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Background: Particulate matter of less than 2.5 micrometers (PM2.5) is associated with various adverse health outcomes. Limited evidence exists however regarding the effects of the individual constituents of indoor PM2.5 and whether their concentrations are affected by the environment or lifestyle. We here investigated the associations between these individual constituents and respiratory outcomes, the living environment, and daily life behaviors in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a prospective panel study involving COPD patients recruited from three hospitals in the Republic of Korea. Detailed questionnaires on living environments and lifestyle practices were completed by the participants. Associations between indoor PM2.5 constituents and respiratory outcomes, living environments, and daily life behaviors were then analyzed. Correlation analyses were conducted using a Spearman’s rank-order or Pearson’s correlation. Results: A total of 89 stable COPD cases were included. Their mean age was 68.1 years and 84 (94.4%) were men. The median indoor PM2.5 concentration was 11.3 μg/m3. Titanium was significantly associated with small airway resistance. Higher concentrations of aluminum, bromine, and silicone correlated with more frequent exacerbations. Regarding the living environment, the copper concentrations were negatively correlated with the distance from a road and with the floor level of residence. A higher manganese concentration was associated with greater traffic volume. An increased ventilation time was associated with lower concentrations of copper and silicone, whereas the air purifier operation time on a day with a heavy dust level was negatively correlated with barium and titanium concentrations. Iron and manganese were negatively correlated with a frequency of cleaning the kitchen ventilator. Conclusion: PM2.5 comprises various chemical constituents, each showing different relationships with clinical parameters in patients with COPD. Such constituents may be affected by environmental factors or lifestyles and should be considered as part of individualized intervention strategies through further studies.

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.

Since macroemulsions tend to break down to lower free energy, they hardly retain their initial drop state. Therefore, studies are being conducted to overcome this based on advanced interface engineering techniques, but it is still challenging. Herein we hypothesize that the stability of giant droplets can be secured without chemical bonding through the interfacial coacervation of polyelectrolyte and associative nanoplatelets.We synthesized associative silica nanoplates (ASNPs) via polypeptide-templated silicification and consecutive wettability adjustment. To produce monodisperse macrodroplets, the inner fluid containing partially positively charged ASNPs and the outer fluid dissolving negatively charged polyacrylic acid (PAA) were coflowed through a capillary-based microfluidic channel.Dynamic interfacial tension and interfacial rheology measurements revealed that the migration of ASNPs and PAA from each phase to the interface led to the formation of a complex bilayered thin membrane with an enhanced interfacial modulus. In addition, we demonstrated that adjusting the surface properties of ASNPs by coupling a fluorochemical enabled the production of monodisperse fluorocarbon-in-oil-in-water double macroemulsions. These results highlighted the applicability of our microfluidics-based interfacial coacervation technology in the development of complex fluid products with visual differentiation and drug encapsulation.

Droplet-based microfluidic technology has enabled the production of emulsions with high monodispersity in sizes ranging from a few to hundreds of micrometers. Taking advantage of this technology, attempts to generate monodisperse emulsion drops with high drug loading capacity, ordered interfacial structure, and multi-functionality have been made in the cosmetics industry. In this article, we introduce the practicality of the droplet-based microfluidic approach to the cosmetic industry in terms of innovation in productivity and marketability. Furthermore, we summarize some recent advances in the production of emulsion drops with enhanced mechanical interfacial stability. Finally, we discuss the future prospects of microfluidic technology in accordance with consumers' needs and industrial attributes.

Background The effect of exposure to particulate matter (PM) on human health is a global public health concern. To develop an effective strategy to reduce PM exposure, we performed detailed questionnaire surveys regarding the type of lifestyle required to avoid PM exposure in patients with chronic obstructive pulmonary disease (COPD). We correlated the data with real-time PM concentration during the winter season. Methods We enrolled 104 patients with COPD aged 40 years or older. Detailed questionnaire surveys were conducted among participants, and internet of things-based sensors were installed at their homes to measure the indoor PM2.5 concentration, which was continuously monitored between December 2019 and February 2020. The associations among PM2.5 concentration, patients' lifestyles, and the impact of both concentration and lifestyle on COPD exacerbation were analyzed. Results Mean outdoor PM2.5 concentration was higher than mean indoor PM2.5 concentration during the study period (21.28 ± 5.09 μg/m3 vs. 12.75 ± 7.64 μg/m3), with a mean difference of 8.53 ± 7.99 μg/m3. Among the various social factors and practices that aim to avoid exposure to PM, six practices and economic statuses were confirmed to reduce indoor PM2.5 concentration compared to outdoor concentration; Contrarily, these practices created a significant difference between the outdoor and indoor PM2.5 concentrations. The six practice items that showed a significant difference were 1) checking air quality forecast (the difference: −13.31 ± 1.35 μg/m3, p = 0.013), 2) indoor air filter operated (−15.43 ± 1.32 μg/m3, p Conclusion Lifestyle and economic levels can affect the indoor PM2.5 concentration, which may impact COPD exacerbation.

Our goal was to develop a topology-insensitive rivet bonding method using the sidewall bond principle for MEMS devices and evaluate its mechanical characteristics. The proposed bonding method is comprised of two fundamental structures with a sidewall bond between them. The first is a male wafer having a relatively thick solder as a donor, and the second is a female wafer as an acceptor with a structure similar to a through-via. The two wafers are bonded laterally by the reflow phenomena of the solder and the excess volume of the donor with the acceptor then generating a rivet. In this study, these structural features were investigated. The rivet bonding led to an enhancement in the bonding strength due to the plastic hardening behavior of the rivet, serving as a cushion for the stress. This was parametrically studied and experimentally verified. © 2011 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

The hepatitis C virus (HCV)-encoded NS5B protein is an RNA-dependent RNA polymerase which plays a substantial role in viral replication. We expressed and purified the recombinant NS5B of an HCV genotype 3a from Esherichia coli , and we investigated its ability to bind to the viral RNA and its enzymatic activity. The results presented here demonstrate that NS5B interacts strongly with the coding region of positive-strand RNA, although not in a sequence-specific manner. It was also determined that more than two molecules of polymerase bound sequentially to this region with the direction 3′ to 5′. Also, we attempted to determine the initiation site(s) of de novo synthesis by NS5B on X RNA, which contains the last 98 nucleotides of HCV positive-strand RNA. The initiation site(s) on X RNA was localized in the pyrimidine-rich region of stem I. However, when more than five of the nucleotides of stem I in X RNA were deleted from the 3′ end, RNA synthesis initiated at another site of the specific ribonucleotide. Our study also showed that the efficiency of RNA synthesis, which was directed by X RNA, was maximized by the GC base pair at the penultimate position from the 3′ end of the stem. These results will provide some clues to understanding the mechanism of HCV genomic RNA replication in terms of viral RNA-NS5B interaction and the initiation of de novo RNA synthesis.

Effort to develop a vaccine to prevent infection of human immunodeficiency virus (HIV) have focused on the induction of neutralizing antibodies. In our previous study, we reported that chimeric gag-env virus-like particles (VLPs) induce neutralizing antibodies which block HIV infection. In addition to the neutralizing antibodies, the cytotoxic T-lymphocyte (CTL) response is considered to be another major immune defense mechanism required for recovery from many different viral infections. In the present study, we have constructed chimeric fusion proteins using HIV-2 gag precursor protein with (1) four neutralizing epitopes from HIV-1 gp160; (2) three tandem copies of consensus V3 domain, which have been derived from 245 different isolates of HIV-1 and carries both the principal neutralizing determinant (PND) and CTL epitopes; and (3) V3 domains from HIV-1IIIB, HIV-1MN, HIV-1RF, and HIV-1SF2. These chimeric fusion proteins were expressed in a large quantity within insect cells, and released as VLPs into the cell culture medium. The purified gag-env VLPs from all three constructs appear to be spherical particles similar to immature HIV but slightly larger than the gag VLPs. Immunoprecipitation analysis showed that the chimeric proteins were recognized not only by HIV-1 positive patient sera, but also by monoclonal and polyclonal antisera raised against V3 peptides of HIV-1IIIB, HIV-1MN, HIV-1RF, and the gp120 antiserum against HIV-1SF2. Balb/C mice immunized with these chimeric VLPs successfully induced CTL activity against V3 peptide-stimulated target cells. In addition, a high degree of cross-reactivity was observed among the four different strains of HIV-1 V3 domain, indicating that the tandem multiple consensus V3 peptide sequence carried by HIV-2 gag can be used as a potential HIV vaccine against various HIVs.

The non-structural protein 5B (NS5B) is an essential component for the genome replication of hepatitis C virus (HCV). Thus, its activity holds the potential of being a target for therapeutic actions against HCV. The availability of large amount of functionally active NS5B enzyme may facilitate the identification of NS5B inhibitors via high-throughput screening (HTS). Here, we expressed the C-terminal 20-amino acids truncated NS5B in a bacterial system using the N-terminal domain of Escherichia coli lysyl-tRNA synthetase (LysN) as a solubility enhancer. The fusion protein (LysN-NS5B) was purified in a yield of 6.2mg/L. The activity of LysN-NS5B was confirmed by in vitro RNA-dependent RNA polymerase (RdRp) activity assay, and the biochemical properties of LysN-NS5B were further characterized by kinetic analysis. The optimal RdRp activity was shown at 30 degrees C with 5mM of Mg(2+) or 10mM of Mn(2+), while the K(m) value for UTP was determined as 5microM. The RdRp activity of LysN-NS5B was strongly inhibited by phenyldiketoacid, a specific inhibitor of HCV NS5B activity. Our results suggest that the LysN fusion system is a suitable approach for producing an active form of NS5B that can be used for HTS of NS5B inhibitors.

This paper presents the RF characteristics of the RF MEMS switch as the silicon substrate resistivity. The larger the resistivity of silicon substrate is, the larger the insertion loss of the RF MEMS switch is. When the RF MEMS switch is fabricated with the single crystalline silicon, the RF characteristics are changed by resistivity of silicon. It is necessary to study the change of RF characteristics as the substrate resistivity. The RF characteristics were simulated with different resistivity of silicon substrate. The RF MEMS switches were fabricated on each substrate with different resistivity. The RF MEMS switch was fabricated with the resistivity of 10 ohm-cm, the insertion loss of that is about 0.2 dB at 6 GHz. And the RF MEMS switch was fabricated with the resistivity of 500 Ohm-cm, the insertion loss of that is about 0.6 dB at 6 GHz.

Group I introns are catalytic RNAs capable of orchestrating two sequential phosphotransesterification reactions that result in self-splicing. To understand how the group I intron active site facilitates catalysis, we have solved the structure of an active ribozyme derived from the orf142-I2 intron from phage Twort bound to a four-nucleotide product RNA at a resolution of 3.6 A. In addition to the three conserved domains characteristic of all group I introns, the Twort ribozyme has peripheral insertions characteristic of phage introns. These elements form a ring that completely envelops the active site, where a snug pocket for guanosine is formed by a series of stacked base triples. The structure of the active site reveals three potential binding sites for catalytic metals, and invokes a role for the 2' hydroxyl of the guanosine substrate in organization of the active site for catalysis.

TLR4- and NOD2-mediated signaling pathways are two fundamentally important cascades in innate immune defense linked with the adaptive defense system. Although both the TLR4- and NOD2-mediated signaling mechanisms have been extensively studied the crosstalk between them is underappreciated. Moreover, the molecular basis of the contribution of certain NOD2 mutations to the susceptibility and severity of Crohn’s disease (CD) remains murky and confounding. We hypothesized that the signaling pathways of TLR4 and NOD2 may converge at a certain point to regulate the production of pro- and/or anti-inflammatory cytokine production and immune effector cell activities and maintain homeostasis. Disturbance in the crosstalk between the two pathways may shift the homeostatic balance, resulting in inflammatory colitis or in the impairment of the crucially important host defense capacities. We undertook the current study to test this hypothesis. Our recent work has led to some highly novel and illuminating findings. We identified a previously unappreciated activity of NOD2, which can “sense” the intensity of the TLR4-mediated signaling, resulting in synergistic stimulation of IL-12 production in a “ligand-independent” manner when the TLR signaling intensity is low or moderate; or in the induction of the transcriptional regulator C/EBPa when the TLR signaling raises to certain threshold of intensity. C/EBPa selectively and directly interacts with the IL-12p35 promoter, blocking the TLR4 ligand-induced transcription and IL-12-driven, Th1-mediated inflammatory responses. By doing so, NOD2 controls excessive activation of antigen presenting cells and T cells, and maintains mucosal homeostasis. Furthermore, three major CD-associated mutant of NOD2, 1007fs, R702W, G908R, by virtue of their inability to bind MDP, lose the activity to induce NF-kB (“loss of function”), which is essential for the production of inflammatory cytokines and host responses to invading pathogens. In this study, we uncovered a “gain of function” activity of these mutants to inhibit IL-12 production in a ligand-independent manner by acting as “dominant negatives” against NOD2 through physical association (dimerization). This latter finding provides a better explanation than the current dogmas for how the disease develops in patients bearing these mutations, which is a highly controversial issue that has been dogging the field of CD research. In summary, our study has elucidated the molecular basis of the crosstalk between two important host defense pathways converging on the molecular link C/EBPa; uncovered a novel, ligand-independent activity of NOD2, thus opening up a whole new area of future exploration. The discovery of the “gain of function” property of the CD-associated major NOD2 mutants challenges the paradigm about how human gene mutations cause diseases, and inspires the designing of novel therapeutic strategies for the treatment of CD and certain genetic disorders.

Summary 6-Pyruvoyl tetrahydropterin synthase is involved in the synthesis of pteridine eye pigments in Drosophila. The purple gene which was known to be one of the target loci of the suppressor mutation su(sj2 has been identified to encode the enzyme, and its cDNA has been cloned recently. The cDNA encoding the 19.3 kDa subunit of the 6-pyruvoyl tetrahydropterin synthase was expressed as fusion proteins in E. coli. The recombinant protein was shown to be active and purified from the E. coli crude extract by metal-chelation chromatography. The fused metal-chelating oilgopeptide was removed by thrombin for further characterization. Apparent Km for the substrate dihydroneopterin triphosphate was determined to be 590 IlM, which was slightly higher than the value of the native enzyme. The isoelectric point of 6.4 was also different from the known value of 4.3 determined by the native enzyme. Heat stability and the stimulatory effect of reducing agents were similar to the native enzyme. The modification of cysteine residues in the recombinant enzyme, one of which is known to be conserved in human and rat enzymes, by iodoacetamide inhibited its activity by up to 80%.