Terahertz high-sensitivity SIS mixer based on Nb–AlN–NbN hybrid superconducting tunnel junctions

The terahertz band,a unique segment of the electromagnetic spectrum,is crucial for observing the cold,dark universe and plays a pivotal role in cutting-edge scientific research,including the study of cosmic environments that support life and imaging black holes.High-sensitivity superconductor–insulator–superconductor(SIS)mixers are essential detectors for terahertz astronomical telescopes and interferometric arrays.Compared to the commonly used classical Nb/AlO_(x)/Nb superconducting tunnel junction,the Nb/AlN/NbN hybrid superconducting tunnel junction has a higher energy gap voltage and can achieve a higher critical current density.This makes it particularly promising for the development of ultra-wideband,high-sensitivity coherent detectors or mixers in various scientific research fields.In this paper,we present a superconducting SIS mixer based on Nb/AlN/NbN parallel-connected twin junctions(PCTJ),which has a bandwidth extending up to490 GHz–720 GHz.The best achieved double-sideband(DSB)noise temperature(sensitivity)is below three times the quantum noise level.

Cisplatin-induced premature senescence with concomitant reduction of gap junctions in human fibroblasts

To examine the role of gap junctions in cell senescence,the changes of gap junctions in cisplatin-induced premature senescence of primary cultured fibroblasts were studied and compared with the replicative senescent human fibroblasts.Dye transfer assay for gap junction function and immunofluorescent staining for connexin 43 protein distribution were done respectively. Furthermore,cytofluorimetry and DAPI fluorescence staining were performed for cell cycle and apoptosis analysis. p53 gene expression level was detected with indirect immunofluorescence. We found that cisplatin (10 mM) treatment could block cell growth cycle at G1 and induced premature senescence. The premature senescence changes included high frequency of apoptosis,elevation of p53 expression,loss of membranous gap junctions and reduction of dye-transfer capacity. These changes were comparable to the changes of replicative senescence of human fibroblasts. It was also concluded that cisplatin could induce premature senescence concomitant with inhibition of gap junctions in the fibroblasts. Loss of functional gap junctions from the cell membrane may account for the reduced intercellular communication in the premature senescent fibroblasts. The cell system we used may provide a model useful for the study of the gap junction thus promoting agents against premature senescence.

Energy gap suppression and excess current in TI2Ba2CaCu208 intrinsic Josephson junctions

Intrinsic Josephson junctions in misaligned T12Ba2CaCu208 thin film were fabricated on LaA103 substrate. The temperature dependence of the critical current is investigated around liquid nitrogen temperature. In the current voltage characteristic, large voltage jump and lack of resistive branch are observed, which shows good consistency with the intrinsic Josephson junctions. By analyzing the large gap voltage in the curve, great suppression of the energy gap is found. Through discussing the temperature dependence of the gap voltage in liquid nitrogen temperature, it is shown that this phenomenon can be caused by the non-equilibrium quasiparticle injection. The temperature influence on the excess current also confirms the non-equilibrium effect.

Connexin therapeutics:blocking connexin hemichannel pores is distinct from blocking pannexin channels or gap junctions

Compounds that block the function of connexin and pannexin protein channels have been suggested to be valuable therapeutics for a range of diseases.Some of these compounds are now in clinical trials,but for many of them,the literature is inconclusive about the molecular effect on the tissue,despite evidence of functional recovery.Blocking the different channel types has distinct physiological and pathological implications and this review describes current knowledge of connexin and pannexin protein channels,their function as channels and possible mechanisms of the channel block effect for the latest therapeutic compounds.We summarize the evidence implicating pannexins and connexins in disease,considering their homeostatic versus pathological roles,their contribution to excesive ATP release linked to disease onset and progression.

Gap junctions enhance the antiproliferative effect by transfer of microRNAs in glioma cells

OBJECTIVE To investigate the permeability of gap junction composed of connexin 43(Cx43)for micro RNAs(mi RNAs)and the impact of gap junction-mediated transfer of mi RNAs in glioma U87 cells.METHODS Co-culture assay demonstrated the transmission of miR NAs through gap junction channel into adjacent cells.U87 cells were labeled with green fluorescein protein(GFP)as receivers and cells were transfected mi RNAs as donors.Receiver cells and donor cells were mixed together in a ratio of 1∶1.After 12 h co-culture,cells were separated using a BD influx flow cytometer based on the GFP labeled.Quantitative real-time polymerase chain reaction(q RT-PCR)was applied detect to the expressions of miR NAs and Cx43 mR NA.Western blotting was performed to detect the protein expressions of Cx43 and GFP in U87 cells.CCK-8 assay is used to detect cell growth.RESULTS Co-culture assays demonstrated mi R-34a could transfer between U87 cells.The role of the contact independent could also transfer of miR-34a.Gap junctions inhibitor(CBX and 18-α-GA)showed lower miR-34a expression than co-culture group,whereas gap junctions enhancer(RA and Galanglin)enhanced miR-34a expression.Knockdown of Cx43 could significantly decrease the transferring of miR-34a between U87 cells.Different length of miR NAs(miR-1827,miR-144,miR-203a and miR-1183)were similar to the expression of miR-34a between U87 cells.Additionally,we demonstrated that gap junctions mediate the effect of antiproliferation mediated by mi R-34a in U87 cells.The functional inhibition of gap junctions using either si RNA or inhibition eliminated the miR-34a mediated antiproliferation,whereas the enhancement of gap junctions treatment augmented this mi R34a-mediated antiproliferation.CONCLUSION Our study demonstrates that gap junction composed of Cx43-mediated transfer mi RNAs in different length of nucleotides and gap junction-mediated transfer of mi R-34a enhance the antiproliferative effect in glioma U87 cells.

Gap junctions enhance the antiproliferative effect of microrna-34a in glioma cells

OBJECTIVE To investigate the effect of gap junctions on the anti-tumor function induced by mi R-34a in glioma U87 cells.METHODS 1.Transfection(miR-34a mimics were transfected into glioma cells to upregulate their expression);2.Co-culture assay(U87cells were transfected with mi R-34a co-cultured with U87 cells that was transfected PCMV-eG FP plasmid);3.Flow cytometry analysis(select the e GFP labed U87 cells);4.RNA isolation and real-time PCR;5.CCK-8 assay;6.Western blotting.RESULTS Mi R-34a mimics transfered between the U87 cells.Parachute assay showed that GJ inhibition(CBX and 18-α-GA)can decrease mi R-34a expression than co-culture group.RA and galanglin enhanced mi R-34a expression than co-culture group.Mi R-34a relative expression reduced after co-culture,while gap junctions composed of Cx43 were down-regulated by sh RNA.Transfected with mi R-34a mimics reduced the survival of U87 cells in a dose-dependent manner.To more specifically establish the role of GJIC in mi R-34a induced growth inhibition of U87 cells,si RNA was used to knockdown the expression of Cx43,the dominant connexin expressed in U87 cells.CCK-8 assay showed that siR NAs have no effect on cell growth,but they could aggravate the growth inhibition of miR-34a to U87 cels.CONCLUSION Gap junctions enhance the antiproliferative effect of miR NA-34a in glioma cells.

The spike timing precision of FitzHugh-Nagumo neuron network coupled by gap junctions

It has been proved recently that the spike timing can play an important role in information transmission, so in this paper we develop a network with N-unlt FitzHugh-Nagumo neurons coupled by gap junctions and discuss the dependence of the spike timing precision on synaptic coupling strength, the noise intensity and the size of the neuron ensemble. The calculated results show that the spike timing precision decreases as the noise intensity increases; and the ensemble spike timing precision increases with coupling strength increasing. The electric synapse coupling has a more important effect on the spike timing precision than the chemical synapse coupling.

The role of gap junctions in cell death and neuromodulation in the retina

Vision altering diseases,such as glaucoma,diabetic retinopathy,age-related macular degeneration,myopia,retinal vascular disease,traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable future.Gap junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells,thereby playing a crucial role in pathophysiology.Since they are permeable for macromolecules,able to cross the cellular barriers,they show duality in illness as a cause and as a therapeutic target.In this review,we take recent advancements in gap junction neuromodulation(pharmacological blockade,gene therapy,electrical and light stimulation)into account,to show the gap junction’s role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

Energy gap suppression and excess current in Tl_2Ba_2CaCu_2O_8 intrinsic Josephson junctions

Intrinsic Josephson junctions in misaligned Tl2Ba2CaCu2O8 thin film were fabricated on LaAlO3 substrate. The temperature dependence of the critical current is investigated around liquid nitrogen temperature. In the current voltage characteristic, large voltage jump and lack of resistive branch are observed, which shows good consistency with the intrinsic Josephson junctions. By analyzing the large gap voltage in the curve, great suppression of the energy gap is found. Through discussing the temperature dependence of the gap voltage in liquid nitrogen temperature, it is shown that this phenomenon can be caused by the non-equilibrium quasiparticle injection. The temperature influence on the excess current also confirms the non-equilibrium effect.

Expression of gap junction genes connexin 32,connexin 43 and their proteins in hepatocellular carcinoma and normal liver tissues

AIM To investigate the significance andmechanism of cx32 mRNA,cx43 mRNA and theirproteins in hepatocarcinogenesis.METHODS Sixty-one cases of HCC and 14cases of normal liver tissues were detected byimmunohistochemical and in situ hybridization(ISH)methods.RESULTS In HCC grades Ⅰ,Ⅱ,Ⅲ and normalliver tissues,the positive rates of Cx32 proteinwere 55.6%,42.1%,18.2% and 92.9%,respectively.The detection rates of Cx43 proteinwere 44.4%,26.3%,12.1% and 78.6%,respectively.There was significant difference inCx32 and Cx43 protein between HCC and normalliver tissues(P【0.01).ISH the positive rates ofcx32 mRNA shown by ISH in HCC grades Ⅰ,Ⅱ,Ⅲ and normal liver tissues were 88.9%,84.2%,87.9% and 92.9%,respectively.Those of cx43mRNA were 77.8%,78.6%,78.8% and 85.7%,respectively.There was no statistical differencein the positive rates of cx32 mRNA and cx43mRNA between HCC and normal liver tissue(P】0.05).CONCLUSION The aberrant location of Cx32and Cx43 proteins could be responsible forprogression of hepatocarcinogenesis,and thedefect of cx genes in post-translationalprocessing might be the possible mechanism.

Interplay between magnetic gap and quasiparticle lifetime in topological insulator ferromagnet/f-wave superconductor junctions

Using the modified Blonder-Tinkham-Klapwijk(BTK)theory,the interplay between the lifetime of quasi particles and the magnetic gap in a topological insulator-based ferromagnet/fwave superconductor(TI-based FM/f-wave SC)tunnel structure is theoretically studied.Two symmetries of f_(1) and f_(2) waves are considered for superconducting pairing states.The results indicate that reducing the finite quasi-particle lifetime will induce a transformation of energy-gap peaks into a zero-bias peak in tunneling conductance spectrum,as well as a transformation of energy-gap dips into a zero-bias dip in shot noise spectrum,ultimately resulting in the smoothing of the zero-bias conductance peak and the zero-bias shot noise dip.An increase in magnetic gap will suppress the tunnel conductance and shot noise when the conventional Andreev retroreflection dominates,but will enhance them when the specular Andreev reflection is dominant.Both specular Andreev reflection and conventional Andreev retro-reflection will be enhanced as the quasi-particle lifetime increases.When Fermi energy equals the magnetic gap,shot noise and tunneling conductance vanish across all energy ranges.These findings not only contribute to a better understanding of specular Andreev reflection in the FM/f-wave SC junction based on TIs but also provide insights for experimentally determining the f-wave pairing symmetry.

Altered Expression of Connexin-43 and Impaired Capacity of Gap Junctional Intercellular Communication in Prostate Cancer Cells

Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-called 'bystander effect' mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis. mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by re- verse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malig- nant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. As- sessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was ab- normally located and markedly diminished as compared with normal prostatic epithelial ones, dis- playing a negative correlation to the pathological grade (χ2=4.025, P<0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indi- cated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein par- ticipated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of 'bystander effect', but also to initiation and progression of prostatic neoplasm.

Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

The gap junction blocker carbenoxolone enhances propofol and sevoflurane-induced loss of consciousness

General anesthetics induce loss of consciousness by inhibiting ascending arousal pathways, and they interfere with gap junction electrical coupling. The present study aimed to determine whether inhibition of gap junction-mediated signaling could influence general anesthetic-induced loss of consciousness. The general anesthetics sevoflurane and propofol were used. Intracerebroventricular administration of carbenoxolone, a gap junction blocker, significantly decreased the time to loss of the righting reflex （P 0.05）, but prolonged the time to recovery of the reflex （P 0.05）. Moreover, intracerebroventricular administration of carbenoxolone increased the sensitivity to sevoflurane, with a leftward shift of the loss of righting reflex dose-response curve, and decreased the 50% effective concentration of sevoflurane. These results suggest that the gap junction blocker carbenoxolone enhances propofol and sevoflurane-mediated general anesthesia.

THE EFFECT OF ALL-TRANS RETINOIC ACID ON GAP JUNCTIONAL INTERCELLULARCOMMUNICATION AND CONNEXIN 43 GENE EXPRESSION IN GLIOMA CELLS

To illuminate the regulating effect of all trans retinoic acid (ATRA ) on gap junctional intercellular communication (GJIC) and connexin 43 (Cx43) ge ne expression in glioma cells, which is tissue and organ specific. Method. Rat C6 glioma cells were exposed to ATRA at a concentration of 1, 10, 10 0 μmol/L respectively, and the GJIC function of the cells was examined with scr ape loading dye transfer assay 24 hours, 48 hours and 72 hours after ATRA treat ment. The effect of ATRA on Cx43 gene expression was measured with semiquantitat ive reverse transcription polymerase chain reaction (RT PCR) 24 hours after ATR A exposure. Results. The GJIC function of C6 glioma cells was significantly increased by ATR A at each concentration applied. The dye passed 4 to 5 rows of cells from the sc raping edge in ATRA treated cells, but only 1 or 2 rows in the control. The augm ent effect was observed 24 hours after each concentration ATRA treatment, and la sted till 72 hours after treatment with 1μmol/L and 10μmol/L ATRA. Forty eigh t hours after exposed to 100μmol/L ATRA, the enhancement of GJIC was less obvi ous. There was no significant increase induced by ATRA on the transcription of C x43 gene, as demonstrated by semiquantitative RT PCR. Conclusion. ATRA turned out to be a potent enhancer on GJIC function in C6 gliom a cells, and the enhancement effect was most probable at post transcriptional l evel.

Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?

AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study.Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.RESULTS: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.

Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line

Our previous study has proven that tea polyphenol has a role in lung neoplasms. The present communication was to investage the anti-proliferation effect of tea polyphenol on the PG cells, which was a high metastatic human lung carcinoma cell line, by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) cell viability assay, and to study the change of intracellular calcium concentration, connexin43 (Cx43) expression, gap junctional intercellular communication (GJIC) and cell cycle distribution after the tea polyphenol treatment by laser scanning confocal microscopy and flow cytometry. The results showed that 1) tea polyphenol could kill the PG cells in a dose-depent manner via inhibiting the PG cell proliferation and blocking the PG cell cycle progression staying in G0/G1 phase and not transfering in S and G2/M phases to reduce the PG cell proliferation index;2) the increases of intracellular calcium concentration, GJIC and Cx43 expression were related with the tea polyphenol doses. The data suggested that tea polyphenol could inhibit the growth of PG cells, which mechanism was associated with the up-regulation of GJIC.

Quantitative Structure-activity Relationship Studies on the Antioxidant Activity and Gap Junctional Communication of Carotenoids

The antioxidant and gap junctional communication（GJC） activities of carotenoids are known to be the two main anticancer mechanisms.Quantitative structure-activity relationship（QSAR） models of the two activities were developed using stepwise regression and multilayer perceptron neural network based on the calculated descriptors of quantum chemistry.The results showed that the significant molecular descriptor related to the antioxidant activity of carotenoids was the HOMO-LUMO energy gap（EHL） and the molecular descriptor related to the GJC was the lowest unoccupied molecular orbital energy（ELUMO）.The two models of antioxidant activity both showed good predictive power,but the predictive power of the neural network QSAR model of antioxidant activity was better.In addition,the two GJC models have similar,moderate predictive power.The possible mechanisms of antioxidant activity and GJC of carotenoids were discussed.

Influence of a Semiconductor Gap’s Energy on the Electrical Parameters of a Parallel Vertical Junction Photocell

The present work is a theoretical study on a parallel vertical junction solar cell under a multi-spectral illumination in static regime. The density of the minority charge carriers was determined based on the diffusion equation. Photocurrent and photovoltage are deducted from such density. All these parameters are studied taking into account the influence of the gap energy (Eg).

Pharmacological Effects of Statins Related to Gap Junction Modulation

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or “statins”, are widely using cholesterol-lowering drugs with pleiotropic pharmacological effects. In this review, we summarized the pharmacological effects of statins related to gap junction modulation. The main function of cellular gap junctions, which are composed of trans-membrane proteins named connexins (Cxs), is to mediate direct cell-to-cell communication through material exchange. Statins could rectify the disturbed expression, distribution, or phosphorylation of Cxs and thus modify the functions of gap junctions in a variety of tissues like the aorta, cardiomyocytes, or tumors. The effects of statins on Cxs and gap junctions were associated with their pharmacological activities against atherosclerosis, arrhythmias, and tumors. Despite some evidences suggested that the anti-inflammatory or HMG-CoA reductase inhibiting effects of statins may contribute in part to the modulation of Cxs and gap junctions, the detailed underlying mechanisms are largely unrevealed and merit further investigation. In addition, it is likely that the modulating effects of statins on gap junctions may also contribute to their pharmacological activities against some diabetic complications. Future studies of these issues will help to provide scientific evidences for the appropriate clinical application of statins.