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Abstract LiNi x Co y Mn1-x-y O2 (0 < x, y

University admission consultation is a professional service that assists students with the university application process. Typically, accessing this service entails exploring university websites, directly contacting faculty members and officers via phone calls or emails, and engaging educational intermediaries. University admission consultation is crucial for both students and institutions. However, conventional consultation methods face challenges such as time and spatial constraints, leading to a growing interest in utilizing chatbots for university admission consultation. In this study, we propose a novel approach that leverages generative pretrained transformer (ChatGPT 3.5) models and implements the retrieval-augmented generation technique using the LlamaIndex framework. To evaluate the effectiveness of this approach, we applied it to undergraduate admission data from three universities: a science and technology university in the United States, a comprehensive university in Kenya, and a comprehensive university in Hong Kong. We also gathered feedback from 53 high school students who tested the chatbot. The results demonstrated a significant improvement in average accuracy, from 41.4% with the ChatGPT 3.5 model to 89.5% with the proposed chatbot, with peak accuracy reaching 94.7%. User reviews also indicated a generally positive perception of the admission chatbot. This methodology has the potential to revolutionize university admissions by utilizing chatbots based on large language models with retrieval-augmented generation.

Abstract This study explores the feasibility, safety, and efficacy of percutaneous transluminal angioplasty (PTA) for reinserting tunneled cuffed catheters (TCC) with a Dacron sheath in the right internal jugular vein (RIJV) in hemodialysis patients with a history of prior RIJV catheterization and subsequent stenosis or occlusion of the RIJV, right innominate vein, and superior vena cava. Clinical data from 21 hemodialysis patients with dysfunctional vascular access who underwent PTA for reinsertion of TCC in the RIJVs from July 2020 to June 2023 at the First and Second Affiliated Hospitals of Bengbu Medical College were retrospectively analyzed. Clinical efficacy during hospitalization, postoperative TCC blood flow, and related complications during follow-up were observed. The procedure was successful in all 21 patients, with postoperative TCC blood flow meeting daily hemodialysis requirements. Only one case experienced acute bleeding with contrast agent extravasation at the intersection of the left and right innominate veins during sharp recanalization. No severe complications, such as arrhythmias, vascular rupture, pneumothorax, mediastinal hematoma, or pericardial tamponade, occurred during the procedures. Upon discharge, all patients exhibited satisfactory TCC blood flow (247.14 ± 11.46 ml/min). Postoperatively, TCC blood flow ranged between 200 and 260 ml/min, meeting the demands of regular hemodialysis. For patients with a history of repeated TCC or non-tunneled catheter (NTC) placement in the RIJV, reinserting TCC in the RIJVs through PTA is a safe and reliable technique. It effectively utilizes vascular resources and prevents vascular resource depletion associated with changing the venous catheter placement location.

Abstract Background Gangrene and perforation are severe complications of acute appendicitis, associated with a higher mortality rate compared to uncomplicated appendicitis. Accurate preoperative identification of Gangrenous or perforated appendicitis (GPA) is crucial for timely surgical intervention. Methods This retrospective multicenter study includes 796 patients who underwent appendectomy. Univariate and multivariate logistic regression analyses are used to develop a nomogram model for predicting GPA based on laboratory tests and computed tomography (CT) findings. The model is validated using an external dataset. Results Seven independent predictors were included in the nomogram: white blood cell count, lymphocyte count, D-dimer, serum glucose, albumin, maximum outer diameter of the appendix, and presence of appendiceal fecalith. The nomogram achieved good discrimination and calibration in both the training and testing sets. In the training set, the AUC was 0.806 (95%CI: 0.763–0.849), and the sensitivity and specificity were 82.1% and 66.9%, respectively. The Hosmer-Lemeshow test showed good calibration (P = 0.7378). In the testing set, the AUC was 0.799 (95%CI: 0.741–0.856), and the sensitivity and specificity were 70.5% and 75.3%, respectively. Decision curve analysis (DCA) confirmed the clinical utility of the nomogram. Conclusion The laboratory test-CT nomogram model can effectively identify GPA patients, aiding in surgical decision-making and improving patient outcomes.

Abstract Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. To address these questions, we utilize Tlr7 and Irf7 deficiency mice, single-cell RNA analysis together with bone marrow transplantation approaches. We demonstrate that at the early phase of infection, SARS-CoV-2 causes the upregulation of Tlr7, Irf7, and IFN pathways in the lungs of the infected mice. The deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma levels in the circulation. The deficiency of Tlr7 tends to cause the reduced production and nuclear translocation of interferon regulatory factor 7 (IRF7) in the lungs of the infected mice, indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7 leading to IFN production on the development of innate and adaptive immunity against COVID-19.

Abstract LINC01089 is a prime example of a long non-coding RNA that plays a pivotal role in the progression of human cancers. The gene encoding this lncRNA is located on 12q24.31. LINC01089 has been demonstrated to exert tumor-suppressive effects in various cancers, including colorectal cancer, gastric cancer, lung cancer, ovarian cancer, cervical cancer, papillary thyroid carcinoma, breast cancer, and osteosarcoma. However, its role in hepatocellular carcinoma shows significant discrepancies across different studies. In this review, we systematically explore the functions of LINC01089 in human cancers through bioinformatics analysis, clinical studies, animal models, and fundamental experimental research. Furthermore, we delve into the biological mechanisms and functions of LINC01089, and discuss its potential as a future biomarker and therapeutic target in detail.

To comprehensively explore the nutritional quality and construct evaluation system, this paper studied the effects of different planting ways and growing years on the 23 nutritional qualities of Tonggu Polygonatum cyrtonema Hua, and constructs of its evaluation system by correlation, factors, and clustering analysis. The results showed that the content of ethanol-soluble extractives, protein, essential amino acids (EAA), medicinal amino acids (MAA), ash and 5 constant mineral elements in Polygonatum cyrtonema Hua from greenhouse planting (GP) was the highest, and the nutritional score of EAA was also the optimal. Also, the content of polysaccharide and saponins in Polygonatum cyrtonema Hua from open planting (OP) was the most, and the four trace elements (Fe, Mn, Zn and Se) were the highest in underwood planting (UP). The Polygonatum cyrtonema Hua from wild (W) had the highest content of flavonoids and total phenols. In addition, as the extension of growing years, the content of ethanol-soluble extractives, lipid, and polysaccharides in Tonggu Polygonatum cyrtonema Hua increased gradually, while there was no significant difference in the saponins, flavonoids and total phenols (P>0.05). However, the content of starch, crude fiber, protein, ash, nutritional score of EAA and mineral elements in Polygonatum cyrtonema Hua was negatively correlated with the growing years. In particular, the decline of nutritional quality in GP was the most significant. Through the analysis of correlation, factor, and cluster, the 22 indicators of nutritional quality were simplified into 13 indicators, and then a comprehensive evaluation model was established by principal component analysis (PCA). It was found that the comprehensive score (−1.331~1.161) of nutritional quality of 8 types was GP-3>UP-3>W-4>GP-5>GP-4>OP-3>UP-4>OP-4, that is, the nutritional quality of GP-3 was optimal. And on this basis, a 6-level standard for the nutritional quality comprehensive evaluation of Polygonatum cyrtonema Hua was established. These results will provide a theoretical basis for the screening of raw materials for development of high-value products and variety improvement of Polygonatum cyrtonema Hua.

Introduction: Orthodontic tooth movement (OTM) involves complex interactions between mechanical forces and periodontal tissue adaptation, mainly mediated by periodontal ligament cells, including periodontal ligament stem cells (PDLSCs), osteoblasts, and osteoclasts. Dopamine (DA), a neurotransmitter known for its critical role in bone metabolism, is investigated in this study for its potential to enhance osteogenic differentiation in PDLSCs, which are pivotal in OTM. This study examined the potential of DA to facilitate OTM by binding to DA receptors (D1R and D2R) and activating the ERK1/2 signaling pathway. We propose that DA's interaction with these receptors on PDLSCs could enhance osteogenic differentiation, thereby accelerating bone remodeling and reducing the duration of orthodontic treatments, which offering a novel approach to improve clinical outcomes in orthodontic care. Methods: This study utilized a rat OTM model, micro-CT, histological analyses, and in vitro assays to investigate dopamine's effect on osteogenesis. PDLSCs were cultured and treated with DA, and cytotoxicity, osteogenic differentiation, gene and protein expression assessed. Results: Dopamine administration significantly increased trabecular bone density and osteogenic marker expression in an OTM rat model. In vitro, DA at 10 nM optimally promoted human PDLSCs osteogenesis without affecting proliferation. Blocking DA receptors or inhibiting the ERK1/2 pathway attenuated these effects, underscoring the importance of dopaminergic signaling in tension-induced osteogenesis during OTM. Conclusion: Taken together, our study reveals that local dopamine administration at a concentration of 10 nM not only enhances tension-induced osteogenesis in vivo but also significantly promotes osteogenic differentiation of PDLSCs in vitro through D1 and D2 receptor-mediated ERK1/2 signaling pathway activation.

ObjectiveTo evaluate the current status of hypertension prevention and control management operation mechanisms in Chinese mainland, explore the impact of their improvement on hypertension prevention and control effects, and provide a reference for enhancing hypertension prevention and control management. MethodsPolicy documents related to hypertension prevention and control from January 1 2000 to December 31, 2018 in 31 provinces (municipalities and autonomous regions) in Chinese mainland were collected. The current status of hypertension prevention and control management operation mechanisms in Chinese mainland was systematically evaluated according to the appropriate public health system evaluation model and standard. A logistic regression model was used to analyze the impact of the improvement of management operation mechanisms on hypertension prevention and control effects. ResultsIn 2018, the appropriateness of hypertension prevention and control management operation mechanisms in Chinese mainland was 43.68%, with an increase of 21.64% compared to 2000, but there was still a gap of 48.61% from the appropriate standard. Among them, the appropriateness of coordination and incentive mechanisms was the lowest (14.03%), and the appropriateness of planning and evaluation mechanisms was the highest (63.04%). In terms of specific positioning, the coverage of medium and long-term plans (100.00%) and the completeness of content and form (94.45%) were relatively high, while the feasibility of management mechanisms was only 9.76%. The results of logistic regression analysis showed that the improvement of management operation mechanisms helped control blood pressure in hypertensive patients (OR = 1.012, P = 0.007) and maintain the stability of patients’ blood pressure (OR = 1.010, P = 0.029). Conclusion From 2000 to 2018, the construction of hypertension prevention and control management mechanisms in Chinese mainland tended to be improved, effectively promoting the improvement of hypertension prevention and control management levels. However, it is still necessary to further establish and improve coordination and incentive mechanisms and clarify the division of departmental responsibilities.

Abstract Background According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. Methods We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. Results The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. Conclusions We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data.

5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase in sugar content in fruit remains unclear. In this study, we found that ALA significantly promoted sucrose accumulation and SPS (sucrose phosphate synthase) activity in peach fruit. At 14, 28, 42, 50 and 60 days after ALA treatment, sucrose content of fruit was increased by 23%, 43%, 37%, 40% and 16%, respectively, compared with control treatment, and SPS enzyme activity was increased by 21%, 28%, 47%, 37% and 29%, respectively. Correlation analysis showed that the sucrose content of peach fruit under ALA treatment was significantly positively correlated with SPS activity. Subsequently, bioinformatics was used to identify SPS gene family members in peach fruit, and it was found that there were four members of the PpSPS gene family, distributed on chromosomes 1, 7 and 8, named PpSPS1, PpSPS2, PpSPS3 and PpSPS4, respectively. The results of qRT-PCR showed that PpSPS2 and PpSPS3 were highly expressed in response to ALA during fruit development, and the expression of PpSPS2 was positively correlated with SPS activity and sucrose accumulation in peach fruit. The results of tobacco subcellular localization showed that PpSPS2 was mainly distributed in the cytoplasm and nucleus, while PpSPS3 was mainly distributed in the nucleus. The results of this study will lay the foundation for further study on the functions of PpSPS and the regulation of sugar metabolism during the development and ripening of peach fruit by ALA.

Abstract Background The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. Methods A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. Results A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001–1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002–1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139–1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165–1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004–1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020–1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029–1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. Conclusions Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Abstract Background Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. Methods We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3β/β-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. Results Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3β/β-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3β/β-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3β/β-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3β/β-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

Soybean (Glycine max) is a short-day crop whose flowering time is regulated by photoperiod. The long-juvenile trait extends its vegetative phase and increases yield under short-day conditions. Natural variation in J, the major locus controlling this trait, modulates flowering time. We report that the three J-family genes influence soybean flowering time, with the triple mutant Guangzhou Mammoth-2 flowering late under short days by inhibiting transcription of E1-family genes. J-family genes offer promising allelic combinations for breeding.

Abstract When a high‐speed train approaches the insulated phase‐splitting section embedded between neighbouring power supply arms, the vacuum circuit breaker (VCB) installed on trains must be disconnected to maintain the traction power supply system as a no‐load condition for completing phase‐switching action, as the train passes through the phase‐splitting section depending on its inertia. However, when operating VCBs, the arc is easily triggered between the mobile contacts inside, accompanied by an overvoltage impulse. Herein, to explore the generating mechanism of inrush current and operational overvoltage, a model describing the ‘substation‐catenary‐train’ traction power supply system is launched based on an equivalent circuit modelling technique. Through the analysis of the transient VCB operational process, the phase of catenary voltage is directly related to the characteristics of the VCB switching‐on overvoltage, as the traction current's phase angle is relevant to the amplitude‐frequency characteristics of the VCB switching‐off overvoltage. Inrush current as a noteworthy element is related to the traction transformer's remanence. The automatic phase‐switching technique is utilised to suppress both operational overvoltage and inrush current, as the optimal combination of VCB switching‐on and switching‐off phases considering the balance between overvoltage and inrush current is achieved based on the particle swarm algorithm.

Abstract Background This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). Methods The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. Results No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. Conclusions The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.

Circular RNA (circRNA) are a unique class of non-coding RNAs characterized by their covalently closed loop structures, which grant them properties such as stability and conservation. Among these, circFOXP1 has been implicated in various diseases, including cancers, respiratory, skeletal, and cardiovascular disorders. This review systematically examines circFOXP1’s role in disease progression, highlighting its involvement in critical biological processes, including cell proliferation, invasion, apoptosis, and autophagy. Mechanistically, circFOXP1 functions through miRNA sponging, protein interactions, and modulation of key signaling pathways such as Wnt and PI3K/AKT. We discuss its potential as a diagnostic and therapeutic target. Our analysis also identifies key unresolved questions, such as the precise regulatory networks involving circFOXP1 and its translation potential, offering pathways for future research.

ObjectiveExplore alterations in topological features of gray matter volume (GMV) and structural networks in non-cognitive impairment end-stage renal disease (Non-CI ESRD).Materials and methodsUtilizing graph theory, we collected structural magnetic resonance imaging (sMRI) data from 38 Non-CI ESRD patients and 50 normal controls (NC). We compared, and extracted the GMV across subject groups, constructed corresponding structural covariance networks (SCNs), and investigated the alterations in SCNs feature parameters between groups.ResultsIn Non-CI ESRD patients, The GMV were reduced in several brain regions, predominantly on the left side (p

Objective The objective of this study is to assess the relationship between non-invasive ventilation (NIV) and the colonisation of oral and nasal microbiota in preterm infants within the neonatal intensive care unit (NICU).Design A prospective cohort study.Setting The NICU of Zhejiang University Children’s Hospital.Patients Patients include preterm infants with a gestational age of 28–35 weeks, enrolled within the first 24 hours of life.Interventions Infants were categorised based on respiratory support: NIV, which included nasal continuous positive airway pressure, nasal intermittent positive pressure ventilation or high-flow nasal cannula; and no respiratory support, defined as room air or low-flow nasal cannula at ≤2 L/min.Main outcome measures The primary outcome was the colonisation of oral and nasal microbiota at 5 days post birth, measured by colony-forming units per millilitre (CFU/mL), with colonisation defined as bacterial growth >103 CFU/mL.Results The study included 100 preterm infants, with 50 in each group. Nasal microbial colonisation was observed in 56% (28/50) of the NIV group, significantly higher than the 28% in the no respiratory support group. No significant differences were found in oral colonisation. Adjusted binary logistic regression showed an association between NIV and increased risk of nasal colonisation (adjusted OR=2.91, 95% CI 1.12 to 7.58, p=0.028).Conclusions NIV in preterm infants was linked to a higher risk of nasal microbial colonisation. This finding suggests the need for further research and consideration of infection control strategies in the NICU.

Objective: To evaluate the safety and efficacy of a novel endovascular thrombectomy device in a modified swine model of iliac vein thrombosis. Methods: A modified swine model for iliac vein thrombosis was created using proximal‒distal balloon occlusion combined with autologous venous thrombus and thrombin injections. The safety and efficacy of the newly developed Zylox endovascular thrombectomy system were evaluated in this animal model and its performance was compared with that of the AcoStream aspiration thrombectomy device. Results: Bilateral iliac vein thrombosis models were successfully created in 12 swine, with 23 iliac veins used for device testing and one for anatomical observation. The thrombus length in the Zylox group was greater than in the AcoStream group (98.42 ± 17.56 mm vs. 84.12 ± 13.30 mm), while thrombus scores were not significantly different between the two groups. Although Grade I thrombus clearance was achieved in all iliac veins in both groups, blood loss in the Zylox group was significantly less than in the AcoStream group (81.09 ± 27.26 ml vs. 162.50 ± 61.96 ml, P

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P

BackgroundLipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, the association between Lp(a) and adverse outcomes in patients with ischemic heart failure (IHF) remains unclear. This study aimed to investigate the relationship between serum Lp(a) levels and the incidence of major adverse cardiovascular events (MACE) in IHF patients.MethodsIn this single-center, retrospective cohort study, 1,168 IHF patients who underwent elective percutaneous coronary intervention (PCI) were enrolled. Patients were divided into four groups based on Lp(a) quartiles. The primary endpoint was MACE, defined as a composite of all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. Cox proportional hazards models were used to evaluate the association between Lp(a) quartiles and adverse outcomes. Restricted cubic spline (RCS) curve were constructed to explore the nonlinear relationship between Lp(a) levels and MACE risk. Subgroup analyses were performed to investigate the association in different subgroups.ResultsThe incidence of MACE increased significantly across Lp(a) quartiles (Quartile 4 vs. Quartile 1: 46.4% vs. 22.9%, P

The exponentially large compositional space of high entropy alloys (HEAs) offers more possibilities for designing alloys with desired properties. However, it also poses challenges to using the traditional “trial and error” approach in alloy design. In this work, an XGBoost model for predicting the elastic properties of the NbTiVZr family across the entire compositional space was established by combining density-functional theory (DFT) calculation results as the dataset with machine learning (ML) algorithms. Furthermore, considerations of charge transfer were incorporated into the solid solution hardening (SSH) model, and the model was further modified. Through comparing plasticity evaluation indices, the parameter D (γSurf/γGSFE) was determined to be suitable for predicting the plasticity of NbTiVZr alloys. A full compositional space model for yield strength and plasticity has been constructed based on the modified SSH model and the parameter D, respectively. Ultimately, an alloy design system combining the full compositional space models for yield strength and plasticity was established, achieving good consistency with experimental results. And a non-equiatomic alloy with a yield strength exceeding that of equiatomic alloys by 32.2 % (1409 MPa), while maintaining 29.27 % compressive strain was discovered. In conclusion, this work provides an efficient design strategy for alloys with desired properties.

Medicinal herbs can be used for the development of antioxidant and anticancer platforms. However, the mechanisms by which the bioactive materials show these properties remain largely unclear. Also, a detailed understanding of the interaction between small compounds and carrier proteins like albumin can provide useful information about the regulation of their stability and circulation time properties. In this paper, the interaction of rhamnazin (C17H14O7), an O-methylated flavonol exists in Rhamnus petiolaris, with human serum albumin (HSA) was investigated. Also, the antioxidant and anti-lung cancer effects of rhamnazin were assessed. The results showed that a static rhamnazin-HSA complex was formed by the contribution of hydrophobic forces, which led to an increase in the content of the α-helix structure of HSA. Cellular assays revealed that rhamnazin (10 µM) recovered cell viability in human proximal renal tubular epithelial cells (HK2) reduced by H2O2 (0.5 mM) through reduction of ROS, restoration of CAT and SOD activities and GSH content, regulation of Bax, Bcl-2, and caspase-3. Moreover, the anti-lung cancer data demonstrated that rhamnazin induced apoptosis on lung adenocarcinoma A549 cells associated with a p53-dependent manner via overexpression of apoptotic Bax and caspase-3 and down-regulation of anti-apoptotic Bcl-2. To summarize, the potential binding of rhamnazin and HSA, as well as its antioxidant/anticancer properties, are critical for understanding the solubility and stability of this bioactive compound in plasma, as well as its therapeutic implications.

Objective: To explore the effect of amyloid-β peptide (Aβ) on mandibular condyle to develop a new treatment for postmenopausal women with Temporomandibular joint osteoarthritis. Methods: A murine bone loss model was established by ovariectomy. Microstructure parameters of the condyle were measured by microcomputed tomography before and after intraperitoneal injection with Aβ. Flow cytometry, Alizarin red staining, RT-qPCR assays, FITC/PI staining, Oil Red O staining and western blotting were used to evaluate the effect of Aβ on the osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs). Results: In vivo, condylar microstructure parameters increased. Serum osteoprotegerin and procollagen type 1 N propeptide increased in a dose-dependent manner after the injection of Aβ, which were opposite the changes observed in c-terminal telopeptides of type I collagen, tumor necrosis factor-α and the high serum level of leptin. In vitro, Aβ promoted calcium nodule formation in the cells. The expression of ALP, Runx2, osteorix and osteocalcin increased significantly. The expression of mRNAs related to the Wnt signaling pathway was significantly upregulated, which could be blocked by DKK1. Conclusion: Aβ can reverse bone loss in the mandibular condyle in ovariectomized mice through promoting the osteogenic differentiation of mBMSCs via the Wnt pathway.

The main aim of this study was to propose a comprehensive risk indicator to identify the potential driving risk caused by the changing environment at tunnel entrance. Driving decisions are affected by many external factors, especially at the entrance of tunnels. However, driving indicators are mostly considering vehicle movement status currently. In this study, a safe potential field model including obstacle potential field, vehicle potential field and lighting potential field is constructed to evaluate influence of roads, drivers, vehicles, and change lighting conditions on driving risk. Furthermore, considering the driving risk distribution and its temporal change rate, a comprehensive driving risk indicator (CDRI) was established to evaluate the magnitude of driving risk. Finally, the comparison between CDRI and the other two classic risk indicators indicates that the CDRI proposed in this paper has a better performance in the safety assessment at tunnel entrance. It is expected that the finding in this study could be valuable in developing control and measures for in-tunnel driving risk declining.

Abstract Scalar fields play an important role in constructing modified gravity theories. In the case of a single scalar field with timelike gradient, the corresponding Lagrangian in the unitary gauge takes the form of spatially covariant gravity (SCG), which is proved useful in analyzing and extending the generally covariant theories. In this work, we apply the SCG method to the scalar-nonmetricity theory, of which the Lagrangian is built of the nonmetricity tensor and a scalar field. We derive the 3+1 decomposition of the geometric quantities and especially covariant derivatives of the scalar field up to the third order in the presence of a nonvanishing nonmetricity tensor. By fixing the unitary gauge, the resulting Lagrangian takes the form of a SCG with nonmetricity, in which all the ingredients are spatial tensors. We then exhaust the scalar monomials of SCG with nonmetricity up to $$d=3$$ d = 3 with d the total number of derivatives. Since the disformation tensor plays as an auxiliary variable, we take the Lagrangian with $$d=2$$ d = 2 as an example to show that after solving the disformation tensor, we can get an effective SCG theory for the metric variables but with modified coefficients. Our results provides a novel approach to extending the scalar-nonmetricity theory.

Narrow gap oscillating laser welding with filler wire is a promising technique for joining high-strength steels in construction machinery. In order to investigate the influence of beam oscillation on the surface morphology and microstructure of weld joints of two types of commonly-used high-strength steels, a comparative study between oscillation welding and non-oscillation welding was conducted. High-speed photography technique was employed to reveal the microstructure and mechanical properties of the dissimilar joints. The results showed that laser beam oscillation produces two effects: one was to enlarge the heated surface of molten pool, while the other was to stir the liquid metal in molten pool periodically. Under the first effect, the fusion between sidewall and weld bead layers was promoted, while under the latter, coarse columnar grains ceased to appear, but finer grains were formed. The weld joints between Q355 and 35 steels exhibited excellent tensile impact bending performance, which was attributed to the grain refinement effect. The results also demonstrated that the oscillation welding with a contact angle less than 50° could avoid lack of fusion in multi-pass wire-filling laser welding. The influence of the oscillation welding process on the quality of welding was further discussed.

Abstract Background Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. Results The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99–0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02–1.04; p 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25–2.17; p

ObjectiveTo analyze the change in service capacity against major epidemics before and after coronavirus disease 2019 (COVID-19) in China for the promotion of the capacity. MethodsVia systematic search on the official websites and the law documents website of Peking University (PKULAW), we collected totally 1 756 policy documents relevant to major epidemic prevention and control issued during 2002 – 2020 by government departments and professional public health institutions in 31 provincial-level administrative divisions of China. Contents about the coverage and assessability of service capacity of major epidemic prevention and control were extracted from the documents and indexes for evaluating national and regional coverage and assessability were calculated based on the extracted contents. Paired signed-rank test was used to analyze changes in the indexes before and during COVID-19 epidemic. ResultsThe coverage of major epidemic prevention and control services has reached 100% in the Chinese mainland in 2019. In comparison to those in 2019 before the emergence of COVID-19 epidemic, the national assessability indexes (%) for service capability of major epidemic prevention and control of pre-, ongoing- and post-stage increased in 2020 by 29.78% (65.59% vs. 50.54%) , 17.54% (72.04% vs. 61.29% ) and 4.34% (38.71% vs. 37.10%). the assessment index for service capability of major epidemic prevention and control of pre-stage increased from 78.79% to 89.39% for eastern region and that of ongoing-stage increased from 65.00% to 76.67% for western region (both P < 0.05); but there was no significant increase in regional assessment index for service capability of major epidemic prevention and control of post-stage. The national assessment index for service capacity of major epidemic prevention and control of whole process increased significantly from 66.00% in 2019 to 73.78% in 2020 after the emergence of COVID-19 epidemic (P < 0.001). ConclusionThe overall service capacity of major epidemic prevention and control has improved after the emergence of COVID-19 epidemic in the Chinese Mainland but the service capacity needs to be improved in central and western regions; in addition, the post-event assessment on the service capacity should be concerned for the promotion of the service capacity.

ObjectiveTo analyze changes in the coverage of incentive measures for promoting major epidemic prevention and control in documents published by governmental and professional departments in the Chinese Mainland before and after coronavirus disease 2019 (COVID-19) epidemic of 2020.MethodsThrough systematically searching websites of government departments and professional institutions in 31 provincial-level administrative divisions (PLADs) of the mainland of China, we retrieved totally 3 864 documents (including laws, regulations, standards, rules, proposals, plans, and guidelines) relevant to major epidemic prevention and control published from 2000 through 2020. The paragraphs related to incentive and disciplinary measures for promoting the containment of major epidemic were extracted to calculate region- and institution-specific coverage of the measures in the retrieved documents. Wilcoxon paired rank sum test was adopted to evaluate differences in the coverage of the established measures before and after COVID-19 epidemic of 2020 among various economic regions and administrative/professional institutions. ResultsThe average coverage of disciplinary measures for the retrieved documents increased from 74.19% before 2020 to 76.34% in 2020, with a significant increase of 2.90% (P < 0.05); while, the average coverage incentive measures was 22.85% for the documents published in 2020, significantly increased in comparison with no incentive measure presented in all the documents published before 2020 (P < 0.001). Compared to those before 2020, the national average combined coverage of incentive and disciplinary measures increased significantly by 11.83%, 30.77%, 42.11%, and 89.66% in 2020, for the documents published by administrative departments, public health institutions, health care institutions, and primary health care institutions, respectively; the national average coverage increased from 37.10% before 2020 to 49.60% in 2020 for the documents published by all the institutions, with an increment of 33.70%; and for the documents published by all the institutions in the PLADs of eastern, central and western region, the coverage increased significantly by 47.47%, 27.54% and 25.00% (all P < 0.05). ConclusionAfter COVID-19 epidemic of 2020, the coverage of incentive and disciplinary measures for promoting major epidemic prevention and control increased significantly in the documents published by governmental and professional departments in the mainland of China and the increase was much higher for the coverage of incentive measures.

Abstract Lithium-ion batteries (LIBs) and plastics are pivotal components of modern society; nevertheless, their escalating production poses formidable challenges to resource sustainability and ecosystem integrity. Here, we showcase the transformation of spent lithium cobalt oxide (LCO) cathodes into photothermal catalysts capable of catalyzing the upcycling of diverse waste polyesters into high-value monomers. The distinctive Li deficiency in spent LCO induces a contraction in the Co−O6 unit cell, boosting the monomer yield exceeding that of pristine LCO by a factor of 10.24. A comprehensive life-cycle assessment underscores the economic viability of utilizing spent LCO as a photothermal catalyst, yielding returns of 129.6 $·kgLCO −1, surpassing traditional battery recycling returns (13–17 $·kgLCO −1). Solar-driven recycling 100,000 tons of PET can reduce 3.459 × 1011 kJ of electric energy and decrease 38,716 tons of greenhouse gas emissions. This work unveils a sustainable solution for the management of spent LIBs and plastics.

Abstract Existing monocular depth estimation driving datasets are limited in the number of images and the diversity of driving conditions. The images of datasets are commonly in a low resolution and the depth maps are sparse. To overcome these limitations, we produce a Synthetic Digital City Dataset (SDCD) which was collected under 6 different weather driving conditions, and 6 common adverse perturbations caused by the data transmission. SDCD provides a total of 930 K high-resolution RGB images and corresponding perfect observed depth maps. The evaluation shows that depth estimation models which are trained on SDCD provide a clearer, smoother, and more precise long-range depth estimation compared to those trained on one of the best-known driving datasets KITTI. Moreover, we provide a benchmark to investigate the performance of depth estimation models in different adverse driving conditions. Instead of collecting data from the real world, we generate the SDCD under severe driving conditions with perfect observed data in the digital world, enhancing depth estimation for autonomous driving.

In the present work, cast iron was used as the carbon source to fabricate WC particle gradient-reinforced W–Cu composites. The results revealed that the surface layer of W–Cu composites after carbonization can be divided into a complete carbonization zone and core-shell structure transition zone, the thickness of the carbonized layer increased gradually with the extension of treatment time. In addition to the W phase and Cu phase, WC and Fe3W3C phases are formed in the surface layer. The hardness and compressive strength of the surface layer show a trend of first increasing and then decreasing, and the arc erosion resistance of the surface layer gradually improves with the treatment time extending. The C atoms diffusion relationship between carbonization layer thickness (D), sintering temperature (T), and treatment time (t) of W–Cu composites with cast iron can be fitted as follows: D=1.9287×1013texp(‐929231RT).

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.

Chloride-induced corrosion of steel reinforcements has been identified as one of the main causes of deterioration of concrete structures. A feasible numerical method is required to predict chloride penetration in concrete structures. In this study, a three-phase model of concrete based on the Boundary Element Method (BEM) is proposed to investigate the diffusion and distribution behavior of chlorides in concrete. Compared with the finite element model (FEM), the proposed model has a higher computational efficiency, and a comparison of the simulated chloride concentration with the corresponding experimental data is proved to be reasonable. Furthermore, the parametric analysis is carried out to evaluate the effect of coarse aggregate parameters on chloride diffusion in concrete. The results show that chloride attack was more susceptible to the coarse aggregate content and less affected by the ITZ diffusion coefficient. This may be due to the fact that the volume fraction of aggregates in concrete is much higher than that in the ITZ. In addition, the low permeability of the coarse aggregate hindered the diffusion of chloride ions, while the ITZ around the aggregate accelerated the diffusion of chloride ions. when the aggregate content increases in a certain range from 12.56 % to 50.24 %, the hindering effect of aggregate on chloride ion diffusion is more obvious than the accelerating effect of ITZ.

ABSTRACTBackground This study investigated the acute effects of various doses of nitrate-rich beetroot juice on the responses to high-intensity interval exercise in women.Methods A double-blinded, randomized, placebo-controlled, crossover trial was conducted with 13 recreationally active young women (age = 23 ± 2 years). All participants performed interval exercise (8 × 1-min bouts of cycling at 85% of peak power output [PPO] interspersed with 1-min active recovery at 20% of PPO) 2.5 h after consumption of the randomly assigned beetroot juice containing 0 mmol (placebo), 6.45 mmol (single-dose), or 12.9 mmol (double-dose) [Formula: see text]. The heart rate (HR), blood pressure, blood lactate, blood glucose, oxygen saturation, rating of perceived exertion (RPE), and emotional arousal were assessed.Results Nitrate supplementation significantly altered the HR and RPE responses across the three trials. The mean HR was lower in the single- and double-dose groups than in the placebo control group during both work intervals and recovery periods, as well as across the overall protocol (all p

ABSTRACTThe South-to-North Water Diversion Project Middle Route (SNWD-MR) annually diverts hundreds of millions of cubic meters of water from the Danjiangkou Reservoir to Beijing, significantly impacting the regional groundwater cycle. To conserve water resources, the government has implemented ecological water replenishment (EWR) in some water systems. This study aimed to study the coupled process of groundwater dynamics and land subsidence (LS) in Yongding River (YDR) basin (Beijing section) following the implementation of the SNWD-MR and EWR. First, an Interferometric Synthetic Aperture Radar (InSAR) time series technique was used to detect spatial and temporal distributions of surface displacement between 2015 and 2020 based on satellite images from Sentinel-1A/B. The results indicated a predominant LS deceleration trend during the InSAR observation period. The area with subsidence velocity below 20 mm/yr decreased significantly by 18.6% after SNWD-MR and EWR (from 2016 to 2020). Then, groundwater level fluctuations during the InSAR observation period were analyzed using groundwater measurement well data. Over 60% of these wells showed a rebound in groundwater levels after the implementation of SNWD-MR and EWR. The polynomial distribution lag model (PDL) revealed the association between LS and groundwater level changes, depicting both short- and long-term lag effect. The results showed significant spatial and temporal heterogeneity on the short- and long-term response between groundwater level change and regional subsidence. In addition, we calculated the differential subsidence slope based on the InSAR-derived LS and analyzed its impact on the river slope after SNWD-MR and EWR. The results show that two sections with significant severe differential subsidence slope occur between 0 and 14,000 m and between 54,000 and 78,000 m along the YDR. The slope change caused by LS may reduce the conveyance capacity of surface canals, and more attention should be paid in those two sections. These findings have an important scientific significance for management strategy for LS control against the background of SNWD-MR and EWR.

This study investigated the impact of sweeteners on the release of heavy metals during the heating and atomization processes in electronic cigarettes. Based on a PG/VG base e-liquid with the addition of 2% and 5% neotame or sucralose, we quantitatively analyzed the impact of sweetener content on the levels of heavy metals such as Ni, Cr, and Fe in the e-liquid and aerosol after heating and atomization. Additionally, the heated e-liquid samples were used to culture SH-SY-5Y and Beas-2B cells, and their cytotoxic effects were assessed using the CCK-8 assay. The results indicated that the e-liquid with 5% sucralose had the highest average levels of heavy metals after heating and atomization, particularly nickel (13.36 ± 2.50 mg/kg in the e-liquid and 12,109 ± 3,229 ng/200 puffs in the aerosol), whereas the e-liquid with neotame had significantly lower average heavy metal content in comparison. Additionally, it was measured that the chloride ion concentration in the e-liquid with 5% sucralose reached 191 mg/kg after heating at 200°C for 1 h, indicating that heating sucralose generated chloride ions, Which might corrode metal parts components leading to heavy metal release. Cytotoxicity tests revealed that the base e-liquid without sweeteners exhibited the highest average cell viability after heating, at 64.80% ± 2.84% in SH-SY-5Y cells and 63.24% ± 0.86% in Beas-2B cells. Conversely, the e-liquid variant with 5% sucralose showed a significant reduction in average cell viability, reducing it to 50.74% ± 0.88% in SH-SY-5Y cells and 53.03% ± 0.76% in Beas-2B cells, highlighting its more pronounced cytotoxic effects compared to other tested e-liquids. In conclusion, sucralose in e-liquids should be limited preferably less than 2%, or replaced with neotame, a safer alternative, to minimize health risks.

Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition of increasing prevalence, is closely related to various metabolic disorders. Hemoglobin, a protein that transports oxygen in red blood cells, is the focus of this study, which seeks to investigate its potential association with NAFLD. Methods: We selected 6,516 eligible adult participants from the United States using the 2017–2020 National Health and Nutrition Examination Survey database for cross-sectional analyses. We analyzed the association of hemoglobin with NAFLD using weighted logistic regression models. Results: The study performed a weighted logistic regression modeling analysis, which verified that hemoglobin levels were positively associated with NAFLD, especially in the higher hemoglobin quartile groups. Subgroup analyses revealed no significant interactions, demonstrating the robustness of the model. The analysis of mediation effects showed that Gamma-Glutamyl Transferase, Alanine Aminotransferase, and triglycerides were important mediating variables in the relationship between hemoglobin and NAFLD. Conclusion: Increased hemoglobin levels were found to be significantly and independently associated with an increased NAFLD risk. This insight is crucial for the risk assessment and early detection of NAFLD, underscoring the need for heightened vigilance in individuals with higher hemoglobin levels.

Endoscopic tattooing plays a pivotal role in modern endoscopic localization of gastrointestinal lesions, facilitating further surgical intervention and aiding in the postoperative identification and repositioning of lesions. However, traditional endoscopic tattoo dyes often suffer from drawbacks such as side effects, short tattoo duration, and high overall costs. In this study, we developed polyvinylpyrrolidone (PVP)-modified polypyrrole (PPy) nanoparticles by oxidizing pyrrole in a PVP aqueous solution to create a PPy/PVP nanoparticle solution. This innovation aims to enhance endoscopic tattooing efficiency and mitigate the limitations associated with current tattooing methods. Both in vitro and in vivo evaluations confirmed the biosafety of PPy/PVP nanoparticles. Endoscopic tattooing experiments conducted in a pig model demonstrated the dye’s stability within the digestive tract. Similarly, subcutaneous tissue tattooing experiments performed in a mouse model revealed the sustained stability of the PPy/PVP tattoo dye for at least 180 days. With its robust stability, safety, and longevity, PPy/PVP nanoparticles hold promise as novel tattoo dyes for marking intestinal lesion sites. This advancement has the potential to enhance the accuracy of lesion localization and long-term tracking.

BackgroundPatients with early-stage breast cancer may have a higher risk of dying from other diseases, making a competing risks model more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors of breast cancer may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor.MethodsTo address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale.ResultsA simulation validated the accuracy of the coefficient estimates in the proposed regression. Applying this model to an older early-stage breast cancer cohort, it was found that 1) the protective effects of positive estrogen receptor and chemotherapy decreased over time; 2) the protective effect of breast-conserving surgery increased over time; and 3) the deleterious effects of stage T2, stage N2, and histologic grade II cancer increased over time. Moreover, from the view of prediction, the mean C-index in external validation reached 0.78.ConclusionDynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist.

Background: Acute respiratory failure is the main clinical manifestation and a major cause of death in patients with COVID-19. However, few reports on its prevention and control have been published because of the need for laboratory predictive indicators. This study aimed to evaluate the predictive value of hematocrit level, serum albumin level difference, and fibrinogen-to-albumin ratio for COVID-19-associated acute respiratory failure. Material and methods: A total of 120 patients with COVID-19 from the First Affiliated Hospital of Anhui Medical University were selected between December 2022 and March 2023. Patients were divided into acute respiratory failure and non-acute respiratory failure groups and compared patient-related indicators between them using univariate and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed to determine the discrimination accuracy. Results: In total, 48 and 72 patients were enrolled in the acute respiratory failure and non-acute respiratory failure groups, respectively. The Quick COVID-19 Severity Index scores, fibrinogen-to-albumin ratio, hematocrit and serum albumin level difference, fibrinogen, and hematocrit levels were significantly higher in the acute respiratory failure group than in the non-acute respiratory failure group. A Quick COVID-19 Severity Index >7, fibrinogen-to-albumin ratio >0.265, and hematocrit and serum albumin level difference >12.792 had a 96.14 % positive predictive rate and a 94.06 % negative predictive rate. Conclusion: Both fibrinogen-to-albumin ratio and hematocrit and serum albumin level difference are risk factors for COVID-19-associated acute respiratory failure. The Quick COVID-19 Severity Index score combined with fibrinogen-to-albumin ratio, and hematocrit and serum albumin level difference predict high and low risks with better efficacy and sensitivity than those of the Quick COVID-19 Severity Index score alone; therefore, these parameters can be used collectively as a risk stratification method for assessing patients with COVID-19.

BackgroundT lymphocytes, integral to the adaptive immune system, wield pivotal influence in bolstering anti-tumor responses, and are strictly regulated by ubiquitination modification. The objective of this investigation was to devise a novel prognostic and immunotherapeutic efficacy predictor for hepatocellular carcinoma patients utilizing T cell-related ubiquitination genes (TCRUG).MethodThe single-cell RNA sequencing (scRNA-seq) data and bulk RNA data of HCC patients are derived from the GEO database and TCGA database. Based on the processing of scRNA-seq, T cell marker genes are obtained and TCRUG is obtained. Further combined with WGCNA, differential analysis, univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis to filter and screen TCRUG. Finally construct a riskscore for predicting the prognosis of HCC patients, the predictive effect of which is validated in the GEO dataset. In addition, we also studied the correlation between riskscore and immunotherapy efficacy. Finally, the oncogenic role of UBE2E1 in HCC was explored through various in vitro experiments.ResultBased on patients’ scRNA-seq data, we finally obtained 3050 T cell marker genes. Combined with bulk RNA data and clinical data from the TCGA database, we constructed a riskscore that accurately predicts the prognosis of HCC patients. This riskscore is an independent prognostic factor for HCC and is used to construct a convenient column chart. In addition, we found that the high-risk group is more suitable for immunotherapy. Finally, the proliferation, migration, and invasion abilities of HCC cells significantly decreased after UBE2E1 expression reduction.ConclusionThis study developed a riskscore based on TCRUG that can accurately and stably predict the prognosis of HCC patients. This riskscore is also effective in predicting the immune therapy response of HCC patients.

Abstract Two‐dimensional (2D) nanomaterials, known for their unique atomic arrangements and exceptional physicochemical properties, have garnered significant attention in biomedical applications, particularly in the realms of immunotherapy for tissue engineering and tumor therapy. These applications necessitate a thorough assessment of the potential influence of 2D nanomaterials on immune cells. Notably, the mononuclear phagocyte system (MPS) cells, which play pivotal roles in both innate and adaptive immunity, are essential for maintaining organismal homeostasis. MPS cells with phagocytic capability contribute to the prevention of foreign body invasion and the elimination of dead or senescent cells. Furthermore, MPS cells, including macrophages and dendritic cells, serve as vital bridges between innate and adaptive immune responses. Therefore, understanding the nano‐bio interactions between 2D nanomaterials and MPS cells is imperative. These nano‐bio interactions including cellular uptake, cytocompatibility, and immunological impact are invaluable for the purposeful design of 2D nanomaterials. Herein, we provide an overview of the latest advancements in understanding the nano‐bio interactions between 2D nanomaterials and MPS cells, and discuss the current challenges and future prospects of employing 2D nanomaterials in the field of nanomedicine.

Purpose: This retrospective study aims to evaluate the safety, practicality, and efficacy of the independent retrograde popliteal approach for recanalization superficial femoral artery (SFA) occlusions when the bilateral common femoral artery approach is unavailable, such as after endovascular aneurysm repair or common iliac artery stenting. Methods: This treatment was considered for patients with contralateral iliac artery occlusion, severe iliac tortuosity, or those who had previously undergone endovascular aneurysm repair or common iliac stenting. Patients with SFA lesions extending into the P1–P2 segment of the popliteal artery or with calcification in the P3 segment were excluded. Angioplasty and stenting were conducted via the popliteal artery approach, with hemostasis at the puncture site achieved using an EXOSEAL vascular closure device. Patients were routinely followed up at 3, 6, and 12 months, and annually thereafter. Results: Forty-eight consecutive patients with SFA occlusion who underwent endovascular treatment via the retrograde popliteal artery approach were included in this study. Retrograde puncture of the popliteal artery was successful in all cases. Six-French sheaths were utilized in all procedures. The EXOSEAL vascular closure device was successfully applied in all 48 cases. No instances of pseudoaneurysms, arteriovenous fistulas, major bleeding, or embolic complications were observed. The technical success rate for SFA recanalization was 100 %. All patients experienced clinical improvement. The ankle-brachial index significantly increased from an initial 0.33 ± 0.11 at admission to 0.81 ± 0.19 at discharge (P

Abstract Objectives The study aims to assess the effect of baseline glycated hemoglobin (HbA1c) levels on atrial fibrillation (AF) recurrence following cryoballoon ablation in patients with and without diabetes. Methods Consecutive AF patients receiving first cryoballoon ablation between April 2018 and April 2021 were included. AF recurrence and other clinical outcomes were recorded for a minimum of 12 months post-ablation, with regular assessments at 3, 6, and 12 months, followed by annual check-ups. The primary outcome was AF recurrence after ablation at longest follow-up. Multivariate Cox proportional hazards regression models were utilized to calculate the hazard ratio (HR) and 95% CI per standard deviation (SD) increase of baseline HbA1c level. Results 335 patients were included in the analysis. The mean age was 61.7 years, 61.8% were male. 12.8% had type 2 diabetes, and 81.7% of patients had paroxysmal AF. The median level of HbA1c was 5.3%, and the mean CHA2DS2-VASc score was 1.8. All cryoballoon ablation procedures, utilizing a 28-mm balloon, achieved successful pulmonary vein isolation. Over a median follow-up of 18 months, 105 patients (31.3%) experienced AF recurrence. In multivariate Cox proportional hazards analysis, a higher HbA1c level, persistent AF (HR 1.91, 95% CI 1.08 to 3.39, P = 0.026), alcohol consumption (HR 2.67, 95% CI 1.33 to 5.37, P = 0.006), and Nadir RSPV (HR 1.04, 95% CI 1.00 to 1.08, P = 0.005) were significant predictors of AF recurrence. Per-SD increase of HbA1c was associated with a 1.75-fold increase risk of AF recurrence (HR 1.75, 95% CI 1.39 to 2.21, P

Abstract Background Functional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation. Methods Adult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80–100%, n = 8,379), group II (KPS 50–70%, n = 8,091), and group III (KPS 10–40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors. Results Patients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P

Abstract Tuberous sclerosis complex 1 (TSC1) plays important roles in regulating innate immunity. However, the precise role of TSC1 in macrophages in the regulation of oxidative stress response and hepatic inflammation in liver ischemia/reperfusion injury (I/R) remains unknown. In a mouse model of liver I/R injury, deletion of myeloid-specific TSC1 inhibited AKT and MST1 phosphorylation, and decreased NRF2 accumulation, whereas activated TLR4/NF-κB pathway, leading to increased hepatic inflammation. Adoptive transfer of AKT- or MST1-overexpressing macrophages, or Keap1 disruption in myeloid-specific TSC1-knockout mice promoted NRF2 activation but reduced TLR4 activity and mitigated I/R-induced liver inflammation. Mechanistically, TSC1 in macrophages promoted AKT and MST1 phosphorylation, and protected NRF2 from Keap1-mediated ubiquitination. Furthermore, overexpression AKT or MST1 in TSC1-knockout macrophages upregulated NRF2 expression, downregulated TLR4/NF-κB, resulting in reduced inflammatory factors, ROS and inflammatory cytokine-mediated hepatocyte apoptosis. Strikingly, TSC1 induction in NRF2-deficient macrophages failed to reverse the TLR4/NF-κB activity and production of pro-inflammatory factors. Conclusions: Macrophage TSC1 promoted the activation of the AKT/MST1 signaling pathway, increased NRF2 levels via reducing Keap1-mediated ubiquitination, and modulated oxidative stress-driven inflammatory responses in liver I/R injury. Our findings underscore the critical role of macrophage TSC1 as a novel regulator of innate immunity and imply the therapeutic potential for the treatment of sterile liver inflammation in transplant recipients. Schematic illustration of macrophage TSC1-mediated AKT/MST1/NRF2 signaling pathway in I/R-triggered liver inflammation. Macrophage TSC1 can be activated in I/R-stressed livers. TSC1 activation promotes phosphorylation of AKT and MST1, which in turn increases NRF2 expression and inhibits ROS production and TLR4/NF-κB activation, resulting in reduced hepatocellular apoptosis in I/R-triggered liver injury.

The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 μg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.