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Abstract Background Autophagy is a crucial mechanism for maintaining cellular homeostasis and responding to environmental stress, and it is closely linked to tumor drug resistance. Through multi-omics analysis, this study explores the expression patterns, functions, and potential role of the autophagy-related gene Angiotensinogen (AGT) in colorectal cancer (CRC), particularly in relation to chemotherapy resistance. Methods This study first compared AGT expression between CRC and normal tissues using the GTEx and TCGA databases. Differences in expression were assessed using Wilcoxon Rank Sum Tests, and the prognostic impact of AGT was evaluated through univariate Cox survival analysis and meta-analysis. Functional enrichment was performed using the limma and fgsea packages. Drug sensitivity analysis was conducted based on the CTRP database, while immune infiltration was assessed using the CIBERSORT and ESTIMATE methods. Spatial transcriptomic characteristics were explored through 10x Visium technology and deconvolution analysis to investigate the correlation between AGT expression levels and tumor cell content.scRNA-seq data from CRC tissues were sourced from Tumor Immune Single Cell Hub (TISCH).Functional annotation was performed with Single-sample gene set enrichment analysis (SSGSEA), and pseudotime analysis using Monocle 2 mapped their developmental trajectories. The potential of AGT inhibitors in the treatment of CRC was analyzed using drug-target Mendelian randomization.Finally, Phenome-Wide Association Study (PheWAS) was conducted to evaluate genetic associations and potential side effects of AGT inhibitors. Results AGT expression was significantly higher in CRC tissues compared to normal tissues and was associated with shorter recurrence-free survival (RFS). Autophagy signaling pathways were markedly enriched in the high AGT expression group. AGT expression was positively correlated with resistance to chemotherapeutic agents such as gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. Spatial transcriptomic analysis revealed that AGT was predominantly expressed in malignant tumor regions. Single-cell analysis identified 21 distinct cell subpopulations across 13 major types. AGT expression was significantly higher in tumor samples, especially in the fibroblast C6 subpopulation. Tumor-related pathways were enriched in C1, C5, C6, and C8 subpopulations. Pseudotime analysis revealed that these subpopulations, particularly C6, were in terminal developmental stages.Drug-target Mendelian randomization analysis indicated a negative causal relationship between AGT inhibitors and the risk of both heart failure(ORdrug = 0.950, 95% CI, 0.912–0.990; P = 0.014) and CRC(ORdrug = 0.874, 95% CI: 0.792–0.964; P = 0.007).PheWAS analysis showed no genetic associations between AGT inhibitors and other traits, indicating its specificity and low risk of side effects. Conclusion Elevated AGT expression in CRC is associated with resistance to chemotherapy, and its inhibition may offer a therapeutic avenue for the treatment of colorectal cancer.

To optimize the extraction process of blackberry polysaccharide and investigate its hypoglycemic activity in vitro, this study used enzymatic extraction to extract blackberry polysaccharide. The effects of pectinase addition, material-liquid ratio, extraction temperature, and extraction time on the yield of blackberry polysaccharides were analyzed. Based on the results of the one-way experiments, the extraction of the blackberry polysaccharide enzyme was optimized using response surface design. The structure of blackberry polysaccharide was characterized by Fourier transform infrared spectroscopy and monosaccharide composition analysis, and its inhibitory capacity on α-glucosidase and α-amylase in vitro were also studied. The results showed that, the optimal conditions for extracting blackberry polysaccharide were 0.42% pectinase, material-liquid ratio of 1:6 g/mL, extraction temperature of 55 ℃, and extraction time of 84 min. Under this condition, the yield of blackberry polysaccharide was 10.68%±0.03%. The extracted blackberry polysaccharide was an acidic polysaccharide with a β-pyranose configuration and exhibited good inhibitory activity against α-glucosidase and α-amylase. The semi-inhibitory concentrations were 0.061 and 0.36 mg/mL, respectively. The enzymatic extraction process optimized in this study can effectively extract blackberry polysaccharides. The extracted blackberry polysaccharides exhibit good in vitro hypoglycemic activity, providing a basis for the potential application of blackberry polysaccharides in the development of hypoglycemic functional foods.

Abstract Acute liver injury (ALI) presents a challenging problem worldwide, prompting extensive research efforts. Cellular senescence has been found to be induced following ALI, and targeting cellular senescence has shown therapeutic potential. Therefore, understanding the expression of senescence-related genes in ALI can help to explore pathogenesis and treatment of this common disease. Carbon tetrachloride (CCl4) is commonly used to study ALI. Although polymerase chain reaction (PCR) is a convenient and economical molecular biology technique widely used in basic medicine, research on selecting suitable reference genes to obtain objective and reproducible PCR data is scarce. Moreover, evidence supporting the choice of reference genes for experimental studies of CCl4-induced ALI and hepatic senescence in mice is limited. In this study, we obtained murine livers at four time points (0, 12, 24, and 48 h) following CCl4 treatment. We used five algorithms (geNorm, BestKeeper, NormFinder, delta Ct, and RefFinder) to rank 12 candidate genes in real-time reverse-transcription quantitative PCR (RT-qPCR) experiments. Focusing on cellular senescence in this model, we adopted four senescence-associated secretory phenotype (SASP) genes (Il6, Il1b, Ccl2, and Ccl5) as target genes. Our results confirmed Gapdh and Tbp as suitable reference genes in murine CCl4-induced ALI models. Furthermore, we provide a table of published studies recommending reference genes for various liver disease models. This study provides a valuable reference for enhancing the reliability and reproducibility of ALI molecular findings.

Abstract Soybean protein is of plant origin and is commonly appropriate for improving the processing characteristics of foods. This study aimed to explore a novel functional ingredient that contained soybean protein isolate (SPI) and blueberry anthocyanins (BANs). The spatial conformation and secondary structure of SPI-BANs complexes were analyzed using circular dichroism and fluorescence spectroscopy, the processing properties were investigated as well as the retention of antioxidant activity during thermal treatments. Results showed that the contents of free sulfhydryl and free amino groups in complexes increased to 3.50 and 1.19 folds than those of SPI, respectively, while the surface hydrophobicity decreased by 74.23%. Compared with SPI, the BANs-modified SPI had a smaller particle size of 29.12 nm and a lower zeta-potential of -8.73 mV and on the other hand, the complexes possessed higher solubility (83.08%) and foaming and emulsifying properties (115.08% and 54.03 m2/g). After fortification with SPI-BANs, the baking loss rate and adhesiveness of chiffon cake were reduced by 10.82% and improved to 0.24 N.mm, respectively. The high antioxidant activities of SPI-BANs under heat led to the cake’s bioactivities largely enhanced by 1.99 ~ 12.71 folds, being 345.19 µg Trolox/g for the DPPH radical scavenging activity. This study developed the functional food ingredients as antioxidants and a substitute for animal-based proteins in bakery products, which was safe and sustainable by using the dietary components from plant resources. Graphical Abstract

To investigate the influence of loading rate on the local deformation and failure characteristics of rock-like models with a locked segment, this study fabricated them using quartz sand and barite powder as aggregates, and gypsum as cementing material. Uniaxial compression tests, combined with strain cube monitoring and the digital image correlation technique, were employed to analyze the mechanical properties, internal and external deformation characteristics, crack propagation, and failure modes at different loading rates. The results showed that as the loading rate increased, the strength of these models initially increased significantly and then slightly decreased, primarily due to the complex interaction between the longitudinal and transverse deformations of the models and the stress concentration intensity at the crack tips. The fluctuation in the principal strain axis's deflection angle revealed the complex process of stress wave propagation and particle adjustment within the models, with more pronounced fluctuations observed at higher loading rates. The stress intensity factors, KI and KII, at the crack tips first increased and then decreased with increasing loading rate, with KI consistently higher than KII. The strain concentration phenomenon in the rock-like models occurred earlier with increasing loading rates, and the corresponding crack closure stress exhibited a decreasing trend. Higher loading rates caused earlier crack initiation and faster propagation. As the loading rate increased, the crack paths shortened, and both damage density and severity increased significantly, indicating brittle failure. This study provides important experimental evidence and theoretical support for understanding the effects of loading rate in rock mass engineering.

This study focused on the co-fermentation of goat milk with functional lactic acid bacteria (LAB) and traditional yoghurt starter culture. The fermentation process was optimised by single factor experiment and response surface methodology (RSM). The physicochemical and sensory properties of goat milk yoghurt were evaluated under chilled (4 °C) storage for 21 days. The optimised conditions were selected as the inoculum amount of Lactobacillus paracasei NM-8 (1.1 × 107 CFU.mL-1; CFU - colony forming unit), sucrose addition (6.8%) and fermentation temperature (41 °C). During milk coagulation, the pH declined to be 4.45 and the viable LAB number arrived at 8.77 log CFU.mL-1. The content of exopolysaccharides (EPS) increased to be 2.13 g.L-1. These changes led to the better viscosity (941.33-792.33 cP) and higher water holding capacity (63.24-56.20%) of yoghurt fermented using L. paracasei NM-8 in storage, compared with those of yoghurt without L. paracasei NM-8. This study provided a theoretical basis for eliminating the whey precipitation and rough texture of goat milk yoghurt.

Abstract Background RNA editing from A (adenine nucleotide) to I (hypoxanthine nucleotide) mediated by ADARs has attracted more and more attention as an important post-transcriptional processing method. This research investigates the regulatory mechanism of A-to-I-edited miR-1251-5p in lung adenocarcinoma (LUAD). Methods RT-qPCR, Western blot, and Immunohistochemistry assays measured miRNA and gene expression. Colony formation, CCK-8, Transwell, Wound-healing, and Animal assays were used to determine MiRNA function. Luciferase reporter assay tested miRNA downstream target. Results ADAR1 increased the A-to-I editing efficiency of miR-1251-5p in LUAD cells. In comparison to the unedited wild-type form, edited miR-1251-5p exhibits a marked inhibition of tumor growth and metastasis in LUAD. Moreover, knockdown of TCF7 also exhibits tumor inhibitory effect in LUAD development. Mechanically, edited miR-1251-5p inactivates Wnt signaling pathway by inhibiting TCF7, MYC, and CCND1 expression. Conclusion Compared with original miR-1251-5p, edited miR-1251-5p has stronger anti-cancer effect on LUAD development through inactivating Wnt signaling pathway by inhibiting TCF7.

Abstract Background Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. Methods The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. Results In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p

High-pressure waterjet-assisted tunnel boring machine (WTBM) is an efficient method for improving the tunneling performance of a tunnel boring machine (TBM) and reducing the wear of its disc cutters in hard rock with high geostresses. Confining pressure directly affects the efficiency of rock breaking and the configuration of the disc cutters. In this study, we evaluated the effect of confining pressure on WTBM rock breaking by developing a self-designed and manufactured experimental system, including confining pressure loading, TBM disc-cutter penetration, and high-pressure waterjet. The macro fracture, acoustic emission (AE), peak normal force drop, and specific energy (SE) were analyzed for four different confining pressures (10, 20, 30, and 35 MPa). The results showed that the cutting depth of the waterjet increased linearly as the waterjet pressure increased and decreased with the gradual increase in the nozzle moving speed. The expansion and development of cracks formed rock debris, and the size of the rock fragments decreased with an increase in confining pressure. When the waterjet pressure was 280 MPa, the nozzle moving velocity was 800 mm/min and the kerf space was 75 mm, which indicated that the confining pressure, which was 23.16 MPa, minimized the cutting SE under this condition. However, regardless of the confining pressure, the maximum normal force of WTBM was less than that of a TBM, whereas the SE of WTBM was less than that of complete TBM cutting mode (CTCM). The average force drop and average drop rate of SE were approximately 25%, and 80%, respectively. The results of this study can inspire the design and mechanism of a TBM assisted by a high-pressure waterjet.

The topological attributes of fracture networks in limestone, subject to intense hydrodynamics and intricate geological discontinuities, substantially influence the mechanical and hydraulic characteristics of the rock mass. The dynamical evolution of fracture networks under stress is crucial for unveiling the interaction patterns among fractures. However, existing models are undirected graphs focused on stationary topology, which need optimization to depict fractures' dynamic development and rupture process. To compensate for the time and destruction terms, we propose the damage network model, which defines the physical interpretation of fractures through the ternary motif. We focus primarily on the evolution of node types, topological attributes, and motifs of the fracture network in limestone under uniaxial stress. Observations expose the varying behavior of the nodes' self-dynamics and neighbors' adjacent dynamics in the fracture network. This approach elucidates the impact of micro-crack behaviors on large brittle shear fractures from a topological perspective and further subdivides the progressive failure stage into four distinct phases (isolated crack growth phase, crack splay phase, damage coalescence phase, and mechanical failure phase) based on the significance profile of the motif. Regression analysis reveals a positive linear and negative power correlation between fracture network density and branch number to the rock damage resistance, respectively. The damage network model introduces a novel methodology for depicting the interaction of two-dimensional (2D) projected fractures, considering the dynamic spatiotemporal development characteristics and fracture geometric variation. It helps dynamically characterize properties such as connectivity, permeability, and damage factors while comprehensively assessing damage in rock mass fracture networks.

Water covers most of the Earth’s surface and is nowhere near a good ecological or recreational state in many areas of the world. Moreover, only a small fraction of the water is potable. As climate change-induced extreme weather events become ever more prevalent, more and more issues arise, such as worsening water quality problems. Therefore, protecting invaluable and useable drinking water is critical. Environmental agencies must continuously check water sources to determine whether they are in a good or healthy state regarding pollutant levels and ecological status. The currently available tools are better suited for stationary laboratory use, and domain specialists lack suitable tools for on-site visualisation and interactive exploration of environmental data. Meanwhile, data collection for laboratory analysis requires substantial time and significant effort. We, therefore, developed an augmented reality system with a Microsoft HoloLens 2 device to explore the visualisation of water quality and status in situ. The developed prototype visualises geo-referenced sensor measurements incorporated into the perspective of the surroundings. Any users interested in water bodies’ conditions can quickly examine and retrieve an overview of water body status using augmented reality and then take necessary steps to address the current situation.

Abstract Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.

Abstract The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index

Abstract Background Calcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia. Methods The retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed. Results The 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p

Abstract PLK1 is currently at the forefront of mitotic research and has emerged as a potential target for small cell lung cancer (SCLC) therapy. However, the factors influencing the efficacy of PLK1 inhibitors remain unclear. Herein, BRCA1 was identified as a key factor affecting the response of SCLC cells to BI-2536. Targeting AURKA with alisertib, at a non-toxic concentration, reduced the BI-2536-induced accumulation of BRCA1 and RAD51, leading to DNA repair defects and mitotic cell death in SCLC cells. In vivo experiments confirmed that combining BI-2536 with alisertib impaired DNA repair capacity and significantly delayed tumor growth. Additionally, GSEA analysis and loss- and gain-of-function assays demonstrated that MYC/MYCN signaling is crucial for determining the sensitivity of SCLC cells to BI-2536 and its combination with alisertib. The study further revealed a positive correlation between RAD51 expression and PLK1/AURKA expression, and a negative correlation with the IC50 values of BI-2536. Manipulating RAD51 expression significantly influenced the efficacy of BI-2536 and restored the MYC/MYCN-induced enhancement of BI-2536 sensitivity in SCLC cells. Our findings indicate that the BRCA1 and MYC/MYCN-RAD51 axes govern the response of small cell lung cancer to BI-2536 and its combination with alisertib. This study propose the combined use of BI-2536 and alisertib as a novel therapeutic strategy for the treatment of SCLC patients with MYC/MYCN activation.

Abstract Background Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. Methods Utilizing patient data from the First Medical Center of the People’s Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. Results The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. Conclusions The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

The topic of zonal fracture in deep surrounding rock roadway under high ground stress is a challenging and widely researched area in geotechnical engineering, with significant implications for the safety of deep engineering project. When the material yield damage occurs, there is a certain dissipation of energy, and as the dissipation proceeds, the material structure also produces some corresponding changes to form a new organizational structure, the process is similar to the self-organization process on the concordance, at this time the traditional elastic-plastic mechanics is not very useful, need to use the physical theory. Deep tunnel surrounding rock under high ground stress, when its deformation exceeds the elastic limit, will also has a similar dissipation structure phenomenon. The surrounding rock structure needs to go through a self-organization process to form a new dissipative structure, and this process is similar to the phenomenon of progressive phase change in physics. This paper explores the deformation and failure process of the surrounding rock in deep roadway, which is characterized as a gradual phase transition from solid to fluid. The study analyzes various zonal fracturing phenomena in field scale, laboratory scale, and simulation tests, and develops a phase transition theoretical model to approximate the nonlinear higher order control equation using Poincare-analytic parametric regression method. The sensitivity of each parameter in the approximate solution is also analyzed. Finally, the study validates the theoretical model by comparing the calculated results with the on-site measured data of zonal fracturing in a 700 m deep horizontal roadway in a metal mine.

Abstract To analyze the current status of "pseudo" unplanned endotracheal extubation in ICU patients in China's tertiary hospitals and to provide a reference for improving the quality of medical care. Through the National Nursing Quality Data Platform, unplanned endotracheal extubation data reported by ICUs in China's tertiary hospitals from 2019 to 2022 were analyzed. The situation of reported hospitals, causes, and the current status of "pseudo" unplanned endotracheal extubation in ICU patients was analyzed. The indicator of unplanned endotracheal extubation in ICUs of China’s tertiary hospitals is mainly from first-class tertiary hospitals (74.9%), most of which are self-extractions by patients (74.6%). The proportion of "pseudo" unplanned endotracheal extubation is 45.1%. "Pseudo" unplanned endotracheal extubation is common in the ICUs of China's tertiary hospitals. As such, management blind spots deserve attention from managers and clinical staff.

Rock macro-indentation plays a fundamental role in mechanical rock breaking for various rock engineering application, such as drilling, tunneling, cutting, and sawing. Over the past decades, extensive research has been conducted to understand the indentation mechanisms and responses through various approaches. This review aims to provide an overview of the current status and recent advancements in theories, experiments, numerical simulations, and applications of macro-indentation in rock engineering. It starts with elaborating on the mechanisms of macro-indentation, followed by a discussion of the merits and limitations of commonly used models. Influence factors and their effects on indentation test results are then summarized. Various numerical simulation methods for rock macro-indentation are highlighted, along with their advantages and disadvantages. Subsequently, the applications of indentation tests and indentation indices in characterizing rock properties are explored. It reveals that compression-tension, compression-shear, and composite models are widely employed in rock macro-indentation. While the compression-tension model is straightforward to use, it may overlook the anisotropic properties of rocks. On the other hand, the composite model provides a more comprehensive description of rock indentation but requires complex calculations. Additionally, factors, such as indentation rate, indenter geometry, rock type, specimen size, and confining pressure, can significantly influence the indentation results. Simulation methods for macro-indentation encompass continuous medium, discontinuous medium, and continuous-discontinuous medium methods, with selection based on their differences in principle. Furthermore, rock macro-indentation can be practically applied to mining engineering, tunneling engineering, and petroleum drilling engineering. Indentation indices serve as valuable tools for characterizing rock strength, brittleness, and drillability. This review sheds light on the development of rock macro-indentation and its extensive application in engineering practice. Specialists in the field can gain a comprehensive understanding of the indentation process and its potential in various rock engineering endeavors.

Abstract Objective To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. Methods Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80–120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. Results The median follow-up was 48.52 months (range, 4–86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. Conclusions The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter 108.5 Gy were associated with better efficacy.

Abstract Background Autosomal‐recessive mutations in SPEG (striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy with or without dilated cardiomyopathy (CNM5). Loss of SPEG is associated with defective triad formation, abnormal excitation–contraction coupling, calcium mishandling and disruption of the focal adhesion complex in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi‐omics tools and analysis to obtain a comprehensive view of the complex biological processes and molecular functions. Methods Skeletal muscles from 2‐month‐old SPEG‐deficient (Speg‐CKO) and wild‐type (WT) mice were used for RNA sequencing (n = 4 per genotype) to profile transcriptomics and mass spectrometry (n = 4 for WT; n = 3 for Speg‐CKO mice) to profile proteomics and phosphoproteomics. In addition, interactomics was performed using the SPEG antibody on pooled muscle lysates (quadriceps, gastrocnemius and triceps) from WT and Speg‐CKO mice. Based on the multi‐omics results, we performed quantitative real‐time PCR, co‐immunoprecipitation and immunoblot to verify the findings. Results We identified that SPEG interacts with myospryn complex proteins CMYA5, FSD2 and RyR1, which are critical for triad formation, and that SPEG deficiency results in myospryn complex abnormalities (protein levels decreased to 22 ± 3% for CMYA5 [P

With the rapid development of urban underground space, the construction of shield-driven cross-river twin tunnels is increasing, and the complex hydro-mechanical coupling effects and twin-tunnel interactions bring huge construction risks to such projects, which have attracted more and more attention. This study aims to understand the excavation effects induced by shield driving of cross-river twin tunnels through numerical simulation. A refined three-dimensional numerical model based on the fully coupled hydro-mechanical theory is established. The model considers the main components of the slurry pressure balance shield (SPBS) machine, including support force, jacking thrust, grouting pressure, shield-rock interaction and lining-grouting interaction, as well as the detailed construction process. The purpose is to examine the excavation effects during construction, including rock deformation around tunnels, the change in pore pressure, and the response of the lining. The results show the influence range of twin-tunnel excavation on rock deformation and pore pressure, as well as the modes of lining response. In addition, this study also systematically investigates the effects of water level fluctuation and burial depth on twin-tunnel excavation. The results indicate that the increase of water level or burial depth will enhance the excavation effects and strengthen the twin-tunnel interactions. These results provide useful insights for estimating the construction impact range and degree of twin tunnels, and serve as basic references for the design of cross-river twin tunnels.

Service robots are becoming increasingly popular in hotels, mainly providing services such as welcome, check-in, and meal delivery. This study examines the relationships among customer participation, perceived value, and behavioral intention in a hotel service robot context. We collected 321 valid samples and performed the Partial Least Squares (PLS) path analysis. The results show that customer participation is positively related to utilitarian and hedonic values, which further lead to service robot satisfaction. Service robot satisfaction is also related to hotel satisfaction, and both service robot satisfaction and hotel satisfaction have positive effects on behavioral intention. This study helps to deepen the understanding of the influence of customer participation in value co-creation on behavioral intention in human-robot interaction context.

Background: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment. Methods: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Results: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were “satisfied” or “very satisfied” with the results of the treatment. Conclusions: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus.

Objective: Behcet's uveitis (BU) is a type of uveitis with a high rate of blindness, characterized by anterior segment inflammation, vitreous opacity, and retinal vasculitis. Its pathogenesis is still unclear. Fuchs syndrome (Fuchs) is another common type of uveitis, which clinically presents with anterior segment inflammation and vitreous opacity, but rarely causes blindness. This study aims to compare the gut microbiota and metabolites of two different types of uveitis to clarify whether the differences in clinical manifestations are relevant to the alterations in gut microbiota. Methods: Faecal samples were collected from new-onset BU (n = 11) patients without systemic treatment and other diseases. 16S rRNA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to analyze gut microbes and metabolites. Fuchs (n = 15) was used as the disease control, and healthy controls (n = 18) without autoimmune diseases and systemic medication were included. Results: Microbial composition and metabolite profiles differed significantly among the three groups. Compared to controls, Fusicatenibacter and eight metabolites were specifically altered in BU patients, and Pantoea and five metabolites in Fuchs. Pathways involving delta-tocopherol, palmitic acid, and serotonin are significantly disrupted in BU patients. Pathways involving linoleic acid are dysregulated considerably in Fuchs. Microbial markers consisting of 4 genera and 7 metabolites can respectively distinguish BU patients from controls. AUC values of metabolite markers were greater than those of microbial markers. Furthermore, serum zonulin levels were significantly elevated in both types of uveitis, with no difference between them. Correlation analysis revealed correlations between zonulin levels and multiple microbes. Conclusions: Patients with BU and Fuchs syndrome showed significant differences in gut microbiota and metabolites. Disruption of the intestinal mucosal barrier was observed in both types of uveitis. However, the mechanism of different intestinal microbiota causing different clinical manifestations needs to be studied in the future.

IntroductionHeritage trees have special historical, cultural, and landscape value in cities and are keystone ecological structures for urban areas. However, these trees are threatened by rapid urbanization. To facilitate the conservation and management of such trees, our study investigated ancient trees in Chengdu, which is one of the hotspot of biodiversity and Historical and Cultural cities in Southwest of China.MethodsThe floristic diversity, Shannon-Wiener index (H), spatial pattern, characteristics, dimension, age, and health status of the trees were estimated by using ecological indexes and mathematical statistics.ResultsA total of 9383 heritage trees belonging to 119 species in 20 districts of Chengdu were surveyed. Dujiangyan (DJY) had the largest Shannon-Weiner index (H) (2.63), species count (76), and tree count (1842) and is therefore the most important district for preserving ancient trees. In contrast, Qingyang (QY) had the largest density of trees (120 trees/10 km2) among the 20 studied districts. In terms of important species, Phoebe zhennan (2351) was the dominant species, followed by Cupressus funebris, Ginkgo biloba, and Ficus virens. Akaike information criterion weights and standard deviation ellipse analysis showed that mean annual rainfall is a critical predictor for species distribution and age.DiscussionFindings from this study suggest that reducing water stress environments will improve the management and conservation of heritage trees in the future.

Background Hibiscus mutabilis L. is a popular regional characteristic plant in China, cultivated for its attractive flower colors, extended bloom time, and medicinal properties. To enhance molecular breeding and gene function studies, we conducted transcriptome analysis and identified valuable genes in previous research. Nonetheless, the current inefficient and labor-intensive transformation techniques have hindered their applications. Virus-induced gene silencing (VIGS) provides a precise and effective strategy for post-transcriptional down-regulation of endogenous gene expression. Methods We investigated the performance of tobacco rattle virus (TRV) as a tool for targeting and silencing the gene encoding the protein involved in chloroplast development, cloroplastos alterados 1 (altered chloroplast; CLA1), of H. mutabilis through Agrobacterium tumefaciens-mediated infiltration. Results By effectively suppressing the CLA1 gene associated with chloroplast development in H. mutabilis via the TRV-VIGS system, we have illustrated the inaugural implementation of VIGS in this species. Quantitative RT-PCR proved that HmCLA1 expression in agro-infiltrated plants was lower than in the mock-infiltrated (mock) and the control (CK) plants. Phenotypic observations corroborated the albino phenotype in leaves following successful HmCLA1 silencing. Conclusions Our study showcases TRV-VIGS as a potential gene silencing tool for H. mutabilis, facilitating functional genomics studies and molecular breeding efforts in this species.

Breast cancer is the most common malignancy in women worldwide, and major challenges in its treatment include drug resistance and metastasis. Three-dimensional cell culture systems have received widespread attention in drug discovery studies but existing models have limitations, that warrant the development of a simple and repeatable three-dimensional culture model for high-throughput screening. In this study, we designed a simple, reproducible, and highly efficient microencapsulated device to co-culture MCF-7 cells and HUVECs in microcapsules to establish an in vitro vascularized micro-tumor model for chemotherapeutic drug screening. First, to construct a three-dimensional micro-tumor model, cell encapsulation devices were created using three different sizes of flat-mouthed needles. Immunohistochemistry and immunofluorescence assays were conducted to determine vascular lumen formation. Cell proliferation was detected using the Cell Counting Kit-8 assay. Finally, to observe the drug reactions between the models, anticancer drugs (doxorubicin or paclitaxel) were added 12 h after the two-dimensional cultured cells were plated or 7 days after cell growth in the core-shell microcapsules. Vascularized micro-tumors were obtained after 14 days of three-dimensional culture. The proliferation rate in the three-dimensional cultured cells was slower than that of two-dimensional cultured cells. Three-dimensional cultured cells were more resistant to anticancer drugs than two-dimensional cultured cells. This novel sample encapsulation device formed core-shell microcapsules and can be used to successfully construct 3D vascularized micro-tumors in vitro . The three-dimensional culture model may provide a platform for drug screening and is valuable for studying tumor development and angiogenesis.

The maturity and patency of arteriovenous fistula (AVF) are essential for patients undergoing hemodialysis. Dysfunction of AVF due to neointimal hyperplasia (NIH) presents a significant clinical challenge. While balloon dilation therapy and open surgery can address this issue, they are associated with a higher likelihood of restenosis and reduced long-term durability. Therefore, there is an urgent need to establish a new method for inhibiting NIH to prolong the patency of AVF treatment. In this study, we developed a local vascular-encapsulated sustained-release drug delivery system containing degradable rapamycin nanofiber membrane patches (R-NFMs). During surgery, R-NFMs were wrapped around the anastomotic site of the AVF and the venous outflow tract. In vitro assessments demonstrated the consistent and stable release of rapamycin from the R-NFMs, confirming the material’s non-toxicity and its support of healthy cellular morphology. Animal studies further revealed that the experimental group showed significant reductions in neointimal and medial hyperplasia, as well as decreased expression of α-SMA, compared to controls. In conclusion, these findings suggest that R-NFMs are effective in inhibiting NIH and may serve as an innovative preventative approach to this pervasive issue.

Deep soil desiccation has become a major obstacle to restoring vegetation in the Loess Plateau region of China. The restoration of deep soil water plays an important role in ecosystem health. In the present study, we compared the effects on moisture variations in deep dry soil of grass cover and clean tillage treatments based on in-situ soil column monitoring for eight years. The results showed that the dry soil layers could temporarily disappear and reappear again with rainfall under clean tillage. However, grass cover effectively increased the deep soil moisture. Grass primarily consumed soil moisture from the shallow layer (0–2 m), and the total amount of water consumed during the whole growth period was less than the annual rainfall in dry years. The average soil desiccation index decreased by 24.20 % and the deep soil water moisture (2–10 m) recovered from 7.5 % to 12.8 % after eight years, with an annual average recovery of 0.66 %. Thus, it would take half a year to recover to the stable field capacity and 14 years to reach the field capacity. Recovery of the soil moisture also depended on the rainfall supply. We found that precipitation had an obvious lagged effect of approximately two years on the supply of deep soil moisture. Our findings contribute to understanding how to alleviate dry soil layer, with potentially helpful implications for the ecological health in arid and semiarid regions.

Summary: Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Cemented soft rock is prone to softening when exposed to water, and its mechanical properties deteriorate rapidly, which is an important reason to induce the instability and failure of engineering soft rock mass. The softening mechanism of soft rock is essentially the deterioration of microstructure caused by the change of water-rock interface. Considering the general characteristics of soft rock, the microstructural evolution characteristics and element loss over varying immersion time are then compared and analyzed. The Interfacial Cemented Bonding (ICB) structure is proposed to describe the evolution of water-rock interface. Based on the diffusion theory, the theoretical equation describing the evolution of water-rock interface is derived and compared with the experimental results. The meso-softening damage factor (MSDF) of soft rock is proposed and introduced into a numerical method to establish a strength degradation discrete element method (SD-DEM) model. The results show that the softening process of soft rock is accompanied by the shedding and suspension of particles and the dissolution of soluble substances. Besides, the softening of soft rock has obvious nonlinear dynamic characteristics. The fitting degree between the theoretical values and the experimental results is relatively high, which verifies the reliability and rationality of the dissolution-diffusion interfacial softening model. The numerical results are in good agreement with the experimental ones. This study provides a new idea for understanding the mechanism of water-induced softening characteristics and strength degradation of soft rock.

Abstract Pulse oximeters measure peripheral arterial oxygen saturation (SpO2) noninvasively, while the gold standard (SaO2) involves arterial blood gas measurement. There are known racial and ethnic disparities in their performance. BOLD is a dataset that aims to underscore the importance of addressing biases in pulse oximetry accuracy, which disproportionately affect darker-skinned patients. The dataset was created by harmonizing three Electronic Health Record databases (MIMIC-III, MIMIC-IV, eICU-CRD) comprising Intensive Care Unit stays of US patients. Paired SpO2 and SaO2 measurements were time-aligned and combined with various other sociodemographic and parameters to provide a detailed representation of each patient. BOLD includes 49,099 paired measurements, within a 5-minute window and with oxygen saturation levels between 70–100%. Minority racial and ethnic groups account for ~25% of the data – a proportion seldom achieved in previous studies. The codebase is publicly available. Given the prevalent use of pulse oximeters in the hospital and at home, we hope that BOLD will be leveraged to develop debiasing algorithms that can result in more equitable healthcare solutions.

Abstract During the processing of deep mining, revealing the distribution of abutment pressure is significant for controlling stability of the entry. In this study, the abutment pressure distribution of roof-cutting coalface was investigated by FLAC3D and self-developed flexible detection unit (FDU). In the numerical simulation, the double-yield model was built to analyze the goaf abutment pressure under the fracturing roofs to maintain entry (FRME). Compared with the non-fracturing side, the peak value of the advanced abutment pressure on the fracturing side is reduced by 19.29% on average, the influence range (span) increases by 30.78% and the distance between the peak value and the working face increases by 66.7%. The goaf abutment pressure within 23m near the cutting side is significantly higher than other areas along the dip. The FDU was employed in the coalface to record the change of advanced abutment stress. And the field measured results are in well agreement with the numerical results.

Abstract Background To evaluate the efficacy of modified uterine stent in the treatment of mild-to-moderate intrauterine adhesions and explore the relative indicators affecting prognosis prediction. Methods A total of 115 patients with mild-to-moderate intrauterine adhesions received a modified uterine stent placement after hysteroscopy adhesiolysis. The second-look hysteroscopy operated after 3 months surgery, and the third-look hysteroscopy operated after 6 months surgery if necessary. The stent was removed when the cavity shape was repaired, then the reproductive outcomes were followed up one year. Results Menstrual blood volume, endometrial thickness and volume had increased significantly after 3 months surgery. The rates of cavity repaired were 86.96% (100/115) after 3 months surgery and 100% (115/115) after 6 months surgery cumulatively. Endometrial thickness after 3-months surgery was positively associated with uterine cavity shape repaired (P

Abstract Background The Asian yellow pond turtle (Mauremys mutica) is an important commercial freshwater aquaculture species in China. This species is a highly sexually dimorphic species, with males growing at a faster rate than females and exhibits temperature-dependent sex determination (TSD), in which the incubation temperature during embryonic development determines the sexual fate. However, the mechanisms of the sex determination or sex differentiation in the Asian yellow pond turtle are remain a mystery. Results Temperature-specific gonadal transcriptomics of the Asian yellow pond turtle were performed during the thermosensitive period (stage 15) using RNA-seq technology to identify candidate genes that initiate gonadal differentiation. We uncovered candidates that were the first to respond to temperature. These candidates were sexually dimorphic in expression, reflecting differences in gonadal (Cirbp, Runx1) and germline differentiation (Vasa, Nanos1, Piwil2), gametogenesis (Hmgb3, Zar1, Ovoinhibitor-like, Kif4), steroid hormone biosynthesis (Hsd17b5, Hsd17b6), heat shock (Dnajb6, Hsp90b1, Hsp90aa1) and transient receptor potential channel genes (Trpm1, Trpm4, Trpm6, Trpv1). Conclusions Our work will provide important genetic information to elucidate the mechanisms of sex control in the Asian yellow pond turtles, and will contribute important genetic resources for further studies of temperature-dependent sex determination in turtles.

Abstract Background Idiopathic granulomatous mastitis (IGM) results in notable clinical symptoms and breast deformity. This study aimed to evaluate the clinical feasibility of microwave ablation (MWA) for the treatment of IGM through comparison with surgical excision. Methods From June 2016 to December 2020, a total of 234 consecutive patients admitted to the hospital were retrospectively included in this study. IGM was pathologically confirmed via breast biopsy in all included patients. These patients were divided into the MWA group (n = 91) and surgical group (n = 143) based on the type of treatment. Patients in both groups received oral prednisone prior to intervention. The clinical remission rate, recurrence rate, operative pain, complications, and BREAST Q score were compared between the two groups. Results There were 340 lesions in the MWA group, and 201 lesions in the surgical group were ultimately included. Significant differences in the complete remission rate (96.7% vs. 86.7%, p = 0.020), recurrence rate (3.3% vs. 13.3%, p = 0.020), operation time (48.7±14.6 min vs. 68.1±36.4 min, p

Geological discontinuity (GD) plays a pivotal role in determining the catastrophic mechanical failure of jointed rock masses. Accurate and efficient acquisition of GD networks is essential for characterizing and understanding the progressive damage mechanisms of slopes based on monitoring image data. Inspired by recent advances in computer vision, deep learning (DL) models have been widely utilized for image-based fracture identification. The multi-scale characteristics, image resolution and annotation quality of images will cause a scale-space effect (SSE) that makes features indistinguishable from noise, directly affecting the accuracy. However, this effect has not received adequate attention. Herein, we try to address this gap by collecting slope images at various proportional scales and constructing multi-scale datasets using image processing techniques. Next, we quantify the intensity of feature signals using metrics such as peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). Combining these metrics with the scale-space theory, we investigate the influence of the SSE on the differentiation of multi-scale features and the accuracy of recognition. It is found that augmenting the image's detail capacity does not always yield benefits for vision-based recognition models. In light of these observations, we propose a scale hybridization approach based on the diffusion mechanism of scale-space representation. The results show that scale hybridization strengthens the tolerance of multi-scale feature recognition under complex environmental noise interference and significantly enhances the recognition accuracy of GD. It also facilitates the objective understanding, description and analysis of the rock behavior and stability of slopes from the perspective of image data.

Abstract In this study, we compared the transcriptome of longissimus dorsi muscle between Guizhou Xiang pigs (XP) and Western commercial Large White pigs (LW), which show diffirent meat quality between them. In terms of meat quality traits, the pH 45 min, color score, backfat thickness, and intramuscular fat (IMF) content were higher in Xiang pigs than in Large White pigs (P

We previously reported that immunoglobulin superfamily member 9 (IGSF9) as a tumor specific immune checkpoint promoted the tumor immune escape, however, as an adhesion molecule, whether IGSF9 promotes tumor invasion and metastasis has not been reported. Here, the full length, the intracellular domain (ID) not extracellular domain (ECD) of IGSF9 could alter tumor cell morphology from a flat and polygonal shape to elongated strips, suggesting that IGSF9 signal pathway has the potential to mediate epithelial-to-mesenchymal transition (EMT). Real-time PCR and western blotting also showed that the mesenchymal markers were significantly up-regulated, and the epithelial markers were significantly down-regulated in IGSF9 and IGSF9-ID groups. Meanwhile, immunofluorescence showed that β-catenin was clearly translocated into the nucleus in IGSF9 and IGSF9-ID groups. The in vitro and in vivo data showed that IGSF9, IGSF9-ID and ECD could promote tumor invasion and metastasis. Mechanistically, IGSF9-ID could recruit GSK-3β to result in the accumulation and nuclear translocation of β-catenin to trigger EMT. Anti-IGSF9 could significantly inhibit the invasion and metastasis, and IGSF9 is an effective candidate for lung cancer therapy.

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease, and understanding its genetic and molecular basis is crucial for early diagnosis, treatment, and prevention.Objective This study aims to explore the association between IL-4 polymorphisms (rs2227284, rs2243267, rs2243270, and rs2243283) and RA risk.Methods The four IL-4 polymorphisms were genotyped in 493 RA patients and 493 healthy controls using Agena MassARRAY. Logistic regression analysis calculated odds ratio (OR) and 95% confidence interval (CI) to estimate the relationship between IL-4 polymorphisms and RA risk.Results Overall analysis revealed that rs2243267 (GG vs. CC: OR = 0.26, FDR-p = .032; Recessive: OR = 0.27, FDR-p = .048) and rs2243270 (AA vs. GG: OR = 0.26, FDR-p = .024; Recessive: OR = 0.27, FDR-p = .024) were associated with a decreased risk of RA. Stratified analysis indicated that rs2243267 and rs2243270 were correlated with reduced RA risk in female, smoking, BMI

Background Induced abortion can seriously harm the physical and mental health of adolescent women. Long-acting reversible contraception (LARC) can effectively reduce unplanned pregnancies and prevent repeated abortions among adolescents. This study aimed to analyse the factors affecting the choice of LARC among adolescents in Chongqing of China.Methods A total of 555 adolescents who underwent induced abortions for unplanned pregnancies between January 2019 and October 2021 were selected as study subjects. Logistic regression analysis was used to determine the factors affecting adolescent LARC choices following induced abortions.Results The factors that affected adolescent LARC choices included an average monthly income ≥ ¥3000 (OR = 3.432, 95% CI: 1.429∼8.244), history of previous abortions (OR = 3.141, 95% CI: 1.632∼6.045), worrying about unplanned pregnancy (OR = 0.365, 95% CI: 0.180∼0.740), parental support for using LARC (OR = 3.549, 95% CI: 1.607∼7.839), sexual partners’ support for using LARC (OR = 2.349, 95% CI: 1.068∼5.167), concerns about using LARC (OR = 0.362, 95% CI: 0.176∼0.745), and willingness to use free IUDs (OR = 13.582, 95% CI: 7.173∼25.717).Conclusion Cost is one of the factors affecting LARC choices. Parents and sexual partners may play important role in the choice of LARC.

BackgroundCytokine network disturbances in primary Sjögren’s syndrome (pSS) have been reported in many studies. However, their functions in patients with primary Sjögren’s syndrome and interstitial lung disease (pSS-ILD) is controversial. In this study, we aim to investigate the associations of immunological characteristics and cytokine profiles with pSS-ILD pathogenesis and explore their predictive values for pSS progression.MethodsA total of 256 patients initially diagnosed with pSS at Henan Provincial People’s Hospital were enrolled. After excluding the patients previously diagnosed with various serious acute and chronic respiratory system diseases and cases with other connective tissue diseases or congenital heart diseases, 94 pSS patients were included for further analysis, including 40 patients with ILD (pSS-ILD) and 54 patients without ILD (pSS-N-ILD). For comparison, 41 age- and sex-matched healthy individuals were included as normal controls. Their clinical symptoms and serological data including cyclic citrullinated peptide (CCP) antibody (anti-CCP), antinuclear antibody (ANA), anti-Ro52, anti-SSA, anti-SSB, C-reactive protein, IgG, IgM, IgA, C3, C4, and 10 cytokines and chemokines were obtained. Wilcoxon test, chi-square test, Spearman correlation analysis, and logistics regression analysis were performed.ResultsHigher positive rates of anti-SSB and higher incidence of dry cough, dyspnea, and arthrosis symptoms were shown in pSS-ILD patients than in the pSS-N-ILD cases. Anti-CCP antibodies and cytokines (IL-1β, TNFα, IL-6, IL-5, IL-12p70, and IL-17) were higher, while C3 was lower in pSS-ILD patients than in pSS-N-ILD cases. Significant negative correlations of IgG with C3 and C4 and positive correlations of IL-12p70 and IL-17 with IL-6 were only shown in pSS-ILD patients. The anti-CCP antibody was positively correlated with IL-5 in pSS-ILD patients, but not in pSS-N-ILD cases. Multi-variable logistics regression analysis revealed the combination of anti-CCP, IL-17, IL-12p70, and IL-5 was effective in predicting the status of pSS-ILD in the pSS cases.ConclusionThere were significant differences in serum marker levels between pSS-ILD and pSS-N-ILD cases. The combination of anti-CCP, IL-17, IL-12p70, and IL-5 might be a potential risk predictor for pSS-ILD occurrence. The cytokines might be involved in the development and progression of pSS-ILD. These results would provide new therapeutic targets for pSS-ILD treatment.

IntroductionThe incidence of knee osteoarthritis (KOA) is moderately correlated with age and body weight and increases with life span and weight gain, associated with tearing and wearing the knee joints. KOA can adjust the force through the human lower limbs, redistribute the load of the knee joint, reduce the pain, and restore mobility when the arthritis changes are mild. However, most of the existing knee orthosis cannot be adjusted adaptively according to the needs of patients.MethodologyThis study establishes a biomechanical model of the knee joint to analyze the medial and lateral forces acting on the joint. The new adjustable knee orthosis is designed. It applies the principle of four-point bending to apply pressure to both sides of the knee joint, thereby adjusting the varus angle and modifying the medial and lateral forces on the knee joint. Through structural optimization, the prototype of the knee orthosis weighs only 324 g. Utilizing three-dimensional scanning technology, discrete point cloud data of the leg surface is obtained, reconstructed, and processed to create a 3D model of the human leg surface. The design ensures a close fit to the human leg surface, offering comfortable wear. A pressure sensing film system is employed to build a pressure sensing test system, where the knee orthosis is worn on a prosthesis for pressure testing to evaluate its ability to adjust knee joint forces.ResultsThe pressure test results demonstrate that the knee orthosis can stably provide an adjustment angle of 0–7° and sustain a maximum force of 10N on both sides of the knee joint over extended periods. A self-developed 8-channel plantar pressure sensing insole is calibrated against commercial plantar pressure sensors. Human wear tests on 15 subjects show that during the operation of the knee orthosis, it significantly adjusts plantar pressures, reducing lateral foot pressures by 22% overall, with more pronounced corrective effects observed in lighter participants.DiscussionIn this study, a wedge-shaped adaptive knee orthosis was provided for KOA patients. The four-point force principle was used to balance the force between femurs and tibia and adjust the meniscus contact gap. The orthotic appliance has the advantages of simple mechanical structure, adjustable correction Angle and good wearing comfort.

This paper presents an innovative framework for the automated diagnosis of gastric cancer using artificial intelligence. The proposed approach utilizes a customized deep learning model called MobileNetV2, which is optimized using a Dynamic variant of the Pelican Optimization Algorithm (DPOA). By combining these advanced techniques, it is feasible to achieve highly accurate results when applied to a dataset of endoscopic gastric images. To evaluate the performance of the model based on the benchmark, its data is divided into training (80 %) and testing (20 %) sets. The MobileNetV2/DPOA model demonstrated an impressive accuracy of 97.73 %, precision of 97.88 %, specificity of 97.72 %, sensitivity of 96.35 %, Matthews Correlation Coefficient (MCC) of 96.58 %, and F1-score of 98.41 %. These results surpassed those obtained by other well-known models, such as Convolutional Neural Networks (CNN), Mask Region-Based Convolutional Neural Networks (Mask R–CNN), U-Net, Deep Stacked Sparse Autoencoder Neural Networks (SANNs), and DeepLab v3+, in terms of most quantitative metrics. Despite the promising outcomes, it is important to note that further research is needed. Specifically, larger and more diverse datasets as well as exhaustive clinical validation are necessary to validate the effectiveness of the proposed method. By implementing this innovative approach in the detection of gastric cancer, it is possible to enhance the speed and accuracy of diagnosis, leading to improved patient care and better allocation of healthcare resources.

Dual-comb photoacoustic spectroscopy (DC-PAS) advances spectral measurements by offering high-sensitivity and compact size in a wavelength-independent manner. Here, we present a novel cantilever-enhanced DC-PAS scheme, employing a high-sensitivity fiber-optic acoustic sensor based on an optical cantilever and a non-resonant photoacoustic cell (PAC) featuring a flat-response characteristic. The dual comb is down-converted to the audio frequency range, and the resulting multiheterodyne sound waves from the photoacoustic effect, are mapped into the response frequency region of the optical cantilever microphone. This cantilever-enhanced DC-PAS method provides advantages such as high sensitivity, compact design, and immunity to electromagnetic interference. Through 10 seconds averaging time, the proposed approach experimentally achieved a minimum detection limit of 860 ppb for acetylene. This technology presents outstanding opportunities for highly sensitive detection of trace gases in a wavelength-independent manner, all within a compact volume.

BackgroundIn the medical field, effective time management by clinical nurses is crucial for enhancing the quality of patient care. However, in recent years, with increasing work pressure for clinical nurses, procrastination has become a prevalent issue. Many nurses use smartphones as a way to alleviate stress and manage emotions, but excessive smartphone use could exacerbate procrastination, thereby jeopardizing patient safety and healthcare quality. Therefore, understanding the current state of work procrastination among clinical nurses, its heterogeneity, and exploring the impact of smartphone addiction and demographic factors on different aspects of nurse procrastination hold significant importance for improving patient care quality.ObjectiveThis study aims to explore the current state of work procrastination among clinical nurses and identify potential profile categories. It further analyzes the impact of mobile phone addiction and demographic factors on work procrastination among clinical nurses.MethodsConvenience sampling was employed to recruit participants from three tertiary hospitals in central China from October to November 2023. Surveys measuring nurses’ work procrastination and smartphone addiction were distributed and collected through online platforms. A total of 1,536 nurses participated in this study. Mplus 8.3 statistical software was used for latent profile analysis of clinical nurses’ work procrastination, and SPSS 26.0 software was utilized for chi-square tests, rank-sum tests, and multi-classification logistic regression analyses.ResultsThe median total score for clinical nurses’ work procrastination was 21.00 (17.00, 28.00), and three subgroups were identified: low procrastination (66.93%), medium-low procrastination (20.66%), and medium-high procrastination (12.41%). Additionally, logistic regression analysis revealed that smartphone addiction and department atmosphere were common influencing factors for medium-low and medium-high work procrastination. Hospitals with stricter management and nurses holding the position of head nurse were more likely to belong to the low work procrastination group. Nurses with higher incomes or those holding intermediate titles were more prone to medium-low work procrastination, while those experiencing career advancement difficulties were more likely to exhibit medium-high work procrastination (p

BackgroundThe atherogenic index of plasma (AIP) and hyperuricemia (HUA) have been shown to be closely associated with morbidity and mortality of coronary artery disease. However, studies targeting predictive value of AIP and HUA for chronic total occlusion (CTO) lesions are still lacking.MethodsIn total, 5,238 patients meeting the eligibility criteria were recruited in this analysis. CTO was defined as the condition of lesions without forward blood flow and with over three months of occlusion time. AIP was calculated as log10 [triglycerides (mmol/L)/high-density lipoprotein cholesterol (mmol/L)]. HUA was defined based on sex-specific criteria: serum uric acid 420 and 360 μmol/L for males and females, respectively.ResultsCTO lesions were presented in 907 (17.3%) patients. Compared with patients showing lower AIP levels and non-HUA, the CTO lesion risks increased by 5.225 and 2.765 times in patients with higher AIP levels and HUA. Patients with AIP >0.15 and HUA exhibited the greatest CTO incidence (odds ratio 11.491; 95% confidence interval 9.019–14.641, P

BackgroundPsychological distress is highly prevalent and has a severe impact on the quality of life among breast cancer survivors. This type of distress is associated with cognitive failure. However, previous studies have focused solely on the total scale scores of these two concepts while ignoring the unique relationship between specific components. In the present study, we utilized network analysis to explore the relationship between psychological distress and cognitive failure in breast cancer survivors.MethodsThe network analysis approach was adopted to estimate the regularized partial correlation network in a cross-sectional sample of 409 breast cancer survivors. All participants were assessed using the Depression Anxiety Stress Scale and the Cognitive Failure Questionnaire. The Gaussian Graphical Model was employed to estimate the network, centrality indices, and edge weights, providing a description of the characteristics of the network.ResultsThe results indicated that anxiety–stress and depression–stress were the strongest edges in the community of psychological distress. Distractibility–memory was the strongest edge in the community of cognitive failure. Distractibility and memory were the most central nodes, with the highest expected influence in the network. Depression and motor coordination acted as important bridge nodes with the highest bridge expected influence.ConclusionDistractibility and memory in cognitive failure played important roles in activating and maintaining the relationship network. Motor coordination was identified as the crucial pathway for the impact of cognitive failure on psychological distress. Interventions targeting these specific issues might be more effective in improving cognitive failure and reducing psychological distress among breast cancer survivors.