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Cheng Peng, Yilin Xu, Jing Wu, Donghai Wu, Lili Zhou, Xinhua Xia School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Xinhua Xia; Lili Zhou, Email xiaxinhua001@hnucm.edu.cn; 004683@hnucm.edu.cnAbstract: The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.Keywords: nanoparticles, biomimetic delivery system, tumor therapy, cell membrane-coating

Variation in canopy water content (CWC) that can be detected from microwave remote sensing of vegetation optical depth (VOD) has been proposed as an important measure of vegetation water stress. However, the contribution of leaf surface water (LWs ), arising from dew formation and rainfall interception, to CWC is largely unknown, particularly in tropical forests and other high-humidity ecosystems. We compared VOD data from the Advanced Microwave Scanning Radiometer for the Earth Observing System (AMSR-E) and CWC predicted by a plant hydrodynamics model at four tropical sites in Brazil spanning a rainfall gradient. We assessed how LWs influenced the relationship between VOD and CWC. The analysis indicates that while CWC is strongly correlated with VOD (R2  = 0.62 across all sites), LWs accounts for 61-76% of the diurnal variation in CWC despite being < 10% of CWC. Ignoring LWs weakens the near-linear relationship between CWC and VOD and reduces the consistency in diurnal variation. The contribution of LWs to CWC variation, however, decreases at longer, seasonal to inter-annual, time scales. Our results demonstrate that diurnal patterns of dew formation and rainfall interception can be an important driver of diurnal variation in CWC and VOD over tropical ecosystems and therefore should be accounted for when inferring plant diurnal water stress from VOD measurements.

Global climate changes have increased the imbalance of water resources, especially in northern China, which comprises typical arid and semiarid regions. Large-scale afforestation has been implemented over the past three decades in northern China. The ecosystem water use efficiency (WUE) connects the carbon cycle and water cycle of the terrestrial ecosystems and is defined as the ratio of the gross primary productivity (GPP) to the evapotranspiration. However, there are still an insufficient number of studies on the impact of the afforestation on the WUE. In this study, we applied the random forest (RF) model to explore the impacts of climate and nonclimate factors on the WUE in northern China. The results showed that in areas with high precipitation, the forests had the highest WUE, while in the arid areas, the croplands had the highest WUE. Of the total area, 44.34% showed a significant increase, and 5.89% showed a significant decrease in the WUE from 1982-2015 in northern China. The main driving factors for the changes in the WUE were climate factors, including the precipitation, temperature and solar radiation, which contributed to approximately 84% of the WUE trends, while human activities, such as afforestation, contributed to approximately 16% of the WUE trends. Overall, although the climate had a larger impact on the WUE dynamics than the human activities, our results suggested that the impacts of the afforestation programs on forest carbon and water cycles should be considered in the context of climate change. © 2019 by the authors.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

Global climate changes have increased the imbalance of water resources, especially in northern China, which comprises typical arid and semiarid regions. Large-scale afforestation has been implemented over the past three decades in northern China. The ecosystem water use efficiency (WUE) connects the carbon cycle and water cycle of the terrestrial ecosystems and is defined as the ratio of the gross primary productivity (GPP) to the evapotranspiration. However, there are still an insufficient number of studies on the impact of the afforestation on the WUE. In this study, we applied the random forest (RF) model to explore the impacts of climate and nonclimate factors on the WUE in northern China. The results showed that in areas with high precipitation, the forests had the highest WUE, while in the arid areas, the croplands had the highest WUE. Of the total area, 44.34% showed a significant increase, and 5.89% showed a significant decrease in the WUE from 1982-2015 in northern China. The main driving factors for the changes in the WUE were climate factors, including the precipitation, temperature and solar radiation, which contributed to approximately 84% of the WUE trends, while human activities, such as afforestation, contributed to approximately 16% of the WUE trends. Overall, although the climate had a larger impact on the WUE dynamics than the human activities, our results suggested that the impacts of the afforestation programs on forest carbon and water cycles should be considered in the context of climate change. © 2019 by the authors.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.

Global climate changes have increased the imbalance of water resources, especially in northern China, which comprises typical arid and semiarid regions. Large-scale afforestation has been implemented over the past three decades in northern China. The ecosystem water use efficiency (WUE) connects the carbon cycle and water cycle of the terrestrial ecosystems and is defined as the ratio of the gross primary productivity (GPP) to the evapotranspiration. However, there are still an insufficient number of studies on the impact of the afforestation on the WUE. In this study, we applied the random forest (RF) model to explore the impacts of climate and nonclimate factors on the WUE in northern China. The results showed that in areas with high precipitation, the forests had the highest WUE, while in the arid areas, the croplands had the highest WUE. Of the total area, 44.34% showed a significant increase, and 5.89% showed a significant decrease in the WUE from 1982-2015 in northern China. The main driving factors for the changes in the WUE were climate factors, including the precipitation, temperature and solar radiation, which contributed to approximately 84% of the WUE trends, while human activities, such as afforestation, contributed to approximately 16% of the WUE trends. Overall, although the climate had a larger impact on the WUE dynamics than the human activities, our results suggested that the impacts of the afforestation programs on forest carbon and water cycles should be considered in the context of climate change. © 2019 by the authors.

Extreme precipitation events, which have intensified with global warming over the past several decades, will become more intense in the future according to model projections. Although many studies have been performed, the occurrence patterns for extreme precipitation events in past and future periods in China remain unresolved. Additionally, few studies have explained how extreme precipitation events developed over the past 58 years and how they will evolve in the next 90 years as global warming becomes much more serious. In this paper, we evaluated the spatiotemporal characteristics of extreme precipitation events using indices for the frequency, quantity, intensity, and proportion of extreme precipitation, which were proposed by the World Meteorological Organization. We simultaneously analyzed the spatiotemporal characteristics of extreme precipitation in China from 2011 to 2100 using data obtained from the Coupled Model Intercomparison Project Phase 5 (CMIP5) models. Despite the fixed threshold, 95th percentile precipitation values were also used as the extreme precipitation threshold to reduce the influence of various rainfall events caused by different geographic locations; then, eight extreme precipitation indices (EPIs) were calculated to evaluate extreme precipitation in China. We found that the spatial characteristics of the eight EPIs exhibited downward trends from south to north. In the periods 1960-2017 and 2011-2100, trends in the EPIs were positive, but there were differences between different regions. In the past 58 years, the extreme precipitation increased in the northwest, southeast, and the Tibet Plateau of China, while decreased in northern China. Almost all the trends of EPIs are positive in the next two periods (2011-2055 and 2056-2100) except for some EPIs, such as intensity of extreme precipitation, which decrease in southeastern China in the second period (2056-2100). This study suggests that the frequency of extreme precipitation events in

There have been hiatuses in global warming since the 1990s, and their potential impacts have attracted extensive attention and discussion. Changes in temperature not only directly affect the greening of vegetation but can also indirectly alter both the growth state and the growth tendency of vegetation by altering other climatic elements. The middle-high latitudes of the Northern Hemisphere (NH) constitute the region that has experienced the most warming in recent decades; therefore, identifying the effects of warming hiatuses on the vegetation greening in that region is of great importance. Using satellite-derived Normalized Difference Vegetation Index (NDVI) data and climatological observation data from 1982-2013, we investigated hiatuses in warming trends and their impact on vegetation greenness in the NH. Our results show that the regions with warming hiatuses in the NH accounted for 50.1% of the total area and were concentrated in Mongolia, central China, and other areas. Among these regions, 18.8% of the vegetation greenness was inhibited in the warming hiatus areas, but 31.3% of the vegetation grew faster. Because temperature was the main positive climatic factor in central China, the warming hiatuses caused the slow vegetation greening rate. However, precipitation was the main positive climatic factor affecting vegetation greenness in Mongolia; an increase in precipitation accelerated vegetation greening. The regions without a warming hiatus, which were mainly distributed in northern Russia, northern central Asia, and other areas, accounted for 49.9% of the total area. Among these regions, 21.4% of the vegetation grew faster over time, but 28.5% of the vegetation was inhibited. Temperature was the main positive factor affecting vegetation greenness in northern Russia; an increase in temperature promoted vegetation greening. However, radiation was the main positive climatic factor in northern central Asia; reductions in radiation inhibited the greenness of ve

Extreme precipitation events, which have intensified with global warming over the past several decades, will become more intense in the future according to model projections. Although many studies have been performed, the occurrence patterns for extreme precipitation events in past and future periods in China remain unresolved. Additionally, few studies have explained how extreme precipitation events developed over the past 58 years and how they will evolve in the next 90 years as global warming becomes much more serious. In this paper, we evaluated the spatiotemporal characteristics of extreme precipitation events using indices for the frequency, quantity, intensity, and proportion of extreme precipitation, which were proposed by the World Meteorological Organization. We simultaneously analyzed the spatiotemporal characteristics of extreme precipitation in China from 2011 to 2100 using data obtained from the Coupled Model Intercomparison Project Phase 5 (CMIP5) models. Despite the fixed threshold, 95th percentile precipitation values were also used as the extreme precipitation threshold to reduce the influence of various rainfall events caused by different geographic locations; then, eight extreme precipitation indices (EPIs) were calculated to evaluate extreme precipitation in China. We found that the spatial characteristics of the eight EPIs exhibited downward trends from south to north. In the periods 1960-2017 and 2011-2100, trends in the EPIs were positive, but there were differences between different regions. In the past 58 years, the extreme precipitation increased in the northwest, southeast, and the Tibet Plateau of China, while decreased in northern China. Almost all the trends of EPIs are positive in the next two periods (2011-2055 and 2056-2100) except for some EPIs, such as intensity of extreme precipitation, which decrease in southeastern China in the second period (2056-2100). This study suggests that the frequency of extreme precipitation events in

As an indicative parameter that represents the ability of the Earth's surface to reflect solar radiation, albedo determines the allocation of solar energy between the Earth's surface and the atmosphere, which plays an important role in both global and local climate change. Urbanization is a complicated progress that greatly affects urban albedo via land cover change, human heat, aerosol, and other human activities. Although many studies have been conducted to identify the effects of these various factors on albedo separately, there are few studies that have quantitatively determined the combined effects of urbanization on albedo. In this study, based on a partial derivative method, vegetation index data and nighttime light data were used to quantitatively calculate the natural climate change and human activities' contributions to albedo variations in the Jing-Jin-Ji region, during its highest population growth period from 2001 to 2011. The results show that (1) 2005 is the year when urbanization starts accelerating in the Jing-Jin-Ji region; (2) albedo trends are equal to 0.0065 year-1 before urbanization and 0.0012 year-1 after urbanization, which is a reduction of 4/5; and (3) the contribution rate of urbanization increases from 15% to 48.4%, which leads to a decrease in albedo of approximately 0.05. Understanding the contribution of urbanization to variations in urban albedo is significant for future studies on urban climate change via energy balance and can provide scientific data for energy conservation policymaking. © 2018 by the authors.

There have been hiatuses in global warming since the 1990s, and their potential impacts have attracted extensive attention and discussion. Changes in temperature not only directly affect the greening of vegetation but can also indirectly alter both the growth state and the growth tendency of vegetation by altering other climatic elements. The middle-high latitudes of the Northern Hemisphere (NH) constitute the region that has experienced the most warming in recent decades; therefore, identifying the effects of warming hiatuses on the vegetation greening in that region is of great importance. Using satellite-derived Normalized Difference Vegetation Index (NDVI) data and climatological observation data from 1982-2013, we investigated hiatuses in warming trends and their impact on vegetation greenness in the NH. Our results show that the regions with warming hiatuses in the NH accounted for 50.1% of the total area and were concentrated in Mongolia, central China, and other areas. Among these regions, 18.8% of the vegetation greenness was inhibited in the warming hiatus areas, but 31.3% of the vegetation grew faster. Because temperature was the main positive climatic factor in central China, the warming hiatuses caused the slow vegetation greening rate. However, precipitation was the main positive climatic factor affecting vegetation greenness in Mongolia; an increase in precipitation accelerated vegetation greening. The regions without a warming hiatus, which were mainly distributed in northern Russia, northern central Asia, and other areas, accounted for 49.9% of the total area. Among these regions, 21.4% of the vegetation grew faster over time, but 28.5% of the vegetation was inhibited. Temperature was the main positive factor affecting vegetation greenness in northern Russia; an increase in temperature promoted vegetation greening. However, radiation was the main positive climatic factor in northern central Asia; reductions in radiation inhibited the greenness of ve

Field measurements of aboveground net primary productivity (ANPP) in temperate grasslands suggest that both positive and negative asymmetric responses to changes in precipitation (P) may occur. Under normal range of precipitation variability, wet years typically result in ANPP gains being larger than ANPP declines in dry years (positive asymmetry), whereas increases in ANPP are lower in magnitude in extreme wet years compared to reductions during extreme drought (negative asymmetry). Whether the current generation of ecosystem models with a coupled carbon–water system in grasslands are capable of simulating these asymmetric ANPP responses is an unresolved question. In this study, we evaluated the simulated responses of temperate grassland primary productivity to scenarios of altered precipitation with 14 ecosystem models at three sites: Shortgrass steppe (SGS), Konza Prairie (KNZ) and Stubai Valley meadow (STU), spanning a rainfall gradient from dry to moist. We found that (1) the spatial slopes derived from modeled primary productivity and precipitation across sites were steeper than the temporal slopes obtained from inter-annual variations, which was consistent with empirical data; (2) the asymmetry of the responses of modeled primary productivity under normal inter-annual precipitation variability differed among models, and the mean of the model ensemble suggested a negative asymmetry across the three sites, which was contrary to empirical evidence based on filed observations; (3) the mean sensitivity of modeled productivity to rainfall suggested greater negative response with reduced precipitation than positive response to an increased precipitation under extreme conditions at the three sites; and (4) gross primary productivity (GPP), net primary productivity (NPP), aboveground NPP (ANPP) and belowground NPP (BNPP) all showed concave-down nonlinear responses to altered precipitation in all the models, but with different curvatures and mean values. Our results in

Extreme precipitation events, which have intensified with global warming over the past several decades, will become more intense in the future according to model projections. Although many studies have been performed, the occurrence patterns for extreme precipitation events in past and future periods in China remain unresolved. Additionally, few studies have explained how extreme precipitation events developed over the past 58 years and how they will evolve in the next 90 years as global warming becomes much more serious. In this paper, we evaluated the spatiotemporal characteristics of extreme precipitation events using indices for the frequency, quantity, intensity, and proportion of extreme precipitation, which were proposed by the World Meteorological Organization. We simultaneously analyzed the spatiotemporal characteristics of extreme precipitation in China from 2011 to 2100 using data obtained from the Coupled Model Intercomparison Project Phase 5 (CMIP5) models. Despite the fixed threshold, 95th percentile precipitation values were also used as the extreme precipitation threshold to reduce the influence of various rainfall events caused by different geographic locations; then, eight extreme precipitation indices (EPIs) were calculated to evaluate extreme precipitation in China. We found that the spatial characteristics of the eight EPIs exhibited downward trends from south to north. In the periods 1960-2017 and 2011-2100, trends in the EPIs were positive, but there were differences between different regions. In the past 58 years, the extreme precipitation increased in the northwest, southeast, and the Tibet Plateau of China, while decreased in northern China. Almost all the trends of EPIs are positive in the next two periods (2011-2055 and 2056-2100) except for some EPIs, such as intensity of extreme precipitation, which decrease in southeastern China in the second period (2056-2100). This study suggests that the frequency of extreme precipitation events in

As an indicative parameter that represents the ability of the Earth's surface to reflect solar radiation, albedo determines the allocation of solar energy between the Earth's surface and the atmosphere, which plays an important role in both global and local climate change. Urbanization is a complicated progress that greatly affects urban albedo via land cover change, human heat, aerosol, and other human activities. Although many studies have been conducted to identify the effects of these various factors on albedo separately, there are few studies that have quantitatively determined the combined effects of urbanization on albedo. In this study, based on a partial derivative method, vegetation index data and nighttime light data were used to quantitatively calculate the natural climate change and human activities' contributions to albedo variations in the Jing-Jin-Ji region, during its highest population growth period from 2001 to 2011. The results show that (1) 2005 is the year when urbanization starts accelerating in the Jing-Jin-Ji region; (2) albedo trends are equal to 0.0065 year-1 before urbanization and 0.0012 year-1 after urbanization, which is a reduction of 4/5; and (3) the contribution rate of urbanization increases from 15% to 48.4%, which leads to a decrease in albedo of approximately 0.05. Understanding the contribution of urbanization to variations in urban albedo is significant for future studies on urban climate change via energy balance and can provide scientific data for energy conservation policymaking. © 2018 by the authors.

There have been hiatuses in global warming since the 1990s, and their potential impacts have attracted extensive attention and discussion. Changes in temperature not only directly affect the greening of vegetation but can also indirectly alter both the growth state and the growth tendency of vegetation by altering other climatic elements. The middle-high latitudes of the Northern Hemisphere (NH) constitute the region that has experienced the most warming in recent decades; therefore, identifying the effects of warming hiatuses on the vegetation greening in that region is of great importance. Using satellite-derived Normalized Difference Vegetation Index (NDVI) data and climatological observation data from 1982-2013, we investigated hiatuses in warming trends and their impact on vegetation greenness in the NH. Our results show that the regions with warming hiatuses in the NH accounted for 50.1% of the total area and were concentrated in Mongolia, central China, and other areas. Among these regions, 18.8% of the vegetation greenness was inhibited in the warming hiatus areas, but 31.3% of the vegetation grew faster. Because temperature was the main positive climatic factor in central China, the warming hiatuses caused the slow vegetation greening rate. However, precipitation was the main positive climatic factor affecting vegetation greenness in Mongolia; an increase in precipitation accelerated vegetation greening. The regions without a warming hiatus, which were mainly distributed in northern Russia, northern central Asia, and other areas, accounted for 49.9% of the total area. Among these regions, 21.4% of the vegetation grew faster over time, but 28.5% of the vegetation was inhibited. Temperature was the main positive factor affecting vegetation greenness in northern Russia; an increase in temperature promoted vegetation greening. However, radiation was the main positive climatic factor in northern central Asia; reductions in radiation inhibited the greenness of ve

Drought-induced tree mortality has recently received considerable attention. Questions have arisen over the necessary intensity and duration thresholds of droughts that are sufficient to trigger rapid forest declines. The values of such tipping points leading to forest declines due to drought are presently unknown. In this study, we have evaluated the potential relationship between the level of tree growth and concurrent drought conditions with data of the tree growth-related ring width index (RWI) of the two dominant conifer species (Pinus edulis and Pinus ponderosa) in the Southwestern United State (SWUS) and the meteorological drought-related standardized precipitation evapotranspiration index (SPEI). In this effort, we determined the binned averages of RWI and the 11 month SPEI within the month of July within each bin of 30 of RWI in the range of 0–3000.Wefound a significant correlation between the binned averages of RWI and SPEI at the regional-scale under dryer conditions. The tipping point of forest declines to drought is predicted by the regression model as SPEItp = −1.64 and RWItp = 0, that is, persistence of the water deficit (11 month) with intensity of −1.64 leading to negligible growth for the conifer species. When climate conditions are wetter, the correlation between the binned averages ofRWI and SPEI is weaker which we believe is most likely due to soil water and atmospheric moisture levels no longer being the dominant factor limiting tree growth.Wealso illustrate a potential application of the derived tipping point (SPEItp = −1.64) through an examination of the 2002 extreme drought event in theSWUSconifer forest regions. Distinguished differences in remote-sensing based NDVI anomalies were found between the two regions partitioned by the derived tipping point.