Enhancing acid-base-water ternary aerosol nucleation with organic acid: a case of tartaric acid.

The new particle formation (NPF) process has been observed globally in clean and polluted environments, where the fundamental mechanisms leading to multicomponent aerosol formation remain elusive. Dicarboxylic acids play an important role in atmospheric NPF. In this study, theoretical calculations are performed to assess the effect of tartaric acid (TA) on the formation of clusters consisting of sulfuric acid (SA), ammonia (AM) or amines (methylamine or dimethylamine, MA/DMA) in the presence of water. Both carboxyl groups and hydroxyl groups in the carbon chain of TA could be involved in hydrogen bonds. The presence of TA triggers proton transfer from SA to the base molecule to form new covalent bonds or strengthens the preexisting covalent bonds, hence, all the hydrated (SA)(TA)(base) cluster formations by adding one TA molecule to the (SA)(base) hydrates are energetically favorable. The dipole-dipole interaction is not only related to the Gibbs energy change for acid affinity reactions to (SA)(W)n and (SA)(base)(W)n (n = 0-4) clusters but also positively related to the reaction rate constant. These results combined with preliminary kinetic results indicate that TA is very likely to participate in clustering and promote subsequent growth involving hydrated SA and (SA)(base) clusters. In addition, our results further indicate that the NPF process can be promoted by multicomponent nucleation involving organic acids, SA, and base species, which will help in understanding NPF in polluted areas and improving global and regional models.

Maternal exposure to ultrafine particles enhances influenza infection during pregnancy.

BACKGROUND: Interactions between air pollution and infectious agents are increasingly recognized and critical to identify, especially to protect vulnerable populations. Pregnancy represents a vulnerable period for influenza infection and air pollution exposure, yet interactions during pregnancy remain unclear. Maternal exposure to ultrafine particles (UFPs, [Formula: see text] 100 nm diameter), a class of particulate matter ubiquitous in urban environments, elicits unique pulmonary immune responses. We hypothesized that UFP exposure during pregnancy would lead to aberrant immune responses to influenza enhancing infection severity. RESULTS: Building from our well-characterized C57Bl/6N mouse model employing daily gestational UFP exposure from gestational day (GD) 0.5-13.5, we carried out a pilot study wherein pregnant dams were subsequently infected with Influenza A/Puerto Rico/8/1934 (PR8) on GD14.5. Findings indicate that PR8 infection caused decreased weight gain in filtered air (FA) and UFP-exposed groups. Co-exposure to UFPs and viral infection led to pronounced elevation in PR8 viral titer and reduced pulmonary inflammation, signifying potential suppression of innate and adaptive immune defenses. Pulmonary expression of the pro-viral factor sphingosine kinase 1 (Sphk1) and pro-inflammatory cytokine interleukin-1ß (IL-1 [Formula: see text]) was significantly increased in pregnant mice exposed to UFPs and infected with PR8; expression correlated with higher viral titer. CONCLUSIONS: Results from our model provide initial insight into how maternal UFP exposure during pregnancy enhances respiratory viral infection risk. This model is an important first step in establishing future regulatory and clinical strategies for protecting pregnant women exposed to UFPs.

Carbenium ion-mediated oligomerization of methylglyoxal for secondary organic aerosol formation.

Secondary organic aerosol (SOA) represents a major constituent of tropospheric fine particulate matter, with profound implications for human health and climate. However, the chemical mechanisms leading to SOA formation remain uncertain, and atmospheric models consistently underpredict the global SOA budget. Small α-dicarbonyls, such as methylglyoxal, are ubiquitous in the atmosphere because of their significant production from photooxidation of aromatic hydrocarbons from traffic and industrial sources as well as from biogenic isoprene. Current experimental and theoretical results on the roles of methylglyoxal in SOA formation are conflicting. Using quantum chemical calculations, we show cationic oligomerization of methylglyoxal in aqueous media. Initial protonation and hydration of methylglyoxal lead to formation of diols/tetrol, and subsequent protonation and dehydration of diols/tetrol yield carbenium ions, which represent the key intermediates for formation and propagation of oligomerization. On the other hand, our results reveal that the previously proposed oligomerization via hydration for methylglyoxal is kinetically and thermodynamically implausible. The carbenium ion-mediated mechanism occurs barrierlessly on weakly acidic aerosols and cloud/fog droplets and likely provides a key pathway for SOA formation from biogenic and anthropogenic emissions.

An unexpected catalyst dominates formation and radiative forcing of regional haze.

Although regional haze adversely affects human health and possibly counteracts global warming from increasing levels of greenhouse gases, the formation and radiative forcing of regional haze on climate remain uncertain. By combining field measurements, laboratory experiments, and model simulations, we show a remarkable role of black carbon (BC) particles in driving the formation and trend of regional haze. Our analysis of long-term measurements in China indicates declined frequency of heavy haze events along with significantly reduced SO2, but negligibly alleviated haze severity. Also, no improving trend exists for moderate haze events. Our complementary laboratory experiments demonstrate that SO2 oxidation is efficiently catalyzed on BC particles in the presence of NO2 and NH3, even at low SO2 and intermediate relative humidity levels. Inclusion of the BC reaction accounts for about 90-100% and 30-50% of the sulfate production during moderate and heavy haze events, respectively. Calculations using a radiative transfer model and accounting for the sulfate formation on BC yield an invariant radiative forcing of nearly zero W m-2 on the top of the atmosphere throughout haze development, indicating small net climatic cooling/warming but large surface cooling, atmospheric heating, and air stagnation. This BC catalytic chemistry facilitates haze development and explains the observed trends of regional haze in China. Our results imply that reduction of SO2 alone is insufficient in mitigating haze occurrence and highlight the necessity of accurate representation of the BC chemical and radiative properties in predicting the formation and assessing the impacts of regional haze.

Remarkable nucleation and growth of ultrafine particles from vehicular exhaust.

High levels of ultrafine particles (UFPs; diameter of less than 50 nm) are frequently produced from new particle formation under urban conditions, with profound implications on human health, weather, and climate. However, the fundamental mechanisms of new particle formation remain elusive, and few experimental studies have realistically replicated the relevant atmospheric conditions. Previous experimental studies simulated oxidation of one compound or a mixture of a few compounds, and extrapolation of the laboratory results to chemically complex air was uncertain. Here, we show striking formation of UFPs in urban air from combining ambient and chamber measurements. By capturing the ambient conditions (i.e., temperature, relative humidity, sunlight, and the types and abundances of chemical species), we elucidate the roles of existing particles, photochemistry, and synergy of multipollutants in new particle formation. Aerosol nucleation in urban air is limited by existing particles but negligibly by nitrogen oxides. Photooxidation of vehicular exhaust yields abundant precursors, and organics, rather than sulfuric acid or base species, dominate formation of UFPs under urban conditions. Recognition of this source of UFPs is essential to assessing their impacts and developing mitigation policies. Our results imply that reduction of primary particles or removal of existing particles without simultaneously limiting organics from automobile emissions is ineffective and can even exacerbate this problem.

In Utero Ultrafine Particulate Exposure Yields Sex- and Dose-Specific Responses to Neonatal Respiratory Syncytial Virus Infection.

Exposure to particulate matter (PM) is associated with lower respiratory tract infections. The role of ultrafine particles (UFPs, ≤0.1 µm) in respiratory disease is not fully elucidated, especially in models of immunologically immature populations. To characterize the effects of maternal UFP exposure on neonatal infection, we exposed time-mated C57Bl/6n mice to filtered air or UFPs at a low dose (LD, ∼55 µg/m3) and high dose (HD, ∼275 µg/m3) throughout gestation. At 5 days of age, offspring were infected with a respiratory syncytial virus (RSV) strain known to mimic infant infection or sham control. Offspring body weights were significantly reduced in response to infection in the LD RSV group, particularly females. Pulmonary gene expression analysis demonstrated significantly increased levels of oxidative stress- and inflammation-related genes in HD-exposed male offspring in sham and RSV-infected groups. In males, the highest grade of inflammation was observed in the HD RSV group, whereas in females, the LD RSV group showed the most marked inflammation. Overall, findings highlight neonatal responses are dependent on offspring sex and maternal UFP dose. Importantly, infant RSV pathology may be enhanced following even low dose UFP exposure signifying the importance of preventing maternal exposure.

1 H NMR-based metabolomics of paired esophageal tumor tissues and serum samples identifies specific serum biomarkers for esophageal cancer.

Serum metabolites of healthy controls and esophageal cancer (EC) patients have previously been compared to predict cancer-specific profiles. However, the association between metabolic alterations in serum samples and esophageal tissues in EC patients remains unclear. Here, we analyzed 50 pairs of EC tissues and distant noncancerous tissues, together with patient-matched serum samples, using 1 H NMR spectroscopy and pattern recognition algorithms. EC patients could be differentiated from the controls based on the metabolic profiles at tissue and serum levels. Some overlapping discriminatory metabolites, including valine, alanine, glucose, acetate, citrate, succinate and glutamate, were identified in both matrices. These results suggested deregulation of metabolic pathways, and potentially revealed the links between EC and several metabolic pathways, such as the tricarboxylic acid cycle, glutaminolysis, short-chain fatty acid metabolism, lipometabolism and pyruvate metabolism. Perturbation of the pyruvate metabolism was most strongly associated with EC progression. Consequently, an optimal serum metabolite biomarker panel comprising acetate and pyruvate was developed, as these two metabolites are involved in pyruvate metabolism, and changes in their serum levels were significantly correlated with alterations in the levels of some other esophageal tissue metabolites. In comparison with individual biomarkers, this panel exhibited better diagnostic efficiency for EC, with an AUC of 0.948 in the test set, and a good predictive ability of 82.5% in the validation set. Analysis of key genes related to pyruvate metabolism in EC patients revealed patterns corresponding to the changes in serum pyruvate and acetate levels. These correlation analyses demonstrate that there were distinct metabolic characteristics and pathway aberrations in the esophageal tumor tissue and in the serum. Changes in the serum metabolic signatures could reflect the alterations in the esophageal tumor profile, thereby emphasizing the importance of distinct serum metabolic profiles as potential noninvasive biomarkers for EC.

Multigeneration Production of Secondary Organic Aerosol from Toluene Photooxidation.

Photooxidation of volatile organic compounds (VOCs) produces secondary organic aerosol (SOA) and light-absorbing brown carbon (BrC) via multiple reaction steps/pathways, reflecting significant chemical complexity relevant to gaseous oxidation and subsequent gas-to-particle conversion. Toluene is an important VOC under urban conditions, but the fundamental chemical mechanism leading to SOA formation remains uncertain. Here, we elucidate multigeneration SOA production from toluene by simultaneously tracking the evolutions of gas-phase oxidation and aerosol formation in a reaction chamber. Large size increase and browning of monodisperse sub-micrometer seed particles occur shortly after initiating oxidation by hydroxyl radical (OH) at 10-90% relative humidity (RH). The evolution in gaseous products and aerosol properties (size/density/optical properties) and chemical speciation of aerosol-phase products indicate that the aerosol growth and browning result from earlier generation products consisting dominantly of dicarbonyl and carboxylic functional groups. While volatile dicarbonyls engage in aqueous reactions to yield nonvolatile oligomers and light-absorbing nitrogen heterocycles/heterochains (in the presence of NH3) at high RH, organic acids contribute to aerosol carboxylates via ionic dissociation or acid-base reaction in a wide RH range. We conclude that toluene contributes importantly to SOA/BrC formation from dicarbonyls and organic acids because of their prompt and high yields from photooxidation and unique functionalities for participation in aerosol-phase reactions.

Unexpected Oligomerization of Small α-Dicarbonyls for Secondary Organic Aerosol and Brown Carbon Formation.

Large amounts of small α-dicarbonyls (glyoxal and methylglyoxal) are produced in the atmosphere from photochemical oxidation of biogenic isoprene and anthropogenic aromatics, but the fundamental mechanisms leading to secondary organic aerosol (SOA) and brown carbon (BrC) formation remain elusive. Methylglyoxal is commonly believed to be less reactive than glyoxal because of unreactive methyl substitution, and available laboratory measurements showed negligible aerosol growth from methylglyoxal. Herein, we present experimental results to demonstrate striking oligomerization of small α-dicarbonyls leading to SOA and BrC formation on sub-micrometer aerosols. Significantly more efficient growth and browning of aerosols occur upon exposure to methylglyoxal than glyoxal under atmospherically relevant concentrations and in the absence/presence of gas-phase ammonia and formaldehyde, and nonvolatile oligomers and light-absorbing nitrogen-heterocycles are identified as the dominant particle-phase products. The distinct aerosol growth and light absorption are attributed to carbenium ion-mediated nucleophilic addition, interfacial electric field-induced attraction, and synergetic oligomerization involving organic/inorganic species, leading to surface- or volume-limited reactions that are dependent on the reactivity and gaseous concentrations. Our findings resolve an outstanding discrepancy concerning the multiphase chemistry of small α-dicarbonyls and unravel a new avenue for SOA and BrC formation from atmospherically abundant, ubiquitous carbonyls and ammonia/ammonium sulfate.

Effect of Emerging Major Infectious Diseases on Sleep Quality of Medical Workers: Findings from Medical Workers Providing Support During the COVID-19 Pandemic.

BACKGROUND The coronavirus disease 2019 (COVID-19) outbreak has exerted immense pressure on medical systems in China and abroad. This study aimed to compare the sleep quality of medical personnel conscripted to the Wuhan Union Cancer Centre to offer support during the early stages of the COVID-19 pandemic to the sleep quality of those who remained at Anhui Medical University Hospital and to determine the role of interventions in improving sleep quality. MATERIAL AND METHODS Questionnaires were completed by 369 individuals who were conscripted to support Wuhan (N=137) and others who were not (the control group; N=232). The Pittsburgh Sleep Quality Index (PSQI) was used to measure the duration and quality of sleep. The Anhui Provincial Health Commission organized a comprehensive intervention, consisting of physical-psychological-social dimensions, over the course of 2 weeks. RESULTS Only 34.21% of the Wuhan support workers reported better sleep quality, as opposed to the 55.60% of the control group at stage 1 (t/χ²=14.005, P<.001). Furthermore, despite the Wuhan support group being more prone to poor sleep quality, their sleep quality significantly improved after the interventions. CONCLUSIONS The findings from this study showed that medical staff who were conscripted to offer support during the early stages of the COVID-19 pandemic suffered from impaired quality of sleep. The use of questionnaire-based sleep assessments may provide individualized approaches to supporting medical personnel during future epidemics and pandemics. Furthermore, our results indicate that relevant interventions can significantly improve sleep quality, while a prolonged break after interventions does not affect sleep quality.

Effect of plasmapheresis versus standard treatment in preventing recurrent acute pancreatitis in Chinese patients with hypertriglyceridemia.

The present study designed to compare the effect of plasmapheresis (PPH) versus standard treatment (STD) in preventing recurrent AP in Chinese patients with severe hypertriglyceridemia. Chinese patients aged 18 to 65 years who had history of hypertriglyceridemia (>1000mg/dl) induced acute pancreatitis were assigned to plasmapheresis (up to 1.5 ml daily TG level reaches 500 mg/dl or less) or standard treatment (1:1). Standard treatment (STD) includes limited oral intake (pancreatic rest), intravenous hydration and pain management. Primary endpoint was incidence of recurrent acute pancreatitis. A total of 14% of patients in PPH group (N=50) had experienced recurrent pancreatitis as compared to 24% of patients in STD group (N=50). Also, TG clearance rate in 24 hours was substantially higher in PPH group as compared to STD. Time required to reach target TG was significantly lower in patients treated with PPH as compared to STD. Lower incidence of local complications was observed in PPH group as compared to STD. Length of stay was significantly shorter in patients of plasmapheresis group as compared to standard treatment. The results of this study recommend the use of plasmapheresis as a better alternative in preventing recurrent AP in Chinese patients with severe hypertriglyceridemia.

Adding DSC PWI and DWI to BT-RADS can help identify postoperative recurrence in patients with high-grade gliomas.

BACKGROUND: The Brain Tumor Reporting and Data System (BT-RADS) category 3 is suitable for identifying cases with intermediate probability of tumor recurrence that do not meet the Response Assessment in Neuro-Oncology (RANO) criteria for progression. The aim of this study was to evaluate the added value of dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC PWI) and diffusion-weighted imaging (DWI) to BT-RADS for differentiating tumor recurrence from non-recurrence in postoperative high-grade glioma (HGG) patients with category 3 lesions. METHODS: Patients with BT-RADS category 3 lesions were included. The maximal relative cerebral blood volume (rCBVmax) and the mean apparent diffusion coefficient (ADCmean) values were measured. The added value of DSC PWI and DWI to BT-RADS was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-one of 91 patients had tumor recurrence, and 40 patients did not. There were significant differences in rCBVmax and ADCmean between the tumor recurrence group and non-recurrence group. Compared to BT-RADS alone, the addition of DSC PWI to BT-RADS increased the area under curve (AUC) from 0.76 (95% confidence interval [CI] 0.66-0.84) to 0.90 (95% CI 0.81-0.95) for differentiating tumor recurrence from non-recurrence. The addition of DWI to BT-RADS increased the AUC from 0.76 (95% CI 0.66-0.84) to 0.88 (95% CI 0.80-0.94). The combination of BT-RADS, DSC PWI, and DWI exhibited the best diagnostic performance (AUC = 0.95; 95% CI 0.88-0.98) for differentiating tumor recurrence from non-recurrence. CONCLUSION: Adding DSC PWI and DWI to BT-RADS can significantly improve the diagnostic performance for differentiating tumor recurrence from non-recurrence in BT-RADS category 3 lesions.

1 H NMR-based metabolomics reveal overlapping discriminatory metabolites and metabolic pathway disturbances between colorectal tumor tissues and fecal samples.

Previous studies have compared fecal metabolites from healthy and colorectal cancer (CRC) patients to predict the pro-CRC signatures. However, the systemic mechanistic link between feces and colonic tissues of CRC patients is still limited. The current study was a paralleled investigation of colonic tumor tissues and their normal adjacent tissues alongside patient-matched feces by using 1 H nuclear magnetic resonance spectroscopy combined with pattern recognition to investigate how fecal metabolic phenotypes are linked to the changes in colorectal tumor profiles. A set of overlapping discriminatory metabolites across feces and tumor tissues of CRC were identified, including elevated levels of lactate, glutamate, alanine, succinate and reduced amounts of butyrate. These changes could indicate the networks for metabolic pathway perturbations in CRC potentially involved in the disruptions of glucose and glycolytic metabolism, TCA cycle, glutaminolysis, and short chain fatty acids metabolism. Furthermore, changes in fecal acetate were positively correlated with alterations of glucose and myo-inositol in colorectal tumor tissues, implying enhanced energy production for rapid cell proliferation. Compared to other fecal metabolites, acetate demonstrated the highest diagnostic performance for diagnosing CRC, with an AUC of 0.843 in the training set, and a good predictive ability in the validation set. Overall, these associations provide evidence of distinct metabolic signatures and metabolic pathway disturbances between the colonic tissues and feces within the same individual, and changes of fecal metabolic signature could reflect the CRC tissue microenvironment, highlighting the significance of the distinct fecal metabolic profiles as potential novel and noninvasive relevant indicators for CRC detection.

Diffusion Kurtosis at 3.0T as an in vivo Imaging Marker for Breast Cancer Characterization: Correlation With Prognostic Factors.

BACKGROUND: Diffusion-kurtosis imaging (DKI) has preliminarily shown promise as a relatively new MRI technique to provide useful information regarding breast lesions, but the diagnostic performance of DKI has not been fully evaluated. PURPOSE: To compare the diagnostic accuracy of DKI, diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE)-MRI) and proton MR spectroscopy (1 H-MRS) in differentiating malignant from benign breast lesions independently or jointly, and explore the correlation between DKI-derived parameters and prognostic factors. STUDY TYPE: Prospective. SUBJECTS: Seventy-one patients with breast lesions (50 malignant, 26 benign). SEQUENCE: DKI, DWI, DCE-MRI, and 1 H-MRS were performed at 3.0T. ASSESSMENT: Mean kurtosis (MK), mean diffusivity (MD), apparent diffusion coefficient (ADC), BI-RADS category, and choline peaks were analyzed by two experienced radiologists. STATISTICAL TESTS: Student's t-test was used for continuous variables; receiver operating characteristic (ROC) analysis for assessing the diagnostic accuracy of imaging parameters; Spearman or Pearson correlations for assessing the associations between imaging parameters and prognostic factors. RESULTS: MK exhibited higher area under the curves (AUCs) for differentiating malignant from benign lesions than did MD, ADC, DCE, and tCho (0.979 vs. 0.928, 0.911, 0.777, and 0.833, respectively, P < 0.05). MK showed a positive association with Ki-67 expression (r = 0.508) and histologic grades (r = 0.551), whereas MD and ADC were negatively correlated with Ki-67 expression (r = -0.416 and r = -0.458) and histologic grades (r = -0.411 and r = -0.319). Moreover, MK showed relatively higher AUCs compared with MD and ADC in detecting breast cancers with lymph nodal involvement, histologic grades, and Ki-67 expression. DATA CONCLUSION: MK has higher diagnostic accuracy compared with ADC, DCE, and tCho regarding detection of breast cancer. Moreover, DKI shows promise as a quantitative imaging technique for characterizing breast lesions, highlighting the potential utility of MK as a promising imaging marker for predicting tumor aggressiveness. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:845-856.

1H NMR-based metabolomics of paired tissue, serum and urine samples reveals an optimized panel of biofluids metabolic biomarkers for esophageal cancer.

Introduction: The goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC). Methods: Urine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique. Results: We identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of "glycine, serine, and threonine metabolism", the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers. Discussion: Overall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients.

Ischemia/reperfusion in clamped lobes facilitates liver regeneration of non-clamped lobes after selective portal vein ligation.

BACKGROUND: Hypertrophy of non-clamped liver lobes and the atrophy of clamped lobes have been shown to be interactive. Here, a rat model of selective lobe occlusion was established to study the effect of contralateral ischemia/reperfusion (I/R) on regeneration of non-clamped lobes. METHODS: Left lateral and middle liver lobes were pretreated with I/R. In the experimental (IR + PVL) group, portal veins of the left and middle lobes were ligated. A group given similar portal vein ligation but no I/R (PVL) was the positive control. RESULTS: Compared with the PVL group, the IR + PVL had higher, but not remarkable, levels of serum transaminases; weights of non-clamped lobes in the IR + PVL group comparatively increased much more notably. At 24-h post-surgery, the IR + PVL group's PCNA mRNA was up-regulated compared with the PVL group. At 72-h post-surgery, PCNA protein was up-regulated significantly, while TGF-ß1 was down-regulated in the IR + PVL group notably, compared with the PVL group. CONCLUSION: The I/R pretreatment given to the clamped lobes facilitates liver regeneration of non-clamped lobes after selective portal vein ligation, which may result from down-regulated TGF-ß1 expression in non-clamped lobes.

NRF2 Protects against Altered Pulmonary T Cell Differentiation in Neonates Following In Utero Ultrafine Particulate Matter Exposure.

Early life exposure to particulate matter (PM) air pollution negatively impacts neonatal health. The underlying mechanisms following prenatal exposure, particularly to ultrafine particles (UFP, diameter ≤ 0.1 µm), are not fully understood; To evaluate the role of Nrf2 in response to in utero UFP exposure, we exposed time-mated Nrf2-deficient (Nrf2-/-) or wildtype (WT) mice to filtered air (FA) or 100 µg/m3 ultrafine PM daily throughout pregnancy. Offspring were evaluated for pulmonary immunophenotypes and pulmonary/systemic oxidative stress on postnatal day 5, a timepoint at which we previously demonstrated viral respiratory infection susceptibility; Nrf2-/- offspring exposed to FA had significantly lower average body weights compared to FA-exposed WT pups. Moreover, PM-exposed Nrf2-/- offspring weighed significantly less than PM-exposed WT pups. Notably, PM-exposed Nrf2-/- offspring showed a decreased pulmonary Th1/Th2 ratio, indicating a Th2 bias. Th17 cells were increased in FA-exposed Nrf2-/- neonates yet decreased in PM-exposed Nrf2-/- neonates. Analysis of oxidative stress-related genes in lung and oxidative stress biomarkers in liver tissues did not vary significantly across exposure groups or genotypes. Collectively, these findings indicate that the lack of Nrf2 causes growth inhibitory effects in general and in response to gestational UFP exposure. Prenatal UFP exposure skews CD4+ T lymphocyte differentiation toward Th2 in neonates lacking Nrf2, signifying its importance in maternal exposure and infant immune responses.

Understanding transmission and intervention for the COVID-19 pandemic in the United States.

The outbreak of the novel coronavirus disease (COVID-19) severely threatens the public health worldwide, but the transmission mechanism and the effectiveness of mitigation measures remain uncertain. Here we assess the role of airborne transmission in spreading the disease and the effectiveness of face covering in preventing inter-human transmission for the top-fifteen infected U.S. states during March 1 and May 18, 2020. For all fifteen states, the curve of total confirmed infections exhibits an initial sub-exponential growth and a subsequent linear growth after implementing social distancing/stay-at-home orders. The linearity extends one to two months for the six states without mandated face covering and to the onset of mandated face covering for the other nine states with this measure, reflecting a dynamic equilibrium between first-order transmission kinetics and intervention. For the states with mandated face covering, significant deviation from this linearity and curve flattening occur after the onset of this measure for seven states, with exceptions for two states. Most states exhibit persistent upward trends in the daily new infections after social distancing/stay-at-home orders, while reversed downward or slowing trends occur for eight states after implementing mandated face covering. The inadequacy of social distancing and stay-at-home measures alone in preventing inter-human transmission is reflected by the continuous linear growth in the total infection curve after implementing these measures, which is mainly driven by airborne transmission. We estimate that the number of the total infections prevented by face covering reaches ~252,000 on May 18 in seven states, which is equivalent to ~17% of the total infections in the nation. We conclude that airborne transmission and face covering play the dominant role in spreading the disease and flattening the total infection curve, respectively. Our findings provide policymakers and the public with compelling evidence that universal face covering, in conjunction with social distancing and hand hygiene, represents the maximal protection against inter-human transmission and the combination of these intervention measures with rapid and extensive testing as well as contact tracing is crucial in containing the COVID-19 pandemic.

Nuclear magnetic resonance-based metabolomics and metabolic pathway networks from patient-matched esophageal carcinoma, adjacent noncancerous tissues and urine.

BACKGROUND: Several studies have demonstrated a correlation between esophageal cancer (EC) and perturbed urinary metabolomic profiles, but none has described the correlation between urine metabolite profiles and those of the tumor and adjacent esophageal mucosa in the same patient. AIM: To investigate how urinary metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors. METHODS: Nuclear magnetic resonance-based metabolomics were applied to esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched urine samples. RESULTS: Analysis revealed that specific metabolite changes overlapped across both metrics, including glucose, glutamate, citrate, glycine, creatinine and taurine, indicating that the networks for metabolic pathway perturbations in EC, potentially involved in but not limited to disruption of fatty acid metabolism, glucose and glycolytic metabolism, tricarboxylic acid cycle and glutaminolysis. Additionally, changes in most urinary biomarkers correlated with changes in biomarker candidates in EC tissues, implying enhanced energy production for rapid cell proliferation. CONCLUSION: Overall, these associations provide evidence for distinct metabolic signatures and pathway disturbances between the tumor tissues and urine of EC patients, and changes in urinary metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues. Further investigation is needed to validate these initial findings using larger samples and to establish the underlying mechanism of EC progression.