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Apolipoprotein E (APOE) regulates lipid metabolism, associated with the development of various cancers. However, its precise prognostic significance and functions in alternative splicing and the tumor immune microenvironment remain unclear. In this study, we extracted APOE expression in pan-cancer from TCGA and analyzed mRNA transcriptome, cell lines, and protein levels. Furthermore, we analyzed the alternative splicing expression of the APOE gene transcript with prognostic profiles using the OncoSplicing database. We obtained 73 common APOE genes to perform functional enrichment analysis, assess the correlation between genes and immune cells using TIMER, EPIC, and ssGSEA methods, and examine the prognostic significance using the UALCAN database. Finally, single-cell data was employed to assess the correlation between APOE genes and cell functions. Our findings revealed that APOE expression varies across different tumor types and cancer cell lines. The alternative splicing analysis demonstrated that APOE transcript expression levels have prognostic value in cancers such as LGG, KIRC, and KIRP. Functional enrichment analysis indicated significant associations between APOE and various immune cells, such as macrophages, CD8 T cells, and NK cells, with significant implications for prognosis. Moreover, single-cell data indicated that APOE was primarily expressed in renal epithelial cells among stromal cells and in macrophages among immune cells, significantly negatively correlated with five functional states. Our study represents the first comprehensive exploration of APOE's function in pan-cancers and identifies APOE as a potential biomarker in cancer pathogenesis, prognosis, and immune therapeutic target. [ABSTRACT FROM AUTHOR]

The emergence of targeted drugs brings hope to patients with advanced liver cancer. However, due to the complex and diverse environment in the human body, the overall response rate of targeted drugs is not high. Therefore, how to efficiently deliver targeted drugs to tumor sites is a major challenge for current research. The project intends to construct mPEG-PLGA nanoparticles loaded with Sora and encapsulate them with exosomes for targeted therapy of hepatocellular carcinoma. mPEG-PLGA drug-loaded nanoparticles were prepared by the dialysis method and characterized by TEM and DLS. The obtained nanoparticles were incubated with the exosomes of liver cancer cells, and the exosomes-encapsulated drug-loaded nanoparticles (Exo-Sora-NPs) were obtained under pulsed ultrasound conditions, and they were characterized by Western blot, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The toxic effect of Exo-Sora-NPs on liver cancer cells was detected by the CCK-8 experiment. The uptake efficiency of nanoparticles by liver cancer cells was detected by a confocal microscope. The accumulation and infiltration depth of nanomedicine in liver cancer tissues were observed by confocal microscope on frozen sections of liver cancer tissue after the H22 liver cancer subcutaneous tumor transplantation model was constructed. The tumor size, body weight, pathology, and serology analysis of mice were measured after administration. The mPEG-PLGA polymer drug-loaded particles encapsulated by exosomes have high targeting ability and biosafety. To a certain extent, they can target the drug to the tumor site with a smaller systemic response and have a highly effective killing effect on the tumor. Nanodrug-loaded particles encapsulated by exosomes have great potential as drug carriers. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized. Methods: The expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting. Results: Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis. Conclusions: CAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future. [ABSTRACT FROM AUTHOR]

The Oligocene to Miocene Baiyangping Cu–Co and Pb–Zn mineralization was deposited during the collision of the India and Asia continents. The mineralization is hosted in veins in faulted carbonate and clastic rocks, which act as fluid pathways. A detailed fluid-inclusion analysis and C–O–S isotopic study are reported, focusing on the origin of the mineralizing fluids and mineralizing processes. The microthermometry of fluid inclusions hosted in quartz and carbonates indicate that the fluid peak temperature for both Cu–Co and Pb–Zn mineralizations ranges from 160 to 200 °C and from 120 to 160 °C, respectively. During these metallogenic hydrothermal events, salinity evolved from 2.7 wt% NaCl equiv to 24.8 wt% NaCl equiv. The δ34S values measured on sphalerite and tennantite range from +5.2‰ to +9.5‰, which indicates that sulfur originated from a reservoir characterized by thermochemical sulfate reduction (TSR). The C–O isotopic values obtained from the carbonate samples suggest that the fluid mainly originates from basinal brines. The combination of C and S isotopic values of the Cu–Co and Pb–Zn mineralization indicate the sedimentary source of the basin. Mineralization is controlled by faults, thermochemical sulfate reduction, and the physicochemical conditions of the fluid. [ABSTRACT FROM AUTHOR]

We obtain the global smooth solution of a nonlinear Schrödinger equations in atomic Bose-Einstein condensates with two-dimensional spaces. By using the Galerkin method and a priori estimates, we establish the global existence and uniqueness of the smooth solution. [ABSTRACT FROM AUTHOR]

We investigate the low regularity local and global well-posedness of the Cauchy problem for the coupled Klein-Gordon-Schrödinger system with fractional Laplacian in the Schrödinger equation in R. We use Bourgain space method to study this problem and prove that this system is locally well-posed for Schrödinger data in H and wave data in H × H for 3/4− α < s ≤ 0 and −1/2 < s < 3/2, where α is the fractional power of Laplacian which satisfies 3/4 < α ≤ 1. Based on this local well-posedness result, we also obtain the global well-posedness of this system for s = 0 and −1/2 < s < 1/2 by using the conservation law for the L norm of u. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers. In this study, our objective was to identify differentially regulated proteins in ESCC using isobaric tag for relative and absolute quantification (iTRAQ) technique and liquid chromatography-tandem mass spectrometry (LC-MS/MS). We compared the protein expression profiles of ESCC tumor tissues with the corresponding adjacent normal tissue from three patients. It was determined that 72 and 57 unique proteins were significantly up-regulated and down-regulated in all three samples. In addition, there were 431 significantly differentially regulated proteins having at least two biological samples. This subject found some of the differential proteins, such as prolyl 4-hydroxylase subunit alpha-1, prolyl 4-hydroxylase subunit alpha-2, and calponin-2, immunoglobulin superfamily containing leucine-rich repeat protein, and prolyl 3-hydroxylase1, which were few studies about them in ESCC. In order to determine the results, we performed another independent experiment. Our results indicated quantitative proteomics, as a robust discovery tool for the identification, differentially regulated proteins in cancers. [ABSTRACT FROM AUTHOR]

Distinguishing hepatocellular carcinoma (HCC) from metastatic tumors is a challenging issue, especially in differential diagnosis between poorly differentiated HCC and metastasis tumors. Expression of Arg-1, HepPar-1, and α-fetoprotein (AFP) in 78 cases of HCC, 34 cases of metastatic tumors, and 228 cases of nonhepatocellular tumors of surgical specimens is measured by immunohistochemistry. Arg-1 immunoreactivity was detected in 75 of 78 (96.1 %) cases of HCC, whereas HepPar-1 and AFP immunoreactivity was detected in 63 of 78 (80.7 %) and 40 of 78 (51.3 %) cases of HCC, respectively. HepPar-1 and AFP expression was observed in three of 34 (8.8 %) cases and one of 34 (2.9 %) cases of metastatic tumors, respectively. In contrast, Arg-1 expression was absent in all 34 (0 %) cases of metastatic tumors. The sensitivity, specificity, positive predictive value, and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors and nonhepatocellular tumors are 96.1, 99.6, 98.7, and 98.8 % compared with 80.7, 92.0, 75.0, and 94.1 % for HepPar-1 and 51.3, 97.7, 87.0, and 87.1 % for AFP, respectively. Arg-1 is a more sensitive and better specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can be easily applied in distinguishing HCC from metastatic tumors. [ABSTRACT FROM AUTHOR]

Background: The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. Methodology/Principal Findings: In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. Conclusions/Significances: In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies. [ABSTRACT FROM AUTHOR]

Steroid 5-α-reductase type 2 ( SRD5A2) V89L and A49T polymorphisms are thought to play a crucial role in the androgen synthesis and metabolic pathway, but their associations with prostate cancer risk remain controversial. To provide a more precise estimation of the associations between V89L and A49T polymorphisms and prostate cancer risk, we performed a meta-analysis using all published case-control studies of prostate cancer since January 1995. We used odds ratio (OR) and its 95 % confidence interval (CI) to assess the strength of the association under various genetic models in both overall and stratified analyses. We also calculated the false-positive report probability, the power of the current study, and the observed P value for significant findings. This analysis included 45 eligible studies of a total of 15,562 cases and 15,385 controls, in which no significant associations were found for the V89L polymorphisms under all genetic models. However, small excess prostate cancer risk was associated with the 49T allele in mixed populations compared with the 49A allele (OR = 1.24, 95 % CI = 1.02-1.50), and similar results were observed in Caucasians (OR = 1.24, 95 % CI = 1.01-1.53). The sensitivity analysis further strengthened the validity of these findings without publication bias. Although there was no overall association between V89L and prostate cancer risk, A49T might play a role in the etiology of prostate cancer among Caucasians. Additional large and well-designed studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

The 8q24 polymorphisms have been implicated in various cancers. Three 8q24 polymorphisms (rs1447295 C>A, rs16901979 C>A, and rs6983267 T>G) have been extensively investigated for their association with prostate cancer (PCa) susceptibility, yet conclusions are contradictory. We conducted a comprehensive meta-analysis to reevaluate the associations between those polymorphisms and PCa susceptibility, according to the latest meta-analysis guidelines (PRISMA). Eligible publications were searched from MEDLINE, EMBASE and CBM. False positive report possibility analysis was performed. We totally collected 20184 cases and 20439 controls from 20 studies for the rs1447295 C>A, 1850 cases and 2090 controls from 7 studies for the rs16901979 C>A, and 12233 cases and 7582 controls from 17 studies for the rs6983267 T>G. Overall, each of studied 8q24 polymorphisms was significantly associated with PCa risk individually. Significant associations were also observed in stratified analysis by ethnicity, source of control, and quality score. Interestingly, the effect of rs1447295 on PCa risk was observed among Caucasians and Asians, but not Africa-Americans. The effect of rs16901979 was more prominent among Africa-Americans than Asians. Likewise, rs6983267 conferred a higher Pca risk among Caucasians than Asians. Collectively, these 8q24 variant(s) may modulate PCa risk in an ethnic-specific manner. [ABSTRACT FROM AUTHOR]