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Abstract Hepatocellular carcinoma (HCC) is a common malignant tumor with a complex immune evasion mechanism posing a challenge to treatment. The role of the S100A10 gene in various cancers has garnered significant attention. This study aims to elucidate the impact of S100A10 on CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, thereby elucidating its role in immune evasion in HCC. By analyzing the HCC-related data from the GEO and TCGA databases, we identified differentially expressed genes associated with lipid metabolism and developed a prognostic risk model. Subsequently, through RNA-seq and PPI analyses, we determined vital lipid metabolism genes and downstream factors S100A10, ACOT7, and SMS, which were significantly correlated with CD8+ T cell infiltration. Given the most significant expression differences, we selected S100A10 for further investigation. Both in vitro and in vivo experiments were conducted, including co-culture experiments of CD8+ T cells with MHCC97-L cells, Co-IP experiments, and validation in an HCC mouse model. S100A10 was significantly overexpressed in HCC tissues and potentially regulates CD8+ T cell exhaustion and lipid metabolism reprogramming through the cPLA2 and 5-LOX axis. Silencing S100A10 could inhibit CD8+ T cell exhaustion, further suppressing immune evasion in HCC. S100A10 may activate the cPLA2 and 5-LOX axis, initiating lipid metabolism reprogramming and upregulating LTB4 levels, thus promoting CD8+ T cell exhaustion in HCC tissues, facilitating immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells. This research highlights the critical role of S100A10 via the cPLA2 and 5-LOX axis in immune evasion in HCC, providing new theoretical foundations and potential targets for diagnosing and treating HCC.

The poppet valves two-stroke (PV2S) aircraft engine fueled with sustainable aviation fuel is a promising option for general aviation and unmanned aerial vehicle propulsion due to its high power-to-weight ratio, uniform torque output, and flexible valve timings. However, its high-altitude gas exchange performance remains unexplored, presenting new opportunities for optimization through artificial intelligence (AI) technology. This study uses validated 1D + 3D models to evaluate the high-altitude gas exchange performance of PV2S aircraft engines. The valve timings of the PV2S engine exhibit considerable flexibility, thus the Latin hypercube design of experiments (DoE) methodology is employed to fit a response surface model. A genetic algorithm (GA) is applied to iteratively optimize valve timings for varying altitudes. The optimization process reveals that increasing the intake duration while decreasing the exhaust duration and valve overlap angles can significantly enhance high-altitude gas exchange performance. The optimal valve overlap angle emerged as 93 °CA at sea level and 82 °CA at 4000 m altitude. The effects of operating parameters, including engine speed, load, and exhaust back pressure, on the gas exchange process at varying altitudes are further investigated. The higher engine speed increases trapping efficiency but decreases the delivery ratio and charging efficiency at various altitudes. This effect is especially pronounced at elevated altitudes. The increase in exhaust back pressure will significantly reduce the delivery ratio and increase the trapping efficiency. This study demonstrates that integrating DoE with AI algorithms can enhance the high-altitude performance of aircraft engines, serving as a valuable reference for further optimization efforts.

Abstract Triple-negative breast Cancer (TNBC) is a highly malignant cancer with unclear pathogenesis. Within the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) vitally influence tumor onset and progression. Thus, this research aimed to identify distinct subgroups of CAF using single-cell and TNBC-related information from the GEO and TCGA databases, respectively. The primary aim was to establish a novel predictive model based on the CAF features and their clinical relevance. Moreover, the CAFs were analyzed for their immune characteristics, response to immunotherapy, and sensitivity to different drugs. The developed predictive model demonstrated significant effectiveness in determining the prognosis of patients with TNBC, TME, and the immune landscape of the tumor. Of note, the expression of GPR34 was significantly higher in TNBC tissues compared to that in other breast cancer (non-TNBC) tissues, indicating that GPR34 plays a crucial role in the onset and progression of TNBC. In summary, this research has yielded a novel predictive model for TNBC that holds promise for the accurate prediction of prognosis and response to immunotherapy in patients with TNBC.

The objective of cross-scene hyperspectral image (HSI) classification is to develop models capable of adapting to the “domain gap” that exists between different scenes, enabling accurate object classification in previously unseen scenes. Many researchers have devised various domain adaptation techniques aimed at aligning the statistical or spectral distributions of data from diverse scenes. However, many previous studies have overlooked the potential benefits of incorporating spatial topological information from hyperspectral imagery, which could provide a more accurate representation of the inherent data structure in HSIs. To overcome this issue, we introduce an innovative approach for cross-scene HSI classification, founded on hierarchical prototype graph alignment. Specifically, this method leverages prototypes as representative embedded representations of all samples within the same class. By employing multiple graph convolution and pooling operations, multi-scale domain alignment is attained. Beyond statistical distribution alignment, we integrate graph matching to effectively reconcile semantic and topological information. Experimental results on several datasets achieve significantly improved accuracy and generalization capabilities for cross-scene HSI classification tasks.

Abstract Purpose Recent studies have revealed an increase in the incidence rate of non-alcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC). Furthermore, the association of Sphingosine 1-phosphate receptor 2 (S1PR2) with various types of tumours is identified, and the metabolism of conjugated bile acids (CBAs) performs an essential function in the onset and development of HCC. However, the association of CBA and S1PR2 with NAFLD-HCC is unclear. Methods The relationship between the expression of S1PR2 and the prognosis of patients suffering from NAFLD-HCC was investigated by bioinformatics techniques. Subsequently, the relationship between S1PR2 and the biological behaviours of HCC cell lines Huh 7 and HepG2 was explored by conducting molecular biology assays. Additionally, several in vivo animal experiments were carried out for the elucidation of the biological impacts of S1PR2 inhibitors on HCC cells. Finally, We used Glycodeoxycholic acid (GCDA) of CBA to explore the biological effects of CBA on HCC cell and its potential mechanism. Results High S1PR2 expression was linked to poor prognosis of the NAFLD-HCC patients. According to cellular assay results, S1PR2 expression could affect the proliferation, invasion, migration, and apoptosis of Huh 7 and HepG2 cells, and was closely associated with the G1/G2 phase of the cell cycle. The experiments conducted in the In vivo conditions revealed that the overexpression of S1PR2 accelerated the growth of subcutaneous tumours. In addition, JTE-013, an antagonist of S1PR2, effectively inhibited the migration and proliferation of HCC cells. Furthermore, the bioinformatics analysis highlighted a correlation between S1PR2 and the PI3K/AKT/mTOR pathway. GCDA administration further enhanced the expression levels of p-AKT, p-mTOR, VEGF, SGK1, and PKCα. Moreover, both the presence and absence of GCDA did not reveal any significant change in the levels of S1PR2, p-AKT, p-mTOR, VEGF, SGK1, and PKCα proteins under S1PR2 knockdown, indicating that CBA may regulates the PI3K/AKT/mTOR pathway by mediating S1PR2 expression. Conclusion S1PR2 is a potential prognostic biomarker in NAFLD-HCC. In addition, We used GCDA in CBAs to treat HCC cell and found that the expression of S1PR2 was significantly increased, and the expression of PI3K/AKT/mTOR signalling pathway-related signal molecules was also significantly enhanced, indicating that GCDA may activate PI3K/AKT/mTOR signalling pathway by up-regulating the expression of S1PR2, and finally affect the activity of hepatocellular carcinoma cells. S1PR2 can be a candidate therapeutic target for NAFLD-HCC. Collectively, the findings of this research offer novel perspectives on the prevention and treatment of NAFLD-HCC.

ObjectiveNonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide. This study guides the prevention and diagnosis of NAFLD by analyzing its risk factors and the diagnostic value of each index for NAFLD.MethodWe collected the clinical information of adults individuals who underwent physical examination in the Physical Examination Center of Qingpu Branch of Zhongshan Hospital, Fudan University, from January 2016 to January 2020, including gender, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). We performed logistic regression analysis and ROC diagnostic analysis.ResultsThe results showed that age, BMI, SBP, ALT, AST, FBG, TBIL, TG, and LDL were risk factors for NAFLD in adults, and HDL was a protective factor (all p-values were less than 0.05). Among them, age, BMI, ALT, TG, and HDL had a predictive value for the occurrence of NAFLD in the adults (AUC = 0.708, 0.836, 0.767, 0.780, and 0.732, respectively). The combination of age, BMI, ALT, TG, and HDL had a diagnostic value for the occurrence of NAFLD (AUC = 0.881).ConclusionHealthy people should pay attention to their BMI levels, manage blood pressure, blood glucose, and lipid levels, and pay attention to changes in ALT and AST index levels to prevent NAFLD. Age, BMI, ALT, TG, and HDL indexes are helpful factors in the diagnosis of NAFLD.

Persimmon is a fruit that contains sugars, vitamins, phenolic compounds, and various other nutrients. The aim of this study was to explore the structure of carboxymethylated persimmon polysaccharide (CM-PFP) and its interaction with the human gut microbiota. Carboxymethyl modification of the persimmon polysaccharide (PFP) increased both the Mw and Mn, enhanced dispersion stability, and decreased thermal stability. Both PFP and CM-PFP promoted the proliferation of Lactobacillus while inhibiting the proliferation of Staphylococcus aureus and Escherichia coli. In the simulated fecal fermentation, the pH of PFP- and CM-PFP-containing media decreased, the content of short-chain fatty acids increased, and the abundance of intestinal flora at the phylum and genus levels changed. The relative abundance of harmful intestinal bacteria was significantly reduced in both PFP and CM-PFP groups. Furthermore, it was found that CM-PFP was more easily metabolized than PFP, glucose, and fructo-oligosaccharide (FOS) and had a proliferation increase effect on Lactobacillus. Therefore, CM-PFP has a significant positive effect on both Lactobacillus proliferation and the human gut microbiota.

Background Bronchoalveolar lavage fluid (BALF) exosomes possess different properties in different diseases, which are mediated through microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), among others. By sequencing the differentially expressed lncRNAs in BALF exosomes, we seek potential targets for the diagnosis and treatment of acute lung injury (ALI). Methods Considering that human and rat genes are about 80% similar, ALI was induced using lipopolysaccharide in six male Wistar rats, with six rats as control (all weighing 200 ± 20 g and aged 6–8 weeks). BALF exosomes were obtained 24 h after ALI. The exosomes in BALF were extracted by ultracentrifugation. The differential expression of BALF exosomal lncRNAs in BALF was analyzed by RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the functions of differentially expressed lncRNAs, which were confirmed by reverse transcription–polymerase chain reaction. Results Compared with the control group, the ALI group displayed a higher wet/dry ratio, tumor necrosis factor-α levels, and interleukin-6 levels (all P < 0.001). The airway injection of exosomes in rats led to significant infiltration by neutrophils. A total of 2,958 differentially expressed exosomal lncRNAs were identified, including 2,524 upregulated and 434 downregulated ones. Five lncRNAs confirmed the reliability of the sequencing data. The top three GO functions were phagocytic vesicle membrane, regulation of receptor biosynthesis process, and I-SMAD binding. Salmonella infection, Toll-like receptor signaling pathway, and osteoclast differentiation were the most enriched KEGG pathways. The lncRNA–miRNA interaction network of the five confirmed lncRNAs could be predicted using miRDB. Conclusions BALF-derived exosomes play an important role in ALI development and help identify potential therapeutic targets related to ALI.

The lithium metal is a promising anode material for batteries; however, the growth of dendrite and its instability against moisture are two technical challenges. Here the authors address both issues by introducing a bifunctional layer consisting of hydrophobic graphite fluoride and lithium fluoride.

This paper presents a stochastic analysis method for linear elastic fracture mechanics using the Monte Carlo simulations (MCs) and the scaled boundary finite element method (SBFEM) based on proper orthogonal decomposition (POD) and radial basis functions (RBF). The semianalytical solutions obtained by the SBFEM enable us to capture the stress intensity factors (SIFs) easily and accurately. The adoption of POD and RBF significantly reduces the model order and increases computation efficiency, while maintaining the versatility and accuracy of MCs. Numerical examples of cracks in homogeneous and bimaterial plates are provided to demonstrate the effectiveness and reliability of the proposed method, where the crack inclination angles are set as uncertain variables. It is also found that the larger the scale of the problem, the more advantageous the proposed method is.

Ni-based superalloy with ceramic thermal barrier coatings (TBCs) is a composite material, which can be used in special environments with high temperature and high pressure such as aeroengine blade. In order to improve the cooling effect of the aeroengine, it is necessary to perform multi-size and large-area holes processing on the surface of blades. As a non-contact processing method with fast processing speed, good processing quality and almost no deformation, laser processing has been one of the important processing methods for film cooling hole processing of aeroengine blades. Percussion drilling is presented using picosecond ultrashort pulse laser in order to explore processing of deep holes in Ni-based superalloy, ceramic TBCs, and ceramic TBCs/substrate multilayer material. The effects of pulses, threshold and wavelength on hole diameter have been discussed, and the experiment on the deep hole ablation with 1064 nm wavelength has been performed. By analyzing the hole size and morphological characteristics of multiple processing parameters, the variation of hole cylindricity is obtained. A high-quality hole, without spatters around the periphery of hole entrance and without recast layer on the side-wall surface, in Ni-based superalloy coated with ceramic TBCs has been drilled. This research has potential applications to blade film cooling holes.

The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers.

AIMS: The aim of this study was to evaluate the combined contribution of 8 polymorphisms to the risk of Alzheimer's disease (AD). METHODS: Through a comprehensive literature search for genetic variants involved in the AD association study, we harvested a total of 6 genes (8 polymorphisms) for the current meta-analyses. These genes consisted of A2M (5bp I/D and V1000I), ABCA2 (rs908832), CHAT (1882G >A, 2384G >A), COMT (Val158Met), HTR6 (267C >T) and LPL (Ser447Ter). RESULTS: A total of 33 studies among 9,453 cases and 10,833 controls were retrieved for the meta-analyses of 8 genetic variants. It was showed that A2M V1000I (odd ratio (OR) = 1.26, 95% confidence interval (CI) = 1.07-1.49, P = 0.007), rs908832 allele of ABCA2 (OR = 1.55, 95% CI = 1.12-2.16, P = 0.009), 2384G >A of CHAT (OR = 1.22, 95% CI = 1.00-1.49, P = 0.05) and Ser447Ter of LPL in the Northern-American population (OR = 0.56, 95% CI = 0.35-0.91, P = 0.02) were significantly associated with the risk of AD. No association was found between the rest of the 5 polymorphisms and the risk of AD. CONCLUSION: Our results showed that A2M V1000I polymorphism in German, Korean, Chinese, Spanish, Italian and Polish populations, rs90883 of ABCA2 gene in French, American, Swiss, Greek and Japanese populations, 2384G >A of CHAT gene in British and Korean populations and LPL Ser447Ter in the Northern-American population were associated with the risk of AD.