The impact of the synergistic effect of SO2 and PM2.5/PM10 on obstructive lung disease in subtropical Taiwan.

Background: Chronic Obstructive lung diseases (COPD) are complex conditions influenced by various environmental, lifestyle, and genetic factors. Ambient air pollution has been identified as a potential risk factor, causing 4.2 million deaths worldwide in 2016, accounting for 25% of all COPD-related deaths and 26% of all respiratory infection-related deaths. This study aims to evaluate the associations among chronic lung diseases, air pollution, and meteorological factors. Methods: This cross-sectional study obtained data from the Taiwan Biobank and Taiwan Air Quality Monitoring Database. We defined obstructive lung disease as patients with FEV1/FVC < 70%. Descriptive analysis between spirometry groups was performed using one-way ANOVA and the chi-square or Fisher's exact test. A generalized additive model (GAM) was used to evaluate the relationship between SO2 and PM2.5/PM10 through equations and splines fitting. Results: A total of 2,635 participants were enrolled. Regarding environmental factors, higher temperature, higher relative humidity, and lower rainfall were risk factors for obstructive lung disease. SO2 was positively correlated with PM10 and PM2.5, with correlation coefficients of 0.53 (p < 0.0001) and 0.52 (p < 0.0001), respectively. Additionally, SO2 modified the relative risk of obstructive impairment for both PM10 [ß coefficient (ß) = 0.01, p = 0.0052] and PM2.5 (ß = 0.01, p = 0.0155). Further analysis per standard deviation (per SD) increase revealed that SO2 also modified the relationship for both PM10 (ß = 0.11, p = 0.0052) and PM2.5 (ß = 0.09, p = 0.0155). Our GAM analysis showed a quadratic pattern for SO2 (per SD) and PM10 (per SD) in model 1, and a quadratic pattern for SO2 (per SD) in model 2. Moreover, our findings confirmed synergistic effects among temperature, SO2 and PM2.5/PM10, as demonstrated by the significant associations of bivariate (SO2 vs. PM10, SO2 vs. PM2.5) thin-plate smoothing splines in models 1 and 2 with obstructive impairment (p < 0.0001). Conclusion: Our study showed high temperature, humidity, and low rainfall increased the risk of obstructive lung disease. Synergistic effects were observed among temperature, SO2, and PM2.5/PM10. The impact of air pollutants on obstructive lung disease should consider these interactions.

Living alone is associated with a higher prevalence of psychiatric morbidity in a population-based cross-sectional study.

Background: Living alone has been linked to poor mental health, however large-scale epidemiological studies on the association between living alone and psychiatric morbidity including depression and anxiety are lacking. The aim of this study was to investigate this issue in a large Taiwanese cohort. Methods: In this cross-sectional study, we enrolled 121,601 volunteers from 29 community recruitment stations in Taiwan and divided them into two groups based on whether or not they lived alone. Psychiatric morbidity was defined as a Generalized Anxiety Disorder 2-item score ≥ 3, Patient Health Questionnaire 2-item score ≥ 3, or self-reported depression. Logistic regression was used to explore the associations between living alone and psychiatric morbidity. Results: The participants who lived alone had a higher prevalence of psychiatric morbidity [odds ratio (OR) = 1.608, 95% confidence interval (CI) = 1.473 to 1.755] after adjusting for potential confounders. In a subgroup analysis, married subjects who lived alone and divorce/separation (OR = 2.013, 95% CI = 1.763 to 2.299) or widowing (OR = 1.750, 95% CI = 1.373 to 2.229) were more likely to have psychiatric morbidity than those who were married and not living alone. Conclusions: Our findings suggest that living alone is a risk factor for psychiatric morbidity, especially for married subjects who live alone in concordance with divorce, separation, or the death of a spouse.

Vocal repertoire and sound characteristics in the variegated cardinalfish, Fowleria variegata (Pisces: Apogonidae).

The variegated cardinalfish Fowleria variegata produces grunt and hoot calls during agonistic and courtship interactions. Both sounds are tonal and occur as single and multiunit calls. Grunts are of short duration with variable frequency spectra. Hoots are longer, have a higher fundamental frequency, and a more developed harmonic structure. Agonistic grunt calls and short hoot calls (1-2 hoots) are produced during chases and when striking an individual or a mirror. Grunts are produced primarily in male-female and mirror-image encounters, and short hoot calls are produced primarily in male-male interactions. During the reproductive period, long hoot calls (three and four hoots) are the main sound type in a mix-sexed tank and at Dongsha Atoll. These are likely produced by males because isolated females are silent, and isolated males emit long hoot calls. Courtship interactions are mostly silent, and males are silent after capturing eggs for oral brooding. Tank sounds peak at dusk to early evening with a smaller peak at noon, although there are dusk and dawn peaks at Dongsha Atoll. Tank sounds exhibit a semilunar rhythm with peaks at the new and full moon. Other cardinalfish species from the atoll produce grunts but not hoot calls.

Carbon fiber ionization mass spectrometry coupled with solid phase microextraction for analysis of Benzo[a]pyrene.

Solid phase micro-extraction (SPME) is an effective technique that can be used to selectively enrich trace analytes of interest from complex samples. Owing to its high sensitivity and high selectivity, mass spectrometry (MS) has been widely used as the detection tool to confirm the analytes enriched on SPME fibers. Generally, thermal desorption or solvent desorption is used to desorb analytes from SPME fibers for MS analysis. A straightforward ionization method called carbon fiber ionization (CFI), which uses a single carbon fiber (diameter: ∼10 µm) as ionization emitter in MS, has been demonstrated lately. Analytes adsorbed on the carbon fiber, which is placed close (∼5 mm) to the inlet of a mass spectrometer, can be readily ionized through corona discharge and detected by the mass spectrometer. One unique feature regarding this approach over other existing ambient ionization methods is that no additional electric contact is applied directly on the carbon fiber. Nevertheless, on the basis of the electric field provided by the mass spectrometer, corona discharge can readily occur for ionizing analytes on the carbon fiber. Carbon fiber has high affinity toward polycyclic aromatic hydrocarbons due to its graphite-like surface structure. We herein explore a hyphenated-technique by combining carbon-fiber based SPME with CFI-MS for extraction of benzo[a]pyrene (BaP), a carcinogen, from aqueous samples. After BaP are adsorbed on a carbon fiber through SPME, the SPME carbon fiber can be readily placed in front of the mass spectrometer for MS analysis. The ions at m/z 252 derived from BaP adsorbed on the carbon fiber can be immediately acquired by the mass spectrometer without the requirement of applying heating or solvent. The limit of detection of BaP using the developed method was as low as ∼60 pM. It is also feasible to detect BaP from complex serum sample. The feasibility of using the approach for quantitative analysis of BaP was also demonstrated. The linear dynamic range toward BaP was 0.2-5 nM. The extraction efficiency using this approach for aqueous samples was ∼91%.

Ultrasonication-assisted spray ionization-based micro-reactors for online monitoring of fast chemical reactions by mass spectrometry.

Microfluidics can be used to handle relatively small volumes of samples and to conduct reactions in microliter-sized volumes. Electrospray ionization can couple microfluidics with mass spectrometry (MS) to monitor chemical reactions online. However, fabricating microfluidic chips is time-consuming. We herein propose the use of a micro-reactor that is sustained by two capillaries and an ultrasonicator. The inlets of the capillaries were individually immersed to two different sample vials that were subjected to the ultrasonicator. The tapered outlets of the two capillaries were placed cross with an angle of ~60° close to the inlet of the mass spectrometer to fuse the eluents. On the basis of capillary action and ultrasonication, the samples from the two capillaries can be continuously directed to the capillary outlets and fuse simultaneously to generate gas phase ions for MS analysis through ultrasonication-assisted spray ionization (UASI). Any electric contact applied on the capillaries is not required. Nevertheless, UASI spray derived from the eluents can readily occur in front of the mass spectrometer. That is, a micro-reactor was created from the fusing of the eluent containing different reactants from these two UASI capillaries, allowing reactions to be conducted in situ. The solvent in the fused droplets was evaporated quickly, and the product ions could be immediately observed by MS because of the extreme rise in the concentration of the reactants. For proof of concept, pyrazole synthesis reaction and cortisone derivatization by Girard T reagent were selected as the model reactions. The results demonstrated the feasibility of using UASI-based micro-reactor for online MS analysis to detect reaction intermediates and products.

Carbon Fiber Ionization Mass Spectrometry for the Analysis of Analytes in Vapor, Liquid, and Solid Phases.

Various ionization methods in mass spectrometry (MS) are available for the analysis of analytes with different properties. Nonetheless, the use of a single ionization method to analyze mixtures containing analytes with different polarities and volatilities in different phases at atmospheric pressure remains a challenge. Exploring an ionization method that can ionize small organics and large biomolecules with different properties for MS analysis is advantageous. Carbon fiber ionization mass spectrometry (CFI-MS), which uses a carbon fiber bundle as the ion source, is useful for the analysis of small organics with low polarities. Voltage needs to be applied on the carbon fiber bundle to initiate corona discharge for ionization of analytes. In this study, we explore the suitability of using CFI-MS in the analysis of analytes in vapor, liquid, and solid phases using a single carbon fiber (length : ∼1 cm; diameter: ∼10 µm) as the ion source. Furthermore direct electric contact on the carbon fiber is not required. We demonstrate that CFI-MS is useful for analyzing not only small and low-polarity organics but also polar biomolecules, such as peptides and proteins. The limits of detection for analytes with high polarities such as dodecyl trimethylammonium bromide and bradykinin are estimated to be ∼16 and ∼53 pM, respectively. Ionization mechanisms, including corona discharge and electrospray, are involved in the ionization of analytes with the polarity from low to high. Furthermore, sesame oil containing aromatic volatiles and compounds with different polarities is used as a model sample to demonstrate the capability of the developed ionization method to provide comprehensive chemical information from a complex sample. In addition, the feasibility of using the developed method for quantitative analysis of nonpolar as well as medium and high polarity analytes is also demonstrated. The sensitivity of the developed method toward analytes with high polarity is higher than those with low polarity. The method precision was estimated to be ∼7.8%.

Evaluation of Chromane-Based Bryostatin Analogues Prepared via Hydrogen-Mediated C-C Bond Formation: Potency Does Not Confer Bryostatin-like Biology.

The synthesis and biological evaluation of chromane-containing bryostatin analogues WN-2-WN-7 and the previously reported salicylate-based analogue WN-8 are described. Analogues WN-2-WN-7 are prepared through convergent assembly of the chromane-containing fragment B-I with the "binding domain" fragment A-I or its C26-des-methyl congener, fragment A-II. The synthesis of fragment B-I features enantioselective double C-H allylation of 1,3-propanediol to form the C2-symmetric diol 3 and Heck cyclization of bromo-diene 5 to form the chromane core. The synthesis of salicylate WN-8 is accomplished through the union of fragments A-III and B-II. The highest binding affinities for PKCα are observed for the C26-des-methyl analogues WN-3 (Ki = 63.9 nM) and WN-7 (Ki = 63.1 nM). All analogues, WN-2-WN-8, inhibited growth of Toledo cells, with the most potent analogue being WN-7. This response, however, does not distinguish between phorbol ester-like and bryostatin-like behavior. In contrast, while many of the analogues contain a conserved C-ring in the binding domain and other features common to analogues with bryostatin-like properties, all analogues evaluated in the U937 proliferation and cell attachment assays displayed phorbol ester-like and/or toxic behavior, including WN-8, for which "bryostatin-like PKC modulatory activities" previously was suggested solely on the basis of PKC binding. These results underscore the importance of considering downstream biological effects, as tumor suppression cannot be inferred from potent PKC binding.

Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.

The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo-, and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k, and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k, and 6m, respectively. Primary alcohols 2a, 2l, and 2p were converted to the siloxy-crotylation products 3a, 3l, and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l, and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes.

Ruthenium-catalyzed C-C coupling of amino alcohols with dienes via transfer hydrogenation: redox-triggered imine addition and related hydroaminoalkylations.

Ruthenium-catalyzed hydrogen transfer from 4-aminobutanol to butadiene results in the pairwise generation of 3,4-dihydro-2H-pyrrole and an allylruthenium complex, which combine to form products of imine anti-crotylation. In couplings of 1-substituted-1,3-dienes, novel C2 regioselectivity is observed. As corroborated by deuterium labeling studies, kinetically preferred hydrometalation of the terminal olefin of the 1-substituted-1,3-diene delivers a 1,1-disubstituted π-allylruthenium complex that isomerizes to a thermodynamically more stable monosubstituted π-allylruthenium complex, which undergoes imine addition with allylic inversion through a closed transition structure. Direct ruthenium-catalyzed diene hydroaminoalkylations with pyrrolidine also are described.

Benzannulation via ruthenium-catalyzed diol-diene [4+2] cycloaddition: one- and two-directional syntheses of fluoranthenes and acenes.

A new benzannulation protocol is described and applied to the synthesis of polycyclic aromatic hydrocarbons. Ruthenium(0)-catalyzed diol-diene [4+2] cycloaddition delivers cyclohex-1-ene-4,5-diols, which are subject to aromatization upon dehydration or Nicholas diol deoxydehydration. Employing diol and tetraol reactants, benzannulation can be conducted efficiently in one- and two-directional modes, respectively, as illustrated in the construction of substituted fluoranthenes and acenes.

Regioselective ruthenium catalyzed hydrohydroxyalkylation of dienes with 3-hydroxy-2-oxindoles: prenylation, geranylation, and beyond.

The direct conversion of secondary to tertiary alcohols via ruthenium(0) catalyzed C-C coupling of substituted 3-hydroxy-2-oxindoles with various dienes is described. Coupling occurs in a completely regioselective manner in the absence of stoichiometric byproducts.

Direct, redox-neutral prenylation and geranylation of secondary carbinol C-H bonds: C4-regioselectivity in ruthenium-catalyzed C-C couplings of dienes to α-hydroxy esters.

The ruthenium catalyst generated in situ from Ru(3)(CO)(12) and tricyclohexylphosphine, PCy(3), promotes the redox-neutral C-C coupling of aryl-substituted α-hydroxy esters to isoprene and myrcene at the diene C4-position, resulting in direct carbinol C-H prenylation and geranylation, respectively. This process enables direct conversion of secondary to tertiary alcohols in the absence of stoichiometric byproducts or premetalated reagents, and is the first example of C4-regioselectivity in catalytic C-C couplings of 2-substituted dienes to carbonyl partners. Mechanistic studies corroborate a catalytic cycle involving diene-carbonyl oxidative coupling.

Self-organizing CMAC control for a class of MIMO uncertain nonlinear systems.

This paper presents a self-organizing control system based on cerebellar model articulation controller (CMAC) for a class of multiple-input-multiple-output (MIMO) uncertain nonlinear systems. The proposed control system merges a CMAC and sliding-mode control (SMC), so the input space dimension of CMAC can be simplified. The structure of CMAC will be self-organized; that is, the layers of CMAC will grow or prune systematically and their receptive functions can be automatically adjusted. The control system consists of a self-organizing CMAC (SOCM) and a robust controller. SOCM containing a CMAC uncertainty observer is used as the principal controller and the robust controller is designed to dispel the effect of approximation error. The gradient-descent method is used to online tune the parameters of CMAC and the Lyapunov function is applied to guarantee the stability of the system. A simulation study of inverted double pendulums system and an experimental result of linear ultrasonic motor motion control show that favorable tracking performance can be achieved by using the proposed control system.