Laminar shear stress alleviates monocyte adhesion and atherosclerosis development via miR-29b-3p/CX3CL1 axis regulation.

Laminar shear stress (Lss) is an important anti-atherosclerosis (anti-AS) factor, but its mechanism network is not clear. Therefore, this study aimed to identify how Lss acts against AS formation from a new perspective. In this study, we analyzed high-throughput sequencing data from static and Lss-treated human aortic and human umbilical vein endothelial cells (HAECs and HUVECs, respectively) and found that the expression of CX3CL1, which is a target gene closely related to AS development, was lower in the Lss group. Lss alleviated the inflammatory response in TNF-α (also known as TNF)-activated HAECs by regulating the miR-29b-3p/CX3CL1 axis, and this was achieved by blocking nuclear factor (NF)-κB signaling. In complementary in vivo experiments, a high-fat diet (HFD) induced inflammatory infiltration and plaque formation in the aorta, both of which were significantly reduced after injection of agomir-miRNA-29b-3p via the tail vein into HFD-fed ApoE-/- mice. In conclusion, this study reveals that the Lss-sensitive miR-29b-3p/CX3CL1 axis is an important regulatory target that affects vascular endothelial inflammation and AS development. Our study provides new insights into the prevention and treatment of AS.

Design method for lens desensitization adapted to refractive index error.

The design of optical systems not only considers the imaging performance but also the manufacturing difficulty and feasibility of the system. In practice, errors in the manufacturing process of glass materials and deviations in glass material parameters introduced in complex environments can both lead to degradation in the imaging quality of optical systems. Optical systems that are sensitive to glass material errors face increased manufacturing difficulty and reduced stability. This paper, based on geometrical optics theory, establishes an evaluation function for refractive index error sensitivity and analyzes its relationship with optical parameters and glass materials. It proposes a design method to reduce the refractive index sensitivity of optical systems. Through simulation verification and analysis using examples, the validity of the desensitization design method is confirmed.

USc2C2 and USc2NC Clusters with U-C Triple Bond Character Stabilized Inside Fullerene Cages.

The chemistry of f-block metal-carbon multiple bonds is underdeveloped compared to well-established carbene complexes of the d-block transition metals. Herein, we report two new actinide-rare earth mixed metal carbides and nitrogen carbide cluster fullerenes, USc2C2@D5h(6)-C80 and USc2NC@D5h(6)-C80, which contain U-C bonds with triple bond character and were successfully synthesized and characterized by mass spectrometry, UV-vis-NIR spectroscopy, Fourier transform infrared spectroscopy, single crystal X-ray diffraction, and DFT calculations. Crystallographic studies show that the two previously unreported clusters, USc2C2 and USc2NC, are stabilized in the D5h(6)-C80 carbon cage and adopt unique trifoliate configurations, in which C2/NC units are almost vertically inserted into the plane defined by the U and two Sc atoms. Combined experimental and theoretical studies further reveal the bonding structure of USc2C2 and USc2NC, which contain C═U(VI)═C and C═U(V)═N bonding motifs. The electronic structures of the two compounds are determined as U6+(Sc2)6+(C4-)2@D5h(6)-C804- and U5+(Sc2)6+(N)3-(C)4-@D5h(6)-C804-, respectively. Quantum-chemical studies confirm that the U-C bonds in both molecules show unprecedented multicenter triple-bond character. The discovery of this unique U-C multiple bond offers a deeper understanding of the fundamentals of uranium chemistry.

Synthesis and Characterization of U≡C Triple Bonds in Fullerene Compounds.

Despite decades of efforts, the actinide-carbon triple bond has remained an elusive target, defying synthesis in any isolable compound. Herein, we report the successful synthesis of uranium-carbon triple bonds in carbide-bridged bimetallic [U≡C-Ce] units encapsulated inside the fullerene cages of C72 and C78. The molecular structures of UCCe@C2n and the nature of the U≡C triple bond were characterized through X-ray crystallography and various spectroscopic analyses, revealing very short uranium-carbon bonds of 1.921(6) and 1.930(6) Å, with the metals existing in their highest oxidation states of +6 and +4 for uranium and cerium, respectively. Quantum-chemical studies further demonstrate that the C2n cages are crucial for stabilizing the [UVI≡C-CeIV] units through covalent and coordinative interactions. This work offers a new fundamental understanding of the elusive uranium-carbon triple bond and informs the design of complexes with similar bonding motifs, opening up new possibilities for creating distinctive molecular compounds and materials.

Desensitization design method of a freeform optical system based on local curve control.

In this Letter, an error sensitivity evaluation function of freeform optical systems is proposed, and a desensitization design method is established. This method adopts the idea of micro-elements and, based on geometric optics theory, studies the relationship between the local curve of the freeform surface and the change of the wavefront error (ΔWE) when the optical system is disturbed by the position error, and realizes the desensitization design of the optical system. By simply changing the evaluation function, the method can be applied to the desensitization design of any optical system with any surface (spherical, aspheric, and freeform surface).

Explainable deep transfer learning model for disease risk prediction using high-dimensional genomic data.

Building an accurate disease risk prediction model is an essential step in the modern quest for precision medicine. While high-dimensional genomic data provides valuable data resources for the investigations of disease risk, their huge amount of noise and complex relationships between predictors and outcomes have brought tremendous analytical challenges. Deep learning model is the state-of-the-art methods for many prediction tasks, and it is a promising framework for the analysis of genomic data. However, deep learning models generally suffer from the curse of dimensionality and the lack of biological interpretability, both of which have greatly limited their applications. In this work, we have developed a deep neural network (DNN) based prediction modeling framework. We first proposed a group-wise feature importance score for feature selection, where genes harboring genetic variants with both linear and non-linear effects are efficiently detected. We then designed an explainable transfer-learning based DNN method, which can directly incorporate information from feature selection and accurately capture complex predictive effects. The proposed DNN-framework is biologically interpretable, as it is built based on the selected predictive genes. It is also computationally efficient and can be applied to genome-wide data. Through extensive simulations and real data analyses, we have demonstrated that our proposed method can not only efficiently detect predictive features, but also accurately predict disease risk, as compared to many existing methods.

U@Cs(4)-C82: A Different Cage Isomer with Reactivity Controlled by U-Sumanene Interaction.

Actinide endohedral metallofullerenes (EMFs) are a fullerene family that possess unique actinide-carbon cage host-guest molecular and electronic structures. In this work, a novel actinide EMF, U@Cs(4)-C82, was successfully synthesized and characterized, and its chemical reactivity was investigated. Crystallographic analysis shows that U@Cs(4)-C82, a new isomer of U@C82, has a Cs(4)-C82 cage, which has never been discovered in the form of empty or endohedral fullerenes. Its unique chemical reactivities were further revealed through the Bingel-Hirsch reaction and carbene addition reaction studies. The Bingel-Hirsch reaction of U@Cs(4)-C82 shows exceptionally high selectivity and product yield, yielding only one major addition adduct. Moreover, the addition sites for both reactions are unexpectedly located on adjacent carbon atoms far away from the actinide metal, despite the nucleophilic (Bingel-Hirsch) and electrophilic (carbene addition) nature of either reactant. Density functional theory (DFT) calculations suggest that this chemical behavior, unprecedented for EMFs, is directed by the unusually strong interaction between U and the sumanene motif of the carbon cage in U@Cs(4)-C82, which makes the energy increase when it is disrupted. This work reveals remarkable chemical properties of actinide EMFs originating from their unique electronic structures and highlights the key role of actinide-cage interactions in the determination of their chemical behaviors.

Optical Temperature Sensing Based on Linear Change of Luminescence Intensity Ratio in Y2O3: Tm3+, Eu3+ Phosphors.

In this work, Y2O3: Tm3+, Eu3+ phosphors were made by homogeneous precipitation with urea as precipitator. The emission spectra varying with temperature of Y2O3: Tm3+, Eu3+ phosphors were measured and analyzed. Analysis show that the luminescence of Eu3+ represents a normal thermal quenching change, while that of Tm3+ exhibits slow thermal enhancement phenomenon. In the temperature range of 303-503 K, the luminescence of Tm3+ showed a trend of first strengthening and then weakening. The reason for this phenomenon of Tm3+ is that there is energy transfer from Eu3+ to Tm3+, and the energy transfer efficiency increases gradually with temperature. Meanwhile, the luminescence of Tm3+ also have thermal quenching effect. Under the combined influence of thermal quenching and energy transfer, the luminescence of Tm3+ first becomes stronger and then then becomes weaker. According to the calculation, the luminescence intensity ratio (LIR) of Tm3+ and Eu3+ conforms to the linear empirical formula with increasing temperature. The relative sensitivity of phosphors decreases with Eu3+ concentration increased, and the maximum Sr reaches 0.460% K-1 (1% Tm3+, 0.3% Eu3+, at 303 K). Moreover, the temperature cycle test present that the LIR of phosphors has good repeatability.

Comparing myopic error in patients with basic and convergence insufficiency intermittent exotropia in China.

PURPOSE: To compare the degree of myopia between the dominant and non-dominant eyes in teenagers with intermittent exotropia (IXT) in China. METHODS: A total of 199 IXT patients with myopia were included in this retrospective study and were divided into two groups according to the difference between near and distance exodeviation: basic IXT and convergence insufficiency (CI) IXT. Refractive errors were analyzed by spherical equivalent (SE) values. Patients were further stratified into anisometropia group and non-anisometropia group based on binocular SE values difference greater than 1.0D or not. RESULTS: There were 127 patients in the CI IXT group, with a near deviation of 46.94 ± 20.53 prism diopters (PD) and a distance deviation of 28.36 ± 14.34 PD, and there were 72 (36.2%) patients in the basic IXT group, with a near deviation of 37.68 ± 22.21 PD and a distance deviation angle of 33.21 ± 23.96 PD. The near exodeviation was significantly larger in the CI group than in the basic IXT group(P < 0.001). In the CI IXT group, the mean SE was - 2.09 ± 1.45 diopters (D) in the dominant eye and - 2.53 ± 1.44D in the non-dominant eye, while in the basic IXT group, the mean SE was - 2.46 ± 1.56D in the dominant eye and - 2.89 ± 1.37D in the non-dominant eye. The anisometropia group included 43 patients, while non-anisometropia group included 156 patients. The near and distance exodeviation in the anisometropia group were 45.26 ± 24.41 PD and 33.53 ± 23.31 PD, respectively, and those in the non-anisometropia group were 43.42 ± 20.69 PD and 29.07 ± 16.84 PD, respectively. There were no significant differences in near and distance deviation (P = 0.78 and P = 0.73 respectively) between the two groups. The SE of the dominant eye was less myopic than of the non-dominant eyes in both the CI and anisometropia groups (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: Our study revealed that convergence insufficiency IXT is more common than the basic type in pediatric myopic population and is characterized by higher inter-eye differences of myopia. The dominant eye was found to be less myopic in IXT patients, particularly in those with convergence insufficiency and anisometropia.

Impact of Practical Online Lessons on Chinese Medical Students' Perception of Radiation Oncology.

Radiotherapy is an essential component of oncology treatment. It is imperative that clinicians and medical students have a fundamental understanding of radiotherapy. However, radiation oncology education is deficient worldwide. This study introduced an hour-long online Massive Open Online Course (MOOC) as a supplement to the basic curriculum for 8-year medical students at Peking Union Medical College and Tsinghua University in China. The students' personal opinions and comprehension of radiation oncology therapy were assessed through pre- and post-test questionnaires before and after the MOOC study. The results indicated that the percentage of students interested in radiotherapy increased, and their knowledge of radiotherapy significantly improved after the online MOOC study, suggesting that short-term MOOC study may stimulate students' interest in learning and improving their knowledge of radiation therapy. The study suggests that the combination of online and offline teaching may be a feasible way to develop radiation oncology education in the future.

Assessment of Non-Occupational 1,4-Dioxane Exposure Pathways from Drinking Water and Product Use.

1,4-Dioxane is a persistent and mobile organic chemical that has been found by the United States Environmental Protection Agency (USEPA) to be an unreasonable risk to human health in some occupational contexts. 1,4-Dioxane is released into the environment as industrial waste and occurs in some personal-care products as an unintended byproduct. However, limited exposure assessments have been conducted outside of an occupational context. In this study, the USEPA simulation modeling tool, Stochastic Human Exposure and Dose Simulator-High Throughput (SHEDS-HT), was adapted to estimate the exposure and chemical mass released down the drain (DTD) from drinking water consumption and product use. 1,4-Dioxane concentrations measured in drinking water and consumer products were used by SHEDS-HT to evaluate and compare the contributions of these sources to exposure and mass released DTD. Modeling results showed that compared to people whose daily per capita exposure came from only products (2.29 × 10-7 to 2.92 × 10-7 mg/kg/day), people exposed to both contaminated water and product use had higher per capita median exposures (1.90 × 10-6 to 4.27 × 10-6 mg/kg/day), with exposure mass primarily attributable to water consumption (75-91%). Last, we demonstrate through simulation that while a potential regulatory action could broadly reduce DTD release, the proportional reduction in exposure would be most significant for people with no or low water contamination.

Jitter-Robust Phase Retrieval Wavefront Sensing Algorithms.

Phase retrieval wavefront sensing methods are now of importance for imaging quality maintenance of space telescopes. However, their accuracy is susceptible to line-of-sight jitter due to the micro-vibration of the platform, which changes the intensity distribution of the image. The effect of the jitter shows some stochastic properties and it is hard to present an analytic solution to this problem. This paper establishes a framework for jitter-robust image-based wavefront sensing algorithm, which utilizes two-dimensional Gaussian convolution to describe the effect of jitter on an image. On this basis, two classes of jitter-robust phase retrieval algorithms are proposed, which can be categorized into iterative-transform algorithms and parametric algorithms, respectively. Further discussions are presented for the cases where the magnitude of jitter is unknown to us. Detailed simulations and a real experiment are performed to demonstrate the effectiveness and practicality of the proposed approaches. This work improves the accuracy and practicality of the phase retrieval wavefront sensing methods in the space condition with non-ignorable micro-vibration.

UCN@Cs(6)-C82: An Encapsulated Triangular UCN Cluster with Ambiguous U Oxidation State [U(III) versus U(I)].

Understanding the chemical behavior of actinide elements is essential for the effective management and use of actinide materials. In this study, we report an unprecedented η2 (side-on) coordination of U by a cyanide in a UCN cluster, which was stabilized inside a C82 fullerene cage. UCN@Cs(6)-C82 was successfully synthesized and fully characterized by mass spectrometry, single crystal X-ray crystallography, cyclic voltammetry, spectroscopy, and theoretical calculations. The bonding analysis demonstrates significant donation bonding between CN- and uranium, and covalent interactions between uranium and the carbon cage. These effects correlate with an observed elongated cyanide C-N bond, resulting in a rare case where the oxidation state of uranium shows ambiguity between U(III) and U(I). The discovery of this unprecedented triangular configuration of the uranium cyanide cluster provides a new insight in coordination chemistry and highlights the large variety of bonding situations that uranium can have.

Diffraction analysis of multiple-disk occulters in external coronagraphs based on uniform boundary wave diffraction theory.

Occulters with multiple-disk structure are commonly used for mitigating the diffraction light from specific incident angles in external coronagraphs. In the design phase of coronagraphs, it is of great importance to calculate the diffraction propagation of the occulters with high accuracy and high efficiency. In this paper, an analytical method is proposed for the diffraction analysis of multiple-disk occulters based on uniform boundary wave (BDW) diffraction theory. First, an analytical propagator with Fresnel functions is derived for single-disk case, of which the accuracy and efficiency are demonstrated by a numerical example. Then it is proved that the propagator in multiple-disk case was just the iterative use of the single-disk one when neglecting the gradient diffraction term. The analytical propagator presents much improvement on simplification and efficiency compared to former numerical propagators, and hence, is of great significance to future external coronagraph design and analysis.

Synthesis and Characterization of Two Isomers of Th@C82: Th@C2v(9)-C82 and Th@C2(5)-C82.

Actinide endohedral fullerenes have demonstrated remarkably different physicochemical properties compared to their lanthanide analogues. In this work, two novel isomers of Th@C82 were successfully synthesized, isolated, and fully characterized by mass spectrometry, X-ray single crystallography, UV-vis-NIR spectroscopy, Raman spectroscopy, and cyclic voltammetry. The molecular structures of the two isomers were determined unambiguously as Th@C2v(9)-C82 and Th@C2(5)-C82 by single-crystal X-ray diffraction analysis. Raman and UV-vis-NIR spectroscopies further confirm the assignment of the cage isomers. Electrochemical gaps suggest that both Th@C2v(9)-C82 and Th@C2(5)-C82 possess a stable closed-shell electronic structure. The computational results further confirm that Th@C2v(9)-C82 and Th@C2(5)-C82 exhibit a unique four-electron charge transfer from the metal to the carbon cage and are among the most abundant isomers of Th@C82.

Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) regulates acetate- and ß-hydroxybutyrate-induced milk fat synthesis by increasing FASN expression in mammary epithelial cells of dairy cows.

Increasing acetate and ß-hydroxybutyrate (BHB) supply to lactating cows will increase milk fat synthesis. However, the underlying molecular mechanism remains largely unknown. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid droplet-associated protein that promotes intracellular triacylglycerol accumulation. In the present study, using gene overexpression and knockdown, we detected the contributions of CIDEC on milk fat synthesis in mammary epithelial cells of dairy cows in the presence of acetate and BHB. The results showed that knockdown of CIDEC decreased fatty acid synthase (FASN) expression and intracellular triacylglycerol content, whereas overexpression of CIDEC had the opposite effect. The transcription factor CCAAT/enhancer-binding protein ß (C/EBPß) regulates cell growth and differentiation in the mammary gland. We demonstrated that the FASN promoter had a canonical C/EBPß binding sequence. CEBPB overexpression upregulated FASN expression and milk fat synthesis, whereas CEBPB knockdown had the opposite effect. Moreover, knockdown of CEBPB attenuated the promoting effects of CIDEC on acetate- and BHB-induced FASN transcription. Taken together, our data showed that acetate and BHB induced FASN expression in mammary epithelial cells of dairy cows in a CIDEC-C/EBPß-dependent manner, which provides new insights into the understanding of the molecular events involved in milk fat synthesis.

Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ-HOMER1 involvement in HCC. To this end, we identified a binding site for miR-1322 via bioinformatics, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and dual-luciferase reporter assays providing evidence of a direct link between circ-HOMER1 and miR-1322. Similarly, the target gene of miR-1322 was investigated. Moreover, we determined the specific function of circ-HOMER1 in HCC with the aid of qRT-PCR based on patient clinical records, Cell Counting Kit-8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound-healing and transwell assays. Notably, circ-HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor-node-metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ-HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ-HOMER1 enhanced the inhibition of miR-1322 on CXCL6 in HCC. Furthermore, we found that circ-HOMER1 promoted HCC cell growth and aggressiveness by miR-1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.

Investigating E-Cigarette Particle Emissions and Human Airway Depositions under Various E-Cigarette-Use Conditions.

E-cigarette use is dramatically increasing, particularly with adolescents. While the chemical composition of e-liquids and e-vapor is well characterized, the particle size distribution and the human airways deposition patterns of e-cigarette particles are understudied and poorly understood despite their likely contribution to adverse health effects from e-cigarette usage. In this study, we examined the impacts of e-cigarette device power, e-liquid composition, and vaping topography on e-cigarette particle sizes and their deposition in human airways. In addition, we observed that particle measurement conditions (dilution ratio, temperature, and humidity) significantly affect measured e-cigarette particle sizes. E-cigarette power output significantly increased particle count median diameters (CMD) from 174 ± 13 (particles generated under 6.4 W) to 236 ± 14 nm (particles generated under 31.1 W). E-cigarette particles generated from propylene glycol-based e-liquids (CMD = 145 ± 8 nm and mass median diameter [MMD] = 3.06 ± 0.17 µm) were smaller than those generated from vegetable glycerin-based e-liquids (CMD = 182 ± 9 nm and MMD = 3.37 ± 0.21 µm). Puff volume also impacted vapor particle size: CMD and MMD were 154 ± 11 nm and 3.50 ± 0.27 µm, 163 ± 6 nm and 3.35 ± 0.24 µm, and 146 ± 12 nm and 2.95 ± 0.14 µm, respectively, for 35, 90, and 170 mL puffs. Estimated e-cigarette particle mass deposition fractions in tracheobronchial and bronchoalveolar regions were 0.504-0.541 and 0.073-0.306, respectively. Interestingly, e-cigarette particles are smaller than the particles generated from cigarette smoking but have similar human airway deposition patterns.

Indoor Air Quality and Passive E-cigarette Aerosol Exposures in Vape-Shops.

INTRODUCTION: Direct emissions of nicotine and harmful chemicals from electronic cigarettes (e-cigarettes) have been intensively studied, but secondhand and thirdhand e-cigarette aerosol (THA) exposures in indoor environments are understudied. AIMS AND METHODS: Indoor CO2, NO2, particulate matter (PM2.5), aldehydes, and airborne nicotine were measured in five vape-shops to assess secondhand exposures. Nicotine and tobacco-specific nitrosamines were measured on vape-shop surfaces and materials (glass, paper, clothing, rubber, and fur ball) placed in the vape-shops (14 days) to study thirdhand exposures. RESULTS: Airborne PM2.5, formaldehyde, acetaldehyde, and nicotine concentrations during shop opening hours were 21, 3.3, 4.0, and 3.8 times higher than the levels during shop closing hours, respectively. PM2.5 concentrations were correlated with the number of e-cigarette users present in vape-shops (ρ = 0.366-0.761, p < .001). Surface nicotine, 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were also detected at levels of 223.6 ± 313.2 µg/m2, 4.78 ± 11.8 ng/m2, and 44.8 ± 102.3 ng/m2, respectively. Substantial amounts of nicotine (up to 2073 µg/m2) deposited on the materials placed within the vape-shops, and NNA (up to 474.4 ng/m2) and NNK (up to 184.0 ng/m2) were also formed on these materials. The deposited nicotine concentrations were strongly correlated with the median number of active vapers present in a vape-shop per hour (ρ = 0.894-0.949, p = .04-.051). NNK levels on the material surfaces were significantly associated with surface nicotine levels (ρ=0.645, p = .037). CONCLUSIONS: Indoor vaping leads to secondhand and THA exposures. Thirdhand exposures induced by e-cigarette vaping are comparable or higher than that induced by cigarette smoking. Long-term studies in various microenvironments are needed to improve our understanding of secondhand and THA exposures. IMPLICATIONS: This study adds new convincing evidence that e-cigarette vaping can cause secondhand and THA exposures. Our findings can inform Occupational Safety and Health Administration, state authorities, and other government agencies regarding indoor air policies related to e-cigarette use, particularly in vape-shops. There is an urgent need to ensure that vape-shops maintain suitable ventilation systems and cleaning practices to protect customers, employees, and bystanders. Our study also demonstrates that nicotine can deposit or be adsorbed on baby's clothes and toys, and that tobacco-specific nitrosamines can form and retain on baby's clothes, highlighting children's exposure to environmental e-cigarette aerosol and THA at home is of a particular concern.

Urban airborne particle exposure impairs human lung and blood Mycobacterium tuberculosis immunity.

RATIONALE: Associations between urban (outdoor) airborne particulate matter (PM) exposure and TB and potential biological mechanisms are poorly explored. OBJECTIVES: To examine whether in vivo exposure to urban outdoor PM in Mexico City and in vitro exposure to urban outdoor PM2.5 (< 2.5 µm median aerodynamic diameter) alters human host immune cell responses to Mycobacterium tuberculosis. METHODS: Cellular toxicity (flow cytometry, proliferation assay (MTS assay)), M. tuberculosis and PM2.5 phagocytosis (microscopy), cytokine-producing cells (Enzyme-linked immune absorbent spot (ELISPOT)), and signalling pathway markers (western blot) were examined in bronchoalveolar cells (BAC) and peripheral blood mononuclear cells (PBMC) from healthy, non-smoking, residents of Mexico City (n=35; 13 female, 22 male). In vivo-acquired PM burden in alveolar macrophages (AM) was measured by digital image analysis. MEASUREMENTS AND MAIN RESULTS: In vitro exposure of AM to PM2.5 did not affect M. tuberculosis phagocytosis. High in vivo-acquired AM PM burden reduced constitutive, M. tuberculosis and PM-induced interleukin-1ß production in freshly isolated BAC but not in autologous PBMC while it reduced constitutive production of tumour necrosis factor-alpha in both BAC and PBMC. Further, PM burden was positively correlated with constitutive, PM, M. tuberculosis and purified protein derivative (PPD)-induced interferon gamma (IFN-γ) in BAC, and negatively correlated with PPD-induced IFN-γ in PBMC. CONCLUSIONS: Inhalation exposure to urban air pollution PM impairs important components of the protective human lung and systemic immune response against M. tuberculosis. PM load in AM is correlated with altered M. tuberculosis-induced cytokine production in the lung and systemic compartments. Chronic PM exposure with high constitutive expression of proinflammatory cytokines results in relative cellular unresponsiveness.