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Background: Anti‐PD1/PD‐L1 antibody plus human epidermal growth factor receptor 2 (HER2) antibody and chemotherapy have become the new first‐line therapy for HER2 overexpression‐positive advanced gastric cancers (GC), suggesting that HER2 and PD‐L1 play a vital role in guiding systemic treatment for patients with GC. This study aimed to depict the genomic and immune landscapes of Chinese patients with GC and investigate their correlations with HER2 amplification and PD‐L1 expression. Patients and Methods: Next‐generation targeted sequencing and PD‐L1 immunohistochemistry were performed on tumor samples from 735 patients with pathologically diagnosed GC. The genomic and immune landscapes and their correlations with HER2 amplification and PD‐L1 expression were analyzed. Results: The most commonly mutated genes in Chinese GC were TP53 (64%), CDH1 (20%), ARID1A (18%), HMCN1 (15%), KMT2D (11%), and PIK3CA (11%). Seventy‐six (10%) patients were HER2 amplification, and 291 (40%) had positive PD‐L1 expression. Classifying the total population based on HER2 amplification and PD‐L1 expression level, 735 patients were divided into four subgroups: HER2+/PD‐L1+ (4.5%), HER2+/PD‐L1− (5.9%), HER2−/PD‐L1+ (35.1%), and HER2−/PD‐L1− (54.5%). The HER2+/PD‐L1− and HER2+/PD‐L1+ subgroups exhibited dramatically higher rate of TP53 mutations, CCNE1 and VEGF amplifications. The HER2+/PD‐L1− subgroup also had a markedly higher rate of MYC amplification and KRAS mutations. The HER2−/PD‐L1+ subgroup had significantly higher rate of PIK3CA mutations. HER2+/PD‐L1− subgroup had the highest TMB level and HER2−/PD‐L1+ subgroup had the highest proportion of patients with microsatellite instability‐high than other subgroups. Furthermore, we observed that different HER2 amplification levels had distinct impacts on the correlations between PD‐L1 expression and therapeutic genomic alterations, but no impact on the prognosis. Conclusion: The combination of HER2 amplification and PD‐L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the leading cause of death for women diagnosed with gynecological cancer. Studies have shown that dysregulated miRNA expression is related to various cancers, including OC. Here, we aimed to explore the biological function and mechanism of miR-585-3p in the occurrence and development of OC. The expression level of miR-585-3p was found to be low in OC tissues and cells. We analyzed the biological function of miR-585-3p in OC through in vitro cell experiments. The results indicated that overexpression of miR-585-3p inhibited the proliferation, invasion, and migration of SW626 cells, while low expression of miR-585-3p had the opposite effect in SKOV3 cells. We then screened the target genes of miR-585-3p through miRDB database and detected the expression of target genes in OC cells. FSCN1 was found to be most significantly upregulated in OC cells. Dual-luciferase reporter assays revealed FSCN1 as a potential target of miR-585-3p. Western blot analysis showed that miR-585-3p targeted FSCN1 to inhibit protein phosphorylation of ERK. In vivo animal experiments also confirmed that miR-585-3p targets FSCN1 to inhibit tumor growth and block the MAPK signaling pathway. In summary, miR-585-3p inhibits the proliferation, migration, and invasion of OC cells by targeting FSCN1, and its mechanism of action may be achieved by inhibiting the activation of the MAPK signaling pathway. miR-585-3p may serve as a potential biomarker and therapeutic target for OC. [ABSTRACT FROM AUTHOR]

Introduction: AF4/FMR2 family member 4 (AFF4) is a core component of super elongation complex (SEC) and regulates the transcription elongation of many genes. AFF4 depletion or amplification is associated with multiple cancers, but its role in colorectal cancer (CRC) has not been investigated so far. Methods: qRT-PCR and Western blot analyzed AFF4 expression in the paired clinical CRC tissues. The patients' overall survival curve was determined using the Kaplan-Meier plotter. In vitro experiments, such as cell proliferation, migration, and invasion, were used to preliminarily ascertain the role of AFF4 in CRC. A CRC cell liver metastasis animal model was well established. Livers were harvested and examined histologically by a series of indicators, such as tumor nodules, liver weight, ALT/AST activity, and tumor cell identification by hematoxylin-eosin (HE) staining. Results: We firstly examined the expression of AFF4 in colorectal cancer and normal tissues by collecting paired CRC tissues and adjacent normal tissues, revealing that AFF4 was significantly downregulated in CRC patients and lower expression of AFF4 was correlated with poor prognosis. Next, we observed that presence or absence of AFF4 in CRC cells had no effect on cancer cell proliferation, while AFF4 depletion significantly promoted the migration or invasion of CRC cells in vitro. Furthermore, we confirmed that AFF4 deficiency enhanced the metastatic capacity of CRC cells in vivo. Mechanistically, we found that AFF4 upregulated the transcription of CDH1 gene, which encodes E-cadherin and suppresses the epithelial-mesenchymal transition (EMT). Knockdown of AFF4 interfered with CDH1 transcription, resulting in downregulation of E-cadherin expression and the progression of CRC. Moreover, restored CDH1 expression could rescue the phenotype of CRC cells without AFF4. Conclusions: Collectively, our data demonstrated that AFF4 served as a significant novel regulator of CRC via CDH1 transcriptional regulation and a potential effective therapy target for patients with CRC. [ABSTRACT FROM AUTHOR]

Prediction of RNA secondary structure is an important part of bioinformatics genomics research. Mastering RNA secondary structure can help us to better analyze protein synthesis, cell differentiation, metabolism, and genetic processes and thus reveal the genetic laws of organisms. Comparative sequence analysis, support vector machine, centroid method, and other algorithms in RNA secondary structure prediction algorithms often use dynamic programming algorithm to predict RNA secondary structure because of their huge time and space consumption and complex data structure. In this article, the domain of RNA secondary structure prediction algorithm based on dynamic programming (DP-SSP) is analyzed in depth, and the domain features are modeled. According to the generative programming method, the DP-SSP algorithm components are interactively designed. With the support of PAR platform, the DP-SSP algorithm component library is formally realized. Finally, the concrete algorithm is generated through component assembly, which improves the efficiency and reliability of algorithm development. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to compare the long-term outcomes of three-port laparoscopic right hemicolectomy (TPLRC) and five-port laparoscopic right hemicolectomy (FPLRC) with retrospective analysis. Methods: A total of 182 patients who accepted laparoscopic right hemicolectomy with either three ports (86 patients) or five ports (96 patients) from January 2012 to June 2017 were non-randomly selected and analyzed retrospectively. Results: More lymph nodes were harvested in the TPLRC group than in the FPLRC group [17.5 (7), 14 (8) ml, p < 0.001]. There was less blood loss in the TPLRC group [50 (80) vs. 100 (125) ml, p = 0.015]. There were no significant differences in the other short-term or oncological outcomes between the two groups. The overall survival and disease-free survival were equivalent. Conclusions: TPLRC is recommendable as it guarantees short- and long-term equivalent outcomes compared with FPLRC. [ABSTRACT FROM AUTHOR]

Unsigned reverse genome rearrangement is an important part of bioinformatics research, which is widely used in biological similarity and homology analysis, revealing biological inheritance, variation, and evolution. Branch and bound, simulated annealing, and other algorithms in unsigned reverse genome rearrangement algorithm are rare in practical application because of their huge time and space consumption, and greedy algorithms are mostly used at present. By deeply analyzing the domain of unsigned reverse genome rearrangement algorithm based on greedy strategy (unsigned reverse genome rearrangement algorithm (URGRA) based on greedy strategy), the domain features are modeled, and the URGRA algorithm components are interactively designed according to the production programming method. With the support of the PAR platform, the algorithm component library of the URGRA is formally realized, and the concrete algorithm is generated by assembly, which improves the reliability of the assembly algorithm. [ABSTRACT FROM AUTHOR]

Objectives: The incidence of colorectal cancer (CRC) is increasing year by year and appears to be younger, due to the low early diagnosis rate and metastasis. It is difficult to remedy by conventional treatment. Here, we reported that tripartite motif containing protein 2 (TRIM2) could promote tumor growth, invasion and metastasis of CRC via a mechanism that involved EMT both in vitro and in vivo. Methods: First, we used immunohistochemistry to detect TRIM2 expression. Next, TCGA database was applied to the coorelation between TRIM2 and CRC progression. Then, the plasmids and lentivirus particles were used to manipulate TRIM2 expression in SW620 or HT29 cells. The assays of proliferation, adhesion, magration and invasion were employed to detect the migration and invasion ability of CRC cells. Finally, a tail injection of CRC cells was used to identify the role of TRIM2 in tumor metastasis. Results: TRIM2 expression was significantly higher in CRC tissues than in non-cancerous tissues and was significantly associated with some clinicopathological factors. Forced overexpression of TRIM2 promoted CRC cell proliferation, migration and invasion in vitro, while opposing results were observed when TRIM2 was depleted by short hairpin RNA. TRIM2 expression had reversely correlated with YAP signaling, which was a novel pathway way referred to tumorigenesis. Furthermore, animal metastasis models confirmed that the in vivo results were consistent with the outcomes in vitro. TRIM2 conducts its function during CRC cell metastasis by epithelial–mesenchymal transition (EMT). These results indicate that TRIM2 is a novel promoter of human colorectal cancer. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer (CRC), one of the most aggressive gastrointestinal malignancies, is a frequently diagnosed life-threatening cancer worldwide. Most CRC patients have poor prognosis mainly because of frequent metastasis and recurrence. Thus, it is crucial to find out some new biomarkers and to show deeper insights into the mechanisms of CRC. MLLT10, Myeloid/lymphoid or mixed-lineage leukemia translocated to 10, also known as AF10, a recurrent MLL partner. In this study, we found that MLLT10 promotes CRC tumor invasion and metastasis both in vitro and in vivo. Methods: Here, the expression of MLLT10 was evaluated by immunohistochemistry. Then, the plasmid and lentivirus particles for MLLT10 overexpression or knockdown were designed and constructed into SW620 and HT29 cells. Finally, cell proliferation assay, cell adhesion assay, transwell migration, and invasion assay were used to detect the migration and invasion ability of MLLT10 in CRC cells. A tail vein injection assay was employed to evaluate the role of MLLT10 in tumor metastases. Results: MLLT10 expression was significantly higher in CRC tissues than in noncancerous tissues and was associated with some clinicopathological factors. In vitro, the overexpression of MLLT10 promoted CRC cell migration and invasion, while after MLLT10 was knocked down, the opposite results were observed. Furthermore, we used animal metastasis models to detect the function of MLLT10 in vivo, the results are same with the outcomes in vitro. In lung metastasis sites, the knockdown of MLLT10 in SW620 cells significantly inhibited Vimentin expression, whereas the E-Cadherin was increased. Conclusions: These results indicate that MLLT10 regulates the metastasis of CRC cells via EMT. [ABSTRACT FROM AUTHOR]

Antimony selenide film doped with Zn2+ was deposited on ultra-white glass by hydrothermal method. The photocatalytic activity was evaluated by photocatalytic decolorization reaction with methylene blue (MB) solution. According to the free radical capture experiment, photogenerated holes (h+) and superoxide radicals (·O2−) are the decisive active substances in the photocatalytic process. [Display omitted] • Zn-doped Sb 2 Se 3 thin films prepared by hydrothermal deposition. • The amount of zinc doping is the key to the enhancement of photocatalytic activity. • The doping of Zn2+ increases the visible light absorbance of the Sb 2 Se 3 thin film. • Metal ion doping provides a simple method for metal selenide photocatalysts. Sb 2 Se 3 is a promising light-absorbing material with low cost and good photocatalytic activity. In this paper, Sb 2 Se 3 thin films doped with zinc (Zn) were deposited on ultra-white glass by hydrothermal method, using ZnCl 2 , sodium selenate and antimony potassium tartrate as raw materials. And the photocatalytic activity was evaluated by photocatalytic decolorization reaction with methylene blue (MB) solution. The results showed that the highest photocatalytic activity was displayed when Zn2+ was doped with 0.10 mmol, and its degradation rate of methylene blue was 1.66 times higher than that of pure Sb 2 Se 3. Zn2+ doped Sb 2 Se 3 film can effectively inhibit the recombination of electron-hole pairs, thereby improving the optical activity. According to the free radical capture experiment, photogenerated holes (h+) and superoxide radicals (·O2−) are the decisive active substances in the photocatalytic process. This method provides a reliable way for transition metal ions doped metal selenides to degrade organic dyes. [ABSTRACT FROM AUTHOR]

Tumor microenvironment (TME) (e.g., stromal cells) has been closely related to the pathological process of colorectal cancer (CRC). In TME, tumor-associated fibroblasts (CAFs) are the main stromal cells. The studies have showed that CAFs promoted tumor growth and metastasis in CRC and led to poor prognosis. Mounting evidence indicates that CAFs-mediated exosomes regulate the pathological process of neighboring tumor cells through the transmission of miRNAs. In our study, we aimed to explore the function of CAFs-derived exosome miR-181b-3p in CRC. First, the expression of miR-181b-3p in CRC was found to be up-regulated and its expression was dramatically up-regulated in CRC cells after co-incubation of CAFs-mediated exosomes with CRC cells. Then, it was found that the CAFs-derived exosomes were markedly enhanced the proliferation and migration of the CRC cells, and substantially reduced apoptosis. To elucidate the influence of CAFs-derived exosome miR-181b-3p on CRC, we overexpressed and knocked down the miR-181b-3p expression in CAFs, respectively. It was found that miR-181b-3p significantly increased the proliferation and migration of CRC cells. Furthermore, we conducted in vivo experiments. Finally, we demonstrated that CAF-derived exosome miR-181b-3p regulated sorting nexin 2 (SNX2) expression in CRC cells by bioinformatics prediction combined with luciferase reporter assay. Further cellular and animal experiments jointly elucidated that miR-181b-3p promoted the pathological process of CRC by SNX2 expression. In brief, our results demonstrated that CAFs-derived exosome miR-181b-3p promoted the pathogenesis of CRC by regulating SNX2 expression, which provides a novel idea for CRC treatment. • CAFs-derived exosome promotes the pathological process of CRC. • CAFs-derived exosome miR-181b-3p promotes the occurrence and development of CRC. • Exosomal miR-181b-3p promotes tumor growth by regulating SNX2-mediated ERK1/2 pathway. [ABSTRACT FROM AUTHOR]

Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip ® PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients. [ABSTRACT FROM AUTHOR]