SENP2-NDR2-p21 axis modulates lung cancer cell growth.

Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G1/S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2-NDR2-p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment.

The impact of microplastics on sulfur REDOX processes in different soil types: A mechanism study.

Microplastics can potentially affect the physical and chemical properties of soil, as well as soil microbial communities. This could, in turn, influence soil sulfur REDOX processes and the ability of soil to supply sulfur effectively. However, the specific mechanisms driving these effects remain unclear. To explore this, soil microcosm experiments were conducted to assess the impacts of polystyrene (PS) and polyphenylene sulfide (PPS) microplastics on sulfur reduction-oxidation (REDOX) processes in black, meadow, and paddy soils. The findings revealed that PS and PPS most significantly decreased SO42- in black soil by 9.4%, elevated SO42- in meadow soil by 20.8%, and increased S2- in paddy soil by 20.5%. PS and PPS microplastics impacted the oxidation process of sulfur in soil by influencing the activity of sulfur dioxygenase, which was mediated by α-proteobacteria and γ-proteobacteria, and the oxidation process was negatively influenced by soil organic matter. PS and PPS microplastics impacted the reduction process of sulfur in soil by influencing the activity of adenosine-5'-phosphosulfate reductase, sulfite reductase, which was mediated by Desulfuromonadales and Desulfarculales, and the reduction process was positively influenced by soil organic matter. In addition to their impacts on microorganisms, it was found that PP and PPS microplastics directly influenced the structure of soil enzymes, leading to alterations in soil enzyme activity. This study sheds light on the mechanisms by which microplastics impact soil sulfur REDOX processes, providing valuable insights into how microplastics influence soil health and functioning, which is essential for optimizing crop growth and maximizing yield in future agricultural practices.

Effect of Air Pollution Particulate Matter on Ischemic and Hemorrhagic Stroke: A Scoping Review.

Air pollution particulate matter (PM) exposure has been established as a risk factor for stroke. However, few studies have investigated the effects of PM exposure on stroke subtypes (ischemic and hemorrhagic stroke). Ischemic (IS) and hemorrhagic strokes (HS) involve distinctive pathophysiological pathways and may be differentially influenced by PM exposure. This review aims to characterize the effects of PM exposure on ischemic and hemorrhagic strokes. It also identifies subpopulations that may be uniquely vulnerable to PM toxicity. Pubmed was queried from 2000 to 2023 to identify clinical and epidemiological studies examining the association between PM exposure and stroke subtypes (ischemic and hemorrhagic stroke). Inclusion criteria were: 1) articles written in English 2) clinical and epidemiological studies 3) studies with a clear definition of stroke, IS, HS, and air pollution 4) studies reporting the effects of PM and 5) studies that included distinct analyses per stroke subtype. Two independent reviewers screened the literature for applicable studies. A total of 50 articles were included in this review. Overall, PM exposure increases ischemic stroke risk in both lightly and heavily polluted countries. The association between PM exposure and hemorrhagic stroke is variable and may be influenced by a country's ambient air pollution levels. A stronger association between PM exposure and stroke is demonstrated in older individuals and those with pre-existing diabetes. There is no clear effect of sex or hypertension on PM-associated stroke risk. Current literature suggests PM exposure increases ischemic stroke risk, with an unclear effect on hemorrhagic stroke risk. Older patients and those with pre-existing diabetes may be the most vulnerable to PM toxicity. Future investigations are needed to characterize the influence of sex and hypertension on PM-associated stroke risk.

Effective Removal of Cd from Aqueous Solutions Using P-Loaded Ca-Mn-Impregnated Biochar.

Cadmium (Cd) pollution in wastewater has become an increasingly widespread concern worldwide. Studies on Cd (II) removal using phosphate-adsorbed sorbents are limited. This study aimed to elucidate the behaviors and mechanisms of Cd (II) sorption on phosphate-loaded Ca-Mn-impregnated biochar (Ps-CMBC). The Cd (II) sorption on Ps-CMBC reached equilibrium within 2 h and exhibited a higher sorption efficiency than biochar and CMBC. Additionally, the Langmuir isotherm could better describe the Cd (II) adsorption on the sorbents. P75-CMBC had a maximum Cd (II) sorption capability of 70.13 mg·g-1 when fitted by the Langmuir isotherm model, which was approximately 3.18 and 2.86 times greater than those of biochar and CMBC, respectively. Higher pH (5-7) had minimal effect on Cd (II) sorption capacity. The results of characterization analyses, such as SEM-EDS, FTIR, and XPS, suggested that there was a considerable difference in the sorption mechanisms of Cd (II) among the sorbents. The primary sorption mechanisms for biochar, CMBC, and Ps-CMBC included electrostatic attraction and surface complexation; additionally, for Ps-CMBC, Cd (II)-π interactions and coordination of Cd (II) with P=O were critical mechanisms for Cd (II) removal. The results of this study demonstrate that phosphate-loaded CMBC can be used as an effective treatment for heavy metal pollution in aqueous media.

Generation of balanced pulse pairs based on a dual-chip coupling structure.

An asymmetric Mach-Zehnder interferometer (AMZI) is an essential device to generate pulse pairs in quantum key distribution systems. An AMZI based on a dual-chip coupling structure in a silica-on-silicon planar light wave circuit platform is proposed, which includes a variable optical splitter (VOS), a delay line (DL), and a directional coupler (DC). The AMZI chip is divided into a VOS-DL part and a DC part, and the two parts are independently manufactured and then coupled. Since the DC part occupies the smallest area of the AMZI chip and is most sensitive to manufacturing errors, separate production can reduce the process difficulty and fabrication errors. In the experiment, balanced pulse pairs with a delay time of 402 ps are obtained in the condition of single photon transmission, and the excess loss is 0.8 dB. This dual-chip coupling structure can improve the yield and reduce the manufacturing cost when producing large chips.

Design and Experiment of a Biomimetic Duckbill-like Vibration Chain for Physical Weed Control during the Rice Tillering Stage.

The widespread use of chemical herbicides has jeopardized concerns about food safety and ecological consequences. To address these issues and reduce reliance on chemical herbicides, a physical weed control device was developed for the tillering stage in paddy fields. This device features a biomimetic duckbill-like vibration chain that effectively controls weed outbreaks. The chain penetrates the soft surface soil of the paddy field under gravity and rapidly stirs the soil through vibration, leading to the detachment of the weed roots anchored in the surface layer. Simultaneously, the device avoids mechanical damage to rice seedlings rooted in deeper soil. This study aimed to investigate the effects of chain structural parameters (the number of chain rows, vibration amplitude, and length of chains) and operational parameters (vibration frequency and working velocity) on weed control efficiency and rice seedling damage. Through a central composite regression field test, the optimal device structure and operational parameters were determined. The optimization results demonstrated that a vibration amplitude of 78.8 mm, a chain length of 93.47 cm, and 3.4 rows of chains, along with a vibration frequency and working velocity ranging from 0.5 to 1.25 m/s, achieved an optimal weeding effect. Under the optimal parameter combination, field test results demonstrated that approximately 80% of the weeds in the field were effectively cleared. This indicates that the design of the biomimetic duckbill-like vibration chain weeding device exhibits a relatively superior weeding performance, offering a practical solution for the management of weeds in rice fields.

Magnetic resonance imaging of white matter response to diesel exhaust particles.

Air pollution is associated with risks of dementia and accelerated cognitive decline. Rodent air pollution models have shown white matter vulnerability. This study uses diffusion tensor imaging (DTI) to quantify changes to white matter microstructure and tractography in multiple myelinated regions after exposure to diesel exhaust particulate (DEP). Adult C57BL/6 male mice were exposed to re-aerosolized DEP (NIST SRM 2975) at a concentration of 100 ug/m3 for 200 hours. Ex-vivo MRI analysis and fractional anisotropy (FA)-aided white matter tractography were conducted to study the effect of DEP exposure on the brain white matter tracts. Immunohistochemistry was used to assess myelin and axonal structure. DEP exposure for 8 weeks altered myelin composition in multiple regions. Diffusion tensor imaging (DTI) showed decreased FA in the corpus callosum (30%), external capsule (15%), internal capsule (15%), and cingulum (31 %). Separate immunohistochemistry analyses confirmed prior findings. Myelin basic protein (MBP) was decreased (corpus callosum: 28%, external capsule: 29%), and degraded MPB increased (corpus callosum: 32%, external capsule: 53%) in the DEP group. White matter is highly susceptible to chronic DEP exposure. This study demonstrates the utility of DTI as a neuroanatomical tool in the context of air pollution and white matter myelin vulnerability.

Rapid and sensitive determination of Se and heavy metals in foods using electrothermal vaporization inductively coupled plasma mass spectrometry with a novel transportation system.

Rapid, sensitive and simultaneous determination of trace multi-elements in various plant food samples such as grain, oilseed, vegetable and tea is always a challenge thus far. In this work, a rapid determination method for Se, Cd, As and Pb in food samples by inductively coupled plasma mass spectrometry (ICP-MS) using slurry sampling electrothermal vaporization (SS-ETV) was developed. To improve the analytical sensitivity and precision as well as eliminate the memory effect, a gas turbulator line and signal delay device (SDD) were for the first time designed for the graphite furnace (GF) ETV coupled with ICP-MS. The signal acquisition parameters of ICP-MS, ashing and vaporization conditions, and the flow rates of carrier gas and gas turbulator were investigated for Se, Cd, As and Pb in food samples. Under the optimized conditions, the limits of determination (LODs) for Se, Cd, As and Pb were 0.5 ng g-1, 0.3 ng g-1, 0.3 ng g-1 and 0.6 ng g-1, respectively; the limits of quantification (LOQs) for Se, Cd, As and Pb were 1.7 ng g-1, 1.0 ng g-1, 1.0 ng g-1 and 1.9 ng g-1, respectively; linearity (R2) in the range of 1 to 4,000 ng g-1 was >0.999 using the standard addition method. This method was used to analyze 5 CRMs including rice, tea and soybeans, and the concentrations detected by this method were within the range of the certified values. The recoveries of Se, Cd, As and Pb in plant food matrices including grain, oilseed, celery, spinach, carrot and tea samples were 86-118% compared to the microwave digestion ICP-MS method; and the relative standard deviations (RSDs) were 1.2-8.9% for real food sample analysis, proving a good precision and accuracy for the simultaneous determination of multi-elements. The analysis time was less than 3 min, slurry preparation time < 5 min without sample digestion process. The proposed direct slurry sampling ICP-MS method is thus suitable for rapid and sensitive determination of Se, Cd, As and Pb in food samples with advantages such as simplicity, green and safety, as well as with a promising application potential in detecting more elements to protect food safety and human health.

Polarization-insensitive 90° optical hybrid using silica-based PLC.

A 90° optical hybrid (OH) based on a 4×4 multimode interference (MMI) coupler is characterized and analyzed using the silica-based planar light circuit. The OH is designed to be polarization-insensitive with an extremely low polarization-dependent loss (<0.18d B) and phase error (w i t h i n±1.3∘). The fabricated chip exhibits an excess loss of 3.4 dB and 3.8 dB for TE and TM polarizations at 1550 nm. The measured phase error is w i t h i n±7.2∘ over 50 nm in the C+L band with a polarization-dependent error w i t h i n±3.5∘. The fabrication tolerance of the MMI width and waveguide sidewall angle is analyzed, which can well explain the deviation from the theoretical calculation.

Particulate matter exposure and chronic cerebral hypoperfusion promote oxidative stress and induce neuronal and oligodendrocyte apoptosis in male mice.

Chronic cerebral hypoperfusion (CCH) may amplify the neurotoxicity of nanoscale particulate matter (nPM), resulting in white matter injury. This study characterized the joint effects of nPM (diameter ≤ 200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) exposure on neuronal and white matter injury in a murine model. nPM was collected near a highway and re-aerosolized for exposure. Ten-week-old C57BL/6 male mice were randomized into four groups: filtered air (FA), nPM, FA + BCAS, and nPM + BCAS. Mice were exposed to FA or nPM for 10 weeks. BCAS surgeries were performed. Markers of inflammation, oxidative stress, and apoptosis were examined. nPM + BCAS exposure increased brain hemisphere TNFα protein compared to FA. iNOS and HNE immunofluorescence were increased in the corpus callosum and cerebral cortex of nPM + BCAS mice compared to FA. While nPM exposure alone did not decrease cortical neuronal cell count, nPM decreased corpus callosum oligodendrocyte cell count. nPM exposure decreased mature oligodendrocyte cell count and increased oligodendrocyte precursor cell count in the corpus callosum. nPM + BCAS mice exhibited a 200% increase in cortical neuronal TUNEL staining and a 700% increase in corpus callosum oligodendrocyte TUNEL staining compared to FA. There was a supra-additive interaction between nPM and BCAS on cortical neuronal TUNEL staining (2.6× the additive effects of nPM + BCAS). nPM + BCAS exposure increased apoptosis, neuroinflammation, and oxidative stress in the cerebral cortex and corpus callosum. nPM + BCAS exposure increased neuronal apoptosis above the separate responses to each exposure. However, oligodendrocytes in the corpus callosum demonstrated a greater susceptibility to the combined neurotoxic effects of nPM + BCAS exposure.

Prophylactic administration of tranexamic acid combined with thromboelastography-guided hemostatic algorithm reduces allogeneic transfusion requirements during pediatric resective epilepsy surgery: A randomized controlled trial.

Background: Intraoperative bleeding and allogeneic transfusion remain common problems in pediatric resective epilepsy surgery. Tranexamic acid (TXA) is a widely recommended antifibrinolytic drug that reduces blood loss and transfusion requirements for bleeding patients. Thromboelastography (TEG)-guided hemostatic algorithm is commonly used in bleeding management. This trial was designed to validate the efficacy of a multimodal coagulation therapy involving continuous TXA infusion with TEG-guided hemostatic algorithm in reducing allogeneic exposure risk in pediatric resective epilepsy surgery. Methods: Eighty-three children undergoing resective epilepsy surgery were randomized into a treatment group (Group T; n = 42) and a control group (Group C; n = 41). Group T received prophylactic TXA (10 mg/kg followed by 5 mg/kg/h) with TEG-guided hemostatic algorithm, whereas Group C received conventional coagulation management. The primary outcome was allogeneic transfusion rate during surgery, and the secondary outcomes were intraoperative blood loss, incidence of postoperative seizures, and thromboembolic events during hospitalization. Results: The incidence of intraoperative allogeneic transfusion reduced by 34.7% with the use of a multimodal coagulation therapy (19.0% in Group T vs. 53.7% in Group C; RR 0.355, 95% CI 0.179-0.704; p = 0.001). This was mainly triggered by a significant reduction (44.1%) in intraoperative plasma transfusion (7.1% in Group T vs. 51.2% in Group C; RR 0.139, 95% CI 0.045-0.432; p = 0.000). The risk of intraoperative RBC transfusion was lower in Group T than in Group C, but the difference was not statistically significant (14.3% in Group T vs. 29.3% in Group C; RR 0.488, 95% CI 0.202-1.177; p = 0.098). No platelets were transfused in both groups. Further, 19 (45.2%) patients in Group T received fibrinogen concentrates guided by TEG data, whereas 1 (2.4%) patient in Group C received fibrinogen concentrates empirically. There were no significant differences in estimated blood loss and postoperative seizures between the two groups, and no thromboembolic events were observed after surgery. Conclusion: Prophylactic administration of TXA combined with TEG-guided hemostatic algorithm can be an effective multimodal coagulation strategy for reducing allogeneic transfusion requirements during pediatric resective epilepsy surgery. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR1800016188.

Neurotoxicity of Diesel Exhaust Particles.

BACKGROUND: Air pollution particulate matter (PM) is strongly associated with risks of accelerated cognitive decline, dementia and Alzheimer's disease. Ambient PM batches have variable neurotoxicity by collection site and season, which limits replicability of findings within and between research groups for analysis of mechanisms and interventions. Diesel exhaust particles (DEP) offer a replicable model that we define in further detail. OBJECTIVE: Define dose- and time course neurotoxic responses of mice to DEP from the National Institute of Science and Technology (NIST) for neurotoxic responses shared by DEP and ambient PM. METHODS: For dose-response, adult C57BL/6 male mice were exposed to 0, 25, 50, and 100µg/m3 of re-aerosolized DEP (NIST SRM 2975) for 5 h. Then, mice were exposed to 100µg/m3 DEP for 5, 100, and 200 h and assayed for amyloid-ß peptides, inflammation, oxidative damage, and microglial activity and morphology. RESULTS: DEP exposure at 100µg/m3 for 5 h, but not lower doses, caused oxidative damage, complement and microglia activation in cerebral cortex and corpus callosum. Longer DEP exposure for 8 weeks/200 h caused further oxidative damage, increased soluble Aß, white matter injury, and microglial soma enlargement that differed by cortical layer. CONCLUSION: Exposure to 100µg/m3 DEP NIST SRM 2975 caused robust neurotoxic responses that are shared with prior studies using DEP or ambient PM0.2. DEP provides a replicable model to study neurotoxic mechanisms of ambient PM and interventions relevant to cognitive decline and dementia.

Production of sesquiterpene patchoulol in mitochondrion-engineered Saccharomyces cerevisiae.

Patchoulol is a natural sesquiterpene, which is widely used in perfumes and cosmetics. In the work, the mitochondria of S. cerevisiae were engineered for patchoulol production. The patchoulol titer of mitochondria-compartmentalized strain (1.79 mg/L) was 2.71-fold higher than that of control strain (0.66 mg/L) using genome-integrated patchoulol synthase, indicating that mitochondria compartmentation resulted in higher concentration of FPP (farnesyl pyrophosphate) precursor for patchoulol production. Moreover, when fused FPP synthase and patchoulol synthase was overexpressed in the strain with a mitochondria-localized DMAPP (dimethylallyl diphosphate) pathway, the production of patchoulol increased significantly to 19.24 mg/L, indicating more precursors were provided for patchoulol production. Nevertheless, the introduction of excess foreign proteins into mitochondria might cause a certain stress on mitochondria and showed a negative effect on the growth of yeast cells, which could hinder the expression of foreign pathways and reduce the patchoulol production. In conclusion, mitochondria-engineered yeast cells showed important potential for the enhanced biosynthesis of patchoulol, and further engineering could be considered based on the present work.

Analysis of Degradation Kinetics and Migration Pattern of Chlorfenapyr in Celery (Apium graveliens L.) and Soil Under Greenhouse Conditions at Different Elevations.

The degradation kinetics and migration pattern of chlorfenapyr in celery and soil at Lhasa and Pengzhou were investigated. A simple, rapid analytical method for the quantification of chlorfenapyr in celery and soil was developed using gas chromatography-tandem mass spectrometer. The results indicated that the half-lives of chlorfenapyr in celeries and soils at Lhasa were 6.3 days and 12.8 days. While the half-lives of chlorfenapyr in celeries and soils at Pengzhou were 6.9 days and 20.4 days. The half-lives of chlorfenapyr in celeries and soils at Lhasa were shorter than that at Pengzhou, while the half-lives of chlorfenapyr in soils at Lhasa and Pengzhou were longer than that in celeries at Lhasa and Pengzhou. The final residues of chlorfenapyr in celeries at Lhasa and Pengzhou were 5.074 ± 0.144 mg/kg and 5.981 ± 0.234 mg/kg after 7 days of spraying, respectively. When chlofenapyr was sprayed to soils only, the average root concentration factor of chlorfenapyr were 3.57-4.02, while the average translocation factor of chlorfenapyr in leaves and stems were 0.28-0.38 and 0.20-0.25, respectively. Chlorfenapyr was easy to migrate from soil to the roots of celery, followed by leaves and stems. The limit value of chlorfenapyr in celery has not been specified in China's National MRL standard (GB 2763 in National food safety standard-maximum residue limits for pesticides in food. Standard, Beijing, 2021), this study was useful to draw up the limit values of chlorfenapyr residues in celery at different elevations.

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion.

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.

Modification of the Calculation Method for Dynamic Reserves in Tight Sandstone Gas Reservoirs.

The determination of dynamic reserves is important for tight sandstone gas reservoirs in production. Based on the geological and gas data of the Yan'an gas field, the influence of pressure on the properties of natural gas is studied by mathematical methods. At the same time, the modified flowing material balance equation is established considering the changes in gas viscosity and compressibility. The result shows that (1) the viscosity of natural gas increases rapidly with pressure; (2) the deviation factor decreases with pressure (P < 15 MPa) and then increases (P > 15 MPa) with temperature; (3) the compressibility decreases rapidly with pressure and increases with temperature; (4) compared with the results of the material balance method, the average error of the flowing material balance method is 33.95%, and the accuracy of the modified flowing material balance method is higher with an average error of 1.25%; and (5) a large change in the production will affect the accuracy of the modified flowing material balance method, especially a shut-in for a long time before the pressure drop production is calculated at a certain time, so data points that are relatively consistent should be selected as far as possible to calculate the dynamic reserves. The findings of this study can help in the accurate evaluation of dynamic reserves of the tight gas reservoir in the Yan'an gas field and are an important guide for the formulation of a rational plan for the gas reservoir and its economic and efficient development.

Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model.

BACKGROUND: Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM. OBJECTIVES: This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter ≤200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. METHODS: nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) FA + BCAS, and d) nPM + BCAS. Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. RESULTS: The joint nPM + BCAS group exhibited synergistic effects on white matter injury (2.3× the additive nPM and FA + BCAS scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and FA + BCAS effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of nPM + BCAS than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the nPM + BCAS cohort demonstrated impaired working memory when compared to the FA + BCAS group. DISCUSSION: Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.

Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model.

Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p<0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p<0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p<0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p<0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model.