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This paper examines whether and to what extent student engagement with the learning management system (LMS) Blackboard affects students' academic performance during the COVID-19 pandemic. We find strong evidence that higher student engagement with Blackboard is associated with better academic performance. We also find that the association between student engagement and student academic performance varies with different blended learning formats. Specifically, the positive effects are more pronounced when synchronous online lectures and face-to-face tutorials are implemented. Given that COVID-19 is a constantly moving situation, this study highlights that a blended learning approach needs to engage students actively to facilitate social interaction with teachers and peers during periods of social restrictions.

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.

Abstract Flueggea virosa (Roxb. ex Willd.) Royle, an evergreen shrub and small tree in the Phyllanthaceae family, holds significant potential in garden landscaping and pharmacological applications. However, the lack of genomic data has hindered further scientific understanding of its horticultural and medicinal values. In this study, we have assembled a haplotype-resolved genome of F. virosa for the first time. The two haploid genomes, named haplotype A genome and haplotype B genome, are 487.33 Mb and 477.53 Mb in size, respectively, with contig N50 lengths of 31.45 Mb and 32.81 Mb. More than 99% of the assembled sequences were anchored to 13 pairs of pseudo-chromosomes. Furthermore, 21,587 and 21,533 protein-coding genes were predicted in haplotype A and haplotype B genomes, respectively. The availability of this chromosome-level genome fills the gap in genomic data for F. virosa and provides valuable resources for molecular studies of this species, supporting future research on speciation, functional genomics, and comparative genomics within the Phyllanthaceae family.

Abstract Dracaena cambodiana Pierre ex Gagn. (Asparagaceae) is the source plant of Dragon’s blood and has high ornamental values in gardening. Currently, this species is classified as the second-class state-protected species in the National Key Protected Wild Plants (NKPWP) of China. However, limited genomic data has hindered a more comprehensive scientific understanding of the processes involved in the production of Dragon’s blood and the related conservation genomics research. In this study, we assembled a haplotype-resolved genome of D. cambodiana. The haploid genomes, haplotype A and haplotype B, are 1,015.22 Mb and 1,003.13 Mb in size, respectively. The completeness of haplotype A and haplotype B genomes was 98.60% and 98.20%, respectively, using the “embryophyta_10” dataset. Haplotype A and haplotype B genomes contained 27,361 and 27,066 protein-coding genes, respectively, with nearly all being functionally annotated. These findings provide new insights into the genomic characteristics of D. cambodiana and will offer additional genomic resources for studying the biosynthesis mechanism of Dragon’s blood and the horticultural application of Dragon trees.

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.

Abstract Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C–H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which’s an important synthetic intermediate of antifungal drug Ravuconazole. Graphical Abstract

AIM: To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure (PHOMS) in myopic children and to investigate factors associated with PHOMS. METHODS: This retrospective observational study included 101 eyes of 101 children (age ≤17y) with myopia. All included patients underwent comprehensive clinical examination. Optic nerve canal parameters, including disc diameter, optic nerve head (ONH) tilt angle, and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Based on the optic disc drusen consortium's definition of PHOMS, eyes were classified as PHOMS group and non-PHOMS group. PHOMS was categorized according to height. RESULTS: Sixty-seven (66.3%) eyes were found with PHOMS. Small PHOMS could only be detected by optical coherence tomography (OCT). Medium PHOMS could be seen with blurred optic disc borders corresponding to OCT. The most frequent location of PHOMS was at the nasosuperior (91%, 61 of 67 eyes) to ONH disc. The axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group (both P

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.

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

Abstract Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α‐Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α‐ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long‐standing catalysis challenge. Herein, an unprecedented TBD‐switched Pd‐catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late‐stage modify pharmaceuticals, scalability to large‐scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd‐catalyzed double isocyanide insertion process, thereby selectively providing the desired α‐ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α‐ketoimine amide are successfully isolated and determined by X‐ray analysis, confirming that they are probable intermediates in the catalytic pathway.

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.