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In order to mitigate the shuttle effect of lithium polysulfides in lithium-sulfur batteries, we propose a yttrium-metal-organic framework-carbon nanotube (Y-MOF-CNT)-derived Y2O3-C@CNT composite for modifying the separator in this study. The Y-MOFs, comprising yttrium (Y) rare earth metal and terephthalic acid, exemplify a prototypical category of metal-organic framework (MOF) materials. They manifest the advantageous attributes associated with MOFs while concurrently possessing distinctive catalytic traits ascribed to rare earth elements. In this study, Y-MOF nanoparticles were synthesized on carbon nanotube (CNT) substrates via a facile aqueous solution method, succeeded by high-temperature carbonization to yield Y2O3-C@CNT composite materials. These composites were subsequently employed as coatings on one side of polyethylene (PE) separators. The resultant Y2O3-C@CNT composite inherits the particle-like morphology and porosity from its precursor Y-MOF, alongside the inherent conductivity in carbon-based materials. This amalgamation is conducive to polysulfide capture and catalytic conversion processes within lithium-sulfur batteries. The application of the Y2O3-C@CNT-coated PE separator effectively mitigated polysulfide shuttle effects and significantly enhanced the battery electrochemical performance. At a sulfur loading level of 3 mg cm-2 under a 0.5 C rate, an initial discharge specific capacity of 900 mAh g-1 was achieved. After 400 cycles, the discharge specific capacity remained at 483.85 mAh g-1 with a capacity retention rate of 53.7%. Upon increasing sulfur loading to 5 mg cm-2, the discharge specific capacity at a lower rate (0.1 C) reached 817.8 mAh g-1; even after 100 cycles, it maintained a value of 700 mAh g-1 with a capacity retention rate of 85.6%. Notably, our modified Y2O3-C@CNT separator demonstrated exceptional cycling stability, even under conditions involving high sulfur loading.
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Background: Our study aims to perform functional exploration and drug prediction of programmed cell death (PCD)-related biomarkers in lung adenocarcinoma (LUAD). Methods: UCSC-Xena obtained LUAD-related genes. DESeq2 screened PCD-specific differentially expressed genes (DEGs), and these DEGs were intersected with genes identified by weighted gene co-expression network analysis (WGCNA) to pinpoint the key genes. KOBAS-i was used for enrichment analysis. String and GeneMania were used to construct protein interaction networks and gene-gene interaction networks, respectively. Using two machine learning algorithms to screen for key genes, and taking the intersection as biomarkers, validating via receiver operating characteristic (ROC) and in vitro experiments. Building a diagnostic model with a nomogram. Construct transcription factor (TF) regulatory network. CIBERSORT was used for immune infiltration analysis. Enrichr predicts targeted drugs and AutodockTools simulates molecular docking. Results: 120 hub genes related to PCD were identified, and an intersection of these genes with DEGs yielded 10 key genes, which were enriched in apoptosis-related pathways. Further machine learning screening of these genes led to the selection of 7 genes, among which 6 genes (FGR, LAPTM5, SIRPA, TLR4, ZEB2, and NLRC4) exhibited significant differences upon ROC validation, ultimately serving as biomarkers, in vitro experiments also confirmed. A nomogram demonstrated their excellent diagnostic performance. These six biomarkers are correlated with the infiltration status of most immune cells, suggesting that they affect LUAD through the immune system. TF regulation analysis identified the upstream miRNAs. Finally, drug prediction yielded three potential drugs: Lenvatinib, methadone, and trimethoprim. Conclusion: PCD-related biomarkers in LUAD were explored, which may contribute to further understanding on PCD in LUAD.
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The M/SSZ-39 catalysts (M = In, Co, Cu, Fe) with different metal species and metal loadings were synthesized using the wet impregnation method on a small-pore SSZ-39 molecular sieve. X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-dehydrogenation and hydrogen temperature program reduction (H2-TPR) were employed to characterize the effects of various metal components and metal loadings on the performance of CH4 selective catalytic reduction of NO reaction (CH4-SCR). The characterization results showed that the In/SSZ-39 catalyst exhibited significantly higher catalytic activity compared to the Cu-, Co-, and Fe/SSZ-39 catalysts, suggesting that indium (In) is a more suitable active ingredient for the CH4-SCR reaction. The xIn/SSZ-39 (x = 1, 2, 3, x represents the In loadings of 1.0 wt%, 2.0 wt% and 3.0 wt%) catalysts, with different In loadings, all present excellent CH4-SCR performance. By varying the In loadings, the type of In species present in the catalyst can be regulated, thus enhancing DeNOx activity and CH4 selectivity in the CH4-SCR reaction. At a low temperature of 400 °C and a low CH4/NO feed ratio (CH4/NO = 1), the 3In/SSZ-39 catalyst, featuring highly active InOx clusters, achieves the best low-temperature CH4-SCR performance, with a high NO conversion rate of up to 90% and a CH4 selectivity of up to 74.2%.
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The shuttle effect of soluble lithium polysulfide (LiPS) is a major obstacle to the practical application of lithium-sulfur (Li-S) batteries. In order to reduce the negative impact of the shuttle effect, Nd-MOF was combined with carbon nanofibers (CNFs) so that Nd-MOF was embedded in the CNFs and the Nd2O3-C/CNF composite was realized as a separation modification material. This embedded structure made the combination between Nd2O3-C and CNFs tighter, and it exhibited better synergistic effects to inhibit the shuttle effect of polysulfides while also enhancing the tensile strength of the separator and improving the safety performance of the battery. Based on these advantages, a lithium-sulfur coin cell with the Nd2O3-C/CNF-modified separator exhibited excellent electrochemical performance.
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BACKGROUND: Esophagogastric junction cancer (EJC) refers to malignant tumors that develop at the junction between the stomach and the esophagus. TUSC1 is a recently identified tumor suppressor gene known for its involvement in various types of cancer. The objective of this investigation was to elucidate the regulatory influence of DNA methylation on TUSC1 expression and its role in the progression of EJC. METHODS: Bioinformatics software was utilized to analyze the expression of TUSC1, enriched pathways, and highly methylated sites in the promoter region. TUSC1 expression in EJC was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry. Methylation-specific PCR was employed to detect the methylation level of TUSC1. To analyze the effects of TUSC1 and 5-AZA-2 on tumor cell proliferation, migration, invasion, cell cycle, and apoptosis, several assays including CCK-8, colony formation, transwell, and flow cytometry were conducted. The expression of MDM2 was assessed using qRT-PCR and WB. WB detected the expression of p53, and p-p53, markers for EJC cell proliferation, epithelial-mesenchymal transition, and apoptosis. The role of TUSC1 in tumor occurrence in vivo was examined using a xenograft mouse model. RESULTS: TUSC1 expression was significantly downregulated in EJC. Overexpression of TUSC1 and treatment with 5-AZA-2 inhibited the malignant progression of EJC cells. In EJC, low methylation levels promoted the expression of TUSC1. Upregulation of TUSC1 suppressed the expression of MDM2 and activated the p53 signaling pathway. Inactivation of this pathway attenuated the inhibitory effect of TUSC1 overexpression on EJC cell proliferation, migration, invasion, and other behaviors. Animal experiments demonstrated that TUSC1 overexpression inhibited EJC tumor growth and metastasis in vivo. CONCLUSION: TUSC1 was commonly downregulated in EJC and regulated by methylation. It repressed the malignant progression of EJC tumors by mediating the p53 pathway, suggesting its potential as a diagnostic and therapeutic target for EJC.
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Proliferação de Células , Metilação de DNA , Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Proteínas Supressoras de Tumor , Humanos , Metilação de DNA/genética , Animais , Proteínas Supressoras de Tumor/genética , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Proliferação de Células/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Progressão da Doença , Junção Esofagogástrica/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Apoptose/genética , Regiões Promotoras Genéticas/genética , Proteína Supressora de Tumor p53/genética , Masculino , Movimento Celular/genética , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Camundongos NusRESUMO
Lithium sulfur battery is a novel kind of secondary battery which has high energy density, however its application is greatly affected by the shuttle effect of polysulfides generated in the redox reaction of cathode electrode. Metal active sites are supposed as effective catalysts which can absorb and accelerate the conversion efficiency of lithium polysulfides, thus the shuttle effect will be alleviated. In this work, we conducted a simple way to prepare a metal Fe doped ketjen black to serve as the sulfur host of lithium sulfur battery. Ketjen black has a large specific surface area and rich porous structure, while Fe nanodot is an excellent catalyst for lithium polysulfides. Because of these advantages, the Fe/KB host can effectively confine a large amount of active material and accelerate its, therefore the Fe/KB-S cathode electrode show an excellent electrochemical performance.
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BACKGROUND: The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. AIM: To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma. METHODS: We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs). RESULTS: Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group. CONCLUSION: In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.
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A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust in vivo compound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.
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Proteínas Serina-Treonina Quinases , eIF-2 Quinase , Humanos , Camundongos , Ratos , Animais , Proteínas Serina-Treonina Quinases/metabolismo , eIF-2 Quinase/metabolismo , Camundongos Endogâmicos C57BL , RNA , Retículo Endoplasmático/metabolismoRESUMO
Novel materials displaying multiple exceptional properties are the backbone of the advancement of various industries. In the field of carbon materials, the combination of different properties has been extensively developed to satisfy diverse application scenarios, for instance, conductivity paired with exceptional hardness, outstanding toughness coupled with super-hardness, or heat resistance combined with super-hardness. In this work, a new carbon allotrope, bcc-C40 carbon, was predicted and investigated using first-principles calculations based on density functional theory. The allotrope exhibits unique structural features, including a combination of sp3 hybridized diatomic carbon and four-fold carbon chains. The mechanical and dynamic stability of bcc-C40 carbon has been demonstrated by its elastic constants and phonon spectra. Additionally, bcc-C40 carbon exhibits remarkable mechanical properties, such as zero homogeneous Poisson's ratio, superhardness with a value of 58 GPa, and stress-adaptive toughening. The analysis of the electronic properties demonstrates that bcc-C40 carbon is a semiconductor with an indirect band gap of 3.255 eV within the HSE06 functional, which increases with the increase in pressure. At a pressure of 150 GPa, bcc-C40 carbon transforms into a direct band gap material. These findings suggest the prospective use of bcc-C40 carbon as a superhard material and a novel semiconductor.
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Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.
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Grain boundaries (GBs), with their diversity in both structure and structural transitions, play an essential role in tailoring the properties of polycrystalline materials1-5. As a unique GB subset, {112} incoherent twin boundaries (ITBs) are ubiquitous in nanotwinned, face-centred cubic materials6-9. Although multiple ITB configurations and transitions have been reported7,10, their transition mechanisms and impacts on mechanical properties remain largely unexplored, especially in regard to covalent materials. Here we report atomic observations of six ITB configurations and structural transitions in diamond at room temperature, showing a dislocation-mediated mechanism different from metallic systems11,12. The dominant ITBs are asymmetric and less mobile, contributing strongly to continuous hardening in nanotwinned diamond13. The potential driving forces of ITB activities are discussed. Our findings shed new light on GB behaviour in diamond and covalent materials, pointing to a new strategy for development of high-performance, nanotwinned materials.
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INTRODUCTION: The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases. METHODS: Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis. RESULT: The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD. CONCLUSION: This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Metabolismo dos Lipídeos , Adenocarcinoma de Pulmão/genética , Carcinogênese , Transcriptoma , Neoplasias Pulmonares/genética , Microambiente Tumoral , PrognósticoRESUMO
Compared with traditional structure prediction methods, the purposeful bottom-up approach is better able to obtain structures with specified performance. In this study, we established two novel carbon phases in purely sp2-bonded networks, termed H61-carbon and H62-carbon, using a self-assembling approach. These carbyne-connected carbon allotropes had helix chains joined by cumulative double-bond chains. We certified the new carbon allotropes to be dynamically and mechanically stable. Both of these carbon allotropes exhibited excellent mechanical properties, and they had metallic and superconductive characteristics featuring superconducting transition temperatures of 10 K (H61-carbon) and 7.4 K (H62-carbon), respectively. These results provide an important strategy for the design of novel carbon allotropes with specified properties.
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OBJECTIVES: This research aimed to construct a prediction model for stages II and III cardia carcinoma (CC), and provide an effective preoperative evaluation tool for clinicians. METHODS: CC mRNA expression matrix was obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. Non-negative matrix factorization was used to cluster data to obtain subgroup information, and weighted gene co-expression network analysis was used to uncover key modules linked to different subgroups. Gene-set enrichment analysis analyzed biological pathways of different subgroups. The related pathways of multiple modules were scrutinized with Kyoto Encyclopedia of Genes and Genomes. Key modules were manually annotated to screen CC-related genes. Subsequently, quantitative real-time polymerase chain reaction assessed CC-related gene expression in fresh tissues and paraffin samples, and Pearson correlation analysis was performed. A classification model was constructed and the predictive ability was evaluated by the receiver operating characteristic curve. RESULTS: CC patients had four subgroups that were associated with brown, turquoise, red, and black modules, respectively. The CC-related modules were mainly associated with abnormal cell metabolism and inflammatory immune pathways. Then, 76 CC-elated genes were identified. Pearson correlation analysis presented that THBS4, COL14A1, DPYSL3, FGF7, and SVIL levels were relatively stable in fresh and paraffin tissues. The area under the curve of 5-gene combined prediction for staging was 0.8571, indicating good prediction ability. CONCLUSIONS: The staging classifier for CC based on THBS4, COL14A1, DPYSL3, FGF7, and SVIL has a good predictive effect, which may provide effective guidance for whether CC patients need emergency surgery.
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Carcinoma , Neoplasias Gástricas , Humanos , Cárdia , Parafina , Neoplasias Gástricas/genética , AlgoritmosRESUMO
Traditional ceramics or metals cannot simultaneously achieve ultrahigh strength and high electrical conductivity. The elemental carbon can form a variety of allotropes with entirely different physical properties, providing versatility for tuning mechanical and electrical properties in a wide range. Here, by precisely controlling the extent of transformation of amorphous carbon into diamond within a narrow temperature-pressure range, we synthesize an in situ composite consisting of ultrafine nanodiamond homogeneously dispersed in disordered multilayer graphene with incoherent interfaces, which demonstrates a Knoop hardness of up to ~53 GPa, a compressive strength of up to ~54 GPa and an electrical conductivity of 670-1,240 S m-1 at room temperature. With atomically resolving interface structures and molecular dynamics simulations, we reveal that amorphous carbon transforms into diamond through a nucleation process via a local rearrangement of carbon atoms and diffusion-driven growth, different from the transformation of graphite into diamond. The complex bonding between the diamond-like and graphite-like components greatly improves the mechanical properties of the composite. This superhard, ultrastrong, conductive elemental carbon composite has comprehensive properties that are superior to those of the known conductive ceramics and C/C composites. The intermediate hybridization state at the interfaces also provides insights into the amorphous-to-crystalline phase transition of carbon.
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The reinforcements represented by graphene nanoplatelets, graphite, and carbon nanotubes have demonstrated the great potential of carbon materials as reinforcements to enhance the mechanical properties of TiO2. However, it is difficult to successfully prepare TiO2-diamond composites because diamond is highly susceptible to oxidation or graphitization at relatively high sintering temperatures. In this work, the TiO2-diamond composites were successfully prepared using high-pressure sintering. The effect of diamond on the phase composition, microstructure, mechanical properties, and tribological properties was systemically investigated. Diamond can improve fracture toughness by the crack deflection mechanism. Furthermore, the addition of diamond can also significantly reduce the friction coefficient. The composite composed of 10 wt.% diamond exhibits optimum mechanical and tribological properties, with a hardness of 14.5 GPa, bending strength of 205.2 MPa, fracture toughness of 3.5 MPaâm1/2, and a friction coefficient of 0.3. These results enlarge the family of titania-based composites and provide a feasible approach for the preparation of TiO2-diamond composites.
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The traditional hardness-toughness tradeoff poses a substantial challenge for the development of superhard materials. Due to strong covalent bonds and intrinsic brittleness, the full advantage of microstructure engineering for enhanced mechanical properties requires further exploration in superhard materials. Here heterogeneous diamond-cBN composites were synthesized from a carefully prepared precursor (hBN microflakes uniformly wrapped by onion carbon nanoparticles) through phase transitions under high pressure and high temperature. The synthesized composites inherit the architecture of the precursors: cBN regions with an anisotropic profile that spans several micrometers laterally and several hundred nanometers in thickness are embedded in a nanograined diamond matrix with high-density nanotwins. A significantly high fracture toughness of 16.9 ± 0.8 MPa m1/2 is achieved, far beyond those of single-crystal diamond and cBN, without sacrificing hardness. A detailed TEM analysis revealed multiple toughening mechanisms closely related to the microstructure. This work sheds light on microstructure engineering in superhard materials for excellent mechanical properties.
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BACKGROUND: Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of C12orf48 in gastric cancer are largely unknown. METHODS: We used bioinformatics approaches and tissue microarray immunohistochemistry to analyze the expression profile of C12orf48 in gastric cancer tissues. Plasmid-mediated over-expression or knockdown were performed. CCK-8 assays and flow cytometry were employed to evaluate cellular proliferation and apoptosis respectively. Transwell assays were used to assess migrative and invasive abilities. The roles of C12orf48 were also evaluated in a xenograft tumor model. RESULTS: We found that C12orf48 was over-expressed in gastric cancer tissue, which associated with advanced stage and poor prognosis. In vitro and in vivo experiments showed depletion of C12orf48 attenuated cancer growth, while facilitated apoptosis. Further, the expression of Poly r(C)-Binding Protein (PCBP) 1 was found negatively regulated by C12orf48. Intended up-regulation of PCBP1 prevented C12orf48-mediated proliferation and rescued cells from apoptosis. Besides, C12orf48 promoted cellular migration and invasion, with E-cadherin down-regulated while vimentin and N-cadherin up-regulated, which was reversed by up-regulated PCBP1. CONCLUSIONS: Our findings indicate that depletion of C12orf48 inhibited gastric cancer growth and metastasis via up-regulating PCBP1. Targeting C12orf48-PCBP1 axis may be a potential therapeutic strategy.