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Obtaining compounds with large nonlinear-optical (NLO) coefficients and wide band gaps is challenging due to their competitive requirements for chemical bonds. Herein, the first member with mixed cations on the A site in the A-M3-Q5 or A-Ag-M6-Q10 (A = alkali metal; M = Ga, In; Q = S, Se, Te) family, viz. Na0.45Ag0.55Ga3Se5 (NAGSe), was obtained by a solid-state reaction. Its structure features [GaSe4] tetrahedra built three-dimensional {[Ga3Se5]-}∞ network, with Na and Na/Ag cations located at the octahedral cavities. Noncentrosymmetric (R32) NAGSe can also be transformed from centrosymmetric RbGa3S5 (P21/c) via multiple-site cosubstitution. NAGSe exhibits the highest NLO response (1.9 × AGS) in the A-Ag-M-Q family. Crystal structure analysis and theoretical calculations suggest that the NLO response is mainly contributed by the regularly arranged [GaSe4] units. This work enriches the exploration of the undeveloped A-M3-Q5 or A-Ag-M6-Q10 family as potential infrared NLO materials.
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AIMS: Herein, we examined the correlation between platelet/high-density lipoprotein cholesterol ratio (PHR) and symptoms of depression among United States adults. METHODS: Data acquired from the 2007-2018 National Health and Nutrition Examination Survey, involving individuals ≥ 20 years of age, with available PHR and depression diagnosis information. We employed weighted uni- and multivariable logistic regression analyses to assess the distinct correlation between PHR and depressive symptoms. Additionally, we conducted subgroup, interaction, and restricted cubic spline analyses. RESULTS: In all, 28,098 subjects were recruited for analysis, with 8.04% depression status and 19.31 ± 0.11 mean PHR value. Depressive symptoms increased with higher quartiles of PHR. Following fully confounder adjustments in model 2, participants with the largest PHR quartiles exhibited a 53% (OR: 1.53, 95%CI: 1.00-2.33, P = 0.05) raised depressive symptoms, relative to participants with least PHR quartiles. Based on the two-piece-wise regression, the breakpoint was PHR = 23.76, and a positive association was more evident when PHR < 23.76 (OR = 1.06, 95%CI: 1.02-1.10, P = 0.01). When PHR ≥ 23.76, the correlation disappeared (P = 0.85). Using subgroup and interaction analyses, we revealed a positive relationship between PHR and depressive symptoms almost consistent among various population settings. CONCLUSIONS: A convenient biomarker, the PHR was independently associated with an increased risk of depressive symptoms and may be a promising new bioindicator for the prediction of depression diagnosis.
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HDL-Colesterol , Depresión , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Depresión/sangre , Depresión/epidemiología , Adulto , Estudios Transversales , Persona de Mediana Edad , HDL-Colesterol/sangre , Plaquetas , Adulto Joven , AncianoRESUMEN
There have been numerous summaries of the runoff purification characteristics of bioretention cells in warm climates. However, little has been done on the effects of freeze-thaw cycles (FTCs) that frequently occur in cold regions on bioretention cell performance. Three experimental columns were constructed to simulate the operation of the bioretention cell under the FTCs. The effects of FTCs on the nutrient removal efficiency of different filling bioretention cells were analyzed. The results showed that the ammonia nitrogen (NH4+-N) concentration in the effluent of the wood chip bioretention cell under the T3 conditions (WBCF) (2.35 mg/L) was significantly higher than that of the wood chip bioretention cell operating at room temperature (WBCR) (0.62 mg/L). The effluent NH4+-N concentration of aluminum sludge bioretention cell (ABCF) (0.096 mg/L) under the FTCs was lower than that of WBCF (0.91 mg/L). Under the T3 condition, the effluent nitrate nitrogen (NO3--N) and total nitrogen (TN) concentrations of WBCF (5.33 mg/L and 8.86 mg/L) were higher than those of WBCR (5 mg/L and 6.11 mg/L) at room temperature. Under FTCs conditions, both WBCF and ABCF had high NO3--N removal efficiency (up to 85.87% and 24.75%) at the initial stage of thawing of the filler, and the efficiency gradually decreased with the thawing of the filler. With the increase of FTCs, the NO3--N removal efficiency of WBCF gradually decreased (always higher than 13.6%), while the removal efficiency of ABCF fluctuated wildly (the removal efficiency was primarily negative). The total phosphorus (TP) concentration in the effluent of WBCF (0.11 mg/L) under the T3 conditions was lower than that of WBCR (0.02 mg/L) at room temperature, and the TP concentration of ABCF (0.021 mg/L) in the effluent under the FTCs was slightly lower than that of WBCF (0.031 mg/L). The FTCs have a more significant impact on removing nitrogen pollutants in runoff, but have little effect on phosphorus. Compared with aluminum sludge, wood chips are more suitable for efficient removal of nitrogen pollutants in runoff under the FTCs. The experimental conclusions can provide a reference for the construction of bioretention cells in cold regions.
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Contaminantes Ambientales , Lluvia , Aluminio , Aguas del Alcantarillado , Fósforo , Nitrógeno/análisis , NutrientesRESUMEN
BACKGROUND RNA N6-methyladenosine (m6A) methylation, the most abundant and prominent form of epigenetic modification, is involved in hepatocellular carcinoma (HCC) initiation and progression. However, the role of m6A methylation in HCC tumor microenvironment (TME) formation is unexplored. This study aimed to reveal the TME features of HCC patients with distinct m6A expression patterns and establish a prognostic model based on m6A signatures for HCC cohorts. MATERIAL AND METHODS We classified the m6A methylation patterns in 365 HCC samples based on 21 m6A modulators using a consensus clustering algorithm. Single-sample gene set enrichment analysis algorithm was used to quantify the abundance of immune cell infiltration. Gene set variation analysis revealed the biological characteristics between the m6A modification patterns. The m6A-based prognostic model was constructed using a training set with least absolute shrinkage and selection operator regression and validated in internal and external datasets. RESULTS Two distinct m6A modification patterns exhibiting different TME immune-infiltrating characteristics, heterogeneity, and prognostic variations were identified in the HCC cohort. After depicting the immune landscape of TME in HCC, we found patients with high LRPPRC m6A modulator expression had depletion of T cells, cytotoxic cells, dendritic cells, and cytolytic activity response. A high m6A score, characterized by suppression of immunity, indicated an immune-excluded TME phenotype, with poor survival. A nomogram was developed to facilitate HCC clinical decision making. CONCLUSIONS Our results highlight the nonnegligible role of m6A methylation in TME formation and reveal a potential clinical application of the m6A-associated prognostic model for patients with HCC.
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Adenosina/análogos & derivados , Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN , Microambiente Tumoral , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Pronóstico , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Aims: The primary objective of this study was to investigate the relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR) and the prevalence of nephrolithiasis within the adult population of the United States. Methods: The data used in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2018. The analysis included a non-pregnant population aged 20 years or older, providing proper PHR index and nephrolithiasis data. The research utilized subgroup analyses and weighted univariate and multivariable logistic regression to evaluate the independent association between the PHR and the susceptibility to nephrolithiasis. Results: The study comprised 30,899 participants with an average PHR value of 19.30 ± 0.11. The overall prevalence rate of nephrolithiasis was estimated at 9.98% with an increase in the higher PHR tertiles (T1, 8.49%; T2, 10.11%; T3, 11.38%, P < 0.0001). An elevated PHR level was closely linked with a higher susceptibility to nephrolithiasis. Compared with patients in T1, and after adjusting for potential confounders in model 2, the corresponding odds ratio for nephrolithiasis in T3 was 1.48 (95% CI: 1.06 to 2.08), with a P-value = 0.02. The results of the interaction tests revealed a significant impact of chronic kidney disease on the relationship between PHR and nephrolithiasis. Furthermore, the restricted cubic spline analyses exhibited a positive, non-linear correlation between PHR and the risk of nephrolithiasis. Conclusion: A convenient biomarker, the PHR, was independently associated with nephrolithiasis and could be a novel biomarker in predicting occurrence in clinical decision.
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Nefrolitiasis , Adulto , Humanos , Estudios Transversales , Encuestas Nutricionales , HDL-Colesterol , Nefrolitiasis/epidemiología , BiomarcadoresRESUMEN
tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5'tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.
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Piruvato Carboxilasa , Neoplasias de la Tiroides , Humanos , Piruvato Carboxilasa/metabolismo , Neoplasias de la Tiroides/genética , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Línea CelularRESUMEN
CONTEXT: The property transition between metal and semiconductor is the key to improving the properties of transition metal dichalcogenides (TMDCs). The adsorption of the NbS2 compound in the defect state was adjusted for the first time. The hybrid system overwrites the original surface mechanism of NbS2 and induces indirect band gaps. This modulation mode makes NbS2 convert into a semiconductor and effectively improves the catalytic activity of the material in the system. In addition, the original local magnetic moment of the compound is concentrated in the vacancy region and is improved. The optical properties of the adsorption system indicate that NbS2 compounds can be effectively applied in visible and low-frequency ultraviolet regions. This provides a new idea for the design of the NbS2 compound as a two-dimensional photoelectric material. METHODS: In the study, we assume that only one atom is adsorbed on the NbS2 supercell of the defect, and the distance between the two adjacent atoms exceeds 12.74 Å, so the interaction between atoms is ignored in the study. Adsorbed atoms include nonmetallic elements (H, B, C, N, O, F), metallic elements (Fe, Co), and noble metal elements (Pt, Au, Ag). The density functional theory (DFT) was used in the experiment. The non-conservative pseudopotential method was used in the calculation to optimize the crystal structure geometrically. The approximate functional is Heyd-Scuseria-Ernzerhof (HSE06). The calculation method includes the spin-orbit coupling (SOC) effect. The crystal relaxation optimization uses a 7 × 7 × 1 k point grid to calculate niobium disulfide's photoelectric and magnetic properties. A vacuum space of 15Å is introduced in the direction outside the plane, and the free boundary condition is adopted to avoid the interaction between atomic layers. For the convergence parameter setting, the interatomic force of all composite systems is less than 0.03 eV/Å, and the lattice stress is less than 0.05 Gpa.
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CONTEXT: Monolayer NbS2 is a promising new two-dimensional material, and it is critical to develop effective methods to make NbS2 a material for nanodevices and photovoltaic applications. This study studied the strain rule of sulfur-deficient NbS2 structure by first principles. The results show that all defect structures introduce impurity states to enhance electron transport. The disulfide defect structure produces an indirect band gap under the action of tensile strain, which can reach up to 0.56eV and become a diluted semiconductor. The hybrid NbS2 exhibits high transparency under infrared, visible, and low-frequency ultraviolet light, improving the material's transmittance, optical response, and catalytic activity. The research results of this paper will provide a basis for the subsequent research of single-layer NbS2 and accelerate the research process of NbS2 as a new semiconductor material. METHODS: We are on the surface perpendicular to the 3×3×1 NbS2 and use a 15 Å vacuum layer to avoid interacting with periodic images. The first-principles simulation uses the CASTEP module in Materials Studio to simulate the hypothetical model and relaxation optimization structure of single-layer NbS2 under strain and defect state. The calculation function is PBE (Perdew-Burke-Ernzerhof) function under the generalized gradient approximation (GGA) for an approximate calculation to describe the interaction between electrons and the interaction between electrons and ions. The pseudopotentials of 3s23p4 and 4d45s1 valence electron configurations were used for S and Nb atoms, respectively. Van der Waals correction is considered in the simulation process. Moreover, it includes spin-orbit coupling (SOC) effects. For the plane wave truncation energy, we set it at 500eV. The arrangement of the Brillouin area is divided by 6×6×1 gamma-centered Monkhorst-Pack grids. The lattice deformation of all hybrid structures is less than 0.05 Gpa, and the interatomic force is less than 0.03 eV/Å.
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The nitrogen removal effect of traditional bioretention cells is generally poor under low temperature conditions, with significant levels of fluctuation and leaching often reported. Therefore, the migration characteristics of nitrogen were explored in bioretention cells under low temperature conditions, with the aim of improving the nitrogen removal effect. Four groups of modified collapsible loess bioretention cells were constructed and operated at 1, 5, 10 and 25 °C. The nitrogen removal effect of the cells was determined at different temperatures and the nitrogen migration and transformation characteristics under low temperature conditions were discussed. Experimental results showed that during the rainfall period, the ammonia nitrogen removal efficiency remained similar at different temperatures (above 97 %), while the nitrate nitrogen removal efficiency varied significantly at 1, 5, 10 and 25 °C, from 28.15 %-65.22 %, 96.68 %-98.8 %, 96.75 %-98.88 % and 80.14 %-96.72 %, respectively. In addition, nitrate nitrogen accumulation occurred in the filler during rainfall events, with lower temperature conditions increasing the final concentration of nitrate nitrogen accumulated. Following a rainfall event, the content of nitrate nitrogen in the filler decreased significantly over a 60 h dry period. However, the nitrate nitrogen reduction rate was significantly lower under low temperature conditions, than at 25 °C. Overall, low temperature conditions had a negative effect on the accumulation of nitrate nitrogen in the filler during rainfall events, as well as the transformation and migration of nitrate nitrogen within the filler during drought periods, with the adverse effects most significant at temperatures lower than 5 °C.
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Nitratos , Nitrógeno , Temperatura , Lluvia , Frío , Excipientes , DesnitrificaciónRESUMEN
CONTEXT: Using a first-principles plane-wave pseudopotential technique within the context of density-functional theory, the electronic structure and optical properties of the molybdenum ditelluride system doped with halogen atoms X (X = F, Cl, Br, I) were investigated. The electronic structure, density of states, charge transfer, and optical properties of halogen atom X doped on MoTe2 monolayer are systematically calculated and analyzed. It shows that the Fermi energy level is shifted upward after doping with halogen atoms. With F-MoTe2 doping, the geometrical distortion is the most pronounced, the charge transfer number is the highest, and the semiconductor shifts from a direct band gap to an indirect band gap. When the torsional deformation is between 1° and 5°, the F-doped MoTe2 system stays an indirect band gap semiconductor and transitions to quasi-metal at 6°. It is shown that the torsional deformation can modulate the electronic properties of the doped structure and realize the semiconductor-metal transition. OPTICAL PROPERTIES: The F-doped system has a strong absorption peak reflection peak after torsion, and with the increase of torsion angle, the absorption peak is red-shifted, and the reflection peak is blue-shifted. Moreover, the absorption and reflection peaks start to decrease with the rise of the torsion angle. METHODS: We apply the generalized gradient approximation plane-wave pseudopotential technique based on Perdew-Burke-Ernzerhof (PBE) generalized functions, under the first principles of the density-functional theory framework. The overall optimization of the intrinsic molybdenum ditelluride structure and the halogen atom X-doped molybdenum ditelluride structure was carried out. Then, the F-doped molybdenum ditelluride system was selected for torsional deformation with torsion angles from 1° to 6° for computational analysis. SPECIFIC METHOD: To make the presentation more accessible, the atoms in the F-doped molybdenum ditelluride system were colored differently. The pink chain edge atoms were first reversed by θ°. Then, the blue chain edge atoms were reversed by θ° in the other direction. The middle row of atoms was adjusted accordingly to the different twisting angles of the two sides by doing the corresponding torsion with the torsion angle θ°/2 and fixing the individual atoms. The calculation employs the Monkhorst-Pack particular K-point sampling method. The 3 × 3 × 1 inverted-space K-point grid is utilized for material structure optimization calculations in each model, and the 9 × 9 × 1 K-point grid is used for material electronic structure calculations. A 15 Å vacuum layer is put on the crystal surface of vertical monolayer molybdenum ditelluride supercells to avoid interactions with adjoining cells.
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CONTEXT: Based on the first principles under the framework of density functional theory, it calculates the effect of vacancy defects in single Zr and single Se atoms and the replacement of Se atoms in ZrSe2 with O, Se, and Te atoms on the optoelectronic properties of monolayer ZrSe2, including geometry, energy band structure, electronic density of states, and optical properties. The doping of the three non-metallic atoms was n-type doping for the O and S atoms and p-type doping for the Te atom. Defects in the Zr atoms and O-atom doping significantly affect the peak reflectance and absorption coefficient of the ZrSe2 system. METHODS: All Density Functional Theory calculations were carried out using the CASTEP module in the Materials-Studio (MS) software. The generalized gradient approximation plane-wave pseudopotential method and the Perdew-Burke-Ernzerfhof (PBE) generalized function were used for structural optimization and total energy calculation of the defect and doping systems. After convergence tests, the plane wave truncation energy was set to 500 eV, and the Brillouin zone K-point grid was set to 4 × 4 × 1. The atomic energy convergence criterion is 1.0 × 10-6 eV/atom, the interatomic interaction force convergence criterion is 0.02 eV/Å, the maximum atomic displacement convergence criterion is 0.001 Å, and the internal crystal stress convergence criterion is 0.05 GPa. In order to avoid the influence of the interaction forces between the layers, a vacuum layer of 15 Å is placed in the Z-axis direction.
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This paper investigated the performance changes brought about by the adsorption of metal and non-metal atoms on monolayer NbS2. First-principles found that the adsorption of non-metallic atoms on the monolayer NbS2significantly changed the surface structure, with non-metallic atoms other than F intercalated into the upper S atoms. Among them, the F atom adsorption modification system changed the metallic properties of NbS2and tended to transform into a semiconductor. Fe and Co atoms effectively change the real part of the dielectric constant, transforming NbS2into a metamaterial. The adsorption of noble metal atoms can improve the activity of the material. Furthermore, F(Fe, Co) atoms can induce p(n)-type doping by adjusting strain. N adsorption expands the system's electromagnetic wave absorption range and improves the material's electrical conductivity. O and Pt adsorption significantly enhanced the polarizability and photoresponse of the material, resulting in enhanced photocatalytic activity.
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OBJECTIVE: Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against drug resistance in triple-negative breast cancer (TNBC). METHODS: Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol) cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry, CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively. RESULTS: In MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, up-regulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on cell activities were similar to the results of mTOR silencing. After RTEs & Taxol injection, xenograft tumor was smaller, and AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased. CONCLUSION: RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy. MICRO: RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-468/Taxol cells. We may provide a new potential strategy for TNBC treatment.
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Antioxidantes/farmacología , Medicamentos Herbarios Chinos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Ratones , Fitoterapia/métodos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Background: An increasing number of studies have shown that Isthmin 1 (ISM1), a secreted protein, is important in tumorigenesis and invasion, including in colorectal cancer (CRC). However, the mechanisms are still unclear. This study aims to explore the function and prognosis capacity of ISM1 in CRC. Methods: We investigated the expression of ISM1 in 18 CRC tissues vs. adjacent normal tissues from GSE50760, 473 CRC tissues vs. 41 normal tissues from The Cancer Genome Atlas (TCGA), and across gastrointestinal cancer types. Differences were further confirmed in CRC tissues via quantitative real-time polymerase chain reaction (qRT-PCR). Then, we analyzed correlations between clinicopathologic features and ISM1 expression, including prognostic prediction value, using the Kaplan-Meier method and multivariate Cox regression. Gene set enrichment analysis (GSEA) was performed to identify ISM1-related pathways. In vitro experiments were performed to verify the role of ISM1 in epithelial-mesenchymal transition (EMT) and CRC progression. Results: Multiple datasets showed that ISM1 is upregulated in CRC tissues, which was validated. Patients with higher ISM1 expression had shorter overall survival (OS), and ISM1 expression served as an independent prognostic factor. Enrichment analysis showed that ISM1 upregulation was positively correlated with cancer-related pathways, such as EMT, hypoxia, and the Notch and KRAS signaling pathways. We were exclusively interested in the connection between ISM1 and EMT because 71% of genes in this pathway were significantly positively co-expressed with ISM1, which may account for why patients with higher ISM1 expression are prone to regional lymph node involvement and progression to advanced stages. In addition, we found that ISM1 was positively correlated with multiple immunosuppressive pathways such as IL2/STAT5, TNF-α/NF-κB, and TGF-ß, and immune checkpoints, including PD-L1, PD-1, CTLA-4, and LAG3, which may account for upregulation of ISM1 in immunotherapy-resistant patients. Notably, through in vitro experiments, we found that ISM1 promoted EMT and colon cancer cell migration and proliferation. Conclusion: ISM1 is critical for CRC development and progression, which enhances our understanding of the low response rate of CRC to immunotherapy via immunosuppressive signaling pathways.
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BACKGROUND: Evidence suggests that metastasis is chiefly responsible for the poor prognosis of colon adenocarcinoma (COAD). The tumor microenvironment plays a vital role in regulating this biological process. However, the mechanisms involved remain unclear. The aim of this study was to identify crucial metastasis-related biomarkers in the tumor microenvironment and investigate its association with tumor-infiltrating immune cells. METHODS: We obtained gene expression profiles and clinical information from The Cancer Genome Atlas database. According to the "Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data" algorithm, each sample generated the immune and stromal scores. Following correlation analysis, the metastasis-related gene was identified in The Cancer Genome Atlas database and validated in the GSE40967 dataset from Gene Expression Omnibus. The correlation between metastasis-related gene and infiltrating immune cells was assessed using the Tumor IMmune Estimation Resource database. RESULTS: The analysis included 332 patients; the metastatic COAD samples showed a low immune score. Correlation analysis results showed that interferon regulatory factor 1 (IRF1) was associated with tumor stage, lymph node metastasis, and distant metastasis. Furthermore, significant associations between IRF1 and CD8+ T cells, T cell (general), dendritic cells, T-helper 1 cells, and T cell exhaustion were demonstrated by Spearmans correlation coefficients and P values. CONCLUSIONS: The present findings suggest that IRF1 is associated with metastasis and the degree of immune infiltration of CD8+ T cells (general), dendritic cells, T-helper 1 cells, and T cell exhaustion in COAD. These results may provide information for immunotherapy in colon cancer.
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Adenocarcinoma/inmunología , Adenocarcinoma/patología , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Factor 1 Regulador del Interferón/inmunología , Linfocitos T/inmunología , Biomarcadores de Tumor , Linfocitos T CD8-positivos/metabolismo , Bases de Datos Genéticas , Células Dendríticas/metabolismo , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática/inmunología , Estadificación de Neoplasias , Pronóstico , Microambiente TumoralRESUMEN
The tumor microenvironment (TME) has attracted attention owing to its essential role in tumor initiation, progression, and metastasis. With the emergence of immunotherapies for various cancers, and their high efficacy, an understanding of the TME in gastric cancer (GC) is critical. The aim of this study was to investigate the effect of various components within the GC TME, and to identify mechanisms that exhibit potential as therapeutic targets. The ESTIMATE algorithm was used to quantify immune and stromal components in GC samples, whose clinicopathological significance and relationship with predicted outcomes were explored. Low tumor mutational burden and high M2 macrophage infiltration, which are considered immune suppressive characteristics and may be responsible for unfavorable prognoses in GC, were observed in the high stromal group (HR = 1.585; 95% CI, 1.112-2.259; P = 0.009). Furthermore, weighted correlation network, differential expression, and univariate Cox analyses were used, along with machine learning methods (LASSO and SVM-RFE), to reveal genome-wide immune phenotypic correlations. Eight stromal-relevant genes cluster (FSTL1, RAB31, FBN1, ANTXR1, LRRC32, CTSK, COL5A2, and ENG) were identified as adverse prognostic factors in GC. Finally, using a combination of TIMER database and single-sample gene set enrichment analyses, we found that the identified genes potentially contribute to macrophage recruitment and polarization of tumor-associated macrophages. These findings provide a different perspective into the immune microenvironment and indicate potential prognostic and therapeutic targets for GC immunotherapies.
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We investigated the role of the competing endogenous RNA (ceRNA) network in the development and progression of pancreatic adenocarcinoma (PAAD). We analyzed the expression profiles of PAAD and normal pancreatic tissues from multiple GEO databases and identified 457 differentially expressed circular RNAs (DEcircRNAs), 19 microRNAs (DEmiRNAs) and 1993 mRNAs (DEmRNAs). We constructed a ceRNA network consisting of 4 DEcircRNAs, 3 DEmiRNAs and 149 DEmRNAs that regulates the NF-kappa B, PI3K-Akt, and Wnt signaling pathways. We then identified and validated five hub genes, CXCR4, HIF1A, ZEB1, SDC1 and TWIST1, which are overexpressed in PAAD tissues. The expression of CXCR4, HIF1A, ZEB1, and SDC1 in PAAD was regulated by circ-UBAP2 and hsa-miR-494. The expression of CXCR4 and ZEB1 correlated with the levels of M2 macrophages, T-regulatory cells (Tregs) and exhausted T cells in the PAAD tissues. The expression of CXCR4 and ZEB1 positively correlated with the expression of CTLA-4 and PD-1. This suggests that CXCR4 and ZEB1 proteins inhibit antigen presentation and promote immune escape mechanisms in PAAD cells. In summary, our data suggest that the circUBAP2-mediated ceRNA network modulates PAAD by regulating the infiltration and function of immune cells.
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Adenocarcinoma , Carcinogénesis/genética , Proteínas Portadoras/genética , Neoplasias Pancreáticas , Microambiente Tumoral , Adenocarcinoma/genética , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Biomarcadores de Tumor , Transformación Celular Neoplásica , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Neoplasias PancreáticasRESUMEN
Poly(styrene)-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM) amphiphilic diblock copolymers were synthesized via reverse iodine transfer polymerization (RITP) firstly. And then the honeycomb structured porous films were fabricated by drop the amphiphilic diblock copolymer solutions on glass substrates. The porous films were characterized using field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM), respectively. The results showed that the regular honeycomb patterned porous film was achieved successfully by employing the block copolymer with a significantly larger polystyrene block proportion into the solution and the pore diameter of the film decreases obviously with the polymer concentration increased. The effects of airflow speed and Ag particles on porous films are also discussed in this study.