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Aqueous zinc ion batteries (ZIBs) hold promises as a safer, more cost-effective, and environmental-friendly alternative to lithium-ion batteries, especially for stationary energy storage. Recent advancements in protective anode coatings, which fine-tune zinc ion solvation structure, have yielded significant improvements in the aqueous ZIB performance, addressing dendrite formation and side reactions, thereby prolonging cycle lifetime. Understanding the underlying mechanisms of these coatings as ions sieves is crucial for further optimization and achieving long-term stability, which is a key requirement for practical applications. This concept explores recent developments in ZIB anode coatings from the view of molecular mechanisms and points out future research directions.
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Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.
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Infecciones por VIH , Profilaxis Pre-Exposición , Piridonas , Humanos , Farmacóforo , Dicetopiperazinas , Infecciones por VIH/prevención & controlRESUMEN
This meta-analysis aims to comprehensively assess the impact of laparoscopic radical prostatectomy (LRP) on wound infection in patients with prostate cancer (PCa). A systematic search was conducted, from database inception to November 2023, in EMBASE, Google Scholar, Cochrane Library, PubMed, Wanfang and China National Knowledge Infrastructure databases for randomized controlled trials (RCTs) comparing LRP with open radical prostatectomy (ORP) in the treatment of PCa. Two researchers independently screened the literature, extracted data and conducted quality assessments based on pre-defined inclusion and exclusion criteria. Stata 17.0 software was employed for data analysis. Overall, 15 RCTs involving 1458 PCa patients were included. The analysis revealed the incidence of wound infection (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.16-0.51, p < 0.001) and complications (OR = 0.27, 95% CI = 0.20-0.37, p < 0.001) was significantly lower in the LRP group compared to the ORP group. This study demonstrates that LRP in PCa patients can effectively reduce the incidence of wound infections and complications, indicating significant therapeutic efficacy and justifying its broader clinical application.
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Laparoscopía , Prostatectomía , Neoplasias de la Próstata , Infección de la Herida Quirúrgica , Humanos , Masculino , Prostatectomía/métodos , Prostatectomía/efectos adversos , Neoplasias de la Próstata/cirugía , Laparoscopía/métodos , Laparoscopía/efectos adversos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Persona de Mediana Edad , Anciano , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Pancreatic cancer (PC) has the lowest survival rate and the highest mortality rate among all cancers due to lack of effective treatments. The objective of the current study was to identify potential therapeutic targets in PC. Three transcriptome datasets, namely GSE62452, GSE46234, and GSE101448, were analyzed for differentially expressed genes (DEGs) between cancer and normal samples. Several bioinformatics methods, including functional analysis, pathway enrichment, hub genes, and drugs were used to screen therapeutic targets for PC. Fisher's exact test was used to analyze functional enrichments. To screen DEGs, the paired t-test was employed. The statistical significance was considered at p <0.05. Overall, 60 DEGs were detected. Functional enrichment analysis revealed enrichment of the DEGs in "multicellular organismal process", "metabolic process", "cell communication", and "enzyme regulator activity". Pathway analysis demonstrated that the DEGs were primarily related to "Glycolipid metabolism", "ECM-receptor interaction", and "pathways in cancer". Five hub genes were examined using the protein-protein interaction (PPI) network. Among these hub genes, 10 known drugs targeted to the CPA1 gene and CLPS gene were found. Overall, CPA1 and CLPS genes, as well as candidate drugs, may be useful for PC in the future.
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Perfilación de la Expresión Génica , Neoplasias Pancreáticas , Humanos , Perfilación de la Expresión Génica/métodos , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Biología Computacional/métodos , Neoplasias PancreáticasRESUMEN
Functional porous coating on zinc electrode is emerging as a powerful ionic sieve to suppress dendrite growth and side reactions, thereby improving highly reversible aqueous zinc ion batteries. However, the ultrafast charge rate is limited by the substantial cation transmission strongly associated with dehydration efficiency. Here, we unveil the entire dynamic process of solvated Zn2+ ions' continuous dehydration from electrolyte across the MOF-electrolyte interface into channels with the aid of molecular simulations, taking zeolitic imidazolate framework ZIF-7 as proof-of-concept. The moderate concentration of 2â M ZnSO4 electrolyte being advantageous over other concentrations possesses the homogeneous water-mediated ion pairing distribution, resulting in the lowest dehydration energy, which elucidates the molecular mechanism underlying such concentration adopted by numerous experimental studies. Furthermore, we show that modifying linkers on the ZIF-7 surface with hydrophilic groups such as -OH or -NH2 can weaken the solvation shell of Zn2+ ions to lower the dehydration free energy by approximately 1â eV, and may improve the electrical conductivity of MOF. These results shed light on the ions delivery mechanism and pave way to achieve long-term stable zinc anodes at high capacities through atomic-scale modification of functional porous materials.
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Membrane separation is an energy-efficient and environmentally friendly process. Two-dimensional (2D) molecular sieving membranes featuring unique nanopores and low transport resistance have the potential to achieve highly permeable and selective mixture separation with low energy consumption. High-aspect-ratio zeolite nanosheets with intrinsic molecular-sieving pores perpendicular to the layers are desirable building blocks for fabricating high-performance 2D zeolite membrane. However, a wider application of 2D zeolitic membranes is restricted by the limited number of recognized zeolite nanosheets. Herein, we report a swollen layered zeolite, ECNU-28, with SZR topology and eight-member ring (8-MR, 3.0â Å×4.8â Å) pores normal to the nanosheets. It can be easily exfoliated to construct 2D membrane, which shows a high hydrogen selectivity up to 130 from natural gas and is promising for hydrogen purification and greenhouse gas capture.
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Nanoporos , Zeolitas , Cromatografía Liquida , HidrógenoRESUMEN
BACKGROUND: The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated. METHODS: 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry. RESULTS: The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis. CONCLUSIONS: Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.
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Trasplante de Riñón , Riñón/fisiopatología , Receptor de Muerte Celular Programada 1/metabolismo , Células T Auxiliares Foliculares/fisiología , Adulto , Aloinjertos , Biomarcadores , Linfocitos T CD8-positivos/fisiología , Femenino , Rechazo de Injerto/diagnóstico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/fisiología , Curva ROC , Receptores CXCR5/metabolismo , Células T Auxiliares Foliculares/metabolismoRESUMEN
Physical-layer key generation technology requires information reconciliation to correct channel estimation errors between two legitimate users. However, sending the reconciliation signals over the public channel increases the communication overhead and the risk of information leakage. Aiming at the problem, integrated secure communication schemes using non-reconciled keys have attracted extensive attention. These schemes exploit channel coding to correct both inconsistent keys and transmission error bits. Meanwhile, more redundant code bits must be added to correct errors, which results in a lower secure transmission rate. To address the problem, we analyze the merit of channel correlation between non-reconciled key generation and secure transmission. Inspired by this, we propose a non-reconciled physical-layer keys-assisted secure communication scheme based on channel correlation. First of all, the signal frame is designed to make use of channel correlation between non-reconciled key generation and secure transmission. Based on the channel correlation, non-reconciled keys are then generated from the wireless channel to encrypt transmitted data. Moreover, an adaptive coding algorithm based on the equivalent channel is presented to encode the data bits before encryption, to guarantee reliable transmission. Finally, theoretical analysis and simulations demonstrate the significant performance of the proposed scheme in terms of low bit error ratio and high secure transmission rate.
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BACKGROUND AND AIMS: Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. APPROACH AND RESULTS: RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis. CONCLUSION: These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.
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Carcinogénesis , Colangiocarcinoma/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Represoras/metabolismo , Animales , Apoptosis , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Línea Celular , Transformación Celular Neoplásica/metabolismo , Colangiocarcinoma/patología , Resistencia a Antineoplásicos , Humanos , Ratones , Estrés OxidativoRESUMEN
In recent years, transition-metal-catalyzed tandem cyclization reactions of alkynes, especially those involving a metal carbene intermediate, have received worthwhile interest, as this type of reaction does not require the use of risky and potentially explosive diazo compounds as starting materials for carbene generation. A significant and general strategy for the stereospecific synthesis of 5-membered cycles is Nazarov cyclization based on the 4π-conrotatory electrocyclization of a conjugated pentadienyl cation to afford a cyclopentenyl cation. In this review, we introduce an overview of recent advances in the transition-metal-catalyzed Nazarov cyclization of alkynes via a metal carbene intermediate, and categorize these reactions according to the structure of the metal carbene. Our aim is to accelerate advancements in this enchanting area of research.
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In this work, the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach was applied to calculate the 13C and 1H nuclear magnetic resonance (NMR) chemical shifts in molecular crystals. Two benchmark sets of molecular crystals were selected to calculate the NMR chemical shifts. Systematic investigation was conducted to examine the convergence of AF-QM/MM calculations and the impact of various density functionals with different basis sets on the NMR chemical shift prediction. The result demonstrates that the calculated NMR chemical shifts are close to convergence when the distance threshold for the QM region is larger than 3.5 Å. For 13C chemical shift calculations, the mPW1PW91 functional is the best density functional among the functionals chosen in this study (namely, B3LYP, B3PW91, M06-2X, M06-L, mPW1PW91, OB98, and OPBE), while the OB98 functional is more suitable for the 1H NMR chemical shift prediction of molecular crystals. Moreover, with the B3LYP functional, at least a triple-ζ basis set should be utilized to accurately reproduce the experimental 13C and 1H chemical shifts. The employment of diffuse basis functions will further improve the accuracy for 13C chemical shift calculations, but not for the 1H chemical shift prediction. We further proposed a fragmentation scheme of dividing the central molecule into smaller fragments. By comparing with the results of the fragmentation scheme using the entire central molecule as the core region, the AF-QM/MM calculations with the fragmented central molecule can not only achieve accurate results but also reduce the computational cost. Therefore, the AF-QM/MM approach is capable of predicting the 13C and 1H NMR chemical shifts for molecular crystals accurately and effectively, and could be utilized for dealing with more complex periodic systems such as macromolecular polymers and biomacromolecules. The AF-QM/MM program for molecular crystals is available at https://github.com/shiman1995/NMR.
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Metal-organic framework membranes are usually prepared by in situ or secondary growth in a solution/hydrogel. The use of organic solvents may cause safety and environmental problems and produce solvent-induced defects. Here, highly oriented and permselective ZIF-95 membranes are prepared for the first time via a solvent-free secondary growth method. The solvent-free growth is not only helpful to control the membrane microstructure and thickness, but also to reduce the intercrystalline defects. In case of solvent-free growth, a perfectly oriented structure leads to an outstanding reduction of intercrystalline defects and transport resistances. For the separation of equimolar binary gas mixtures by using the highly oriented ZIF-95 membrane at 25 °C and 1â bar, the mixture separation factors of H2 /CO2 and H2 /CH4 are 184 and 140, respectively, with H2 permeance of over 1.9×10-7 â mol m-2 s-1 Pa-1 which are much higher than those of the randomly oriented ZIF-95 membrane.
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Here we report a series of nonequilibrium dynamic Monte Carlo simulations combined with dual control volume (DCV-DMC) to explore the separation selectivity of CH4/CO2 gas mixtures in the ZIF-8 membrane with a thickness of up to about 20 nm. Meanwhile, an improved DCV-DMC approach coupled with the corresponding potential map (PM-DCV-DMC) is further developed to speed up the computational efficiency of conventional DCV-DMC simulations. Our simulation results provide the molecular-level density and selectivity profiles along the permeation direction of both CH4 and CO2 molecules in the ZIF-8 membrane, indicating that the parts near membrane surfaces at both ends play a key role in determining the separation selectivity. All densities initially show a sharp increase in the individual maximum within the first outermost unit cell at the feed side and follow a long fluctuating decrease process. Accordingly, the corresponding selectivity profiles initially display a long fluctuating increase in the individual maximum and follow a sharp decrease near the membrane surface at the permeation side. Furthermore, the effects of feed composition, temperature, and pressure on the relevant separation selectivity are also discussed in detail, where the temperature has a greater influence on the separation selectivity than the feed composition and pressure. More importantly, the predicted separation selectivities from our PM-DCV-DMC simulations are well consistent with previous experimental results.
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Dióxido de Carbono , Simulación por Computador , Gases , Adsorción , Metano , Método de MontecarloRESUMEN
BACKGROUND: Neurodegenerative diseases are characterized by a gradual decline in motor and/or cognitive function caused by the selective degeneration and loss of neurons in the central nervous system, but their pathological mechanism is still unclear. Previous research has revealed that many forms of cell death, such as apoptosis and necrosis, occur in neurodegenerative diseases. Research in recent years has noticed that there is a new type of cell death in neurodegenerative diseases: ferroptosis. An increasing body of literature provides evidence for an involvement of ferroptosis in neurodegenerative diseases. SUMMARY: In this article, we review a new form of cell death in neurodegenerative diseases: ferroptosis. Ferroptosis is defined as an iron-dependent form of regulated cell death, which occurs through the lethal accumulation of lipid-based reactive oxygen species when glutathione-dependent lipid peroxide repair systems are compromised. Several salient and established features of neurodegenerative diseases (including lipid peroxidation and iron dyshomeostasis) are consistent with ferroptosis, which means that ferroptosis may be involved in the progression of neurodegenerative diseases. In addition, as the center of energy metabolism in cells, mitochondria are also closely related to the regulation of iron homeostasis in the nervous system. At the same time, neurodegenerative diseases are often accompanied by degeneration of mitochondrial activity. Mitochondrial damage has been found to be involved in lipid peroxidation and iron dyshomeostasis in neurodegenerative diseases. Key Messages: Based on the summary of the related mechanisms of ferroptosis, we conclude that mitochondrial damage may affect neurodegenerative diseases by regulating many aspects of ferroptosis, including cell metabolism, iron dyshomeostasis, and lipid peroxidation.
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Apoptosis , Ferroptosis , Hierro/metabolismo , Mitocondrias , Enfermedades Neurodegenerativas/fisiopatología , Peroxidación de Lípido , Mitocondrias/metabolismo , Mitocondrias/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Control of the microstructure grain orientation, grain boundaries and thickness are crucial for MOF membranes. We report a novel synthesis strategy to prepare highly c-oriented ZIF-95 membranes through vapor-assisted in-plane epitaxial growth. In a mixed DMF/water vapor atmosphere, in-plane epitaxial growth of a ZIF-95 seeds layer was achieved to obtain an oriented and well-intergrown ZIF-95 membrane with a thickness of only 600â nm. Demonstrated by both experimental and simulation studies, the c-oriented ZIF-95 membrane displayed superior separation performance because a perfectly oriented structure resulted in a notable reduction of intercrystalline defects and transport pathways. For the separation of equimolar binary mixtures at 100 °C and 1â bar, the mixture separation factors of H2 /CO2 and H2 /CH4 were 32.2 and 53.7, respectively, with an H2 permeance of over 7.9×10-7 â mol m-2 s-1 Pa-1 , which was 4.6 times higher than that of a randomly oriented ZIF-95 membrane.
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BACKGROUND: Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF. METHODS: Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database. RESULTS: We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process. CONCLUSION: In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.
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Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Melanoma/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Proteína 61 Rica en Cisteína/genética , Fosfatasa 1 de Especificidad Dual/genética , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética/métodos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Ribonucleasas/genética , Análisis de Supervivencia , Melanoma Cutáneo MalignoRESUMEN
As one of the major cell organelles responsible for ATP production, it is important that neurons maintain mitochondria with structural and functional integrity; this is especially true for neurons with high metabolic requirements. When mitochondrial damage occurs, mitochondria are able to maintain a steady state of functioning through molecular and organellar quality control, thus ensuring neuronal function. And when mitochondrial quality control (MQC) fails, mitochondria mediate apoptosis. An apparently key molecule in MQC is the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α). Recent findings have demonstrated that upregulation of PGC-1α expression in neurons can modulate MQC to prevent mitochondrial dysfunction in certain in vivo and in vitro aging or neurodegenerative encephalopathy models, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease. Because mitochondrial function and quality control disorders are the basis of pathogenesis in almost all neurodegenerative diseases (NDDs), the role of PGC-1α may make it a viable entry point for the treatment of such diseases. This review focuses on multi-level MQC in neurons, as well as the regulation of MQC by PGC-1α in these major NDDs.
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Enfermedad de Alzheimer/fisiopatología , Enfermedad de Huntington/fisiopatología , Mitocondrias/fisiología , Enfermedad de Parkinson/fisiopatología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/fisiología , Animales , Humanos , Neuronas/fisiología , Biogénesis de OrganelosRESUMEN
This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient's colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein-protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2, ACTG2, MYH11, CALD1, MYL9, TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Transducción de Señal/genética , Edad de Inicio , Neoplasias Colorrectales/patología , Conjuntos de Datos como Asunto , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Humanos , Mapas de Interacción de Proteínas/genética , Análisis de Matrices Tisulares/métodos , Regulación hacia ArribaRESUMEN
BACKGROUND: Increasing evidence indicates that Six2 contributes to tumorigenesis in various tumor including hepatocellular carcinoma (HCC). This study aimed to determine the role of Six2 in HCC and to elucidate the association of Six2 with clinical pathological characteristics. METHODS: The expressions of Six2 in HCC tumor, para-tumor tissue and portal vein tumor thrombus (PVTT) were detected by tissue microarray technique, immunohistochemistry, real-time RT-PCR and Western blotting. Chi-square and Kaplan-Meier analysis were used to analyze the correlation between Six2 expression and prognosis of HCC patients. Lentivirus mediated Six2 knockdown, spheroid formation assay, proliferation assay and subcutaneous tumor implantation were performed to determine the function of Six2. RESULTS: In 274 HCC samples, Six2 was strongly expressed. Kaplan-Meier analysis revealed that high expression of Six2 was correlated with a shorter overall survival (OS) and disease-free survival (DFS). Moreover, Six2 expression was associated with sex, alpha-fetoprotein, tumor size and portal vein invasion. Six2 was highly expressed in PVTT. Six2 knockdown inhibited HCC cell lines proliferation, migration, and self-renewal in vitro and in vivo. In addition, low-expression of Six2 weakened TGF-ß induced Smad4 activation and epithelial-mesenchymal transition in HCC cell lines. CONCLUSIONS: Elevated Six2 expression in HCC tumor patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-ß/Smad signal pathway.