High-resolution ultrasound and speckle tracking: a non-invasive approach to assess in vivo gastrointestinal motility during development.

Gastrointestinal motor activity has been extensively studied in adults; however, only few studies have investigated fetal motor skills. It is unknown when the gastrointestinal tract starts to contract during the embryonic period and how this function evolves during development. Here, we adapted a non-invasive high-resolution echography technique combined with speckle tracking analysis to examine the gastrointestinal tract motor activity dynamics during chick embryo development. We provided the first recordings of fetal gastrointestinal motility in living embryos without anesthesia. We found that, although gastrointestinal contractions appear very early during development, they become synchronized only at the end of the fetal period. To validate this approach, we used various pharmacological inhibitors and BAPX1 gene overexpression in vivo. We found that the enteric nervous system determines the onset of the synchronized contractions in the stomach. Moreover, alteration of smooth muscle fiber organization led to an impairment of this functional activity. Altogether, our findings show that non-invasive high-resolution echography and speckle tracking analysis allows visualization and quantification of gastrointestinal motility during development and highlight the progressive acquisition of functional and coordinated gastrointestinal motility before birth.

Loss of function of the maternal membrane oestrogen receptor ERα alters expansion of trophoblast cells and impacts mouse fertility.

The binding of 17ß-oestradiol to oestrogen receptor alpha (ERα) plays a crucial role in the control of reproduction, acting through both nuclear and membrane-initiated signalling. To study the physiological role of membrane ERα in the reproductive system, we used the C451A-ERα mouse model with selective loss of function of membrane ERα. Despite C451A-ERα mice being described as sterile, daily weighing and ultrasound imaging revealed that homozygous females do become pregnant, allowing the investigation of the role of ERα during pregnancy for the first time. All neonatal deaths of the mutant offspring mice resulted from delayed parturition associated with failure in pre-term progesterone withdrawal. Moreover, pregnant C451A-ERα females exhibited partial intrauterine embryo arrest at about E9.5. The observed embryonic lethality resulted from altered expansion of Tpbpa-positive spiral artery-associated trophoblast giant cells into the utero-placental unit, which is associated with an imbalance in expression of angiogenic factors. Together, these processes control the trophoblast-mediated spiral arterial remodelling. Hence, loss of membrane ERα within maternal tissues clearly alters the activity of invasive trophoblast cells during placentogenesis. This previously unreported function of membrane ERα could open new avenues towards a better understanding of human pregnancy-associated pathologies.

Meteorological, chemical and biological evaluation of the coupled chemistry-climate WRF-Chem model from regional to urban scale. An impact-oriented application for human health.

Extreme climatic conditions, like heat waves or cold spells, associated to high concentrations of air pollutants are responsible for a broad range of effects on human health. Consequently, in the recent years, the question on how urban and peri-urban forests may improve both air quality and surface climate conditions at city-scale is receiving growing attention by scientists and policymakers, with previous studies demonstrating how nature-based solutions (NBS) may contribute to reduce the risk of population to be exposed to high pollutant levels and heat stress, preventing, thus, premature mortality. In this study we present a new modeling framework designed to simulate air quality and meteorological conditions from regional to urban scale, allowing thus to assess the impacts of both air pollution and heat stress on human health at urban level. To assess the model reliability, we evaluated the model's performances in reproducing several relevant meteorological, chemical, and biological variables. Results show how our modeling system can reliably reproduce the main meteorological, chemical, and biological variables over our study areas, thus this tool can be used to estimate the impact of air pollution and heat stress on human health. As an example of application, we show how common heat stress and air pollutant indices used for human health protection change when computed from regional to urban scale for the cities of Florence (Italy) and Aix en Provence (France).

Detection of morphological and eco-physiological traits of ornamental woody species to assess their potential Net O3 uptake.

Urban greening can improve cities' air quality by filtering the main gaseous pollutants such as tropospheric ozone (O3). However, the pollutant removal capacity offered by woody species strongly depends on eco-physiological and morphological traits. Woody species with higher stomatal conductance (gs) can remove more gases from the atmosphere, but other species can worsen air quality due to high O3 forming potential (OFP), based on their emitting rates of biogenic volatile organic compounds (bVOCs) and Leaf Mass per Area (LMA). Presently, there is a lack of data on eco-physiological (gs, bVOCs emissions) and foliar traits (LMA) for several ornamental species used in urban greening programs, which does not allow assessment of their O3 removal capacity and OFP. This study aimed to (i) parameterize gs, assess bVOCs emissions and LMA of 14 ornamental woody species commonly used in Mediterranean urban greening, and (ii) model their Net O3 uptake. The gs Jarvis model was parameterized considering various environmental conditions alongside isoprene and monoterpene foliar bVOCs emission rates trapped in the field and quantified by gas chromatography-mass spectrometry. The results are helpful for urban planning and landscaping; suggesting that Catalpa bignonioides and Gleditsia triacanthos have excellent O3 removal capacity due to their high maximum gs (gmax) equal to 0.657 and 0.597 mol H2O m-2 s-1. Regarding bVOCs, high isoprene (16.75 µg gdw-1 h-1) and monoterpene (13.12 µg gdw-1 h-1) emission rates were found for Rhamnus alaternus and Cornus mas. In contrast, no bVOCs emissions were detected for Camellia sasanqua and Paulownia tomentosa. In conclusion, 11 species showed a positive Net O3 uptake, while the use of large numbers of R. alaternus, C. mas, and Chamaerops humilis for urban afforestation planning are not recommended due to their potential to induce a deterioration of outdoor air quality.

Human exposure to formaldehyde and health risk assessment: a 46-year systematic literature review.

After confirming that formaldehyde (FA) is carcinogenic, many studies were conducted in different countries to investigate this finding. Therefore, according to the dispersion of related studies, a bibliometric review of the current literature was performed with the aim of better understanding the exposure to FA and the resulting health risk, for the first time, using the Scopus database and the two open-source software packages, Bibliometrix R package. After screening the documents in Excel, the data was analyzed based on three aspects including performance analysis, conceptual structure, and intellectual structure, and the results were presented in tables and diagrams. A total of 468 documents were analyzed over period 1977-2023, in which 1956 authors from 56 countries participated. The number of scientific publications has grown significantly from 1977 (n = 1) to 2022 (n = 19). Zhang Y., from the Yale School of Public Health (USA), was identified as the most impactful author in this field. The Science of the Total Environment journal was identified as the main source of articles related to exposure to formaldehyde by publishing 25 studies. The United States and China were the most active countries with the most international collaboration. The main topics investigated during these 46 years included "formaldehyde" and "health risk assessment", which have taken new directions in recent years with the emergence of the keyword "asthma". The present study provides a comprehensive view of the growth and evolution of studies related to formaldehyde and the resulting health risks, which can provide a better understanding of existing research gaps and new and emerging issues.

Surface ozone risk to human health and vegetation in tropical region: The case of Thailand.

Tropospheric ozone (O3) is a threat to vegetation and human health over the world, in particular in Asia. Knowledge on O3 impacts on tropical ecosystems is still very limited. An O3 risk assessment to crops, forests, and people from 25 monitoring stations across the tropical and subtropical Thailand during 2005-2018 showed that 44% of sites exceeded the critical levels (CLs) of SOMO35 (i.e., the annual Sum Of daily maximum 8-h Means Over 35 ppb) for human health protection. The concentration-based AOT40 CL (i.e., sum of the hourly exceedances above 40 ppb for daylight hours during the assumed growing season) was exceeded at 52% and 48% of the sites where the main crops rice and maize are present, respectively, and at 88% and 12% of the sites where evergreen or deciduous forests are present, respectively. The flux-based metric PODY (i.e., Phytotoxic Ozone Dose above a threshold Y of uptake) was calculated and was found to exceed the CLs at 1.0%, 1.5%, 20.0%, 1.5%, 0% and 68.0% of the sites where early rice, late rice, early maize, late maize, evergreen forests, and deciduous forests can grow, respectively. Trend analysis indicated that AOT40 increased over the study period (+5.9% year-1), while POD1 decreased (- 5.3% year-1), suggesting that the role of climate change in affecting the environmental factors that control stomatal uptake cannot be neglected. These results contribute novel knowledge on O3 threat to human health, forest productivity, and food security in tropical and subtropical areas.

Sublethal chemical stimulation of arthropod parasitoids and parasites of agricultural and environmental importance.

An increasing number of studies have reported stimulation of various organisms in the presence of environmental contaminants. This has created a need to critically evaluate sublethal stimulation and hormetic responses of arthropod parasitoids and parasites following exposure to pesticides and other contaminants. Examining this phenomenon with a focus on arthropods of agricultural and environmental importance serves as the framework for this literature review. This review shows that several pesticides, with diverse chemical structures and different modes of action, applied individually or in combination at sublethal doses, commonly stimulate an array of arthropod parasitoids and parasites. Exposure at sublethal doses can enhance responses related to physiology (e.g., respiration, total lipid content, and total protein content), behavior (e.g., locomotor activity, antennal drumming frequency, host location, and parasitization), and fitness (longevity, growth, fecundity, population net and gross reproduction). Concordantly, the parasitic potential (e.g., infestation efficacy, parasitization rate, and parasitoid/parasite emergence) can be increased, and as a result host activities inhibited. There is some evidence illustrating hormetic dose-responses, but the relevant literature commonly included a limited number and range of doses, precluding a robust differentiation between sub- and superNOAEL (no-observed-adverse-effect level) stimulation. These results reveal a potentially significant threat to ecological health, through stimulation of harmful parasitic organisms by environmental contaminants, and highlight the need to include sublethal stimulation and hormetic responses in relevant ecological pesticide risk assessments. Curiously, considering a more utilitarian view, hormesis may also assist in optimizing mass rearing of biological control agents for field use, a possibility that also remains neglected.

Involvement of Vasopressin in Tissue Hypoperfusion during Cardiogenic Shock Complicating Acute Myocardial Infarction in Rats.

Acute heart failure (AHF) due to acute myocardial infarction (AMI) is likely to involve cardiogenic shock (CS), with neuro-hormonal activation. A relationship between AHF, CS and vasopressin response is suspected. This study aimed to investigate the implication of vasopressin on hemodynamic parameters and tissue perfusion at the early phase of CS complicating AMI. Experiments were performed on male Wistar rats submitted or not to left coronary artery ligation (AMI and Sham). Six groups were studied Sham and AMI treated or not with either a vasopressin antagonist SR-49059 (Sham-SR, AMI-SR) or agonist terlipressin (Sham-TLP, AMI-TLP). Animals were sacrificed one day after surgery (D1) and after hemodynamic parameters determination. Vascular responses to vasopressin were evaluated, ex vivo, on aorta. AHF was defined by a left ventricular ejection fraction below 40%. CS was defined by AHF plus tissue hypoperfusion evidenced by elevated serum lactate level or low mesenteric oxygen saturation (SmO2) at D1. Mortality rates were 40% in AMI, 0% in AMI-SR and 33% in AMI-TLP. Immediately after surgery, a sharp decrease in SmO2 was observed in all groups. At D1, SmO2 recovered in Sham and in SR-treated animals while it remained low in AMI and further decreased in TLP-treated groups. The incidence of CS among AHF animals was 72% in AMI or AMI-TLP while it was reduced to 25% in AMI-SR. Plasma copeptin level was increased by AMI. Maximal contractile response to vasopressin was decreased in AMI (32%) as in TLP- and SR- treated groups regardless of ligation. Increased vasopressin secretion occurring in the early phase of AMI may be responsible of mesenteric hypoperfusion resulting in tissue hypoxia. Treatment with a vasopressin antagonist enhanced mesenteric perfusion and improve survival. This could be an interesting therapeutic strategy to prevent progression to cardiogenic shock.

Assessing the effect of COVID-19 pandemic on air quality change and human health outcomes in a capital city, southwestern Iran.

The aimsof this study were to assess the spatial variation of PM2.5, NO2, and O3 between 2019 (before) and 2020 (during COVID-19 pandemic); and calculation the health outcomes of exposure to these pollutants. The daily PM2.5, NO2, and O3 concentrations were applied to assess health effects by relative risk, and baseline incidence. The annual PM2.5 and NO2 mean concentrations exceeded the WHO guideline values, while O3 did not exceed. The restrictive measures associated to COVID-19 led to reduction at the annual means of PM2.5 and NO2 by -25.5% and -23.1%, respectively, while the annual mean of O3 increased by +7.9%. The number of M-CVD and M-RD (-25.6%, -26.1%) related to PM2.5 exposure, and HA-COPD and HA-RD >65 years old (-21% and -3.84%) related to NO2 exposure were reduced in 2020, and O3 exposure-related M-CVD (+30.1%) and HA-RD >65 years old (+23.4%) increased compared to the previous year 2019.

Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide.

All-trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all-trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients' relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide. We previously developed a self-nanoemulsifying drug delivery system enriched with tocotrienols to deliver all-trans retinoic acid (SNEDDS-TRF-ATRA). Herein, we have evaluated if tocotrienols can help revert ATRA resistance in an APL cell line (NB4-R2 compared to sensitive NB4 cells) and mitigate the cardiotoxic effects of arsenic trioxide in a murine model. SNEDDS-TRF-ATRA enhanced all-trans retinoic acid cytotoxicity in NB4-R2 (resistant) cells but not in NB4 (sensitive) cells. Moreover, SNEDDS-TRF-ATRA did not significantly change the differentiative properties of all-trans retinoic acid in both NB4 and NB4-R2 cells. Combined administration of SNEDDS-TRF-ATRA and arsenic trioxide could revert QTc interval prolongation caused by ATO but evoked other electrocardiogram alterations in mice, such as T wave flattening. Therefore, SNEDDS-TRF-ATRA may enhance the antileukemic properties of all-trans retinoic acid but may influence ECG changes caused by arsenic trioxide administration. SNEDDS-TRF-ATRA presents cytotoxicity in resistant APL cells (NB4-R2). Combined administration of ATO and SNEDDS-TRF-ATRA in mice prevented the prolongation of the QTc interval caused by ATO but evoked ECG abnormalities such as T wave flattening.

Strategic roadmap to assess forest vulnerability under air pollution and climate change.

Although it is an integral part of global change, most of the research addressing the effects of climate change on forests have overlooked the role of environmental pollution. Similarly, most studies investigating the effects of air pollutants on forests have generally neglected the impacts of climate change. We review the current knowledge on combined air pollution and climate change effects on global forest ecosystems and identify several key research priorities as a roadmap for the future. Specifically, we recommend (1) the establishment of much denser array of monitoring sites, particularly in the South Hemisphere; (2) further integration of ground and satellite monitoring; (3) generation of flux-based standards and critical levels taking into account the sensitivity of dominant forest tree species; (4) long-term monitoring of N, S, P cycles and base cations deposition together at global scale; (5) intensification of experimental studies, addressing the combined effects of different abiotic factors on forests by assuring a better representation of taxonomic and functional diversity across the ~73,000 tree species on Earth; (6) more experimental focus on phenomics and genomics; (7) improved knowledge on key processes regulating the dynamics of radionuclides in forest systems; and (8) development of models integrating air pollution and climate change data from long-term monitoring programs.

Assessment of ozone risk to Central European forests: Time series indicates perennial exceedance of ozone critical levels.

In this study, the stomatal ozone (O3) fluxes were investigated at five low-elevation forest sites in Western Germany (Rhineland Palatinate) over the time period 1998-2019. The Phytotoxic Ozone Dose with an hourly threshold of uptake (Y), to represent the detoxification capacity of trees (POD1 in mmol m-2 per leaf area, with Y = 1 nmol O3 m-2 s-1), and the number of exceedances of the O3 critical level of 5.2 mmol O3 m-2 per leaf area for European beech and 9.2 mmol O3 m-2 per leaf area for Norway spruce were calculated by using the DO3SE model. A Principal Component Analysis revealed strong correlations between daily O3 concentrations, daytime O3 (for hours with global radiation exceeding 50 W m-2), POD1, global radiation, vapor pressure deficit and air temperature. Moreover, a significant correlation was obtained between POD1 and soil water content (SWC) at all sites (r = 0.51-0.74). The Random Forests Analysis confirmed that the SWC is the most important predictor of stomatal O3 fluxes. The soil water supply is very important for POD1 estimation, because drought decreases stomatal conductance, leading to a reduction of transpiration, as well as to lower O3 uptake through stomata. Between 1998 and 2019, the drier and warmer climate induced a soil drought (on average, SWC - 0.15 % per year) leading to lower stomatal O3 uptake by forests (- 0.36 mmol O3 m-2 per year). Hence, during growing seasons with sufficient water supply and often lower O3 levels compared to hot and dry periods, forests are at higher O3 risk than during hot and dry periods when the drought stress is more significant than O3 stress despite relatively higher O3 levels. Irrespective of these differences in O3 uptake between relatively cool and humid as compared to relatively hot and dry years in the study region, the Critical Level for O3 was exceeded in late spring/early summer (May/June) during all 22 years. Risk assessment for the protection of European forests, which is urgently needed due to the forests current critical state after several successive years of drought and exceedance of the O3 critical level in large areas of Europe, should therefore become flux-based to account for the inter-twined effects of drought and O3 on the physiology and health of forest trees in the region. For stomatal O3 fluxes estimation, a better soil water and leaf parameterization is needed e.g., by taking into account both O3- and drought-induced effects.

Ozone modelling and mapping for risk assessment: An overview of different approaches for human and ecosystems health.

Tropospheric ozone (O3) is one of the most concernedair pollutants dueto its widespread impacts on land vegetated ecosystems and human health. Ozone is also the third greenhouse gas for radiative forcing. Consequently, it should be carefully and continuously monitored to estimate its potential adverse impacts especially inthose regions where concentrations are high. Continuous large-scale O3 concentrations measurement is crucial but may be unfeasible because of economic and practical limitations; therefore, quantifying the real impact of O3over large areas is currently an open challenge. Thus, one of the final objectives of O3 modelling is to reproduce maps of continuous concentrations (both spatially and temporally) and risk assessment for human and ecosystem health. We here reviewedthe most relevant approaches used for O3 modelling and mapping starting from the simplest geo-statistical approaches andincreasing in complexity up to simulations embedded into the global/regional circulation models and pro and cons of each mode are highlighted. The analysis showed that a simpler approach (mostly statistical models) is suitable for mappingO3concentrationsat the local scale, where enough O3concentration data are available. The associated error in mapping can be reduced by using more complex methodologies, based on co-variables. The models available at the regional or global level are used depending on the needed resolution and the domain where they are applied to. Increasing the resolution corresponds to an increase in the prediction but only up to a certain limit. However, with any approach, the ensemble models should be preferred.

Evaluation of the anthropogenic black carbon emissions and deposition on Norway spruce and silver birch foliage in the Baltic region.

This study investigates potential influence of urban trees on black carbon (BC) removal by Norway spruce and silver birch along with the BC formation, mass concentration in air, and source apportionment. The main sources of BC in urban areas are transport, household and industry. BC concentrations monitored in urban background station in Vilnius (Lithuania) showed that biomass burning was a significant contributor to BC emissions even during warm period of the year. Therefore, BC emission levels were determined for the most common biomass fuels (mixed wood pellets, oak, ash, birch and spruce firewood) and two types of agro-biomass (triticale and rapeseed straw pellets) burned in modern and old heating systems. The highest emissions were obtained for biomass fuels especially birch firewood. BC aerosol particles produced by the condensation mechanism during the combustion processes were found in all samples taken from the leaf surface. The short-term effect of BC exposure on photosynthetic pigments (chlorophyll a and b; and carotenoids) in the foliage of one-year-old Norway spruce and silver birch seedlings was evaluated by the experiment carried out in the phytotron greenhouse. The seedlings showed different short-term responses to BC exposure. All treatments applied in the phytotron greenhouse resulted in lower chlorophyll content in spruce foliage compared to natural conditions but not differed for birch seedlings. However, the exposure of BC particles on the spruce and birch seedlings in the phytotron increased the content of photosynthetic pigments compared to the control seedlings in the phytotron. Overall, urban trees can help improve air quality by reducing BC levels through dry deposition on tree foliage, and needle-like trees are more efficient than broad-leaved trees in capturing BC. Nevertheless, a further study could assess the longer-term effects of BC particles on tree biochemical and chemical reactions.

Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.

Correction: Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.

[This corrects the article DOI: 10.1371/journal.pgen.1007502.].

Early cerebrovascular and long-term neurological modifications ensue following juvenile mild traumatic brain injury in male mice.

Clinical evidence suggests that a mild traumatic brain injury occurring at a juvenile age (jmTBI) may be sufficient to elicit pathophysiological modifications. However, clinical reports are not adequately integrated with experimental studies examining brain changes occurring post-jmTBI. We monitored the cerebrovascular modifications and assessed the long-term behavioral and electrographic changes resulting from experimental jmTBI. In vivo photoacoustic imaging demonstrated a decrease of cerebrovascular oxygen saturation levels in the impacted area hours post-jmTBI. Three days post-jmTBI oxygenation returned to pre-jmTBI levels, stabilizing at 7 and 30 days after the injury. At the functional level, cortical arterioles displayed no NMDA vasodilation response, while vasoconstriction induced by thromboxane receptor agonist was enhanced at 1 day post-jmTBI. Arterioles showed abnormal NMDA vasodilation at 3 days post-jmTBI, returning to normality at 7 days post injury. Histology showed changes in vessel diameters from 1 to 30 days post-jmTBI. Neurological evaluation indicated signs of anxiety-like behavior up to 30 days post-jmTBI. EEG recordings performed at the cortical site of impact 30 days post-jmTBI did not indicate seizures activity, although it revealed a reduction of gamma waves as compared to age matched sham. Histology showed decrease of neuronal filament staining. In conclusion, experimental jmTBI triggers an early cerebrovascular hypo­oxygenation in vivo and faulty vascular reactivity. The exact topographical coherence and the direct casualty between early cerebrovascular changes and the observed long-term neurological modifications remain to be investigated. A potential translational value for cerebro-vascular oxygen monitoring in jmTBI is discussed.

Ozone weekend effect in cities: Deep insights for urban air pollution control.

Studying weekend-weekday variation in ground-level ozone (O3) allows one to better understand O3 formation conditions, with a potential for developing effective strategies for O3 control. Reducing inappropriately the O3 precursors emissions can either produce no reduction or increase surface O3 concentrations. This paper analyzes the weekend-weekday differences of O3 at 300 rural and 808 urban background stations worldwide from 2005 to 2014, in order to investigate the O3 weekend effect over time and assess the effectiveness of the precursors emissions control policies for reducing O3 levels. Data were analyzed with the non-parametric Mann-Kendall test and Theil-Sen estimator. Rural sites typically did not experience a weekend-weekday effect. In all urban stations, the mean O3 concentration on the weekend was 12% higher than on weekdays. Between 2005 and 2014, the annual mean of daily O3 concentrations increased at 74% of urban sites worldwide (+ 0.41 ppb year-1) and decreased in the United Kingdom (- 0.18 ppb year-1). Over this time period, emissions of O3 precursors declined significantly. However, a greater decline in nitrogen oxides (NOx) emissions caused an increase in Volatile Organic Compounds (VOCs) to NOx ratios leading to O3 formation. In France, South Korea and the United Kingdom, most urban stations showed a significant upward trend (+ 1.15% per year) for O3 weekend effect. Conversely, in Canada, Germany, Japan, Italy and the United States, the O3 weekend effect showed a significant downward trend (- 0.26% per year). Further or inappropriate control of anthropogenic emissions in Canada, Southern Europe, Japan, South Korea and the United States might result in increased daily O3 levels in urban areas.

Prolonged elevated levels of c-kit+ progenitor cells after a myocardial infarction by beta 2 adrenergic receptor priming.

Endogenous progenitor cells may participate in cardiac repair after a myocardial infarction (MI). The beta 2 adrenergic receptor (ß2-AR) pathway induces proliferation of c-kit+ cardiac progenitor cells (CPC) in vitro. We investigated if ß2-AR pharmacological stimulation could ameliorate endogenous CPC-mediated regeneration after a MI. C-kit+ CPC ß1-AR and ß2-AR expression was evaluated in vivo and in vitro. A significant increase in the percentage of CPCs expressing ß1-AR and ß2-AR was measured 7 days post-MI. Accordingly, 24 hrs of low serum and hypoxia in vitro significantly increased CPC ß2-AR expression. Cell viability and differentiation assays validated a functional role of CPC ß2-AR. The effect of pharmacological activation of ß2-AR was studied in C57 mice using fenoterol administered in the drinking water 1 week before MI or sham surgery or at the time of the surgery. MI induced a significant increase in the percentage of c-kit+ progenitor cells at 7 days, whereas pretreatment with fenoterol prolonged this response resulting in a significant elevated number of CPC up to 21 days post-MI. This increased number of CPC correlated with a decrease in infarct size. The immunofluorescence analysis of the heart tissue for proliferation, apoptosis, macrophage infiltration, cardiomyocytes surface area, and vessel density showed significant changes on the basis of surgery but no benefit due to fenoterol treatment. Cardiac function was not ameliorated by fenoterol administration when evaluated by echocardiography. Our results suggest that ß2-AR stimulation may improve the cardiac repair process by supporting an endogenous progenitor cell response but is not sufficient to improve the cardiac function.

Right coronary artery ligation in mice: a novel method to investigate right ventricular dysfunction and biventricular interaction.

Right ventricular (RV) dysfunction can lead to complications after acute inferior myocardial infarction (MI). However, it is unclear how RV failure after MI contributes to left-sided dysfunction. The aim of the present study was to investigate the consequences of right coronary artery (RCA) ligation in mice. RCA ligation was performed in C57BL/6JRj mice ( n = 38). The cardiac phenotypes were characterized using high-resolution echocardiography performed up to 4 wk post-RCA ligation. Infarct size was measured using 2,3,5-triphenyltetrazolium chloride staining 24 h post-RCA ligation, and the extent of the fibrotic area was determined 4 wk after MI. RV dysfunction was confirmed 24 h post-RCA ligation by a decrease in the tricuspid annular plane systolic excursion ( P < 0.001) and RV longitudinal strain analysis ( P < 0.001). Infarct size measured ex vivo represented 45.1 ± 9.1% of the RV free wall. RCA permanent ligation increased the RV-to-left ventricular (LV) area ratio ( P < 0.01). Septum hypertrophy ( P < 0.01) was associated with diastolic septal flattening. During the 4-wk post-RCA ligation, LV ejection fraction was preserved, yet it was associated with impaired LV diastolic parameters ( E/ E', global strain rate during early diastole). Histological staining after 4 wk confirmed the remodeling process with a thin and fibrotic RV. This study validates that RCA ligation in mice is feasible and induces RV heart failure associated with the development of LV diastolic dysfunction. Our model offers a new opportunity to study mechanisms and treatments of RV/LV dysfunction after MI. NEW & NOTEWORTHY Right ventricular (RV) dysfunction frequently causes complications after acute inferior myocardial infarction. How RV failure contributes to left-sided dysfunction is elusive because of the lack of models to study molecular mechanisms. Here, we created a new model of myocardial infarction by permanently tying the right coronary artery in mice. This model offers a new opportunity to unravel mechanisms underlying RV/left ventricular dysfunction and evaluate drug therapy.