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Background Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Methods Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. Results In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer. Conclusions Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

Gastric cancer of young adults is poorly differentiated and has a poor prognosis. However, there are few reports regarding the genetic alteration in gastric cancer of young adults. Bioinformatics methods were used to screen the key genes and signaling pathways of gastric cancer in young adults, and molecular biology techniques were used to verify the key proteins involved in the occurrence and development of gastric cancer in young adults. RNA expression profile microarray data of gastric cancer patients ≤ 45 years old and > 45 years old were downloaded from the TCGA database, and differentially expressed genes were screened by Limma package. GO analysis and KEGG enrichment analysis of DEG were performed in the Gene Function annotation database (DAVID). CytoHubba is used to construct protein interaction networks (PPI) and perform visual analysis to screen out core genes. We obtained 10 hub molecules, including FBXO44, FBXO6, HERC5, FBXL13, FBXO41, NT5E, BMP4, TRIM36, ACAN, ALPL by PPI network with MCODE. Ingenuity Pathway Analysis predicts TBX1, DFNB31, TGFBR3, FBXO44, SLC7A8, DNM1, KITLG, MSH5, MLLT3, DUSP5, ADAMTSL4, ACPP and TBX1 as the transcription factors directly regulated by OTX2. OTX2 had the highest positive expression rate in gastric cancer of young adults by immunohistochemistry. Interference with OTX2 expression inhibits proliferation, migration, invasion and promotes differentiation, apoptosis of NUGC-4 cells (from 35 year old female). Moreover, after interfering OTX2 expression, the downstream proteins and signaling Pathways of OTX2 in NUGC-4 were further analyzed by Transcriptome sequencing and Ingenuity Pathways Analysis. We found interference with OTX2 expression inhibits CEBPB expression and activates calcitriol by IPA analysis, thereby promoting differentiation of NUGC-4. Therefore, OTX2 plays important roles in restraining the differentiation and promoting progression of gastric cancer cells in young adults. Moreover, OTX2/CEBPB signal axis is likely to be a key molecular event in regulating the differentiation of gastric cancer cells in young adults.

Background Approximately 5.0–24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients. Methods A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS). Results Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28–1.67, P  = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14–2.22, P  = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01–1.31, P  = 0.042), TNM stage (OR = 1.28, stage IV/I–III, 95% CI 1.03–1.58, P  = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20–1.67, P  < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85–2.70, P  < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37–3.34, P  = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study. Conclusions This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.

Background: Gastric cancer (GC) is a worldwide popular malignant tumor. However, the survival rate of advanced GC remains low. Pyroptosis and long non-coding RNAs (lncRNAs) are important in cancer progression. Thus, we aimed to find out a pyroptosis-related lncRNAs (PRLs) signature and use it to build a practical risk model with the purpose to predict the prognosis of patients with GC. Methods: Univariate Cox regression analysis was used to identify PRLs linked to GC patient’s prognosis. Subsequently, to construct a PRLs signature, the least absolute shrinkage and selection operator regression, and multivariate Cox regression analysis were used. Kaplan–Meier analysis, principal component analysis, and receiver operating characteristic curve analysis were performed to assess our novel lncRNA signature. The correlation between risk signature and clinicopathological features was also examined. Finally, the relationship of pyroptosis and immune cells were evaluated through the CIBERSORT tool and single-sample lncRNA set enrichment analysis (ssGSEA). Results: A PRLs signature comprising eight lncRNAs was discerned as a self-determining predictor of prognosis. GC patients were sub-divided into high-risk and low-risk groups via this risk-model. Stratified analysis of different clinical factors also displayed that the PRLs signature was a good prognosis factor. According to the risk score and clinical characteristics, a nomogram was established. Moreover, the difference between the groups is significance in immune cells and immune pathways. Conclusion: This study established an effective prognostic signature consist of eight PRLs in GC, and constructed an efficient nomogram model. Further, the PRLs correlated with immune cells and immune pathways.

This study evaluated the effectiveness of scleral taping combined with C3F8 gas filling for the management of complex retinal detachment (CRD) and to objectively assessed its clinical value. Forty consecutive patients (40 eyes) with CRD who underwent surgical treatment were included. Patients were divided into two groups: the study group underwent scleral buckling (SB) combined with C3F8 gas filling, and the control group received scleral buckling alone. Each group comprised 20 patients (20 eyes). After anaesthesia, traction sutures were placed at the rectus muscle in all patients. Retinal breaks and degenerative areas were examined and treated with cryotherapy. A silicone sponge was positioned on the scleral surface, and the sutures were tightened to produce an indenting effect. Additionally, patients in the study group received an intravitreal injection of C3F8 gas. Both uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) improved in the study and control groups on the first post-operative day. However, the improvement was statistically significant only in the control group. Visual acuity in both groups improved significantly at 1 week, 1 month, and 3 months post-operatively compared with baseline and the first post-operative day. Intraocular pressure (IOP) in the study group was significantly elevated at 1 week, 1 month, and 3 months post-operatively compared with baseline. The retinal reattachment rate was 95% in the study group, significantly higher than 70% in the control group. The recurrence rate was 5% in the study group. No serious complications, including retinal incarceration, haemorrhage, anterior segment ischemia, or infection, were observed in either group. Scleral buckling combined with C3F8 gas filling is a safe and effective treatment for CRD. It significantly improves post-operative visual acuity, enhances retinal reattachment, reduced the recurrence rate with minimal complications.

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diagenode Inc, Denville, NJ, USA), the best performing kit in that study. We find that both MethylMiner and MethylCap are two well performing MBD-enrichment kits. However, MethylMiner shows somewhat better enrichment efficiency and lower levels of background \"noise\". In addition, for the purpose of MWAS where we want to investigate the majority of CpGs, we find MethylMiner to be superior as it allows tailoring the enrichment to the regions where most CpGs are located. Using targeted bisulfite sequencing we confirmed that sites where methylation was detected by either MethylMiner or by MethylCap indeed were methylated.

In this study, five kinds of (Zr0.2Ta0.2Ti0.2Cr0.2Hf0.2)Si2 high-entropy ceramics were prepared by a two-step method under different vacuum pressureless pre-sintering processes, and the microstructures and mechanical properties of the ceramics under different parameters of the pre-sintering process were systematically discussed. The results show that the physical structure of the ceramic samples remains basically unchanged by changing the pre-sintering conditions; the longer the holding time of the initial pre-sintering, the higher the densification of the samples and all of them are above 95%. The hardness of the ceramics was around 10 GPa, with the best hardness of 10.11 GPa at 1300 °C for 3 h. This conclusion provides data support for the optimization of the high-entropy ceramics preparation process.

In this study, five kinds of (Zr[sub.0.2]Ta[sub.0.2]Ti[sub.0.2]Cr[sub.0.2]Hf[sub.0.2])Si[sub.2] high-entropy ceramics were prepared by a two-step method under different vacuum pressureless pre-sintering processes, and the microstructures and mechanical properties of the ceramics under different parameters of the pre-sintering process were systematically discussed. The results show that the physical structure of the ceramic samples remains basically unchanged by changing the pre-sintering conditions; the longer the holding time of the initial pre-sintering, the higher the densification of the samples and all of them are above 95%. The hardness of the ceramics was around 10 GPa, with the best hardness of 10.11 GPa at 1300 °C for 3 h. This conclusion provides data support for the optimization of the high-entropy ceramics preparation process.

Messenger RNA vaccines have shown strong prophylactic efficacy against viral infections. Here we show that antigen-encoding small circular RNAs (circRNAs) loaded in lipid nanoparticles elicit potent and durable T cell responses for robust tumour immunotherapy after subcutaneous injection in mice, particularly when combined with immune checkpoint inhibition. The small circRNA vaccines are highly stable and show low levels of activation of protein kinase R as well as low cytotoxicity, enabling long-lasting antigen translation (longer than 1 week in cells). Relative to large protein-encoding unmodified or modified mRNAs and circRNAs, small circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice and accounted for 30–75% of the total peripheral CD8 + T cells over 6 months. Small circRNA vaccines encoding tumour-associated antigens, neoantigens and oncoviral or viral antigens elicited substantial CD8 + and CD4 + T cell responses in young adult mice and in immunosenescent aged mice. Combined with immune checkpoint inhibition, monovalent and multivalent circRNA vaccines reduced tumour-induced immunosuppression and inhibited poorly immunogenic mouse tumours, including melanoma resistant to immune checkpoint blockade. Small circular RNAs encoding one or more antigens and enclosed in subcutaneously injected lipid nanoparticles can elicit potent and durable antitumour T cell responses for robust tumour immunotherapy, particularly in combination with immune checkpoint inhibition, as shown in multiple mouse models of tumours.

Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. Using immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial-mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis. In the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-[beta] treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a-CD36 cells, suggesting that TGF-[beta] synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-[beta] in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-[beta] were up-regulated in C33a-CD36 cells. These results imply that CD36 and TGF-[beta] interact with each other to promote the EMT in cervical cancer. Our findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.