Unveiling the hidden dangers: enteropathogens carried by flies in Pudong New Area.

BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.

In Silico Discovery of Stapled Peptide Inhibitor Targeting the Nur77-PPARγ Interaction and Its Anti-Breast-Cancer Efficacy.

The binding of peroxisome proliferator-activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti-breast-cancer therapy. However, developing an inhibitor of the Nur77-PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST-CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a KD value of 3.247 × 10-8 M by in silico analysis, rational design, and structural modification. ST-CY14 effectively increases Nur77 protein levels by blocking the Nur77-PPARγ interaction, thereby inhibiting lipid metabolism in breast tumor cells. Notably, ST-CY14 significantly suppresses breast cancer growth and bone metastasis in mice. The findings demonstrate the feasibility of exploiting directly Nur77-PPARγ interaction in breast cancer, and generate what to the best knowledge is the first direct inhibitor of the Nur77-PPARγ interaction available for impeding fatty acid uptake and therapeutic development.

Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study.

Background: Numerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, a clear causative association between the gut microbiota and GERD has yet to be definitively ascertained, given the presence of confounding variables. Methods: The genome-wide association study (GWAS) pertaining to the microbiome, conducted by the MiBioGen consortium and comprising 18,340 samples from 24 population-based cohorts, served as the exposure dataset. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. The inverse variance-weighted (IVW) method was performed as a primary analysis, the other four methods were used as supporting analyses. Furthermore, sensitivity analyses encompassing Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and leave-one-out methodology were carried out to identify potential heterogeneity and horizontal pleiotropy. Ultimately, a reverse MR assessment was conducted to investigate the potential for reverse causation. Results: The IVW method's findings suggested protective roles against GERD for the Family Clostridiales Vadin BB60 group (P = 0.027), Genus Lachnospiraceae UCG004 (P = 0.026), Genus Methanobrevibacter (P = 0.026), and Phylum Actinobacteria (P = 0.019). In contrast, Class Mollicutes (P = 0.037), Genus Anaerostipes (P = 0.049), and Phylum Tenericutes (P = 0.024) emerged as potential GERD risk factors. In assessing reverse causation with GERD as the exposure and gut microbiota as the outcome, the findings indicate that GERD leads to dysbiosis in 13 distinct gut microbiota classes. The MR results' reliability was confirmed by thorough assessments of heterogeneity and pleiotropy. Conclusions: For the first time, the MR analysis indicates a genetic link between gut microbiota abundance changes and GERD risk. This not only substantiates the potential of intestinal microecological therapy for GERD, but also establishes a basis for advanced research into the role of intestinal microbiota in the etiology of GERD.

Progress in RAS-targeted therapeutic strategies: From small molecule inhibitors to proteolysis targeting chimeras.

As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle "undruggable" targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study.

Background: A number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis. Methods: An investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran's Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings. Results: A total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288-2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran's Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP). Conclusion: Our first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease's treatment.

Nanotechnology-based photo-immunotherapy: a new hope for inhibition of melanoma growth and metastasis.

Melanoma is the most aggressive form of skin cancer and there is a need for the development of effective anti-melanoma therapies as it shows high metastatic ability and low response rate. In addition, it has been identified that traditional phototherapy could trigger immunogenic cell death (ICD) to activate antitumor immune response, which could not only effectively arrest primary tumour growth, but also exhibit superior effects in terms of anti-metastasis, anti-recurrence for metastatic melanoma treatment. However, the limited tumour accumulation of photosensitizers/photothermal agents and immunosuppressive tumour microenvironment severely weaken the immune effects. The application of nanotechnology facilitates a higher accumulation of photosensitizers/photothermal agents at the tumour site, which can thus improve the antitumor effects of photo-immunotherapy (PIT). In this review, we summarise the basic principles of nanotechnology-based PIT and highlight novel nanotechnologies that are expected to enhance the antitumor immune response for improved therapeutic efficacy.

A novel aptamer beacon for rapid screening of recombinant cells and in vivo monitoring of recombinant proteins.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

Chinese medicinal herbs as potential prodrugs for obesity.

Obesity is a leading worldwide health threat with ever-growing prevalence, it promotes the incidence of various diseases, particularly cardiovascular disease, metabolic syndrome, diabetes, hypertension, and certain cancers. Traditional Chinese Medicine (TCM) has been used to control body weight and treat obesity for thousands of years, Chinese medicinal herbs provide a rich natural source of effective agents against obesity. However, some problems such as complex active ingredients, poor quality control, and unclear therapeutic mechanisms still need to be investigated and resolved. Prodrugs provide a path forward to overcome TCM deficiencies such as absorption, distribution, metabolism, excretion (ADME) properties, and toxicity. This article aimed to review the possible prodrugs from various medicinal plants that demonstrate beneficial effects on obesity and seek to offer insights on prodrug design as well as a solution to the global obesity issues.

Passive smoking and urinary oxidative biomarkers: A pilot study of healthy travelers from Los Angeles to Beijing.

There is a great heterogeneity in smoking prevalence and tobacco control policy across different countries. However, it is unknown whether this heterogeneity could cause increased passive smoking and adverse health effects among international travelers. In this pilot study, we collected 190 urine samples from 26 Los Angeles residents before (LA-before), during (Beijing), and after (LA-after) a 10-week visit to Beijing to measure biomarkers of passive smoking (cotinine), exposure to polycyclic aromatic hydrocarbons (OH-PAHs), and oxidative stress (malondialdehyde, 8-isoprostane, and uric acid). The geometric mean concentrations of urinary cotinine were 0.14, 1.52, and 0.22 µg/g creatinine in LA-before, Beijing, and LA-after, respectively. Likewise, OH-PAH levels were significantly higher in Beijing as compared to LA-before or LA-after, in association with the urinary cotinine levels. One-fold increase in urinary cotinine levels was associated with 10.1% (95% CI: 5.53-14.8%), 8.75% (95% CI: 2.33-15.6%), and 25.4% (95%CI: 13.1-39.1%) increases in urinary levels of malondialdehyde, 8-isoprotane, and uric acid, respectively. OH-PAHs mediated 9.1-23.3% of the pro-oxidative effects associated with passive smoking. Taken together, our findings indicate that traveling to a city with higher smoking prevalence may increase passive smoking exposure, in association with pro-oxidative effects partially mediated by PAHs.

Arachidonic acid metabolism and inflammatory biomarkers associated with exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with systemic inflammation, yet what mechanisms regulate PAHs' inflammatory effects are less understood. This study evaluated the change of arachidonic acid (ARA) metabolites and inflammatory biomarkers in response to increased exposure to PAHs among 26 non-smoking healthy travelers from Los Angeles to Beijing. Traveling from Los Angeles to Beijing significantly increased urinary metabolites of dibenzofuran (800%), fluorene (568%), phenanthrene (277%), and pyrene (176%), accompanied with increased C-reactive protein, fibrinogen, IL-8, and IL-10, and decreased MCP-1, sCD40L, and sCD62P levels in the blood. Meanwhile, the travel increased the levels of ARA lipoxygenase metabolites that were positively associated with a panel of pro-inflammatory biomarkers. Concentrations of cytochrome P450 metabolite were also increased in Beijing and were negatively associated with sCD62P levels. In contrast, concentrations of ARA cyclooxygenase metabolites were decreased in Beijing and were negatively associated with anti-inflammatory IL-10 levels. Changes in both inflammatory biomarkers and ARA metabolites were reversed 4-7 weeks after participants returned to Los Angeles and were associated with urinary PAH metabolites, but not with other exposures such as secondhand smoke, stress, or diet. These results suggested possible roles of ARA metabolic alteration in PAHs-associated inflammatory effects.

Selenium protects against the likelihood of fetal neural tube defects partly via the arginine metabolic pathway.

BACKGROUND AND AIMS: Neural tube defects (NTDs) are severe congenital malformations and have a complex etiology. This study aimed to explore the association between selected essential trace elements (ETEs) and metabolic pathway markers in the serum of women and the likelihood of NTDs. METHODS: The study included 99 mothers of offspring with and 114 mothers of offspring without NTDs. Five ETEs (iron, zinc, selenium [Se], cobalt, and molybdenum) and 106 metabolic pathway markers in maternal serum were quantified. The associations between ETEs and metabolic pathway markers and the chance of NTDs were examined. Mediating effects of the metabolic pathway markers on the association between Se and the likelihood of NTDs were evaluated. RESULTS: Compared to a Se concentration below the median, a concentration above the median was associated with a decreased chance of NTDs with an odds ratio of 0.29 (95% confidence interval: 0.11-0.66). The concentrations of 32 metabolic pathway markers differed between mothers of offspring with and without NTDs; five of these (asymmetric dimethylarginine, ornithine, glutamate, proline, and phenylalanine) were associated with increased chances of NTDs, with adjusted odds ratios of 3.01 (1.31-7.31), 2.79 (1.18-6.86), 2.38 (1.03-5.75), 2.41 (1.05-5.75), and 2.27 (1.09-5.40), respectively, for the higher interquartile of concentration compared to the lower one. Three arginine pathway metabolic markers (i.e., dimethylarginine, ornithine, and proline) mediated the association between Se and the occurrence of NTDs. CONCLUSION: This study suggests an association between Se and a reduced chance of NTDs. The arginine pathway may play a role in mediating this association.

Acyl-CoA Identification in Mouse Liver Samples Using the In Silico CoA-Blast Tandem Mass Spectral Library.

Acyl-coenzyme A derivatives (acyl-CoAs) are core molecules in the fatty acid and energy metabolism across all species. However, in vivo, many other carboxylic acids can form xenobiotic acyl-CoA esters, including drugs. More than 2467 acyl-CoAs are known from the published literature. In addition, more than 300 acyl-CoAs are covered in pathway databases, but as of October 2020, only 53 experimental acyl-CoA tandem mass spectra are present in NIST20 and MoNA libraries to enable annotation of the mass spectra in untargeted metabolomics studies. The experimental spectra originated from low-resolution ion trap and triple quadrupole mass spectrometers as well as high-resolution quadrupole-time of flight and orbital ion trap instruments at various collision energies. We used MassFrontier software and the literature to annotate fragment ions to generate fragmentation rules and intensities for the different instruments and collision energies. These rules were then applied to 1562 unique species based on [M+H]+ and [M-H]- precursor ions to generate two mass spectra per instrument platform and collision energy, amassing an in silico library of 10,934 accurate mass MS/MS spectra that are freely available at github.com/urikeshet/CoA-Blast. The spectra can be imported into a commercial or freely available mass spectral search tool. We used the libraries to annotate 23 acyl-CoA esters in mouse liver, including 8 novel species.

No evidence for a negative effect of growing season photosynthesis on leaf senescence timing.

The length of the growing season has a large influence on the carbon, water, and energy fluxes of global terrestrial ecosystems. While there has been mounting evidence of an advanced start of the growing season mostly due to elevated spring air temperatures, the mechanisms that control the end of the growing season (EOS) in most ecosystems remain relatively less well understood. Recently, a strong lagged control of EOS by growing season photosynthesis has been proposed, suggesting that more productive growing seasons lead to an earlier EOS. However, this relationship has not been extensively tested with in-situ observations across a variety of ecosystems. Here, we use observations from 40 eddy-covariance flux tower sites in temperate and boreal ecosystems in the northern hemisphere with more than 10 years of observations (594 site-years), ground observations of phenology, satellite observations from the Moderate Resolution Imaging Spectroradiometer (MODIS), and three leaf senescence models to test the extent of a relationship between growing season photosynthesis and end of season senescence. The results suggest that there is no significant negative relationship between growing season photosynthesis and observed leaf senescence, flux-inferred EOS estimates, or remotely sensed phenological metrics, in most ecosystems. On the contrary, while we found negative effects of summer air temperatures and autumn vapor pressure deficit on EOS, more productive growing seasons were typically related to a later, not earlier, EOS. Our results challenge recent reports of carry-over effects of photosynthesis on EOS timing, and suggest those results may not hold over a large range of ecosystems.

Triglyceride profiles are associated with subacute exposure to bisphenol A in healthy young adults.

Conflicted results from previous epidemiological studies call for mechanistic evidence to associate exposure to bisphenol A (BPA) with cardiometabolic diseases. In this natural experiment among healthy travelers from Los Angeles (LA) to Beijing, we collected paired urine and blood samples before their departure, 6-8 weeks after their arrival to Beijing, and 4-7 weeks after their return to LA for the assessment of urinary BPA and lipidome in the serum fraction of blood, to study the effects of drastically changed BPA exposure on the lipid metabolism in relation to the development of cardiometabolic disorders. We used linear mixed-effects models with random intercepts for participant and phase to examine the associations between urinary BPA and serum lipidome. Among 744 lipid species from seven classes, triglyceride (TGs) species showed the strongest associations with BPA exposure. The elevation in BPA exposure was associated with increases in TGs with short carbon chains or few double bonds, and decreases in TGs with long carbon chains or many double bonds. A significant linear relationship was observed between BPA-associated TG changes and the number of carbons and double-bonds in the acyl chain. No modification effects of gender but of body mass index (BMI) were observed on the associations between BPA exposure and TGs. This interdisciplinary environmental research substantiated the cardiometabolic effects of BPA according to the perturbations of TG profiling.

Modeling Isoprene Emission Response to Drought and Heatwaves Within MEGAN Using Evapotranspiration Data and by Coupling With the Community Land Model.

We introduce two new drought stress algorithms designed to simulate isoprene emission with the Model of Emissions of Gases and Aerosols from Nature (MEGAN) model. The two approaches include the representation of the impact of drought on isoprene emission with a simple empirical approach for offline MEGAN applications and a more process-based approach for online MEGAN in Community Land Model (CLM) simulations. The two versions differ in their implementation of leaf-temperature impacts of mild drought. For the online version of MEGAN that is coupled to CLM, the impact of drought on leaf temperature is simulated directly and the calculated leaf temperature is considered for the estimation of isoprene emission. For the offline version, we apply an empirical algorithm derived from whole-canopy flux measurements for simulating the impact of drought ranging from mild to severe stage. In addition, the offline approach adopts the ratio (f PET) of actual evapotranspiration to potential evapotranspiration to quantify the severity of drought instead of using soil moisture. We applied the two algorithms in the CLM-CAM-chem (the Community Atmosphere Model with Chemistry) model to simulate the impact of drought on isoprene emission and found that drought can decrease isoprene emission globally by 11% in 2012. We further compared the formaldehyde (HCHO) vertical column density simulated by CAM-chem to satellite HCHO observations. We found that the proposed drought algorithm can improve the match with the HCHO observations during droughts, but the performance of the drought algorithm is limited by the capacity of the model to capture the severity of drought.

Risk factors in air pollution exposome contributing to higher levels of TNFα in COPD patients.

BACKGROUND: Air pollutants are found associated with various health effects in chronic obstructive pulmonary patients. Given the complicate chemical components of air pollutants, it is not clear which components are the main risk factors for these health effects. OBJECTIVES: Based on the COPD in Beijing (COPDB) study and exposome concept, we examined comprehensively the air pollution components to screen out high-risk factors for systemic inflammation of COPD patients. METHODS: Concentrations of PM with aerodynamic diameter ≤ 2.5 µm (PM2.5), ultrafine and accumulated-mode particles (UFPs and Acc), PM2.5-contained carbonaceous components/elements/water soluble ions, gaseous pollutants, temperature, and relative humidity (RH) were continuously monitored around participants. Urinary polycyclic aromatic hydrocarbons (PAHs) and cotinine, and serum tumor necrosis factor α (TNFα) were measured from 53 COPD and 82 non-COPD participants. Lifestyle variables were recorded using follow-up questionnaire. Linear mixed effects (LME) models were used to assess the associations of TNFα differences with exposure to air pollutants, meteorological variations, and lifestyle. RESULTS: In COPD patients, the associations of TNFα differences with exposure to ozone, Cd, UFPs, Acc, 2-hydroxydibenzofuran, temperature and RH parameters, and several elements in PM2.5 were significant in certain time-windows. For example, per interquartile range (IQR) increase in average ozone concentration 14 d before visits was associated with 17.3% (95% confidence interval: 6.8%, 27.7%) TNFα difference. Associations between ozone, Cd, UFPs, Acc, the maximum value of RH, and 2-hydroxydibenzofuran exposure and TNFα differences remained robust in two-pollutant models, and contributed to 19.0%, 10.5%, 2.2%, 1.6%, 2.1%, and 1.5% TNFα differences, respectively. Among the high-risk factors for COPD patients, the responses to UFPs, Acc, and 2-hydroxydibenzofuran were not robust in non-COPD participants. DISCUSSION: Ozone, Cd, UFPs, Acc, PAHs exposure and RH variation were high-risk factors of systemic inflammation for COPD patients, and the profile of high-risk factors were different from those in general population.

A metabolome atlas of the aging mouse brain.

The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remain poorly understood. Here, we generate a metabolome atlas of the aging wildtype mouse brain from 10 anatomical regions spanning from adolescence to old age. We combine data from three assays and structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between brain regions or age groups, but not by sex. A shift in sphingolipid patterns during aging related to myelin remodeling is accompanied by large changes in other metabolic pathways. Functionally related brain regions (brain stem, cerebrum and cerebellum) are also metabolically similar. In cerebrum, metabolic correlations markedly weaken between adolescence and adulthood, whereas at old age, cross-region correlation patterns reflect decreased brain segregation. We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available ( https://mouse.atlas.metabolomics.us/ ) and serves as a foundation dataset for future metabolomic studies.

Association between exposure to polycyclic aromatic hydrocarbons and lipid peroxidation in patients with chronic obstructive pulmonary disease.

Polycyclic aromatic hydrocarbons (PAHs) are toxic airborne pollutants and may cause adverse effects at high level of oxidative stress. Here we hypothesized that individuals with impaired lung function are susceptible to PAHs associated oxidative damage. Hence, we carried out a panel study and conducted four follow-up visits on 40 chronic obstructive pulmonary disease (COPD) patients and 75 healthy controls. Hydroxylated PAHs (OH-PAHs) and malonaldehyde (MDA) were measured in urine as exposure and oxidative stress markers, respectively, which showed significant association in all participants. Quantitatively, a 1-fold increase in OH-PAHs was associated with a 4.1-15.1% elevation of MDA. The association between OH-PAHs and MDA levels became stronger in participants with impaired lung function. For 1% decrease of FEV1/FVC, the increase of MDA associated with a 1-fold increase in OH-PAHs was up to 0.49%, suggesting an increased susceptibility to PAH-induced oxidative damage in individuals with worse lung function. This study observed that impaired lung function modified the association between PAH exposure and oxidative damage, which might accelerate the aggravation of COPD, and therefore highlighted the necessity of protection measures to decrease the additional adverse effects of air pollution exposure. CAPSULE: Individuals with worse lung function may be more susceptible to PAH-induced lipid peroxidation.

Susceptibility of individuals with lung dysfunction to systemic inflammation associated with ambient fine particle exposure: A panel study in Beijing.

BACKGROUND: The underlying mechanism on the susceptibility of chronic obstructive pulmonary disease (COPD) patients to air pollution has yet to be clarified. OBJECTIVES: Based on the COPD in Beijing (COPDB) study, we examined whether lung dysfunction contributed to pollutant-associated systemic inflammation in COPD patients. METHODS: Proinflammatory biomarkers including interleukin-8 (IL-8) and tumor necrosis factor α (TNFα) were measured in serum samples collected from 53 COPD and 82 healthy participants. Concentrations of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), carbonaceous components in PM2.5, and PM size distribution were continuously monitored. Linear mixed effects models were used to examine the associations of biomarker differences with particle exposure, between COPD and healthy participants, and across subgroups with different levels of lung dysfunction. RESULTS: COPD patients showed higher differences in IL-8 and TNFα levels associated with exposure to measured pollutants, comparing to healthy controls. In advanced analysis, particle-associated differences in IL-8 and TNFα levels were higher in participants with poorer lung ventilation and diffusion capacity, and higher ratio of residual volume. For example, an interquartile range increase in average PM2.5 concentration 2 weeks before visits was associated with a 15.7% difference in IL-8 level in participants with the lowest ratio of measured value to predicted value of forced expiratory volume in 1 s (FEV1%pred) (65.2%), and the association decreased monotonically with increasing FEV1%pred. Associations between differences in TNFα level and average ultrafine particle concentration 1 week before visits increased gradually with increasing ratio of measured value to predicted value of residual volume/total lung capacity. CONCLUSIONS: COPD patients, especially those with poorer lung function, are more susceptible to systemic inflammation associated with fine particle exposure.

Metabolomic Changes after Subacute Exposure to Polycyclic Aromatic Hydrocarbons: A Natural Experiment among Healthy Travelers from Los Angeles to Beijing.

Emerging epidemiological evidence has associated exposure to polycyclic aromatic hydrocarbons (PAHs) with chronic diseases including cardiometabolic diseases and neurodegeneration. However, little information is available about their subacute effects, which may accumulate over years and contribute to chronic disease development. To fill this knowledge gap, we designed a natural experiment among 26 healthy young adults who were exposed to elevated PAHs for 10 weeks after traveling from Los Angeles to Beijing in 2014 and 2015. Serum was collected before, during, and after the trip for metabolomics analysis. We identified 50 metabolites that significantly changed 6-8 weeks after the travel to Beijing (FDR < 5%). The network analysis revealed two main independent modules. Module 1 was allocated to oxidative homeostasis-related response and module 2 to delayed enzymatic deinduction response. Remarkably, the module 1 metabolites were recovered 4-7 weeks after participants' return, while the module 2 metabolites were not. Urinary hydroxylated PAHs were significantly associated with metabolites from both modules, while PAH carboxylic acids, likely metabolites of alkylated PAHs, were only associated with antioxidation-related metabolites. These results suggested differential subacute effects of unsubstituted and alkylated PAHs. Further studies are warranted to elucidate the role of the reversibility of metabolite changes in adverse health effects of PAHs.