Blockade of the Phagocytic Receptor MerTK on Tumor-Associated Macrophages Enhances P2X7R-Dependent STING Activation by Tumor-Derived cGAMP.

Clearance of apoptotic cells by macrophages prevents excessive inflammation and supports immune tolerance. Here, we examined the effect of blocking apoptotic cell clearance on anti-tumor immune response. We generated an antibody that selectively inhibited efferocytosis by phagocytic receptor MerTK. Blockade of MerTK resulted in accumulation of apoptotic cells within tumors and triggered a type I interferon response. Treatment of tumor-bearing mice with anti-MerTK antibody stimulated T cell activation and synergized with anti-PD-1 or anti-PD-L1 therapy. The anti-tumor effect induced by anti-MerTK treatment was lost in Stinggt/gt mice, but not in Cgas-/- mice. Abolishing cGAMP production in Cgas-/- tumor cells, depletion of extracellular ATP, or inactivation of the ATP-gated P2X7R channel also compromised the effects of MerTK blockade. Mechanistically, extracellular ATP acted via P2X7R to enhance the transport of extracellular cGAMP into macrophages and subsequent STING activation. Thus, MerTK blockade increases tumor immunogenicity and potentiates anti-tumor immunity, which has implications for cancer immunotherapy.

Global hotspots for soil nature conservation.

Soils are the foundation of all terrestrial ecosystems1. However, unlike for plants and animals, a global assessment of hotspots for soil nature conservation is still lacking2. This hampers our ability to establish nature conservation priorities for the multiple dimensions that support the soil system: from soil biodiversity to ecosystem services. Here, to identify global hotspots for soil nature conservation, we performed a global field survey that includes observations of biodiversity (archaea, bacteria, fungi, protists and invertebrates) and functions (critical for six ecosystem services) in 615 composite samples of topsoil from a standardized survey in all continents. We found that each of the different ecological dimensions of soils-that is, species richness (alpha diversity, measured as amplicon sequence variants), community dissimilarity and ecosystem services-peaked in contrasting regions of the planet, and were associated with different environmental factors. Temperate ecosystems showed the highest species richness, whereas community dissimilarity peaked in the tropics, and colder high-latitudinal ecosystems were identified as hotspots of ecosystem services. These findings highlight the complexities that are involved in simultaneously protecting multiple ecological dimensions of soil. We further show that most of these hotspots are not adequately covered by protected areas (more than 70%), and are vulnerable in the context of several scenarios of global change. Our global estimation of priorities for soil nature conservation highlights the importance of accounting for the multidimensionality of soil biodiversity and ecosystem services to conserve soils for future generations.

A Real-Time Image-Based Efferocytosis Assay for the Discovery of Functionally Inhibitory Anti-MerTK Antibodies.

Efferocytosis is a phagocytic process by which apoptotic cells are cleared by professional and nonprofessional phagocytic cells. In tumors, efferocytosis of apoptotic cancer cells by tumor-associated macrophages prevents Ag presentation and suppresses the host immune response against the tumor. Therefore, reactivating the immune response by blockade of tumor-associated macrophage-mediated efferocytosis is an attractive strategy for cancer immunotherapy. Even though several methods have been developed to monitor efferocytosis, an automated and high-throughput quantitative assay should offer highly desirable advantages for drug discovery. In this study, we describe a real-time efferocytosis assay with an imaging system for live-cell analysis. Using this assay, we successfully discovered potent anti-MerTK Abs that block tumor-associated macrophage-mediated efferocytosis in mice. Furthermore, we used primary human and cynomolgus monkey macrophages to identify and characterize anti-MerTK Abs for potential clinical development. By studying the phagocytic activities of different types of macrophages, we demonstrated that our efferocytosis assay is robust for screening and characterization of drug candidates that inhibit unwanted efferocytosis. Moreover, our assay is also applicable to investigating the kinetics and molecular mechanisms of efferocytosis/phagocytosis.

Unearthing the soil-borne microbiome of land plants.

Plant-soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate organisms consistently associated with land plants (i.e., their consistent soil-borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.

Livestock grazing modifies soil nematode body size structure in mosaic grassland habitats.

Body size is closely related to the trophic level and abundance of soil fauna, particularly nematodes. Therefore, size-based analyses are increasingly prominent in unveiling soil food web structure and its responses to anthropogenic disturbances, such as livestock grazing. Yet, little is known about the effects of different livestock on the body size structure of soil nematodes, especially in grasslands characterized by local habitat heterogeneity. A four-year field grazing experiment from 2017 to 2020 was conducted in a meadow steppe characterized by typical mosaics of degraded hypersaline patches and undegraded hyposaline patches to assess the impacts of cattle and sheep grazing on the body size structure of soil nematodes within and across trophic groups. Without grazing, the hypersaline patches harbored higher abundance of large-bodied nematodes in the community compared to the hyposaline patches. Livestock grazing decreased large-bodied nematodes within and across trophic groups mainly by reducing soil microbial biomass in the hypersaline patches, with sheep grazing resulting in more substantial reductions compared to cattle grazing. The reduction in large-bodied nematode individuals correspondingly resulted in decreases in nematode community-weighted mean (CWM) body size, nematode biomass, and size spectra slopes. However, both cattle and sheep grazing had minimal impacts on the CWM body size and size spectra of total nematodes in the hyposaline patches. Our findings suggest that livestock grazing, especially sheep grazing, has the potential to simplify soil food webs by reducing large-bodied nematodes in degraded habitats, which may aggravate soil degradation by weakening the bioturbation activities of soil fauna. In light of the widespread land use of grasslands by herbivores of various species and the ongoing global grassland degradation of mosaic patches, the recognition of the trends revealed by our findings is critical for developing appropriate strategies for grassland grazing management.

Translatability of In Vitro Stress for Predicting Deamidation and Oxidation Biotransformation on Biotherapeutics.

Biotransformation leading to single residue modifications (e.g., deamidation, oxidation) can contribute to decreased efficacy/potency, poor pharmacokinetics, and/or toxicity/immunogenicity for protein therapeutics. Identifying and characterizing such liabilities in vivo are emerging needs for biologics drug discovery. In vitro stress assays involving PBS for deamidation or AAPH for oxidation are commonly used for predicting liabilities in manufacturing and storage and are sometimes considered a predictive tool for in vivo liabilities. However, reports discussing their in vivo translatability are limited. Herein, we introduce a mass spectrometry workflow that characterizes in vivo oxidation and deamidation in pharmacokinetically relevant compartments for diverse protein therapeutic modalities. The workflow has low bias of <10% in quantitating degradation in the relevant pharmacokinetic concentration range for monkey and rabbit serum/plasma (1-100 µg/mL) and allows for high sequence coverage (∼85%) for discovery/monitoring of amino acid modifications. For oxidation and deamidation, the assay was precise, with percent coefficient of variation of <8% at 1-100 µg/mL and ≤6% method-induced artifacts. A high degree of in vitro and in vivo correlation was observed for deamidation on the six diverse protein therapeutics (seven liability sites) tested. In vivo translatability for oxidation liabilities were not observed for the 11 molecules tested using in vitro AAPH stress. One of the molecules dosed in eyes resulted in a false positive and a false negative prediction for in vivo oxidation following AAPH stress. Finally, peroxide stress was also tested but resulted in limited success (1 out of 4 molecules) in predicting oxidation liabilities.

Insight on genetic features prevalent in five Ipomoea species using comparative codon pattern analysis reveals differences in major codons and reduced GC content at the 5' end of CDS.

Ipomoea plants possess important commercial, medicinal, and ornamental value. Molecular and morphological studies have confirmed that most species of this genus exhibit similar phenotypes but complex phylogenetic relationships. To date, limited information is available on these evolutionary relationships. In this study, systematic analysis of diverse species from Ipomoea was used to elucidate the relationships in this genus. To this end, we employed the concept of codon usage bias (CUB) to analyze the codon usage bias of five Ipomoea species such as effective number of codons (ENC) and GC content at the third synonym codon position (GC3s). Three types of plots including ENC-GC3s, parity rule 2 (PR2) and neutrality plots were employed to discover the factors determining CUB, and the frequency of hydrogen bonds and nucleotide were calculated to dissect changes in GC content at the 5'-end of the coding sequence. Our results showed little distinctness in CUB among the five species, with a reduction of hydrogen bonds content at the 5'-end (with similar changes in cytosines). In addition, optimal codons of Ipomoea aquatica ended with G or C, different from those of the other four species, which ended in A or T. These results may be useful for exploring the evolutionary relationships among this group, and for understanding the reasons for the variation among Ipomoea species.

Effect of different substituents on the fluorescence properties of precursors of synthetic GFP analogues and a polarity-sensitive lipid droplet probe with AIE properties for imaging cells and zebrafish.

The green fluorescent protein (GFP) is a purely natural specialty protein that has been widely used to design synthetic fluorescent probes. In the present work we designed and synthesized a series of fluorescent compounds akin to GFP precursors by a one-step method, and investigated the luminescence properties of the fluorescent compounds by varying the substituents. We presented the first systematic summary of the photophysical data including extinction coefficients and fluorescence quantum yields for this class of fluorescent dyes. We also carried out density functional theory (DFT) calculations for these dyes to investigate the effect of electronic effects due to different substituents. These studied optical properties may provide a reference for later probe design. More interestingly, we have developed a polarity-sensitive lipid droplet probe T-LD with AIE properties on this basis. The probe exhibited not only favorable pH stability and kinetic stability in terms of optical properties, but also solvent discolouration and polarity-sensitive properties, and was able to label intracellular lipid droplets. We successfully applied the probe for intracellular lipid droplet level monitoring and zebrafish imaging.

Isolated unilateral oculomotor palsy caused by pure midbrain infarction: a case report.

Purpose: Multiple etiologies may cause oculomotor nerve palsies. Identification of different etiologies is very important for subsequent treatment. Midbrain infarction is a rare cause of oculomotor nerve palsy. Materials and methods: We herein present a case of isolated unilateral oculomotor paresis caused by pure midbrain infarction. Results: Her pupillary sphincter and inferior rectus muscles were selectively spared. The symptoms were completely relieved after two months of antiplatelet therapy. We proposed that fibers from Edinger-Westphal nucleus and inferior rectus nucleus do not course through the paramedian area of the midbrain. Conclusions: Our report adds to the understanding of fascicles arrangement in the midbrain.

Integrated Transcriptomic and Metabolomic Analyses Uncover the Differential Mechanism in Saline-Alkaline Tolerance between Indica and Japonica Rice at the Seedling Stage.

Saline-alkaline stress is one of the major damages that severely affects rice (Oryza sativa L.) growth and grain yield; however, the mechanism of the tolerance remains largely unknown in rice. Herein, we comparatively investigated the transcriptome and metabolome of two contrasting rice subspecies genotypes, Luohui 9 (abbreviation for Chao2R under study, O. sativa ssp. indica, saline-alkaline-sensitive) and RPY geng (O. sativa ssp. japonica, saline-alkaline-tolerant), to identify the main pathways and important factors related to saline-alkaline tolerance. Transcriptome analysis showed that 68 genes involved in fatty acid, amino acid (such as phenylalanine and tryptophan), phenylpropanoid biosynthesis, energy metabolism (such as Glycolysis and TCA cycle), as well as signal transduction (such as hormone and MAPK signaling) were identified to be specifically upregulated in RPY geng under saline-alkaline conditions, implying that a series of cascade changes from these genes promotes saline-alkaline stress tolerance. The transcriptome changes observed in RPY geng were in high accordance with the specifically accumulation of metabolites, consisting mainly of 14 phenolic acids, 8 alkaloids, and 19 lipids based on the combination analysis of transcriptome and metabolome. Moreover, some genes involved in signal transduction as hub genes, such as PR5, FLS2, BRI1, and NAC, may participate in the saline-alkaline stress response of RPY geng by modulating key genes involved in fatty acid, phenylpropanoid biosynthesis, amino acid metabolism, and glycolysis metabolic pathways based on the gene co-expression network analysis. The present research results not only provide important insights for understanding the mechanism underlying of rice saline-alkaline tolerance at the transcriptome and metabolome levels but also provide key candidate target genes for further enhancing rice saline-alkaline stress tolerance.

PEGylation of anti-MerTK Antibody Modulates Ocular Biodistribution.

Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers. Despite reduced binding to MerTK on cells, site-specifically PEGylated anti-MerTK retained similar potency in inhibiting MerTK-mediated macrophage efferocytosis of apoptotic cells. Importantly, we found that PEGylation of anti-MerTK significantly reduced MerTK receptor occupancy in RPE cells in both naïve mice and MC-38 tumor-bearing mice, with the branched PEG exhibiting a greater effect than linear PEG. Furthermore, similar to unconjugated anti-MerTK, PEGylated anti-MerTK antibody triggered type I IFN response and exhibited antitumor effect in syngeneic mouse tumor studies. Our results demonstrate the potential of PEGylation to control ocular biodistribution of antibodies.

Automatic coronary artery segmentation and diagnosis of stenosis by deep learning based on computed tomographic coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has rapidly developed in the coronary artery disease (CAD) field. However, manual coronary artery tree segmentation and reconstruction are time-consuming and tedious. Deep learning algorithms have been successfully developed for medical image analysis to process extensive data. Thus, we aimed to develop a deep learning tool for automatic coronary artery reconstruction and an automated CAD diagnosis model based on a large, single-centre retrospective CCTA cohort. METHODS: Automatic CAD diagnosis consists of two subtasks. One is a segmentation task, which aims to extract the region of interest (ROI) from original images with U-Net. The second task is an identification task, which we implemented using 3DNet. The coronary artery tree images and clinical parameters were input into 3DNet, and the CAD diagnosis result was output. RESULTS: We built a coronary artery segmentation model based on CCTA images with the corresponding labelling. The segmentation model had a mean Dice value of 0.771 ± 0.021. Based on this model, we built an automated diagnosis model (classification model) for CAD. The average accuracy and area under the receiver operating characteristic curve (AUC) were 0.750 ± 0.056 and 0.737, respectively. CONCLUSION: Herein, using a deep learning algorithm, we realized the rapid classification and diagnosis of CAD from CCTA images in two steps. Our deep learning model can automatically segment the coronary artery quickly and accurately and can deliver a diagnosis of ≥ 50% coronary artery stenosis. Artificial intelligence methods such as deep learning have the potential to elevate the efficiency in CCTA image analysis considerably. KEY POINTS: • The deep learning model rapidly achieved a high Dice value (0.771 ± 0.0210) in the autosegmentation of coronary arteries using CCTA images. • Based on the segmentation model, we built a CAD autoclassifier with the 3DNet algorithm, which achieved a good diagnostic performance (AUC) of 0.737. • The deep neural network could be used in the image postprocessing of coronary computed tomography angiography to achieve a quick and accurate diagnosis of CAD.

Effects of grazing on C:N:P stoichiometry attenuate from soils to plants and insect herbivores in a semi-arid grassland.

Understanding the processing of limiting nutrients among organisms is an important goal of community ecology. Less known is how human disturbances may alter the stoichiometric patterns among organisms from different trophic levels within communities. Here, we investigated how livestock grazing affects the C:N:P ecological stoichiometry of soils, plants (Leymus chinensis), and grasshoppers (Euchorthippus spp.) in a semi-arid grassland in northeastern China. We found that grazing significantly enhanced soil available N and leaf N content of the dominant L. chinensis grass by 15% and 20%, respectively. Grazing also reduced (soluble) C:N of L. chinensis leaves by 22%. However, grazing did not affect total C, N, or P contents nor their ratios in Euchorthippus grasshoppers. Our results reveal that the effects of grazing disturbances on elemental composition attenuated from lower to higher trophic levels. These findings support the theory that organisms from higher trophic levels have relatively stronger stoichiometric homeostasis compared to those from lower trophic levels. Moreover, grasshopper abundance dropped by 66% in the grazed areas, and they reduced the feeding time on their host L. chinensis grass by 43%, presumably to limit the intake of excess nitrogen from host plants. The energetic costs associated with the maintenance of elemental homeostasis likely reduced grasshopper individual performance and population abundance in the grazed areas. A comprehensive investigation of stoichiometric properties of organisms across trophic levels may enable a better understanding of the nature of species interactions, and facilitate predictions of the consequences of future environmental changes for a community organization.

Growth Rate of Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Meta-Analysis of Natural History Studies and Implications for Designing Future Trials.

INTRODUCTION: There is no effective treatment for geographic atrophy (GA). To help design future GA treatment trials, we conducted a meta-analysis for GA growth rate and its variability in natural history studies. METHODS: Literatures were searched up to April 30, 2020. Data were extracted independently by 2 authors and analyzed using random-effects models. RESULTS: The pooled mean GA growth rate was 1.66 mm2/year (SD = 1.27 mm2/year, I2 = 97.0%, p < 0.001) from 23 studies (3,078 patients) reported with growth rate in mm2/year and 0.33 mm/year (SD = 0.17 mm/year, I2 = 83.0%, p < 0.001) from 12 studies (1,808 patients) reported with growth rate in mm/year. Larger mean baseline GA area in mm2 was associated with larger mean growth rate in both mm2/year and mm/year (p < 0.001). The sample size at 85% power for detecting 15% reduction in growth rate in a 2-arm GA trial is 464 and 209 patients per arm, respectively, for using mm2/year and mm/year as the primary outcome. DISCUSSION/CONCLUSION: GA natural history studies had a pooled mean (SD) GA growth rate of 1.66 (1.27) mm2/year or 0.33 (0.17) mm/year. Because GA growth rate using mm/year requires smaller sample size than using mm2/year, GA growth rate in mm/year is recommended as the primary outcome measure for future GA trials.

Ridge-furrow with grass straw mulching farming system to boost rainfed wheat productivity and water use efficiency in semiarid Kenya.

BACKGROUND: Ridge-furrow mulching farming systems (RFMs) aim to increase field productivity and improve water use efficiency. To explore environment-friendly and efficient farming systems is a central aspect of rainfed wheat field management in Kenya where rainfall utilization is at a low level. We introduced RFMs (including plastic film and grass straw mulching) to semiarid Kenya to evaluate the effects on field productivity, rainwater utilization, soil quality and economic profitability using old and modern wheat cultivars from 2012 to 2013. RESULTS: Across the cultivars, the RFMs increased grain yield, aboveground biomass and water use efficiency by 74-163%, 36-104% and 89-273%, respectively, compared with conventional flat planting (control). RFMs significantly shortened the vegetative period while prolonging the reproductive period. The net economic output under RFMs was 74-165% higher than that of the control. Grass straw mulching achieved the highest economic output to input ratio, almost 45% higher than plastic film mulching, despite the former harvested only 82% of the maximum field productivity of the latter. Compared with the control, grass straw mulching promoted the contents of soil organic carbon, total nitrogen and C:N ratio by 14%, 8% and 5%, respectively, while obviously decreased values of these parameters were observed under plastic mulching. CONCLUSIONS: Through reducing soil water loss, and improving rainwater use efficiency and soil quality, ridge-furrow grass straw mulching would be a sustainable option for boosting field productivity and thus ensuring local food security in rainfed agricultural areas of Kenya. © 2020 Society of Chemical Industry.

Arabidopsis thaliana trehalose-6-phosphate phosphatase gene TPPI enhances drought tolerance by regulating stomatal apertures.

Transpiration occurs through stomata. The alteration of stomatal apertures in response to drought stress is an important process associated with water use efficiency (WUE). Trehalose-6-phosphate phosphatase (TPP) family genes have been reported to participate in adjustment of stomatal aperture. However, there have been no reports of the trehalose metabolism pathway genes improving WUE, and the upstream signalling pathway modulating these genes is not clear. Here, we demonstrate that a member of the TPP gene family, AtTPPI, confers drought resistance and improves WUE by decreasing stomatal apertures and improving root architecture. The reduced expression of AtTPPI caused a drought-sensitive phenotype, while its overexpression significantly increased drought tolerance. Abscisic acid (ABA)-induced stomatal closure experiments confirmed that AtTPPI mutation increased the stomatal aperture compared with that of wild-type plants; in contrast, overexpression plants had smaller stomatal apertures than those of wild-type plants. Moreover, AtTPPI mutation also caused stunted primary root length and compromised auxin transport, while overexpression plants had longer primary root lengths. Yeast one-hybrid assays showed that ABA-responsive element-binding factor1 (ABF1), ABF2, and ABF4 directly regulated AtTPPI expression. In summary, the way in which AtTPPI responds to drought stress suggests that AtTPPI-mediated stomatal regulation is an important mechanism to cope with drought stress and improve WUE.

Prevalence of myopia and vision impairment in school students in Eastern China.

BACKGROUND: Prevention of myopia has become a public health priority in China. This study is to investigate the prevalence of myopia and vision impairment, and their associated factors in school students in eastern China. METHOD: In this cross-sectional school-based study of 4801 students from 16 schools ranging from kindergarten to high school, students underwent refraction using non-cycloplegic autorefractor and visual acuity testing using logMAR chart with tumbling E. Myopia was defined as spherical equivalent (SPHE) ≤ - 0.5 diopter (D) and uncorrected visual acuity (UCVA) 20/25 or worse. High myopia was defined as SPHE ≤ - 6.0 D and UCVA 20/25 or worse. Vision impairment was defined as UCVA 20/40 or worse. Logistic regression models were used to determine factors associated with myopia and vision impairment. RESULTS: Among 4801 children (55% male) with mean age (standard deviation) 12.3 (3.8) years, 3030 (63.1, 95% CI: 61.7-64.5%) had myopia, 452 (9.4, 95% CI: 8.6-10.3%) had high myopia, and 2644 (55.1, 95% CI, 53.7-56.5%) had vision impairment. The prevalence rate of myopia increased with grade in a non-linear manner, 12% in kindergarten, 32% in grade 2, 69% in grade 5, and approximately 90% by grade 10 or above. The prevalence rate of high myopia was relatively low in grade 4 or below (< 1.5%), 4-7% in grade 5 to 7, 13-15% in grade 8-9, and > 20% in grade 10 to 12. The prevalence rate of vision impairment was 4% in kindergarten, 37% in elementary school, 77% in middle school and 87% in high school students. Higher grade (p < 0.0001), female (p < 0.0001) and higher school workload (p = 0.007) were independently associated with higher prevalence rates of myopia and vision impairment, while higher grade (p < 0.0001) and higher school workload (p < 0.0001) were independently associated with higher prevalence of high myopia. CONCLUSION: Prevalence of myopia and vision impairment was high among Chinese school students and increased with grade in a non-linear manner, reaching alarming high in high school students accompanied by high prevalence of high myopia. Increasing study burden on school students at younger age plays an important role on the higher prevalence rate of myopia and vision impairment.

Astigmatism in school students of eastern China: prevalence, type, severity and associated risk factors.

BACKGROUND: China has been undergoing dramatic economic development, accompanied by increased education load on the young children. This study is to investigate the prevalence, type, severity, and associated risk factors of astigmatism in school students in eastern China. METHOD: In this cross-sectional school-based study, students underwent refraction using NIDEK non-cycloplegic autorefractor. Astigmatism was defined as cylinder 1.5 diopter (D) or greater, and high astigmatism was defined as cylinder 3.0 D or greaterMultivariate regression models were used to determine factors associated with astigmatism. RESULTS: Among 4801 children (55% male) with mean age (±standard deviation) 12.3 (±3.8) years, 680 (14.2, 95% confidence interval (95% CI): 13.2-15.2%) had astigmatism (85% were with-the-rule) and 103 (2.2, 95% CI: 1.8-2.6%) had high astigmatism. The prevalence rate of astigmatism was 7-8% in grades 4 or below, 15-16% in grades 6-8, 20% in grade 9, and 20-25% in grade 10 or above. In multivariate analyses, higher grade and male gender were associated with higher prevalence of astigmatism (all p < 0.0001) and high astigmatism (p = 0.04 for grade, p = 0.001 for gender). When multivariate models were further adjusted by spherical equivalent, only gender remained statistically associated with astigmatism (odds ratio (OR) = 1.65, p < 0.0001) and high astigmatism (OR = 2.21, p = 0.0004), myopic and hyperopic refractive error were significantly associated with higher risk of astigmatism and high astigmatism (all p < 0.0001). CONCLUSION: Astigmatism is common in Chinese school-age children and increases with grade. Majority of astigmatism is with-the-rule. Male gender and myopic or hyperopic refractive error are significantly associated with higher prevalence and severity of astigmatism.

[Clinical practice guidelines for Leber's hereditary optic neuropathy].

Leber's hereditary optic neuropathy (LHON) is a genetic disease featuring maternal inheritance. mtDNA m.11778G>A, m.14484T>C and m.3460G>A mutations are its main molecular basis, but the disease is also affected by nuclear genes, genetic background of mtDNA and environmental factors. By referring to basic and clinical research in the related fields at home and abroad, guidelines and consensus issued by other countries, and combined with data from the Chinese population, this guideline aims to summarize the genetics knowledge and clinical treatment of LHON, with an aim to improve the clinical diagnosis and standardize the clinical management of patients.

Tunable Electrochemical C-N versus N-N Bond Formation of Nitrogen-Centered Radicals Enabled by Dehydrogenative Dearomatization: Biological Applications.

Herein, an environmentally friendly electrochemical approach is reported that takes advantage of the captodative effect and delocalization effect to generate nitrogen-centered radicals (NCRs). By changing the reaction parameters of the electrode material and feedstock solubility, dearomatization enabled a selective dehydrogenative C-N versus N-N bond formation reaction. Hence, pyrido[1,2-a]benzimidazole and tetraarylhydrazine frameworks were prepared through a sustainable transition-metal- and exogenous oxidant-free strategy with broad generality. Bioactivity assays demonstrated that pyrido[1,2-a]benzimidazoles displayed antimicrobial activity and cytotoxicity against human cancer cells. Compound 21 exhibited good photochemical properties with a large Stokes shift (approximately 130 nm) and was successfully applied to subcellular imaging. A preliminary mechanism investigation and density functional theory (DFT) calculations revealed the possible reaction pathway.