Fluvoxamine alleviates bleomycin-induced lung fibrosis via regulating the cGAS-STING pathway.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9-5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-ß1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.

SLAM and 3D Semantic Reconstruction Based on the Fusion of Lidar and Monocular Vision.

Monocular camera and Lidar are the two most commonly used sensors in unmanned vehicles. Combining the advantages of the two is the current research focus of SLAM and semantic analysis. In this paper, we propose an improved SLAM and semantic reconstruction method based on the fusion of Lidar and monocular vision. We fuse the semantic image with the low-resolution 3D Lidar point clouds and generate dense semantic depth maps. Through visual odometry, ORB feature points with depth information are selected to improve positioning accuracy. Our method uses parallel threads to aggregate 3D semantic point clouds while positioning the unmanned vehicle. Experiments are conducted on the public CityScapes and KITTI Visual Odometry datasets, and the results show that compared with the ORB-SLAM2 and DynaSLAM, our positioning error is approximately reduced by 87%; compared with the DEMO and DVL-SLAM, our positioning accuracy improves in most sequences. Our 3D reconstruction quality is better than DynSLAM and contains semantic information. The proposed method has engineering application value in the unmanned vehicles field.

N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation.

Psoriasis is an incurable autoimmune disease that affects 2-3% of the world's population. Limited understanding of its pathogenesis hinders the development of therapies for the disease. Herein, we reported that N-acylethanolamine acid amidase (NAAA), a cysteine enzyme that catalyzes the hydrolysis of fatty acid ethanolamides (FAEs), was upregulated in psoriasis patients and imiquimod (IMQ)-induced mouse model of psoriasis. The upregulated NAAA contributes to the progression of psoriasis via enhancing dendritic cell (DCs) maturation. Transgenic expression of NAAA in mice accelerated the development of psoriasis, whereas genetic ablation of NAAA or local administration of NAAA inhibitor F96 ameliorated psoriasis. NAAA expressed in dendritic cells (DCs), but not in macrophages, T cells, or keratinocytes plays a critical role in psoriasis development. In addition, the results showed that NAAA degrades palmitoylethanolamide (PEA) and reduces PEA-PPARα-mediated dissociation of NF-κB p65 from Sirtuin 1 (SIRT1), subsequently, repressing the acetylation of p65 and down-regulating IL10 production. The decreased IL10 then leads to the maturation of DCs, thus promoting the development of psoriasis. These results provide new insights into the pathophysiological mechanism of psoriasis and identify NAAA as a novel target for the treatment of psoriasis.

Diverse phylogenomic datasets uncover a concordant scenario of laurasiatherian interordinal relationships.

Resolving the interordinal relationships in the mammalian superorder Laurasiatheria has been among the most intractable problems in higher-level mammalian systematics, with many conflicting hypotheses having been proposed. The present study collected three different sources of genome-scale data with comprehensive taxon sampling of laurasiatherian species, including two protein-coding datasets (4,186 protein-coding genes for an amino acid dataset comprising 2,761,247 amino acid residues and a nucleotide dataset comprising 5,516,340 nucleotides from 1st and 2nd codon positions), an intronic dataset (1,210 introns comprising 1,162,723 nucleotides) and an ultraconserved elements (UCEs) dataset (1,246 UCEs comprising 1,946,472 nucleotides) from 40 species representing all six laurasiatherian orders and 7 non-laurasiatherian outgroups. Remarkably, phylogenetic trees reconstructed with the four datasets using different tree-building methods (RAxML, FastTree, ASTRAL and MP-EST) all supported the relationship (Eulipotyphla, (Chiroptera, ((Carnivora, Pholidota), (Cetartiodactyla, Perissodactyla)))). We find a resolution of interordinal relationships of Laurasiatheria among all types of markers used in the present study, and the likelihood ratio tests for tree comparisons confirmed that the present tree topology is the optimal hypothesis compared to other examined hypotheses. Jackknifing subsampling analyses demonstrate that the results of laurasiatherian tree reconstruction varied with the number of loci and ordinal representatives used, which are likely the two main contributors to phylogenetic disagreements of Laurasiatheria seen in previous studies. Our study provides significant insight into laurasiatherian evolution, and moreover, an important methodological strategy and reference for resolving phylogenies of adaptive radiation, which have been a long-standing challenge in the field of phylogenetics.

Key factors influencing the TCM nomenclature in international standards.

Amid the globalization of traditional Chinese medicine (TCM), the English translation of related texts is in full swing. Several representative international organizations in fields regarding standardization and healthcare, one after another, have published a series of international standards for TCM nomenclature. With these efforts, the internationalization of TCM has been dramatically advanced. When selecting parallel texts for reference, translators need to be aware of key factors influencing the English translation of TCM terms in international standards, including the distinctive characteristics of this discipline and relevant influences of international standard makers. In this way, proper standards and reasonable English expression can be chosen for specific terms, thus stimulating the effective use of TCM nomenclature with consensus.

Molecular cloning of complement component C3 gene from pearl mussel, Hyriopsis cumingii and analysis of the gene expression in response to tissue transplantation.

Complement component C3 is well recognized as the central mediator of complement system, whose activation is responsible for the immune surveillance and elimination of non-self-antigens. In this study, C3 gene (HcC3) from a pearl making mussel, Hyriopsis cumingii, was successfully identified. The putative HcC3 possessed the canonical domains and highly conserved functional residues of C3 family members. In phylogenetic analysis, HcC3 was also clustered into C3 subfamily and separated from α2 macroglobulin clade. HcC3 gene was constitutively expressed in a wide range of tissues of pearl mussels, among which the immune-related tissues like hemocytes got highest expression. After allograft surgery of mantle tissues for aquaculture pearl production, the gene expression of HcC3 exhibited a rapid upregulation on day 1, dropped back on day 3, peaked the value on day 7, and restored to the level similar to control samples on day 14 after mantle allograft. The biphasic expression within the two weeks post the surgery suggests the important roles for HcC3 in alloimmune responses and an intricate complement activation mechanism in mollusks during tissue allograft.

Resveratrol Suppresses the Growth and Enhances Retinoic Acid Sensitivity of Anaplastic Thyroid Cancer Cells.

Anaplastic thyroid cancer (ATC) is a highly lethal undifferentiated malignancy without reliable therapies. Retinoic acid (RA) has been employed to promote redifferentiation of thyroid cancers by increasing their I131 uptake and radio-sensitivity, but its effect(s) on ATCs has not yet been ascertained. Likewise, resveratrol induces cancer redifferentiation but, also in this case, its effects on ATCs remain unknown. These issues have been addresses in the current study using three human ATC cell lines (THJ-11T, THJ-16T, and THJ-21T) through multiple experimental approaches. The results reveal that RA exerts a small inhibitory effect on these cell lines. In comparison with normally cultured cells, the total cell number in resveratrol-treated THJ-16T and THJ-21T cultures significantly decreased (p < 0.05), and this effect was accompanied by reduced Cyclin D1 immuno-labeling, increased apoptotic fractions, and distinct caspase-3 activation. Resveratrol failed to inhibit growth but enhanced RA sensitivity of THJ-11T cells, suppressed peroxisome proliferator-activated receptor-ß/δ (PPAR-ß/δ), and upregulated cellular retinoic acid-binding protein 2 (CRABP2) and retinoic acid receptor beta (RAR-ß) expression. Increased thyroglobulin (Tg) and E-cadherin levels and appearance of membranous E-cadherin were evidenced in resveratrol-treated THJ-11T cells. Our results demonstrate for the first time: (1) the therapeutic value of resveratrol by itself or in combination with RA in the management of ATCs, (2) the capacity of resveratrol to overcome RA resistance in ATC cells by reprogramming CRABP2/RAR- and fatty acid-binding protein 5 (FABP5)/PPAR-ß/δ-mediated RA signaling, and (3) the redifferentiating potential of resveratrol in ATC cells.

Assessment of aquifer specific vulnerability to total nitrate contamination using ensemble learning and geochemical evidence.

Henan Province's plain area is the granary of China, yet its regional aquifer is being polluted by industrial wastewater, agricultural pesticide, fertilizer and domestic wastewater. In order to safeguard the security of food and drinking water, and in response to the problem of low prediction accuracy caused by the lack of samples and unevenly distributed groundwater monitoring data, we propose a new way to predict the aquifer vulnerability in large areas by rich small-scale data, so as to identify the pollution risks and to address the issue of sample shortage. In small regions with abundant nitrate data, we employed a Random Forest model to screen key impact indicators, using them as features and nitrate-N concentration as the target variable. Consequently, we established six machine learning prediction models, and then selected the best bagging model (R2 = 0.86) to predict the vulnerability of aquifers in larger regions lacking nitrate data. The predicted results showed that highly vulnerable areas accounted for 20 %, which were mainly affected by aquifer thickness (65.91 %). High nitrate-N concentration implies serious aquifer contamination. Therefore, a long series of groundwater nitrate-N concentration monitoring data in a large scale, the trend and slope of nitrate-N concentration showed a significant correlation with the model prediction results (Spearman's correlation coefficients are 0.75 and 0.58). This study can help identify the risk of aquifer contamination, solve the problem of sample shortage in large areas, thus contributing to the security of food and drinking water.

Disproportional erosion of the middle-lower Yangtze River following the operation of the Three Gorges Dam.

The operation of the Three Gorges Dam (TGD) modifies downstream flow and sediment regimes, triggering disproportional fluvial responses at different distances downstream. However, our understanding of the downstream geomorphic changes in the middle-lower Yangtze River remains incomplete due to the complexity of the river responses across temporal and spatial scales. Here, we leverage data on discharge, suspended sediment concentration (SSC), riverbed grain size, cross-sectional profiles and high-resolution channel bathymetric maps at different locations downstream of the TGD to investigate geomorphic responses. The results show that the magnitude of fluvial erosion decreases downstream, with the Yichang-Luoshan Reach (the first ~500 km downstream) experiencing the most severe erosion in 2003-2020 (~9.05 × 104 t/km/yr). Local changes in riverbed morphology include channel bar erosion, channel incision (~0.43 m/yr in CS1 near the dam site over 2002-2019), riverbank retreat and bed material coarsening (an increase in D50 from 0.175 to 43.1 mm at Yichang station from 2002 to 2017). Such marked erosion is caused by the sharply reduced SSC in the dominant discharge range (10,000-30,000 m3/s) and the extended duration of this dominant discharge range. The sediment erosive magnitude in the Luoshan-Datong Reach is relatively small (3.85 × 104 t/km/yr) in 2002-2020. The Luoshan-Hukou Reach (~500-1000 km downstream) exhibits moderate channel incision, minor bed material coarsening and moderate mid-channel bar lateral erosion. The Hukou-Datong Reach (below 1000 km downstream) experienced minor geomorphic change without significant evidence of bed material coarsening. The relatively small impact of the TGD on the lower reach from Luoshan to Datong can be mainly attributed to the progressive SSC recovery along the river induced by upstream channel erosion providing sediment replenishment. These findings have significant implications for estimating geomorphic changes in response to upstream damming and thus could inform better river management and ecological assessment in other similar alluvial rivers.

Conductive carrier promotes synchronous biofilm formation and granulation of anammox bacteria.

The extracellular electron transfer capability of some anaerobic ammonium oxidation (anammox) bacteria was confirmed in recent years. However, the effect of conductive carriers on the synchronous formation of anammox biofilm and granules is rarely reported. Anammox biofilm and granules with compact and stable structures accelerate the initiation and enhance the stability of the anammox process. In this study, we found that the conductive carbon fiber brush (CB) carrier promoted synchronous biofilm formation and granulation of anammox bacteria in the internal circulation immobilized blanket (ICIB) reactor. Compared with polyurethane sponge and zeolite carrier, the ICIB reactor packed with CB carrier can be operated under the highest total nitrogen loading rate of 6.53 kg-N/(m3·d) and maintain the effluents NH4+-N and NO2--N at less than 1 mM. The volatile suspended solids concentration in the ICIB reactor packed with conductive carrier increased from 5.17 ± 0.40 g/L of inoculum sludge to 24.24 ± 1.20 g/L of biofilm, and the average particle size of granules increased from 222.09 µm to 879.80 µm in 150 days. Fluorescence in situ hybridization analysis showed that anammox bacteria prevailed in the biofilm and granules. The analysis of extracellular polymeric substances indicated that protein and humic acid-like substances played an important role in the formation of anammox biofilm and granules. Microbiome analysis showed that the relative abundance of Candidatus Jettenia was increased from 0.18% to 38.15% in the biofilm from CB carrier during start-up stage. This study provides a strategy for rapid anammox biofilm and granules enrichment and carrier selection of anammox process.

Polymer/Ordered mesoporous carbon nanocomposite platelets as superior sensing materials for gas detection with surface acoustic wave devices.

We have prepared nanocomposites of polymers and platelet CMK-5-like carbon and have demonstrated their superior performance for gravimetric gas detection. The zirconium-containing platelet SBA-15 was used as hard template to prepare CMK-5-like carbon, which was then applied as a lightweight and high-surface-area scaffold for the growth of polymers by radical polymerization. Mesoporous nanocomposites composed of four different polymers were used as sensing materials for surface acoustic wave devices to detect ppm-level ammonia gas. The sensors showed much better sensitivity and reversibility than those coated with dense polymer films, and the sensor array could still generate a characteristic pattern for the analyte with a concentration of 16 ppm. The results show that the nanocomposite sensing materials are promising for highly sensitive gravimetric-type electronic nose applications.

Inactivation of PDH can Reduce Anaplastic Thyroid Cancer Cells' Sensitivity to Artemisinin.

BACKGROUND: Anaplastic Thyroid Cancer (ATC) is a rare subtype of thyroid tumors with a high mortality rate. Targeted therapies against ATC are ineffective and mostly transient. Artemisinin has shown excellent anti-tumor activity in several cancers, but its effects on ATC are still unknown. OBJECTIVE: To evaluate the effects of artemisinin on ATC cells and assess the mechanism underlying drug resistance. METHODS: The viability and proliferation rates of the artemisinin-treated CAL-62 and BHT-101 cells were analyzed by MTT and EdU incorporation assays. The protein expression levels were determined by Tandem Mass Tag (TMT) labeling quantitative proteomics and western blotting. RESULTS: Artemisinin treatment significantly decreased the expression levels of COX2 and COX7A2 and increased that of COX14, YEM1l1, ALAS1, and OAT after 48h. In addition, FTL was upregulated in the CAL-62 cells and downregulated in BHT-101 cells. The CAL-62 cells showed transient and reversible resistance to artemisinin, which was correlated to time-dependent changes in HIF1α, PDK1, and PDHA levels. CONCLUSION: Artemisinin targets the mitochondrial respiratory chain proteins in ATC cells. CAL-62 cells show transient resistance to artemisinin via PDH downregulation, indicating that PDH activation may enhance the cytotoxic effects of artemisinin on ATC cells.

Anticancer effects of natural phytochemicals in anaplastic thyroid cancer (Review).

Anaplastic thyroid cancer (ATC) is an aggressive and lethal malignancy having a dismal prognosis. Phytochemicals are bioactive components obtained from plants that have been proven useful to treat numerous diseases. Phytochemicals are also an important source of novel anticancer drugs and an important area of research due to the numerous available candidates that can potentially treat cancers. This review discusses naturally occurring phytochemicals and their derivatives that show promising anticancer effects in anaplastic thyroid cancer. Anticancer effects include cell growth inhibition, induction of apoptosis, promoting cell cycle arrest, suppressing angiogenesis, modulating autophagy, and increasing the production of reactive oxygen species. Phytochemicals are not only prospective candidates in the therapy of anaplastic thyroid cancer but also exhibit potential as adjuvants to improve the anticancer effects of other drugs. Although some phytochemicals have excellent anticancer properties, drug resistance observed during the use of resveratrol and artemisinin in different anaplastic thyroid cancer cell lines is still a problem. Anaplastic thyroid cancer cells have several biological, clinical, and drug­resistance features that differ from differentiated thyroid cancer cells. Phytochemicals such as resveratrol and quercetin exhibit different biological effects in anaplastic thyroid cancer and differentiated thyroid cancer. Tumor cells depend on increased aerobic glycolysis by mitochondrial oxidative phosphorylation to provide energy for their rapid growth, invasiveness, and drug resistance. Phytochemicals can alter signaling cascades, modulate the metabolic properties of cancer cells, and influence the mitochondrial membrane potential of anaplastic thyroid cancer cells. These findings enrich our knowledge of the anticancer effects of phytochemicals and highlight alternative therapies to prevent drug resistance in anaplastic thyroid cancer.

Preparation and Properties of Highly Elastic, Lightweight, and Thermally Insulating SiO2 Fibrous Porous Materials.

Fibrous porous materials are one of the most commonly used high-temperature insulation materials because of their high porosity and low thermal conductivity. Due to their wide applications in the aerospace and energy industries, the investigation of high-elastic thermally insulating porous materials has attracted increasing attention. In order to improve the elasticity of fibrous porous materials, quartz fibers with high aspect ratio were used as matrix, sodium hexametaphosphate (SHMP) was selected as dispersant. We innovatively reported that a unique three-dimensional skeleton structure was constructed by adjusting the dispersion of fibers in the slurry, and the lightweight, thermal insulating and elastic SiO2 fibrous porous material was then prepared by the compression molding method. The characterization results of zeta potential and absorbance showed that the addition of SHMP was an effective method to enhance the dispersibility of quartz fibers in the slurry. SiO2 fibrous porous materials with 0.4 wt% SHMP content exhibited an ideal three-dimensional skeleton structure, which endowed the porous material with high porosity (89.39%), low density (0.04751 g/cm3), and low thermal conductivity (0.0356 W·m-1·K-1). The three-dimensional skeleton structure formed by overlapping fibers with high aspect ratios endowed the porous material with excellent elasticity. SiO2 fibrous porous materials with 0.4 wt% SHMP content could undergo large strains of 30% and achieved a resilience ratio of 81.69% under the 30th compression cycle. Moreover, after heat treatment at 800 °C, SiO2 fibrous porous materials also maintained good elasticity with a resilience ratio of more than 80%.

Pyrvinium pamoate can overcome artemisinin's resistance in anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid carcinoma is a highly lethal subtype of thyroid cancer without effective therapies. Drug resistance in anaplastic thyroid carcinoma poses a significant problem. Although artemisinin exerts antitumor effects, but its efficacy in anaplastic thyroid carcinoma is unknown. METHODS: We used RNA sequencing to identify differentially expressed genes. Next, we determined the cause of ART resistance by testing the expression and activity of ß-catenin, and enhanced ART activity with a WNT signaling inhibitor. RESULTS: Artemisinin suppressed the growth of BHT-101 but not human thyroid anaplastic carcinoma (CAL-62) cells. The mechanism of artemisinin resistance in CAL-62 was associated with the aberrant activation of WNT signaling. Pyrvinium pamoate, an inhibitor of WNT signaling, was used to overcome ART resistance in CAL-62 cells. The combination of artemisinin and pyrvinium pamoate suppressed the growth of CAL-62 cells and induced the apoptosis. CONCLUSIONS: Our study is the first to prove the efficacy of ART as monotherapy or in combination with PP in the management of anaplastic thyroid cancer, and that the inhibition of WNT signaling may overcome ART resistance.

Response of vegetation to submergence along Jingjiang Reach of the Yangtze River.

This work explores the changes in vegetation coverage and submergence time of floodplains along the middle and lower reaches of the Yangtze River (i.e., the Jingjiang River) and the relations between them. As the Three Gorges Dam has been operating for more than 10 years, the original vegetative environment has been greatly altered in this region. The two main aspects of these changes were discovered by analyzing year-end image data from remote sensing satellites using a dimidiate pixel model, based on the normalized difference vegetation index, and by calculating water level and topographic data over a distance of 360 km from 2003-2015. Given that the channels had adjusted laterally, thus exhibiting deeper and broader geometries due to the Three Gorges Dam, 11 floodplains were classified into three groups with distinctive features. The evidence shows that, the floodplains with high elevation have formed steady vegetation areas and could hardly be affected by runoff and usually occupied by humans. The low elevation group has not met the minimal threshold of submerging time for vegetation growth, and no plants were observed so far. Based on the facts summed up from the floodplains with variable elevation, days needed to spot vegetation ranges from 70 to 120 days which happened typically near 2006 and between 2008 and 2010, respectively, and a negative correlation was detected between submergence time and vegetation coverage within a certain range. Thus, floods optimized by the Three Gorges Dam have directly influenced plant growth in the floodplains and may also affect our ability to manage certain types of large floods. Our conclusions may provide a basis for establishing flood criteria to manage the floodplain vegetation and evaluating possible increases in resistance caused by high-flow flooding when these floodplains are submerged.

Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFß signaling through PPARα.

Postoperative adhesions and scarring are the particular complication after strabismus surgery, for which there is currently no comprehensive treatment available. Preventing inflammation and fibrosis in the extraocular muscle are crucial for treatment of postoperative adhesions. In the present study, we found that administration of palmitoylethanolamide (PEA) attenuated postoperative inflammation and fibroproliferation through activating peroxisome proliferator-activated receptor α (PPARα), thus prevented scar formation. Inhibition of PEA degradation by N-Acylethanolamine acid amidase (NAAA) inhibitor F96 led to the same pharmacological results. PPARα activation suppressed both canonical and non-canonical TGFß signaling. Mechanistically, we found that PPARα directly bound to TGFß-activated kinase 1 (TAK1), thus preventing its hyperphosphorylation and the activation of downstream p38 and JNK1/2 signaling. Taken together, current study suggested that PEA could be a novel therapeutic approach for postoperative adhesions after strabismus surgery.

NAAA inhibitor F96 attenuates BBB disruption and secondary injury after traumatic brain injury (TBI).

Traumatic brain injury (TBI) is a leading cause of death worldwide, for which there is currently no comprehensive treatment available. Preventing blood-brain barrier (BBB) disruption is crucial for TBI treatment. N-acylethanolamine acid amidase (NAAA)-regulated palmitoylethanolamide (PEA) signaling play an important role in the control of inflammation. However, the role of NAAA in BBB dysfunction following TBI remains unclear. In the present study, we found that TBI induces the increase of PEA levels in the injured cortex, which prevent the disruption of BBB after TBI. TBI also induces the infiltration of NAAA-contained neutrophils, increasing the contribution of NAAA to the PEA degradation. Neutrophil-derived NAAA weakens PEA/PPARα-mediated BBB protective effects after TBI, facilitates the accumulation of immune cells, leading to secondary expansion of tissue injury. Inactivation of NAAA increased PEA levels in injured site, prevents early BBB damage and improves secondary injury, thereby eliciting long-term functional improvements after TBI. This study identified a new role of NAAA in TBI, suggesting that NAAA is a new important target for BBB dysfunction related CNS diseases.

Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses.

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.