected as instrumental variables (IVs) for each disease. The inverse variance weighted (IVW) method was primary used for estimating the causal association between UDs and BC. To further evaluate the consistency and dependability of the results, we also utilized the weighted median, weighted mode, simple mode, and MR-Egger methods, along with sensitivity analyses. Furthermore, a supplementary analysis focusing on the variants linked to BC and UDs was conducted. This involved identifying corresponding genes and subsequently performing KEGG/GO analyses to investigate potential molecular mechanisms. Results: The results indicated significant associations between genetic susceptibility to endometriosis, EC, and UL with BC risk. The odds ratios (ORs) were as follows: endometriosis at 0.963 (95 % CI, 0.942–0.984; p = 7.11e-5), EC at 1.056 (95 % CI, 1.033–1.081; p = 2.39e-6), and UL at 1.027 (95 % CI, 1.006–1.048; p = 0.010). Conversely, the predisposition to BC inferred from genetic factors was markedly correlated with an elevated risk of EC indicated by an OR of 1.066 (95 % CI, 1.019–1.116; p = 0.006), and was correlated with UP risk (OR, 1.001,95 % CI, 1.000–1.002; p = 0.001).Sensitivity analyses provided weak evidence for these effects, suggesting that the study's outcomes are consistent and trustworthy. Further analysis of the genetic variants associated with BC, and these related genes are enriched in Cellular senescence, GnRH secretion, Phosphatidylinositol signaling system, and so on. Conclusion: This study corroborates the existence of a reciprocal causal relationship between BC and EC, as well as highlighting the substantial correlations between a genetic susceptibility to UL and endometriosis with BC. BC may exert their influence on EC and UP through Cellular senescence, GnRH secretion, and other pathways. These discoveries offer fresh perspectives on the genetic pathogenesis of BC and UDs, and can guide future experimental studies. Additionally, they lay down a groundwork for the development of tailored preventative and therapeutic strategies moving forward.

BackgroundDepression is a significant burden on individuals and society, which requires our attention and action. As the aging wave collides with digitalization, further research is needed to understand how internet use relates to depression in older adults. This study aimed to investigate whether volunteer activity participation and friend networks played a chain mediating role in this relationship from the perspective of the socioemotional selectivity theory.MethodThis study’s data was derived from the 2018 China Longitudinal Aging Social Survey (CLASS), comprising 5,558 samples. The study employed the OLS model for benchmark regression and multiple robust check methods, including altering variable settings and utilizing the instrumental variable model. In addition, the generalized structural equation model (GSEM) was used to analyze the mechanism.ResultUsing the internet was significantly associated with reduced depression in older adults (coefficient = −0.9321, p

ObjectiveThe relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves’ disease (GD).MethodsDatasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran’s Q test, and robustness was assessed via leave-one-out sensitivity analysis.ResultsMR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran’s Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust.ConclusionsEvidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders.

Four novel species of subgenus Russula crown clade collected from northwestern China are described based on morphological and phylogenetic evidence. Morphologically, R. griseorosea Y.Song sp. nov. (subsection Puellarinae) is characterized by its brown pileus with a grayish pink tint, basidiospores with warts often connected by fine lines, orthochromatic pileipellis with long terminal cells and septate pileocystidia; R. micangshanensis Y.Song sp. nov. (subsection Olivaceinae) is diagnosed by its large basidia, hymenial cystidia and basidiospores, and spore ornamentations with unequal crests and often twinned warts, which give the spore distinctive appearance; R. minirosea Y.Song sp. nov. (subsection Laricinae) has very small basidiocarp with pileus less than 3.3 cm in diameter, basidiospores with fine reticulum, small basidia, and septate pileocystidia; R. purpureomarginalis F.Li & Y.Song sp. nov. (subsection Xerampelinae) has large basidiospores with often isolated ornamentations, slim basidia and often septate flexuous pileocystidia. Differences between the four novel species and their closely related taxa were analyzed. Phylogenetic analyses based on both ITS and multi-locus (LSU, rpb2 and tef1) were carried out to confirm the distinct taxonomic status of the four novel species.

This article summarized the experience of integrated Chinese and western medicine nursing of a patient with septic gastrointestinal injury-intestinal obstruction (toxic megacolon). According to the theory of pathogenesis integration of Chinese and western medicine, the appropriate nursing technology of Chinese medicine was implemented in three stages. The first stage was clearing heat and detoxification, smoothing the liver and awakening the blood, including ear bloodletting; In the second stage, measures was taken to promote lung qi, including Traditional Chinese Medicine retention enema and auricular acupoint pressure; In the third stage, the skin needle therapy and Traditional Chinese Medicine hot package therapy were carried out. After 40 days of treatment, the patient's body temperature returned to the normal level, the symptoms of abdominal pain, abdominal distension and diarrhea disappeared, and the pressure ulcer treatment was continued in our hospital. (本文总结1例基于“中西医病机融通理论”治疗脓毒症胃肠损伤-肠痹(中毒性巨结肠)患者的护理体会。通过护理评估和中医辨证, 在常规护理的基础上, 依据“中西医病机融通理论”, 分3个阶段实施耳部放血、中药保留灌肠、耳穴贴压、中药热奄包、皮内针疗法等中医适宜护理技术, 缓解患者不适症状, 改善胃肠功能。)

Abstract Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens. Graphical abstract

Abstract The diagnostic accuracy of clinically significant prostate cancer (csPCa) of Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) is limited by subjectivity in result interpretation and the false positive results from certain similar anatomic structures. We aimed to establish a new model combining quantitative contrast-enhanced ultrasound, PI-RADSv2, clinical parameters to optimize the PI-RADSv2-based model. The analysis was conducted based on a data set of 151 patients from 2019 to 2022, multiple regression analysis showed that prostate specific antigen density, age, PI-RADSv2, quantitative parameters (rush time, wash-out area under the curve) were independent predictors. Based on these predictors, we established a new predictive model, the AUCs of the model were 0.910 and 0.879 in training and validation cohort, which were higher than those of PI-RADSv2-based model (0.865 and 0.821 in training and validation cohort). Net Reclassification Index analysis indicated that the new predictive model improved the classification of patients. Decision curve analysis showed that in most risk probabilities, the new predictive model improved the clinical utility of PI-RADSv2-based model. Generally, this new predictive model showed that quantitative parameters from contrast enhanced ultrasound could help to improve the diagnostic performance of PI-RADSv2 based model in detecting csPCa.

Abstract Objective To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD). Methods Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated. Results Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed. Conclusion Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.