Search

Abstract Background Cutaneous malignant melanoma is a very aggressive and metastatic form of skin cancer, typically linked with poor outcomes. Advances in genomic analysis have underscored the crucial role of T cells in tumor immunity. Immune checkpoint inhibitors have notably transformed melanoma treatment by boosting T cell activity. Studies of gene expression have found that the phosphatidylinositol-4-phosphate kinase 2A (PIP4K2A) gene is abnormally expressed in various tumors, indicating its potential role in tumor progression. Utilizing single-cell sequencing and machine learning, researchers can now explore the complex interactions between T cells and melanoma cells at a genomic level. This study aimed to investigate the role of the PIP4K2A gene in cutaneous malignant melanoma, with a focus on its influence on T cell-mediated immune responses. Methods Samples from cutaneous melanoma patients were analysed by single-cell transcriptome for differentially expressed genes and signalling pathways associated with cutaneous melanoma. Then, genes were identified and predictive models were built based on the transcriptomic data using machine learning models to assess whether the expression level of PIP4K2A could effectively predict the malignancy and prognosis of cutaneous melanoma. In addition, we also performed drug therapy predictive analysis and immunotherapy analysis.Finally, the critical role of PIP4K2A in cutaneous melanoma was further confirmed by immunohistochemistry. Results The PIP4K2A gene exhibited a significantly elevated expression level in cutaneous malignant melanoma, showing a strong correlation with the clinical stage and patient prognosis. At the therapeutic level, high PIP4K2A expression is less responsive to immunotherapy, and this gene is a risk factor for drug therapy in cutaneous malignant melanoma. Additionally, our experimental outcomes validated this observation. Conclusions The PIP4K2A gene could be a crucial prognostic marker for cutaneous malignant melanoma, as it significantly affects T cell activity within the tumor microenvironment. This study offers essential insights into melanoma pathogenesis and assists in pinpointing new early diagnostic markers and therapeutic targets. Utilizing advanced genomic tools and computational techniques, the research enhances our understanding of T cell dynamics in melanoma, facilitating the development of personalized medicine and more effective immunotherapy strategies.

Abstract Carrollian amplitude is the natural object that defines the correlator of the boundary Carrollian field theory. In this work, we will elaborate on its proper definition in general dimensions. We use the vielbein field on the unit sphere to define the fundamental field with non-vanishing helicity in the local Cartesian frame which is the building block of the Carrollian amplitude. In general dimensions, the Carrollian amplitude is related to the momentum space scattering matrix by a modified Fourier transform. The Poincaré transformation law of the Carrollian amplitude in this definition has been discussed. We also find an isomorphism between the local rotation of the vielbein field and the superduality transformation.

Abstract Background Decision-making in the management of Crohn’s disease (CD)-related spontaneous intra-abdominal abscess (IAA) is challenging. This study aims to reveal predictive factors for percutaneous drainage and/or surgery in the treatment of CD-related spontaneous IAA through long-term follow-up. Methods Data were collected, including clinical manifestations, radiography and treatment strategies, in Chinese patients with CD-related IAA in a tertiary medical center. Univariate and Multivariate Cox analysis were conducted to identify predictors for invasive therapy. Results Altogether, 48 CD patients were identified as having IAA through enhanced CT scans. The median follow-up time was 45.0 (23.3, 58.0) months. 23 (47.9%) patients underwent conservative medical treatment, and 25 (52.1%) patients underwent percutaneous drainage and/or surgical intervention (invasive treatment group). The 1-, 2-, and 5-year overall survival rates without invasive treatment were 75.0%, 56.1%, and 46.1%, respectively. On univariate Cox analysis, the computerized tomography (CT) features including nonperienteric abscess (HR: 4.22, 95% CI: 1.81–9.86, p = 0.001), max abscess diameter (HR: 1.01, 95% CI: 1.00-1.02, p

Multi-component alloys have been confirmed to be excellent reinforcing phases in high-entropy alloy-based composite. However, achieving a balance between strength and ductility by controlling the reinforcement content remains a major challenge in the design of high-entropy alloy-based composites. In this study, CoCrFeMnNi HEA/NiCoFeAlTi HER high-entropy alloy composites were prepared using SLM technology. Interestingly, gas-atomized NiCoFeAlTi high-entropy intermetallic (HER) powder was selected as the reinforcing phase, and the CoCrFeMnNi HEA matrix was used for comparison. The influence of the reinforcement content on the composite was investigated, and high-performance HEA/HER composites were obtained, with the strengthening mechanism elucidated. The results showed that the composite with 1 wt% HER reinforcement exhibited the optimal performance, with hardness, yield strength, ultimate tensile strength, and ductility at room temperature being approximately 226.9 HV, 562 MPa, 683 MPa, and 16%, respectively. The excellent mechanical properties at both room and elevated temperatures are attributed to the synergistic effects of heterogeneous microstructure strengthening, grain refinement, and precipitation strengthening. This work provides a foundation for the development of high-entropy alloy composites reinforced by high-entropy intermetallics.

The AlN particles reinforced Mg-10Gd-3Y–1Zn (GWZ) composites were prepared by mixing AlN/Al particles using ball milling followed by stirring casting method. The influence of AlN/Al particles on the microstructural evolution and high-temperature mechanical properties of GWZ alloys were revealed and discussed. With AlN/Al particles added into the as-cast alloys, the Mg3RE phase was transformed into lamellar LPSO phase, while the content of Al2RE and LPSO phase increased. Since the Al2RE and AlN were effective nucleation sites for α-Mg, the grain size of AlN/Al-GWZ composites was reduced obviously from 126.1 to 39.8 μm. After homogenization, due to the coherent lattice matching relationships between 18R-LPSO phase and Al2RE or AlN particles, the 18R-LPSO phase nucleated on the Al2RE and AlN particles. After ageing treatment, the 2AlN/Al-GWZ composite showed the optimum mechanical properties at 250 °C, with the yield strength, ultimate tensile strength and elongation of 247.1 MPa, 265.5 MPa and 4.0%, respectively. The strengthening effect was primarily originated from the AlN particles, Al2RE and LPSO phases in the 2AlN/Al-GWZ composite. Besides, the composites can achieve the enhancement of high-temperature strength without the sacrifice of plasticity due to the coordinated deformation of AlN particles as well as the refinement of grains.

Alloying is one of the effective approaches to boost the discharge property of magnesium (Mg) anodes for primary Mg-air batteries and recently micro-alloying is highly recommended at the aim of developing advanced primary Mg system. In this study, micro-alloyed extruded Mg0.5Zn0.2Ge (in wt.%) alloy is evaluated as an anode candidate for primary Mg-air batteries in both half-cell and Mg-air full cell configurations, in comparison with commercially accepted Mg anodes, typified by as-cast HP Mg and extruded AZ31 alloy. The corrosion behavior at open circuit potential (OCP) condition of the three materials is also compared through electrochemical tests. Mg0.5Zn0.2Ge alloy displays the most negative OCP value and the highest corrosion resistance at OCP. During discharge, Mg0.5Zn0.2Ge anode exhibits low wasteful-discharge rate and homogeneous dissolution that gives rise to the absence of “chunk effect”. Consequently, the anodic efficiency and specific capacity of Mg0.5Zn0.2Ge anode are superior to those of HP Mg and AZ31 anodes, e.g. 57.3% and 1257 mAh g−1 at 1 mA cm−2. Additionally, Mg-air battery based on Mg0.5Zn0.2Ge anode offers higher cell voltage and specific energy than those assembled with HP Mg and AZ31 anodes, which can be further optimized by addition of electrolyte additives. Therefore, micro-alloyed Mg0.5Zn0.2Ge alloy can serve as a promising candidate for anode material of primary Mg-air batteries.

Background/Aims Crohn’s disease (CD) has a progressive nature and commonly perianal involvement. The aim of this study is to assess the prevalence, surgical treatment, and outcome of perianal fistulizing CD with associated risk factors in a large Chinese cohort. Methods Hospitalized patients diagnosed with CD in our center were consecutively enrolled between January 2000 and December 2018. Transition of disease behavior was classified according to the presence or absence of penetrating behavior (B3 in the Montreal classification) at diagnosis and at a median follow-up of 102 months. Results A total of 504 patients were included, of whom 207 (41.1%) were classified as B3 and 348 (69.0%) as L2/3 at follow-up. Transition of behavior to B3 was observed in 86 patients (17.1%). The incidence of perianal fistulizing lesions was 10.9% at 10 years with a final prevalence of 27.0% (n = 136) at the end of follow-up. Multivariate Cox regression identified independent risks of perianal fistulizing lesions for persistent B3 (hazard ratio, 4.72; 95% confidence interval, 1.91–11.66) and behavior transition of progressed to B3 (hazard ratio, 9.90; 95% confidence interval, 4.60–21.33). Perianal surgical treatments were performed in 104 patients (20.6%). Thirty-six cases (7.1%) were refractory, and it is independently associated with behavior of persistent B3 (P=0.011). Conclusions Perianal fistulizing lesions occurred frequently in Chinese CD patients. Its incidence and refractory outcome were closely associated with the penetrating CD behavior. An additional risk of perianal fistulizing lesions was indicated for CD patients with behavior of progressing to B3, suggesting further attention.

Abstract This study aims to develop machine learning (ML)-assisted models for analyzing datasets related to Gleason scores in prostate cancer, conducting statistical analyses on the datasets, and identifying meaningful features. We retrospectively collected data from 717 hormone-sensitive prostate cancer (HSPC) patients at Yunnan Cancer Hospital. Of these, data from 526 patients were used for modeling. Seven auxiliary models were established using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), Extreme gradient boosting tree (XGBoost), Adaptive Boosting (Adaboost), and artificial neural network (ANN) based on 21 clinical biochemical indicators and features. Evaluation metrics included accuracy (ACC), precision (PRE), specificity (SPE), sensitivity (SEN) or regression rate(Recall), and f1 score. Evaluation metrics for the models primarily included ACC, PRE, SPE, SEN or Recall, f1 score, and area under the curve(AUC). Evaluation metrics were visualized using confusion matrices and ROC curves. Among the ensemble learning methods, RF, XGBoost, and Adaboost performed the best. RF achieved a training dataset score of 0.769 (95% CI: 0.759—0.835) and a testing dataset score of 0.755 (95% CI: 0.660—0.760) (AUC: 0.786, 95%CI: 0.722—0.803), while XGBoost achieved a training dataset score of 0.755 (95% CI: 95%CI: 0.711—0.809) and a testing dataset score of 0.745 (95% CI: 0.660—0.764) (AUC: 0.777, 95% CI: 0.726—0.798). Adaboost scored 0.789 on the training dataset (95% CI: 0.782—0.857) and 0.774 on the testing dataset (95% CI: 0.651—0.774) (AUC: 0.799, 95% CI: 0.703—0.802). In terms of feature importance (FI) in ensemble learning, Bone metastases at first visit, prostatic volume, age, and T1-T2 have significant proportions in RF’s FI. fPSA, TPSA, and tumor burden have significant proportions in Adaboost’s FI, while f/TPSA, LDH, and testosterone have the highest proportions in XGBoost. Our findings indicate that ensemble learning methods demonstrate good performance in classifying HSPC patient data, with TNM staging and fPSA being important classification indicators. These discoveries provide valuable references for distinguishing different Gleason scores, facilitating more accurate patient assessments and personalized treatment plans.

Abstract TNF inhibitors have been used to treat autoimmune and autoinflammatory diseases. Here we report an unexpected mechanism underlying the therapeutic effects of TNF inhibitors in Behçet’s disease (BD), an autoimmune inflammatory disorder. Using serum metabolomics and peripheral immunocyte transcriptomics, we find that polymorphonuclear neutrophil (PMN) from patients with BD (BD-PMN) has dysregulated mevalonate pathway and subsequently increased farnesyl pyrophosphate (FPP) levels. Mechanistically, FPP induces TRPM2-calcium signaling for neutrophil extracellular trap (NET) and proinflammatory cytokine productions, leading to vascular endothelial inflammation and damage. TNF, but not IL-1β, IL-6, IL-18, or IFN-γ, upregulates TRPM2 expression on BD-PMN, while TNF inhibitors have opposite effects. Results from mice with PMN-specific FPP synthetase or TRPM2 deficiency show reduced experimental vasculitis. Meanwhile, analyses of public datasets correlate increased TRPM2 expressions with the clinical benefits of TNF inhibitors. Our results thus implicate FPP-TRPM2-TNF/NETs feedback loops for inflammation aggravation, and novel insights for TNF inhibitor therapies on BD.

Abstract Faced with the increasing number of flights, efficient and orderly operations have become a critical issue for busy airports. The closely spaced parallel runway paired approach technology has been proven to be an effective solution for increasing runway capacity and operational efficiency. This research focuses on determining the safety separation between paired aircraft, particularly the collision safety limit. This study refines the kinematic modeling process by constructing a three-dimensional kinematic model and advancing the starting point of paired approach, making the simulation process more aligned with reality. Subsequently, the Monte Carlo simulation method is applied, integrating the kinematic model and considering collision risks to simulate the entire paired approach process. Multiple scenarios are created, and simulation experiments are conducted to determine the safety separation between the two paired aircraft. Finally, by adjusting parameter settings and taking the example of the two closely spaced parallel runways at Chongqing Jiangbei International Airport, the correlation between various influencing factors and the safety separation is analyzed. Different scenarios are simulated 100,000 times each, and the results show that the speed difference between the two paired aircraft has the most significant impact on the safety separation, followed by the paired approach mode and runway centerline spacing. The wake turbulence category matching has a minimal effect on the safety separation. The results provide a theoretical basis for airports with closely spaced parallel runways to further reduce the separation between paired aircraft, thereby enhancing airport capacity and runway operational efficiency.

Understanding the response of solid combustibles under high radiant fluxes is critical in predicting the thermal damage from extreme scenarios. Unlike the more moderate radiant fluxes in conventional hydrocarbon fires, extreme events such as strong explosion, concentrated sunlight and directed energy can generate dynamic radiant fluxes at the MW/m2 level, creating a unique threat to materials. This study investigates the pyrolysis and spontaneous ignition behaviors of corrugated cardboard by using both experimental and numerical methods, under 10-cm dynamic high radiant fluxes ranging from 0.2 to 1.25 MW/m2 for 10 s. The spontaneous ignition process at dynamic high radiant fluxes was recorded and quantified. Two ignition modes were found at the critical radiant flux of 0.4 MW/m2, namely hot-gas spontaneous ignition and hot-residue piloted ignition. The latter is not the focus of this paper due to its extremely small probability of occurrence. The research reveals that the increase in flux intensity induces shorter delay times for both pyrolysis and ignition, lower ignition energy density, along with a corresponding rise in the critical mass flux and surface temperature at ignition moment. The simulation results are generally aligned with the experimental findings, despite some divergences may be attributed to model simplifications and parameter assumptions. The work contributes to a deeper insight into material behavior under extreme radiation, with valuable implications for fire safety and hazard assessment.

Abstract Background The aim was to assess the knowledge, attitudes, and practices (KAPs) of endoscopy among gastroenterologists in the diagnosis and management of IBD in China. Methods A multicenter cross-sectional KAP study was performed. The questionnaire was developed and improved using feedback and opinions from a team of experienced IBD specialist professors and then distributed and collected online. In addition, eight fellow gastroenterologists participated in an IBD endoscopy training program were asked to review endoscopic images, and the consistency of the endoscopic scores before and after training was calculated. Results A total of 193 participants from 12 provincial-level administrative regions encompassing both the Northern and Southern parts of China completed the study questionnaire. The median age of the participants was 40 (36, 45) years, with the majority being female (70.5%). The median professional experience as gastroenterologists was 11 (7, 17) years, while the median experience as endoscopists was 8 (3, 15) years. The median knowledge score was 8 out of 10 points for single-choice questions; however, most gastroenterologists believed that some concepts in these endoscopic indices were vague, including those regarding deep ulcerations, ulcerated surfaces, affected surfaces and narrowing in open-answer questions. The UCEIS and SES-CD were considered most consistent with clinical activity score in the evaluation of UC and CD, respectively. IBD subspecialists and gastroenterologists who had previously received IBD endoscopy screening training were more likely to use endoscopic indices (p

Abstract Background Allergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic diseases. Objective The aim of the study is to provide a comprehensive web tool for multiple analysis in allergic diseases. Methods We retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user feedback. Results We developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution images. Conclusions CTPAD largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://smuonco.shinyapps.io/CTPAD/ .

Abstract Background Hypoxia stress resulted in mortality during the fish aquaculture program, affecting the sustainable development of the aquaculture industry. The Egyptian strain of O. niloticus showed a strong ability to hypoxia. In this study, a Nile tilapia strain that was kept and selected for 45 years by the author’s team was used to elucidate the mechanism of the hypoxia response in the liver, including the identification of metabolic pathways and genes, involved in the hypoxia response of this strain. Results The effects of hypoxia stress were detected at 0-hour, 6-hour, and 72-hour time points (0 h, 6 h, 72 h) on tilapia liver at 1 mg/L dissolved oxygen conditions. The blood triglyceride, blood glucose and cholesterol values exhibited significantly different change trends, but the hemoglobin content showed no significant differences between 0 h, 6 h and 72 h (P > 0.05). The activities of catalase (CAT), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), lactate dehydrogenase (LDH), and acid phosphatase (ACP) in the liver tissue gradually increased at 0 h, 6 h and 72 h (P

Abstract Background Although laparoscopic inguinal hernia repair (LIHR) has advantages over open surgery, postoperative seroma formation remains an issue. This study aimed to investigate the risk factors and clinical outcomes of seroma formation in patients undergoing LIHR. Methods From January 2016 to March 2023, clinical data of patients who underwent LIHR were retrospectively analyzed. Patients who developed seroma and those who did not were classified into the seroma and non-seroma groups, respectively. The demographic and clinical characteristics were compared between the two groups. Univariate and multivariate logistic regression analyses were performed for variables of interest. The receiver operating characteristic curve was used to evaluate the risk factors of the binary logistic model, and the cutoff value for each risk factor was obtained. Results Data of 128 patients were evaluated. Compared with patients in the non-seroma group, those in the seroma group had a higher body mass index (BMI) (P 24.5 kg/m2), hernial orifice size (> 2.5 cm), TEP, and PSAL (

Abstract Molten silicates at depth are crucial for planetary evolution, yet their local structure and physical properties under extreme conditions remain elusive due to experimental challenges. In this study, we utilize in situ X-ray diffraction (XRD) at the Matter in Extreme Conditions (MEC) end-station of the Linear Coherent Linac Source (LCLS) at SLAC National Accelerator Laboratory to investigate liquid silicates. Using an ultrabright X-ray source and a high-power optical laser, we probed the local atomic arrangement of shock-compressed liquid (Mg,Fe)SiO3 with varying Fe content, at pressures from 81(9) to 385(40) GPa. We compared these findings to ab initio molecular dynamics simulations under similar conditions. Results indicate continuous densification of the O-O and Mg-Si networks beyond Earth’s interior pressure range, potentially altering melt properties at extreme conditions. This could have significant implications for early planetary evolution, leading to notable differences in differentiation processes between smaller rocky planets, such as Earth and Venus, and super-Earths, which are exoplanets with masses nearly three times that of Earth.