Special Issue on Flexible and Wearable Sensors for Robotics and HealthJ. Semicond. Volume 40錛 Number 11 November 2019RESEARCH HIGHLIGHTSStretchable artificial synapse for soft robotsChuan WangJ. Semicond. 2019錛 40(11): 110201doi: 10.1088/1674-4926/40/11/110201MXene-based wearable biosensorYou Meng錛 Johnny C HoJ. Semicond. 2019錛 40(11): 110202doi: 10.1088/1674-4926/40/11/110202EDITORIALPreface to the Special Issue on Flexible and Wearable Sensors for Robotics and HealthZhiyong Fan錛 Johnny C Ho錛 Chuan Wang錛 Yun-Ze Long錛 Huan LiuJ. Semicond. 2019錛 40(11): 110101doi: 10.1088/1674-4926/40/11/110101REVIEWSSmart gas sensor arrays powered by artificial intelligenceZhesi Chen錛 Zhuo Chen錛 Zhilong Song錛 Wenhao Ye錛 Zhiyong FanJ. Semicond. 2019錛 40(11): 111601doi: 10.1088/1674-4926/40/11/111601Recent advances in flexible photodetectors based on 1D nanostructuresSenpo Yip錛 Lifan Shen錛 Johnny C HoJ. Semicond. 2019錛 40(11): 111602doi: 10.1088/1674-4926/40/11/111602Electrospun flexible sensorQi Liu錛 Seeram Ramakrishna錛 Yun-Ze LongJ. Semicond. 2019錛 40(11): 111603doi: 10.1088/1674-4926/40/11/111603Flexible and stretchable photodetectors and gas sensors for wearable healthcare based on solution-processable metal chalcogenidesQi Yan錛 Liang Gao錛 Jiang Tang錛 Huan LiuJ. Semicond. 2019錛 40(11): 111604doi: 10.1088/1674-4926/40/11/111604Recent advances in lithographic fabrication of micro-/nanostructured polydimethylsiloxanes and their soft electronic applicationsDonghwi Cho錛 Junyong Park錛 Taehoon Kim錛 Seokwoo JeonJ. Semicond. 2019錛 40(11): 111605doi: 10.1088/1674-4926/40/11/111605Preparation and application of carbon nanotubes flexible sensorsShuo Li錛 Xiao Feng錛 Hao Liu錛 Kai Wang錛 Yun-Ze Long錛 S. RamakrishnaJ. Semicond. 2019錛 40(11): 111606doi: 10.1088/1674-4926/40/11/111606Advances in flexible and wearable pH sensors for wound healing monitoringMei Qin錛 Hao Guo錛 Zhang Dai錛 Xu Yan錛 Xin NingJ. Semicond. 2019錛 40(11): 111607doi: 10.1088/1674-4926/40/11/111607Recent progress on gas sensors based on graphene-like 2D/2D nanocompositesSongyang Yuan錛 Shaolin ZhangJ. Semicond. 2019錛 40(11): 111608doi: 10.1088/1674-4926/40/11/111608ARTICLESScreen-printed soft triboelectric nanogenerator with porous PDMS and stretchable PEDOT:PSS electrodeHaochuan Wan錛 Yunqi Cao錛 Li-Wei Lo錛 Zhihao Xu錛 Nelson Sep□lveda錛 Chuan WangJ. Semicond. 2019錛 40(11): 112601doi: 10.1088/1674-4926/40/11/112601One-pot preparation and applications of self-healing錛 self-adhesive PAA-PDMS elastomersYujin Yao錛 Huiling Tai錛 Dongsheng Wang錛 Yadong Jiang錛 Zhen Yuan錛 Yonghao ZhengJ. Semicond. 2019錛 40(11): 112602doi: 10.1088/1674-4926/40/11/112602Detection of Selenocysteine with a Ratiometric near-Infrared Fluorescent Probe in Cells and in Mice Thyroid Diseases ModelXianzhu Luo【羅賢柱】 Rui Wang【王銳】 Chuanzhu Lv 【呂傳柱】Guang Chen【陳光】* Jinmao You【尤進茂】* Fabiao Yu【于法標】*AbstractThe pathological progression of thyroid diseases poses a serious threat to human health. Because thyroid diseases are closely related to selenocysteine (Sec)錛 it is necessary to investigate the relationship between Sec and thyroid diseases. Herein錛 we design and synthesize a ratiometric near-infrared fluorescent probe (Mito-Cy-Sec) to analyze the fluctuations and roles of Sec in cells and in mice thyroid diseases model. The probe is composed of a near-infrared heptamethine cyanine fluorophore錛 an acrylamide as the response moiety錛 and a lipophilic triphenylphosphonium cation as the mitochondrial localization group. After reacting with Sec for 5 min錛 the probe Mito-Cy-Sec exhibits a distinct ratiometric fluorescence signal accompanied by a color change from green to blue. The applicability of Mito-Cy-Sec in mitochondrial localization is assessed via the super-resolution imaging. Mito-Cy-Sec has been successfully applied to detect the fluctuations of Sec concentration in human thyroid epithelial/cancer cell lines (Nthy-ori-3 cells/BHT101 cells) and mice thyroid disease (thyroiditis and thyroid cancer) models. Besides錛 both of our probes Mito-Cy-Sec and commercial ROSGreen H2O2 are employed to examine the interrelationship between H2O2 and Sec in cells and in mice models. The results demonstrate that the relevant-levels between H2O2 and Sec are exactly negative correlation. The related-levels of Sec and H2O2 may be identified as diagnostic indicators for the auxiliary diagnosis of thyroid diseases. We suppose that our probe Mito-Cy-Sec can be employed as a promising chemical tool for the diagnosis of thyroid diseases.Publication Date:December 9錛 2019https://doi.org/10.1021/acs.analchem.9b04860Scheme 1. The molecular structure of Mito-Cy-Sec and its proposed response mechanism towards selenocysteineFigure 1. Spectral properties and selectivity of Mito-Cy-Sec. Data were recorded after 5 min incubated with different concentration of Sec (0 – 15 μM) at 37 oC in HEPES (pH 7.4錛 10 mM). Dose-dependent absorbance spectra a)錛 emission spectra b) (λex = 630 nm錛 λem = 720 – 780 nm) and c) (λex = 730 nm錛 λem = 780 – 840 nm).d) The linear relationship between lg (F765 nm/F825 nm) and Sec. Insert: Ratiometric intensity changes with different concentrations of Sec. e) Time-dependent fluorescent ratio (F765 nm/F825 nm) toward Sec during 0 – 390 s錛 and probe was added at 30 s. f) The fluorescent ratio (F765 nm/F825 nm) response of Mito-Cy-Sec to various reactive species at 5 min: 1錛 blank錛 2錛 150 μM GSH; 3錛 150 μM Cys; 4錛 150 μM Hcy; 5錛 15 μM NaHS; 6錛 15 μMNAC; 7錛 15 μM selenomethionine; 8錛 15 μMselenocystine; 9錛 15 μM Se-methylselenocysteine; 10錛 15 μM ascorbic acid; 11錛 15 μM GPx; 12錛 15 μM TrxR; 13錛 15 μM Na2SeO3; 14錛 15 μM DTT; 15錛 15 μM Sec. The experiments were repeated three times and the data were shown as mean (± S.D.).Figure 2. Fluorescence images and flow cytometry analyses of endogenous and exogenous Sec in Hela cells. a) Incubated with Mito-Cy-Sec (10 μM) for 10 min as control. Another two cell groups were pretreated with (Sec)2 (2 μM) and Na2SeO3 (5 μM) for 12 h錛 then incubated with 10 μM probe for 10 min錛 respectively. Fluorescence collection windows for Ch 1: 720 – 780 nm (λex = 630 nm)錛 Ch 2: 780 – 840 nm (λex = 730 nm). b) Corresponding flow cytometry analysis. c) The average ratiometric values in a. d) Mean ratiometric values in b. The experiments were repeated three times and the data were shown as mean (± S.D.). Figure 3. Mitochondrial colocalization with Mito-Cy-Sec and Mito Tracker Green FM in HepG2 cells. Fluorescence collection windows for green channel: 500 – 550 nm (λex = 488 nm)錛 and red channel: 780 – 840 nm (λex = 730 nm). a) Cells were stained with MitoTracker Green FM (200 nM) for 30 min and Mito-Cy-Sec (10 μM) for 10 min錛 scale bar: 10 μm. b) Enlarged images in the field view of the cyan frame in a) for mitochondrial colocalization. c) Super-resolution imaging of mitochondria with the same region in b)錛 scale bar: 2 μm. d) The colocalization and correlation between the selected red and green channels in a). e) and f) Intensity profile of the blue arrow in b) and c) across cell錛 respectively. Figure 4. Imaging of endogenous Sec in Nthy-ori3-1 and BHT101 cells. a) Pseudo-color ratiometric images of endogenous Sec generation in Nthy-ori3-1 cells and BHT101 cells at different time points: 0 min錛 2 min錛 4 min錛 6 min錛 8 min錛 and 10 min. b) Flow cytometry analysis for a). c) and d) Average ratiometric intensities changes of Mito-Cy-Sec toward Nthy-ori3-1 and BHT101 cells in a) and b)錛 respectively. The experiments were repeated three times and the data were shown as mean (± S.D.).Figure 5. Ratiometric fluorescence images of Sec in different types of thyroid disease cell models with Mito-Cy-Sec (10 μM) and ROSGreen H2O2 (5 μM) by confocal microscopic imaging and flow cytometry analysis. a) The ratiometric images of endogenous Sec in thyroid model cells. Group a: Nthy-ori3-1 cells; Group b: Nthy-ori3-1 cells stimulated by INF-γ for 24 h; Group c: Nthy-ori3-1 cells stimulated by INF-γ/LPS for 6 h; Group d: BHT101 cells; Group e: Nthy-ori3-1 cells incubated with 50 μM selenocysteine (Sec)2 for 2 h before stimulated by INF-γ; Group f: Nthy-ori3-1 cells incubated with 50 μM (Sec)2 for 2 h before stimulated by INF-γ/LPS; and Group g: BHT101 cells incubated with 50 μM (Sec)2 for 2 h. Fluorescence collection windows for Ch 1: 720 – 780 nm (λex = 630 nm)錛 Ch 2: 780 – 840 nm(λex = 730 nm)錛 and Ch 3: 500 – 550 nm(λex = 488 nm). b) Flow cytometry analysis of the cells in a). c) The average ratio (Ch 1 : Ch 2) values in a). d) Mean fluorescent intensities of Ch 3 in a). e) The average ratio (Ch 1 : Ch 2) values in b). f) Mean fluorescent intensities of Ch 3 in b). g) Apoptosis and necrosis assays of group a – g in a) by Annexin V-FITC/Propidium Iodide (PI). Q1): necrosis錛 Q2): late apoptosis錛 Q3): early apoptosis錛 Q4): viable. Scale bar: 20 μm. The experiments were repeated three times and the data were shown as mean (± S.D.).Figure 6. In vivo imaging of Sec in different mice thyroid diseases model. a) Fluorescence images of mice in group a – group e. group a: control group; group b: thyroiditis mice group; group c: thyroid cancer mice; group d: BALB/c mice were pretreated with 500 μg.kg-1 selenocystine (intraperitoneal injection錛 (i.p.)) in saline daily for eight weeks before the same treatment of group b; and group e: BALB/c mice were pretreated with 500 μg.kg-1 selenocystine (i.p.) in saline daily for eight weeks before the same treatment as group c. All the mice models were treated with Mito-Cy-Sec (10 μM錛 50 μL in DMSO : saline = 1 : 99錛 v:v) and ROSGreen H2O2 (5 μM錛 50 μL in DMSO : saline = 1 : 99錛 v:v) for 30 min through neck injection before in vivo fluorescence imaging. Fluorescence collection windows for Ch 1: 720 – 780 nm (λex = 630 nm)錛 Ch 2: 780 – 840 nm (λex = 730 nm)錛 Ch 3: 500 – 550 nm (λex = 488 nm)錛 and ratio: Ch 1 vs Ch 2. b) H&E stained thyroid tissues histopathology images. c) Masson's stained slices of thyroid tissues. d) Fluorescence images of different fresh mice thyroid diseases slices by simultaneously incubated with Mito-Cy-Sec (10 μM) and ROSGreen H2O2 (5 μM) for 20 min. e) The average ratio (Ch 1 vs Ch 2) values in a). f) Mean fluorescent intensities of Ch 3 in a). g) The average ratio (Ch 1 vs Ch 2) values in d). h) Mean fluorescent intensities of Ch 3 in d).Figure 7. Fluorescence 3D images of different mice thyroid diseases slices incubated with Mito-Cy-Sec (10 μM) and ROSGreen H2O2 (5 μM) for 20 min. Fluorescence collection windows for Ch 1: 720 – 780 nm (λex = 630 nm)錛 Ch 2: 780 – 840 nm (λex = 730 nm)錛 Ch 3: 500 – 550 nm (λex = 488 nm)錛 and Ratio images: Ch 1 : Ch 2.，
