Ambient air pollution (AAP) and particulate matters (PM) have been closely associated with adverse health effects such as respiratory disease and cardiovascular diseases. Previous studies have ...examined the adverse health effects associated with short- and long-term exposure to AAP and outdoor PM on respiratory disease. However, the effect of PM size (PM
2.5
and PM
10
) on cardiovascular disease has not been well studied. Thus, it remains unclear how the size of the inhalable particles (coarse, fine, or ultrafine) affects mortality and morbidity. Airborne PM concentrations are commonly used for ambient air quality management worldwide, owing to the known effects on cardiorespiratory health. In this article, we assess the relationship between cardiovascular diseases and PM, with a particular focus on PM size. We discuss the association of PM
2.5
and PM
10
, nitrogen dioxide (NO
2
), and elemental carbon with mortality and morbidity due to cardiovascular diseases, stroke, and altered blood pressure, based on epidemiological studies. In addition, we provide evidence that the adverse health effects of AAP and PM are more pronounced among the elderly, children, and people with preexisting cardiovascular and respiratory conditions. Finally, we critically summarize the literature pertaining to cardiovascular diseases, including atherosclerosis and stroke, and introduce potential studies to better understand the health significance of AAP and PM on cardiovascular disease.
As an essential nutrient and trace element, selenium is required for living organisms and its beneficial roles in human health have been well recognized. The role of selenium is mainly played through ...selenoproteins synthesized by the selenium metabolic system. Selenoproteins have a wide range of cellular functions including regulation of selenium transport, thyroid hormones, immunity, and redox homeostasis. Selenium deficiency contributes to various diseases, such as cardiovascular disease, cancer, liver disease, and arthropathy-Kashin-Beck disease (KBD) and osteoarthritis (OA). A skeletal developmental disorder, KBD has been reported in low-selenium areas of China, North Korea, and the Siberian region of Russia, and can be alleviated by selenium supplementation. OA, the most common form of arthritis, is a degenerative disease caused by an imbalance in matrix metabolism and is characterized by cartilage destruction. Oxidative stress serves as a major cause of the initiation of OA pathogenesis. Selenium deficiency and dysregulation of selenoproteins are associated with impairments to redox homeostasis in cartilage. We review the recently explored roles of selenium metabolism and selenoproteins in cartilage with an emphasis on two arthropathies, KBD and OA. Moreover, we discuss the potential of therapeutic strategies targeting the biological functions of selenium and selenoproteins for OA treatment.
The structural and various electrical properties of (1-x)Pb(Zr1-zTiz)O3-xPb(Zn0.4Ni0.6)1/3Nb2/3O3 (1-x)P(Z1-zTz)-xPZNN piezoceramics have been systematically investigated to ascertain the ...compositions that manifest a rhombohedral-pseudocubic-tetragonal (R-PC-T) multistructure. Rietveld refinement results indicate that the pseudocubic (PC) structure observed in the (1-x)P(Z1-zTz)-xPZNN piezoceramics closely resembles the Pm3m cubic structure. Nonetheless, the PC structure cannot be classified as cubic, given that piezoceramics exhibiting the PC structure also demonstrate ferroelectric and piezoelectric properties. The R-PC-T multistructure was detected in (1-x)P(Z1-zTz)-xPZNN piezoceramics for compositions where 0.335 ≤ x ≤ 0.44, across various z values. Compositions exhibiting the R-PC-T multistructure are identified as particularly promising. Notably, the piezoceramic with the composition 0.58 P(Z0.41T0.59)-0.42PZNN (x = 0.42 and z = 0.59) displayed remarkable piezoelectric properties, including a high piezoelectric charge constant, d33, of 825 pC/N, a coupling coefficient, kp, of 0.7, and a strain of 0.185% at 3.0 kV/mm, alongside a high Curie temperature (TC) of 240 °C.
•(1-x)P(Z1-zTz)-xPZNN piezoceramics with R-PC-T multistructure were identified.•The PC structure of (1-x)P(Z1-zTz)-xPZNN ceramics is close to the Pm3m C structure.•Most piezoceramics with R-PC-T multistructure exhibit excellent piezoelectricity.•0.58 P(Z0.41T0.59)-0.42PZNN piezoceramic shows a large d33 (825 pC/N) and kp (0.7).
Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The resulting state of oxidative stress drives the pathological ...transition of chondrocytes during OA development. However, the specific molecular pathways involved in disrupting chondrocyte redox homeostasis remain unclear. Here, we show that selenophosphate synthetase 1 (SEPHS1) expression is downregulated in human and mouse OA cartilage. SEPHS1 downregulation impairs the cellular capacity to synthesize a class of selenoproteins with oxidoreductase functions in chondrocytes, thereby elevating the level of reactive oxygen species (ROS) and facilitating chondrocyte senescence. Cartilage-specific Sephs1 knockout in adult mice causes aging-associated OA, and augments post-traumatic OA, which is rescued by supplementation of N-acetylcysteine (NAC). Selenium-deficient feeding and Sephs1 knockout have synergistic effects in exacerbating OA pathogenesis in mice. Therefore, we propose that SEPHS1 is an essential regulator of selenium metabolism and redox homeostasis, and its dysregulation governs the progression of OA.
Human cytomegalovirus (HCMV) infects peripheral blood monocytes and triggers biological changes that promote viral dissemination and persistence. We have shown that HCMV induces a proinflammatory ...state in infected monocytes, resulting in enhanced monocyte motility and transendothelial migration, prolonged monocyte survival, and differentiation toward a long-lived M1-like macrophage phenotype. Our data indicate that HCMV triggers these changes, in the absence of
viral gene expression and replication, through engagement and activation of epidermal growth factor receptor (EGFR) and integrins on the surface of monocytes. We previously identified that HCMV induces the upregulation of multiple proinflammatory gene ontologies, with the interferon-associated gene ontology exhibiting the highest percentage of upregulated genes. However, the function of the HCMV-induced interferon (IFN)-stimulated genes (ISGs) in infected monocytes remained unclear. We now show that HCMV induces the enhanced expression and activation of a key ISG transcriptional regulator, signal transducer and activator of transcription (STAT1), via an IFN-independent but EGFR- and integrin-dependent signaling pathway. Furthermore, we identified a biphasic activation of STAT1 that likely promotes two distinct phases of STAT1-mediated transcriptional activity. Moreover, our data show that STAT1 is required for efficient early HCMV-induced enhanced monocyte motility and later for HCMV-induced monocyte-to-macrophage differentiation and for the regulation of macrophage polarization, suggesting that STAT1 may serve as a molecular convergence point linking the biological changes that occur at early and later times postinfection. Taken together, our results suggest that HCMV reroutes the biphasic activation of a traditionally antiviral gene product through an EGFR- and integrin-dependent pathway in order to help promote the proviral activation and polarization of infected monocytes.
HCMV promotes multiple functional changes in infected monocytes that are required for viral spread and persistence, including their enhanced motility and differentiation/polarization toward a proinflammatory M1 macrophage. We now show that HCMV utilizes the traditionally IFN-associated gene product, STAT1, to promote these changes. Our data suggest that HCMV utilizes EGFR- and integrin-dependent (but IFN-independent) signaling pathways to induce STAT1 activation, which may allow the virus to specifically dictate the biological activity of STAT1 during infection. Our data indicate that HCMV utilizes two phases of STAT1 activation, which we argue molecularly links the biological changes that occur following initial binding to those that continue to occur days to weeks following infection. Furthermore, our findings may highlight a unique mechanism for how HCMV avoids the antiviral response during infection by hijacking the function of a critical component of the IFN response pathway.
Viral dissemination is a key mechanism responsible for persistence and disease following human cytomegalovirus (HCMV) infection. Monocytes play a pivotal role in viral dissemination to organ tissue ...during primary infection and following reactivation from latency. For example, during primary infection, infected monocytes migrate into tissues and differentiate into macrophages, which then become a source of viral replication. In addition, because differentiated macrophages can survive for months to years, they provide a potential persistent infection source in various organ systems. We broadly note that there are three phases to infection and differentiation of HCMV-infected monocytes: (1) Virus enters and traffics to the nucleus through a virus receptor ligand engagement event that activates a unique signalsome that initiates the monocyte-to-macrophage differentiation process. (2) Following initial infection, HCMV undergoes a "quiescence-like state" in monocytes lasting for several weeks and promotes monocyte differentiation into macrophages. While, the initial event is triggered by the receptor-ligand engagement, the long-term cellular activation is maintained by chronic viral-mediated signaling events. (3) Once HCMV infected monocytes differentiate into macrophages, the expression of immediate early viral (IE) genes is detectable, followed by viral replication and long term infectious viral particles release. Herein, we review the detailed mechanisms of each phase during infection and differentiation into macrophages and discuss the biological significance of the differentiation of monocytes in the pathogenesis of HCMV.
Na(Nb1-xSbx)O3 N(N1-xSx) templates were fabricated to texture the 0.96(Na0.5K0.5)(Nb1-ySby)O3-0.01BaZrO3-0.03(Bi0.5Ag0.5)ZrO3 KN(N1-ySy)-BZ-BAZ piezoceramics along the 001 direction. To the best of ...our knowledge, this is the first study that fabricated these templates. Thus far, NaNbO3 (NN) templates have been utilized to texture KNN-modified piezoceramics; however, they produce many holes in the piezoceramics because of the dissolution of the NN templates during sintering. N(N0.9S0.1) templates with an average size of ∼18 μm were produced by the molten-salt and topochemical methods utilizing Bi2.5Na3.5(Nb0.9Sb0.1)5O18 precursors. Due to their high melting temperature, the N(N0.9S0.1) templates did not dissolve during sintering. Therefore, no holes were present in the KN(N0.95S0.05)-BZ-BAZ piezoceramic textured using the N(N0.9S0.1) templates. The piezoceramic textured using the N(N0.9S0.1) templates showed a large hardness (7.56 ± 0.26 GPa) and an elastic modulus (154 ± 5 GPa) similar to those of the untextured piezoceramic. However, the piezoceramic textured using the NN templates showed reduced hardness (5.94 ± 0.58 GPa) and elastic modulus (127 ± 14 GPa) because of the presence of the holes. The KN(N0.95S0.05)-BZ-BAZ piezoceramics textured using the N(N0.9S0.1) templates provided large d33 (740 pC/N) and kp (0.62) values. Cantilever-type piezoelectric energy harvesters (CPEHs) were produced using the KN(N0.95S0.05)-BZ-BAZ piezoceramic textured with N(N1-xSx) templates and the CPEH produced using the piezoceramic textured by N(N0.9S0.1) templates generated the largest power of 2.92 mW. Therefore, N(N0.9S0.1) is a promising template for the 001 texturing of KNN-based piezoceramics with good mechanical properties.
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•Rectangular-shaped N(N0.9S0.1) seeds were well produced at a size of ∼15 μm.•KN(N0.95S0.05)-BZ-BAZ ceramic was textured using N(N0.9S0.1) seeds without holes.•Textured KN(N0.95S0.05)-BZ-BAZ ceramic exhibited excellent mechanical properties.•Textured piezoceramic provides good piezoelectricity (d33 = 740 pC/N and kp = 0.63).•CPEH produced by textured piezoceramic generated a high output power (2.92 mW).
Viruses have evolved diverse strategies to manipulate cellular signaling pathways in order to promote infection and/or persistence. Human cytomegalovirus (HCMV) possesses a number of unique ...properties that allow the virus to alter cellular events required for infection of a diverse array of host cell types and long-term persistence. Of specific importance is infection of bone marrow derived and myeloid lineage cells, such as peripheral blood monocytes and CD34
hematopoietic progenitor cells (HPCs) because of their essential role in dissemination of the virus and for the establishment of latency. Viral induced signaling through the Epidermal Growth Factor Receptor (EGFR) and other receptors such as integrins are key control points for viral-induced cellular changes and productive and latent infection in host organ systems. This review will explore the current understanding of HCMV strategies utilized to hijack cellular signaling pathways, such as EGFR, to promote the wide-spread dissemination and the classic life-long herpesvirus persistence.
Human cytomegalovirus (HCMV) infection of peripheral blood monocytes plays a key role in the hematogenous dissemination of the virus to multiple organ systems following primary infection or ...reactivation of latent virus in the bone marrow. Monocytes have a short life span of 1⁻3 days in circulation; thus, HCMV must alter their survival and differentiation to utilize these cells and their differentiated counterparts-macrophages-for dissemination and long term viral persistence. Because monocytes are not initially permissive for viral gene expression and replication, HCMV must control host-derived factors early during infection to prevent apoptosis or programmed cell death prior to viral induced differentiation into naturally long-lived macrophages. This review provides a short overview of HCMV infection of monocytes and describes how HCMV has evolved to utilize host cell anti-apoptotic pathways to allow infected monocytes to bridge the 48⁻72 h viability gate so that differentiation into a long term stable mature cell can occur. Because viral gene expression is delayed in monocytes following initial infection and only occurs (begins around two to three weeks post infection in our model) following what appears to be complete differentiation into mature macrophages or dendritic cells, or both; virally-encoded anti-apoptotic gene products cannot initially control long term infected cell survival. Anti-apoptotic viral genes are discussed in the second section of this review and we argue they would play an important role in long term macrophage or dendritic cell survival following infection-induced differentiation.
Manganese (Mn) is used in industrial metal alloys and can be released into the atmosphere during methylcyclopentadienyl manganese tricarbonyl combustion. Increased Mn deposition in the brain after ...long-term exposure to the metal by inhalation is associated with altered dopamine metabolism and neurobehavioral problems, including impaired motor skills. However, neurotoxic effects of short-term exposure to inhaled Mn are not completely characterized. The purpose of this study is to define the neurobehavioral and neurochemical effects of short-term inhalation exposure to Mn at a high concentration using rats. Male Sprague-Dawley rats were exposed to MnCl2 aerosol in a nose-only inhalation chamber for 3 weeks (1.2 µm, 39 mg/m3). Motor coordination was tested on the day after the last exposure using a rotarod device at a fixed speed of 10 rpm for 2 min. Also, dopamine transporter and dopamine receptor protein expression levels in the striatum region of the brain were determined by Western blot analysis. At a rotarod speed of 10 rpm, there were no significant differences in the time on the bar before the first fall or the number of falls during the two-minute test observed in the exposed rats, as compared with controls. The Mn-exposed group had significantly higher Mn levels in the lung, blood, olfactory bulb, prefrontal cortex, striatum, and cerebellum compared with the control group. A Mn concentration gradient was observed from the olfactory bulb to the striatum, supporting the idea that Mn is transported via the olfactory pathway. Our results demonstrated that inhalation exposure to 39 mg/m3 Mn for 3 weeks induced mild lung injury and modulation of dopamine transporter expression in the brain, without altering motor activity.
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