The role of calcium-activated potassium channels and store-operated calcium channels in human macrophages

Intracellular Ca2+ is an important regulator of diverse functions of macrophages. Store-operated Ca2+ entry (SOCE) is the major Ca2+ influx pathway of human macrophages. Ca2+ activated potassium channels of the KCa3.1 subtype (IKCa channels) are expressed in human macrophages. We hypothesized that IKCa may be activated by store-operated Ca2+ entry and that .the resulting hyperpolarization may serve to sustain the Ca2+ influx through store-operated channels (SOCs). Human macrophages were differentiated from peripheral blood mononuclear cells and had the typical morphological properties and expressed the macrophage marker CD14. The calcium stores were depleted in Ca2+-free solution by activation of P2Y purinergic receptors with UTP or by application of the calcium pump inhibitor thapsigargin. Current-clamp experiments showed that re-addition of Ca2+ to the bath solution resulted in membrane hyperpolarization. This hyperpolarization was inhibited by IKCa blocker charybdotoxin (CHTX) and by the SOC blocker 2-APB. Whole-cell patch clamp at 0 mV showed that SOCE induced an outward current which was also blocked by CHTX and 2-APB. These data indicate that IKCa channels are the dominant KCa channels in human macrophages and can be activated by SOCE, which results in hyperpolarization of macrophages. By using cesium-based pipette solution, we recorded the inward current carried by calcium-release-activated channels (ICRAC) after depletion of the intracellular calcium stores with the calcium buffer EGTA, with the purinergic agonist UTP or the Ca2+-pump blocker thapsigargin. ICRAC had a reversal potential >+50 mV and could be blocked by 2-APB. Fluoro¬metric measurements of intra¬cellu¬lar free Ca2+ with fluo-3 showed that UTP or thapsigargin induced a transient increase of intracellular Ca2+ in Ca2+ free solution, which was followed by a sustained Ca2+ influx after re-addition of Ca2+ to bath solution. Blockage of IKCa with CHTX resulted in accelerated decay of Ca2+ fluorescence but had no effects on initial rate of Ca2+ influx. These findings suggest that Ca2+ influx activates IKCa and hyperpolarizes the membrane potential, which will maintain the driving force for Ca2+ influx by providing counter ions for Ca2+ -influx through store-operated channels. Very recent studies have shown that protein Orai1, 2, 3 may be the molecular candidates of ICRAC and that the protein STIM1 may represent the sensor of ER Ca2+ content. Using RT-PCR, we found that Orai1, Orai 2, Orai3 and STIM1 were expressed by human macrophages. These results suggest that one or more members of Orai protein family may form the store-operated Ca2+ entry pathway in human macrophages and that STIM1 may act as a Ca2+ sensor. Our data indicate that IKCa channels and SOCE may provide a feedback loop for Ca2+ influx, The sustained Ca2+ influx is important for proper function of immune system

Synthesis of ultrathin platinum nanoplates for enhanced oxygen reduction activity.

Ultrathin Pt nanostructures exposing controlled crystal facets are highly desirable for their superior activity and cost-effectiveness in the electrocatalytic oxygen reduction reaction (ORR), and they are conventionally synthesized by epitaxial growth of Pt on a limited range of templates, such as Pd nanocrystals, resulting in a high cost and less structural diversity of the ultrathin Pt nanostructures. To solve this problem, we demonstrate that ultrathin Pt nanostructures can be synthesized by templating conveniently available Ag nanocrystals without involving galvanic replacement, which enables a much-reduced cost and controllable new morphologies, such as ultrathin Pt nanoplates that expose the {111} facets. The resulting ultrathin Pt nanoplates are ∼1-2 nm in thickness, which show an ∼22-fold increase in specific activity (5.3 mA cm-2), an ∼9.5-fold increase in mass activity (1.62 A mg-1) and significantly enhanced catalytic stability in the ORR, compared with the commercial Pt/C catalyst. We believe this strategy opens a door to a highly extendable family of ultrathin noble metal nanostructures, thus promising excellent activity and stability in a broad range of catalytic applications

Self-assembly of noble metal nanoparticles into sub-100 nm colloidosomes with collective optical and catalytic properties.

Self-assembly at the nanoscale represents a powerful tool for creating materials with new structures and intriguing collective properties. Here, we report a novel strategy to synthesize nanoscale colloidosomes of noble metals by assembling primary metal nanoparticles at the interface of emulsion droplets formed by their capping agent. This strategy produces noble metal colloidosomes of unprecedentedly small sizes (<100 nm) in high yield and uniformity, which is highly desirable for practical applications. In addition, it enables the high tunability of the composition, producing a diversity of monometallic and bimetallic alloy colloidosomes. The colloidosomes exhibit interesting collective properties that are different from those of individual colloidal nanoparticles. Specifically, we demonstrate Au colloidosomes with well-controlled interparticle plasmon coupling and Au-Pd alloy colloidosomes with superior electrocatalytic performance, both thanks to the special structural features that arise from the assembly. We believe this strategy provides a general platform for producing a rich class of miniature colloidosomes that may have fascinating collective properties for a broad range of applications

Aspirin "Allergy"-Induced Thrombocytopenia: A Case Report

Aspirin is clinically widely used to inhibit platelet aggregation after coronary intervention. Herein we describe a case of aspirin-induced thrombocytopenia that may be related to allergy to aspirin. A 47-year-old man developed a delayed hypersensitivity reaction to aspirin, with pruritus, purpura and thrombocytopenia, increased peripheral blood eosinophils and enlarged inguinal lymph node. All the symptoms disappeared in 2 years after stopping aspirin. Aspirin-induced thrombocytopenia related to allergy is rarely reported. Aspirin hypersensitivity should be taken into consideration in case of unexplained thrombocytopenia in patients taking aspirin. Aspirin "allergy"-induced thrombocytopenia may involve both aspirin related IgG and IgE antibodies

Medium-sized Au\u3csub\u3e40\u3c/sub\u3e(SR)\u3csub\u3e24\u3c/sub\u3e and Au\u3csub\u3e52\u3c/sub\u3e(SR)\u3csub\u3e32\u3c/sub\u3e nanoclusters with distinct gold-kernel structures and spectroscopic features

We have analyzed the structures of two medium-sized thiolateprotected gold nanoparticles (RS-AuNPs) Au40(SR)24 and Au52(SR)32 and identified the distinct structural features in their Au kernels [Sci. Adv., 2015, 1, e1500425]. We find that both Au kernels of the Au40(SR)24 and Au52(SR)32 nanoclusters can be classified as interpenetrating cuboctahedra. Simulated X-ray diffraction patterns of the RS-AuNPs with the cuboctahedral kernel are collected and then compared with the X-ray diffraction patterns of the RS-AuNPs of two other prevailing Au-kernels identified from previous experiments, namely the Ino-decahedral kernel and icosahedral kernel. The distinct X-ray diffraction patterns of RS-AuNPs with the three different types of Au-kernels can be utilized as signature features for future studies of structures of RS-AuNPs. Moreover, the simulated UV/Vis absorption spectra and Kohn–Sham orbital energy-level diagrams are obtained for the Au40(SR)24 and Au52(SR)32, on the basis of time-dependent density functional theory computation. The extrapolated optical bandedges of Au40(SR)24 and Au52(SR)32 are 1.1 eV and 1.25 eV, respectively. The feature peaks in the UV/Vis absorption spectra of the two clusters can be attributed to the d → sp electronic transition. Lastly, the catalytic activities of the Au40(SR)24 and Au52(SR)32 are examined using CO oxidation as a probe. Both medium-sized thiolate-protected gold clusters can serve as effective stand-alone nanocatalysts

Unraveling a generic growth pattern in structure evolution of thiolate-protected gold nanoclusters

Precise control of the growth of thiolate-protected gold nanoclusters is a prerequisite for their applications in catalysis and bioengineering. Here, we bring to bear a new series of thiolateprotected nanoclusters with a unique growth pattern, i.e., Au20(SR)16, Au28(SR)20, Au36(SR)24, Au44(SR)28, and Au52(SR)32. These nanoclusters can be viewed as resulting from the stepwise addition of a common structural motif [Au8(SR)4]. The highly negative values of the nucleus-independent chemical shift (NICS) in the center of the tetrahedral Au4 units suggest that the overall stabilities of these clusters stem from the local stability of each tetrahedral Au4 unit. Generalization of this growth-pattern rule to large-sized nanoclusters allows us to identify the structures of three new thiolateprotected nanoclusters, namely, Au60(SR)36, Au68(SR)40, and Au76(SR)44. Remarkably, all three large-sized nanoclusters possess relatively large HOMO–LUMO gaps and negative NICS values, suggesting their high chemical stability. Further extension of the growth-pattern rule to the infinitely long nanowire limit results in a one-dimensional (1D) thiolate-protected gold nanowire (RS-AuNW) with a band gap of 0.78 eV. Such a unique growth-pattern rule offers a guide for precise synthesis of a new class of large-sized thiolate-protected gold nanoclusters or even RS-AuNW which, to our knowledge, has not been reported in the literature

Medium-sized Au\u3csub\u3e40\u3c/sub\u3e(SR)\u3csub\u3e24\u3c/sub\u3e and Au\u3csub\u3e52\u3c/sub\u3e(SR)\u3csub\u3e32\u3c/sub\u3e nanoclusters with distinct gold-kernel structures and spectroscopic features

We have analyzed the structures of two medium-sized thiolateprotected gold nanoparticles (RS-AuNPs) Au40(SR)24 and Au52(SR)32 and identified the distinct structural features in their Au kernels [Sci. Adv., 2015, 1, e1500425]. We find that both Au kernels of the Au40(SR)24 and Au52(SR)32 nanoclusters can be classified as interpenetrating cuboctahedra. Simulated X-ray diffraction patterns of the RS-AuNPs with the cuboctahedral kernel are collected and then compared with the X-ray diffraction patterns of the RS-AuNPs of two other prevailing Au-kernels identified from previous experiments, namely the Ino-decahedral kernel and icosahedral kernel. The distinct X-ray diffraction patterns of RS-AuNPs with the three different types of Au-kernels can be utilized as signature features for future studies of structures of RS-AuNPs. Moreover, the simulated UV/Vis absorption spectra and Kohn–Sham orbital energy-level diagrams are obtained for the Au40(SR)24 and Au52(SR)32, on the basis of time-dependent density functional theory computation. The extrapolated optical bandedges of Au40(SR)24 and Au52(SR)32 are 1.1 eV and 1.25 eV, respectively. The feature peaks in the UV/Vis absorption spectra of the two clusters can be attributed to the d → sp electronic transition. Lastly, the catalytic activities of the Au40(SR)24 and Au52(SR)32 are examined using CO oxidation as a probe. Both medium-sized thiolate-protected gold clusters can serve as effective stand-alone nanocatalysts

Is the epithelial barrier hypothesis the key to understanding the higher incidence and excess mortality during COVID-19 pandemic? The case of Northern Italy

The high incidence and increased mortality of COVID-19 make Italy among the most impacted countries by SARS-CoV-2 outbreak. In the beginning of the pandemic, Northern regions accounted for 40% of cases and 45% of deaths from COVID-19 in Italy. Several factors have been suggested to explain the higher incidence and excess mortality from COVID-19 in these regions. It is noticed that Northern Italian regions, and particularly the cities in Po Valley, are the areas with the highest air pollution due to commercial vehicle traffic, industry and a stagnant meteorological condition, with one of the highest levels in Italy and Europe of fine particulate matter 2.5 micron or smaller in size (PM2.5). PM2.5, the major environmental pollutant deriving mainly by factory and automobile exhaust emissions and coal combustion, increases the expression of angiotensin-converting enzyme 2, the epithelial cell entry receptor for SARS-CoV-2, and thus increase the susceptibility to this virus. The epithelial barrier hypothesis proposes that many diverse diseases may rise from the disruption of epithelial barrier of skin, respiratory tract and gastrointestinal system, including allergic diseases, metabolic and autoimmune diseases, and chronic neuropsychiatric conditions. There is evidence of a close correlation between air pollution and airway epithelial barrier dysfunction. Air pollution, causing lung epithelial barrier dysfunction, may contribute to local chronic inflammation, microbiome dysbiosis and impaired antiviral immune response against SARS-CoV-2, all of which contribute to the high incidence and excess mortality from COVID-19. In addition, air pollution and epithelial barrier dysfunction contribute also to the higher prevalence of several comorbidities of COVID-19, such as diabetes, chronic obstructive pulmonary disease and obesity, which have been identified as risk factors for mortality of COVID-19. In this article, on the basis of epidemiological and environmental monitoring data in Northern Italy, it is suggested that epithelial barrier hypothesis may help to understand the excess burden and mortality from COVID-19