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Diagnostic sensing device using exhaled breath of human have critical advantages due to the noninvasive diagnosis and high potential for portable device with simple analysis process. Here, we report ultrafast as well as highly sensitive bumpy WO3hemitube nanostructure assisted by O2plasma surface modification with functionalization of graphene-based material for the detection of acetone (CH3COCH3) and hydrogen sulfide (H2S) which are biomarkers for the diagnosis of diabetes and halitosis, respectively. 0.1 wt % graphene oxide (GO)- and 0.1 wt % thin layered graphite (GR)- WO3hemitube composites showed response times of 11.5 ± 2.5 s and 13.5 ± 3.4 s to 1 ppm acetone as well as 12.5 ± 1.9 s and 10.0 ± 1.6 s to 1 ppm of H2S, respectively. In addition, low limits of detection (LOD) of 100 ppb (Rair/Rgas= 1.7 for acetone and Rair/Rgas= 3.3 for H2S at 300 °C) were achieved. The superior sensing properties were ascribed to the electronic sensitization of graphene based materials by modulating space charged layers at the interfaces between n-type WO3hemitubes and p-type graphene based materials, as identified by Kelvin Probe Force Microscopy (KPFM). Rapid response and superior sensitivity of the proposed sensing materials following cyclic thermal aging demonstrates good potential for real-time exhaled breath diagnosis of diseases.

Sensitive detection of acetone and hydrogen sulfide levels in exhaled human breath, serving as breath markers for some diseases such as diabetes and halitosis, may offer useful information for early diagnosis of these diseases. Exhaled breath analyzers using semiconductor metal oxide (SMO) gas sensors have attracted much attention because they offer low cost fabrication, miniaturization, and integration into portable devices for noninvasive medical diagnosis. However, SMO gas sensors often display cross sensitivity to interfering species. Therefore, selective real-time detection of specific disease markers is a major challenge that must be overcome to ensure reliable breath analysis. In this work, we report on highly sensitive and selective acetone and hydrogen sulfide detection achieved by sensitizing electrospun SnO2nanofibers with reduced graphene oxide (RGO) nanosheets. SnO2nanofibers mixed with a small amount (0.01 wt %) of RGO nanosheets exhibited sensitive response to hydrogen sulfide (Rair/Rgas= 34 at 5 ppm) at 200 °C, whereas sensitive acetone detection (Rair/Rgas= 10 at 5 ppm) was achieved by increasing the RGO loading to 5 wt % and raising the operation temperature to 350 °C. The detection limit of these sensors is predicted to be as low as 1 ppm for hydrogen sulfide and 100 ppb for acetone, respectively. These concentrations are much lower than in the exhaled breath of healthy people. This demonstrates that optimization of the RGO loading and the operation temperature of RGO–SnO2nanocomposite gas sensors enables highly sensitive and selective detection of breath markers for the diagnosis of diabetes and halitosis.

In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A–induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2–mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through “normalization” of vascular permeability in addition to previously described antiangiogenic effects.

In cancer, VEGF-induced increase in vascular permeability results in increased interstitial pressure, reducing perfusion and increasing hypoxia, which reduce delivery of chemotherapeutic agents and increase resistance to ionizing radiation. Here, we show that both TIMP-2 and Ala + TIMP-2, a TIMP-2 mutant without matrix metalloproteinase inhibitory activity, antagonize the VEGF-A–induced increase in vascular permeability, both in vitro and in vivo. Like other agents known to preserve endothelial barrier function, TIMP-2 elevates cytosolic levels of cAMP and increases cytoskeletal-associated vascular endothelial cadherin in human microvascular endothelial cells. All of these effects are completely ablated by selective knockdown of integrin α3β1 expression, expression of a dominant negative protein tyrosine phosphatase Shp-1 mutant, administration of the protein tyrosine phosphatase inhibitor orthovanadate, or the adenylate cyclase inhibitor SQ22536. This TIMP-2–mediated inhibition of vascular permeability involves an integrin α3β1-Shp-1-cAMP/protein kinase A-dependent vascular endothelial cadherin cytoskeletal association, as evidenced by using siRNAs to integrin α3β1 and Shp-1, or treatment with Shp-1 inhibitor NSC87877 and protein kinase A inhibitor H89. Our results demonstrate the potential utility for TIMP-2 in cancer therapy through “normalization” of vascular permeability in addition to previously described antiangiogenic effects.