Computational Deconvolution of Cell Type-Specific Gene Expression in COPD and IPF Lungs Reveals Disease Severity Associations.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are debilitating diseases associated with divergent histopathological changes in the lungs. At present, due to cost and technical limitations, profiling cell types is not practical in large epidemiology cohorts (n>1000). Here, we used computational deconvolution to identify cell types in COPD and IPF lungs whose abundances and cell type-specific gene expression are associated with disease diagnosis and severity. METHODS: We analyzed lung tissue RNA-seq data from 1026 subjects (COPD, n=465; IPF, n=213; control, n=348) from the Lung Tissue Research Consortium. We performed RNA-seq deconvolution, querying thirty-eight discrete cell-type varieties in the lungs. We tested whether deconvoluted cell-type abundance and cell type-specific gene expression were associated with disease severity. RESULTS: The abundance score of twenty cell types significantly differed between IPF and control lungs. In IPF subjects, eleven and nine cell types were significantly associated with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), respectively. Aberrant basaloid cells, a rare cells found in fibrotic lungs, were associated with worse FVC and DLCO in IPF subjects, indicating that this aberrant epithelial population increased with disease severity. Alveolar type 1 and vascular endothelial (VE) capillary A were decreased in COPD lungs compared to controls. An increase in macrophages and classical monocytes was associated with lower DLCO in IPF and COPD subjects. In both diseases, lower non-classical monocytes and VE capillary A cells were associated with increased disease severity. Alveolar type 2 cells and alveolar macrophages had the highest number of genes with cell type-specific differential expression by disease severity in COPD and IPF. In IPF, genes implicated in the pathogenesis of IPF, such as matrix metallopeptidase 7, growth differentiation factor 15, and eph receptor B2, were associated with disease severity in a cell type-specific manner. CONCLUSION: Utilization of RNA-seq deconvolution enabled us to pinpoint cell types present in the lungs that are associated with the severity of COPD and IPF. This knowledge offers valuable insight into the alterations within tissues in more advanced illness, ultimately providing a better understanding of the underlying pathological processes that drive disease progression.

Heritability of cognitive abilities and regional brain structures in middle-aged to elderly East Asians.

This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer's and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.

Potential of Gut Microbe-Derived Extracellular Vesicles to Differentiate Inflammatory Bowel Disease Patients from Healthy Controls.

Background/Aims: This study aimed to evaluate the potential of the stool microbiome and gut microbe-derived extracellular vesicles (EVs) to differentiate between patients with inflammatory bowel disease (IBD) and healthy controls, and to predict relapse in patients with IBD. Methods: Metagenomic profiling of the microbiome and bacterial EVs in stool samples of controls (n=110) and patients with IBD (n=110) was performed using 16S rRNA sequencing and then compared. Patients with IBD were divided into two enterotypes based on their microbiome, and the cumulative risk of relapse was evaluated. Results: There was a significant difference in the composition of the stool microbiome and gut microbe-derived EVs between patients with IBD and controls. The alpha diversity of the microbiome in patients with IBD was significantly lower than that in controls, while the beta diversity also differed significantly between the two groups. These findings were more prominent in gut microbe-derived EVs than in the stool microbiome. The survival curve tended to be different for enterotypes based on the gut microbe-derived EVs; however, this difference was not statistically significant (log-rank test, p=0.166). In the multivariable analysis, elevated fecal calprotectin (>250 mg/kg) was the only significant risk factor associated with relapse (adjusted hazard ratio, 3.147; 95% confidence interval, 1.545 to 6.408; p=0.002). Conclusions: Analysis of gut microbe-derived EVs is better at differentiating patients with IBD from healthy controls than stool microbiome analysis.

Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites.

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (ß = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (ß = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.

Relative contributions of the host genome, microbiome, and environment to the metabolic profile.

BACKGROUND: Metabolic syndrome is as a well-known risk factor for cardiovascular disease, which is associated with both genetic and environmental factors. Recently, the microbiome composition has been shown to affect the development of metabolic syndrome. Thus, it is expected that the complex interplay among host genetics, the microbiome, and environmental factors could affect metabolic syndrome. OBJECTIVE: To evaluate the relative contributions of genetic, microbiome, and environmental factors to metabolic syndrome using statistical approaches. METHODS: Data from the prospective Korean Association REsource project cohort (N = 8476) were used in this study, including single-nucleotide polymorphisms, phenotypes and lifestyle factors, and the urine-derived microbial composition. The effect of each data source on metabolic phenotypes was evaluated using a heritability estimation approach and a prediction model separately. We further experimented with various types of metagenomic relationship matrices to estimate the phenotypic variance explained by the microbiome. RESULTS: With the heritability estimation, five of the 11 metabolic phenotypes were significantly associated with metagenome-wide similarity. We found significant heritability for fasting glucose (4.8%), high-density lipoprotein cholesterol (4.9%), waist-hip ratio (7.7%), and waist circumference (5.6%). Microbiome compositions provided more accurate estimations than genetic factors for the same sample size. In the prediction model, the contribution of each source to the prediction accuracy varied for each phenotype. CONCLUSION: The effects of host genetics, the metagenome, and environmental factors on metabolic syndrome were minimal. Our statistical analysis suffers from a small sample size, and the measurement error is expected to be substantial. Further analysis is necessary to quantify the effects with better accuracy.

Author Correction: Type-2 Diabetics Reduces Spatial Variation of Microbiome Based on Extracellular Vesicles from Gut Microbes across Human Body.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Type-2 Diabetics Reduces Spatial Variation of Microbiome Based on Extracellur Vesicles from Gut Microbes across Human Body.

As a result of advances in sequencing technology, the role of gut microbiota in the mechanism of type-2 diabetes mellitus (T2DM) has been revealed. Studies showing wide distribution of microbiome throughout the human body, even in the blood, have motivated the investigation of the dynamics in gut microbiota across the humans. Particularly, extracellular vesicles (EVs), lipid bilayer structures secreted from the gut microbiota, have recently come into the spotlight because gut microbe-derived EVs affect glucose metabolism by inducing insulin resistance. Recently, intestine hyper-permeability linked to T2DM has also been associated with the interaction between gut microbes and leaky gut epithelium, which increases the uptake of macromolecules like lipopolysaccharide from the membranes of microbes leading to chronic inflammation. In this article, we firstly investigate the co-occurrence of stool microbes and microbe-derived EVs across serum and urine in human subjects (N = 284), showing the dynamics and stability of gut derived EVs. Stool EVs are intermediate, while the bacterial composition in both urine and serum EVs is distinct from the stool microbiome. The co-occurrence of microbes was compared between patients with T2DM (N = 29) and matched in healthy subjects (N = 145). Our results showed significantly higher correlations in patients with T2DM compared to healthy subjects across stool, serum, and urine, which could be interpreted as the dysfunction of intestinal permeability in T2DM. Therefore, the significant correlation of EVs might give insight into the pathophysiological mechanisms of T2DM, as well as the role of EVs as a biomarker in the intestinal permeability of T2DM.

Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

BACKGROUND: Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. OBJECTIVE: We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. METHODS: Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. RESULTS: The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P < .05). CONCLUSIONS: Alterations in the gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function.

Photocurrent enhancement of dye-sensitized solar cells owing to increased dye-adsorption onto silicon-nanoparticle-coated titanium-dioxide films.

The inverse-micellar preparation of Si nanoparticles (Nps) was improved by utilizing sodium naphthalide. The Si Nps were subsequently functionalized with 4-vinylbenzoic acid for their attachment onto TiO(2) films of dye-sensitized solar cells (DSSCs). The average diameter of the COOH-functionalized Si (Si-COOH) Nps was 4.6(±1.7) nm. Depth profiling by secondary-ion mass spectrometry revealed that the Si Nps were uniformly attached onto the TiO(2) films. The number of Ru(II) dye molecules adsorbed onto a TiO(2) film that was treated with the Si-COOH Nps was 42 % higher than that on the untreated TiO(2) film. As a result, DSSCs that incorporated the Si-COOH Nps exhibited higher short-circuit photocurrent density and an overall energy-conversion efficiency than the untreated DSSCs by 22 % and 27 %, respectively. This enhanced performance, mostly owing to the intramolecular charge-transfer to TiO(2) from the dye molecules that were anchored to the Si-COOH Nps, was confirmed by comparing the performance with two different Ru(II) -bipyridine dyes (N719 and N749).

High performance dye-sensitized solar cells with alkylpyridinium iodide salts in electrolytes.

Pyridinium iodide salts, which are competitive to the conventional imidazolium iodide salts, have been used for dye-sensitized solar cells as iodide sources and ionic conductivities. Pyridinium iodide series are easy to prepare and less expensive than the imidazolium series salts. In this research, quite comparable efficiencies were obtained from electrolytes with pyridinium iodide salts. For the experiments, pyridinium salts with a few different alkyl chains are applied. When a pyridinium head is modified to picolinium, which has a methyl group on the pyridinium head, a noticeable V(oc) drop has been observed. However, the length of the alkyl chains on the pyridinium head does not affect V(oc) effectively. The odd-numbered alkyl chains showed slightly lower V(oc) compared to that of the even-numbered alkyl chains. Finally, the performances of the cells with pyridinium salts are compared to those of the conventional cells with imidazolium salts.

Treatment of TiO2 with COOH-functionalized germanium nanoparticles to enhance the photocurrent of dye-sensitized solar cells.

A dye-sensitized solar cell (DSSC) containing a TiO(2) film treated with COOH-functionalized germanium nanoparticles (Ge-COOH Nps) exhibited a higher short-circuit photocurrent density (J(sc); 15.4 mA cm(-2)) compared to the corresponding untreated DSSC (13.4 mA cm(-2)) using N719 and a 12 µm thick TiO(2) film at 100 mW cm(-2). The amount of N719 attached to the treated TiO(2) film was 21% greater than that attached to the untreated TiO(2) film. Enhancement of the J(sc) value by 15% was attributed mostly to an intramolecular charge transfer from N719 attached to the Ge-COOH Nps to the TiO(2) conduction band through the Ge-COOH Nps.

Method to protect charge recombination in the back-contact dye-sensitized solar cell.

We prepared a back-contact dye-sensitized solar cell and investigated effect of the sputter deposited thin TiO2 film on the back-contact ITO electrode on photovoltaic property. The nanocrystalline TiO2 layer with thickness of about 11 µm formed on a plain glass substrate in the back-contact structure showed higher optical transmittance than that formed on an ITO-coated glass substrate, which led to an improved photocurrent density by about 6.3%. However, photovoltage was found to decrease from 817 mV to 773 mV. The photovoltage recovered after deposition of a 35 nm-thick thin TiO2 film on the surface of the back-contact ITO electrode. Little difference in time constant for electron transport was found for the back-contact ITO electrodes with and without the sputter deposited thin TiO2 film. Whereas, time constant for charge recombination increased after introduction of the thin TiO2 film, indicating that such a thin TiO2 film protected back electron transfer, associated with the recovery of photovoltage. As the result of the improved photocurrent density without deterioration of photovoltage, the back-contact dye-sensitized solar cell exhibited 13.6% higher efficiency than the ITO-coated glass substrate-based dye-sensitized solar cell.

Influence of nylon 6 in I3(-)/I(-) redox electrolyte on the photovoltaic performance and stability of dye-sensitized solar cells.

Nylon 6 fibers are used, for the first time, in dye-sensitized solar cells (DSSCs). The overall energy conversion efficiency obtained with 0.18 M nylon 6 reaches 6.2%, which is comparable to that (6.7%) obtained without adding nylon 6 on the day of cell fabrication. However, it is found that the long-term stability of the DSSCs with nylon 6 is superior to that of a reference electrolyte as a result of the complexation of nylon 6 with I(3)(-). Furthermore, nylon 6 is found to be a corrosion inhibitor for silver metal in the electrolyte containing I(3)(-).

High-performance quasi-solid-state dye-sensitized solar cell based on an electrospun PVdF-HFP membrane electrolyte.

An electrospun membrane was prepared from a 16 wt % solution of poly(vinylidenefluoride- co-hexafluoropropylene) (PVdF-HFP) in a mixture of acetone/ N, N-dimethylacetamide (7:3 wt %) at an applied voltage of 12 kV. It was then activated by immersing it in 0.6 M 1-hexyl-2,3-dimethylimidazolium iodide, 0.1 M LiI, 0.05 M I 2, and 0.5 M 4- tert-butylpyridine in ethylene carbonate/propylene carbonate (1:1 wt %) to obtain the corresponding membrane electrolyte with an ionic conductivity of 10 (-5) S cm (-1) at 25 degrees C. On the basis of this electrospun membrane electrolyte, quasi-solid-state dye-sensitized solar cells were fabricated, which showed an open-circuit voltage ( V oc) of 0.76 V, a fill factor of 0.62, and a short-circuit current density ( J sc) of 15.57 mA cm (-2) at an incident light intensity of 100 mW cm (-2). This yields a light-to-electricity conversion efficiency of 7.3%. Moreover, this cell possessed better long-term stability than that fabricated with conventional liquid electrolyte.

Determination of polychlorinated biphenyls in transformer oil using various adsorbents for solid phase extraction.

Various adsorbents for a solid phase extraction (SPE) method were used to study their ability to separate PCBs from transformer oil to rapidly determine their sub-ppm concentration in the transformer oil. Approximately 90% of the transformer oil could be removed from the PCBs by using a hydrophilic-lipophilic balanced copolymer (HLB) adsorbent, but the recovery of deca-chlorobiphenyl (deca-CB) used as a surrogate was only 24.5% due to lose during this cleanup process. The use of a silica adsorbent gave good results with 89.9% recovery of the deca-CB. The recovery of Aroclor 1242 and 1260 were 95.4 and 90.3% on silica, and 98.9 and 83.5% on HLB, respectively. Acid treatment was an essential step in removing the ambiguous interference peaks to help identify the PCBs. A decreased sensitivity of the electron capture detection (ECD) for PCBs was observed due to the presence of the remaining trace oil after the workup procedure. This loss in sensitivity was allowed for by using tetrachloroxylene as an internal standard, and this was found to be reliable for the criteria of quality control by employing an experiment in which LCS was spiked with 2mg/l of Aroclor 1260 and analyzed each day over a 25 day period. The MDL for the analytical method established in this study is 0.05 mg/l.

CTAB-promoted prussian blue-modified electrode and its cation transport characteristics for K+, Na+, Li+, and NH4+ ions.

A Prussian blue (PB) film was deposited on a glassy carbon (GC) electrode by cyclic voltammetry in the presence of the cationic surfactant cetyltrimethylammonium bromide (CTAB). The electrode thus formed showed 4-fold enhancements in redox current and charge values in pure KCl electrolyte as well as greater stability than an electrode prepared in the absence of CTAB. This improved performance of a PB+CTAB electrode versus a PB electrode was further demonstrated using SEM, XRD, and electrochemical impedance spectroscopy (EIS) measurements. A comparative study was undertaken on the cation transport characteristics of PB and PB+CTAB electrodes for Na+, Li+, and NH4+ ions. We obtained a CV pattern for a CTAB-promoted PB film, which showed ideal Nernstian behavior at all scan rates from 5 to 140 mV s(-1). Conditions for the formation and preservation of these ideal and stable PB films are discussed. Possible mechanisms for the beneficial effects of CTAB are proposed.

Structural analysis of platycosides in Platycodi Radix by liquid chromatography/electrospray ionization-tandem mass spectrometry.

Platycosides extracted from Platycodi Radix were analyzed by HPLC coupled with electrospray ionization multistage tandem mass spectrometry (HPLC/ESI-MS(n)). Predominant [M+Na](+) ions in positive mode and [M-H](-) ions in negative mode in the direct ESI-MS spectra of extract provided information on molecular weights, but minor components and isomers could not be discriminated. However, combining HPLC and ESI-MS(n), allowed eleven platycosides, including four acetylated platycodin isomers and two prosapogenines to be analyzed. During MS(2) analysis conducted to elucidate the structures of platycosides, fragment ions provided information on sugar moieties attached at C-28 of triterpene structure of the platycosides. Glycosidic bond cleavages at C-3 were revealed by fragment ions in MS(3) spectra. Some characteristic fragment ions not related to sugar bond cleavage revealed that an esterified triterpene is linked to sugars at C-28. The only sugar ring-cross cleavage corresponding to 90 Da in the negative MS(2) spectrum took place at an arabinosyl sugar moiety. By using HPLC/ESI-MS(n), three acetylated platycosides in Platycodi Radix extract were newly identified.