Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. Methods: We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for in vitro and in vivo experiments, respectively, to further validate the role of ELOVL4. Results: Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, in vitro and in vivo experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. Conclusion: In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.

Molecular near-infrared triplet-triplet annihilation upconversion with eigen oxygen immunity.

Molecular triplet-triplet annihilation upconversion often experiences drastic luminescence quenching in the presence of oxygen molecules, posing a significant constraint on practical use in aerated conditions. We present an oxygen-immune near-infrared triplet-triplet annihilation upconversion system utilizing non-organometallic cyanine sensitizers (λex = 808 nm) and chemically synthesized benzo[4,5]thieno[2,3-b][1,2,5]thiadiazolo[3,4-g]quinoxaline dyes with a defined dimer structure as annihilators (λem = 650 nm). This system exhibits ultrastable upconversion under continuous laser irradiance (>480 mins) or extended storage (>7 days) in aerated solutions. Mechanistic investigations reveal rapid triplet-triplet energy transfer from sensitizer to annihilators, accompanied by remarkably low triplet oxygen quenching efficiencies ( η O 2 < 13% for the sensitizer, <3.7% for the annihilator), endowing the bicomponent triplet-triplet annihilation system with inherent oxygen immunity. Our findings unlock the direct and potent utilization of triplet-triplet annihilation upconversion systems in real-world applications, demonstrated by the extended and sensitive nanosensing of peroxynitrite radicals in the liver under in vivo nitrosative stress.

Effects of Glutamine Synthetase on Neovascularization in Glioma: In Vivo MR Vessel Size Imaging and Histology.

BACKGROUND: Glutamine Synthetase (GS) could induce vascular sprouting through the improvement of endothelial cell migration in inflammatory diseases. MR vessel-size imaging has been proposed as a valuable approach for visualizing the underlying angiogenic processes in the brain. OBJECTIVE: This study aims to investigate the role of GS in the neovascularization of gliomas through the utilization of MR vessel-size imaging and histopathological techniques. METHODS: In this exploratory animal study, we randomly divided the C6 glioma rat models into a control group and an L-methionine sulfoximine (MSO) treatment group. Daily intraperitoneal injections were administered for three consecutive days, starting from day 10 following the implantation of C6 glioma cells in rats. Subsequently, MR vessel size imaging was conducted using a BRUKER 7 T/200 mm MRI scanner, and the MRI results were validated through histopathological examination. RESULTS: A significant decrease in microvessel density was observed in both the tumor periphery and center areas in the MSO treatment group compared to that in the control group. The mean vessel diameter (mVD) and vessel size index (VSI) did not exhibit significant changes compared to the control group. Moreover, the staining intensity of platelet endothelial cell adhesion molecule-1 (CD31) and GS in the tumor periphery was significantly decreased in the MSO treatment group. Additionally, the MSO treatment demonstrated a substantial inhibition of tumor growth. CONCLUSION: GS inhibitors significantly reduced angiogenesis in the periphery area of C6 glioma, exerting an inhibitory effect on tumor progression. Thus, GS inhibitors could be potential therapeutic agents for treating glioma. Additionally, in vivo MR vessel size imaging detects changes in vascularrelated parameters after tumor treatment, making it a promising method for detecting neovascularization in glioma.

In Silico Identification of Therapeutic Targets and Novel Drug Candidates for Malignant Peripheral Nerve Sheath Tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of sarcomas with a poor prognosis and limited treatment options. Therefore, new therapeutic targets are urgently needed to identify novel drugs. METHODS: Based on the Gene Expression Omnibus database, an integrated analysis was performed to identify differentially expressed genes (DEGs) in MPNSTs compared to neurofibromas (NFs). Then functional enrichment analyses, protein-protein interaction (PPI) network construction, and hub gene selection were conducted. We explored DEG-guided repurposable drugs to treat MPNST based on the Library of Integrated Network-Based Cellular Signatures (LINCS) database. Furthermore, the binding affinity between predicted drug candidates and the MPNST-associated hub gene was calculated using molecular docking. RESULTS: We identified 89 DEGs in common with all three MPNSTs datasets. In the PPI networks, twist family bHLH transcription factor 1 (Twist1) with higher node degrees was further evaluated as a therapeutic target. Cytochalasin-d, cabozantinib, everolimus, refametinib, and BGT-226 were extracted from the LINCS database, which showed lower normalized connectivity scores (-1.88, -1.81, -1.78, -1.76, and -1.72, respectively) and was considered as drug candidates. In addition, the results of molecular docking between the five drugs and Twist1 showed a binding affinity of -6.61, -7.03, -7.73, -3.94, and -7.07 kcal/mol, respectively. CONCLUSIONS: Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

The cancer/testis antigen HORMAD1 promotes gastric cancer progression by activating the NF-κB signaling pathway and inducing epithelial-mesenchymal transition.

OBJECTIVES: HORMAD1 is a cancer/testis antigen (CTAs) that regulates DNA homologous recombination, mismatch repair, and other tumor characteristics. However, its role and regulatory mechanisms in gastric cancer remain unclear. METHODS: We performed transcriptomic profiling on seven gastric cancers and paired tissues; HORMAD1 was significantly upregulated in gastric cancer samples and was related to poor prognosis survival. Furthermore, cancer pathway microarray, bioinformatic analysis, western blot, and immunochemistry assay demonstrated that HORMAD1 affected the NF-κB signaling pathway. RESULTS: In vitro and vivo studies confirmed that HORMAD1 knockdown inhibited cell growth and invasion, whereas overexpression reversed these effects. Mechanistically, HORMAD1 regulates the epithelial-mesenchymal transition process (EMT) via the NF-κB pathway by increasing the phosphorylation levels of NF-κB (p-65) and Iκκ-ß. Downstream target genes of the NF-κB signaling pathway, such as c-Myc, CyclinD1, may be involved in HORMAD1-induced tumorigenesis in gastric cancer (GC). CONCLUSIONS: HORMAD1 plays an important role in gastric cancer progression and could be a promising prognostic biomarker and therapeutic target.

Assessing the Intensity of Marine Biogenic Influence on the Lower Atmosphere: An Insight into the Distribution of Marine Biogenic Aerosols over the Eastern China Seas.

Marine biological activities make a non-negligible contribution to atmospheric aerosols, leading to potential impacts on the regional atmospheric environment and climate. The eastern China seas are highly productive with significant emissions of biogenic substances, but the spatiotemporal variations of marine biogenic aerosols are not well known. Air mass exposure to chlorophyll a (AEC) can be used to indicate the influence of biogenic sources on the atmosphere to a certain degree. In this study, the 12 year (2009-2020) daily AEC were calculated over the eastern China seas, showing the spatial and seasonal patterns of marine biogenic influence intensity which were co-controlled by surface phytoplankton biomass and boundary layer height. By combining the AEC values, relevant meteorological parameters, and extensive observations of a typical biogenic secondary aerosol component, methanesulfonate (MSA), a parameterization scheme for MSA simulation was successfully constructed. This AEC-based approach with observation constraints provides a new insight into the distribution of marine biogenic aerosols. Meanwhile, the wintertime air mass retention over land exhibited a significant decrease, showing a decadal weakening trend of terrestrial transport, which is probably related to the weakening of the East Asian winter monsoon. Thus, marine biogenic aerosols may play an increasingly important role in the studied region.

Oblique radiograph with methylene blue marking: A reliable technique for upper thoracic level localization.

Purpose: Traditionally, plain radiographs are used in intraoperative spinal level localization (SLL), whereas counting vertebrae is often hampered by shoulders and scapulae in lateral views, thus increasing the potential for wrong-level surgery. To improve the localization accuracy, this study evaluated the safety and feasibility of oblique radiographs with methylene blue markings for SLL and explored the optimal angle and height of oblique radiographs. Methods: The clinical data of 33 patients with upper thoracic spine lesions who were operated on in our hospital from January 2021 to April 2022 were retrospectively analyzed. Oblique radiographs with methylene blue markings were used for intraoperative SLL. Results: A total of 33 patients were included in this study. The average BMI was 24.3 ± 0.7 kg/m2. The ipsilateral lamina structures were clearly shown in all cases. The median radiographing times of all the patients was 3, and the median radiographing duration was 2 min and 25 s. The average angle of oblique radiographs was 55.1 ± 3.8°, and the average distance from the skin to the root of the spinous process was 4.9 ± 1.2 cm. Conclusions: Using oblique radiographs with methylene blue markings, not only the bone structure of an upper thoracic spine can be revealed clearly, but also the positioning deviation of traditional needle localization can be avoided. The lesion segment can be precisely located by this technology during surgery. Our angle of oblique radiographs and height determination method can be used to reduce the radiation exposure and shorten the operation time.

Spinal extradural arachnoid cysts: A novel formation mechanism and dural defect location technology.

Purpose: The formation mechanism of spinal extradural arachnoid cysts (SEACs) remains unclear. There are several hypotheses for the formation of SEACs, but none of them can fully explain its pathological findings and surgical procedures. In this study, we retrospectively analyzed the cases of SEACs, aiming to clarify the formation mechanism of SEACs. In addition, we summarize a concise method for locating dural defects preoperatively and formulate a putative explanation of this method. Methods: The clinical data of 14 patients with SEACs underwent surgery in our hospital from January 2017 to December 2021 were retrospectively analyzed. Results: Fourteen patients were identified during the study period. The cysts all spanned the T12/L1 segment, and dural defects were also located at the T12/L1 level (2 cases not recorded) as well as the middle or the upper-middle level of the cysts. Nine cases were treated with total cyst excision, 2 cases were treated with dural defect closure only, and 3 cases were treated with total cyst excision and dural defect closure. Histopathological examination demonstrated that the cyst wall contained both the arachnoid epithelial and compact fibrous connective tissue. The symptoms were relieved in all patients, and no recurrence was observed. Conclusions: According to intraoperative and pathological findings, the dural outer layer cyst (DOLC) is a more reasonable hypothesis about SEACs formation. When CT myelography or cinematic MRI cannot determine the location of the dural defect preoperatively, it can be located according to the middle level of the SEACs with high accuracy.

Clinical value of microRNA-135a and MMP-13 in colon cancer.

The aim of the present study was to investigate the expression and prognostic value of microRNA-135a (miR-135a) and matrix metalloproteinase-13 (MMP-13) in serum of colon cancer (CC). A total of 117 cases of patients admitted to Sheng Li Oil Field Central Hospital from May 2015 to May 2017 were enrolled in the research group (RG), and 120 cases of subjects undergoing normal health examination were included in the control group (CG). The expression of miR-135 and MMP-13 in peripheral blood of the two groups were compared, and their values were analyzed. It was found that miR-135a was decreased and MMP-13 was increased in the RG (P<0.050), both of which were closely related to the pathological features and prognosis of CC (P<0.050), and was also significantly correlated with CEA (P<0.001). ROC curve analysis showed that both of them had great predictive value for the occurrence, prognosis and death of CC. In conclusion, miR-135a was low expressed in CC, while MMP-13 was increased in CC, suggesting that the combined detection of the two had a good diagnostic effect on the occurrence of CC, and was closely related to the prognosis of CCC patients, which might be an excellent potential indicator for the diagnosis and treatment of CC in the future.

Transanterior obturator nerve gateway: a novel approach to achieving intracorporeal distal rectal transection for ultralow rectal cancer.

BACKGROUND: Intracorporeal rectal transection at the anorectal junction for ultralow rectal cancer is technically difficult due to pelvic width and limited roticulation, which might require a transanal transection or an oblique transection with multiple firings. These procedures were reported to be associated with the increased risk of morbidity. To address these problems, we presented a novel technique Transanterior Obturator Nerve Gateway (TANG) to transect rectum for ultralow rectal cancer and evaluated its safety and feasibility in this study. METHODS: A total of 210 consecutive patients who underwent laparoscopic coloanal anastomosis with or without partial intersphincteric resection (CAA/pISR) for rectal cancers between January 2017 and January 2020 were included. Eighty of these patients were analyzed using propensity score matching (PSM). The perioperative characteristics, TANG-related variables, and genitourinary and anal function outcomes were analyzed. RESULTS: Among these enrolled patients, 170 patients underwent traditional transection, and 40 underwent TANG transection; the patients were matched to include 40 patients in each group by PSM. After PSM, there were no significant differences in the operating time (p = 0.351) or bleeding volume (p = 0.474) between the two groups. However, the TANG group had fewer cases of conversion to transanal transection (0 vs. 13, p < 0.001). Moreover, the patients in TANG group had a more desirable transection with longer distal resection margin (1.7 vs. 1.1 cm, p < 0.001), shorter stapling line (6.6 vs. 10.3 cm, p < 0.001) and fewer stapler firings (p < 0.001). The overall postoperative complication rates and genitourinary and anal function outcomes were not significantly different between the two groups. CONCLUSIONS: The TANG approach appears to be a safe, feasible and effective approach for intracorporeal ultralow rectal transection with more distal resection, more vertical transection and fewer stapler firings.

A Human Case of Lumbosacral Canal Sparganosis in China.

In this study, we intended to describe a human case of lumbosacral canal sparganosis in People's Republic of China (China). A 56-year-old man was admitted to Xiangya Hospital Central South University in Changsha, Hunan province, China after having an experience of perianal pain for a week. An enhancing mass, a tumor clinically suggested, was showed at the S1-S2 level of the lumbosacral spine by the examination of magnetic resonance imaging (MRI) with gadolinium contrast. The patient was received the laminectomy from S1 to S2, and an ivory-white living worm was detected in inferior margin of L5. In ELISA-test with cerebrospinal fluid (CSF) and serum samples, anti-sparganum antibodies were detected. He had a ingesting history of undercooked frog meat in his youth. By the present study, a human case of spinal sparganosis invaded in lumbosacral canal at the S1-S2 level was diagnosed in China. Although the surgical removal of larvae is known to be the best way of treatment for sparganosis, we administered the high-dosage of praziquantel, albendazole and dexamethasone to prevent the occurrence of another remain worms in this study.

Mechanism of long noncoding RNAs as transcriptional regulators in cancer.

Dysregulation of gene expression, often interpreted by gene transcription as an endpoint response, is tightly associated with human cancer. Long noncoding RNAs (lncRNAs), derived from the noncoding elements in the genome and appeared no less than 200nt in length, have emerged as a novel class of pivotal regulatory component. Recently, great attention has been paid to the cancer-related lncRNAs and growing evidence have shown that lncRNAs act as key transcriptional regulators in cancer cells through diverse mechanisms. Here, we focus on the nucleus-expressed lncRNAs and summarize their molecular mechanisms in transcriptional control during tumorigenesis and cancer metastasis. Six major mechanisms will be discussed in this review: association with transcriptional factor, modulating DNA methylation or histone modification enzyme, influencing on chromatin remodelling complex, facilitating chromosomal looping, interaction with RNA polymerase and direct association with promoter.

Antecedents of satisfaction and engagement of low-carbon bicycle-sharing using in China.

Transport sector contributed numerous carbon emissions in China. It is important to promote low-carbon bicycle-sharing using in China. This paper aims to analyze the influencing factors of the satisfaction and engagement of bicycle-sharing in China. An extended model of customer satisfaction is established, which considers both customer satisfaction theory and customer engagement theory. We explore the different effect of convenience, health, safety, and facility on satisfaction of bicycle-sharing using. We also explore the role of satisfaction on three different dimensions of engagement: enthusiasm, participation, and social interaction. Multi-group structure equation model is employed to explore the different roles of gender on the determinants of satisfaction and engagement of bicycle-sharing using. The findings reveal that facilities had the larger effect on satisfaction of bicycle-sharing using than safety and health for male. Safety had the largest influence on satisfaction of bicycle-sharing using for female, followed by facility, convenience, and health.

Glycemic reduction alters white blood cell counts and inflammatory gene expression in diabetes.

OBJECTIVE: Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. RESEARCH DESIGN AND METHODS: This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. RESULTS: After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ±â€¯1.8 to 6.8 ±â€¯0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; krüppel-like factor 5; and IL-1. Also, circulating levels of IL-1ß and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. CONCLUSION: Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

MicroRNA-30a increases the chemosensitivity of U251 glioblastoma cells to temozolomide by directly targeting beclin 1 and inhibiting autophagy.

Temozolomide (TMZ) is one of the most commonly used drugs for the clinical treatment of glioblastomas. However, it has been reported that treatment with TMZ can induce autophagy, which leads to tumor resistance and increases the survival of tumor cells. MicroRNA-30a (miR-30a) has been found to have inhibitory effects on autophagy by directly targeting beclin 1. However, the exact role of miR-30a in TMZ-treated glioblastoma cells has not been studied previously. The present study aimed to investigate whether miR-30a increased the cytotoxicity of TMZ to glioblastoma U251 cells, as well as the underlying mechanism. MTT and flow cytometry assay results showed that treatment with TMZ inhibited the proliferation of U251 cells while inducing cell apoptosis in a dose-dependent manner. Western blotting data showed that the expression levels of LC3-II and beclin 1 as well as the ratio of LC3-II to LC3-I were markedly increased in TMZ-treated U251 cells compared with the untreated control cells, indicating that treatment with TMZ induced autophagy. Moreover, reverse transcription-quantitative polymerase chain reaction data showed that treatment with TMZ led to a significant reduction in miR-30a levels in a dose-dependent manner in U251 cells. Elevation of the miR-30a level significantly inhibited TMZ-induced autophagy, demonstrated by the decreased LC3-II and beclin 1 levels and ratio of LC3-II to LC3-I, accompanied by the reduced proliferation and increased apoptosis in TMZ-treated U251 cells. Furthermore, luciferase reporter assay data indicated that beclin 1 was a direct target of miR-30a in U251 cells. In summary, this study demonstrated that miR-30a increases the chemosensitivity of glioblastoma U251 cells to temozolomide by directly targeting beclin 1 and inhibiting autophagy. Therefore, autophagy may be a promising target for the treatment of TMZ-resistant tumors.

Genome-wide expression profiling and bioinformatics analysis of deregulated genes in human gastric cancer tissue after gastroscopy.

AIM: The aim of this study was to analyze the gene expression profile and biological processes enriched in gastric cancer. METHODS: We collected five human advanced gastric cancer tissues by gastroscopy and five peritumor normal tissues as controls and examined the gene expression changes by microarray. KEGG Orthology Based Annotation System annotation was used to identify pathways and biological processes regulated by the deregulated genes. Protein-protein interaction network analysis identified protein complex and functional modules. We also selected 14 genes for further verification by real-time quantitative Polymerase Chain Reaction (PCR). RESULTS: Human gene expression profile analysis showed that 2028 deregulated genes were detected in gastric cancer compared with the control group (at least a 2.0-fold change and P < 0.05), among which there were 689 upregulated and 1339 downregulated genes. Interestingly, we identified some important genes, such as CXCL17, OTX1 and CCDC125, which have not previously been reported in gastric cancer. Real-time quantitative PCR results verified that CXCL8, OTX1, CEBPB, FOSL1, FOXS1, ARFRP1 and IRF9 were upregulated in gastric cancer and CCDC125, PPP1R36, SOX2, JUN and MIA2 were downregulated. Moreover, bioinformatics analysis demonstrated that the biological processes of inflammatory response, angiogenesis, cell migration and pathways of chemokine signaling pathway, TNF signaling pathway were enriched. We also selected the top 30 significant Gene Ontology terms and select pathways for a brief summary. CONCLUSION: We performed a global analysis of the mRNA landscape in gastric cancer. Our results may stimulate a deeper understanding of the disease, and lead to the development of potential therapies and the identification of novel biomarkers.