Impulse oscillometry and its independent role in the diagnosis of chronic obstructive pulmonary disease.

Background: Pulmonary function test, particularly in patients with COVID-19, is problematic because it involves forced expiration. Impulse oscillometry (IOS) reduces the potential exposure of health-care staff to infectious droplets. In this study, we investigated the correlation between IOS and spirometry and whether IOS can precisely predict spirometry-based diagnoses of chronic obstructive pulmonary disease (COPD). Methods: We retrospectively analyzed the data (January 1 to December 31, 2021) of patients who underwent both spirometry and IOS on the same date. One-way analysis of variance was performed to evaluate the IOS results of patients stratified into two (COPD and non-COPD) groups by spirometry results. IOS results were also analyzed using receiver operator characteristics curves to diagnose advanced COPD, which was indicated by a postbronchodilator (BD) forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio of <0.6. We further evaluated the accuracy of oscillometry as a predictor of spirometry-based COPD diagnosis. Results: A total of 115 patients were included in the analysis. The best parameters assessed for spirometry-based COPD diagnosis were area under reactance (AX) and airway resistance (predicted R5% × resonant frequency) in relation to body mass index (BMI). However, when the post-BD FEV1/FVC ratio was <0.6, BMI-adjusted airway resistance had an area under curve (0.782; 95 % confidence interval: 0.620-0.945) value larger than the corresponding AX. A BMI-adjusted airway resistance value of >160 moderately predicted spirometry-based COPD diagnosis. Conclusions: BMI-adjusted airway resistance is a potential predictor of spirometry-based COPD diagnosis; the cutoff values of this parameter differ between individuals with and without obesity.

A sequential tape stripping approach for the assessment of the impact of personal cleansing products on the stratum corneum surface layers' acid mantle properties and antimicrobial defense.

BACKGROUND: Stratum corneum (SC) plays a critical role in skin barrier function for protection and defense in nature. The acidic skin pH, which is also known as the acid mantle, is very important in fighting against outer environmental threats, especially, bacteria. Furthermore, recent research has shown that the transient bacteria could potentially penetrate into deeper layer of the SC down to a few micrometers while posing an additional threat to the deeper layers of the skin. AIM: To develop a sequential tape stripping method for assessing the impact of personal cleansing product on the SC surface layers' acid mantle properties and antimicrobial defense against transient bacteria. METHODS: Fifty-five subjects were recruited. High pH soap-based Product 1 and low pH synthetic surfactant-based Product 2 were applied on the left and right forearms of each subject. Sequential tape stripping was performed on the same spots to access multiple layers of the skin SC. Both antimicrobial defense property and skin pH of different skin layers were evaluated at baseline and 12 h after treatment. RESULTS: The skin's antimicrobial defense was significantly higher 12 h after treatment of the low pH Product 2 as compared to the treatment of high pH Product 1. In fact, this trend was consistent across all three skin layers (Layer 1 to Layer 3) as measured in this study (p < 0.01). Furthermore, the skin surface pH of Layer 1 and Layer 3 were also lower 12 h after the treatment of low pH Product 2 as compared to that of the high pH Product 1 (p < 0.01). CONCLUSION: The results of this investigation demonstrated the benefits of 12-h long lasting and deeper protection of SC acid mantle properties and antimicrobial defense using a low pH skin cleansing product as compared to a high pH product.

Persistent Halogenated Organic Pollutants in Deep-Water-Deposited Particulates from South China Sea.

POP data are limited in the marine environment; thus, this study aimed to investigate background persistent organic pollutant (POP) levels in oceanic deep-water-deposited particulates in the South China Sea (SCS). Six POPs, including polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DL-PCBs), polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs), polychlorinated diphenyl ethers (PCDEs), and polybrominated biphenyls (PBBs), were investigated in eight pooled samples from the SCS from 20 September 2013 to 23 March 2014 and 15 April 2014 to 24 October 2014 at depths of 2000 m and 3500 m. PBDEs were the most predominant compounds, with the highest mean Σ14PBDE of 125 ± 114 ng/g dry weight (d.w.), followed by Σ17PCDD/F, Σ12PBDD/F, and Σ12DL-PCB (275 ± 1930, 253 ± 216, and 116 ± 166 pg/g d.w., respectively). Most PBDD/F, PBB, and PCDE congeners were below the detection limits. PCDDs had the highest toxic equivalency (TEQ), followed by PBDDs and DL-PCBs. Among the six POPs, PBDEs were the major components of the marine-deposited particles, regarding both concentrations and mass fluxes. Compared to 3500 m, PBDE levels were higher at a depth of 2000 m. PBDE mass fluxes were 20.9 and 14.2 ng/m2/day or 68.2 and 75.9 ng/m2/year at deep-water 2000 and 3500 m, respectively. This study first investigated POP levels in oceanic deep-water-deposited particles from existing global data.

Effects of vitamin D and zinc deficiency in acute and long COVID syndrome.

OBJECTIVES: Acute inflammatory or neuropsychiatric symptoms, such as headache, fatigue, anosmia, and hyposmia, sometimes persist for more than 30 days or longer than 12 weeks after infection with the Omicron variant of SARS­CoV­2 (hereafter referred to as COVID-19). The aim of this study was to determine whether detection of zinc concentration or vitamin D concentration could provide treatment benefits for patients with COVID-19, thus reducing the risk of them experiencing long COVID. METHODS: The interval between the date of COVID-19 diagnosis and the date of visit to pulmonary department for prolonged symptoms of COVID-19 was recorded for statistical analysis. Inductively coupled plasma mass spectrometry for detecting zinc and chemiluminescence immunoassay for detecting vitamin D were performed in laboratory tests. RESULTS: Fifty-five patients were included. Of the participants, 29.1 % and 27.3 % had vitamin D and zinc deficiency, respectively. On average, the patients underwent long COVID treatment for 31.7 ± 17.7 days. A positive statistical correlation was observed between vitamin D and zinc concentrations (Pearson's correlation = 0.378). Compared with sufficient zinc levels, zinc deficiency was associated with a higher fibrinogen level (p < 0.05). Within 30 days, the observed vitamin D deficiency rate was only 21.4 %; after 30 days, the vitamin D deficiency rate rose to 37.0 % (McNemar's chi-square test; p < 0.05). CONCLUSION: Zinc deficiency correlates to acute and persistent inflammation and vitamin D deficiency is associated with delayed recovery in long COVID syndrome.

Design and synthesis of naturally-inspired SARS-CoV-2 inhibitors.

A naturally inspired chemical library of 25 molecules was synthesised guided by 3-D dimensionality and natural product likeness factors to explore a new chemical space. The synthesised chemical library, consisting of fused-bridged dodecahydro-2a,6-epoxyazepino[3,4,5-c,d]indole skeletons, followed lead likeness factors in terms of molecular weight, C-sp3 fraction and Clog P. Screening of the 25 compounds against lung cells infected with SARS-CoV-2 led to the identification of 2 hits. Although the chemical library showed cytotoxicity, the two hits (3b, 9e) showed the highest antiviral activity (EC50 values of 3.7 and 1.4 µM, respectively) with an acceptable cytotoxicity difference. Computational analysis based on docking and molecular dynamics simulations against main protein targets in SARS-CoV-2 (main protease Mpro, nucleocapsid phosphoprotein, non-structural protein nsp10-nsp16 complex and RBD/ACE2 complex) were performed. The computational analysis proposed the possible binding targets to be either Mpro or the nsp10-nsp16 complex. Biological assays were performed to confirm this proposition. A cell-based assay for Mpro protease activity using a reverse-nanoluciferase (Rev-Nluc) reporter confirmed that 3b targets Mpro. These results open the way towards further hit-to-lead optimisations.

High-throughput droplet-based analysis of influenza A virus genetic reassortment by single-virus RNA sequencing.

The segmented RNA genome of influenza A viruses (IAVs) enables viral evolution through genetic reassortment after multiple IAVs coinfect the same cell, leading to viruses harboring combinations of eight genomic segments from distinct parental viruses. Existing data indicate that reassortant genotypes are not equiprobable; however, the low throughput of available virology techniques does not allow quantitative analysis. Here, we have developed a high-throughput single-cell droplet microfluidic system allowing encapsulation of IAV-infected cells, each cell being infected by a single progeny virion resulting from a coinfection process. Customized barcoded primers for targeted viral RNA sequencing enabled the analysis of 18,422 viral genotypes resulting from coinfection with two circulating human H1N1pdm09 and H3N2 IAVs. Results were highly reproducible, confirmed that genetic reassortment is far from random, and allowed accurate quantification of reassortants including rare events. In total, 159 out of the 254 possible reassortant genotypes were observed but with widely varied prevalence (from 0.038 to 8.45%). In cells where eight segments were detected, all 112 possible pairwise combinations of segments were observed. The inclusion of data from single cells where less than eight segments were detected allowed analysis of pairwise cosegregation between segments with very high confidence. Direct coupling analysis accurately predicted the fraction of pairwise segments and full genotypes. Overall, our results indicate that a large proportion of reassortant genotypes can emerge upon coinfection and be detected over a wide range of frequencies, highlighting the power of our tool for systematic and exhaustive monitoring of the reassortment potential of IAVs.

Color-complexity enabled exhaustive color-dots identification and spatial patterns testing in images.

Our computational developments and analyses on experimental images are designed to evaluate the effectiveness of chemical spraying via unmanned aerial vehicle (UAV). Our evaluations are in accord with the two perspectives of color-complexity: color variety within a color system and color distributional geometry on an image. First, by working within RGB and HSV color systems, we develop a new color-identification algorithm relying on highly associative relations among three color-coordinates to lead us to exhaustively identify all targeted color-pixels. A color-dot is then identified as one isolated network of connected color-pixel. All identified color-dots vary in shapes and sizes within each image. Such a pixel-based computing algorithm is shown robustly and efficiently accommodating heterogeneity due to shaded regions and lighting conditions. Secondly, all color-dots with varying sizes are categorized into three categories. Since the number of small color-dot is rather large, we spatially divide the entire image into a 2D lattice of rectangular. As such, each rectangle becomes a collective of color-dots of various sizes and is classified with respect to its color-dots intensity. We progressively construct a series of minimum spanning trees (MST) as multiscale 2D distributional spatial geometries in a decreasing-intensity fashion. We extract the distributions of distances among connected rectangle-nodes in the observed MST and simulated MSTs generated under the spatial uniformness assumption. We devise a new algorithm for testing 2D spatial uniformness based on a Hierarchical clustering tree upon all involving MSTs. This new tree-based p-value evaluation has the capacity to become exact.

SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission, France, January to April 2020.

BackgroundChildren's role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020.AimsThis retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures.MethodsBetween 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020.ResultsIn the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils' parents and relatives (p < 0.001). Among the six primary schools, three children attending separate schools at the outbreak start, while symptomatic, might have introduced SARS-CoV-2 there, but symptomatic secondary cases related to them could not be definitely identified. In the primary schools overall, antibody prevalence in pupils sharing classes with symptomatic cases was higher than in pupils from other classes: 15/65 (23.1%) vs 30/445 (6.7%) (p < 0.001). Among 46 SARS-CoV-2 seropositive pupils < 12 years old, 20 were asymptomatic. Whether past HKU1 and OC43 seasonal coronavirus infection protected against SARS-CoV-2 infection in 6-11 year olds could not be inferred.ConclusionsViral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.

A comparison of four serological assays for detecting anti-SARS-CoV-2 antibodies in human serum samples from different populations.

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their differing antibody response profiles. Here, we performed a pilot study of four serological assays to assess the amounts of anti-SARS-CoV-2 antibodies in serum samples obtained from 491 healthy individuals before the SARS-CoV-2 pandemic, 51 individuals hospitalized with COVID-19, 209 suspected cases of COVID-19 with mild symptoms, and 200 healthy blood donors. We used two ELISA assays that recognized the full-length nucleoprotein (N) or trimeric spike (S) protein ectodomain of SARS-CoV-2. In addition, we developed the S-Flow assay that recognized the S protein expressed at the cell surface using flow cytometry, and the luciferase immunoprecipitation system (LIPS) assay that recognized diverse SARS-CoV-2 antigens including the S1 domain and the carboxyl-terminal domain of N by immunoprecipitation. We obtained similar results with the four serological assays. Differences in sensitivity were attributed to the technique and the antigen used. High anti-SARS-CoV-2 antibody titers were associated with neutralization activity, which was assessed using infectious SARS-CoV-2 or lentiviral-S pseudotype virus. In hospitalized patients with COVID-19, seroconversion and virus neutralization occurred between 5 and 14 days after symptom onset, confirming previous studies. Seropositivity was detected in 32% of mildly symptomatic individuals within 15 days of symptom onset and in 3% of healthy blood donors. The four antibody assays that we used enabled a broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different subpopulations within one region.

Engineering Cell-Permeable Proteins through Insertion of Cell-Penetrating Motifs into Surface Loops.

Effective delivery of proteins into the cytosol of mammalian cells would open the door to a wide range of applications. However, despite great efforts from numerous investigators, effective protein delivery in a clinical setting is yet to be accomplished. Herein we report a potentially general approach to engineering cell-permeable proteins by genetically grafting a short cell-penetrating peptide (CPP) to an exposed loop of a protein of interest. The grafted peptide is conformationally constrained, exhibiting enhanced proteolytic stability and cellular entry efficiency. Applying this technique to enhanced green fluorescent protein (EGFP), protein-tyrosine phosphatase 1B (PTP1B), and purine nucleoside phosphorylase (PNP) rendered all three proteins cell-permeable and biologically active in cellular assays. When added into growth medium at 0.5-5 µM concentrations, the engineered PTP1B dose-dependently reduced the phosphotyrosine levels of intracellular proteins, while the modified PNP corrected the metabolic deficiency of PNP-deficient mouse T lymphocytes, providing a potential enzyme replacement therapy for a rare genetic disease.

Influenza virus polymerase subunits co-evolve to ensure proper levels of dimerization of the heterotrimer.

The influenza A virus RNA-dependent RNA polymerase complex consists in three subunits, PB2, PB1 and PA, that perform transcription and replication of the viral genome through very distinct mechanisms. Biochemical and structural studies have revealed that the polymerase can adopt multiple conformations and form oligomers. However so far it remained unclear whether the available oligomeric crystal structures represent a functional state of the polymerase. Here we gained new insights into this question, by investigating the incompatibility between non-cognate subunits of influenza polymerase brought together through genetic reassortment. We observed that a 7:1 reassortant virus whose PB2 segment derives from the A/WSN/33 (WSN) virus in an otherwise A/PR/8/34 (PR8) backbone is attenuated, despite a 97% identity between the PR8-PB2 and WSN-PB2 proteins. Independent serial passages led to the selection of phenotypic revertants bearing distinct second-site mutations on PA, PB1 and/or PB2. The constellation of mutations present on one revertant virus was studied extensively using reverse genetics and cell-based reconstitution of the viral polymerase. The PA-E349K mutation appeared to play a major role in correcting the initial defect in replication (cRNA -> vRNA) of the PR8xWSN-PB2 reassortant. Strikingly the PA-E349K mutation, and also the PB2-G74R and PB1-K577G mutations present on other revertants, are located at a dimerization interface of the polymerase. All three restore wild-type-like polymerase activity in a minigenome assay while decreasing the level of polymerase dimerization. Overall, our data show that the polymerase subunits co-evolve to ensure not only optimal inter-subunit interactions within the heterotrimer, but also proper levels of dimerization of the heterotrimer which appears to be essential for efficient viral RNA replication. Our findings point to influenza polymerase dimerization as a feature that is controlled by a complex interplay of genetic determinants, can restrict genetic reassortment, and could become a target for antiviral drug development.

Cyclic Cell-Penetrating Peptides with Single Hydrophobic Groups.

A new family of cyclic cell-penetrating peptides (CPPs) has been discovered; they differ from previously reported cyclic CPPs by containing only a single hydrophobic residue. The optimal CPP structure consists of four arginine residues and a hydrophobic residue with a long alkyl chain (e.g., a decyl group) in a cyclohexapeptide ring. The most active member of this family, CPP 17, has an intrinsic cellular entry efficiency similar to that of cyclic CPP12, the most active CPP reported to date. However, CPP 17 is 2.8 times more active than CPP12 under high serum protein concentrations, presumably because of the lower protein binding. CPP 17 enters the cell primarily by direct translocation at a relatively low concentration (≥5 µm).

Assessing the endocrine disrupting potentials and genotoxicity in environmental samples from Taiwanese rivers.

BACKGROUND: Surface waters receive a variety of organic pollutants via wastewater discharge, and sediment represents a sink for hydrophobic contaminants. In this study, we used in vitro yeast-based reporter gene assays and a Bacillus subtilis Rec-assay to examine the occurrence of endocrine disrupting activities and genotoxic potentials in samples collected from three Taiwanese rivers. Levels of 51 polycyclic aromatic hydrocarbons (PAHs) in muscles of fish captured from same rivers were also analyzed to assess in vivo pollution of PAHs. RESULTS: Antagonist activities for androgen receptor and retinoid X receptor (RXR) were detected in river water extracts at environmentally relevant concentrations., and sediment extracts exhibited RXR agonist, RXR antagonist, and genotoxic potentials concurrently. Σ16 PAHs in fish muscles ranged from 44.9-242.4 ng g- 1 dry weight, representing 38 to 59% of the total 51 PAHs concentrations, and methylated PAHs of low molecular weight PAHs were often detected as well. CONCLUSION: Taiwanese river sediment samples concomitantly exhibited RXR disrupting potentials and genotoxic activities, whereas RXR agonist and antagonist activities were simultaneously detected in several dry-season sediment extracts. PAH levels in fish muscles were categorized as minimally polluted by aromatic compounds, nonetheless, the presence of methylated PAHs in muscles samples may be of concern owing to the higher toxic potentials than their parent compounds.

Novel application of Influenza A virus-inoculated chorioallantoic membrane to characterize a NP-specific monoclonal antibody for immunohistochemistry assaying.

Monoclonal antibodies (MAbs) are widely applied in disease diagnoses. Herein, we report a MAb, WF-4, against Influenza A virus nucleoprotein (NP), its broad response with Influenza A virus, and its application in an immunohistochemistry (IHC) assay. WF-4 was screened by immunofluorescence assay (IFA). The results showed that its reactivity with baculovirus-expressed full-length recombinant NP (rNP) in Western blot (WB), indicating its IHC applicability. Fifteen Influenza A virus (reference subtypes H1 to H15) infected chicken embryonated chorioallantoic membranes (CAM), fixed by formalin, were all detectable in the WF-4-based IHC assay. Also, the reactivity of the IHC test with NP from experimentally inoculated H6N1 and from all recent outbreaks of H5 subtype avian Influenza A virus (AIV) field cases in Taiwan showed positive results. Our data indicate that CAM, a by-product of Influenza A virus preparation, is helpful for Influenza A virus-specific MAb characterization, and that the WF-4 MAb recognizes conserved and linear epitopes of Influenza A virus NP. Therefore, WF-4 is capable of detecting NP antigens via IHC and may be suitable for developing various tests for diagnosis of Influenza A virus and, especially, AIV infection.

Targeting Ras with Macromolecules.

Activating Ras mutations are associated with ∼30% of all human cancers and the four Ras isoforms are highly attractive targets for anticancer drug discovery. However, Ras proteins are challenging targets for conventional drug discovery because they function through intracellular protein-protein interactions and their surfaces lack major pockets for small molecules to bind. Over the past few years, researchers have explored a variety of approaches and modalities, with the aim of specifically targeting oncogenic Ras mutants for anticancer treatment. This perspective will provide an overview of the efforts on developing "macromolecular" inhibitors against Ras proteins, including peptides, macrocycles, antibodies, nonimmunoglobulin proteins, and nucleic acids.

Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 µg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17ß-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 µg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment.

Exploring potential contributors to endocrine disrupting activities in Taiwan's surface waters using yeast assays and chemical analysis.

Surface waters serve as sinks for anthropogenic contaminants, including naturally occurring hormones and a variety of synthetic endocrine active substances. To investigate the presence of endocrine active contaminants in the aquatic environment in Taiwan, river water and suspended solids were analyzed by yeast assays to examine the distribution of estrogenic, androgenic, and aryl hydrocarbon receptor agonist activities. The results showed that dry-season river samples exhibited strong estrogenic and aryl hydrocarbon receptor agonist activities, but no androgenic activity was detected. Owing to the ubiquitous detection of estrogenic activities in Taiwan's surface waters, samples were further subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for quantification of selected estrogenic compounds. LC-MS/MS results indicated that natural estrogens, such as estrone and 17ß-estradiol were often the most contributing compounds for the bioassay-derived estrogenic activities due to their strong estrogenic potencies and high detection frequencies, whereas high concentrations of bisphenol A and nonylphenol also posed a threat to the aquatic ecosystems in Taiwan. Water samples eliciting strong estrogenic activities were further fractionated using high performance liquid chromatography, and significant estrogenic activities were detected in fractions containing estrone, 17ß-estradiol, 17α-ethynylestradiol, and bisphenol A. Also, the presence of unidentified estrogenic compounds was found in few river water samples. Further identification of unknown endocrine active substances is necessary to better protect the aquatic environment in Taiwan.

Synthesis and in vitro anticancer activity evaluation of novel bioreversible phosphate inositol derivatives.

The chemistry and biology of phosphorylated inositols have become intense areas of research during the last two decades due to their involvement in various cellular signaling processes. However, the metabolic instability by phosphatases or kinases and poor penetration make it difficult to become a drug used in the clinic. The bioreversible protection technique can enhance membrane penetration characteristics and increase the stability of phosphorylated inositols against enzymatic degradation and is applied widely in drug discovery and development. In this paper, we described the design and synthesis of 22 bioreversible phosphotriester inositols, along with the initial antitumor activity results. Most compounds exhibited significant cytotoxic activity against human cancer cell lines A549, MDA-MB-231 and HeLa, but lower cellular toxicity on normal cell MCF10A in comparison with Cisplatin. These compounds can be used as probes to study the mechanism of intracellular signal transduction mediated by phosphate inositol or as leads of phosphate inositol drugs in the clinic.

Atmospheric concentrations of persistent organic pollutants over the Pacific Ocean near southern Taiwan and the northern Philippines.

This study investigates the atmospheric occurrence of persistent organic pollutants (POPs) over the Pacific Ocean near southern Taiwan and the northern Philippines. We determined sixty-six compounds, including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (DLPCBs), polybrominated diphenyl ethers (PBDEs), as well as polychlorinated diphenyl ethers (PCDEs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), and polybrominated biphenyls (PBBs), in air samples simultaneously collected from the offshore oceanic atmosphere (n=6) and over a rural area (n=2). We calculated the atmospheric World Health Organization 2005 toxic equivalency levels (WHO2005-TEQ), for the total dioxin-like POPs, including PCDD/Fs, DLPCBs, and PBDD/Fs, being 0.00612 pg WHO2005-TEQ/m(3) and 0.0138 pg WHO2005-TEQ/m(3) over the ocean and land, respectively. We found unexpected lower averaged atmospheric PBDE concentrations in the rural area (15.9 pg/m(3)) than over the ocean (31.1 pg/m(3)) due to higher levels of the BDE209 congener, although the difference was not statistically significant. We have compared and reported our field results with previously published datasets over the global oceans, which suggest PCBs and PBDEs are the dominant chemical contaminants in the global oceanic atmosphere among these halogenated POPs (e.g. PCBs and Σdi-hepta PBDEs could be found in the range of 0.09-48.7 and 8.07-94.0 pg/m(3), respectively, including our dataset). However, there are still very few investigations on the global atmospheric levels of PBDD/Fs, PCDEs and PBBs and our data sums to these earlier studies. Finally, we point out that the halogenated POPs originated from Taiwan or the continental East Asia which could easily reach remote ocean sites via atmospheric transport.