Climate match is key to predict range expansion of the world's worst invasive terrestrial vertebrates.

Understanding the determinants of the range expansion of invasive alien species is crucial for developing effective prevention and control strategies. Nevertheless, we still lack a global picture of the potential factors influencing the invaded range expansion across taxonomic groups, especially for the world's worst invaders with high ecological and economic impacts. Here, by extensively collecting data on 363 distributional ranges of 19 of world's worst invasive terrestrial vertebrates across 135 invaded administrative jurisdictions, we observed remarkable variations in the range expansion across species and taxonomic groups. After controlling for taxonomic and geographic pseudoreplicates, model averaging analyses based on generalized additive mixed-effect models showed that species in invaded regions having climates more similar to those of their native ranges tended to undergo a larger range expansion. In addition, as proxies of propagule pressure and human-assisted transportation, the number of introduction events and the road network density were also important predictors facilitating the range expansion. Further variance partitioning analyses validated the predominant role of climate match in explaining the range expansion. Our study demonstrated that regions with similar climates to their native ranges could still be prioritized to prevent the spread of invasive species under the sustained global change.

Social media unveils the hidden but high magnitude of human-mediated biological invasions in China.

Humans are responsible for the release of many non-native animals into the wild. However, these releases occur randomly and are difficult to monitor. Here, using two of the worst invasive herpetofauna as model taxa, we applied an iEcology approach and found a high magnitude of human-mediated releases in China, suggesting this approach can be used to monitor introductions and advise management bodies in a timely manner.

Study on the mechanism of NLRP3 effect on the skeleton of de-ovalized mice.

Postmenopausal osteoporosis caused by estrogen deficiency affects millions of women worldwide. By influencing both osteoblast and osteoclast development, NOD-like receptor thermoprotein structural domain-associated protein 3 (NLRP3) is a key player in the etiology of osteoporosis (OP). The purpose of this research was to look into the mechanism of action of NLRP3 in osteoporosis caused by a lack of estrogen, highlighting that NLRP3 induces osteoblast pyroptosis and thus inflammatory responses in de-ovulated mice, thereby inhibiting osteogenic differentiation and participating in the development of osteoporosis. In de-ovulated mice, we found an enhanced inflammatory response and suppression of osteogenic activity. In vitro experiments, we found a significant increase in markers of cell pyroptosis and inflammatory responses and a significant decrease in markers of osteogenic differentiation in osteoblasts from de-ovulated mice. However, knockdown of the NLRP3 gene inhibited this cell pyroptosis and improved osteogenic differentiation of osteoblasts. Our findings indicate a potential therapeutic potential for the treatment of estrogen deficiency-induced osteoporosis by demonstrating the critical role that NLRP3 inflammatory vesicles and their downstream-mediated cellular pyroptosis play in bone differentiation.

Metal-polyphenol network coated magnetic hydroxyapatite for pH-activated MR imaging and drug delivery.

Engineered nanoparticles responsive to tumor microenvironment parameters such as pH have been developed as drug carriers and for magnetic resonance imaging (MRI) as contrast agents (CA). Nanoscale hydroxyapatite (HAP) has good biocompatibility and specific inhibition of tumor cells. However, the inherent tendency of nanoscale HAP to agglomerate and degrade under natural conditions has hindered its further application. To address this challenge, polyacrylic acid-coordinated Mn2+ and F- co-doped nanoscale HAP (MnxFHA-PAA) were developed for MRI and doxorubicin (DOX) loading. Moreover, the metal-polyphenol network (MPN) formed by ligating tannic acid (TA) and Fe3+ was successfully functionalized onto the surface of MnxFHA-PAA-DOX. The pH-sensitive MPN improves biocompatibility and therapeutic efficacy while preventing the premature release of DOX in a neutral environment. It was demonstrated that the mesoporous structure of MnxFHA-PAA@TA-Fe nanoparticles with good dispersion, high specific surface area and large pore size, which can reach more than 90 % encapsulation efficiency (EE) for DOX. MnxFHA-PAA-DOX@TA-Fe degrades at low pH and releases Mn2+ and DOX that are confined in the nanoparticles. Binding of Mn2+ to proteins leads to increased relaxation and enhanced MRI contrast. Such nanoparticles with sensitive pH responsiveness have great potential for tumor diagnosis and therapeutic synergy.

Preferred prey reduce species realized niche shift and improve range expansion prediction.

Many studies have detected realized climatic niche shifts during range changes; this is challenging the fundamental theory of the niche conservatism hypothesis (NCH) and the usefulness of the ecological niche model (ENM) for predicting the distributions of species in space and time by tracking environmental change. Biotic factors such as predatory interactions are important components of species realized niches but are generally difficult to quantify during NCH testing and ENM building. Identifying species' preferred prey may provide a unique opportunity to include trophic interactions in assessing the NCH and determine whether more precise ENM predictions are generated. In this study, we focused on a range-expanding predatory bird, the Asian openbill (Anastomus oscitans). The main prey of the Asian openbill include 136 snail species. We observed a realized climatic niche shift during the northward expansion of the Asian openbill by considering only climates; however, niche conservatism was detected after incorporating their preferred prey. ENMs including preferred snails also predicted the distributions of the Asian openbill better than climate-only models and models including nonpreferred snails or only habitat variables. The results of our study suggested the importance of incorporating preferred prey in evaluating the NCH and developing a framework for predicting the range shifts of both native and alien species in response to global climate change.

LncRNA SNHG7 Knockdown Aggravates Hepatic Ischemia-Reperfusion Injury and Promotes Apoptosis in Hemorrhagic Shock Pregnant Rats by Modulating miR-34a-5p/YWHAG Axis.

Hemorrhagic shock is a frequent threat to pregnant women, and blood transfusions can contribute to organ damage, including hepatic ischemia-reperfusion (HIR) injury. LncRNA SNHG7 (SNHG7) has been reported to exert an essential role in various diseases, while the effect of SNHG7 on HIR injury induced by hemorrhagic shock and reperfusion in pregnant rats is still unclear. In our study, we examined the function and mechanism of SNHG7 in the progression of HIR injury in pregnant rats. The results showed that SNHG7 expression was low in the hepatic tissues of pregnant rats after the hemorrhagic shock and reperfusion modeling. Knockdown of SNHG7 further aggravated hepatic injury, apoptosis, and oxidative stress induced by hemorrhagic shock and reperfusion during pregnancy. Additionally, SNHG7 was bound directly to miR-34a-5p, and miR-34a-5p inhibitors partially reversed the effect of SNHG7 silencing on models of hemorrhagic shock and reperfusion. Furthermore, YWHAG is a direct target of miR-34a-5p and is negatively regulated by miR-34a-5p mimics. Overexpression of YWHAG effectively eliminated the effect of SNHG7 knockdown on pregnant rats. In summary, this investigation proved that SNHG7 knockdown exacerbated HIR injury after hemorrhagic shock in pregnant rats, and reperfusion might by mediating miR-34a-5p/YWHAG axis, indicating that SNHG7 can serve as a target gene for the treatment of HIR injury caused by hemorrhagic shock and reperfusion during pregnancy.

Quantitative detection of captopril in urine by smartphone-assisted ratiometric fluorescence sensing platform.

Captopril (CP) is a widely used antihypertensive drug. In this study, a smartphone-assisted sensing platform on the basis of ratiometric fluorescent test strips was developed, which can accomplish visualization for the quantitative detection of captopril. Ratiometric fluorescent probe was constructed from carbon dots (CDs) and gold nanoclusters (Au NCs). After adding Cu2+ to fluorescent probe, Cu2+ can complex the amino and carboxyl groups on the surface of Au NCs and aggregate Au NCs, which will quench the fluorescence of Au NCs. Compared with amino and carboxyl groups, -SH in CP has a higher affinity for Cu2+ and can capture Cu2+ to restore Au NCs fluorescence. In this process, CDs remained essentially unchanged as background fluorescence. As CP concentration increased, the fluorescence color showed a distinct change from blue to purple to orange. Based on this principle, a sensing platform combining smartphone and fluorescent test strips was constructed to visualize the quantitative detection of CP by RGB values. Under optimal conditions, the wide linear range of CP detection for both fluorescence spectrometer and smartphone paper-based sensing platform was 0.25-50 µM. The limits of detection were as low as 76 nM and 101.3 nM, respectively. Furthermore, it was implemented successfully for the detection of CP in urine. The satisfactory recoveries were 96.0-103.3% and 92.0-108.0% for fluorescence spectrometer and smartphone platform, respectively. This smartphone-assisted platform provided a new approach for visual detection of CP, which showed its great potential in bioanalytical assays.

Biological invasions facilitate zoonotic disease emergences.

Outbreaks of zoonotic diseases are accelerating at an unprecedented rate in the current era of globalization, with substantial impacts on the global economy, public health, and sustainability. Alien species invasions have been hypothesized to be important to zoonotic diseases by introducing both existing and novel pathogens to invaded ranges. However, few studies have evaluated the generality of alien species facilitating zoonoses across multiple host and parasite taxa worldwide. Here, we simultaneously quantify the role of 795 established alien hosts on the 10,473 zoonosis events across the globe since the 14th century. We observe an average of ~5.9 zoonoses per alien zoonotic host. After accounting for species-, disease-, and geographic-level sampling biases, spatial autocorrelation, and the lack of independence of zoonosis events, we find that the number of zoonosis events increase with the richness of alien zoonotic hosts, both across space and through time. We also detect positive associations between the number of zoonosis events per unit space and climate change, land-use change, biodiversity loss, human population density, and PubMed citations. These findings suggest that alien host introductions have likely contributed to zoonosis emergences throughout recent history and that minimizing future zoonotic host species introductions could have global health benefits.

Screening and Demulsification Mechanism of Fluorinated Demulsifier Based on Molecular Dynamics Simulation.

In order to solve the problem of demulsification difficulties in Liaohe Oilfield, 24 kinds of demulsifiers were screened by using the interface generation energy (IFE) module in the molecular dynamics simulation software Materials Studio to determine the ability of demulsifier molecules to reduce the total energy of the oil-water interface after entering the oil-water interface. Neural network analysis (NNA) and genetic function approximation (GFA) were used as technical means to predict the demulsification effect of the Liaohe crude oil demulsifier. The simulation results show that the SDJ9927 demulsifier with ethylene oxide (EO) and propylene oxide (PO) values of 21 (EO) and 44 (PO) reduced the total energy and interfacial tension of the oil-water interface to the greatest extent, and the interfacial formation energy reached -640.48 Kcal/mol. NNA predicted that the water removal amount of the SDJ9927 demulsifier was 7.21 mL, with an overall error of less than 1.83. GFA predicted that the water removal amount of the SDJ9927 demulsifier was 7.41mL, with an overall error of less than 0.9. The predicted results are consistent with the experimental screening results. SDJ9927 had the highest water removal rate and the best demulsification effect. NNA and GFA had high correlation coefficients, and their R2s were 0.802 and 0.861, respectively. The higher R2 was, the more accurate the prediction accuracy was. Finally, the demulsification mechanism of the interfacial film breaking due to the collision of fluorinated polyether demulsifiers was studied. It was found that the carbon-fluorine chain had high surface activity and high stability, which could protect the carbon-carbon bond in the demulsifier molecules to ensure that there was no re-emulsion due to the stirring external force.

Production of Class II MHC Proteins in Lentiviral Vector-Transduced HEK-293T Cells for Tetramer Staining Reagents.

Class II major histocompatibility complex peptide (MHC-IIp) multimers are precisely engineered reagents used to detect T cells specific for antigens from pathogens, tumors, and self-proteins. While the related Class I MHC/peptide (MHC-Ip) multimers are usually produced from subunits expressed in E. coli, most Class II MHC alleles cannot be produced in bacteria, and this has contributed to the perception that MHC-IIp reagents are harder to produce. Herein, we present a robust constitutive expression system for soluble biotinylated MHC-IIp proteins that uses stable lentiviral vector-transduced derivatives of HEK-293T cells. The expression design includes allele-specific peptide ligands tethered to the amino-terminus of the MHC-II ß chain via a protease-cleavable linker. Following cleavage of the linker, HLA-DM is used to catalyze efficient peptide exchange, enabling high-throughput production of many distinct MHC-IIp complexes from a single production cell line. Peptide exchange is monitored using either of two label-free methods, native isoelectric focusing gel electrophoresis or matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of eluted peptides. Together, these methods produce MHC-IIp complexes that are highly homogeneous and that form the basis for excellent MHC-IIp multimer reagents. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Lentivirus production and expression line creation Support Protocol 1: Six-well assay for estimation of production cell line yield Support Protocol 2: Universal ELISA for quantifying proteins with fused leucine zippers and His-tags Basic Protocol 2: Cultures for production of Class II MHC proteins Basic Protocol 3: Purification of Class II MHC proteins by anti-leucine zipper affinity chromatography Alternate Protocol 1: IMAC purification of His-tagged Class II MHC Support Protocol 3: Protein concentration measurements and adjustments Support Protocol 4: Polishing purification by anion-exchange chromatography Support Protocol 5: Estimating biotinylation percentage by streptavidin precipitation Basic Protocol 4: Peptide exchange Basic Protocol 5: Analysis of peptide exchange by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry Alternate Protocol 2: Native isoelectric focusing to validate MHC-II peptide loading Basic Protocol 6: Multimerization Basic Protocol 7: Staining cells with Class II MHC tetramers.

Characterization of a new smog chamber for evaluating SAPRC gas-phase chemical mechanism.

A new state-of-the-art indoor smog chamber facility (CAPS-ZJU) has been constructed and characterized at Zhejiang University, which is designed for chemical mechanism evaluation under well-controlled conditions. A series of characterization experiments were performed to validate the well-established experimental protocols, including temperature variation pattern, light spectrum and equivalent intensity (JNO2), injection and mixing performance, as well as gases and particle wall loss. In addition, based on some characterization experiments, the auxiliary wall mechanism has been setup and examined. Fifty chamber experiments were performed across a broad range of experimental scenarios, and we demonstrated the ability to utilize these chamber data for evaluating SAPRC chemical mechanism. It was found that the SAPRC-11 can well predict the O3 formation and NO oxidation for almost all propene runs, with 6 hr Δ(O3 - NO) model error of -3% ± 7%, while the final O3 was underestimated by ~20% for isoprene experiments. As for toluene and p-xylene experiments, it was confirmed that SAPRC-11 has significant improvement on aromatic chemistry than earlier version of SAPRC-07, although the aromatic decay rate was still underestimated to some extent. The model sensitivity test has been carried out, and the most sensitive parameters identified are the initial concentrations of reactants and the light intensity as well as HONO offgasing rate and O3 wall loss rate. All of which demonstrated that CAPS-ZJU smog chamber could derive high quality experimental data, and could provide insights on chamber studies and chemical mechanism development.

The effects of humidity and ammonia on the chemical composition of secondary aerosols from toluene/NOx photo-oxidation.

The secondary aerosol formation mechanism in the presence of ammonia (NH3), is poorly understood, especially under high relative humidity (RH) conditions. In this study, a total of seven experiments were conducted from toluene/NOx photo-oxidation in the presence/absence of NH3 under dry (~7% RH) and wet (>60% RH) conditions in a ~3 m3 smog chamber. A series of instruments including gas analysers, scanning mobility particle sizer (SMPS), aerosol mass spectrometry (HR-ToF-AMS) etc. were applied to measure the NOx and O3 concentrations, the mass concentration and chemical composition of secondary aerosol. It was found that NH3 could enhance the mass loading of secondary aerosol, especially under wet condition. However, the presence of NH3 or increasing RH did not have a significant influence on SOA yield. The organic aerosol mass spectrum from AMS showed that the most abundant fragment was at m/z = 44, which was mainly from the fragmentation of carboxylic acids. Compared to the absence of NH3, the fraction of fragment at m/z = 44 and O:C was higher in the presence of NH3, regardless of dry or wet conditions. The highest O:C value of 0.71-0.75 was observed in the presence of NH3 under wet condition, suggesting there could be a synergetic effect between the high RH and the presence of NH3, which jointly contributed to the photochemical aging process of SOA. The N:C increased in the presence of NH3 under both dry and wet conditions, which might be attributed to the carboxylates and organic nitrates formed from the reaction between NH3 and carboxylic acids. The results implied that SOA modelling should consider the role of NH3 and water vapour, which might fill the gap of O:C between laboratory studies and field measurements.

Meteorological and chemical impacts on PM2.5 during a haze episode in a heavily polluted basin city of eastern China.

Haze formation involves many interacting factors, such as secondary aerosol formation, unfavourable synoptic conditions and regional transport. The interaction between these factors complicates scientific understanding of the mechanism behind haze formation. In this study, we investigated the factors resulting in haze events in Longyou, a city located in a basin in China. Aerosol samples of PM2.5 were collected for subsequent chemical composition analysis between 11 January and 5 February 2018. The impacts of wind on PM2.5, SO2 and NO2 concentrations were analysed. Besides, the origin of air parcels and potential sources of PM2.5 were analysed by backward trajectory, potential source contribution function (PSCF) and concentration-weighted trajectories (CWT). Among the water-soluble ions identified, NO3- had the highest concentration, with further analysis demonstrating the haze evolution was mainly driven by the reactions involving NO3- formation. The dramatic increase of nitrate is mainly due to the homogeneous reaction of nitric acid with ammonia, while sulfate is likely due to heterogeneous reactions of NO2, SO2 and NH3. The average wind speed was less than 2 m/s during the aerosol sampling period, which could be considered as a stagnant state. Pollutants emitted by industrial area located in the northeast Longyou were probably brought to observation sites by continuous wind from northeast and accumulated gradually. Air parcels originating from the northeast of Zhejiang province also had large effects on haze pollution in Longyou. Together, our results showed that rapid secondary aerosol formation and unfavourable synoptic conditions are the main factors resulting in haze pollution in Longyou.

Correction to "The Discovery of 3,3'-Spiro[azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection".

[This corrects the article DOI: 10.1021/acsmedchemlett.7b00418.].

Discovery of 3,3'-Spiro[Azetidine]-2-oxo-indoline Derivatives as Fusion Inhibitors for Treatment of RSV Infection.

A new series of 3,3'-spirocyclic-2-oxo-indoline derivatives was synthesized and evaluated against respiratory syncytial virus (RSV) in a cell-based assay and animal model. Extensive structure-activity relationship study led to a lead compound 14h, which exhibited excellent in vitro potency with an EC50 value of 0.8 nM and demonstrated 71% oral bioavailability in mice. In a mouse challenge model of RVS infection, 14h demonstrated superior efficacy with a 3.9log RSV virus load reduction in the lung following an oral dose of 50 mg/kg.

Social-demographics, health behaviors, and telomere length in the Mexican American Mano a Mano Cohort.

In the current study, we examined cross-sectional associations among social-demographics, lifestyle behaviors, and relative telomere length (RTL) in peripheral blood leukocytes, as well as longitudinal relationships among major chronic diseases, weight gain, and RTL, among 12,792 Mexican Americans aged 20 to 85 years in the Mano-A-Mano, the Mexican American Cohort. As expected, RTL was inversely correlated with age (ρ=-0.15, ρ<0.001). In the multivariate analysis, we found that RTL was positively correlated with levels of education (ρ=0.021), self-insurance (ρ=0.041), body mass index (BMI) (ρ<0.001), and sleeping time per day (ρ for trend<0.001), and RTL was inversely correlated with sitting time per day (ρ for trend =0.001). In longitudinal analysis, we found that longer RTL was modestly but positively associated with increased risks of overall cancer (adjusted hazard ratio (adj.HR)=1.05, 95% conference interval (95%CI)=1.02-1.09). In quartile analysis, 4th quartile (longest RTL) was associated with 1.53-fold increased risk of overall cancer (adj.HR=1.53, 95%CI=1.11-2.10), compared to 1st quartile (shortest RTL). RTL was reversely associated with the risk of type-2 diabetes (adj.HR=0.89, 95%CI=0.82-0.94). In quartile analysis, 4th quartile (longest RTL) was associated with 48% decreased risk of typle-2 diabetes (adj.HR=0.52, 95%CI=0.32-0.70), compared to 1st quartile (shortest RTL). In addition, longer RTL was a positive predictor of at least 10% weight gain (adj.HR=1.03, 95%CI=1.00-1.05). In summary, our results in Mexican Americans support the notion that telomere length is a biological mechanism by which social demographics and health behaviors "get under the skin" to affect health.

TRAF6 Restricts p53 Mitochondrial Translocation, Apoptosis, and Tumor Suppression.

Mitochondrial p53 is involved in apoptosis and tumor suppression. However, its regulation is not well studied. Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction between p53 and MCL-1/BAK. Genotoxic stress reduces this ubiquitination in cytosol by S13/T330 phosphorylation-dependent translocation of TRAF6 from cytosol to nucleus, where TRAF6 also facilitates the K63-linked ubiquitination of nuclear p53 and its transactivation by recruiting p300 for p53 acetylation. Functionally, K63-linked ubiquitination of p53 compromised p53-mediated apoptosis and tumor suppression. Colorectal cancer samples with WT p53 reveal that TRAF6 overexpression negatively correlates with apoptosis and predicts poor response to chemotherapy and radiotherapy. Together, our study identifies TRAF6 as a critical gatekeeper to restrict p53 mitochondrial translocation, and such mechanism may contribute to tumor development and drug resistance.

AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas.

BACKGROUND: AXL is a well-characterized, protumorigenic receptor tyrosine kinase that is highly expressed and activated in numerous human carcinomas and sarcomas, including aggressive subtypes of liposarcoma. However, the role of AXL in the pathogenesis of well-differentiated (WDLPS), dedifferentiated (DDLPS), and pleomorphic liposarcoma (PLS) has not yet been determined. METHODS: Immunohistochemical analysis of AXL expression was conducted on two tissue microarrays containing patient WDLPS, DDLPS, and PLS samples. A panel of DDLPS and PLS cell lines were interrogated via western blot for AXL expression and activity and by ELISA for growth arrest-specific 6 (GAS6) production. AXL knockdown was achieved by siRNA or shRNA. The effects of AXL knockdown on cell proliferation, migration, and invasion were measured in vitro. In addition, AXL shRNA-containing DDLPS cells were assessed for their tumor-forming capacity in vivo. RESULTS: In this study, we determined that AXL is expressed in a subset of WDLPS, DDLPS, and PLS patient tumor samples. In addition, AXL and its ligand GAS6 are expressed in a panel of DDLPS and PLS cell lines. We show that the in vitro activation of AXL via stimulation with exogenous GAS6 resulted in a significant increase in cell proliferation, migration, and invasion in DDLPS and PLS cell lines. Transient knockdown of AXL resulted in attenuation of these protumorigenic phenotypes in vitro. Stable AXL knockdown not only decreased migratory and invasive characteristics of DDLPS and PLS cells in vitro but also significantly diminished tumorigenicity of two dedifferentiated liposarcoma xenograft models in vivo. CONCLUSIONS: Our results suggest that AXL signaling contributes to the aggressiveness of DDLPS and PLS, and that AXL is therefore a potential therapeutic target for treatment of these rare, yet devastating tumors.

Michael acceptor in gambogic acid--Its role and application for potent antitumor agents.

Gambogic acid (GA), a natural product with unique structure, was reported to have broad antiproliferation activities against cancer cell lines. As a reactive Michael acceptor, the 10-position of GA is susceptible to nucleophiles, thus limiting its clinical application as an anticancer agent. Moreover, the 6-OH forms an intramolecular hydrogen bond with 8-CO, which can make the 9, 10 double bond more reactive to nucleophiles. In this essay, two strategies (A and B) were applied to solve the above-mentioned problems. Strategy A was to increase the steric hindrance of C-10 to reduce the activity of GA towards nucleophiles. Strategy B was to replace the hydroxyl of C-6 with other substituents based on the assumption that the intra-molecular hydrogen bond could increase the electrophilicity of C-10. Results showed the electrophilicity of C-10 disappeared as well as the antiproliferation activity against cancer cell lines by introducing a methyl group at C-10. Strategy B showed that the electrophilicity of C-10 was reduced dramatically while maintained the activity by replacement of the hydroxyl of C-6 with neutral or basic groups.

Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells.

Phagocytic clearance of the spent photoreceptor outer segments (OS) by RPE cells is regulated by circadian rhythm cycle and is essential for photoreceptor integrity and function. Mertk regulates RPE phagocytosis and a deficiency in Mertk causes photoreceptor degeneration and visual loss. This study aimed to investigate Mertk regulation of the microRNAs (miRNA), potentially regulating expression of their target genes, which affect phagocytosis. The differentially expressed miRNAs were identified using miRCURY(TM) microRNA Arrays from total RNA isolated at 0900 h and 1900 h from the mechanically dissociated RPE sheets of the WT and Mertk (-/-) mice, which were housed in a 12-h light-dark cycle with the lighting onset at 0700 h (7:00am). Validation of the differentially expressed miRNAs and assessment of the putative miRNA target gene expression were performed by real-time PCR. Among the differentially expressed miRNAs in the Mertk (-/-) RPE, seven miRNAs were up-regulated and 13 were down-regulated in the morning groups. Similarly, 24 miRNAs were found to be up-regulated and 13 were down-regulated in the evening groups. To search for those that may participate in regulating expression of cytoskeletal proteins, we examined the predicted target genes that might participate in phagocytosis were examined by real-time PCR. Of nine potential altered targets, four deregulated genes were myosin subunits. Notably, multiple members of the 21 up-regulated miRNAs can theoretically recognize these down-regulated mRNAs, particularly MyH14 and Myl3. This study shows that loss of Mertk alters miRNA expression, which in turn affects expression of the downstream target genes, potentially affecting phagocytosis.