Highly Dispersed, Adhesive Carbon Nanotube Ink for Strain and Pressure Sensors.

Carbon nanotubes (CNT) with prominent electrical and mechanical properties are ideal candidates for flexible wearable devices. However, their poor dispersity in solvents greatly limits their applications as a conductive ink in the fabrication of wearable sensors. Herein, we demonstrate a kind of CNT-based conductive dispersion with high dispersity and adhesiveness using cellulose derivatives as the solvent, in which γ-aminopropyl triethoxy silane as a cross-linking agent reacts with cellulose to form copolymer networks, and simultaneously it also acts as an initiator to induce the self-polymerization of dopamine. Based on the conductive CNT ink, we also demonstrated textile-based strain sensors by stencil printing and sponge-based pressure sensors by the dipping method. The textile-based strain sensors could respond to external stimuli promptly. Then, the strain sensors were encapsulated via polydimethylsiloxane with the expansion of working ranges from less than 20 to nearly 70%. The encapsulated textile sensors exhibited excellent sensing performance as wearable strain sensors to monitor human motions including smile, throat vibration, finger folding, wrist bending, and elbow twisting. The sponge sensors hold high sensitivity and excellent durability as well. The conductive CNT-based ink provides an alternative idea in the development of flexible wearable devices.

Characterization of hazard infiltrating immune cells and relative risk genes in bladder urothelial carcinoma.

OBJECTIVES: Bladder urothelial carcinoma (BLCA) is one of the most common malignancies in urinary system. With the development of next-generation sequencing technology, we intended to investigate prognostic immune cells and related signature to predict the prognosis of BLCA and potential therapeutic targets. METHODS: We obtained the transcriptome profiles of 573 BLCA patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The fractions of immune cells in each sample was calculated by "CIBERSORT" algorithm. Tumor Infiltrating Immune Cells Scores (TIICS) was accordingly derived and Receiver Operating Characteristic (ROC) curve was conducted to evaluate the predictive efficiency. Moreover, differential analysis was performed between two TIICS groups and hub TIICS-related immune signature was identified. The correlation of key immune genes and immune-infiltrating immune cells was evaluated based on the TIMER database. An Immune Signature Prognostic Index (ISPI) based on these signatures was constructed with superior predictive accuracy. Last, the TIICS model or related immune signature were all validated in an independent cohort from the GSE13507. RESULTS: The least absolute shrinkage and selection operator (LASSO) algorithm was utilized to screen the 6 hub tumor-infiltrating immune cells in TCGA cohort, where higher infiltrating levels of M0 Macrophages, M2 Macrophages and Neutrophils were hazard factors, while CD8+ T cells and memory activated CD4+ T cells were protective factors. CONCLUSION: Taken together, our study identified several prognostic immune cells and related immune signature in BLCA, shedding insight on the individualized immunotherapy or potential drug targets.

Characterization of the Active Components of the Multimerized sTNFRIIAdiponectin Fusion Protein Showing Both TNFα-Antagonizing and Glucose Uptake-Promoting Activities.

BACKGROUND: The sTNFRII-adiponectin fusion protein previously showed strong TNFα antagonistic activity. However, the fusion protein exists as mixture of different multimers. The aim of the present study was to characterize its active components. METHODS: In this study, the fusion protein was isolated and purified by Ni-NTA affinity and gel exclusion chromatography, and further identified by Coomassie staining and western blotting. The TNFα antagonistic and glucose uptake-promoting activities were determined in vitro. The glucose detection kit and 2- NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose) were used to measure their effects on glucose metabolism (including glucose consumption and glucose uptake in HepG2 and H9C2 cells). The effect of the fusion protein on glucose uptake was also examined in free fatty acid (FFA)- induced insulin resistance cell model. RESULTS: The sTNFRII-adiponectin fusion protein was found to exist in three forms: 250 kDa (hexamer), 130 kDa (trimer), and 60 kDa (monomer), with the final purity of 90.2%, 60.1%, and 81.6%, respectively. The fusion protein could effectively antagonize the killing effect of TNFα in L929 cells, and the multimer was found to be superior to the monomer. In addition, the fusion protein could increase glucose consumption without impacting the number of cells (HepG2, H9C2 cells) in a dosedependent manner. Mechanistically, glucose uptake was found to be enhanced by the translocation of GLUT4. However, it could not improve glucose uptake in the cell model of insulin resistance. CONCLUSION: In summary, the active components of the fusion protein are hexamers and trimers. The hexamer and trimer of sTNFRII-adiponectin fusion protein had both TNFα-antagonizing and glucose uptake-promoting activities, although neither of them could improve glucose uptake in the cell model of insulin resistance.

Gut dysbiosis is associated with the reduced exercise capacity of elderly patients with hypertension.

Hypertension is a global health issue, and a reduced exercise capacity is unavoidable for older people. According to recent clinical studies, the intestinal microbiota play a crucial role in the pathogenesis of many human diseases. We investigated whether specific alterations in the gut microbiota contribute to the reduced exercise capacity of elderly patients with hypertension. This study enrolled 56 subjects, and all patients performed a cardiopulmonary exercise test and underwent fecal bacteria sequencing (16 s ribosomal RNA V4 region). According to peak oxygen uptake values, patients were divided into three groups (Weber A = 19, Weber B = 20, and Weber C = 17). The alpha diversity was not significantly different among the three groups. Regarding the beta diversity, Weber A samples were separate from the other two groups in the nonmetric multidimensional scaling ordination plot (ANOSIM pairwise comparisons generated an R > 0.5; p < 0.05). The abundance of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Faecalibacterium and Ruminococcaceae was diminished in subjects with a reduced exercise capacity (LDA score > 4.0). Escherichia coli are a primary producer of trimethylamine and inflammation in the human gut, and the abundance of this bacteria was increased in patients with a reduced exercise capacity (LDA score > 4.0). On the other hand, Lachnospiraceae-Eubacterium_hallii_group, Lachnospiraceae-Lachnoclostridium, Lachnospiraceae-Blautia-Ruminococcus_sp__5_1_39BFAA, and Ruminococcaceae-Faecalibacterium belong to the order Clostridiales that are likely to produce short-chain fatty acids (LDA score > 4.0), and some of these species were enriched in the Weber B or Weber C group in multiple comparisons. Our data pointed to an altered gut microbiota as a potential contributor to the pathogenesis and progression of the reduced exercise capacity of elderly patients with hypertension.

Calcein-acetoxymethy ester enhances the antitumor effects of doxorubicin in nonsmall cell lung cancer by regulating the TopBP1/p53RR pathway.

Calcein acetoxymethyl ester (calcein-AM) treatment has been reported to exert antitumor effects in certain cancer cells; however, the detailed mechanism of action of calcein-AM in cancers remains unclear, especially in nonsmall cell lung cancer (NSCLC). This study focused on the function and mechanism of action of calcein-AM in NSCLC. We used cell viability assays, western blotting, and EdU proliferation assay combined with calcein-AM treatment or siRNA interference to investigate the role of topoisomerase IIß binding protein 1 (TopBP1) and p53 in NSCLC chemotherapy. We found that calcein-AM has antitumor effects in lung cancer and enhances the antitumor effects of doxorubicin in NSCLC. Furthermore, we found that TopBP1, which we previously showed was involved in doxorubicin resistance through upregulation of aberrant p53, was involved in calcein-AM-mediated increased doxorubicin sensitivity. Doxorubicin upregulated the expression of aberrant p53. Calcein-AM repressed the expression of TopBP1, which resulted in reduced expression of aberrant p53 and disrupted the antiapoptotic activity mediated by the TopBP1/mutp53 pathway in NSCLC. Together, our findings show that calcein-AM, the cell-permeable derivative of calcein, exerts significant antitumor effects in NSCLC, and can enhance the antitumor effect of doxorubicin by regulating the TopBP1/mutp53 pathway. These findings provide novel insight into lung cancer treatment.

Glutathione S-Transferase T1 Null Genotype is Associated with Susceptibility to Inflammatory Bowel Disease.

BACKGROUND: The published literature contains conflicting results regarding the impact of the glutathione S-transferase T1 (GSTT1) null genotype on the susceptibility to inflammatory bowel disease. Therefore, we conducted a meta-analysis of observational studies to assess the association. METHODS: We searched four online databases for eligible studies. The odds ratio (OR) with 95% CI was used to assess the gene-disease association. We also performed subgroup analyses by type of inflammatory bowel disease and ethnicity. RESULTS: There were 16 individual studies from 11 publications included in the analysis. There were 3366 cases with inflammatory bowel disease and 6013 controls. The meta-analysis of all 16 studies showed the GSTT1 null genotype was associated with increased susceptibility to inflammatory bowel disease (OR = 1.98, 95%CI 1.39-2.84, P < 0.001). The subgroup analysis by ethnicity further identified an association between the GSTT1 null genotype and inflammatory bowel disease in Caucasians, Asians, and Africans. The GSTT1 null genotype was associated with both ulcerative colitis (OR = 1.96, P = 0.004) and Crohn's disease (OR = 2.01, P = 0.022). The GSTT1 null genotype was still significantly associated with ulcerative colitis (OR = 1.63, P < 0.0001) and Crohn's disease (OR = 1.40, P = 0.023) after adjusting for study heterogeneity. CONCLUSION: The GSTT1 null genotype is significantly associated with an increased susceptibility to inflammatory bowel disease and is a risk factor for both ulcerative colitis and Crohn's disease.

Clostridium difficile colonization in preoperative colorectal cancer patients.

The entire process of Clostridium difficile colonization to infection develops in large intestine. However, the real colonization pattern of C. difficile in preoperative colorectal cancer patients has not been studied. In this study, 33 C. difficile strains (16.1%) were isolated from stool samples of 205 preoperative colorectal cancer patients. C. difficile colonization rates in lymph node metastasis patients (22.3%) were significantly higher than lymph node negative patients (10.8%) (OR=2.314, 95%CI=1.023-5.235, P =0.025). Meanwhile, patients positive for stool occult blood had lower C. difficile colonization rates than negative patients (11.5% vs. 24.0%, OR=0.300, 95%CI=0.131-0.685, P =0.019). A total of 16 sequence types were revealed by multilocus sequence typing. Minimum spanning tree and time-space cluster analysis indicated that all C. difficile isolates were epidemiologically unrelated. Antibiotic susceptibility testing showed all isolates were susceptible to vancomycin and metronidazole. The results suggested that the prevalence of C. difficile colonization is high in preoperative colorectal cancer patients, and the colonization is not acquired in the hospital. Since lymph node metastasis colorectal cancer patients inevitably require adjuvant chemotherapy and C. difficile infection may halt the ongoing treatment, the call for sustained monitoring of C. difficile in those patients is apparently urgent.

TopBP1 contributes to the chemoresistance in non-small cell lung cancer through upregulation of p53.

Resistance to chemotherapeutic drugs is a major obstacle in non-small cell lung cancer (NSCLC) therapy. The molecular determinants of NSCLC resistance to doxorubicin are unknown. In the present study, we investigated whether topoisomerase IIß binding protein 1 (TopBP1) was involved in the chemoresistance to doxorubicin in NSCLC cancer. We found that p53-deficient lung cancer cells (NCI-H1299) displayed the greatest resistance to doxorubicin compared with NCI-H358, A549, and HCC827 cells with p53 expression. The expression of TopBP1 was significantly higher in NCI-H1299 cells than the other three tumor cell lines. In addition, TopBP1 knockdown with specific small interfering RNA in NCI-H1299 cells enhanced the doxorubicin chemosensitivity and decreased the expression of p53 in the presence of doxorubicin. After doxorubicin administration, co-immunoprecipitation assay showed that TopBP1 promoted the expression of p53 in NCI-H1299 cells. These results for the first time demonstrated that TopBP1 plays an important role in NSCLC chemoresistance via upregulation of p53. Therefore, inhibition of TopBP1, in combination with chemotherapy, may represent a novel strategy for the treatment of chemotherapy-resistant NSCLC.

CYP2E1 T7632A and 9-bp insertion polymorphisms and colorectal cancer risk: a meta-analysis based on 4,592 cases and 5,918 controls.

Previous studies suggest that genetic factors play important roles in the development of colorectal cancer. CYP2E1 T7632A and 9-bp insertion polymorphisms may influence the risk of colorectal cancer, but published results are conflicting. We therefore conducted a meta-analysis comprising 9 case-control studies with 4,592 cases and 5,918 controls. Odds ratios (ORs) with 95 % confidence interval (95 % CI) were used to assess the strength of the associations of CYP2E1 T7632A and 9-bp insertion polymorphisms with colorectal cancer. For CYP2E1 T7632A polymorphism, meta-analysis showed that there was no significant association between the CYP2E1 T7632A polymorphism and colorectal cancer risk under all contrast models (A vs. T: OR = 1.06, 95 % CI 0.88-1.29, P = 0.528; AA vs. TT: OR = 0.85, 95 % CI 0.61-1.19, P = 0.351; AA/TA vs. TT: OR = 1.08, 95 % CI 0.87-1.34, P = 0.484; and AA vs. TT/TA: OR = 0.87, 95 % CI 0.62-1.21, P = 0.395). For CYP2E1 96-bp insertion polymorphism, meta-analysis showed that there was a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk under the allele contrast model and the dominant contrast model (for the allele contrast model: OR = 1.20, 95 % CI 1.06-1.36, P = 0.005; for the dominant contrast model: OR = 1.25, 95 % CI 1.07-1.45, P = 0.005). Subgroup analysis by race suggested that there was an obvious association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk in Asians under the codominant contrast model. In conclusion, our meta-analysis demonstrates that there is a significant association between the CYP2E1 96-bp insertion polymorphism and colorectal cancer risk, and CYP2E1 9-bp insertion polymorphism is a risk factor for developing colorectal cancer.

The combined treatment of CT-guided percutaneous 125I seed implantation and chemotherapy for non-small-cell lung cancer.

PURPOSE: Gemcitabine plus cisplatin (GP) is a first-line treatment for advanced non-small-cell lung cancer (NSCLC). In this study, we evaluated the efficacy and safety of a combined treatment consisting of CT-guided percutaneous (125)I seed implantation with GP chemotherapy for advanced NSCLC. METHODS: Fifty-three patients with advanced NSCLC were enrolled in a nonrandomized, two-armed clinical trial. Of these patients, 24 received a combination treatment of CT-guided percutaneous (125) I seed implantation and GP (the combo group), while 29 were treated with GP only (the control group). RESULTS: Patients in the combo group received (125)I seed implantation with prescription dose of 100-140 Gy and a total of 55 cycles of GP, and patients in the control group received a total of 73 cycles of GP. The overall response rate was 79.2% in the combo group and 41.4% in the control group. The median overall survival time was 13.5 ± 1.5 months in the combo group and 9.0 ± 1.8 months in the control group. The progression-free survival time was 8.0 ± 1.2 months in the combo group and 5.0 ± 0.8 months in the control group. The 1- and 2-year survival rates were 62.5 and 16.7% in the combo group, respectively, and 41.4 and 13.8% in the control group. The interventional complications in the combo group included 5 cases of pneumothorax and 4 cases of hemoptysis. There were no complications due to radiation pneumonia or radiation esophagitis in the combo group, and no patients had lethal hemoptysis or esophagotracheal fistula. Chemotherapy treatment-related toxicities, including Grade 3/4 myelosuppression and Grade 3 gastrointestinal toxicity, were similar in both groups. CONCLUSIONS: Our initial experience showed that combined CT-guided (125)I radioactive seed implantation and GP chemotherapy are effective and safe for treating advanced NCSLC.