Electron-Redistributed NiCo@NiFe-LDH Core-Shell Heterostructure for Significantly Enhancing Electrochemical Water Splitting.

Layered double hydroxides (LDHs) are some of the most promising precursors for the development of economically stable and efficient electrocatalysts for water splitting. An effective strategy for designing excellent performance electrocatalysts is to assemble core-shell heterostructures with a tunable electronic structure. In this work, three core-shell heterostructure electrocatalysts (NiCo@NiFe-LDH100/150/200) are developed by a simple hydrothermal and subsequent electrodeposition method on Ni foam. Among them, NiCo@NiFe-LDH150/NF exhibits the best oxygen evolution reaction electrocatalytic activity and long-term stability with a low overpotential of 197 mV to deliver a current density of 10 mA cm-2. In addition, an efficient and stable alkaline electrolytic cell with NiCo@NiFe-LDH150/NF both as the cathode and anode achieves a voltage of 1.66 V at a current density of 10 mA cm-2 and realization of ultralong stability at current densities of 20 and 200 mA cm-2 for 200 h. Density functional theory calculations reveal the strong electron interaction at the heterogeneous interface of the NiCo@NiFe-LDH150/NF core-shell structure, which effectively improves the intrinsic electron conductivity and ion diffusion kinetics and makes an important contribution to the electrocatalytic performance of the material. This work provides a new idea for the selection of materials for electrochemical water splitting by the construction of heterojunction interfaces.

MOF-Derived CoSe2@NiFeOOH Arrays for Efficient Oxygen Evolution Reaction.

Water electrolysis is a compelling method for the production of environmentally friendly hydrogen, minimizing carbon emissions. The electrolysis of water heavily relies on an effective and steady oxygen evolution reaction (OER) taking place at the anode. Herein, we introduce a highly promising catalyst for OER called CoSe2@NiFeOOH arrays, which are supported on nickel foam. This catalyst, referred to as CoSe2@NiFeOOH/NF, is fabricated through a two-step process involving the selenidation of a Co-based porous metal organic framework and subsequent electrochemical deposition on nickel foam. The CoSe2@NiFeOOH/NF catalyst demonstrates outstanding activity for the OER in an alkaline electrolyte. It exhibits a low overpotential (η) of 254 mV at 100 mA cm-2, a small Tafel slope of 73 mV dec-1, and excellent high stability. The good performance of CoSe2@NiFeOOH/NF can be attributed to the combination of the high conductivity of the inner layer and the synergistic effect between CoSe2 and NiFeOOH. This study offers an effective method for the fabrication of highly efficient catalysts for an OER.

A quaternary heterojunction nanoflower for significantly enhanced electrochemical water splitting.

Designing highly-efficient, cost-effective, and stable electrocatalysts for water splitting is essential to producing green hydrogen. In this work, a nanoflower quaternary heterostructured Ni(NO3)2(OH)4/Ni(OH)2/Ni3S2/NiFe-LDH electrocatalyst is successfully synthesized by two-step hydrothermal reactions. The sulfur in the electrocatalyst induces higher valence state metal atoms as active sites to accelerate the formation of O2. As expected, benefiting from the unique structural features and solid electronic interactions, Ni(NO3)2(OH)4/Ni(OH)2/Ni3S2/NiFe-LDH exhibits remarkable oxygen evolution reaction performance with a low overpotential of 223 mV at a current density of 100 mA cm-2, a slight Tafel slope of 65.4 mV dec-1, and outstanding stability in alkaline media. Attractively, using Ni(NO3)2(OH)4/Ni(OH)2/Ni3S2/NiFe-LDH as both a cathode and an anode, the alkaline electrolyzer delivers a current density of 10 mA cm-2 only at a cell voltage of 1.67 V, accompanied by superior durability. This work provides a facile method for the rational design of high-performance quaternary electrocatalysts.

MOF-Derived Iron-Cobalt Bimetallic Selenides for Water Electrolysis with High-Efficiency Oxygen Evolution Reaction.

Highly active and stable oxygen evolution reaction (OER) electrocatalysts for water electrolysis are currently in high demand. Herein, a rationally designed three-dimensional (3D) CoFe selenide porous array (Fe-CoSe PA) is synthesized through ion exchange from zeolitic imidazolate framework-L (ZIF-L) nanoarray, followed by a facile selenization under hydrothermal conditions for OER electrocatalysis. During the OER process, the surface of Fe-CoSe PA is rapidly oxidized to CoFe oxides/hydroxides, which prevents the inner layer from being oxidized. Benefiting from the high porosity, abundant active sites, and the high conductivity of inner Fe-CoSe, Fe-CoSe PA exhibits excellent OER performance, with an overpotential of 285 mV at a current density of 10 mA cm-2, and a small Tafel slope of 68 mV dec-1, as well as high stability under 50 h of continuous testing. The present work could provide a facile route for fabricating 3D porous selenides for highly efficient OER catalysis.

Effects of Circ_0109046 Regulating Mir-338-3p on the Malignant Behavior of A2780 Cells.

Objective: The objective is to explore the action and mechanism of circ_0109046 on the malignant phenotypes of ovarian cancer cells. Methods: Circ_0109046 and miR-338-3p expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In vitro assays were conducted to investigate the action of circ_0109046 and miR-338-3p on ovarian cancer cell growth and metastasis. Western blotting was utilized to investigate the contents of apoptosis-related markers. The binding between circ_0109046 and miR-338-3p was validated using dual-luciferase reporter assay. Results: Circ_0109046 was increased, while miR-338-3p content was decreased in ovarian cancer tissues. Deficiency of circ_0109046 or the upregulation of miR-338-3p was observed to weaken cell proliferative, migratory, and invasive abilities and elevated cell apoptosis rate in ovarian cancer. Circ_0109046 targetedly suppressed miR-338-3p. Down-regulation of miR-338-3p was able to reverse the repressing impacts of circ_0109046 silencing on ovarian cancer growth and mobility. Conclusion: Circ_0109046 silencing impaired the proliferation, migration, and invasion of ovarian cancer cells through negatively regulating miR-338-3p in vitro, indicating the potential implication of circ_0109046 in ovarian cancer progression.

Assessing the Outbreak Risk of Epidemics Using Fuzzy Evidential Reasoning.

Epidemic diseases (EDs) present a significant but challenging risk endangering public health, evidenced by the outbreak of COVID-19. Compared to other risks affecting public health such as flooding, EDs attract little attention in terms of risk assessment in the current literature. It does not well respond to the high practical demand for advanced techniques capable of tackling ED risks. To bridge this gap, an adapted fuzzy evidence reasoning method is proposed to realize the quantitative analysis of ED outbreak risk assessment (EDRA) with high uncertainty in risk data. The novelty of this article lies in (1) taking the lead to establish the outbreak risk evaluation system of epidemics covering the whole epidemic developing process, (2) combining quantitative and qualitative analysis in the fields of epidemic risk evaluation, (3) collecting substantial first-hand data by reviewing transaction data and interviewing the frontier experts and policymakers from Chinese Centers for Disease Control and Chinese National Medical Products Administration. This work provides useful insights for the regulatory bodies to (1) understand the risk levels of different EDs in a quantitative manner and (2) the sensitivity of different EDs to the identified risk factors for their effective control. For instance, in the case study, we use real data to disclose that influenza has the highest breakout risk level in Beijing. The proposed method also provides a potential tool for evaluating the outbreak risk of COVID-19.

Kinesin Family Member C1 (KIFC1) Regulated by Centrosome Protein E (CENPE) Promotes Proliferation, Migration, and Epithelial-Mesenchymal Transition of Ovarian Cancer.

BACKGROUND Centrosome amplification is recognized as a hallmark of cancer. Kinesin family member C1 (KIFC1), a centrosome-clustering molecule, is essential for the viability of extra centrosome-bearing cancer cells and may be the basis for the progression of ovarian cancer. However, its biological function and mechanism in ovarian cancer have not yet been studied. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was performed to detect the levels of KIFC1 and centrosome protein E (CENPE). Further, cell viability was analyzed with CCK-8 assay, and immunofluorescence was used to measure the expression of Ki67 and PCNA. Cell migration was analyzed with wound healing and transwell assays. Western blot analysis was performed to measure the expression of proteins in ovarian cancer cells. The relationship between KIFC1 and CENPE was investigated by performing co-immunoprecipitation. RESULTS KIFC1 was upregulated in ovarian cancer cells, especially in SKOV3 cells. Additionally, we found that KIFC1 silencing in SKOV3 cells inhibited cell proliferation and downregulated the expression of Ki67 and PCNA. Further, the knockdown of KIFC1 suppressed cell migration and epithelial-mesenchymal transition (EMT) and regulated the expression of matrix metalloproteinase (MMP)2, MMP9, E-cadherin, N-cadherin, Snail, and ZEB1. Next, we found that KIFC1 bound to and positively regulated CENPE, a tumor promoter in certain human cancers. All the suppressive effects triggered by KIFC1 inhibition were reversed by CENPE overexpression. CONCLUSIONS KIFC1 contributed to cell proliferation, migration, and EMT via interacting with CENPE in ovarian cancer. KIFC1 might be a potential biomarker and therapeutic target in ovarian cancer patients.

UCHL3 promotes proliferation of colorectal cancer cells by regulating SOX12 via AKT/mTOR signaling pathway.

OBJECTIVE: The dysregulation of deubiquitinating enzymes is important in the development of many cancers, including colorectal cancer (CRC). However, the precise function and potential mode of action of the deubiquitinating enzyme UCHL3 in CRC progression are poorly elucidated. METHODS: The expression levels of UCHL3 in patient samples were analyzed by western blotting, real-time PCR and immunohistochemistry and its association with overall survival was analyzed using Kaplan-Meier method. Colony formation, CCK-8 and Transwell were used to examine the effects of UCHL3 knockdown or over-expression on CRC cells growth, invasion and migration. The functional effects of UCHL3 and SOX12 on tumor growth were further examined using xenograft tumor mouse models in vivo. RESULTS: Here, we found high expression of UCHL3 in CRC tissues which showed an association with the development of tumor and CRC patient survival. Studies conducted in vitro showed that UCHL3 overexpression facilitates proliferation, invasion, migration, and EMT (epithelial-mesenchymal transition) in cells of CRC, and a knockdown of UCHL3 had a reverse effect. Likewise, experiments conducted in vivo also showed enhanced tumor growth due to UCHL3 overexpression. In addition, UCHL3 was found regulates SOX12 expression in CRC cells. PI3K/AKT/mTOR pathway is required for UCHL3-mediated SOX12 expression. Mechanically, UCHL3 regulates SOX12 via AKT/mTOR signaling pathway and facilitated tumor progression. CONCLUSION: UCHL3 plays an oncogenic role through the AKT/mTOR/SOX12 axis and can be considered as a potential target for therapy and CRC prognostic biomarker.

IFN-α2b inhibits the ethanol enriched-HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx in liver.

Hepatitis B virus (HBV) is a major risk factor for liver diseases, in which HBV covalently closed circular DNA (cccDNA), as the genomic form that templates viral transcription, plays crucial roles in sustaining viral persistence. Clinically, the excessive ethanol intake accelerates the progression of liver diseases with HBV infection. Here, we supposed that ethanol might trigger HBV cccDNA in the liver. Interestingly, we observed that the ethanol remarkably elevated the levels of HBeAg, HBsAg, HBV DNA and cccDNA in HBV-expressing hepatoma cells. Mechanically, the ethanol increased the levels of HBx and MSL2 in vivo and in HBV-expressing HepG2 cells, but not in HBV-free HepG2 cells. Moreover, the down-regulation of MSL2 by small interference RNA could block the ethanol-promoted HBV cccDNA in HepG2.2.15 cells. As a commonly administered treatment for HBV, the effect of IFNα on ethanol-triggered HBV cccDNA remains poorly understood. Strikingly, we showed that the treatment with IFN-α2b inhibited the ethanol-promoted cccDNA through depressing MSL2 in the cells. Thus, we conclude that IFN-α2b inhibits the ethanol-enriched HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx. Our finding provides new insights into the mechanism by which IFN-α2b inhibits ethanol-enhanced HBV cccDNA. Therapeutically, IFNα may contribute to the cccDNA induced by ethanol in liver.

Exposure to deltamethrin in adolescent mice induced thyroid dysfunction and behavioral disorders.

Deltamethrin (DM) has become one of the most widely used insecticides in the world due to its low toxicity, high efficiency and low persistence in soil. However, it is still unknown whether DM exposure has any effects on the Hypothalamic-Pituitary-Thyroid (HPT) axis in adolescent mice. In this study, the open field test and circadian activity test showed that DM exposure increased activity. There was no significant difference between the groups in the light/dark box test and nest building test. Forced swimming test showed that after 6 and 12 mg kg-1 DM exposure 28 days, the immobility time was increased and the swimming time was reduced. After 6 mg kg-1 DM treatment, the thyroid stimulating hormone (TSH) content increased, and thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4) decreased. After exposure to 6 and 12 mg kg-1 DM, mRNA levels of HPT axis-related genes were destroyed. The histological examination showed that, the DM groups mice thyroid tissues appeared expanded thyroid follicles, scanty colloid and hyperplastic thyroid cells. Western blot results showed that the expression level of tyrosine hydroxylase (TH) protein decreased and the content of dopamine transporter (DAT) protein increased in DM treated mice striatum. Collectively, our results indicated that DM exposure could induce thyroid dysfunction and behavioral disorders in adolescent mice.

Encorafenib inhibits migration, induces cell cycle arrest and apoptosis in colorectal cancer cells.

Encorafenib, a new-generation BRAF inhibitor, has been approved by FDA for the treatment of melanoma in combination with binimetinib. However, the mechanism of the drug works in colorectal cancer (CRC) is still unclear. In this study, the suppression of growth of CRC cells by encorafenib was investigated. The effects of treatment of encorafenib on pathways linked to cancer were studied, and the effective inhibition of cell proliferation was documented. Our findings showed that cell migration was inhibited by encorafenib through a likely involvement of MPP and TIMP modulation. Furthermore, encorafenib treatment also induced cell cycle arrest. In addition, induction of apoptosis in CRC cells by elevating levels of PUMA. These observations indicate the potential therapeutic efficacy of encorafenib on CRC.

The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

Imaging-based amplitude laser beam shaping for material processing by 2D reflectivity tuning of a spatial light modulator.

We have demonstrated an imaging-based amplitude laser-beam-shaping technique for material processing by 2D reflectivity tuning of a spatial light modulator. Intensity masks with 256 gray levels were designed to shape the input laser beam in the outline profile and inside intensity distribution. Squared and circular flattop beam shapes were obtained at the diffractive near-field and then reconstructed at an image plane of an f-theta lens (f∼100 mm). The observed intensity distribution inside the beam-shaping geometry was much more even than using binary masks. The ablation footprint well matches the desired beam shape.

A comprehensive collection of systems biology data characterizing the host response to viral infection.

The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

Effect of early orthodontic force on periodontal healing after autotransplantation of permanent incisors in beagle dogs.

BACKGROUND: Masticatory stimulation during the healing period may promote periodontal ligament healing. The aim of the present study is to investigate the effect of orthodontic force on the periodontal healing of autotransplanted teeth. METHODS: A total of 30 teeth from four dogs were endodontically treated to prevent subsequent inflammatory root resorption. The teeth were atraumatically extracted and autotransplanted to the other side of the same jaw. A continuous 50-g orthodontic force was applied during the first, second, and fourth weeks after autotransplantation. After 8 weeks, the animals were sacrificed using vital perfusion fixation, and the teeth were histologically prepared and evaluated following the Andreasen method. RESULTS: The application of force in the first, second, and fourth weeks after autotransplantation resulted in a lower occurrence of ankylosis. The first- and second-week loading groups differed significantly from the control group (P <0.05); however, significantly more resorption and less complete healing were observed in the first-week loading group than in the other groups (P <0.05). CONCLUSION: The results of this study demonstrate that orthodontic force promotes periodontal ligament healing and that early force loading may prevent dentoalveolar ankylosis; however, a period of rest of ≥2 weeks is recommended for the autotransplants before loading.

Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk.

Therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) is a major complication of cancer treatment. We compared gene expression in CD34+ cells from patients who developed t-MDS/AML after autologous hematopoietic cell transplantation (aHCT) for lymphoma with controls who did not develop t-MDS/AML. We observed altered gene expression related to mitochondrial function, metabolism, and hematopoietic regulation in pre-aHCT samples from patients who subsequently developed t-MDS/AML. Progression to overt t-MDS/AML was associated with additional alterations in cell-cycle regulatory genes. An optimal 38-gene PBSC classifier accurately distinguished patients who did or did not develop t-MDS/AML in an independent group of patients. We conclude that genetic programs associated with t-MDS/AML are perturbed long before disease onset, and accurately identify patients at risk for this complication.

Differential microRNA expression and virulence of avian, 1918 reassortant, and reconstructed 1918 influenza A viruses.

Infections with highly pathogenic H5N1 avian (HPAI) and 1918 pandemic H1N1 influenza viruses cause uncontrolled local and systemic inflammation. The mechanism for this response is poorly understood, despite its importance as a determinant of virulence. Therefore we profiled cellular microRNAs of lung tissue from cynomolgus macaques (Macaca fascicularis) infected with a HPAI and a less pathogenic 1918 H1N1 reassortant virus to understand microRNA contribution to host response. We identified 23 microRNAs associated with the extreme virulence of HPAI, with expression patterns inversely correlated with that of predicted gene targets. Pathway analyses confirmed that these targets were associated with aberrant and uncontrolled inflammatory responses and increased cell death. Importantly, similar microRNAs were associated with lethal 1918 pandemic virus infections in mice. This study suggests that virulence of highly pathogenic influenza viruses may be mediated in part by cellular microRNA through dysregulation of genes critical to the inflammatory process.

MicroRNA expression and virulence in pandemic influenza virus-infected mice.

The worst known H1N1 influenza pandemic in history resulted in more than 20 million deaths in 1918 and 1919. Although the underlying mechanism causing the extreme virulence of the 1918 influenza virus is still obscure, our previous functional genomics analyses revealed a correlation between the lethality of the reconstructed 1918 influenza virus (r1918) in mice and a unique gene expression pattern associated with severe immune responses in the lungs. Lately, microRNAs have emerged as a class of crucial regulators for gene expression. To determine whether differential expression of cellular microRNAs plays a role in the host response to r1918 infection, we compared the lung cellular "microRNAome" of mice infected by r1918 virus with that of mice infected by a nonlethal seasonal influenza virus, A/Texas/36/91. We found that a group of microRNAs, including miR-200a and miR-223, were differentially expressed in response to influenza virus infection and that r1918 and A/Texas/36/91 infection induced distinct microRNA expression profiles. Moreover, we observed significant enrichment in the number of predicted cellular target mRNAs whose expression was inversely correlated with the expression of these microRNAs. Intriguingly, gene ontology analysis revealed that many of these mRNAs play roles in immune response and cell death pathways, which are known to be associated with the extreme virulence of r1918. This is the first demonstration that cellular gene expression patterns in influenza virus-infected mice may be attributed in part to microRNA regulation and that such regulation may be a contributing factor to the extreme virulence of the r1918.

Relationships between deficits in tissue mass and transcriptional programs after partial hepatectomy in mice.

Liver regeneration after two-thirds partial hepatectomy (2/3 PH) results in synchronized proliferation of hepatocytes and rapid restoration of liver mass. Understanding the mechanisms that regulate this process has both biological and clinical importance. Using cDNA microarray analysis, we investigated whether gene activation after 2/3 PH is specifically related to liver growth and hepatocyte proliferation. We generated gene expression profiles at 4, 12, 20, and 30 hours after 2/3 PH and compared them with profiles obtained at the same time points after 1/3 PH, a procedure that causes minimal DNA replication. Surprisingly, a significant number of genes whose expression is altered after 2/3 PH are similarly up- or down-regulated after 1/3 PH, particularly at 4 hours. We identified a number of genes and transcription factors that are more highly expressed ("preferential expression") after 2/3 PH and show that a shift in transcriptional programs in the regenerating liver occurs between 4 and 12 hours after 2/3 PH, a time at which the decision to replicate appears to be made. These results show that the liver responds to PH with massive changes of gene expression, even in the absence of DNA replication. We suggest that the changes in gene expression during the first 4 to 6 hours after 2/3 PH may induce chromatin remodeling and facilitate the binding of new sets of transcription factors required for DNA replication.

cDNA microarray analysis reveals fundamental differences in the expression profiles of primary human monocytes, monocyte-derived macrophages, and alveolar macrophages.

We report the systematic use of large-scale cDNA microarrays to study the gene expression profiles of primary human peripheral blood monocytes (MONO) in comparison with in vitro-differentiated, M-CSF-induced MONO-derived macrophages (MAC) and primary human alveolar MAC (AM), obtained by bronchoalveolar lavage from the lungs of normal volunteers. These studies revealed large-scale differences in the gene expression profile between both MAC types (MAC and AM) and MONO. In addition, large differences were observed in the gene expression profiles of the two MAC types. Specifically, 21% of genes on the array (2904 out of 13,582) were differentially expressed between AM and MONO, and 2229 out of 13,583 probes were differentially expressed between MAC and AM. Our expression data show remarkable differences in gene expression between different MAC subpopulations and emphasize the heterogeneity of different MAC populations. This study underscores the need to scrutinize models of MAC biology for relevance to specific disease processes.