Hyperoside alleviates photoreceptor degeneration by preventing cell senescence through AMPK-ULK1 signaling.

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age-related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration-related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence-associated ß-galactosidase activity, DNA damage, oxidative stress and inflammation-related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti-aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU-induced injury and aging of photoreceptors via AMPK-ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU-induced photoreceptor degeneration by inhibiting cell senescence via the AMPK-ULK1 pathway.

Analysis of shared ceRNA networks and related-hub genes in rats with primary and secondary photoreceptor degeneration.

Introduction: Photoreceptor degenerative diseases are characterized by the progressive death of photoreceptor cells, resulting in irreversible visual impairment. However, the role of competing endogenous RNA (ceRNA) in photoreceptor degeneration is unclear. We aimed to explore the shared ceRNA regulation network and potential molecular mechanisms between primary and secondary photoreceptor degenerations. Methods: We established animal models for both types of photoreceptor degenerations and conducted retina RNA sequencing to identify shared differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Using ceRNA regulatory principles, we constructed a shared ceRNA network and performed function enrichment and protein-protein interaction (PPI) analyses to identify hub genes and key pathways. Immune cell infiltration and drug-gene interaction analyses were conducted, and hub gene expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 37 shared differentially expressed lncRNAs, 34 miRNAs, and 247 mRNAs and constructed a ceRNA network consisting of 3 lncRNAs, 5 miRNAs, and 109 mRNAs. Furthermore, we examined 109 common differentially expressed genes (DEGs) through functional annotation, PPI analysis, and regulatory network analysis. We discovered that these diseases shared the complement and coagulation cascades pathway. Eight hub genes were identified and enriched in the immune system process. Immune infiltration analysis revealed increased T cells and decreased B cells in both photoreceptor degenerations. The expression of hub genes was closely associated with the quantities of immune cell types. Additionally, we identified 7 immune therapeutical drugs that target the hub genes. Discussion: Our findings provide new insights and directions for understanding the common mechanisms underlying the development of photoreceptor degeneration. The hub genes and related ceRNA networks we identified may offer new perspectives for elucidating the mechanisms and hold promise for the development of innovative treatment strategies.

Retinal Artery Angles in High Axial Myopia and Its Relationship With Visual Function.

Purpose: To evaluate the retinal artery angles in high axial myopia and assess the correlation with other morphometric and functional parameters. Methods: This cross-sectional study included 112 eyes of 112 patients with high axial myopia. Based on axial length (AL), the participants were divided into three groups: group 1 (26 ≤ AL < 28 mm), group 2 (28 ≤ AL < 31 mm), and group 3 (≥31 mm). Scanning laser ophthalmoscopy imaging was used to analyze the retinal artery angle (Yugami correlated angle [YCA]). Retinal vascular densities (VDs) in both superficial capillary plexuses (SCPs) and deep capillary plexuses were evaluated. Fixation behavior, including retinal mean sensitivity (MS), macular fovea 2°, 4° fixation rate (P1, P2), and 68.2% bivariate contour ellipse area, were analyzed by microperimetry. Finally, the correlation between YCAs and AL, VDs, best-corrected visual acuity (BCVA), and fixation behavior was assessed. Results: The YCAs showed significant differences among the three groups (all P < 0.001, respectively). Compared to group 1, the YCA decreased in group 2 (P < 0.001) and continued to decrease in group 3 (P = 0.043). The correlation analysis revealed that smaller YCAs (YCA, YCA1/2, YCA1/4) were positively correlated with the longer AL (ρ = 0.580, 0.545, 0.448, P < 0.001) and lower VDs in any sector in SCPs (all P ≤ 0.05). Furthermore, smaller YCAs were positively correlated with decreased BCVA (ρ = 0.392, 0.387, 0.262; all P < 0.001) and reduced MS (ρ= 0.300, 0.269, 0.244; all P < 0.05). Conclusions: Smaller YCAs were correlated with longer AL, lower VD in SCP, decreased BCVA, and reduced MS. The YCAs might reflect vascular deformation caused by axial elongation and could potentially be useful in predicting visual function in high axial myopia. Translational Relevance: The quantitative analysis of YCAs in fundus photography holds potential clinical value in predicting visual function in high axial myopia.

Large spatial variation and stagnation of cropland gross primary production increases the challenges of sustainable grain production and food security in China.

Sustainable crop grain production and food security is a grand societal challenge. Substantial investments in China's agriculture have been made in the past decades, but our knowledge on cropland gross primary production in China remains limited. Here we analyzed gross primary production (GPP), solar-induced chlorophyll fluorescence (SIF), terrestrial water storage, crop grain production, and agricultural investment and policy during 2000-2018. We found that based on croplands in 2000, approximately 52 × 106 ha (~37%) had continuous increasing trends in GPP during 2000-2018, which were mainly located in northern China. GPP for 63% of croplands was stagnant, declined, or had no significant change. At the national scale, annual cropland GPP increased during 2000-2008 but became stagnant in 2009-2018, which was inconsistent with the interannual trend in the crop grain production data for 2009-2018. The spatial mismatch between crop production and water availability became worse. The major grain exporting provinces, mostly located in water-stressed regions, experienced increased water resource constraints, which posed a challenge for sustainable grain production. The stagnant cropland GPP and increasing water resource constraints highlight the urgent need for sustainable management for crop production and food security in China.

Tracking annual changes of coastal tidal flats in China during 1986-2016 through analyses of Landsat images with Google Earth Engine.

Tidal flats (non-vegetated area), along with coastal vegetation area, constitute the coastal wetlands (intertidal zone) between high and low water lines, and play an important role in wildlife, biodiversity and biogeochemical cycles. However, accurate annual maps of coastal tidal flats over the last few decades are unavailable and their spatio-temporal changes in China are unknown. In this study, we analyzed all the available Landsat TM/ETM+/OLI imagery (~ 44,528 images) using the Google Earth Engine (GEE) cloud computing platform and a robust decision tree algorithm to generate annual frequency maps of open surface water body and vegetation to produce annual maps of coastal tidal flats in eastern China from 1986 to 2016 at 30-m spatial resolution. The resulting map of coastal tidal flats in 2016 was evaluated using very high-resolution images available in Google Earth. The total area of coastal tidal flats in China in 2016 was about 731,170 ha, mostly distributed in the provinces around Yellow River Delta and Pearl River Delta. The interannual dynamics of coastal tidal flats area in China over the last three decades can be divided into three periods: a stable period during 1986-1992, an increasing period during 1993-2001 and a decreasing period during 2002-2016. The resulting annual coastal tidal flats maps could be used to support sustainable coastal zone management policies that preserve coastal ecosystem services and biodiversity in China.

Gainers and losers of surface and terrestrial water resources in China during 1989-2016.

Data and knowledge of the spatial-temporal dynamics of surface water area (SWA) and terrestrial water storage (TWS) in China are critical for sustainable management of water resources but remain very limited. Here we report annual maps of surface water bodies in China during 1989-2016 at 30m spatial resolution. We find that SWA decreases in water-poor northern China but increases in water-rich southern China during 1989-2016. Our results also reveal the spatial-temporal divergence and consistency between TWS and SWA during 2002-2016. In North China, extensive and continued losses of TWS, together with small to moderate changes of SWA, indicate long-term water stress in the region. Approximately 569 million people live in those areas with deceasing SWA or TWS trends in 2015. Our data set and the findings from this study could be used to support the government and the public to address increasing challenges of water resources and security in China.

Mapping coastal wetlands of China using time series Landsat images in 2018 and Google Earth Engine.

Coastal wetlands, composed of coastal vegetation and non-vegetated tidal flats, play critical roles in biodiversity conservation, food production, and the global economy. Coastal wetlands in China are changing quickly due to land reclamation from sea, aquaculture, industrialization, and urbanization. However, accurate and updated maps of coastal wetlands (including vegetation and tidal flats) in China are unavailable, and the detailed spatial distribution of coastal wetlands are unknown. Here, we developed a new pixel- and phenology-based algorithm to identify and map coastal wetlands in China for 2018 using time series Landsat imagery (2,798 ETM+/OLI images) and the Google Earth Engine (GEE). The resultant map had a very high overall accuracy (98%). There were 7,474.6 km2 of coastal wetlands in China in 2018, which included 5,379.8 km2 of tidal flats, 1,856.4 km2 of deciduous wetlands, and 238.3 km2 of evergreen wetlands. Jiangsu Province had the largest area of coastal wetlands in China, followed by Shandong, Fujian, and Zhejiang Provinces. Our study demonstrates the high potential of time series Landsat images, pixel- and phenology-based algorithm, and GEE for mapping coastal wetlands at large scales. The resultant coastal wetland maps at 30-m spatial resolution serve as the most current dataset for sustainable management, ecological assessments, and conservation of coastal wetlands in China.

Large increases of paddy rice area, gross primary production, and grain production in Northeast China during 2000-2017.

China is the largest rice producer and consumer in the world. Accurate estimations of paddy rice planting area and rice grain production is important for feeding the increasing population in China. However, Southern China had substantial losses in paddy rice area over the last three decades in those regions where paddy rice has traditionally been produced. Several studies have shown increased paddy rice area in Northeast China. Here we document the annual dynamics of paddy rice area, gross primary production (GPP), and grain production in Northeast China (Heilongjiang, Jilin and Liaoning provinces) during 2000-2017 using agricultural statistical data, satellite images, and model simulations. Annual maps derived from satellite images show that paddy rice area in Northeast China has increased by 3.68 million ha from 2000 to 2017, which is more than the total combined paddy rice area of North Korea, South Korea, and Japan. Approximately 82% of paddy rice pixels had an increase in annual GPP during 2000-2017. The expansion of paddy rice area slowed down substantially since 2015. Annual GPP from those paddy rice fields cultivated continuously over the 18 years were moderately higher than that from other paddy rice fields, which suggested that improved management practices could increase grain production in the region. There was a strong linear relationship between annual GPP and annual rice grain production in Northeast China by province and year, which illustrates the potential of using satellite-based data-driven model to track and assess grain production of paddy rice in the region. Northeast China is clearly an emerging rice production base and plays an increasing role in crop production and food security in China. However, many challenges for the further expansion and sustainable cultivation of paddy rice in Northeast China remain.

p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells.

How ubiquitous transcription factors (TFs) coordinate temporal inputs from broadly expressed epigenetic factors to control cell fate remains poorly understood. Here, we uncover a molecular relationship between p53, an abundant embryonic TF, and WDR5, an essential member of the MLL chromatin modifying complex, that regulates mouse embryonic stem cell fate. Wild-type Wdr5 or transient Wdr5 knockout promotes a distinct pattern of global chromatin accessibility and spurs neuroectodermal differentiation through an RbBP5-dependent process in which WDR5 binds to, and activates transcription of, neural genes. Wdr5 rescue after its prolonged inhibition targets WDR5 to mesoderm lineage-specifying genes, stimulating differentiation toward mesoderm fates in a p53-dependent fashion. Finally, we identify a direct interaction between WDR5 and p53 that enables their co-recruitment to, and regulation of, genes known to control cell proliferation and fate. Our results unmask p53-dependent mechanisms that temporally integrate epigenetic WDR5 inputs to drive neuroectoderm and mesoderm differentiation from pluripotent cells.

Continuous monitoring of lake dynamics on the Mongolian Plateau using all available Landsat imagery and Google Earth Engine.

Lakes are important water resources on the Mongolian Plateau (MP) for human's livelihood and production as well as maintaining ecosystem services. Previous studies, based on the Landsat-based analyses at epoch scale and visual interpretation approach, have reported a significant loss in the lake areas and numbers, especially from the late 1990s to 2010. Given the remarkable inter- and intra-annual variations of lakes in the arid and semi-arid region, a comprehensive picture of annual lake dynamics is needed. Here we took advantages of the power of all the available Landsat images and the cloud computing platform Google Earth Engine (GEE) to map water body for each scene, and then extracted lakes by post-processing including raster-to-vector conversion and separation of lakes and rivers. Continuous dynamics of the lakes over 1 km2 was monitored annually on the MP from 1991 to 2017. We found a significant shrinkage in the lake areas and numbers of the MP from 1991 to 2009, then the decreasing lakes on the MP have recovered since circa 2009. Specifically, Inner Mongolia of China experienced more dramatic lake variations than Mongolia. A few administrative regions with huge lakes, including Hulunbuir and Xilin Gol in Inner Mongolia and Ubsa in Mongolia, dominated the lake area variations in the study area, suggesting that the prior treatments on these major lakes would be critical for water management on the MP. The varied drivers of lake variations in different regions showed the complexity of factors impacting lakes. While both natural and anthropogenic factors significantly affected lake dynamics before 2009, precipitation played increasingly important role for the recovery of lakes on the MP after 2009.

HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis.

Aberrant expression of HOXA9 is a prominent feature of acute leukemia driven by diverse oncogenes. Here we show that HOXA9 overexpression in myeloid and B progenitor cells leads to significant enhancer reorganizations with prominent emergence of leukemia-specific de novo enhancers. Alterations in the enhancer landscape lead to activation of an ectopic embryonic gene program. We show that HOXA9 functions as a pioneer factor at de novo enhancers and recruits CEBPα and the MLL3/MLL4 complex. Genetic deletion of MLL3/MLL4 blocks histone H3K4 methylation at de novo enhancers and inhibits HOXA9/MEIS1-mediated leukemogenesis in vivo. These results suggest that therapeutic targeting of HOXA9-dependent enhancer reorganization can be an effective therapeutic strategy in acute leukemia with HOXA9 overexpression.

Divergent trends of open-surface water body area in the contiguous United States from 1984 to 2016.

The contiguous United States (CONUS), especially the West, faces challenges of increasing water stress and uncertain impacts of climate change. The historical information of surface water body distribution, variation, and multidecadal trends documented in remote-sensing images can aid in water-resource planning and management, yet is not well explored. Here, we detected open-surface water bodies in all Landsat 5, 7, and 8 images (∼370,000 images, >200 TB) of the CONUS and generated 30-meter annual water body frequency maps for 1984-2016. We analyzed the interannual variations and trends of year-long water body area, examined the impacts of climatic and anthropogenic drivers on water body area dynamics, and explored the relationships between water body area and land water storage (LWS). Generally, the western half of the United States is prone to water stress, with small water body area and large interannual variability. During 1984-2016, water-poor regions of the Southwest and Northwest had decreasing trends in water body area, while water-rich regions of the Southeast and far north Great Plains had increasing trends. These divergent trends, mainly driven by climate, enlarged water-resource gaps and are likely to continue according to climate projections. Water body area change is a good indicator of LWS dynamics in 58% of the CONUS. Following the 2012 prolonged drought, LWS in California and the southern Great Plains had a larger decrease than surface water body area, likely caused by massive groundwater withdrawals. Our findings provide valuable information for surface water-resource planning and management across the CONUS.

Global patterns of extreme drought-induced loss in land primary production: Identifying ecological extremes from rain-use efficiency.

Quantifying the ecological patterns of loss of ecosystem function in extreme drought is important to understand the carbon exchange between the land and atmosphere. Rain-use efficiency [RUE; gross primary production (GPP)/precipitation] acts as a typical indicator of ecosystem function. In this study, a novel method based on maximum rain-use efficiency (RUEmax) was developed to detect losses of ecosystem function globally. Three global GPP datasets from the MODIS remote sensing data (MOD17), ground upscaling FLUXNET observations (MPI-BGC), and process-based model simulations (BESS), and a global gridded precipitation product (CRU) were used to develop annual global RUE datasets for 2001-2011. Large, well-known extreme drought events were detected, e.g. 2003 drought in Europe, 2002 and 2011 drought in the U.S., and 2010 drought in Russia. Our results show that extreme drought-induced loss of ecosystem function could impact 0.9% ±â€¯0.1% of earth's vegetated land per year and was mainly distributed in semi-arid regions. The reduced carbon uptake caused by functional loss (0.14 ±â€¯0.03 PgC/yr) could explain >70% of the interannual variation in GPP in drought-affected areas (p ≤ 0.001). Our results highlight the impact of ecosystem function loss in semi-arid regions with increasing precipitation variability and dry land expansion expected in the future.

Continued decrease of open surface water body area in Oklahoma during 1984-2015.

Oklahoma contains the largest number of manmade lakes and reservoirs in the United States. Despite the importance of these open surface water bodies to public water supply, agriculture, thermoelectric power, tourism and recreation, it is unclear how these water bodies have responded to climate change and anthropogenic water exploitation in past decades. In this study, we used all available Landsat 5 and 7 images (16,000 scenes) from 1984 through 2015 and a water index- and pixel-based approach to analyze the spatial-temporal variability of open surface water bodies and its relationship with climate and water exploitation. Specifically, the areas and numbers of four water body extents (the maximum, year-long, seasonal, and average extents) were analyzed to capture variations in water body area and number. Statistically significant downward trends were found in the maximum, year-long, and annual average water body areas from 1984 through 2015. Furthermore, these decreases were mainly attributed to the continued shrinking of large water bodies (>1km2). There were also significant decreases in maximum and year-long water body numbers, which suggested that some of the water bodies were vanishing year by year. However, remarkable inter-annual variations of water body area and number were also found. Both water body area and number were positively related to precipitation, and negatively related to temperature. Surface water withdrawals mainly influenced the year-long water bodies. The smaller water bodies have a higher risk of drying under a drier climate, which suggests that small water bodies are more vulnerable under climate-warming senarios.

The time process of post-earthquake recovery: the Yao'an earthquake in China.

Post-disaster recovery is a constantly changing and developing process. The authors conducted three real-name follow-up surveys at 1, 12 and 18 months after the Yao'an earthquake, which had a surface wave magnitude of 6.0. They also calculated recovery ratios at different times and drew post-earthquake domestic life recovery curves. Based on the recovery curves, the time trajectory of domestic life recovery takes on an approximate S-type development and change process. The recovery time process of domestic life can be divided into four periods: emergency period (weeks 0-2(5)), early recovery period (weeks 2(5)-24), rapid recovery period (weeks 24-34) and late recovery period (weeks 34-60(80)).

PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130.

Maintenance of the Golgi apparatus (GA) structure and function depends on Golgi matrix proteins. The posttranslational modification of Golgi proteins such as phosphorylation of members of the golgin and GRASP families is important for determining Golgi architecture. Some Golgi proteins including golgin-84 are also known to be methylated, but the function of golgin methylation remains unclear. Here, we show that the protein arginine methyltransferase 5 (PRMT5) localizes to the GA and forms complexes with several components involved in GA ribbon formation and vesicle tethering. PRMT5 interacts with the golgin GM130, and depletion of PRMT5 causes defects in Golgi ribbon formation. Furthermore, PRMT5 methylates N-terminal arginines in GM130, and such arginine methylation appears critical for GA ribbon formation. Our findings reveal a molecular mechanism by which PRMT5-dependent arginine methylation of GM130 controls the maintenance of GA architecture.