Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway

<div><p>Background</p><p>Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR).</p><p>Methods</p><p>Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro.</p><p>Results</p><p>Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP <i>in vitro</i>.</p><p>Conclusion</p><p>Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.</p></div

Mouse chlorine exposure system.

<p>A, a container filled with NaOCl solution was placed in the cage and mice were exposed to naturally vaporizing chlorine gas 8 hours a day, 5 times a week, for 4 weeks. B, a container with holes on the top surface to avoid direct skin contact with the NaOCl solution.</p

Effect of low dose chronic chlorine exposure on allergen-induced airway hyperresponsiveness and inflammation 6 weeks old BALB/c mice were sensitized and challenged with OVA allergen with or without low dose chlorine exposure.

<p>A, Airway hyperresponsiveness was determined by whole body phlethysmography *<i>p</i><0.05 vs. other groups. B, Lung inflammatory response were measured by BAL cell recovery. Macro, macrophages; Neutro, neutrophils; Eosino, eosinophils; Lympho, lymphocytes. *<i>p</i><0.05 vs. other groups. C, H&E staining (x200). D, Quantification of eosinophil in the lung tissue. E, PAS staining (x200), F: Semi-quantified mucus index score in the PAS staining. Values in panels A, B, D and F are mean ± SEM of evaluations in a minimum of 5 mice. Panel C and E is a representative of a minimum of four similar experiments.</p

Effect of low dose chronic chlorine exposure on Th2 cytokine and IL-17 expression in OVA sensitized and challenged mice.

<p>A-C, the mRNA expression of IL-4 (A), IL-5(B) and IL-13(C) was evaluated by RT-qPCR. D. The level of IL-17 in BAL was measured by ELISA. Values in these panels are mean ± SEM of evaluations in a minimum of 5 mice. *<i>p</i><0.05 vs. OVA only group.</p

Effect of low dose chronic chlorine exposure on the expression of epithelial alarmines.

<p>A, The levels of IL-33 expression in the lungs from the mice sensitized and challenged by OVA with or without chlorine exposure were evaluated by RT-qPCR. *<i>p</i><0.05 vs. groups without chlorine exposure. B, The mRNA expressions of IL-33 in murine MLE12 epithelial cells were measured by qRT-PCR after 48 and 96 hrs stimulation of 0.001% NaOCl. *<i>p</i><0.05 vs. control. C, TSLP protein expression was evaluated by Western blot analysis. Values in panels A and B are mean ± SEM of evaluations in a minimum of 5 mice. Panel C is a representative of a minimum of three similar experiments.</p

Large Electroabsorption Susceptibility Mediated by Internal Photoconductive Gain in Ge Nanowires

Large spectral modulation in the photon-to-electron conversion near the absorption band-edge of a semiconductor by an applied electrical field can be a basis for efficient electro-optical modulators. This electro-absorption effect in Group IV semiconductors is, however, inherently weak, and this poses the technological challenges for their electro-photonic integration. Here we report unprecedentedly large electro-absorption susceptibility at the direct band-edge of intrinsic Ge nanowire (NW) photodetectors, which is strongly diameter-dependent. We provide evidence that the large spectral shift at the 1.55 μm wavelength, enhanced up to 20 times larger than Ge bulk crystals, is attributed to the internal Franz–Keldysh effect across the NW surface field of ∼10⁵ V/cm, mediated by the strong photoconductive gain. This classical size-effect operating at the nanometer scale is universal, regardless of the choice of materials, and thus suggests general implications for the monolithic integration of Group IV photonic circuits

Enhanced Device Performance of Germanium Nanowire Junctionless (GeNW-JL) MOSFETs by Germanide Contact Formation with Ar Plasma Treatment

In this study, germanium nanowire junctionless (GeNW-JL) metal-oxide-semiconductor-field-effect-transistors (MOSFETs) exhibited enhanced electrical performance with low source/drain (S/D) contact resistance under the influence of Ar plasma treatment on the contact regions. We found that the transformation of the surface oxide states by Ar plasma treatment affected the S/D contact resistance. With Ar plasma treatment, the germanium dioxide on the GeNW surface was effectively removed and increased oxygen vacancies were formed in the suboxide on the GeNW, whose germanium-enrichment surface was obtained to form a germanide contact at low temperature. After a rapid thermal annealing process, Ni-germanide contacts were formed on the Ar-plasma-treated GeNW surface. Ni-germanide contact resistance was improved by more than an order of magnitude compared to that of the other devices without Ni-germanide contact. Moreover, the peak field effect mobility value of the GeNW-JL MOSFETs was dramatically improved from 15 cm²/(V s) to 550 cm²/(V s), and the <i>I</i>_on/off ratio was enhanced from 1 × 10 to 3 × 10³ due to Ar plasma treatment. The Ar plasma treatment process is essential for forming uniform Ni-germanide-contacts with reduced time and low temperature. It is also crucial for increasing mass productivity and lowering the thermal budget without sacrificing the performance of GeNW-JL MOSFETs

Tunable Catalytic Alloying Eliminates Stacking Faults in Compound Semiconductor Nanowires

Planar defects in compound (III–V and II–VI) semiconductor nanowires (NWs), such as twin and stacking faults, are universally formed during the catalytic NW growth, and they detrimentally act as static disorders against coherent electron transport and light emissions. Here we report a simple synthetic route for planar-defect free II–VI NWs by tunable alloying, i.e. Cd_1–<i>x</i>Zn_<i>x</i>Te NWs (0 ≤ <i>x</i> ≤ 1). It is discovered that the eutectic alloying of Cd and Zn in Au catalysts immediately alleviates interfacial instability during the catalytic growth by the surface energy minimization and forms homogeneous zinc blende crystals as opposed to unwanted zinc blende/wurtzite mixtures. As a direct consequence of the tunable alloying, we demonstrated that intrinsic energy band gap modulation in Cd_1–<i>x</i>Zn_<i>x</i>Te NWs can exploit the tunable spectral and temporal responses in light detection and emission in the full visible range