Neutrophil extracellular traps and neutrophil extracellular traps-related genes are involved in new-onset atrial fibrillation in LPS-induced sepsis.

BACKGROUND: Sepsis is considered a high risk factor for new-onset atrial fibrillation (NOAF), with neutrophil extracellular traps (NETs) being implicated in the pathogenesis of numerous diseases. However, the precise role of NETs and NETs-related genes (NRGs) in the occurrence of NOAF in sepsis remains inadequately elucidated. The objective of this study was to identify hub NRGs connecting sepsis and AF, and to investigate the potential association between NETs and NOAF in sepsis. METHODS: The AF and sepsis microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database for analysis of shared pathophysiological mechanisms and NRGs implicated in both sepsis and AF using bioinformatics techniques. The CIBERSORT algorithm was employed to assess immune cell infiltration and identify common immune characteristics in these diseases. Additionally, a rat model of lipopolysaccharide (LPS)-induced sepsis was utilized to investigate the association between NETs, NRGs, and sepsis-induced AF. Western blotting, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence were employed to assess the expression of NRGs, the formation of NETs, and the infiltration of neutrophils. Electrophysiological analysis and multi-electrode array techniques were utilized to examine the vulnerability and conduction heterogeneity of AF in septic rats. Furthermore, intervention was conducted in LPS-induced sepsis rats using DNase I, a pharmacological agent that specifically targets NETs, in order to assess its impact on neutrophil infiltration, NETs formation, hub NRGs protein expression, and AF vulnerability. RESULTS: A total of 61 commonly differentially expressed genes (DEGs) and four hub DE-NRGs were identified in the context of sepsis and AF. Functional enrichment analysis revealed that these DEGs were predominantly associated with processes related to inflammation and immunity. Immune infiltration analysis further demonstrated the presence of immune infiltrating cells, specifically neutrophil infiltration, in both sepsis and AF. Additionally, a positive correlation was observed between the relative expression of the four hub DE-NRGs and neutrophil infiltration. In rats with LPS-induced sepsis, we observed a notable upregulation in the expression of four DE-NRGs, the formation of NETs, and infiltration of neutrophils in atrial tissue. Through electrophysiological assessments, we identified heightened vulnerability to AF, reduced atrial surface conduction velocity, and increased conduction heterogeneity in LPS-induced sepsis rats. Notably, these detrimental effects can be partially ameliorated by treatment with DNase I. CONCLUSIONS: Through bioinformatics analysis and experimental validation, we identified four hub NRGs in sepsis and AF. Subsequent experiments indicated that the formation of NETs in the atria may contribute to the pathogenesis of NOAF in sepsis. These discoveries offer potential novel targets and insights for the prevention and treatment of NOAF in sepsis.

The role of Tetraspanins in digestive system tumor development: update and emerging evidence.

Digestive system malignancies, including cancers of the esophagus, pancreas, stomach, liver, and colorectum, are the leading causes of cancer-related deaths worldwide due to their high morbidity and poor prognosis. The lack of effective early diagnosis methods is a significant factor contributing to the poor prognosis for these malignancies. Tetraspanins (Tspans) are a superfamily of 4-transmembrane proteins (TM4SF), classified as low-molecular-weight glycoproteins, with 33 Tspan family members identified in humans to date. They interact with other membrane proteins or TM4SF members to form a functional platform on the cytoplasmic membrane called Tspan-enriched microdomain and serve multiple functions including cell adhesion, migration, propagation and signal transduction. In this review, we summarize the various roles of Tspans in the progression of digestive system tumors and the underlying molecular mechanisms in recent years. Generally, the expression of CD9, CD151, Tspan1, Tspan5, Tspan8, Tspan12, Tspan15, and Tspan31 are upregulated, facilitating the migration and invasion of digestive system cancer cells. Conversely, Tspan7, CD82, CD63, Tspan7, and Tspan9 are downregulated, suppressing digestive system tumor cell metastasis. Furthermore, the connection between Tspans and the metastasis of malignant bone tumors is reviewed. We also summarize the potential role of Tspans as novel immunotherapy targets and as an approach to overcome drug resistance. Finally, we discuss the potential clinical value and therapeutic targets of Tspans in the treatments of digestive system malignancies and provide some guidance for future research.

Carboxypeptidase Vitellogenic-Like Promotes the Proliferation and Metastasis of Osteosarcoma through the TGF-ß/Smad Signaling Pathway.

OBJECTIVE: This research explored the biological role and underlying mechanisms of carboxypeptidase vitellogenic-like (CPVL) in the progression of osteosarcoma. METHODS: Through mining of microarray data from the GEO database and utilization of qRT-PCR and Western blot analyses, CPVL expression in osteosarcoma tissues and cells was evaluated. RNA interference and lentiviral transduction techniques were applied to edit the CPVL gene. RNA-seq was used to screen for the downstream target genes of CPVL. RESULTS: In both osteosarcoma biopsy samples and cell lines, the expression of CPVL was abnormally higher than that in normal cells or osteoblasts. CPVL silencing notably inhibited the proliferative activity of osteosarcoma cells, whereas CPVL overexpression had the opposite effect. CPVL silencing had potent tumor-suppressive ability in a xenograft osteosarcoma model in nude mice. CPVL silencing significantly suppressed osteosarcoma cell migration, invasion and EMT, whereas CPVL overexpression accelerated these events. Downstream genes related to the occurrence and development of osteosarcoma, including TGF-ß/Smad signaling pathway molecules (TGF-ß2, TGF-ßR1, Smad2/3, and Smad5), were suppressed by CPVL silencing. CONCLUSIONS: High CPVL expression in osteosarcoma not only promoted tumor growth but also induced the EMT process through the TGF-ß/Smad signaling pathway. CPVL may be a new antitumor therapeutic target for osteosarcoma.

Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is one of the most aggressive malignancies, lacking novel diagnostic and prognostic biomarkers. Exosome noncoding RNAs (ncRNA) were previously proposed as a potential source of biomarkers in several cancers. This study aimed to interpret the value of specific bile-derived ncRNA as predictors for early diagnosis and prognosis of CCA. Methods: We recruited 100 patients who received endoscopic retrograde cholangiopancreatography at our hospital for bile duct obstruction due to CCA (n = 50) and biliary stone (n = 50). They were further divided into training set and validation set (3:2). A panel of CCA-specific ncRNAs including 5 miRNAs (PMID: 30165035) and 2 lncRNAs (PMID: 29050258) were detected in both serum and bile exosomes. The diagnostic accuracy was assessed using the area under the receiver operating characteristic curve. Logistic analysis was used to classify the potential predictors of CCA and further establish the diagnostic model. And the prognostic value of the ncRNAs was also assessed. Results: Exosomes were successfully collected from bile and serum. Exosomal miR-141-3p, miR-200a-3p, miR-200c-3p in serum and bile, as well as miR-200b-3p and ENST00000588480.1 in bile showed AUCs of >0.70 in the diagnosis of CCA. Bile exosomal miR-200c-3p displayed the best diagnostic value with the AUC of 0.87. The combination of serum CA19-9 into the model could increase the AUC to 0.906. Bile exosomal miR-200a-3p and miR-200c-3p were found to be independent predictors of CCA. Among exosomal ncRNAs in human bile and blood, 3 (serum and bile exosomal miR-200c-3p, bile exosomal miR-200a-3p) showed significant value in predicting cancer recurrence and 1 (serum exosomal miR-200c-3p) had great predictive ability of cancer death. High levels of serum exosomal miR-200c-3p showed unfavorable tumor-free survival and overall survival. Conclusion: The bile exosomal miR-200 family, particularly miR-200c-3p, was verified to be a potential biomarker for the early detection of CCA. The diagnostic ability of exosomal ncRNAs in human bile is better than that in blood. Moreover, high levels of bile exosomal miR-200a-3p, miR-200c-3p, and serum exosomal miR-200c-3p represented adverse clinical outcomes.

Tetraspanin 7 promotes osteosarcoma cell invasion and metastasis by inducing EMT and activating the FAK-Src-Ras-ERK1/2 signaling pathway.

BACKGROUND: Tetraspanins are members of the 4-transmembrane protein superfamily (TM4SF) that function by recruiting many cell surface receptors and signaling proteins into tetraspanin-enriched microdomains (TEMs) that play vital roles in the regulation of key cellular processes including adhesion, motility, and proliferation. Tetraspanin7 (Tspan7) is a member of this superfamily that plays documented roles in hippocampal neurogenesis, synaptic transmission, and malignant transformation in certain tumor types. How Tspan7 influences the onset or progression of osteosarcoma (OS), however, remains to be defined. Herein, this study aimed to explore the relationship between Tspan7 and the malignant progression of OS, and its underlying mechanism of action. METHODS: In this study, the levels of Tspan7 expression in human OS cell lines were evaluated via qRT-PCR and western blotting. The effect of Tspan7 on proliferation was examined using CCK-8 and colony formation assays, while metastatic role of Tspan7 was assessed by functional assays both in vitro and in vivo. In addition, mass spectrometry and co-immunoprecipitation were performed to verify the interaction between Tspan7 and ß1 integrin, and western blotting was used to explore the mechanisms of Tspan7 in OS progresses. RESULTS: We found that Tspan7 is highly expressed in primary OS tumors and OS cell lines. Downregulation of Tspan7 significantly suppressed OS growth, metastasis, and attenuated epithelial-mesenchymal transition (EMT), while its overexpression had the opposite effects in vitro. Furthermore, it exhibited reduced OS pulmonary metastases in Tspan7-deleted mice comparing control mice in vivo. Additionally, we proved that Tspan7 interacted with ß1 integrin to facilitate OS metastasis through the activation of integrin-mediated downstream FAK-Src-Ras-ERK1/2 signaling pathway. CONCLUSION: In summary, this study demonstrates for the first time that Tspan7 promotes OS metastasis via interacting with ß1 integrin and activating the FAK-Src-Ras-ERK1/2 pathway, which could provide rationale for a new therapeutic strategy for OS.

Tspan9 Induces EMT and Promotes Osteosarcoma Metastasis via Activating FAK-Ras-ERK1/2 Pathway.

Object: At present, there are few effective treatment options available to patients suffering from osteosarcoma (OS). Clarifying the signaling pathways that govern OS oncogenesis may highlight novel approaches to treating this deadly form of cancer. Recent experimental evidence suggests that the transmembrane protein tetraspanin-9 (Tspan9) plays a role in tumor development. This study was thus formulated to assess the molecular role of Tspan9 as a regulator of OS cell metastasis. Methods: Gene expression in OS cell lines was evaluated via qRT-PCR, while CCK-8, colony formation, Transwell, and wound healing assays were used to explore the in vitro proliferative, invasive, and migratory activities of OS cells. The relationship between Tspan9 and in vivo OS cell metastasis was assessed by injecting these cells into the tail vein of nude mice. Interactions between the Tspan9 and integrin ß1 proteins were explored through mass spectrometric and co-immunoprecipitation, and Western blotting to assess the functional mechanisms whereby Tspan9 shapes OS pathogenesis. Results: Both primary OS tumors and OS cell lines commonly exhibited Tspan9 upregulation, and the knockdown of this tetraspanin suppressed the migration, invasion, and epithelial-mesenchymal transition (EMT) activity in OS cells, whereas Tspan9 overexpression resulted in opposite phenotypes. Tumor lung metastasis were significantly impaired in mice implanted with HOS cells in which Tspan9 was downregulated as compared to mice implanted with control HOS cells. Tspan9 was also found to interact with ß1 integrin and to contribute to OS metastasis via the amplification of integrin-mediated downstream FAK/Ras/ERK1/2 signaling pathway. Conclusion: These data suggest that Tspan9 can serve as a promising therapeutic target in OS.

Pt and Mo Co-Decorated MnO2 Nanorods with Superior Resistance to H2O, Sintering, and HCl for Catalytic Oxidation of Chlorobenzene.

MnO2 nanorods with exposed (110), (100), or (310) facets were prepared and investigated for catalytic oxidation of chlorobenzene, then the (110)-exposed MnO2 nanorod was screened as the candidate parent and further modified by Pt and/or Mo with different contents. The loading of Pt enhanced activity and versatility of the pristine MnO2, but the polychlorinated byproducts and Cl2 were promoted, conversely, as the decoration of Mo inhibited the polychlorinated byproducts and improved durability. Determination of structure and properties suggested that Pt facilitated the formation of more oxygen vacancies/Mn3+ and surface adsorbed oxygen weakened the bonds of surface lattice oxygen, while Mo stabilized surface lattice oxygen and increased acid sites, especially Brønsted acid sites. Expectedly, Pt and Mo bifunctionally modified MnO2 presented a preferable activity, selectivity, and durability along with the super resistance to H2O, high-temperature, and HCl, and no prominent deactivation was observed within 30 h at 300 °C under dry and humid conditions, even at high-temperature aging at 600 °C and HCl-pretreatment (7 h). In this work, the optimized Mo and Pt codecorated MnO2 was considered a promising catalyst toward practical applications for catalytic oxidation of actual Cl-VOCs emissions.

Erythrocyte membrane protein band 4.1-like 3 inhibits osteosarcoma cell invasion through regulation of Snai1-induced epithelial-to-mesenchymal transition.

Erythrocyte membrane protein band 4.1-like 3 (EPB41L3) is an important membrane skeletal protein that may interact with numerous membrane proteins. Loss of EPB41L3 is reported in multiple cancer types, and it is originally identified as a tumor suppressor. In this study, through analyzing expression profiling retrieved from the Gene Expression Omnibus (GEO) dataset, we find that EPB41L3 is upregulated in primary osteosarcoma (OS) and osteosarcoma cell lines. Importantly, EPB41L3 may promote osteosarcoma cell proliferation and suppress osteosarcoma cell migration and invasion. Reduced EPB41L3 leads to a decrease of E-cadherin as well as an increase of N-cadherin and Vimentin, implying a prominent epithelial-to-mesenchymal transition. Furthermore, we demonstrate that EPB41L3 inhibits the epithelial-to-mesenchymal transition through destabilizing the Snai1 protein, one of the most important transcription factors of the epithelial-to-mesenchymal transition process. Collectively, our study has first established the complex and vital roles of EPB41L3 and implicated EPB41L3 as a potential biomarker in osteosarcoma.

Identification of a Prognostic 3-Gene Risk Prediction Model for Thyroid Cancer.

Objective: We aimed to screen the genes associated with thyroid cancer (THCA) prognosis, and construct a poly-gene risk prediction model for prognosis prediction and improvement. Methods: The HTSeq-Counts data of THCA were accessed from TCGA database, including 505 cancer samples and 57 normal tissue samples. "edgeR" package was utilized to perform differential analysis, and weighted gene co-expression network analysis (WGCNA) was applied to screen the differential co-expression genes associated with THCA tissue types. Univariant Cox regression analysis was further used for the selection of survival-related genes. Then, LASSO regression model was constructed to analyze the genes, and an optimal prognostic model was developed as well as evaluated by Kaplan-Meier and ROC curves. Results: Three thousand two hundred seven differentially expressed genes (DEGs) were obtained by differential analysis and 23 co-expression genes (|COR| > 0.5, P < 0.05) were gained after WGCNA analysis. In addition, eight genes significantly related to THCA survival were screened by univariant Cox regression analysis, and an optimal prognostic 3-gene risk prediction model was constructed after genes were analyzed by the LASSO regression model. Based on this model, patients were grouped into the high-risk group and low-risk group. Kaplan-Meier curve showed that patients in the low-risk group had much better survival than those in the high-risk group. Moreover, great accuracy of the 3-gene model was revealed by ROC curve and the remarkable correlation between the model and patients' prognosis was verified using the multivariant Cox regression analysis. Conclusion: The prognostic 3-gene model composed by GHR, GPR125, and ATP2C2 three genes can be used as an independent prognostic factor and has better prediction for the survival of THCA patients.

Exosomal miR-200 family as serum biomarkers for early detection and prognostic prediction of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a common and lethal disease but lacks of efficient biomarkers for early detection. A previous study using CCA cell lines showed a CCA-specific exosomal microRNA profile. We aimed to verify the results in CCA patients and evaluate the potential roles of these exosomal microRNAs as serum biomarkers. Peripheral blood samples were collected from 36 CCA patients and 12 healthy controls. Twenty exosomal microRNAs were compared between CCA and control group. The diagnostic value was assessed using area under receiver operating characteristic curve (AUC). Out of 20 exosomal microRNAs, 5 significantly differentially expressed between CCA and control group. Four microRNAs in miR-200 family (miR-141-3p, miR-200a-3p, miR-200b-3p, and miR-200c-3p) showed higher AUCs than CA19-9 (0.78). MiR-200c-3p presented the best diagnostic ability with the AUC of 0.93. Furthermore, miR-200a/c-3p was positively correlated with tumor stage (P < 0.05). Patients with advance tumor stage (III-IV) showed significantly higher serum exosomal miR-200a/c-3p levels than those with early stage (I-II) (P < 0.05). In conclusion, serum exosomal miR-200 family, particularly miR-200c-3p, could be efficient biomarkers for CCA. The serum levels of exosomal miR-200a/c-3p also represented the rate of CCA progression.

[Relationship between NMDA receptor and postoperative fatigue syndrome and its associated central mechanism].

OBJECTIVE: To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. METHODS: After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg), POFS model(70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups(70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase III((KATIII() by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy(TEM). RESULTS: As compared to control group, exercise score decreased(P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT III( decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1, and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats, while such damage was improved in antagonist group. CONCLUSION: The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Risk factors for postoperative fatigue after gastrointestinal surgery.

BACKGROUND: Postoperative fatigue (POF) is an important complication that is commonly observed postoperatively and is also one of the most serious obstacles to postoperative convalescence. However, the risk factors for POF have not been fully addressed, and there is no effective method to predict POF. The aim of the present study was to investigate the risk factors for POF and to explore prediction of the degree of POF. METHODS: A prospective observational study was conducted of patients undergoing elective gastrointestinal surgery. Fatigue score, grip strength, length of postoperative hospital stay (LOS), as well as preoperative and intraoperative factors were collected. χ(2) was used to compare categorical variables, and multivariate logistic regression analysis was used to further analyze correlation between POF and preoperative and intraoperative factors. RESULTS: A total of 155 patients were included in our analysis without loss in follow-up. Multivariate logistic regression analysis after adjustment for factors with severe POF in univariate analysis including preoperative fatigue, plasma albumin and hemoglobin level, and cardiopulmonary function demonstrated that old age, gastrectomy, and a nutritional risk screening 2002 score ≥ 3 were associated with a higher relative risk of severe POF. Moreover, laparoscopic-assisted surgery was associated with lower relative risk of severe POF. CONCLUSIONS: Old age, nutritional risk screening 2002 score ≥ 3 and gastrectomy were risk factors for POF in patients undergoing elective gastrointestinal surgery. POF was reduced in laparoscopic-assisted surgery. Consideration of these factors could be important for the prevention and treatment of POF.

[A web-based biomedical image mosaicing system].

This paper describes a web service for biomedical image mosaicing. A web site based on CGI (Common Gateway Interface) is implemented. The system is based on Browser/Server model and is tested in www. Finally implementation examples and experiment results are provided.

Kinetic phase transition in A2 + B2 -->2AB reaction system.

Three lattice gas models for A2 + B2 -->2AB reaction system are studied by Monte Carlo simulation in two-dimensional triangular lattice surface. When both A2 and B2 adsorb and dissociate on the catalytic surface in the random dimer-filling mechanism or in the end-on dimer-filling mechanism, there is no reactive window in the reaction system and just a discontinuous phase transition appears from a "B+vacancy" poisoned state to an "A+vacancy" poisoned state. However, a reactive window appears when one of the two dimers, A2, dissociates in the random dimer-filling mechanism but another dimer, B2, is in the end-on dimer-filling mechanism and the system exhibits a discontinuous phase transition from the active reaction state to a B+ vacancy poisoned state and a continuous phase transition to an "A+vacancy" poisoned state. Furthermore, we show that the critical behavior of the continuous phase transition with infinitely many absorbing states belongs to the robust directed percolation universality class.