Pan-cancer transcriptome analysis reveals widespread regulation through alternative tandem transcription initiation.

Abnormal transcription initiation from alternative first exon has been reported to promote tumorigenesis. However, the prevalence and impact of gene expression regulation mediated by alternative tandem transcription initiation were mostly unknown in cancer. Here, we developed a robust computational method to analyze alternative tandem transcription start site (TSS) usage from standard RNA sequencing data. Applying this method to pan-cancer RNA sequencing datasets, we observed widespread dysregulation of tandem TSS usage in tumors, many of which were independent of changes in overall expression level or alternative first exon usage. We showed that the dynamics of tandem TSS usage was associated with epigenomic modulation. We found that significant 5' untranslated region shortening of gene TIMM13 contributed to increased protein production, and up-regulation of TIMM13 by CRISPR-mediated transcriptional activation promoted proliferation and migration of lung cancer cells. Our findings suggest that dysregulated tandem TSS usage represents an addtional layer of cancer-associated transcriptome alterations.

The landscape and clinical relevance of intronic polyadenylation in human cancers.

Intronic polyadenylation (IPA) is an RNA 3' end processing event which has been reported to play important roles in cancer development. However, the comprehensive landscape of IPA events across various cancer types is lacking. Here, we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas (TCGA) project. We totally identify 21,835 IPA events, almost half of which are ubiquitously expressed. We identify 2761 unique dynamically changed IPA events across cancer types. Furthermore, we observe 8855 non-redundant clinically relevant IPA events, which could potentially be used as prognostic indicators. Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response. Finally, we develop a user-friendly data portal, IPACancer Atlas (http://www.tingni-lab.com/Pancan_IPA/), to search and explore IPAs in cancer.

Selective hydrodeoxygenation of α, ß-unsaturated carbonyl compounds to alkenes.

Achieving selective hydrodeoxygenation of α, ß-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, ß-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Prenatal exposure to a mixture of organophosphate flame retardants and infant neurodevelopment: A prospective cohort study in Shandong, China.

BACKGROUND: Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE: This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS: A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS: The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 µg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION: Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

Bisphenol chemicals in colostrum from Shanghai, China during 2006-2019: Concentration, temporal variation, and potential influence on birth parameters.

Bisphenol A (BPA) and its alternatives bisphenol S (BPS) and bisphenol F (BPF) are identified as endocrine disruptors that have negative impacts on infant growth. Their temporal variations in human milk and potential effects on fetal growth are not well known. In this study, colostrum collecting at four time points between 2006 and 2019 and paired urine in 2019 from Shanghai, China, were analyzed for eight bisphenols. The total concentrations in colostrum in 2019 were up to 3.43 ng/mL, with BPA being dominant, followed by BPS and BPF. BPA levels in colostrum noticeably decreased from 2010 to 2013. Additionally, obvious percentage changes in bisphenols were observed in 2019. The BPA concentrations in paired colostrum and urine were not significantly correlated. High levels of BPA in colostrum were linked to a significant reduction in birth head circumference in 2019 (p = 0.031). BPA and BPS in colostrum might have similar negative effect on fetal growth in 2019, but these effects were generally non-significant. Further studies are needed to testify the potential impact. The hazard indexes for infants in the first week of life were below 1, suggesting no obvious health risks. However, the high contribution from BPA still warrants further attention.

[Ecological Risk Assessment and Migration and Accumulation Characteristics of Heavy Metals in Farmland Soil-crop System from Typical Pyrite Mining Area].

To evaluate the ecological risk of heavy metals in the soil-crop system in the superimposed high background and human activities from pyrite mining, the heavy metal contents and chemical speciation in soil and crop samples were analyzed, and these data were used to assess the potential ecological risk and factors affecting the migration ability of heavy metals using bioconcentration factors(BCF), potential ecological risk index(RI), risk assessment code(RAC), and correlation analysis. The results indicate that the average Cd, Cu, Pb, and Zn concentrations exceeded the background values of soils in Zhejiang Province and China. Cd had the greatest potential ecological harm, followed by that of Hg. The bioactive components and potential bioactive components of Cd accounted for 46% and 33%, respectively, indicating relatively high bioavailability. Cu and Pb were mainly in potential bioactive components accounting for 60% and 73%, respectively. The As, Cr, Hg, Ni, and Zn were predominantly residual and accounted for >60%, which indicated low biological activity. The RAC levels were in the following order:Cd>Zn>Cu>Pb>Ni>As>Cr>Hg; soil Cd had the highest ecological risk, mainly with high and extremely high levels, whereas other elements had no risk or low risk. Compared with Cd content in soil, only eight rice samples had Cd contents exceeding the safety limit, and sweet potato samples did not exceed the standard. The migration and enrichment capability of rice in order from strong to weak was s follows:Cd>Zn>Cu>Hg>As>Ni>Cr>Pb; the bioactive component of Cd played a significant role in promoting Cd absorption by rice. Soil OM had a bi-directional effect on Cd bioavailability, whereas soil texture had an indirect effect. This comprehensive study shows that the total amount of heavy metals in soil, chemical speciation, biological activities, absorption, and enrichment of heavy metals by crops should be taken into consideration when assessing the ecological risks in the superimposed areas affected by high background and human activities, such as the pyrite mining area.

Maternal exposure to organophosphate flame retardants and neonatal anthropometric measures.

BACKGROUND: Organophosphate flame retardants (OPFRs) are widely used as flame retardants and plasticizers. Laboratory evidence has suggested that maternal OPFR exposure may adversely affect fetal growth, but the epidemiological data are limited. OBJECTIVES: To investigate the association of maternal OPFR exposure with neonatal anthropometric measures. METHODS: This study included 354 mother-newborn pairs from the Laizhou Wan Birth Cohort (LWBC), China. Ten OPFR metabolites were measured in maternal urine samples collected before delivery. Neonatal anthropometric data was collected from medical records and standardized into z-scores using the WHO standards (2007), including the weight-for-age (WAZ), length-for-age (LAZ), body mass index-for-age (BMIZ), weight-for-length (WLZ), and head circumference-for-age z-score (HCZ). Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of individual OPFR metabolites and their mixtures with neonatal anthropometrics, respectively. Stratified analysis by sex was performed. RESULTS: The detection rates of BCEP, DPHP, BCIPP, BDCIPP, BBOEP, DnBP and DiBP were above 60%, with median concentrations ranging from 0.14 to 3.60 µg/g creatinine. Most OPFR metabolites (i.e., BCIPP, BDCIPP, DiBP, DnBP, or BBOEP) were associated with decreased offspring WAZ and HCZ. When using WQS analysis, the OPFR metabolite mixture was inversely associated with the WAZ, BMIZ and HCZ, whereas DnBP had the highest weights. After stratified by gender, the negative associations were more pronounced among males. CONCLUSIONS: Maternal OPFR exposure was negatively associated with offspring WAZ, BMIZ, and HCZ, and males seemed to be more vulnerable to the developmental toxicity of certain OPFRs.

The association between sleep duration, respiratory symptoms, asthma, and COPD in adults.

Introduction: The association between sleep duration and cough, wheezing, and dyspnea was unclear. This research aimed to test this relationship. Methods: Research data were obtained from people who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. We used weighted logistic regression analysis and fitted curves to explore the association between sleep and respiratory symptoms. In addition, we investigated the association between sleep duration, chronic obstructive pulmonary disease (COPD), and asthma. The stratified analysis is used to analyze inflection points and specific populations. Results: The 14,742 subjects are weighted to reflect the 45,678,491 population across the United States. Weighted logistic regression and fitted curves show a U-shaped relationship between sleep duration and cough and dyspnea. This U-shaped relationship remained in people without COPD and asthma. The stratified analysis confirmed that sleep duration before 7.5 h was negatively associated with cough (HR 0.80, 95% CI 0.73-0.87) and dyspnea (HR 0.82, 95% CI 0.77-0.88). In contrast, it was positively associated with cough and (HR 1.30, 95% CI 1.14-1.48) dyspnea (HR 1.12, 95% CI 1.00-1.26) when sleep duration was >7.5 h. In addition, short sleep duration is associated with wheezing, asthma, and COPD. Conclusion: Both long and short sleep duration are associated with cough and dyspnea. And short sleep duration is also an independent risk factor for wheezing, asthma, and COPD. This finding provides new insights into the management of respiratory symptoms and diseases.

The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer.

Cryptic transcription initiation has been previously linked to activation of oncogenic transcripts. However, the prevalence and impact of cryptic antisense transcription from the opposite strand of protein-coding genes were mostly unknown in cancer. Applying a robust computational pipeline to publicly available transcriptome and epigenome datasets, we identified hundreds of previously unannotated cryptic antisense polyadenylated transcripts (CAPTs) that were enriched in tumor samples. We showed that the activation of cryptic antisense transcription was associated with increased chromatin accessibility and active histone marks. Accordingly, we found that many of the antisense transcripts were inducible by treatment of epigenetic drugs. Moreover, CRISPR-mediated epigenetic editing assays revealed that transcription of a noncoding RNA LRRK1-CAPT promoted LUSC cell proliferation, suggesting its oncogenic role. Our findings largely expand our understanding of cancer-associated transcription events, which may facilitate the development of novel strategies for cancer diagnosis and treatment.

Computational and experimental studies on the micellar morphology and emission mechanisms of AIE and H-bonding fluorescent composites.

In this work, we use density functional theory (DFT) calculated competitive hydrogen bonds and dissipative particle dynamics (DPD) simulated micellar structural information to uncover the CO2-expanded liquid (CXL)-aided self-assembled structure and emission mechanisms of the self-assembled fluorescent composites (SAFCs). Herein, the SAFCs are formed through the self assembly between diblock copolymer polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) blend and the dye molecule 4-(9-(2-(4-hydroxyphenyl)ethynyl)-7,10-diphenylfluoranthen-8-yl)phenol (4) in CO2-expanded toluene at 313.2 K and varied pressures. Firstly, from DPD simulation, we have demonstrated that the addition of CO2 to toluene favors both the expansion of the solvophobic P4VP phase and contraction of solvophilic PS chains, which facilitates the continuous morphological transitions of SAFCs from spherical micelles (3.0 MPa) through wormlike plus spherical micelles (4.0-4.8 MPa) to large vesicles (6.0-6.5 MPa) with pressure rise. Secondly, the DFT calculated bonding energies and IR spectra of the competitive hydrogen bonds help us to clarify the major type of hydrogen bonds determining the fluorescence (FL) performance of the SAFCs. Furthermore, we have revealed the SAFC emission mechanism via the pressure-tunable changes in the aggregation degrees and amount of hydrogen bonds involving 4 and P4VP chains. This work provides a good understanding for the morphology-property control of the self-assembled polymer composites in both microscopic and mesoscopic scales.

Association between B-vitamins intake and frailty among patients with chronic obstructive pulmonary disease.

PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.

Effects of cinnamaldehyde against planktonic bacteria and biofilm formation of Shigella flexneri.

Cinnamaldehyde (CA) has demonstrated anti-inflammatory, anti-tumor and anti-cancer activities; Its antimicrobial and antibiofilm actions against Shigella flexneri, on the other hand, have not been investigated. Sh. flexneri is a gram-negative foodborne pathogen that can be widely found in nature and some industrial production environments. In this current research, our aim was to examine the influences of CA on planktonic bacteria and biofilm formation. The minimum inhibitory concentration (MIC) of CA against Sh. flexneri strain was 100 µg/mL, while bacteria treated with CA showed a longer lag phase compared with the untreated control. CA effectively inactivated the Sh. flexneri in LB broth and fresh lettuce juice. CA treatment resulted in cell membrane permeability changes and dysfunction, as proven by cell membrane depolarization, decreased intracellular ATP concentration. In addition, CA was also discovered to increase the level of reactive oxygen species (ROS) in cells, and induce morphological changes in cells. Crystal violet staining showed that the biomass of biofilm was decreased significantly with CA in 24 h. Light microscopy and field emission scanning electron microscopy (FESEM) observations demonstrated decreased biofilm adhesion and destruction of biofilm architecture after treatment with CA. These findings indicated that CA acts as a natural bacteriostatic agent to control Sh. flexneri in food processing and production.

Simultaneous determination of 16 urinary metabolites of organophosphate flame retardants and organophosphate pesticides by solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry.

Organophosphate flame retardants (OPFRs) and organophosphate pesticides (OPPs), pertaining to organophosphate esters, are ubiquitous in environment and have been verified to pose noticeable risks to human health. To evaluate human exposures to OPFRs and OPPs, a fast and sensitive approach based on a solid phase extraction (SPE) followed by the ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the simultaneous analysis of multiple organophosphorus metabolites in urine. The method allows the identification and quantification of ten metabolites of the most common OPFRs and all six dialkylphosphates (DAPs) of OPPs concerning the population exposure characteristics. The method provided good linearities (R2 = 0.998-0.999), satisfactory method detection limits (MDLs) (0.030-1.129 ng/mL) and only needed a small volume (200 µL) of urine. Recovery rates ranged 73.4-127.1% at three spiking levels (2, 10 and 25 ng/mL urine), with both intra- and inter-day precision less than 14%. The good correlations for DAPs in a cross-validation test with a previous gas chromatography-mass spectrometry (GC-MS) method and a good inter-laboratory agreement for several OPFR metabolites in a standard reference material (SRM 3673) re-enforced the precision and validity of our method. Finally, the established method was successfully applied to analyze 16 organophosphorus metabolites in 35 Chinese children's urine samples. Overall, by validating the method's sensitivity, accuracy, precision, reproducibility, etc., data reliability and robustness were ensured; and the satisfactory pilot application on real urine samples demonstrated feasibility and acceptability of this method for being implemented in large population-based studies.

[Heavy Metal Concentration Characteristics and Health Risks of Farmland Soils in Typical Pyrite Mining Area of the Central Zhejiang Province, China].

In order to ascertain the impact of pyrite mining on the surrounding farmland soil environment and human health, 42 surface soil samples (from 0-20 cm) were collected around the pyrite mining area in Longyou county. In this study, the concentrations of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and the pH in the topsoil were analyzed, and the concentration characteristics of heavy metals, source analysis, and human health risks assessment were studied using statistical analysis (SA), geo-accumulation index (Igeo), positive matrix factorization (PMF), and the health risk model. The average of ω(Cd), ω(Cu), ω(Pb), and ω(Zn) concentrations exceeded the background values of soils in Zhejiang province and China. According to the agricultural land pollution risk screening values (GB 15618-2018), Cd, Cu, Pb, and Zn were up to 82%, 49%, 42%, and 31%, respectively. The Igeo shows that the major pollutant element in the soils was Cd, followed by Cu, Pb, and Zn. The PMF analysis indicates that nature sources (As, Cr, and Ni), comprehensive pollution sources caused by high geological background and mining of ore-forming geological bodies (Cd, Cu, Pb, and Zn), and anthropogenic sources (Hg) were the three major sources of heavy metals in the study area, with contributions of 32%, 46%, and 22%, respectively. The results of the health risk assessment indicate that the major non-carcinogenic factor triggering risks was the ingestion of Pb; Cr exposure had carcinogenic risk for adults, and Cr and As exposure had carcinogenic risk for children.

Highly efficient catalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid using bimetallic Pt-Cu alloy nanoparticles as catalysts.

Bimetallic platinum-copper alloy nanoparticles are highly active catalysts for the oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) under base-free conditions, with a high turnover frequency of up to 135 h-1 in aqueous solution. The Pt-Cu1.5/AC alloyed catalyst promoted the rate-determining step in the tandem oxidation compared with the monometallic Pt/AC catalyst, thus improving the catalytic performance.

Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study.

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10-4), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10-4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.

Organic amine mediated cleavage of Caromatic-Cα bonds in lignin and its platform molecules.

The activation and cleavage of C-C bonds remains a critical scientific issue in many organic reactions and is an unmet challenge due to their intrinsic inertness and ubiquity. Meanwhile, it is crucial for the valorization of lignin into high-value chemicals. Here, we proposed a novel strategy to enhance the Caromatic-Cα bond cleavage by pre-functionalization with amine sources, in which an active amine intermediate is first formed through Markovnikov hydroamination to reduce the dissociation energy of the Caromatic-Cα bond which is then cleaved to form target chemicals. More importantly, this strategy provides a method to achieve the maximum utilization of the aromatic nucleus and side chains in lignin or its platform molecules. Phenols and N,N-dimethylethylamine compounds with high yields were produced from herbaceous lignin or the p-coumaric acid monomer in the presence of industrially available dimethylamine (DMA).

Identification of Mucus-Associated Molecular Subtypes of Chronic Obstructive Pulmonary Disease: A Latent Profile Analysis Based on MUC5B-Associated Genes.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a disease with high heterogeneity, which is a major challenge in clinical individualized treatment. A mucus phenotype is one of the main characteristics of COPD. MATERIAL AND METHODS Gene expression profiles of lung tissue samples were from the Lung Genomics Research Consortium. MUC5B-associated gene signatures were obtained based on a nonlinear feature screening algorithm. These signatures were used to fit a latent profile analysis (LPA) model to identify COPD molecular subtypes and build a subtype classifier to verify the subtypes. Then, we explored the characteristics of cilium assembly and beating signatures, transcriptome features, immune infiltration among the 3 subtypes by xCell, single-sample gene set enrichment analysis, network perturbation amplitude, and weighted gene co-expression network analysis algorithms. An external dataset was used to verify the above COPD subtypes. RESULTS Three subtypes associated with mucus were identified by LPA and verified in an external dataset. Subtype 1 displayed higher T helper type 1 (Th1) and basophil infiltration, higher Th17/regulatory T cells (Tregs) ratio, a higher level of cilium assembly and beating, and lower mast cell and Treg infiltration. The subtypes 2 and 3 demonstrated higher macrophage M2 infiltration in lung tissue, while subtype 3 had higher neutrophil and eosinophil infiltration than subtype 2. CONCLUSIONS Overall, this work identified 3 mucus-associated molecular subtypes related to MUC5B expression, which deepens the understanding of airway mucus secretion in COPD and potentially provides valuable information for precision therapy.

Identification of Metabolism-Associated Molecular Subtypes of Chronic Obstructive Pulmonary Disease.

Purpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage. Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes. Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets. Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes.

Porous and nanowire-structured NiO/AgNWs composite electrodes for significantly-enhanced supercapacitive and electrochromic performances.

NiO/AgNWs composite films which specially contain both porous and one-dimensional (1D) nanowire structures are prepared uniformly via a simple chemical bath deposition method. The supercapacitive electrodes constructed by the as-prepared NiO/AgNWs composite films exhibit a high specific capacitance (980 F g-1at 1 A g-1), much higher than that of the pure NiO films. Particularly, a large optical modulation (84.3% at 550 nm) and short switching times for the coloration and bleaching (5.4 and 6.5 s) are also observed if these NiO/AgNWs films serve as the electrochromic materials. The superior capacitive and electrochromic properties of the NiO/AgNWs composite films are attributed to the large electrochemically effective surface areas and enhanced conductivity induced by the addition of 1D AgNWs, which efficiently shorten the ions/electrons diffusion paths and accelerate the reversible redox reactions. Therefore, the NiO/AgNWs composite films hold a great potential for applications as a novel electrode material in supercapacitive and electrochromic devices.