Air pollutants, genetic susceptibility, and incident schizophrenia in later life: A prospective study in the UK Biobank.

OBJECTIVE: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late-onset schizophrenia and evaluate whether genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. RESULTS: An interquartile range increase in PM2.5, PM10, NO2, and NOx was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure-response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM10, NO2, and NOx with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. CONCLUSION: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late-onset schizophrenia in an aging era, especially among those with high genetic risks.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Air Pollution and Cardiac Arrest: A More Significant Intermediate Role of COPD than Cardiac Events.

No prior studies have linked long-term air pollution exposure to incident sudden cardiac arrest (SCA) or its possible development trajectories. We aimed to investigate the association between long-term exposure to air pollution and SCA, as well as possible intermediate diseases. Based on the UK Biobank cohort, Cox proportional hazard model was applied to explore associations between air pollutants and SCA. Chronic obstructive pulmonary disease (COPD) and major adverse cardiovascular events (MACE) were selected as intermediate conditions, and multistate model was fitted for trajectory analysis. During a median follow-up of 13.7 years, 2884 participants developed SCA among 458 237 individuals. The hazard ratios (HRs) for SCA were 1.04-1.12 per interquartile range increment in concentrations of fine particulate matter, inhalable particulate matter, nitrogen dioxide, and nitrogen oxides. Most prominently, air pollutants could induce SCA through promoting transitions from baseline health to COPD (HRs: 1.06-1.24) and then to SCA (HRs: 1.16-1.27). Less importantly, SCA could be developed through transitions from baseline health to MACE (HRs: 1.02-1.07) and further to SCA (HRs: 1.12-1.16). This study provides novel and compelling evidence that long-term exposure to air pollution could promote the development of SCA, with COPD serving as a more important intermediate condition than MACE.

Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.

Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analyzed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance (NGT) throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly different during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5 possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolic pathway might play a crucial role in GDM and that Cys supplementation represents a potential new treatment strategy for GDM patients.

Long-term exposure to ambient air pollution and incident gout: A prospective cohort study in the UK Biobank.

Gout is a chronic disorder characterized by the accumulation of uric acid in the body, leading to recurrent episodes of joint inflammation and pain. There remains a lack of studies investigating the association between long-term exposure to ambient air pollution and the incidence of gout. We conducted this prospective cohort study involving participants aged 38-70 from the UK Biobank who were enrolled in 2006-2010 and followed until 2023. Baseline residential concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were predicted using land-use regression models. Cox proportional hazards models were employed to examine the relationship between air pollution and incident gout events. A total of 443,587 individuals were included in the analyses and a total of 6589 incident gout cases were identified over a follow-up of 6,130,439 person-years. There were significant associations between higher levels of air pollution and an increased incidence risk of gout. Higher risk of incident gout was associated with each interquartile range increase in concentrations of PM2.5 (hazard ratio:1.05, 95% confidence intervals: 1.02-1.09), PM10 (1.04, 1.00-1.07), NO2 (1.08, 1.05-1.12) and NOx (1.04, 1.02-1.07). The magnitude of associations was larger at higher concentrations. The association was more prominent among older adults, smokers, and individuals with lower and moderate physical activity. This prospective cohort study provides novel and compelling evidence of increased risk of incident gout associated with long-term air pollution exposures.

Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation. METHODS: Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms. RESULTS: In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6. CONCLUSIONS: In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.

The study collectively indicated that valeric acid (VA) was consistently negatively related to the disease severity of UC, and hypofunction of macrophage driven by VA impeded the progression of UC.

Gypenoside Pretreatment Alleviates the Cerebral Ischemia Injury via Inhibiting the Microglia-Mediated Neuroinflammation.

Neuroinflammation is closely related to prognosis in ischemic stroke. Microglia are the main immune cells in the nervous system. Under physiological conditions, microglia participate in clearance of dead cells, synapse pruning and regulation of neuronal circuits to maintain the overall health of the nervous system. Once ischemic stroke occurs, microglia function in the occurrence and progression of neuroinflammation. Therefore, the regulation of microglia-mediated neuroinflammation is a potential therapeutic strategy for ischemic stroke. The anti-inflammatory activity of gypenosides (GPs) has been confirmed to be related to the activity of microglia in other neurological diseases. However, the role of GPs in neuroinflammation after ischemic stroke has not been studied. In this study, we investigated whether GPs could reduce neuroinflammation by regulating microglia and the underlying mechanism through qRT-PCR and western blot. Results showed that GPs pretreatment mitigated blood-brain barrier (BBB) damage in the mice subjected to middle cerebral artery occlusion (MCAO) and improved motor function. According to the results of immunofluorescence staining, GPs pretreatment alleviated neuroinflammation in MCAO mice by reducing the number of microglia and promoting their phenotypic transformation from M1 to M2. Furthermore, GPs pretreatment reduced the number of astrocytes in the penumbra and inhibited their polarization into the A1 type. We applied oxygen and glucose deprivation (OGD) on BV2 cells to mimic ischemic conditions in vitro and found similar effect as that in vivo. At the molecular level, the STAT-3/HIF1-α and TLR-4/NF-κB/HIF1-α pathways were involved in the anti-inflammatory effects of GPs in vitro and in vivo. Overall, this research indicates that GPs are potential therapeutic agents for ischemic stroke and has important reference significance to further explore the possibility of GPs application in ischemic stroke.

Caregiver-child interaction as an effective tool for identifying autism spectrum disorder: evidence from EEG analysis.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. METHODS: We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. RESULTS: Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). CONCLUSION: Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.

Air pollution may increase the sleep apnea severity: A nationwide analysis of smart device-based monitoring.

Obstructive sleep apnea (OSA) can lead to sleep deprivation, accidents, and cardiovascular diseases. However, research on the short-term effects of air pollutants on OSA severity is limited and inconsistent. We conducted a novel case time series analysis using a nationwide dataset among Huawei smart device users to assess the association between air pollution and OSA severity in a population at moderate-to-severe risk of OSA. Fixed-effects regression models were used to assess the associations between air pollution and the risk of OSA exacerbation, apnea-hypopnea index (AHI), and oxygen saturation. A total of 51,842 participants who were at moderate-to-severe risk of OSA (mean age [SD]: 45.4 [11.0], 95.5% male) were included, with 6,232,056 person-days of monitoring. The associations of fine particulate matter, nitrogen dioxide, carbon monoxide, and sulfur dioxide with OSA severity could occur during the sleep period, and last for 2 days. An increase of 1 interquartile range in the moving average concentrations of air pollution during the sleep period and the 2 previous days was associated with a 1.14%-4.31% increase in the risk of OSA exacerbation, an increase in AHI by 0.05-0.17 events/h, and a decrease in oxygen saturation (%) by 0.003-0.014. The exposure-response curves were almost linear. The associations between air pollutants and OSA were consistently stronger in participants aged 45 years or older. By virtue of the smart device-based technology, this large-scale, nationwide, longitudinal study provides compelling evidence that short-term exposure to air pollution may worsen sleep apnea. Our findings highlight the significance of ongoing efforts to improve air quality in mitigating OSA severity and the relevant disease burden in an aging era.

Vibrio parahaemolyticus becomes lethal to post-larvae shrimp via acquiring novel virulence factors.

IMPORTANCE: As a severe emerging shrimp disease, TPD has heavily impacted the shrimp aquaculture industry and resulted in serious economic losses in China since spring 2020. This study aimed to identify the key virulent factors and related genes of the Vp TPD, for a better understanding of its pathogenicity of the novel highly lethal infectious pathogen, as well as its molecular epidemiological characteristics in China. The present study revealed that a novel protein, Vibrio high virulent protein-2 (MW >100 kDa), is responsible to the lethal virulence of V. parahaemolyticus to shrimp post-larvae. The results are essential for effectively diagnosing and monitoring novel pathogenic bacteria, like Vp TPD, in aquaculture shrimps and would be beneficial to the fisheries department in early warning of Vp TPD emergence and developing prevention strategies to reduce economic losses due to severe outbreaks of TPD. Elucidation of the key virulence genes and genomics of Vp TPD could also provide valuable information on the evolution and ecology of this emerging pathogen in aquaculture environments.

Clinical protective effects of polyhexamethylene biguanide hydrochloride (PHMB) against Vibrio parahaemolyticus causing translucent post-larvae disease (VpTPD) in Penaeus vannamei.

A new emerging disease called "translucent post-larvae disease" (TPD) in Penaeus vannamei, caused by a novel type of highly lethal Vibro parahaemolyticus (VpTPD), has become an urgent threat to the shrimp farming industry in China. In order to develop an effective disinfectant for the prevention and control of the VpTPD, the clinical protective effects of polyhexamethylene biguanide hydrochloride (PHMB) against VpTPD in Penaeus vannamei were investigated by carrying out an acute toxicity test of PHMB on post-larvae of P. vannamei and its effect of treatment test on VpTPD infection. The results showed that the median lethal concentration of disinfectant (LC50) values of PHMB to post-larvae of P. vannamei after treatment for 24 h, 48 h, 72 h, 96 h were 16.13 mg/L (14.18-18.57), 10.77 mg/L (9.93-11.72), 9.68 mg/L (8.53-11.64), 9.14 mg/L (7.70-10.99), respectively. In addition, a clinical trial showed that 1 mg/L PHMB showed a strong protective effect on the post-larvae of shrimp challenged with 101-104 CFU/ml of VpTPD. The relative percentage survival (RPS) of 1 mg/L PHMB on post-larvae of P. vannamei challenged with VpTPD at 101, 102, 103 and 104 CFU/ml were 63.65 %±6.81, 62.96 %±5.56, 60.00 %±3.75 and 66.67 %±3.75 at 96 hours post infection. The results highlight the clinical protective effects of the PHMB and therefor PHMB can be used as a preventive measure to control early TPD infection in shrimp culture. This study also provides valuable information for the prevention of other bacterial diseases in shrimp culture.

Establishment of two visual interpretation methods of DIV1 LAMP amplification products.

Viral diseases have become a significant impediment to the sustainable development of the global shrimp aquaculture industry. Decapod iridescent virus 1 (DIV1) is an emerging shrimp virus that has affected shrimp in China recent years. Rapid detection of DIV1 could improve enhance the effectiveness of prevention, control and treatment in the absence of good prevention and control measures. This study established loop-mediated isothermal amplification (LAMP) along with two visual interpretation methods, LAMP-dye and LAMP-LFD, to detect DIV1. The newly developed method would not cause cross-reactions with other shrimp pathogens such as white spot syndrome virus (WSSV), infectious hypodermal and hematopoietic necrosis virus (IHHNV), Enterocytozoon hepatopenaei (EHP), and Vibrio parahaemolyticus acute hepatopancreatic necrosis disease (VpAHPND). The detection limit of DIV1 LAMP was as low as 103 copies of DIV1 per reaction, with a reaction time of less than 40 min. The diagnostic sensitivity and diagnostic specificity of this method were determined to be 88% and 100%, respectively, when compared with the conventional PCR. Both of the LAMP-dye and LAMP-LFD methods are cost-effective and do not require expensive amplification equipment. They can be combined with LAMP and other temperature amplification methods for rapid on-site detection, effectively prevent aerosol contamination, and which are convenient and suitable for field testing or preliminary infection rish prediction experiments to predict the risk of infection.

Residential greenspace counteracts PM2.5 on the risks of preterm birth subtypes: A multicenter study.

BACKGROUND: The association between residential greenspace and preterm birth (PTB) risk remained inconclusive. The PTB subtypes have been ignored and the effect of co-exposure of PM2.5 on PTB risk is still unclear. OBJECTIVE: To investigate the independent, interactive, and mixed effects of residential greenspace and PM2.5 on the risk of PTB subtypes. METHODS: A total of 19,900 singleton births from 20 hospitals in Shanghai, China, from 2015 to 2017 were included. The Normalized Difference Vegetation Index (NDVI) within 500 m and 1000 m buffers of the maternal residence and a combined geoscience-statistical model-derived PM2.5 and its six components were used as the exposure measures. PTB (<37 completed weeks of gestation) were divided into early PTB (24-33 weeks) vs. late PTB (34-36 weeks) and into spontaneous PTB (sPTB), preterm premature rupture of the fetal membranes (PPROM), and iatrogenic PTB. Multivariable logistic regression models were applied to assess the independent and interactive effects of NDVI and PM2.5 on PTB in each trimester. The quantile g-computation approach was employed to explore the mixture effect of PM2.5 components and greenspace across the pregnancy and to determine the main contributors. RESULTS: Levels of PM2.5 and greenspace were associated with increased [aOR (95%CI) ranging from 1.18 (1.07, 1.30) to 3.36 (2.45, 4.64)] and decreased risks [aORs (95%CI) ranging from 0.64 (0.53, 0.78) to 0.86 (0.73, 0.99)] of PTB subtypes, respectively. At the same PM2.5 level, higher residential greenspace was associated with lower risks, and vice versa. All these associations were more pronounced in late pregnancy. Early PTB and PPROM were the main affected subtypes, and the main drivers in PM2.5 were black carbon and ammonium. CONCLUSIONS: Residential greenspace may mitigate the PTB risks due to PM2.5 exposure during pregnancy.

Quantitative Studies on Local Structure of Molten Binary Potassium Germanates.

In situ high temperature Raman spectra of xK2O-(100-x)GeO2, samples containing 0, 5, 11.11, 20, 25, 33.3, 40, and 50 %mol K2O, were measured. The structure units and a series of model clusters have been designed, optimized, and calculated by quantum chemistry ab initio calculations. The computational simulation in conjunction with the experiments put forward a novel method to correct the experimental Raman spectra of the melts. Deconvolution of the stretching vibrational bands of nonbridging oxygen of [GeO4] tetrahedra of Raman spectra by Gaussian functions was carried out, and the quantitative distribution of different Qn species in molten binary potassium germanates was obtained. The result on all molten samples show that four-fold coordinated germanium atoms occupy a dominant position in the melt and only four-fold coordinated exists in the melt when the K2O content exceeds a certain amount. For melts with high GeO2 content, with the increasing K2O content, the structure of [GeO4] tetrahedra gradually changes from a three-dimensional network consisting of both six-membered and three-membered rings to a three-dimensional network that presents all three-membered rings.

Impacts of physical activity and particulate air pollution on the onset, progression and mortality for the comorbidity of type 2 diabetes and mood disorders.

OBJECTIVE: The co-occurrence of type 2 diabetes (T2D) and mood disorders (depression or anxiety) is an exceedingly common comorbidity with poor prognosis. We aimed to explore the effects of physical activity (PA), fine particulate matter (PM2.5) air pollution or their interactions on the initiation, progression and subsequent mortality of this comorbidity. METHODS: The prospective analysis was based on 336,545 participants in UK Biobank. Multi-state models were applied to capture potential impacts in all transition phases simultaneously along the natural history of the comorbidity. RESULTS: PA [walking (4th vs 1st quantile), moderate (4th vs 1st quantile) and vigorous activities (yes vs no)] protected against incident T2D and comorbid mood disorders afterwards, incident mood disorders, and all-cause mortality from baseline health and T2D, with the risk reductions ranging from 9 % to 23 %. Moderate and vigorous activities further prevented T2D development or mortality among depressive/anxious population. PM2.5 was associated with higher risks of developing incident mood disorders [Hazard ratio (HR) per interquartile range increase = 1.03], as well as of developing incident T2D (HR = 1.04) and further transition to comorbid mood disorders (HR = 1.10). The impacts of PA and PM2.5 were stronger during transitions to comorbidities than the occurrence of first diseases. The benefits of PA remained across all PM2.5 levels. CONCLUSIONS: Physical inactivity and PM2.5 could accelerate the initiation and progression of the comorbidity of T2D and mood disorders. PA and reducing pollution exposure may be included in health promotion strategies to decrease the comorbidity burden.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

Single von Willebrand factor C-domain protein confers host defense against white spot syndrome virus by functioning as a pattern recognition receptor in Macrobrachium nipponense.

The single von Willebrand factor C-domain proteins (SVWCs), also known as Vago, are primarily found in arthropods. Their expression was induced by nutritional status, bacterial and viral infections. Despite the prominence of SVWCs in antiviral immunity, the detailed molecular mechanisms remain poorly explained. SVWC has been proposed to elicit antiviral activities through its function as an interferon analog. In contrast, herein, we illustrate that an SVWC homolog from Macrobrachium nipponense (MnSVWC) confers host defense against white spot syndrome virus (WSSV) and covert mortality nodavirus (CMNV) as a pattern recognition receptor (PRR). qRT-PCR analyses demonstrated that the expression of MnSVWC was enhanced upon WSSV infection in all detected tissues, including gills, nerve cords, and hemocytes. Coating WSSV with recombinant MnSVWC (rMnSVWC) promoted the phagocytic activity of hemocytes and subsequent clearance of invasive WSSV from the prawn. On the other hand, the knockdown of MnSVWC with RNAi improved the proliferation ability of WSSV and CMNV in the prawn. Analysis of ELISA and Co-immunoprecipitation (Co-IP) showed that rMnSVWC could bind WSSV by interacting with the vesicle proteins VP26 and VP28. Co-IP analysis verified the interaction between MnSVWC and calmodulin, which implies a vesicle protein-SVWC-calmodulin-clathrin-dependent mechanism underlying the hemocyte-mediated phagocytosis against WSSV. Subsequently, MnSVWC was recognized to activate the expression of transcription factor STAT and an interferon-stimulating gene Viperin, illustrating its involvement in modulating humoral immunity via activation of the JAK/STAT pathway after WSSV infection. These findings indicate that MnSVWC could bind to WSSV as a PRR and participate in the promotion of hemocyte-mediated phagocytosis and the activation of the JAK/STAT pathway in prawns.

Assembly and Network Stability of Planktonic Microorganisms under the Influence of Salinity Gradient: an Arctic Case Study from the Lena River Estuary to the Laptev Sea.

The diversity and primary productivity in the Arctic ecosystem are rapidly changing due to global warming. Microorganisms play a vital role in biogeochemical cycling. However, the diversity of planktonic microorganism communities in the Laptev Sea, one of the most important marginal seas of the Western Arctic Ocean, have not been studied sufficiently in depth. The diversity and community structure of the planktonic microorganisms in the surface water were investigated at 20 stations on the Lena River flowing into the Laptev Sea. Multivariate statistical analyses demonstrated clear spatial patterns in the α diversity and community structure for microorganisms under different salinity levels. Co-occurrence networks of microbial communities revealed that spatial variation promoted differentiation of the characteristics and stability of microbial networks in the Laptev Sea. Contrary to expectations, abundant taxa were found to not have a large influence on the stability and resilience of microbial interactions in the region. On the contrary, less-abundant taxa were found to have far greater influence. The stability and resilience of the prokaryotic and microeukaryotic networks in the Lena River estuary and the continental shelf provided valuable insights into the impact of freshwater and land inflow disturbances on microbial assemblage. Overall, these results enhance our understanding of the composition of microbial communities and provide insights into how spatial changes of abundant versus rare species alter the nature and stability of microbial networks from the Lena River estuary to the Laptev Sea. In addition, this study explored microbial interactions and their ability to resist future disturbances. IMPORTANCE The regime of the Laptev Sea depends closely on the runoff of the Lena River. Microorganisms are essential components of aquatic food webs and play a significant role in polar ecosystems. In this study, we provided a basic microbial data set as well as new insights into the microbial networks from the Lena River estuary to the Laptev Sea, while exploring their potential to resist future disturbances. A comprehensive and systematic study of the community structure and function of the planktonic microorganisms in the Laptev Sea would greatly enhance our understanding of how polar microbial communities respond to the salinity gradient under climate warming.

Genome-Wide Profiling of Exosomal Long Noncoding RNAs Following Air Pollution Exposure: A Randomized, Crossover Trial.

Changes in human genome-wide long noncoding RNAs (lncRNAs) associated with air pollution are unknown. This study aimed to investigate the effect of air pollution on human exosomal lncRNAs. A randomized, crossover trial was conducted among 35 healthy adults. Participants were allocated to 4 h exposure in road (high air pollution) and park (low air pollution) sessions in random order with a 2 week washout period. RNA sequencing was performed to measure lncRNAs. Differential lncRNAs were identified using a linear mixed-effect model. Mean concentrations of air pollutants such as ultrafine particles (UFP), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were 2-3 times higher in the road than those in the park. Fifty-five lncRNAs [false discovery rate (FDR) < 0.05] including lncRNA NORAD, MALAT1, and H19 were changed in response to air pollution exposure. We found that 54 lncRNAs were associated with CO, 49 lncRNAs with UFP, 49 lncRNAs with BC, 48 lncRNAs with NO2, and 4 lncRNAs with PM2.5 (FDR < 0.05). These differential lncRNAs participated in dozens of pathways including cardiovascular signaling, epithelial cell proliferation, inflammation, and transforming growth factor. This trial for the first time profiled changes of human exosomal lncRNAs following air pollution. Our findings revealed multiple biological processes moderated by lncRNAs and provided epigenetic insights into cardiovascular effects of air pollution.