Comparative Analysis of Molecular Landscape in Mouse Models and Patients Reveals Conserved Inflammation Pathways in Age-Related Macular Degeneration.

Purpose: The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD. Methods: Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort. Results: Retinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls. Conclusions: Our study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.

Epitranscriptomic investigation of myopia-associated RNA editing in the retina.

Myopia is one of the most common causes of vision loss globally and is significantly affected by epigenetics. Adenosine-to-inosine (A-to-I RNA) editing is an epigenetic process involved in neurological disorders, yet its role in myopia remains undetermined. We performed a transcriptome-wide analysis of A-to-I RNA editing in the retina of form-deprivation myopia mice. Our study identified 91 A-to-I RNA editing sites in 84 genes associated with myopia. Notably, at least 27 (32.1%) of these genes with myopia-associated RNA editing showed existing evidence to be associated with myopia or related ocular phenotypes in humans or animal models, such as very low-density lipoprotein receptor (Vldlr) in retinal neovascularization and hypoxia-induced factor 1 alpha (Hif1a). Moreover, functional enrichment showed that RNA editing enriched in FDM was primarily involved in response to fungicides, a potentially druggable process for myopia prevention, and epigenetic regulation. In contrast, RNA editing enriched in controls was mostly involved in post-embryonic eye morphogenesis. Our results demonstrate altered A-to-I RNA editing associated with myopia in an experimental mouse model and warrant further study on its role in myopia development.

Host A-to-I RNA editing signatures in intracellular bacterial and single-strand RNA viral infections.

Background: Microbial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections. Results: Herein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections. Conclusion: Our study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.

Simultaneous extracting area and quantity of agricultural greenhouses in large scale with deep learning method and high-resolution remote sensing images.

Greenhouses are an important part of modern facility-based agriculture. While creating well-being for human society, greenhouses also bring negative impacts such as air pollution, soil pollution, and water pollution. Therefore, it is of great significance to obtain information such as the area and quantity of greenhouses. It is still a challenging task to find a low-cost, high-efficiency, and easy-to-use method for the dual extraction of greenhouse area and quantity on a large scale. In this study, relatively easy-to-obtain high-resolution Google Earth remote sensing images are used as the experimental data source, and an area and quantity simultaneous extraction framework (AQSEF) is constructed to extract both the area and quantity of greenhouses. The AQSEF uses UNet and YOLO v5 series networks as core operators to complete model training and prediction, and main components such as SWP, OSW&NMS and GCA complete data postprocessing. To evaluate the feasibility of our method, we take Beijing, China, as the research area and select multiple accuracy evaluation indicators in the two branches for accuracy verification. The results show that the mIoU, OA, Kappa, Recall and Precision with the best performance model in the area extraction branch can reach 0.931, 0.987, 0.867, 0.91 and 0.914, respectively. Additionally, the Recall, Precision, AP@0.5 and mAP@0.5: 0.95 values of the best performance model are 0.781, 0.891, 0.812 and 0.509, respectively, in the extraction of the quantity of greenhouses. Finally, in Beijing, the area covered by greenhouses is approximately 85.443 km2, and the quantity of greenhouses is approximately 155,464. With the proposed method, the time consumed for area extraction and quantity extraction is 6.73 h and 12.97 h, respectively. The experimental results show that AQSEF helps to overcome the spatiotemporal diversity of greenhouses and quickly and accurately map a high-spatial-resolution greenhouse distribution product within the research area.

Prevalence of and factors associated with astigmatism in preschool children in Wuxi City, China.

PURPOSE: To investigate the status of astigmatism in preschool children in Wuxi City, and explore the risk factors related to astigmatism. The risk factors related to astigmatism development as predictors can help us identify preschool children who need vision screening at an early stage to ensure good visual quality. METHODS: The cross-sectional study was conducted in 10 kindergartens randomly selected in five districts of Wuxi City in November 2018. All preschool children were measured by objective refractometry under non-cycloplegic refraction. The basic information of preschool children was collected. The relevant factors of astigmatism in the questionnaire were completed by parents. Spss 26. 0 software was used for univariate and multivariate correlation analysis. RESULTS: A total of 889 preschool children participated in the study, 864 were finally included in the study. The prevalence of astigmatism was 36.0%. The risk of astigmatism in premature children was higher than that in non-premature children (adjusted odds ratio = 1.841). The prevalence of astigmatism with parents' astigmatism history was higher, compared with preschool children without parents' astigmatism history (adjusted odds ratio = 2.037). When maternal age at childbirth was older (≥ 35 years old), the risk of astigmatism increased in preschool children (adjusted odds ratio = 2.181). Compared with bottle feeding, the risk of astigmatism for mixed feeding and breastfeeding reduced in preschool children. Compared with preschool children exposed to electronic screen for less than 2 h every day, preschool children exposed to electronic screen for more than 2 h had an increased risk of astigmatism (P = 0.004). CONCLUSION: The prevalence of astigmatism among preschool children in Wuxi City was high. Some risk factors such as premature birth, parents' astigmatism history, maternal age at childbirth, feeding pattern, and electronic screen exposure time were closely related to the occurrence of astigmatism among preschool children. For preschool children with significant risk factors, their eyesight should be checked regularly to ensure their visual quality.

Host shifts in economically significant fruit flies (Diptera: Tephritidae) with high degree of polyphagy.

Insects tend to feed on related hosts. Coevolution tends to be dominated by interactions resulting from plant chemistry in defense strategies, and evolution of secondary metabolisms being in response to insect herbivory remains a classic explanation of coevolution. The present study examines whether evolutionary constraints existing in host associations of economically important fruit flies in the species-rich tribe Dacini (Diptera: Tephritidae) and to what extent these species have evolved specialized dietary patterns. We found a strong effect of host phylogeny on associations on the 37 fruit flies tested, although the fruit fly species feeding on ripe commercially grown fruits that lost the toxic compounds after long-term domestication are mostly polyphagous. We assessed the phylogenetic signal of host breadth across the fruit fly species, showing that the results were substantially different depending on partition levels. Further, we mapped main host family associations onto the fruit fly phylogeny and Cucurbitaceae has been inferred as the most likely ancestral host family for Dacini based on ancestral state reconstruction.

Prostaglandin E2 promotes pathological retinal neovascularisation via EP4R-EGFR-Gab1-AKT signaling pathway.

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E2 (PGE2) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP4R). The aim of this study was to investigate the role of PGE2/EP4R signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE2, cay10598 (an EP4R agonist) or AH23848 (an EP4R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE2 or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE2-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE2 or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE2-or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE2/EP4R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.

A novel missense mutation of RPGR identified from retinitis pigmentosa affects splicing of the ORF15 region and causes loss of transcript heterogeneity.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP), in which exon open reading frame 15 (ORF15) of RPGR has been implicated to play a substantial role. We identified a novel hemizygous missense mutation E585K of RPGR from whole-exome sequencing of RP. RNA-Seq analysis and functional study were conducted to investigate the underlying pathogenic mechanism of the mutation. Our results showed that the mutation actually affected RPGR ORF15 splicing. RNA-Seq analysis of the human retina followed by validation in cells revealed a complex splicing pattern near the 3' boundary of RPGR exon 14 in the ORF15 region, resulting from a variety of alternative splicing events (ASEs). The wildtype RPGR mini-gene expressed in human 293T cells confirmed these ASEs in vitro. In contrast, without new RNA species detected, the mutant mini-gene disrupted the splicing pattern of the ORF15 region, and caused loss of RPGR transcript heterogeneity. The RNA species derived from the mutant mini-gene were predominated by a minor out-of-frame transcript that was also observed in wildtype RPGR, resulting from an upstream alternative 5' splice site in exon 14. Our findings therefore provide insights into the influence of RPGR exonic mutations on alternative splicing of the ORF15 region, and the underlying molecular mechanism of RP.

Species identification, phylogenetic analysis and detection of herbicide-resistant biotypes of Amaranthus based on ALS and ITS.

The taxonomically challenging genus Amaranthus (Family Amaranthaceae) includes important agricultural weed species that are being spread globally as grain contaminants. We hypothesized that the ALS gene will help resolve these taxonomic challenges and identify potentially harmful resistant biotypes. We obtained 153 samples representing 26 species from three Amaranthus subgenera and included in that incorporated ITS, ALS (domains C, A and D) and ALS (domains B and E) sequences. Subgen. Albersia was well supported, but subgen. Amaranthus and subgen. Acnida were not. Amaranthus tuberculatus, A. palmeri and A. spinosus all showed different genetic structuring. Unique SNPs in ALS offered reliable diagnostics for most of the sampled Amaranthus species. Resistant ALS alleles were detected in sixteen A. tuberculatus samples (55.2%), eight A. palmeri (27.6%) and one A. arenicola (100%). These involved Ala122Asn, Pro197Ser/Thr/Ile, Trp574Leu, and Ser653Thr/Asn/Lys substitutions, with Ala122Asn, Pro197Thr/Ile and Ser653Lys being reported in Amaranthus for the first time. Moreover, different resistant mutations were present in different A. tuberculatus populations. In conclusion, the ALS gene is important for species identification, investigating population genetic diversity and understanding resistant evolution within the genus Amaranthus.

KCNQ1OT1 affects the progression of diabetic retinopathy by regulating miR-1470 and epidermal growth factor receptor.

Long noncoding RNAs have been reported to play important roles in the pathogenesis of diabetic retinopathy (DR), which has been considered as the most common disease leading to vision loss. However, it is still unclear whether KCNQ1 overlapping transcript 1 (KCNQ1OT1) could affect DR. In this study, regarding quantitative reverse transcription polymerase chain reaction assay, KCNQ1OT1 level was upregulated while microRNA-1470 (miR-1470) was decreased in DR patients and human retinal endothelial cells. High KCNQ1OT1 expression was correlated with DR stage and low visual function. Using miR-1470 mimic or knockdown of KCNQ1OT1 could lead to the similar phenomenon; phospho-AKT, Bax, B-cell lymphoma 2, and cleaved poly-ADP ribose polymerase (PARP) were regulated, while vascularization was inhibited and apoptosis was promoted. Regarding bioinformatics analysis and in vitro dual luciferase reporter assay, there should be a negative correlation between KCNQ1OT1 and miR-1470. Additionally, mRNA of epidermal growth factor receptor (EGFR) was proved as the target of miR-1470 and EGFR targeting by miR-1470 initiated KCNQ1OT1 deficiency-induced apoptosis and promoted proliferation. KCNQ1OT1 and miR-1470 were proved to be the promoter and repressor of EGFR, respectively. The results suggested that KCNQ1OT1 could sponge miR-1470 and further regulate EGFR in DR.

Asymmetric response of different functional insect groups to low-grazing pressure in Eurasian steppe in Ningxia.

In recent years, the continued loss and fragmentation of steppe has caused decreased ecosystem functions and species losses in insect diversity. In the 2000s, the Chinese government developed a series of national projects, such as the construction of enclosures, to conserve natural ecosystems, including steppe. However, the effects of these enclosures on steppe arthropod community are largely unknown. In the present study, we selected enclosed and low-grazing regions at eight National Grassland Fixed Monitoring Stations to examine the compositional differences in four insect functional groups and their associated ecological functions. The results showed that diversity significantly differed between the enclosed and low-grazing regions, with the number of insect families being significantly higher in enclosed regions than in regions with low-grazing pressure. The responses of the insect community to steppe management also varied among the four groups (herbivores, predators, parasitoids, and pollinators). The abundances of herbivores, predators, and parasitoids were higher in enclosed regions than in low-grazing regions, while there was no significant difference in pollinators. Additionally, there were no significant differences in the predator/prey ratio between enclosed regions and low-grazing regions in any of the steppe types. The parasitic wasp/prey ratio was higher in enclosed regions than in low-grazing regions in meadow steppe and typical steppe, while there were no significant differences between the enclosed and low-grazing regions in desert steppe and steppe desert. Herbivores were observed to benefit much more from enclosures than predators, parasitoids, and pollinators. Therefore, we recommend low-grazing should be considered in steppe conservation, which could conserve biodiversity and achieve biocontrol functions of arthropod community.

Impact of climate and host availability on future distribution of Colorado potato beetle.

Colorado Potato Beetle (CPB) is a devastating invasive pest of potato both in its native North America and now across Eurasia. It also damages eggplant, tomato and feeds on several wild species in the Solanaceae, such as S. eleagnifolium and S. rostratum Dunal (SR). Since first categorized as a pest in 1864, CPB has spread rapidly across North America, Europe and Asia. In light of its invasiveness and economic importance, it is necessary to study how climate change and host availability may alter the distribution of the CPB. Maximum Entropy (MaxEnt) models were used to anticipate global range expansion as influenced by environmental conditions, and by the possibility of cooperative invasion of CPB and its wild host SR. The results indicate that both CPB and SR can occupy warm areas of North America, South Africa, Europe, China, and Australia. Future climate conditions may promote CPB expansion into northern regions and SR into the circumpolar latitudes. The existing range and continued spread of SR may also assist the global expansion of CPB. Future management of this pest should consider the impacts of global climate change and host availability on its potential global distribution.

The first complete mitochondrial genome of Dacus longicornis (Diptera: Tephritidae) using next-generation sequencing and mitochondrial genome phylogeny of Dacini tribe.

The genus Dacus is one of the most economically important tephritid fruit flies. The first complete mitochondrial genome (mitogenome) of Dacus species - D. longicornis was sequenced by next-generation sequencing in order to develop the mitogenome data for this genus. The circular 16,253 bp mitogenome is the typical set and arrangement of 37 genes present in the ancestral insect. The mitogenome data of D. longicornis was compared to all the published homologous sequences of other tephritid species. We discovered the subgenera Bactrocera, Daculus and Tetradacus differed from the subgenus Zeugodacus, the genera Dacus, Ceratitis and Procecidochares in the possession of TA instead of TAA stop codon for COI gene. There is a possibility that the TA stop codon in COI is the synapomorphy in Bactrocera group in the genus Bactrocera comparing with other Tephritidae species. Phylogenetic analyses based on the mitogenome data from Tephritidae were inferred by Bayesian and Maximum-likelihood methods, strongly supported the sister relationship between Zeugodacus and Dacus.

Application of fundamental equations to species-area theory.

BACKGROUND: Species-area relationship (SAR), endemics-area relationship (EAR) and overlap-area relationship (OAR) are three important concepts in biodiversity study. The application of fundamental equations linking the SAR, EAR and OAR, can enrich the axiomatic framework of the species-area theory and deepen our understanding of the mechanisms of community assembly. RESULTS: Two fundamental equations are derived and extended to power law model and random replacement model of species-area distribution. Several important parameters, including the overlap index and extinction rate, are defined and expressed to enrich the species-area theory. For power law model, both EAR and OAR have three parameters, with one more parameter of the total area than SAR does. The EAR equation is a monotonically increasing function for parameter c and z, and a monotonically decreasing function for parameter A. The extinction rate, with two parameters, is a monotonically increasing function for parameter z, and a monotonically decreasing function for parameter A. The overlap index is a monotonically increasing function for parameter A, and a monotonically decreasing function for parameter z, independent of parameter c. CONCLUSIONS: The general formats of SAR, EAR, OAR, overlap index, overlap rate, sampling rate and extinction rate, are derived and extended to power law model and random replacement model as the axiomatic framework of species-area theory. In addition, if the total area is underestimated, the extinction rate will be overestimated.

Potential Global-Local Inconsistency in Species-Area Relationships Fitting.

The Species-Area Relationship (SAR) has been widely employed to assess species diversity and predict species extinction. Thus far, although many functions were proposed to fit SAR based on field observations or simulation results, the shape of SAR curve has been debated extensively over decades. Here we uncover a potential global-local inconsistency in SARs fitting simulation blocked by the limitation of large area sampling before. The results indicated that power and logarithm SAR formulas were good for the fitting if the sampling area range is not large which is also the practical sampling interval in the field. However, for the logarithm SAR fitting, a sigmoid curve occurred in the log10 Area-Number of Species plane, and for the power SAR fitting, the curve is convex instead of a straight line as assumed when linear regression was applied. In conclusion, neither the power SAR nor the logarithm SAR fitted to simulated data is linear at large sampling range as commonly assumed in previous studies, no matter the distribution of species abundance is log-normal or negative-binomial, which unmasks the global-local inconsistency in SARs fitting. Thus, misestimates of total number of species or other derivation parameters can occur if the fitted relationship is extrapolated beyond the range of the small and intermediate sampling size.

Emissions of ammonia and greenhouse gases during combined pre-composting and vermicomposting of duck manure.

Combined pre-composting and vermicomposting has shown potential for reclamation of solid wastes, which is a significant source of ammonia (NH3), and greenhouse gases (GHG), including nitrous oxide (N2O), methane (CH4), and carbon dioxide (CO2). Earthworms and amendments may both affect physico-chemical characteristics that control gas-producing processes, and thus affect NH3 and GHG emissions. Here, we used two-way ANOVA to test the effects of addition of reed straw and combined addition of reed straw and zeolite on NH3 and GHG emissions during pre-composting of duck manure, either with or without a follow-up phase of vermicomposting. Results showed that cumulative N2O, CH4, and CO2 emissions during pre-composting and vermicomposting ranged from 92.8, 5.8, and 260.6 mg kg(-)(1) DM to 274.2, 30.4, and 314.0 mg kg(-1) DM, respectively. Earthworms and amendments significantly decreased N2O and CH4 emissions. Emission of CO2 was not affected by earthworms, but increased in responses to addition of reed straw. Cumulative NH3 emission ranged from 3.0 to 8.1 g kg(-1) DM, and was significantly decreased by reed straw and zeolite addition. In conclusion, combined pre-composting and vermicomposting with reed straw and zeolite addition would be strongly recommended in mitigating emissions of N2O, CH4, and NH3 from duck manure. Moreover, this method also provides nutrient-rich products that can be used as a fertilizer.

Meta-modeling soil organic carbon sequestration potential and its application at regional scale.

Upscaling the results from process-based soil-plant models to assess regional soil organic carbon (SOC) change and sequestration potential is a great challenge due to the lack of detailed spatial information, particularly soil properties. Meta-modeling can be used to simplify and summarize process-based models and significantly reduce the demand for input data and thus could be easily applied on regional scales. We used the pre-validated Agricultural Production Systems sIMulator (APSIM) to simulate the impact of climate, soil, and management on SOC at 613 reference sites across Australia's cereal-growing regions under a continuous wheat system. We then developed a simple meta-model to link the APSIM-modeled SOC change to primary drivers, i.e., the amount of recalcitrant SOC, plant available water capacity of soil, soil pH, and solar radiation, temperature, and rainfall in the growing season. Based on high-resolution soil texture data and 8165 climate data points across the study area, we used the meta-model to assess SOC sequestration potential and the uncertainty associated with the variability of soil characteristics. The meta-model explained 74% of the variation of final SOC content as simulated by APSIM. Applying the meta-model to Australia's cereal-growing regions reveals regional patterns in SOC, with higher SOC stock in cool, wet regions. Overall, the potential SOC stock ranged from 21.14 to 152.71 Mg/ha with a mean of 52.18 Mg/ha. Variation of soil properties induced uncertainty ranging from 12% to 117% with higher uncertainty in warm, wet regions. In general, soils in Australia's cereal-growing regions under continuous wheat production were simulated as a sink of atmospheric carbon dioxide with a mean sequestration potential of 8.17 Mg/ha.

Fundamental equations for species-area theory.

Species-area theory is an important concept in ecology. However, debates still surround the species-area relationship (SAR) or endemics-area relationship (EAR) and their relations to expected extinction rates. In this paper, I introduce the concept of overlap-area relationship (OAR) to link SAR and EAR. Two fundamental equations are derived from the relationship between the area and species number in a limited whole area A: 1) the sum of species number in area a and species number, here defined as endemics, in area A - a is the total species number in area A; 2) the number of species common to both areas a and A - a (overlapping species) equals the species number in area a minus the endemics number in area a. Thus, we should carefully consider the total area on which EAR depends, when estimating extinction rate based on SAR.