Inhibitory Effects of Blockage of Intermediate Conductance Ca^(2+) -Activated K^+ Channels on Proliferation of Hepatocellular Carcinoma Cells

The roles of intermediate conductance Ca2＋-activated K＋ channel （IKCal） in the pathogene- sis of hepatocellular carcinoma （HCC） were investigated. Immunohistochemistry and Western blotting were used to detect the expression of IKCal protein in 50 HCC and 20 para-carcinoma tissue samples. Real-time PCR was used to detect the transcription level of IKCal mRNA in 13 HCC and 11 para-carcinoma tissue samples. The MTT assay was used to measure the function of IKCal in human HCC cell line HepG2 in vitro. TRAM-34, a specific blocker of IKCal, was used to intervene with the function of IKCal. As compared with para-carcinoma tissue, an over-expression of IKCal protein was detected in HCC tissue samples （P〈0.05）. The mRNA expression level of IKCal in HCC tissues was 2.17 times higher than that in para-carcinoma tissues. The proliferation of HepG2 cells was suppressed by TRAM-34 （0.5, 1.0, 2.0 and 4.0 pxnol/L） in vitro （P〈0.05）. Our results suggested that IKCal may play a role in the proliferation of human HCC, and IKCal blockers may represent a potential therapeutic strategy for HCC.

Effects of isoflurane and ethanol on large conductance Ca^(2+)-activated K^+ channels

Objective: To study the effect of isoflurane and ethanol on large conductance Ca 2+-activated K + channels(BK channels). Methods: The cRNA of mslo1 encoding BK channels was injected into Xenopus oocytes. Oocytes were incubated in ND96 (96 mmol/L NaCl, 2.0 mmol/L KCl, 1.8 mmol/L CaCl 2, 1.0 mmol/L MgCl 2, and 5.0 mmol/L HEPES, pH 7.4) at 4 ℃. Patch clamp recording (outside-out) were performed after 2-3 d. Isoflurane was administrated by the vaporizer driven by air, ethanol was applied by a closed, manual-controlled administration system. Different test potentials from 0 to 10 mV were given to observe changes of currents. Results: 0.7 mmol/L and 1.2 mmol/L of isoflurane could inhibit BK currents obviously at different command potentials, but 50 mmol/L, 100 mmol/L, or 200 mmol/L of ethanol had no any effect on BK currents. Conclusion: Clinical concentration of isoflurane can distinctly inhibit isolating BK currents.

Conductive Channel for Energy Transmission

Laser spark obtained by using a conical optics is much more appropriate to form conducting channels in atmosphere. Only two types of lasers are actively considered to be used in forming high-conductivity channels in atmosphere, controlled by laser spark： pulsed sub-microsecond gas and chemical lasers （CO2, DF （deuterium fluoride））, short pulse solid-state and UV （ultraviolet） lasers. Main advantage of short pulse lasers is their ability in forming of super long ionized channels with a characteristic diameter of- 100 mm in atmosphere along the beam propagation direction. At estimated electron densities below 1,016 cm3 in these filaments and laser wavelengths in the range of 0.5-1.0 mm, the plasma barely absorbs laser radiation. In this case, the length of the track composed of many filaments is determined by the laser intensity and may reach many kilometers at a femtosecond pulse energy of-100 mJ. However, these lasers could not be used to form high-conductivity long channels in atmosphere. The ohmic resistance of this type a conducting channels turned out to be very high, and the gas in the channels could not be strongly heated （〈 1 J）. An electric breakdown controlled by radiation of femtosecond solid-state laser was implemented in only at a length of 3 m with a voltage of 2 MV across the discharge gap （670 kV/m）. Not so long ago scientific group from P.N. Lebedev physical institute has improved that result, the discharge gap （-1m） had been broken under KrF laser irradiation when switching high-voltage （up to 390 kV/m） electric discharge by 100-ns UV pulses. Our previous result -16 m long conducting channel controlled by a laser spark at the voltage -3 MV was obtained more than 20 years ago in Russia and Japan by using pulsed CO2 laser with energy -0.5 kJ. An average electric field strength was 〈 190 kV/m. It is still too much for efficient applications.

Carbon nanotubes assisting interchain charge transport in semiconducting polymer thin films towards much improved charge carrier mobility

Conjugated polymers attracted much attention in the past few decades due to their wide applications in various optoelectronic devices and circuits. The charge transport process in conjugated polymers mainly occurs in the intrachain and interchain parts, where the interchain charge transport is generally slower than intrachain transport and may slow down the whole charge transport properties. Aiming at this issue, herein we employ semiconducting single-walled carbon nanotubes(s-SWNTs) as efficient charge-transporting jointing channels between conjugated polymer chains for improving the charge transport performance. Taking the typical conjugated polymer, ploy-N-alkyl-diketopyrrolopyrrole-dithienylthieno[3,2-b]thiophene(PDPP-TT) as an example, polymer thin film transistors(PTFTs) based on the optimized blended films of PDPP-TT/s-SWNTs exhibit an obviously increasing device performance compared with the devices based on pure PDPP-TT films, with the hole and electron mobility increased from 2.32 to 12.32 cm^2 V^-1 s^-1 and from 2.02 to 5.77 cm^2 V^-1 s^-1, respectively. This result suggests the importance of forming continuous conducting channels in conjugated polymer thin films, which can also be extended to other polymeric electronic and optoelectronic devices to promote their potential applications in large-area, low-cost and high performance polymeric electronic devices and circuits.

Construction of continuous heat conductive channel,a double harvest strategy to enhance thermal conductance and bending strength of C/SiC composites

The development of efficient and quick method to prepare structure-function integrative C/SiC composites is always a major challenge in this feld.Herein,the thermal conductivity and bending strength of C/SiC composites were enhanced simultaneously via continuous high heat conductive channels constructed by continuous wave laser machining and pitch-based high thermal conductivity carbon fber in thickness direction.Results revealed that the thermal conductivity of the modifed C/SiC composites is three times higher than that of referential C/SiC composites due to its highly ordered heat conducive channel in the thickness direction.Importantly,the bending strength of modifed C/SiC composites increased to 457MPa.To better understand the enhance mechanism,the micro-structure for both the composites and heat conductive channel was systematically analyzed.The results demonstrated that the rivet effect of heat conductive channel and the formed two phases structure on the fbers dispersed partial of load and fnally enhanced the property of the composites.In a word,this method holds a nice applicable future in constructing structure-function integrative C/SiC composites.

Layout Design of Conductive Heat Channel by Emulating Natural Branch Systems

To design effective and easy-to-manufacture conductive heat channels, a heuristic method by emulating the natural branch systems is suggested. The design process of the method is divided into two steps, which are the principal channel design and the lateral channel design. During the process, the width of each channel is controlled by the bifurcation law, and the end point of the channel is located at the point with the maximum temperature while the start points of the principal channel and the lateral channel are respectively determined by the location of the heat sink and the law of the minimum thermal resistance. Four design examples with different boundary conditions are studied by the suggested method, and the design results are compared with that of the traditional structural topology optimization method. Not only lower maximum temperature and relatively uniform distribution of temperature are obtained by the suggested method, but also straight channels are achieved without gray element, which is easy to manufacture. The suggested method inspired by the natural branch systems can provide an effective solution for heat channel design in the heat dissipation structures.

Molecular mechanisms of diabetic coronary dysfunction due to large conductance Ca2＋-activated K＋ channel impairment

Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2＋, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.

otassium channels in airway smooth muscle and airway hyperreactivity in asthma

Our knowledge of the physiology of ion channels has increased tremendously during the past 20 years because of the advances of the single-channel recording and molecular cloning techniques. More than 50 different identified potassium channels have already been found.1,2 They are distributed ubiquitously in wide variety of cells including airway smooth muscle （ASM） cells and inflammatory cells in airway such as eosinophils, basophils, macrophages and so on.3 Several types of K+ channels have been identified in ASM cells, e.g., a large-conductance, voltgage-dependent Ca2+-activated K+ channel(BKCa), a voltage-dependent delayed-rectifier K+ channel（Kv）, and an ATP-sensitve K+ channel(KATP).1 In such excitable cells,

Forensic Significance of Messenger RNA and Protein Expression of Genes Downstream of Hypoxia Inducible Factor 2 in Myocardial Tissue for Death Discrimination

Background: As a heterodimeric transcription factor, hypoxia-inducible factor 2 alpha subunit (HIF2A), is an important member of the HIF family. It plays a significant role in the hypoxia adaptation process by regulating the different types of downstream transcription factors and auxiliary regulatory factors. HIF2A-related factors are believed to participate in the progression of myocardial injury or myocardial ischemia, support the protection of ischemic myocardium, and provide guiding significance for the diagnosis and discrimination of sudden cardiac death in forensic pathology. Aim and Objectives: This study aimed to explore the discriminability and applicability of HIF2A-related factors in myocardial infarction cases compared with other causes of death, provide further insights for the forensic diagnosis of heart failure (HF) cases with myocardial infarction, and support the clinical treatment of patients with HF after myocardial infarction. Materials and Methods: The relative expression levels of HIF2A, amphiregulin (AREG), potassium large conductance calcium-activated channel subfamily M β1 (KCNMB1), peroxisome proliferator-activated receptor α (PPARA), vascular endothelial growth factor (VEGF), and VEGFR2 messenger RNAs (mRNAs) in myocardial tissue samples were performed using quantitative reverse transcriptase-polymerase chain reaction. A partial least squares-discriminant analysis model was constructed to select the indicators with better identification effects for myocardial infarction cases. The protein levels of HIF2A, AREG, KCNMB1, and PPARA were further detected by immunohistochemistry. The forensic autopsy cases (27 cases in total, postmortem interval <72 h) included seven cases of acute myocardial infarction and ten cases of myocardial ischemia. There were ten cases in the control group, including four cases of traffic injury, one case of injury by fall from height, and five cases of blunt force injury. Results: Characteristic results were observed in the myocardial ischemia/infarction samples. Compared with the control group, the relative mRNA expression levels of AREG, KCNMB1, and PPARA were significantly increased during the progression of myocardial ischemia, but this was not observed for HIF2A, VEGF, or VEGFR2 mRNA. Immunohistochemistry assays further verified the expression levels of the related factors at the protein level, and H and E staining showed signs of angiogenesis and inflammation in the ischemia/infarction group. Conclusions: By controlling the expression of downstream target genes (AREG, KCNMB1, and PPARA) during myocardial cell hypoxia adaptation, HIF2A has a potential significance in the diagnosis of myocardial infarction in forensic medicine. We believe that HIF2A, AREG, KCNMB1, and PPARA can be used as molecular pathological biomarkers for the discrimination of causes of death in myocardial infarction cases.

Emerging of two-dimensional materials in novel memristor

The rapid development of big-data analytics(BDA),internet of things(IoT)and artificial intelligent Technology(AI)demand outstanding electronic devices and systems with faster processing speed,lower power consumption,and smarter computer architecture.Memristor,as a promising Non-Volatile Memory(NVM)device,can effectively mimic biological synapse,and has been widely studied in recent years.The appearance and development of two-dimensional materials(2D material)accelerate and boost the progress of memristor systems owing to a bunch of the particularity of 2D material compared to conventional transition metal oxides(TMOs),therefore,2D material-based memristors are called as new-generation intelligent memristors.In this review,the memristive(resistive switching)phenomena and the development of new-generation memristors are demonstrated involving graphene(GR),transition-metal dichalcogenides(TMDs)and hexagonal boron nitride(h-BN)based memristors.Moreover,the related progress of memristive mechanisms is remarked.

In situ polymerization of 1,3-dioxolane infiltrating 3D garnet framework with high ionic conductivity and excellent interfacial stability for integrated solid-state Li metal battery

The polymer-ceramic composite electrolyte is considered as one of promising electrolytes for solid-state battery.However,in previous research,ceramic particles are usually dispersed in polymer matrix and could not form continuous Li+conductive channels.The agglomeration of ceramic particles could also lead to low ionic conductivity and poor interfacial electrode/electrolyte contact.In this paper,self-supported porous Li_(6.4)La_(3) Zr_(1.4)Ta_(0.6)O_(12)(LLZTO) electrolyte is synthesized by gelcasting process,which possesses three-dimensional(3D) interconnected pore channels and relatively high strength.The 1,3-dioxolane(DOL) could penetrate into the porous LLZTO framework for its excellent fluidity.The subsequent in situ polymerization process by thermal treatment could completely fill the internal pores and improve the interfacial contact with electrode.The resulting 3D composite electrolyte with dual continuous Li+transport channels in ceramic and polymer components exhibits high ionic conductivity of 2.8 × 10^(-4) S·cm^(-1) at room temperature and low Li/electrolyte interfacial resistance of 94 Ω·cm^(2) at 40 ℃.The corresponding Li/Li symmetric cell delivers stable voltage profiles for over 600 h under 0.1 and 0.2 mA·cm^(-2).The solid-state Li/LiFePO_(4) battery shows superior rate and cycling performance under 0.1 C and 0.2 C.This work guides the preparation of composite electrolyte with dual continuous Li+conductive paths as well as high ceramic ratio and interface modification strategy for solid-state Li metal battery.

Growth and transport properties of CaFeAsF_(1-x) single crystals

Using self-flux method,we have successfully grown the parent phase of the single crystals of CaFeAsF1-x.The X-ray di?raction indicates good crystallinity.In-plane resistivity shows a bad metallic behavior with a sharp drop of resistivity at about T SDW=119K.This anomaly is associated with the possible spin density wave(SDW)order.Interestingly near T SDW,the resistivity exhibits a cusp-like feature,which may be understood as the strong coupling effect between the electrons and the antiferromagnetic(AF)spin fluctuations.A reduction of fluorine or application of a high pressure will suppress the SDW feature and induce superconductivity.Hall effect measurements reveal a positive Hall coefficient below T SDW indicating a dominant role of the hole-like charge carriers in the parent phase.Strong magnetoresistance has been observed below T SDW suggesting multiple conduction channels of the charge carriers.